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  1. Primary ovarian malignant melanoma

    Directory of Open Access Journals (Sweden)

    Kostov Miloš

    2010-01-01

    Full Text Available Background. Primary ovarian malignant melanoma is extremely rare. It usually appears in the wall of a dermoid cyst or is associated with another teratomatous component. Metastatic primary malignant melanoma to ovary from a primary melanoma elsewhere is well known and has been often reported especially in autopsy studies. Case report. We presented a case of primary ovarian malignant melanoma in a 45- year old woman, with no evidence of extraovarian primary melanoma nor teratomatous component. The tumor was unilateral, macroscopically on section presented as solid mass, dark brown to black color. Microscopically, tumor cells showed positive immunohistochemical reaction for HMB-45, melan-A and S-100 protein, and negative immunoreactivity for estrogen and progesteron receptors. Conclusion. Differentiate metastatic melanoma from rare primary ovarian malignant melanoma, in some of cases may be a histopathological diagnostic problem. Histopathological diagnosis of primary ovarian malignant melanoma should be confirmed by immunohistochemical analyses and detailed clinical search for an occult primary tumor.

  2. Primary cilium depletion typifies cutaneous melanoma in situ and malignant melanoma.

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    Jinah Kim

    Full Text Available Cutaneous melanoma is a lethal malignancy that arises spontaneously or via in situ precursor neoplasms. While melanoma in situ and locally invasive malignant melanoma can be cured surgically, these lesions can sometimes be difficult to distinguish from melanocytic nevi. Thus, the identification of histolopathologic or molecular features that distinguish these biologically distinct lesions would represent an important advance. To this end, we determined the abundance of melanocytic primary cilia in a series of 62 cases composed of typical cutaneous melanocytic nevi, melanoma in situ, invasive melanoma, and metastatic melanoma. Primary cilia are sensory organelles that modulate developmental and adaptive signaling and notably, are substantially depleted from the neoplastic epithelium of pancreatic carcinoma at a stage equivalent to melanoma in situ. In this series, we find that while nearly all melanocytes in 22 melanocytic nevi possessed a primary cilium, a near-complete loss of this organelle was observed in 16 cases of melanoma in situ, in 16 unequivocal primary invasive melanomas, and in 8 metastatic tumors, each associated with a cutaneous primary lesion. These findings suggest that the primary cilium may be used to segregate cutaneous invasive melanoma and melanoma in situ from melanocytic nevi. Moreover, they place the loss of an organelle known to regulate oncogenic signaling at an early stage of melanoma development.

  3. PRIMARY MALIGNANT MELANOMA OF ARYEPIGLOTTIC FOLD

    African Journals Online (AJOL)

    2015-12-01

    Dec 1, 2015 ... commonly in larynx, tongue, and tonsil.2 Primary mel- anoma of the larynx and trachea are very rare among the group of non-cutaneous melanomas. In primary melanoma of the larynx, the least common site is the subglottic mucosa.3 Here we present a case of primary malignant melanoma of aryepiglottic ...

  4. Primary Anorectal Melanoma: An Update

    Directory of Open Access Journals (Sweden)

    P Carcoforo, M.T Raiji, G.M Palini, M Pedriali, U Maestroni, G Soliani, A Detroia, M.V Zanzi, A.L Manna, J.G Crompton, R.C Langan, A Stojadinovic, I Avital

    2012-01-01

    Full Text Available The anorectum is a rare anatomic location for primary melanoma. Mucosal melanoma is a distinct biological and clinical entity from the more common cutaneous melanoma. It portrays worse prognosis than cutaneous melanoma, with distant metastases being the overwhelming cause of morbidity and mortality. Surgery is the treatment of choice, but significant controversy exists over the extent of surgical resection. We present an update on the state of the art of anorectal mucosal melanoma. To illustrate the multimodality approach to anorectal melanoma, we present a typical patient.

  5. ADAM15 expression is downregulated in melanoma metastasis compared to primary melanoma

    International Nuclear Information System (INIS)

    Ungerer, Christopher; Doberstein, Kai; Buerger, Claudia; Hardt, Katja; Boehncke, Wolf-Henning; Boehm, Beate; Pfeilschifter, Josef; Dummer, Reinhard; Mihic-Probst, Daniela; Gutwein, Paul

    2010-01-01

    Research highlights: → Strong ADAM15 expression is found in normal melanocytes. → ADAM15 expression is significantly downregulated in patients with melanoma metastasis. → TGF-β can downregulate ADAM15 expression in melanoma cells. → Overexpression of ADAM15 in melanoma cells inhibits migration, proliferation and invasion of melanoma cells. → Conclusion: ADAM15 represents an tumor suppressor protein in melanoma. -- Abstract: In a mouse melanoma metastasis model it has been recently shown that ADAM15 overexpression in melanoma cells significantly reduced the number of metastatic nodules on the lung. Unfortunately, the expression of ADAM15 in human melanoma tissue has not been determined so far. In our study, we characterized the expression of ADAM15 in tissue micro-arrays of patients with primary melanoma with melanoma metastasis. ADAM15 was expressed in melanocytes and endothelial cells of benign nevi and melanoma tissue. Importantly, ADAM15 was significantly downregulated in melanoma metastasis compared to primary melanoma. We further demonstrate that IFN-γ and TGF-β downregulate ADAM15 protein levels in melanoma cells. To investigate the role of ADAM15 in melanoma progression, we overexpressed ADAM15 in melanoma cells. Importantly, overexpression of ADAM15 in melanoma cells reduced the migration, invasion and the anchorage dependent and independent cell growth of melanoma cells. In summary, the downregulation of ADAM15 plays an important role in melanoma progression and ADAM15 act as a tumorsuppressor in melanoma.

  6. ADAM15 expression is downregulated in melanoma metastasis compared to primary melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Ungerer, Christopher; Doberstein, Kai [Pharmazentrum Frankfurt/ZAFES, University Hospital Goethe University Frankfurt, Frankfurt am Main (Germany); Buerger, Claudia; Hardt, Katja; Boehncke, Wolf-Henning [Department of Dermatology, Clinic of the Goethe-University, Theodor-Stern-Kai, Frankfurt (Germany); Boehm, Beate [Division of Rheumatology, Goethe University, Frankfurt am Main (Germany); Pfeilschifter, Josef [Pharmazentrum Frankfurt/ZAFES, University Hospital Goethe University Frankfurt, Frankfurt am Main (Germany); Dummer, Reinhard [Department of Pathology, Institute of Surgical Pathology, University Hospital, Zurich (Switzerland); Mihic-Probst, Daniela [Department of Dermatology, University Hospital Zurich (Switzerland); Gutwein, Paul, E-mail: p.gutwein@med.uni-frankfurt.de [Pharmazentrum Frankfurt/ZAFES, University Hospital Goethe University Frankfurt, Frankfurt am Main (Germany)

    2010-10-22

    Research highlights: {yields} Strong ADAM15 expression is found in normal melanocytes. {yields} ADAM15 expression is significantly downregulated in patients with melanoma metastasis. {yields} TGF-{beta} can downregulate ADAM15 expression in melanoma cells. {yields} Overexpression of ADAM15 in melanoma cells inhibits migration, proliferation and invasion of melanoma cells. {yields} Conclusion: ADAM15 represents an tumor suppressor protein in melanoma. -- Abstract: In a mouse melanoma metastasis model it has been recently shown that ADAM15 overexpression in melanoma cells significantly reduced the number of metastatic nodules on the lung. Unfortunately, the expression of ADAM15 in human melanoma tissue has not been determined so far. In our study, we characterized the expression of ADAM15 in tissue micro-arrays of patients with primary melanoma with melanoma metastasis. ADAM15 was expressed in melanocytes and endothelial cells of benign nevi and melanoma tissue. Importantly, ADAM15 was significantly downregulated in melanoma metastasis compared to primary melanoma. We further demonstrate that IFN-{gamma} and TGF-{beta} downregulate ADAM15 protein levels in melanoma cells. To investigate the role of ADAM15 in melanoma progression, we overexpressed ADAM15 in melanoma cells. Importantly, overexpression of ADAM15 in melanoma cells reduced the migration, invasion and the anchorage dependent and independent cell growth of melanoma cells. In summary, the downregulation of ADAM15 plays an important role in melanoma progression and ADAM15 act as a tumorsuppressor in melanoma.

  7. Surgery of Primary Melanomas

    Energy Technology Data Exchange (ETDEWEB)

    Rutkowski, Piotr, E-mail: rutkowskip@coi.waw.pl; Zdzienicki, Marcin; Nowecki, Zbigniew I. [Soft Tissue/Bone Sarcoma and Melanoma Department, M. Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw (Poland); Akkooi, Alexander C. J. van [Erasmus University Medical Center-Daniel den Hoed Cancer Center, Rotterdam (Netherlands)

    2010-05-11

    Surgery remains the mainstay of melanoma therapy, regardless of the tumor site. Only the early diagnosis combined with proper surgical therapy currently gives patients affected by this malignancy the chance for a full cure. The main goal of surgical therapy is to provide the local control of the disease and to secure long-term survival of the patient without reasonable functional and esthetic impairment. The recommended method of biopsy—excisional biopsy, as an initial diagnostic and, to some extent, therapeutic procedure—is performed under local anesthesia as an elliptical incision with visual clear margins of 1–3 mm and with some mm of subcutaneous tissue. The extent of radical excision of the primary tumor (or scar after excisional biopsy) is based on the histopathologic characteristics of the primary tumor and usually consists of 1–2 cm margins with primary closure. The philosophy behind conducted randomized clinical trials has been to find the most conservative surgical approach that is able to guarantee the same results as more demolitive treatment. This has been the background of the trials designed to define the correct margins of excision around a primary cutaneous melanoma. Much less definition can be dedicated to the surgical management of patients with non-cutaneous melanomas.

  8. Surgery of Primary Melanomas

    International Nuclear Information System (INIS)

    Rutkowski, Piotr; Zdzienicki, Marcin; Nowecki, Zbigniew I.; Akkooi, Alexander C. J. van

    2010-01-01

    Surgery remains the mainstay of melanoma therapy, regardless of the tumor site. Only the early diagnosis combined with proper surgical therapy currently gives patients affected by this malignancy the chance for a full cure. The main goal of surgical therapy is to provide the local control of the disease and to secure long-term survival of the patient without reasonable functional and esthetic impairment. The recommended method of biopsy—excisional biopsy, as an initial diagnostic and, to some extent, therapeutic procedure—is performed under local anesthesia as an elliptical incision with visual clear margins of 1–3 mm and with some mm of subcutaneous tissue. The extent of radical excision of the primary tumor (or scar after excisional biopsy) is based on the histopathologic characteristics of the primary tumor and usually consists of 1–2 cm margins with primary closure. The philosophy behind conducted randomized clinical trials has been to find the most conservative surgical approach that is able to guarantee the same results as more demolitive treatment. This has been the background of the trials designed to define the correct margins of excision around a primary cutaneous melanoma. Much less definition can be dedicated to the surgical management of patients with non-cutaneous melanomas

  9. Surgery of Primary Melanomas

    Directory of Open Access Journals (Sweden)

    Piotr Rutkowski

    2010-05-01

    Full Text Available Surgery remains the mainstay of melanoma therapy, regardless of the tumor site. Only the early diagnosis combined with proper surgical therapy currently gives patients affected by this malignancy the chance for a full cure. The main goal of surgical therapy is to provide the local control of the disease and to secure long-term survival of the patient without reasonable functional and esthetic impairment. The recommended method of biopsy—excisional biopsy, as an initial diagnostic and, to some extent, therapeutic procedure—is performed under local anesthesia as an elliptical incision with visual clear margins of 1–3 mm and with some mm of subcutaneous tissue. The extent of radical excision of the primary tumor (or scar after excisional biopsy is based on the histopathologic characteristics of the primary tumor and usually consists of 1–2 cm margins with primary closure. The philosophy behind conducted randomized clinical trials has been to find the most conservative surgical approach that is able to guarantee the same results as more demolitive treatment. This has been the background of the trials designed to define the correct margins of excision around a primary cutaneous melanoma. Much less definition can be dedicated to the surgical management of patients with non-cutaneous melanomas.

  10. Pathogenesis, diagnosis and management of primary melanoma of the colon

    Directory of Open Access Journals (Sweden)

    Imam Ayesha

    2011-02-01

    Full Text Available Abstract Background Melanomas within the alimentary tract are usually metastatic in origin. On the other hand, primary melanomas of the gastrointestinal tract are relatively uncommon. There are several published reports of melanomas occurring in the esophagus, stomach, small bowel, and anorectum. The occurrence of primary melanoma of the colon has, however, only been rarely reported. The optimum modus operandi for the management of primary colonic melanoma remains nebulous due to the limited number of reports in literature. Methods A comprehensive search of Medline, Cochrane and Highwire was performed using the following keywords: 'melanoma', 'malignant melanoma', 'primary melanoma', 'colon', 'gastrointestinal tract', 'alimentary tract', 'digestive tract', and 'large bowel'. All patients with primary melanoma localized to the colon were included in the review. Patients with metastatic melanomas to the gastrointestinal (GI tract and primary melanomas localized to the GI tract in anatomic locations other than colon were excluded. Results There have been only 12 reported cases of primary melanoma of the colon to date. The average age of patients on presentation was 60.4 years without any significant gender predilection. Right colon (33% and cecum (33% were the most common sites for the occurrence of primary colonic melanoma while abdominal pain (58% and weight loss (50% were the most common presenting complaints. Colonoscopy is the most reliable diagnostic investigation and offers the additional advantage of obtaining tissue for diagnosis. S-100 and HMB-45 are highly sensitive and specific for the diagnosis of this malignancy. For primary colonic melanomas that have not metastasized to any distant parts of the body, surgical resection with wide margins appears to be the treatment of choice. Although the management was individualized in every case, most of the authors preferred traditional hemicolectomy as the favored surgical approach

  11. Integrative Genome Comparison of Primary and Metastatic Melanomas

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    Feng, Bin; Nazarian, Rosalynn M.; Bosenberg, Marcus; Wu, Min; Scott, Kenneth L.; Kwong, Lawrence N.; Xiao, Yonghong; Cordon-Cardo, Carlos; Granter, Scott R.; Ramaswamy, Sridhar; Golub, Todd; Duncan, Lyn M.; Wagner, Stephan N.; Brennan, Cameron; Chin, Lynda

    2010-01-01

    A cardinal feature of malignant melanoma is its metastatic propensity. An incomplete view of the genetic events driving metastatic progression has been a major barrier to rational development of effective therapeutics and prognostic diagnostics for melanoma patients. In this study, we conducted global genomic characterization of primary and metastatic melanomas to examine the genomic landscape associated with metastatic progression. In addition to uncovering three genomic subclasses of metastastic melanomas, we delineated 39 focal and recurrent regions of amplification and deletions, many of which encompassed resident genes that have not been implicated in cancer or metastasis. To identify progression-associated metastasis gene candidates, we applied a statistical approach, Integrative Genome Comparison (IGC), to define 32 genomic regions of interest that were significantly altered in metastatic relative to primary melanomas, encompassing 30 resident genes with statistically significant expression deregulation. Functional assays on a subset of these candidates, including MET, ASPM, AKAP9, IMP3, PRKCA, RPA3, and SCAP2, validated their pro-invasion activities in human melanoma cells. Validity of the IGC approach was further reinforced by tissue microarray analysis of Survivin showing significant increased protein expression in thick versus thin primary cutaneous melanomas, and a progression correlation with lymph node metastases. Together, these functional validation results and correlative analysis of human tissues support the thesis that integrated genomic and pathological analyses of staged melanomas provide a productive entry point for discovery of melanoma metastases genes. PMID:20520718

  12. SVM classifier on chip for melanoma detection.

    Science.gov (United States)

    Afifi, Shereen; GholamHosseini, Hamid; Sinha, Roopak

    2017-07-01

    Support Vector Machine (SVM) is a common classifier used for efficient classification with high accuracy. SVM shows high accuracy for classifying melanoma (skin cancer) clinical images within computer-aided diagnosis systems used by skin cancer specialists to detect melanoma early and save lives. We aim to develop a medical low-cost handheld device that runs a real-time embedded SVM-based diagnosis system for use in primary care for early detection of melanoma. In this paper, an optimized SVM classifier is implemented onto a recent FPGA platform using the latest design methodology to be embedded into the proposed device for realizing online efficient melanoma detection on a single system on chip/device. The hardware implementation results demonstrate a high classification accuracy of 97.9% and a significant acceleration factor of 26 from equivalent software implementation on an embedded processor, with 34% of resources utilization and 2 watts for power consumption. Consequently, the implemented system meets crucial embedded systems constraints of high performance and low cost, resources utilization and power consumption, while achieving high classification accuracy.

  13. Primary gastric melanoma: case report of a rare malignancy

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    Alexander Augustyn

    2015-03-01

    Full Text Available We report the case of a 64-year-old white male who presented to his primary care physician with complaints of fatigue. Physical exam was unremarkable and laboratory studies revealed profound anemia, for which the patient received a transfusion. Esophagogastroduodenoscopy revealed a bleeding mass in the proximal stomach that was histologically determined to be malignant melanoma, with immunohistochemical staining demonstrating positivity for SOX10, S100, MART-1, and HMG-45. After an extensive dermatological exam no other primary lesion was identified. Whole body positron emission tomography (18-FDG-PET/CT demonstrated pathologic uptake only in the area of the proximal stomach. For this reason, primary gastric melanoma was suspected in this patient. The patient underwent subtotal gastrectomy with mass excision followed by Roux-en-Y reconstruction. Very few cases of primary gastric melanoma have been reported. We report this case and present diagnostic criteria for primary non-cutaneous melanoma and discuss potential non-surgical therapies.

  14. Extensive screening for primary tumor is redundant in melanoma of unknown primary

    DEFF Research Database (Denmark)

    Tos, Tina; Klyver, Helle; Drzewiecki, Krzysztof T

    2011-01-01

    For decades, patients in our institution with metastastic melanoma of unknown primary have been subjected to extensive examinations in search of the primary tumor. This retrospective study questions the results, and thus the feasibility of these examinations. Of 103 patients diagnosed with unknow......, for patients referred with metastastic melanoma of unknown primary, we recommend that a detailed history is obtained, and a standard physical examination performed, in addition to a histopathological review and CT/PET for staging....

  15. Analytical validation of a melanoma diagnostic gene signature using formalin-fixed paraffin-embedded melanocytic lesions.

    Science.gov (United States)

    Warf, M Bryan; Flake, Darl D; Adams, Doug; Gutin, Alexander; Kolquist, Kathryn A; Wenstrup, Richard J; Roa, Benjamin B

    2015-01-01

    These studies were to validate the analytical performance of a gene expression signature that differentiates melanoma and nevi, using RNA expression from 14 signature genes and nine normalization genes that generates a melanoma diagnostic score (MDS). Formalin-fixed paraffin-embedded melanocytic lesions were evaluated in these studies. The overall SD of the assay was determined to be 0.69 MDS units. Individual amplicons within the signature had an average amplification efficiency of 92% and a SD less than 0.5 CT. The MDS was reproducible across a 2000-fold dilution range of input RNA. Melanin, an inhibitor of PCR, does not interfere with the signature. These studies indicate this signature is robust and reproducible and is analytically validated on formalin-fixed paraffin-embedded melanocytic lesions.

  16. Primary Malignant Melanoma of the Lung: A Case Report

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    Karagianni Evangelia

    2003-11-01

    Full Text Available Abstract Background Primary melanoma of the lung is an extremely rare pathological entity and sparsely reported in the literature. Case presentation A case of primary malignant melanoma of the lung in a 41-year-old female is reported. The clinical, radiological and histopathological features are discussed. The initial symptom was cough, whereas the chest radiography showed a round opacity of the right lung. The computed tomography of the chest revealed a well-demarcated mass lesion in the right upper lobe. Endobronchial mass causing obstruction of the upper lobar bronchus was the bronchoscopic finding. Patient underwent pneumonectomy. A diagnosis of melanoma was confirmed postoperatively after the immunohistochemistry. Primary nature of the tumour in the lung results from the demonstration of characteristic junctional pattern of melanoma cells beneath the bronchial epithelium on histopathology, and from exclusion of other potential primary sites in the clinical, paraclinical and laboratory examination. Conclusions Primary melanoma of the lung represents a rare pathological entity. Careful interpretation of histopathological information in correlation with all other findings from clinical and paraclinical studies can establish a diagnosis. Follow-up is necessary in order to diagnose potential dissemination or secondary sites of the disease. Due to the small number of cases reported in the literature, there is no experience on the management and the prognosis of the disease, but surgical resection remains the cornerstone of the treatment.

  17. Aggressive solitary intracranial metastatic malignant melanoma from a primary mediastinal tumour.

    Science.gov (United States)

    Sivaraju, Laxminadh; Aryan, Saritha; Hegde, Vinay S; Ghosal, Nandita; Hegde, Alangar S

    2016-08-01

    Malignant melanoma is the third most common tumour to cause cerebral metastases, following breast and lung cancer. Central nervous system metastases occur in 10-40% of patients with melanoma. Intracranial metastasis from a primary malignant melanoma of the anterior mediastinum is uncommon. We report a case of solitary intracranial metastatic melanoma arising from a primary mediastinal tumour. We then discuss the clinico-radiological features and treatment options. © The Author(s) 2016.

  18. Local melanoma recurrences in the scar after limited surgery for primary tumor

    DEFF Research Database (Denmark)

    Drzewiecki, K T; Andersson, A P

    1995-01-01

    The clinical and histologic records of 46 consecutive patients were reviewed who during the period 1980-1993 had recurrence from melanoma in the scar after limited surgery for a skin tumor. They constituted about 50% of all patients admitted with local recurrence from melanoma during this period....... At reexamination of the primary tumors, 16 were found to be malignant melanomas and 9 were nevi (four atypical and five benign). Twenty-one were missing, 11 of which had never been set for histologic examination. The median thickness of nine measurable melanomas was 0.66 mm. The recurrences in scar consisted of 34...... recurrences in the form of a new primary in a scar following limited surgery supports the theory of limited field change around a primary melanoma. Furthermore, limited procedures for primary melanoma, if followed by a recurrence in the scar, worsen the prognosis....

  19. Primary Tumor Thickness is a Prognostic Factor in Stage IV Melanoma: A Retrospective Study of Primary Tumor Characteristics.

    Science.gov (United States)

    Luen, Stephen; Wong, Siew Wei; Mar, Victoria; Kelly, John W; McLean, Catriona; McArthur, Grant A; Haydon, Andrew

    2018-01-01

    Stage IV melanoma exhibits a diverse range of tumor biology from indolent to aggressive disease. Many important prognostic factors have already been identified. Despite this, the behavior of metastatic melanoma remains difficult to predict. We sought to determine if any primary tumor characteristics affect survival following the diagnosis of stage IV melanoma. All patients diagnosed with stage IV melanoma between January 2003 and December 2012 were identified from the Victorian Melanoma Service database. Retrospective chart review was performed to collect data on primary tumor characteristics (thickness, ulceration, mitotic rate, melanoma subtype, or occult primary). Known and suspected prognostic factors were additionally collected (time to diagnosis of stage IV disease, age, sex, stage, receipt of chemotherapy, and era of recurrence). The effect of primary tumor characteristics on overall survival from the date of diagnosis of stage IV disease was assessed. A total of 227 patients with a median follow-up of 5 years from diagnosis of stage IV disease were identified. Median overall survival of the cohort was 250 days.Of the primary tumor characteristics assessed, only tumor thickness affected survival from diagnosis of stage IV disease, hazard ratio=1.09 (1.02 to 1.16), P=0.008. This remained significant in multivariate analysis, P=0.007. Other primary tumor characteristics did not significantly influence survival. Primary tumor thickness is a significant prognostic factor in stage IV melanoma. Our data suggest that the biology of the primary melanoma may persist to influence the behavior of metastatic disease.

  20. Impact of hypothyroidism on primary anal malignant melanoma: A rare entity

    Directory of Open Access Journals (Sweden)

    Siddharth Singh

    2014-01-01

    Full Text Available Primary melanoma of the anal canal is rare and highly malignant condition, which is 1% of all invasive tumors in this site. This condition is often mistaken for benign conditions as either hemorrhoids or rectal polyp. Thyroid-stimulating hormone stimulation causes high proliferation of malignant melanoma. The association of hypothyroidism with primary malignant melanoma of anal canal is very rare. We are reporting such a very rare case.

  1. Impact of hypothyroidism on primary anal malignant melanoma: a rare entity.

    Science.gov (United States)

    Singh, Siddharth; Verma, Satyajeet; Kala, Sanjay

    2014-01-01

    Primary melanoma of the anal canal is rare and highly malignant condition, which is 1% of all invasive tumors in this site. This condition is often mistaken for benign conditions as either hemorrhoids or rectal polyp. Thyroid-stimulating hormone stimulation causes high proliferation of malignant melanoma. The association of hypothyroidism with primary malignant melanoma of anal canal is very rare. We are reporting such a very rare case.

  2. Primary malignant melanoma

    Directory of Open Access Journals (Sweden)

    A. Ferhat Mısır

    2016-04-01

    Full Text Available Malignant melanomas (MM of the oral cavity are extremely rare, accounting for 0.2% to 8.0% of all malignant melanomas. Malignant melanomas is more frequently seen at the level of the hard palate and gingiva. Early diagnosis and treatment are important for reducing morbidity. Malignant melanoma cells stain positively with antibodies to human melanoma black 45, S-100 protein, and vimentin; therefore, immunohistochemistry can play an important role in evaluating the depth of invasion and the location of metastases. A 76-year-old man developed an oral malignant melanoma, which was originally diagnosed as a bluish reactive denture hyperplasia caused by an ill-fitting lower denture. The tumor was removed surgically, and histopathological examination revealed a nodular-type MM. There was no evidence of recurrence over a 4-year follow-up period.

  3. Intussusception of the small intestine caused by a primary melanoma?

    Science.gov (United States)

    Schoneveld, M; De Vogelaere, K; Van De Winkel, N; Hoorens, A; Delvaux, G

    2012-01-01

    Although the gastrointestinal tract is a fairly frequent site of melanoma metastases, reports of small bowel intussusception caused by melanoma are very rare. We report the case of a 77-year-old man who was admitted to our hospital with epigastric pain, melena and anaemia. After clinical examination, laboratory evaluation and radiological work-up the diagnosis of a jejunal intussusception was made. Exploratory laparoscopy revealed a large tumour arising from the jejunum, approximately 20 cm distal to the angle of Treitz. Small bowel resection with an end-to-end anastomosis was performed. Histological examination showed an intestinal melanoma. There are different theories concerning the origin of malignant melanoma in the small bowel. Although the small and large intestines normally contain no melanocytes, these cells have occasionally been found in the alimentary and respiratory tracts and even in lymph nodes, which supports the theory of a primary origin of melanoma at these sites. Since this was a solitary intestinal lesion and there was no history of cutaneous melanoma, we conclude that this could be an example of a very rare primary melanoma of the small intestine.

  4. Intussusception of the Small Intestine Caused by a Primary Melanoma

    Directory of Open Access Journals (Sweden)

    M. Schoneveld

    2012-01-01

    Full Text Available Although the gastrointestinal tract is a fairly frequent site of melanoma metastases, reports of small bowel intussusception caused by melanoma are very rare. We report the case of a 77-year-old man who was admitted to our hospital with epigastric pain, melena and anaemia. After clinical examination, laboratory evaluation and radiological work-up the diagnosis of a jejunal intussusception was made. Exploratory laparoscopy revealed a large tumour arising from the jejunum, approximately 20 cm distal to the angle of Treitz. Small bowel resection with an end-to-end anastomosis was performed. Histological examination showed an intestinal melanoma. There are different theories concerning the origin of malignant melanoma in the small bowel. Although the small and large intestines normally contain no melanocytes, these cells have occasionally been found in the alimentary and respiratory tracts and even in lymph nodes, which supports the theory of a primary origin of melanoma at these sites. Since this was a solitary intestinal lesion and there was no history of cutaneous melanoma, we conclude that this could be an example of a very rare primary melanoma of the small intestine.

  5. A Case of Primary Subglottic Malignant Melanoma with a Successful Surgical Treatment

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    Shahzad Ahmad

    2014-01-01

    Full Text Available Primary subglottic malignant melanoma is a very rare and underdiagnosed neoplasm. We are reporting a case of primary malignant melanoma of subglottic mucosa in a 78-year-old woman who presented to our hospital with shortness of breath and hoarseness of voice. Laryngoscopy and excisional biopsy along with immunoreactivity to S-100 and human melanoma black-45 (HMB-45 confirmed the diagnosis. The patient was treated with laryngectomy followed by radiotherapy. Five years following surgical treatment, she continues to be asymptomatic. To our knowledge, there is only one reported case of primary malignant melanoma of subglottic mucosa in the medical literatures.

  6. Primary pulmonary malignant melanoma: a clinicopathologic study of two cases.

    Science.gov (United States)

    Gong, Li; Liu, Xiao-Yan; Zhang, Wen-Dong; Zhu, Shao-Jun; Yao, Li; Han, Xiu-Juan; Lan, Miao; Li, Yan-Hong; Zhang, Wei

    2012-09-19

    Malignant melanoma involving the respiratory tract is nearly always metastatic in origin, and primary tumors are very rare. To our knowledge, about 30 cases have been reported in the English literature, one of which involved multiple brain metastases. Here, we report two cases of primary pulmonary malignant melanoma. The first case, which occurred in a 52-year-old Chinese female patient who died 4 months after the initial diagnosis, involved rapid intrapulmonary and intracranial metastases. The second patient, a 65-year-old female, underwent surgical excision, and clinical examination, histopathological characteristics, and immunohistochemical features supported the diagnosis of pulmonary malignant melanoma. No evidence for recurrence and/or metastasis has been found more than one year after the initial surgery. To establish the diagnosis of primary pulmonary malignant melanoma, any extrapulmonary origin must be excluded by detailed examination. Moreover, the tumor should be removed surgically whether it occurs as a single lesion or multiple lesions. The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1480477335765055.

  7. Primary pulmonary malignant melanoma: a clinicopathologic study of two cases

    Directory of Open Access Journals (Sweden)

    Gong Li

    2012-09-01

    Full Text Available Abstract Malignant melanoma involving the respiratory tract is nearly always metastatic in origin, and primary tumors are very rare. To our knowledge, about 30 cases have been reported in the English literature, one of which involved multiple brain metastases. Here, we report two cases of primary pulmonary malignant melanoma. The first case, which occurred in a 52-year-old Chinese female patient who died 4 months after the initial diagnosis, involved rapid intrapulmonary and intracranial metastases. The second patient, a 65-year-old female, underwent surgical excision, and clinical examination, histopathological characteristics, and immunohistochemical features supported the diagnosis of pulmonary malignant melanoma. No evidence for recurrence and/or metastasis has been found more than one year after the initial surgery. To establish the diagnosis of primary pulmonary malignant melanoma, any extrapulmonary origin must be excluded by detailed examination. Moreover, the tumor should be removed surgically whether it occurs as a single lesion or multiple lesions. Virtual slide The virtual slide(s for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1480477335765055.

  8. Skin protection behaviour and sex differences in melanoma location in patients with multiple primary melanomas.

    Science.gov (United States)

    Warren, Matthew; McMeniman, Erin; Adams, Agnieszka; De'Ambrosis, Brian

    2017-02-01

    Previous studies have shown that sunscreen usage, sun-protection measures and self-examination rates in patients with single primary melanomas (SPM) are similar to that in the general population. This study hypothesises that these rates would be different in a population with multiple primary melanomas (MPM). We further hypothesise that there would be a sex difference in melanoma location in patients with MPM. The objectives of this study were to determine skin protection measures, self-examinations and melanoma location in a cohort of patients with MPM. A survey was conducted on 137 patients with MPM examining their sun-protection measures, skin self-examination rates and medical and phenotypic characteristics. These data were combined with a review of their medical records to examine the patients' skin cancer history. Patients with MPM had higher rates of skin self-evaluation (74% vs 22%), sunscreen usage (70% vs 45%) and other sun-protection measures (95% vs 46%) than has been published for patients with a history of a SPM. We have also shown that women have a higher risk of developing melanomas on their arms (p skin self-examination, sunscreen usage and other sun-protection methods in patients with MPM is higher than in studies of patients with SPM. It also highlighted sex differences in terms of melanoma location for patients with MPM. Further studies to examine the cause of the differences in these forms of protective behaviour could help improve the utilisation of these important preventative measures in all patients. © 2015 The Australasian College of Dermatologists.

  9. In vivo and ex vivo proton MR spectroscopy of primary and secondary melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Bourne, Roger M.; Stanwell, Peter; Stretch, Jonathan R.; Scolyer, Richard A.; Thompson, John F.; Mountford, Carolyn E.; Lean, Cynthia L

    2005-03-01

    In vivo magnetic resonance (MR) spectroscopy at 1.5T was performed on a large polypoid cutaneous melanoma, and two enlarged lymph nodes containing metastatic melanoma, from three patients. Spectra were acquired in vivo from voxels wholly within the primary tumour or secondary lymph node and were thus uncontaminated by signals from adjacent tissue. Tissue biopsies taken after resection of primary tumours and secondary lymph nodes were examined by 8.5T magnetic resonance spectroscopy (MRS) and the results compared with the in vivo spectra, and with spectra from normal skin and a benign skin lesion. There was good agreement between the dominant features of 1.5T spectra acquired in vivo and 8.5T spectra acquired from resected tissue. However, less intense resonances observed at 8.5T in malignant biopsy tissue were not consistently observed at 1.5T in vivo. In vivo spectra from primary and metastatic melanoma showed high levels of choline metabolites. An intense lactate resonance was also present in the in vivo spectrum of primary melanoma. All 8.5T spectra of biopsies from primary and secondary melanoma showed high levels of choline metabolites and lactate, and additional resonances consistent with elevated levels of taurine, alanine, lysine, and glutamate/glutamine relative to normal and benign tissue. Elevated levels of choline, lactate, taurine, and amino acids appear to be clinically useful markers for identifying the pathology of primary and metastatic melanoma.

  10. Quantitative Proteomics Identifies Activation of Hallmark Pathways of Cancer in Patient Melanoma.

    Science.gov (United States)

    Byrum, Stephanie D; Larson, Signe K; Avaritt, Nathan L; Moreland, Linley E; Mackintosh, Samuel G; Cheung, Wang L; Tackett, Alan J

    2013-03-01

    Molecular pathways regulating melanoma initiation and progression are potential targets of therapeutic development for this aggressive cancer. Identification and molecular analysis of these pathways in patients has been primarily restricted to targeted studies on individual proteins. Here, we report the most comprehensive analysis of formalin-fixed paraffin-embedded human melanoma tissues using quantitative proteomics. From 61 patient samples, we identified 171 proteins varying in abundance among benign nevi, primary melanoma, and metastatic melanoma. Seventy-three percent of these proteins were validated by immunohistochemistry staining of malignant melanoma tissues from the Human Protein Atlas database. Our results reveal that molecular pathways involved with tumor cell proliferation, motility, and apoptosis are mis-regulated in melanoma. These data provide the most comprehensive proteome resource on patient melanoma and reveal insight into the molecular mechanisms driving melanoma progression.

  11. [Primary malignant melanoma of the central nervous system: A diagnostic challenge].

    Science.gov (United States)

    Quillo-Olvera, Javier; Uribe-Olalde, Juan Salvador; Alcántara-Gómez, Leopoldo Alberto; Rejón-Pérez, Jorge Dax; Palomera-Gómez, Héctor Guillermo

    2015-01-01

    The rare incidence of primary malignant melanoma of the central nervous system and its ability to mimic other melanocytic tumors on images makes it a diagnostic challenge for the neurosurgeon. A 51-year-old patient, with a tumor located in the right forniceal callosum area. Total surgical excision was performed. Histopathological result was consistent with the diagnosis of primary malignant melanoma of the central nervous system, after ruling out extra cranial and extra spinal melanocytic lesions. The primary malignant melanoma of the central nervous system is extremely rare. There are features in magnetic resonance imaging that increase the diagnostic suspicion; nevertheless there are other tumors with more prevalence that share some of these features through image. Since there is not an established therapeutic standard its prognosis is discouraging. Copyright © 2015 Academia Mexicana de Cirugía A.C. Published by Masson Doyma México S.A. All rights reserved.

  12. Prognostic Parameters for the Primary Care of Melanoma Patients: What Is Really Risky in Melanoma

    International Nuclear Information System (INIS)

    Goppner, D.; Leverkus, M.

    2011-01-01

    Due to intensified research in recent years, the understanding of the molecular mechanisms involved in the development of melanoma has dramatically improved. The discovery of specific, causal mutations such as BRAF or KIT oncogenes not only renders a targeted and thus more effective therapeutic approach possible, but also gives rise to a new genetic-based classification. Targeting just a few out of several potential mutations, BRAF-Inhibitors such as PLX 4032 achieved already tremendous results in the therapy of metastatic melanoma. Up to now, the correlation of clinical, histomorphologic, and genetic features is, however, not understood. Even more, is it not well known precisely what kind of molecular changes predispose the primary melanoma for metastasis. The identification of morphological surrogates and prognostic parameters in tumors with such genetic alteration seems therefore crucial when differentiating and classifying this heterogeneous tumor entity in more detail and thus facilitates the stratification of prognosis as well as therapy. This review summarizes the current understanding of carcinogenesis and gives a detailed overview of known morphologic and potentially future genetic prognostic parameters in malignant melanoma.

  13. Analysis of trends and seasonal variation in primary cutaneous melanoma: an Irish study.

    LENUS (Irish Health Repository)

    Downes, M R

    2010-11-10

    A seasonal variation in the presentation of cutaneous melanoma has been documented in several studies. We performed a retrospective review of primary cutaneous melanomas (n = 263) from our institution to examine whether the seasonal patterns of presentation noted in the literature would be similar in Ireland, a climate with low ambient sunshine. A summer : winter ratio was determined for age, gender, subtype, location and Breslow thickness. We found an increase in total numbers of melanomas, particularly in men. The summer : winter ratio was 2.39 for all patients (95% CI 1.60-3.57, P < 0.001), with seasonal variations noted for location, thickness and subtype (excluding lentigo). Melanomas presenting over the summer tended towards a greater Breslow thickness than did those presenting in winter. This subclassification of primary cutaneous melanoma with summer : winter ratios based on patient and tumour characteristics gave remarkably similar results to previously published reports, notwithstanding the low levels of annual ambient sunshine in Ireland.

  14. Primary Malignant Melanoma of the Esophagus

    OpenAIRE

    Oya Yonal; Duygu Ibrisim; Yıldıran Songur; Yılmaz Cakaloglu; Koray Tuncer; Hale Kırımlıoglu; Sadakat Ozdil

    2013-01-01

    Primary malignant melanoma of the esophagus (PMME) comprises only 0.1?0.2% of all malignant esophageal tumors. PMME tumors are highly aggressive and metastasize early via hematogenic and lymphatic pathways. Treatment outcome is poor because the cancer has often advanced at the time of diagnosis. Inoperability, unsuccessful treatment with radiotherapy and chemotherapy in advanced tumors and metastases have contributed to its poor prognosis. Here, we present the endoscopic features, endoscopic ...

  15. Digital dewaxing of Raman signals: discrimination between nevi and melanoma spectra obtained from paraffin-embedded skin biopsies.

    Science.gov (United States)

    Tfayli, Ali; Gobinet, Cyril; Vrabie, Valeriu; Huez, Regis; Manfait, Michel; Piot, Olivier

    2009-05-01

    Malignant melanoma (MM) is the most severe tumor affecting the skin and accounts for three quarters of all skin cancer deaths. Raman spectroscopy is a promising nondestructive tool that has been increasingly used for characterization of the molecular features of cancerous tissues. Different multivariate statistical analysis techniques are used in order to extract relevant information that can be considered as functional spectroscopic descriptors of a particular pathology. Paraffin embedding (waxing) is a highly efficient process used to conserve biopsies in tumor banks for several years. However, the use of non-dewaxed formalin-fixed paraffin-embedded tissues for Raman spectroscopic investigations remains very restricted, limiting the development of the technique as a routine analytical tool for biomedical purposes. This is due to the highly intense signal of paraffin, which masks important vibrations of the biological tissues. In addition to being time consuming and chemical intensive, chemical dewaxing methods are not efficient and they leave traces of the paraffin in tissues, which affects the Raman signal. In the present study, we use independent component analysis (ICA) on Raman spectral images collected on melanoma and nevus samples. The sources obtained from these images are then used to eliminate, using non-negativity constrained least squares (NCLS), the paraffin contribution from each individual spectrum of the spectral images of nevi and melanomas. Corrected spectra of both types of lesion are then compared and classified into dendrograms using hierarchical cluster analysis (HCA).

  16. Primary Anorectal Melanoma

    Directory of Open Access Journals (Sweden)

    Maliha Khan

    2014-03-01

    Full Text Available Primary malignant melanoma of the anus and rectum is a rare and aggressive neoplasm that tends to invade locally and metastasize early in the course of the disease. It is often misdiagnosed as hemorrhoids or as one of the other benign anorectal conditions and is thus linked to an overall poor prognosis and a 5-year survival rate of less than 20%. Optimal treatment is still controversial, and current evidence does not show any preferential survival benefit from abdominoperineal resection over wide local excision. Chemotherapy or radiotherapy may be used for advanced disease. We report a 71-year-old female presenting with painful bowel movements and blood in stools. She was eventually found to have a mass arising from the anorectal junction with regional lymph node involvement. The patient underwent an abdominoperineal resection and is currently scheduled for chemotherapy.

  17. Cytology of primary vaginal melanoma: An unusual report on fine needle aspiration.

    Science.gov (United States)

    Agarwal, Poojan; Kaushal, Manju

    2017-03-01

    Primary malignant melanoma of the vagina is an extremely uncommon malignancy comprising of less than 10% malignancies of the female genital tract and 0.3% of all melanomas. Melanoblasts are neural crest derivatives and are notorious for causing primary cutaneous neoplasms. However, they involve virtually every organ of the body including eye, intestines and ocular mucosa, probably due to aberrancies in cell migration. Vagina is a rare site and primary melanoma of the vagina occurs in postmenopausal women with vaginal discharge, bleeding, or mass as common presenting complaints. Only a handful of case reports are available describing this entity on biopsy and PAP smear samples; however, fine needle aspiration has seldom been discussed. In the present report we discuss a case of an elderly female who complained of mass protruding through the vaginal opening, FNAC was done from the mass as well as from the right inguinal lymph node. An extensive clinicoradiological workup, and immunohistochemical confirmation is essential to rule out metastatic lesions and confirm primary. Diagn. Cytopathol. 2017;45:252-256. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  18. Pelvis metastasis from primary choroidal melanoma: a case report

    Directory of Open Access Journals (Sweden)

    Xiong Y

    2014-11-01

    Full Text Available Yan Xiong, Yun Lang, Chongqi Tu, Hong Duan Department of Orthopedics, West China Hospital, Sichuan University, Chengdu, People's Republic of China Abstract: The patient, a 16-year-old girl, was admitted to our hospital with complaints of right hip pain and claudication. Her past medical history indicated that 2 years earlier she had undergone enucleation of her left eye for a primary choroidal melanoma. Imaging studies revealed a osteolytic destruction with soft tissue mass involving the right hemipelvis (zone I–II. Single-photon emission computed tomography (SPECT and positron emission tomography–computed tomography (PET–CT showed no other sites of metastases. Consequently, the patient underwent hemipelvic prosthesis reconstruction after tumor resection. Postoperative pathological diagnosis was metastatic malignant melanoma. Thirty months after treatment, imaging studies indicated no evidence of recurrence, and functional recovery was excellent. To our knowledge, the literature does not reveal any previously reported cases of ocular choroidal melanoma that metastasized to pelvis, meanwhile was carried out hemipelvic prosthesis reconstruction after pelvic tumor resection. Keywords: melanoma, metastasis, pelvis, tumor, reconstruction

  19. Effects of Tyrosine Kinase inhibitor Imatinib (Glivec) on PDGFR-positive primary and metastatic melanoma cells

    International Nuclear Information System (INIS)

    Straface, E.; Gambardella, L.; Vona, R.

    2009-01-01

    In summary these preliminary results indicate that Imatinib is able to induce apoptosis in metastatic cells and to sensitize these cells to pro-apoptotic agents commonly used in melanoma therapy, e.g. radiation or Cisplatin. Conversely, primary melanoma cells seem to be intrinsically resistant either to Imatinib given alone or in combination with Cisplatin or radiation. By contrast, these cells underwent autophagy and replicative senescence boostering their survival. Interestingly, the use of Imatinib in combination with anti-CD95/Fas antibodies sensitizes primary melanoma cells to apoptosis

  20. Primary Care for Melanoma: Should We Be Screaming for Screening?

    Directory of Open Access Journals (Sweden)

    Dennis J. Baumgardner

    2014-01-01

    Full Text Available The incidence of cutaneous malignant melanoma continues to rise in the United States. This deadly disease is potentially curable if caught at an early stage, however screening programs remain controversial. The United States Preventive Services Task Force cites insufficient evidence to recommend screening, by total-body skin examination (TBSE, for early detection of cutaneous melanoma. While definitive studies may be cost-prohibitive in the United States, more recent evidence suggests that organized programs to increase TBSE reduce mortality from melanoma. The positive impact of TBSE, and education regarding risk reduction and skin self-examination, is most likely to be cost-effective in high-risk patients such as middle-aged and older men. This population also includes those with changing moles or those who always or usually sunburn; those with melanoma in a first-degree relative, or dysplastic nevi or extensive moles; and those with high-risk ultraviolet (UV exposure or other risk factors. The role of new technology, such as in-office and in-home dermoscopy, continues to evolve. Primary care clinicians are challenged in everyday practice to appropriately prioritize TBSE and empower their patients for “skin awareness” and self-detection of melanoma.

  1. The Melanoma care study: protocol of a randomised controlled trial of a psycho-educational intervention for melanoma survivors at high risk of developing new primary disease.

    Science.gov (United States)

    Dieng, Mbathio; Kasparian, Nadine A; Morton, Rachael L; Mann, Graham J; Butow, Phyllis; Menzies, Scott; Costa, Daniel S J; Cust, Anne E

    2015-01-01

    Despite a good prognosis for most melanoma survivors, many experience substantial fear of new or recurrent melanoma, worry and anxiety about the future, and unmet healthcare needs. In this protocol, we outline the design and methods of the Melanoma Care Study for melanoma survivors at high risk of developing new primary disease. The objective of this study is to evaluate the efficacy and cost-effectiveness of a psycho-educational intervention for improving psychological and behavioural adjustment to melanoma risk. The study design is a two-arm randomised controlled trial comparing a psycho-educational intervention to usual care. The intervention is comprised of a newly-developed psycho-educational booklet and three telephone sessions delivered by a trained psychologist. A total of 154 melanoma survivors at high risk of developing new primary disease who are attending one of three melanoma high risk clinics in New South Wales, Australia, will be recruited. Participants will be assessed at baseline (6 weeks before their high risk clinic dermatological appointment), and then 4 weeks and 6 months after their appointment. If effectiveness of the intervention is demonstrated at 6 months, an additional assessment at 12 months is planned. The primary outcome is fear of new or recurrent melanoma, as assessed by the Fear of Cancer Recurrence Inventory (FCRI). Secondary outcomes include anxiety, depression, unmet supportive care needs, satisfaction with clinical care, knowledge, behavioural adjustment to melanoma risk, quality of life, and cost-effectiveness of the intervention from a health system perspective. Following the intention-to-treat principle, linear mixed models will be used to analyse the data to account for repeated measures. A process evaluation will also be carried out to inform and facilitate potential translation and implementation into clinical practice. This study will provide high quality evidence on the efficacy and cost-effectiveness of a psycho

  2. Differing lectin-binding patterns of malignant melanoma and nevocellular and Spitz nevi.

    Science.gov (United States)

    Kohchiyama, A; Oka, D; Ueki, H

    1987-01-01

    The lectin-binding patterns of primary malignant melanoma, nevocellular nevus, and Spitz nevus were studied on formalin-fixed, paraffin-embedded sections using a series of biotinylated lectins--concanavalin A (ConA), Ricinus communis agglutinin-1 (RCA1), dolichos biflorus agglutinin (DBA), soybean agglutinin (SBA), maclura pomifera agglutinin (MPA), peanut agglutinin (PNA), wheat germ agglutinin (WGA), and Ulex europeus agglutinin-1(UEA1)--and employing the avidin-biotin-peroxidase complex method. In nevocellular and Spitz nevi, all of the nevus cells were positively stained with ConA and RCA1. No positive staining was observed, however, with the other lectins and no change in binding patterns occurred following neuraminidase pretreatment. In malignant melanoma, all of the melanoma cells were positively stained with ConA and RCA1, and some were also stained with MPA, PNA, and WGA. In addition, DBA, SBA, MPA, PNA, and WGA labeled all of the melanoma cells after neuraminidase pretreatment. No positive staining was observed with UEA1 despite neuraminidase pretreatment. The present results showed that malignant melanoma and nevocellular and Spitz nevi have different lectin-binding patterns and different responses to neuraminidase pretreatment. We, therefore, believe that the lectin staining on paraffin-embedded sections can be a useful probe for the differentiation of these diseases.

  3. Cytoplasmic BRMS1 expression in malignant melanoma is associated with increased disease-free survival

    Directory of Open Access Journals (Sweden)

    Slipicevic Ana

    2012-02-01

    Full Text Available Abstract Background/aims Breast cancer metastasis suppressor 1 (BRMS1 blocks metastasis in melanoma xenografts; however, its usefulness as a biomarker in human melanomas has not been widely studied. The goal was to measure BRMS1 expression in benign nevi, primary and metastatic melanomas and evaluate its impact on disease progression and prognosis. Methods Paraffin-embedded tissue from 155 primary melanomas, 69 metastases and 15 nevi was examined for BRMS1 expression using immunohistochemistry. siRNA mediated BRMS1 down-regulation was used to study impact on invasion and migration in melanoma cell lines. Results A significantly higher percentage of nevi (87%, compared to primary melanomas (20% and metastases (48%, expressed BRMS1 in the nucelus (p Waf1/Cip1 (p = 0.009. Cytoplasmic score index was inversely associated with nuclear p-Akt (p = 0.013 and positively associated with cytoplasmic p-ERK1/2 expression (p = 0.033. Nuclear BRMS1 expression in ≥ 10% of primary melanoma cells was associated with thicker tumors (p = 0.016 and decreased relapse-free period (p = 0.043. Nuclear BRMS1 was associated with expression of fatty acid binding protein 7 (FABP7; p = 0.011, a marker of invasion in melanomas. In line with this, repression of BRMS1 expression reduced the ability of melanoma cells to migrate and invade in vitro. Conclusion Our data suggest that BRMS1 is localized in cytoplasm and nucleus of melanocytic cells and that cellular localization determines its in vivo effect. We hypothesize that cytoplasmic BRMS1 restricts melanoma progression while nuclear BRMS1 possibly promotes melanoma cell invasion. Please see related article: http://www.biomedcentral.com/1741-7015/10/19

  4. Thin and thick primary cutaneous melanomas reveal distinct patterns of somatic copy number alterations.

    Science.gov (United States)

    Montagnani, Valentina; Benelli, Matteo; Apollo, Alessandro; Pescucci, Chiara; Licastro, Danilo; Urso, Carmelo; Gerlini, Gianni; Borgognoni, Lorenzo; Luzzatto, Lucio; Stecca, Barbara

    2016-05-24

    Cutaneous melanoma is one of the most aggressive type of skin tumor. Early stage melanoma can be often cured by surgery; therefore current management guidelines dictate a different approach for thin (thick (>4mm) melanomas. We have carried out whole-exome sequencing in 5 thin and 5 thick fresh-frozen primary cutaneous melanomas. Unsupervised hierarchical clustering analysis of somatic copy number alterations (SCNAs) identified two groups corresponding to thin and thick melanomas. The most striking difference between them was the much greater abundance of SCNAs in thick melanomas, whereas mutation frequency did not significantly change between the two groups. We found novel mutations and focal SCNAs in genes that are embryonic regulators of axon guidance, predominantly in thick melanomas. Analysis of publicly available microarray datasets provided further support for a potential role of Ephrin receptors in melanoma progression. In addition, we have identified a set of SCNAs, including amplification of BRAF and ofthe epigenetic modifier EZH2, that are specific for the group of thick melanomas that developed metastasis during the follow-up. Our data suggest that mutations occur early during melanoma development, whereas SCNAs might be involved in melanoma progression.

  5. Conjunctival amelanotic malignant melanoma arising in primary acquired melanosis sine pigmento.

    Science.gov (United States)

    Jay, V; Font, R L

    1998-01-01

    The authors describe an amelanotic malignant melanoma of the conjunctiva in association with primary acquired melanosis (PAM) sine pigmento, and highlight the clinical and pathologic features of this rare entity. Histopathologic and immunohistochemical studies were performed on a conjunctival tumor in a 54-year-old white woman. Case report. Histopathologic examination revealed an invasive amelanotic melanoma of the conjunctiva, with anterior orbital extension arising from intraepithelial dysplastic melanocytes that lacked melanin pigment (PAM sine pigmento). Both the malignant melanoma cells and the intraepithelial dysplastic melanocytes in the areas of PAM exhibited S-100 and HMB-45 positivity. The patient underwent an orbital exenteration that disclosed tumor within the anterior orbit inferiorly. Amelanotic invasive malignant melanoma can arise in association with PAM sine pigmento, as seen in our patient who had orbital invasion necessitating exenteration. This aggressive form of conjunctival melanoma is often associated with a poor prognosis and risk of metastatic disease. Absence of conjunctival pigmentation in PAM sine pigmento prevents early clinical detection of this variant of PAM. This lack of pigmentation also makes clinical diagnosis virtually impossible, and diagnosis can only be established histopathologically. Awareness of this nonpigmented variety of PAM is crucial for early recognition and appropriate management of the associated melanoma.

  6. Gallium-67-labeled lactam bridge-cyclized alpha-melanocyte stimulating hormone peptide for primary and metastatic melanoma imaging.

    Science.gov (United States)

    Guo, Haixun; Yang, Jianquan; Shenoy, Nalini; Miao, Yubin

    2009-12-01

    The purpose of this study was to examine the melanoma imaging properties of a novel 67Ga-labeled lactam bridge-cyclized alpha-melanocyte stimulating hormone (alpha-MSH) peptide. A lactam bridge-cyclized alpha-MSH peptide, DOTA-GlyGlu-CycMSH {DOTA-Gly-Glu-c[Lys-Nle-Glu-His-DPhe-Arg-Trp-Gly-Arg-Pro-Val-Asp]}, was synthesized and radiolabeled with 67Ga. The melanoma targeting and pharmacokinetic properties of 67Ga-DOTA-GlyGlu-CycMSH were determined in B16/F1 flank primary melanoma-bearing and B16/F10 pulmonary metastatic melanoma-bearing C57 mice. Flank primary melanoma and pulmonary metastatic melanoma imaging were performed by small animal single photon emission computed tomography (SPECT)/CT using 67Ga-DOTA-GlyGlu-CycMSH as an imaging probe. 67Ga-DOTA-GlyGlu-CycMSH was readily prepared with greater than 95% radiolabeling yield. 67Ga-DOTA-GlyGlu-CycMSH exhibited substantial tumor uptake (12.93 +/- 1.63%ID/g at 2 h postinjection) and prolonged tumor retention (5.02 +/- 1.35%ID/g at 24 h postinjection) in B16/F1 melanoma-bearing C57 mice. The uptake values for nontarget organs were generally low (<0.30%ID/g) except for the kidneys at 2, 4, and 24 h postinjection. 67Ga-DOTA-GlyGlu-CycMSH exhibited significantly (p < 0.05) higher uptakes (1.44 +/- 0.75%ID/g at 2 h postinjection and 1.49 +/- 0.69%ID/g at 4 h postinjection) in metastatic melanoma-bearing lung than those in normal lung (0.15 +/- 0.10%ID/g and 0.17 +/- 0.11%ID/g at 2 and 4 h postinjection, respectively). Both flank primary B16/F1 melanoma and B16/F10 pulmonary melanoma metastases were clearly visualized by SPECT/CT using 67Ga-DOTA-GlyGlu-CycMSH as an imaging probe 2 h postinjection. 67Ga-DOTA-GlyGlu-CycMSH exhibited favorable melanoma targeting and imaging properties, highlighting its potential as an effective imaging probe for early detection of primary and metastatic melanoma.

  7. Quantification of microRNA-21 and microRNA-125b in melanoma tissue

    DEFF Research Database (Denmark)

    Wandler, Anne; Riber-Hansen, Rikke; Hager, Henrik

    2017-01-01

    Although microRNAs (miRNAs) have emerged as potent mediators of melanoma development and progression, a precise understanding of their oncogenic role remains unclear. In this study, we analysed formalin-fixed and paraffin-embedded tissues from two separate melanoma cohorts and from a series...... the important involvement of different miRNAs in melanoma biology and may serve as solid basics for further miRNA investigations in melanoma formalin-fixed and paraffin-embedded tissue. In particular, there is increased expression of miR-21 in melanomas compared with benign nevi....

  8. HMB-45 may be a more sensitive maker than S-100 or Melan-A for immunohistochemical diagnosis of primary oral and nasal mucosal melanomas.

    Science.gov (United States)

    Yu, Chuan-Hang; Chen, Huang-Hsu; Liu, Chia-Ming; Jeng, Yung-Ming; Wang, Jeng-Tzung; Wang, Yi-Ping; Liu, Bu-Yuan; Sun, Andy; Chiang, Chun-Pin

    2005-10-01

    Primary mucosal melanomas (MMs) of the head and neck are a rare entity. Melanomas with characteristic melanin-pigmented tumor cells are easy to diagnose, but those without melanin-pigmented tumor cells, amelanotic melanomas, are difficult to identify and need immunohistochemistry (IHC) to confirm the final diagnosis. In this study, we examined the expression of three melanocytic differentiation markers, HMB-45, S-100, and Melan-A in primary oral and nasal MMs. We tried to evaluate whether HMB-45, S-100, and Melan-A were useful for diagnosis of primary oral and nasal MMs and to find out which marker was the best of the three. This study used IHC to examine the expression of HMB-45, S-100, and Melan-A in 17 formalin-fixed paraffin-embedded specimens of primary oral and nasal MMs. The staining intensities (SIs) and labeling indices (LIs) of HMB-45, S-100, and Melan-A in 17 MMs were calculated and compared between any two markers. Immunostaining results showed that the positive rate was 94% (16 of 17) for HMB-45, 88% (15 of 17) for S-100, and 71% (12 of 17) for Melan-A in 17 MMs. The SI of HMB-45 was significantly higher than that of S-100 (P = 0.0011) or of Melan-A (P = 0.0034). In addition, the mean LI of Melan-A (59 +/- 43%) was significantly lower than that of HMB-45 (83 +/- 28%, P = 0.0065) or of S-100 (79 +/- 33%, P = 0.0237). Our results indicate that both HMB-45 and S-100 show a high positive rate and LI in MMs and therefore may be good markers for immunohistochemical diagnosis of primary oral and nasal MMs. In addition, HMB-45 may be a more sensitive marker than S-100 because HMB-45 shows a significantly higher SI than S-100 in this study.

  9. One Step Melanoma Surgery for Patient with Thick Primary Melanomas: "To Break the Rules, You Must First Master Them!"

    Science.gov (United States)

    Tchernev, Georgi

    2018-02-15

    We present to the attention of the medical, dermatological and oncosurgical community data that serves to indicate the indispensability of optimisation of the algorithm and recommendations for diagnosis and surgical treatment of cutaneous melanoma. These recommendations could be referred to different subgroups of patients in different clinical stages as well as to patients with different initial characterisation (histological morphology) of the primary tumours. One step surgery is not a myth, even more, it could prove to be one of the best solutions for some patient collectives with advanced stages of melanoma. We present a case of a 74 - year old patient with a congenital medium sized melanocytic nevus, located directly above the lateral part of the elbow joint. In one month and a half, an achromatic nodular formation evolves with a diameter of 2.7 x 2.3 cm, prominent over the skin level, painful by palpation and spontaneously bleeding. By the anamnestic, clinical and dermoscopic findings the patient was diagnosed with nodular melanoma associated with a congenital medium sized melanocytic nevus. A primary excision with a field of safety 0.5 cm in all directions was performed. After confirmation of the primary diagnosis (tumour thickness 8 mm with no ultrasonographic detection of enlarged lymph nodes), seven days later are - excision was performed with an additional field of surgical safety of 1.5 cm in all directions. In this case remains unclear the following question: For what reason a preoperative high - frequent ultrasonography (HFUS) is not recommended to be used as it will allow only one surgical excision with the elimination of a tumour with a safety field of 2cm in all directions? The enigma about the obstacles preventing such a rational optimisation of the current diagnostic and therapeutic algorithm in patients with melanomas remains unresolved. One step surgery for cutaneous melanoma is widely used in many countries although it continues to be

  10. Assessment of the influence of one's education on early diagnosis of multiple primary cancer in patients with uveal melanoma.

    Science.gov (United States)

    Mierzwa-Dobranowska, Marzena; Romanowska-Dixon, Bozena

    2012-01-01

    This study will show a comparison of two groups of patients with uveal melanoma; one group with multiple primary cancer, and a second group with no identifiable second cancer, in terms of education and occupation. Study concerns 240 patients, who were isolated from patients being treated with uveal melanoma at the Department of Ophthalmology and Ocular Oncology Jagiellonian University Medical College in the period from 1998 to 2007. On the basis of medical history and medical records 97 patients were diagnosed with the one or more independent primary cancers. These patients were subjected to comparative analysis with a group of 143 patients with uveal melanoma as a control group. Analyzing the impact of education on the recognition of multiple primary cancer, there were significantly more frequent diagnoses of second primary cancers among patients with secondary and higher education than among those who had primary and vocational education. Among the obtained data on patients in the study group, the largest occupational group (according to the ISCO-88 (COM)) constituted "professionals". In the control group prevailed "craft and related trades workers". The results suggest the great importance of knowledge about risk factors for the development of cancer among patients with uveal melanoma and the ensuing more scrupulous search for succesive primary neoplasm and indicate the neccesity of organizing broad prophylactic actions. uveal melanoma, multiple primary cancer.

  11. Early detection and longitudinal monitoring of experimental primary and disseminated melanoma using [18F]ICF01006, a highly promising melanoma PET tracer

    International Nuclear Information System (INIS)

    Rbah-Vidal, Latifa; Vidal, Aurelien; Besse, Sophie; Audin, Laurent; Degoul, Francoise; Miot-Noirault, Elisabeth; Moins, Nicole; Auzeloux, Philippe; Chezal, Jean-Michel; Cachin, Florent; Bonnet, Mathilde; Askienazy, Serge; Dolle, Frederic

    2012-01-01

    Here, we report a new and rapid radiosynthesis of 18 F-N-[2-(diethylamino)ethyl]-6-fluoro-pyridine-3-carboxamide ([ 18 F]ICF01006), a molecule with a high specificity for melanotic tissue, and its evaluation in a murine model for early specific detection of pigmented primary and disseminated melanoma. [ 18 F]ICF01006 was synthesized using a new one-step bromine-for-fluorine nucleophilic heteroaromatic substitution. Melanoma models were induced by subcutaneous (primary tumour) or intravenous (lung colonies) injection of B16BL6 melanoma cells in C57BL/6J mice. The relevance and sensitivity of positron emission tomography (PET) imaging using [ 18 F]ICF01006 were evaluated at different stages of tumoural growth and compared to 18 F-fluorodeoxyglucose ([ 18 F]FDG). The fully automated radiosynthesis of [ 18 F]ICF01006 led to a radiochemical yield of 61 % and a radiochemical purity >99 % (specific activity 70-80 GBq/μmol; total synthesis time 42 min). Tumours were visualized before they were palpable as early as 1 h post-injection with [ 18 F]ICF01006 tumoural uptake of 1.64 ± 0.57, 3.40 ± 1.47 and 11.44 ± 2.67 percentage of injected dose per gram of tissue (%ID/g) at days 3, 5 and 14, respectively. [ 18 F]ICF01006 PET imaging also allowed detection of melanoma pulmonary colonies from day 9 after tumour cell inoculation, with a lung radiotracer accumulation correlated with melanoma invasion. At day 21, radioactivity uptake in lungs reached a value of 5.23 ± 2.08 %ID/g (versus 0.41 ± 0.90 %ID/g in control mice). In the two models, comparison with [ 18 F]FDG showed that both radiotracers were able to detect melanoma lesions, but [ 18 F]ICF01006 was superior in terms of contrast and specificity. Our promising results provide further preclinical data, reinforcing the excellent potential of [ 18 F]ICF01006 PET imaging for early specific diagnosis and follow-up of melanin-positive disseminated melanoma. (orig.)

  12. Metastatic melanoma after 23 years of primary ocular melanoma.

    LENUS (Irish Health Repository)

    Karde, Supriya Ramesh

    2016-11-23

    We describe a case of 52-year-old man who presented with an episode of tonic-clonic seizures. He had right ocular melanoma 23 years ago with subsequent enucleation which was the standard treatment at that time. CT scans of the brain and of the thorax-abdomen-pelvis revealed widespread metastatic lesions in the brain, lung and liver. Further investigations including bronchoscopy with cytopathology uncovered that the metastatic disease was a recurrence of ocular melanoma. He received palliative radiotherapy and died 6 months later. Ocular melanoma is often associated with fulminant metastatic disease after a period of dormancy. Thus, despite successful treatment of the localised disease at initial presentation, an effort is needed for optimal long-term follow-up plan in order to improve survival in case of recurrence.

  13. Melanoma-specific marker expression in skin biopsy tissues as a tool to facilitate melanoma diagnosis.

    Science.gov (United States)

    Alexandrescu, Doru T; Kauffman, C Lisa; Jatkoe, Timothy A; Hartmann, Dan P; Vener, Tatiana; Wang, Haiying; Derecho, Carlo; Rajpurohit, Yashoda; Wang, Yixin; Palma, John F

    2010-07-01

    Diagnosis of cutaneous melanoma requires accurate differentiation of true malignant tumors from highly atypical lesions, which lack the capacity to develop uncontrolled proliferation and to metastasize. We used melanoma markers from previous work to differentiate benign and atypical lesions from melanoma using paraffin-embedded tissue. This critical step in diagnosis generates the most uncertainty and discrepancy between dermatopathologists. A total of 193 biopsy tissues were selected: 47 melanomas, 48 benign nevi, and 98 atypical/suspicious, including 48 atypical nevi and 50 melanomas as later assigned by expert dermatopathologists. Performance for SILV, GDF15, and L1CAM normalized to TYR in unequivocal melanoma versus benign nevi resulted in an area under the curve (AUC) of 0.94, 0.67, and 0.5, respectively. SILV also differentiated atypical cases classified as melanoma from atypical nevi with an AUC=0.74. Furthermore, SILV showed a significant difference between suspicious melanoma and each suspicious atypia group: melanoma versus severe atypia and melanoma versus moderate atypia had P-values of 0.0077 and 0.0009, respectively. SILV showed clear discrimination between melanoma and benign unequivocal cases as well as between different atypia subgroups in the group of suspicious samples. The role and potential utility of this molecular assay as an adjunct to the morphological diagnosis of melanoma are discussed.

  14. Progressive Increase in Telomerase Activity From Benign Melanocytic Conditions to Malignant Melanoma

    Directory of Open Access Journals (Sweden)

    Ruben D. Ramirez

    1999-04-01

    Full Text Available The expression of telomerase activity and the in situ localization of the human telomerase RNA component (hTR in melanocytic skin lesions was evaluated in specimens from sixty-three patients. Specimens of melanocytic nevi, primary melanomas and subcutaneous metastases of melanoma were obtained from fifty-eight patients, whereas metastasized lymph nodes were obtained from five patients. Telomerase activity was determined in these specimens by using a Polymerase Chain Reaction—based assay (TRAP. High relative mean telomerase activity levels were detected in metastatic melanoma (subcutaneous metastasess = 54.5, lymph node metastasess = 56.5. Much lower levels were detected in primary melanomas, which increased with advancing levels of tumor cell penetration (Clark II = 0.02, Clark III = 1.1, and Clark IV = 1.9. Twenty-six formalin-fixed, paraffin-embedded melanocytic lesions were sectioned and analyzed for telomerase RNA with a radioactive in situ hybridization assay. In situ hybridization studies with a probe to the template RNA component of telomerase confirmed that expression was almost exclusively confined to tumor cells and not infiltrating lymphocytes. These results indicate that levels of telomerase activity and telomerase RNA in melanocytic lesions correlate well with clinical stage and could potentially assist in the diagnosis of borderline lesions.

  15. Time-trend of melanoma screening practice by primary care physicians: A meta-regression analysis

    OpenAIRE

    Valachis, Antonis; Mauri, Davide; Karampoiki, Vassiliki; Polyzos, Nikolaos P; Cortinovis, Ivan; Koukourakis, Georgios; Zacharias, Georgios; Xilomenos, Apostolos; Tsappi, Maria; Casazza, Giovanni

    2009-01-01

    Objective To assess whether the proportion of primary care physicians implementing full body skin examination (FBSE) to screen for melanoma changed over time. Methods Meta-regression analyses of available data. Data Sources: MEDLINE, ISI, Cochrane Central Register of Controlled Trials. Results Fifteen studies surveying 10,336 physicians were included in the analyses. Overall, 15%?82% of them reported to perform FBSE to screen for melanoma. The proportion of physicians using FBSE screening ten...

  16. Melanoma Patients with Unknown Primary Site or Nodal Recurrence after Initial Diagnosis Have a Favourable Survival Compared to Those with Synchronous Lymph Node Metastasis and Primary Tumour

    OpenAIRE

    Weide, Benjamin; Faller, Christine; Els?sser, Margrit; B?ttner, Petra; Pflugfelder, Annette; Leiter, Ulrike; Eigentler, Thomas Kurt; Bauer, J?rgen; Meier, Friedegund; Garbe, Claus

    2013-01-01

    BACKGROUND: A direct comparison of prognosis between patients with regional lymph node metastases (LNM) detected synchronously with the primary melanoma (primary LNM), patients who developed their first LNM subsequently (secondary LNM) and those with initial LNM in melanoma with unknown primary site (MUP) is missing thus far. PATIENTS AND METHODS: Survival of 498 patients was calculated from the time point of the first macroscopic LNM using Kaplan Meier and multivariate Cox hazard regression ...

  17. An Endogenous Electron Spin Resonance (ESR signal discriminates nevi from melanomas in human specimens: a step forward in its diagnostic application.

    Directory of Open Access Journals (Sweden)

    Eleonora Cesareo

    Full Text Available Given the specific melanin-associated paramagnetic features, the Electron Spin Resonance (ESR, called also Electron Paramagnetic Resonance, EPR analysis has been proposed as a potential tool for non-invasive melanoma diagnosis. However, studies comparing human melanoma tissues to the most appropriate physiological counterpart (nevi have not been performed, and ESR direct correlation with melanoma clinical features has never been investigated. ESR spectrum was obtained from melanoma and non-melanoma cell-cultures as well as mouse melanoma and non-melanoma tissues and an endogenous ESR signal (g = 2.005 was found in human melanoma cells and in primary melanoma tissues explanted from mice, while it was always absent in non-melanoma samples. These characteristics of the measured ESR signal strongly suggested its connection with melanin. Quantitative analyses were then performed on paraffin-embedded human melanoma and nevus sections, and validated on an independent larger validation set, for a total of 112 sections (52 melanomas, 60 nevi. The ESR signal was significantly higher in melanomas (p = 0.0002 and was significantly different between "Low Breslow's and "High Breslow's" depth melanomas (p<0.0001. A direct correlation between ESR signal and Breslow's depth, expressed in millimetres, was found (R = 0.57; p<0.0001. The eu/pheomelanin ratio was found to be significantly different in melanomas "Low Breslow's" vs melanomas "High Breslow's" depth and in nevi vs melanomas "High Breslow's depth". Finally, ROC analysis using ESR data discriminated melanomas sections from nevi sections with up to 90% accuracy and p<0.0002. In the present study we report for the first time that ESR signal in human paraffin-embedded nevi is significantly lower than signal in human melanomas suggesting that spectrum variations may be related to qualitative melanin differences specifically occurring in melanoma cells. We therefore conclude that this ESR signal

  18. primary malignant amelanotic melanoma arising from a vitiligo patch

    African Journals Online (AJOL)

    2014-05-05

    May 5, 2014 ... Malignant melanoma is a rare tumour in people of. African descent including those affected by albinism. (1). The incidence of malignant melanoma in Africans is estimated to ranging from 0.5 to 1.5 per 100,000 people (2). Acrolentiginous melanoma is the most common type of melanoma in this population.

  19. Primary Dermal Melanoma in a Patient with a History of Multiple Malignancies: A Case Report with Molecular Characterization

    Directory of Open Access Journals (Sweden)

    Germana Sini

    2013-07-01

    Full Text Available Introduction: Primary dermal melanoma (PDM is a recently described clinical entity accounting for less than 1% of all melanomas. Histologically, it is located in the dermis or subcutaneous tissue, and it shows no connections with the overlying epidermis. The differential diagnosis is principally made along with that of metastatic cutaneous melanoma. Case Report: A 72-year-old Caucasian woman with a history of multiple cancers (metachronous bilateral breast cancer, meningioma, clear cell renal cell carcinoma, uterine fibromatosis and intestinal adenomatous polyposis, came to our attention with a nodular lesion on her back. After removal of the lesion, the histology report indicated malignant PDM or metastatic malignant melanoma. The clinical and instrumental evaluation of the patient did not reveal any other primary tumour, suggesting the primitive nature of the lesion. The absence of an epithelial component argued for a histological diagnosis of PDM. Subsequently, the patient underwent a wide surgical excision with sentinel node biopsy, which was positive for metastatic melanoma. Finally, the mutational status was studied in the main genes that regulate proliferation, apoptosis and cellular senescence. No pathogenetic mutations in CDKN2A, BRAF, NRAS, KRAS, cKIT, TP53 and PTEN genes were observed. This suggests that alternative pathways and low-frequency alterations may be involved. Conclusions: The differential diagnosis between PDM and isolated metastatic melanoma depends on the negativity of imaging studies and clinical findings for other primary lesions. This distinction is important because 5-year survival rates in such cases are higher than in metastatic cases (80-100 vs. 5-20%, respectively.

  20. Development of a primary melanoma in situ within a full-thickness skin graft overlying a free muscle flap: a case report.

    Science.gov (United States)

    Dabek, Robert J; Baletic, Nemanja; McUmber, Harrison; Nahed, Brian; Haynes, Alex; Eberlin, Kyle R; Bojovic, Branko

    2018-01-01

    The development of a primary melanoma within the confines of free tissue transfer is a rare occurrence. In this report, we describe the development of a primary melanoma in situ within a full-thickness skin graft overlying a free latissimus dorsi muscle flap used to cover a scalp defect.

  1. Primary Malignant Melanoma of the Genitourinary Tract with Upper and Lower Tracts Involvement

    Directory of Open Access Journals (Sweden)

    Broderick Sutton

    2013-01-01

    Full Text Available A 91-year-old female presented with lower extremity swelling and shortness of breath. Laboratory analysis revealed elevations in blood urea nitrogen and creatinine along with microscopic hematuria on urinalysis. Computed tomography imaging showed moderate right hydronephrosis with dilatation of the proximal ureter with a soft tissue density at a transition point. Endoscopic evaluation revealed multiple raised, fleshy, and hemorrhagic masses throughout the bladder which are present in both ureters. Biopsy of these lesions revealed malignant melanoma invading the lamina propria. No dermatologic lesions were identified suggesting a primary malignant melanoma of the genitourinary system.

  2. Dark sputum: An atypical presentation of primary pulmonary malignant melanoma

    Directory of Open Access Journals (Sweden)

    Alida Filippini

    2015-01-01

    Primary lung melanoma is an uncommon neoplasm that may be confused with more conventional types of lung cancer. Careful interpretation of histopathological information in correlation with all other clinical, laboratory and imaging studies may be needed to establish a diagnosis. Evaluation for metastases should include looking at the eyes, brain, skin. Due to the small number of cases reported in literature, there is no experience on the management and the prognosis of the disease.

  3. Primary malignant melanoma of the female urethra: Report of a rare neoplasm of the urinary tract

    Directory of Open Access Journals (Sweden)

    Namita Bhutani

    Full Text Available Introduction: Melanoma is a malignant tumor that can affect any area of the anatomical economy. Its occurance in the female urethra is extremely rare. We report a case of primary malignant urethral melanoma developed in an elderly female patient. Presentation of case: A 70 years old female presented with dysuria, poor stream, gross haematuria, intermittent blood spots, and a painful mass. On physical examination, there were no suspicious lesions on the skin. On external genital examination, a lesion at the level of the urethral meatus was observed. The mass was removed by wide local excision under spinal anaesthesia. The pathological diagnosis was malignant melanoma of the urethra. Discussion: The common presentations include bleeding and/or discharge per urethra, voiding dysfunction and the presence of tumor mass. Survival depends on the stage, location and size of the neoplasm at the time of diagnosis. Despite major surgery, radiotherapy or immunotherapy; malignant melanoma usually has a poor prognosis. Conclusion: Melanoma of the female urethra is an extremely uncommon pathology leading to paucity of literature and any definite recommendations regarding management. The histological and immunohistochemical findings can be helpful in making an early and accurate diagnosis of malignant melanoma in the urogenital region. Keywords: Case report, Female urethral cancer, Immunohistochemistry, Malignant melanoma, Urethral neoplasm

  4. Gingival osteogenic melanoma in two dogs.

    Science.gov (United States)

    Ellis, Angela E; Harmon, Barry G; Miller, Debra L; Northrup, Nicole C; Latimer, Kenneth S; Uhl, Elizabeth W

    2010-01-01

    Osteogenic melanoma is a rare variant of metaplastic malignant melanoma in human medicine and appears to be a similarly rare variant in dogs. Two dogs with oral malignant melanoma with neoplastic bone formation are reported in this study. Both tumors were characterized by malignant melanocytes that transitioned into neoplastic bone at the deep margins of the neoplasm. Immunohistochemical analysis revealed S100- and Melan-A-positive neoplastic cells adjacent to, and occasionally embedded within, an osteoid and chondroblastic matrix. Scattered clusters of neoplastic cells were also positive for osteocalcin. The findings indicate that in dogs, as in humans, neoplastic melanocytes have metaplastic potential and can be osteogenic.

  5. Time-trend of melanoma screening practice by primary care physicians: a meta-regression analysis.

    Science.gov (United States)

    Valachis, Antonis; Mauri, Davide; Karampoiki, Vassiliki; Polyzos, Nikolaos P; Cortinovis, Ivan; Koukourakis, Georgios; Zacharias, Georgios; Xilomenos, Apostolos; Tsappi, Maria; Casazza, Giovanni

    2009-01-01

    To assess whether the proportion of primary care physicians implementing full body skin examination (FBSE) to screen for melanoma changed over time. Meta-regression analyses of available data. MEDLINE, ISI, Cochrane Central Register of Controlled Trials. Fifteen studies surveying 10,336 physicians were included in the analyses. Overall, 15%-82% of them reported to perform FBSE to screen for melanoma. The proportion of physicians using FBSE screening tended to decrease by 1.72% per year (P =0.086). Corresponding annual changes in European, North American, and Australian settings were -0.68% (P =0.494), -2.02% (P =0.044), and +2.59% (P =0.010), respectively. Changes were not influenced by national guide-lines. Considering the increasing incidence of melanoma and other skin malignancies, as well as their relative potential consequences, the FBSE implementation time-trend we retrieved should be considered a worrisome phenomenon.

  6. Cryotherapy for conjunctival primary acquired melanosis and malignant melanoma. Experience with 62 cases.

    Science.gov (United States)

    Jakobiec, F A; Rini, F J; Fraunfelder, F T; Brownstein, S

    1988-08-01

    Sixty-two patients were treated by some combination of cryotherapy and surgery with an average follow-up of 3.3 years for one of the following diseases: focal or diffuse flat conjunctival primary acquired melanosis (PAM) with atypia but without a nodule of melanoma (10 cases); unifocal malignant melanoma with or without focal or diffuse PAM (30 cases); and multinodular/multicentric melanoma with and without PAM (22 cases). Of the ten patients who had PAM with atypia, invasive nodules of malignant melanoma did not develop. A second treatment was required to control the disease in four of the ten patients with extensive or diffuse lesions, and one has mild persistent disease. Of the 30 patients with unifocal nodules of malignant melanoma, 27 remained free of recurrence after one treatment, and 2 are asymptomatic after two treatments. One patient with a thick nodule at presentation required a parotidectomy and radical neck dissection for cervical metastases after recurrence in the conjunctival sac. In the group of 22 patients with multinodular malignant melanoma, only two did not have recurrent disease after one treatment. Of those who received multiple therapies, seven remained free of recurrence for at least 2 years after the last treatment; regional or distant metastases developed in nine; four required exenteration; and eight died. Conjunctival adjunctive cryotherapy avoids exenteration in extensive lesions of pure PAM and in unifocal melanoma, but even after multiple therapies, multinodular malignant melanoma had a 45% rate of metastasis. Metastasis was related to the presence of PAM sine pigmento in four patients (microscopically but not clinically detectable PAM); to the location of the nodules (9 of 10 patients who experienced metastases had forniceal, palpebral, and/or caruncular nodules); to the thickness or depth of invasion of the nodules (greater than 2 mm); and to the development of intralymphatic spread ("in-transit" local metastasis) within the

  7. DNA-index and stereological estimation of nuclear volume in primary and metastatic malignant melanomas

    DEFF Research Database (Denmark)

    Sørensen, Flemming Brandt; Kristensen, I B; Grymer, F

    1990-01-01

    The aim of this study was to investigate the relationship between physical nuclear volume and ploidy level in malignant melanomas, and to analyse the heterogeneity of these two parameters among primary and corresponding secondary tumours. Unbiased stereological estimates of nuclear volume can...

  8. High expression of Wee1 is associated with poor disease-free survival in malignant melanoma: potential for targeted therapy.

    Directory of Open Access Journals (Sweden)

    Gry Irene Magnussen

    Full Text Available Notoriously resistant malignant melanoma is one of the most increasing forms of cancer worldwide; there is thus a precarious need for new treatment options. The Wee1 kinase is a major regulator of the G(2/M checkpoint, and halts the cell cycle by adding a negative phosphorylation on CDK1 (Tyr15. Additionally, Wee1 has a function in safeguarding the genome integrity during DNA synthesis. To assess the role of Wee1 in development and progression of malignant melanoma we examined its expression in a panel of paraffin-embedded patient derived tissue of benign nevi and primary- and metastatic melanomas, as well as in agarose-embedded cultured melanocytes. We found that Wee1 expression increased in the direction of malignancy, and showed a strong, positive correlation with known biomarkers involved in cell cycle regulation: Cyclin A (p<0.0001, Ki67 (p<0.0001, Cyclin D3 (p = 0.001, p21(Cip1/WAF1 (p = 0.003, p53 (p = 0.025. Furthermore, high Wee1 expression was associated with thicker primary tumors (p = 0.001, ulceration (p = 0.005 and poor disease-free survival (p = 0.008. Transfections using siWee1 in metastatic melanoma cell lines; WM239(WTp53, WM45.1(MUTp53 and LOX(WTp53, further support our hypothesis of a tumor promoting role of Wee1 in melanomas. Whereas no effect was observed in LOX cells, transfection with siWee1 led to accumulation of cells in G(1/S and S phase of the cell cycle in WM239 and WM45.1 cells, respectively. Both latter cell lines displayed DNA damage and induction of apoptosis, in the absence of Wee1, indicating that the effect of silencing Wee1 may not be solely dependent of the p53 status of the cells. Together these results reveal the importance of Wee1 as a prognostic biomarker in melanomas, and indicate a potential role for targeted therapy, alone or in combination with other agents.

  9. Melanoma with second myxoid stromal changes after personally applied prolonged phototherapy.

    Science.gov (United States)

    Ulamec, Monika; Soldo-Belić, Antica; Vucić, Majda; Buljan, Marija; Kruslin, Bozo; Tomas, Davor

    2008-04-01

    Most malignant melanomas are easily diagnosed; however, melanoma is also one of the lesions most frequently reported to mimic other tumors. One of the most difficult patterns to recognize is characterized by prominent myxoid matrix. A case is presented of primary cutaneous melanoma with abundant myxoid matrix in a patient who underwent prolonged phototherapy. Three years before, after getting sunburns, the patient noticed changes of a congenital nevus located in the area of sunburns. It became darker, started to blanch, and grew, with occasional bleeding. Without consulting a physician, the patient applied phototherapy onto the area for 30 months. He used a Bioptron lamp with polarized, polychromatic, incoherent light, at a wavelength from 480 to 3400 nm, without ultraviolet radiation. Clinically, the lesion was unevenly pigmented, ulcerated, covered with hemorrhagic crust, and measuring 3.5 cm in greatest dimension, with a satellite nodule. Multiple metastatic subcutaneous nodules were also found on the scalp and trunk. Histologically, the primary tumor and metastases were composed of nests and pseudotubular formations of polygonal, spindle, and stellate cells embedded in abundant myxoid stroma that comprised more than 80% of the tumor mass. Focally, in the epidermis and papillary dermis, nests of atypical melanocytes and numerous melanophages were observed. Chemotherapy and immunotherapy were administered as suggested by an oncologist. The patient died from distant metastases 6 months after the diagnosis. Although some authors believe that myxoid changes do not seem to alter the behavior of melanoma, it remains an important differential diagnosis issue.

  10. The monoclonal antibody SM5-1 recognizes a fibronectin variant which is widely expressed in melanoma

    Directory of Open Access Journals (Sweden)

    Guo Yajun

    2006-01-01

    Full Text Available Abstract Background Previously we have generated the monoclonal antibody SM5-1 by using a subtractive immunization protocol of human melanoma. This antibody exhibits a high sensitivity for primary melanomas of 99% (248/250 tested and for metastatic melanoma of 96% (146/151 tested in paraffin embedded sections. This reactivity is superior to the one obtained by HMB-45, anti-MelanA or anti-Tyrosinase and is comparable to anti-S100. However, as compared to anti-S100, the antibody SM5-1 is highly specific for melanocytic lesions since 40 different neoplasms were found to be negative for SM5-1 by immunohistochemistry. The antigen recognized by SM5-1 is unknown. Methods In order to characterize the antigen recognized by mAb SM5-1, a cDNA library was constructed from the metastatic human melanoma cell line SMMUpos in the Uni-ZAP lambda phage and screened by mAb SM5-1. The cDNA clones identified by this approach were then sequenced and subsequently analyzed. Results Sequence analysis of nine independent overlapping clones (length 3100–5600 bp represent fibronectin cDNA including the ED-A, but not the ED-B region which are produced by alternative splicing. The 89aa splicing variant of the IIICS region was found in 8/9 clones and the 120aa splicing variant in 1/9 clones, both of which are included in the CS1 region of fibronectin being involved in melanoma cell adhesion and spreading. Conclusion The molecule recognized by SM5-1 is a melanoma associated FN variant expressed by virtually all primary and metastatic melanomas and may play an important role in melanoma formation and progression. This antibody is therefore not only of value in immunohistochemistry, but potentially also for diagnostic imaging and immunotherapy.

  11. Primary localization and tumor thickness as prognostic factors of survival in patients with mucosal melanoma.

    Directory of Open Access Journals (Sweden)

    Tarun Mehra

    Full Text Available Data on survival with mucosal melanoma and on prognostic factors of are scarce. It is still unclear if the disease course allows for mucosal melanoma to be treated as primary cutaneous melanoma or if differences in overall survival patterns require adapted therapeutic approaches. Furthermore, this investigation is the first to present 10-year survival rates for mucosal melanomas of different anatomical localizations.116 cases from Sep 10 1984 until Feb 15 2011 retrieved from the Comprehensive Cancer Center and of the Central Register of the German Dermatologic Society databases in Tübingen were included in our analysis. We recorded anatomical location and tumor thickness, and estimated overall survival at 2, 5 and 10 years and the mean overall survival time. Survival times were analyzed with the Kaplan-Meier method. The log-rank test was used to compare survival times by localizations and by T-stages.We found a median overall survival time of 80.9 months, with an overall 2-year survival of 71.7%, 5-year survival of 55.8% and 10-year survival of 38.3%. The 10-year survival rates for patients with T1, T2, T3 or T4 stage tumors were 100.0%, 77.9%, 66.3% and 10.6% respectively. 10-year survival of patients with melanomas of the vulva was 64.5% in comparison to 22.3% of patients with non-vulva mucosal melanomas.Survival times differed significantly between patients with melanomas of the vulva compared to the rest (p = 0.0006. It also depends on T-stage at the time of diagnosis (p < 0.0001.

  12. Melanoma patients with unknown primary site or nodal recurrence after initial diagnosis have a favourable survival compared to those with synchronous lymph node metastasis and primary tumour.

    Directory of Open Access Journals (Sweden)

    Benjamin Weide

    Full Text Available BACKGROUND: A direct comparison of prognosis between patients with regional lymph node metastases (LNM detected synchronously with the primary melanoma (primary LNM, patients who developed their first LNM subsequently (secondary LNM and those with initial LNM in melanoma with unknown primary site (MUP is missing thus far. PATIENTS AND METHODS: Survival of 498 patients was calculated from the time point of the first macroscopic LNM using Kaplan Meier and multivariate Cox hazard regression analysis. RESULTS: Patients with secondary LNM (HR = 0.67; p = 0.009 and those with initial LNM in MUP (HR = 0.45; p = 0.008 had a better prognosis compared to patients with primary LNM (median survival time 52 and 65 vs. 24 months, respectively. A high number of involved nodes, the presence of in-transit/satellite metastases and male gender had an additional independent unfavourable effect. CONCLUSIONS: Survival of patients with LNM in MUP and with secondary LNM is similar and considerably more favourable compared to those with primary LNM. This difference needs to be considered during patient counselling and for stratification purposes in clinical trials. The assumption of an immune privilege of patients with MUP which is responsible for rejection of the primary melanoma, and results in a favourable prognosis is not supported by our data.

  13. Immunohistochemical detection of XIAP in melanoma.

    Science.gov (United States)

    Emanuel, Patrick O M; Phelps, Robert G; Mudgil, Adarsh; Shafir, Michail; Burstein, David E

    2008-03-01

    The X-linked inhibitor of apoptosis protein (XIAP) is the most potent of the inhibitor of apoptosis family of eight proteins. High levels of XIAP have been found in melanoma cell lines and are believed to play a role in therapeutic resistance in a number of malignancies. XIAP expression has not been investigated in clinically obtained melanoma tissue samples, nor have studies attempted to correlate XIAP expression with prognostic variables or clinical aggressiveness of melanomas. Sixty-seven patients with primary cutaneous malignant melanoma for whom clinical follow up was available were identified from the records of the Mount Sinai Hospital, comprising 37 thin melanomas (Breslow thickness 1.0 mm). Archival paraffin sections from primary lesions and corresponding metastases were stained with monoclonal anti-XIAP antibody using routine immunohistochemical methods. Six benign intradermal nevi and four in situ melanomas were XIAP negative. 9 of 37 thin melanomas (24%) were XIAP positive. In contrast, 21 of 30 (73%) thick melanomas were XIAP positive, including 3 of 4 ulcerated melanomas that were strongly positive. Over a follow-up period ranging from 6 months to 6 years, 23 melanomas metastasized (22 thick, 1 thin). In total, XIAP was immunohistochemically detected in 17 of 23 metastases (74%). Metastasis occurred in 1 of 9 XIAP-positive thin melanomas; 0 of 28 XIAP-negative thin melanomas; 17 of 22 XIAP-positive thick melanomas, and 5 of 8 XIAP-negative thick melanomas (63%). XIAP is immunohistochemically detectable nearly three times more frequently in thick compared with thin melanomas. These results suggest that XIAP elevation may be correlated with increasing melanoma thickness and tumor progression.

  14. Melanoma of unknown origin: a case series.

    LENUS (Irish Health Repository)

    Kelly, J

    2010-12-01

    The natural history of metastatic melanoma involving lymph nodes, in the absence of a known primary site (cutaneous, ocular or mucosal) has, to date, been poorly defined; and the optimal management of this rare subtype of disease is therefore unclear. Melanomas of unknown primary site (MUP) are estimated to comprise between 3.7 and 6% of all melanomas (Anbari et al. in Cancer 79:1861-1821, 1997).

  15. Metastatic melanoma of mesentery

    International Nuclear Information System (INIS)

    Shamim, M. S.; Ali, S.A.; Shirazi, B.; Shamim, M.

    2004-01-01

    A case of malignant melanoma metastatic to small bowel mesentery in an old female is reported. Her primary malignant melanoma of nasal mucosa was already treated. She presented with intestinal obstruction, underwent surgical excision of the tumour and was tumour-free postoperatively. (author)

  16. RARE METASTASES OF MALIGNANT MELANOMA

    Directory of Open Access Journals (Sweden)

    Marija Trenkić-Božinović

    2014-09-01

    Full Text Available Melanomas are malignant neoplasms that originate from melanocytes. The most common are on the skin and mucous membranes. Choroidal melanomas are quite different from cutaneous melanomas with regard to presentation, metastases, and treatment. We report two cases of metastatic gastric malignant melanoma of the eye and skin, with reference to the literature. The first patient was a woman aged 23 years, who underwent gastrectomy 22 months after enucleation of the eye due to malignant choroid melanoma. The second patient was a man, 72 years old, who underwent surgery 28 months before because of malignant melanoma of the skin of the forehead. Paraffin sections, 4 μm thick were stained using a classic method, as well as immunohistochemical DAKO APAAP method, using a specific S - 100 antibody and Melan A antibodies. The stomach is considered a rare place for the development of metastases. Metastases in the stomach are often limited to the submucosal as well as the serousmuscular layer, as noted in one of our patients. Metastatic melanoma of the gastrointestinal tract should be suspected in any patient with a history of malignant melanoma and new gastrointestinal symptoms. Because of the similarity between certain common histopathological types of malignant melanoma, primarily achromatic, and types of primary cancers of the stomach, the following immunohistochemical studies are needed: Melan A and S - 100 protein ( markers of malignant melanoma , as well as mucins: MUC5AC, MUC2 and CDX2 ( markers of different types of primary gastric carcinoma.

  17. Primary melanoma of oral mucosa: A case report and review of literature

    Directory of Open Access Journals (Sweden)

    Raman Preet Kaur Bhullar

    2012-01-01

    Full Text Available Primary oral melanoma is a rare neoplasm of melanocytic origin, accounting for 0.5% of all oral malignancies. The "chameleonic" presentation of a mainly asymptomatic condition, rarity of this lesion, poor prognosis, and the necessity of a highly specialized treatment are factors that should be seriously considered by the involved health provider. Here is a case report presenting a malignant melanoma of oral mucosa in 48-year-old male patient on maxillary gingiva. The lesion was removed by partial maxillectomy and patient is disease free after 11 months of regular followup. This case provides an example of how dental clinicians play a major role in the identification of pigmented lesions of oral cavity and also emphasize on the fact that any pigmented lesion detected in the oral cavity may exhibit potential growth and should be submitted to biopsy to exclude malignancy.

  18. Primary amelanotic malignant melanoma of the male urethra with inguinal lymph node metastasis successfully controlled by nivolumab: A case report

    Directory of Open Access Journals (Sweden)

    Takashi Tokita

    2018-05-01

    Full Text Available We report a rare case of primary amelanotic malignant melanoma of the male urethra. A 65-year-old man with a urethral mass was referred to our hospital. A pathological diagnosis of a biopsy specimen revealed malignant melanoma. Thereafter, the patient underwent partial penectomy. The histopathological diagnosis was amelanotic malignant melanoma of the urethra. The patient had received DAV-Feron in an adjuvant setting; however, PET-CT revealed multiple metastasis. After receiving more than 10 cycles of nivolumab, the accumulation of FDG was no longer observed on PET-CT. The patient is currently free from recurrence at 20 months after nivolumab treatment. Keywords: Melanoma, Urethral neoplasm, Inguinal lymphadenectomy, Nivolumab

  19. Proteomics in uveal melanoma.

    LENUS (Irish Health Repository)

    Ramasamy, Pathma

    2014-01-01

    Uveal melanoma is the most common primary intraocular malignancy in adults, with an incidence of 5-7 per million per year. It is associated with the development of metastasis in about 50% of cases, and 40% of patients with uveal melanoma die of metastatic disease despite successful treatment of the primary tumour. The survival rates at 5, 10 and 15 years are 65%, 50% and 45% respectively. Unlike progress made in many other areas of cancer, uveal melanoma is still poorly understood and survival rates have remained similar over the past 25 years. Recently, advances made in molecular genetics have improved our understanding of this disease and stratification of patients into low risk and high risk for developing metastasis. However, only a limited number of studies have been performed using proteomic methods. This review will give an overview of various proteomic technologies currently employed in life sciences research, and discuss proteomic studies of uveal melanoma.

  20. Characterization of Melanin Radicals in Paraffin-embedded Malignant Melanoma and Nevus Pigmentosus Using X-band EPR and EPR Imaging.

    Science.gov (United States)

    Nakagawa, Kouichi; Minakawa, Satoko; Sawamura, Daisuke; Hara, Hideyuki

    2017-01-01

    Continuous wave electron paramagnetic resonance (CW EPR) and X-band (9 GHz) EPR imaging (EPRI) were used to nondestructively investigate the possible differentiation between malignant melanoma (MM) and nevus pigmentosus (NP) melanin radicals in paraffin-embedded specimens. The EPR spectra of both samples were analyzed using linewidth, spectral pattern, and X-band EPRI. The CW-EPR spectra of the MM showed an additional signal overlap. Eumelanin- and pheomelanin-related radicals were observed in the MM specimens. The EPR results revealed that the peak-to-peak linewidths (ΔH pp ) of paraffin-embedded MM and NP samples were 0.65 ± 0.01 and 0.69 ± 0.01 mT, respectively. The g-value was 2.005 for both samples. Moreover, the two-dimensional (2D) EPRI of the MM showed different signal intensities at the different tumor stages, unlike the NP, which displayed fewer variations in signal intensity. Thus, the present results suggest that EPR and 2D EPRI can be useful for characterization of the two melanin radicals in the MM and for determination of their size and concentration.

  1. Melanoma cell-derived exosomes promote epithelial-mesenchymal transition in primary melanocytes through paracrine/autocrine signaling in the tumor microenvironment

    Science.gov (United States)

    Xiao, Deyi; Barry, Samantha; Kmetz, Daniel; Egger, Michael; Pan, Jianmin; Rai, Shesh N; Qu, Jifu; McMasters, Kelly M.; Hao, Hongying

    2016-01-01

    The tumor microenvironment is abundant with exosomes that are secreted by the cancer cells themselves. Exosomes are nanosized, organelle-like membranous structures that are increasingly being recognized as major contributors in the progression of malignant neoplasms. A critical element in melanoma progression is its propensity to metastasize, but little is known about how melanoma cell-derived exosomes modulate the microenvironment to optimize conditions for tumor progression and metastasis. Here, we provide evidence that melanoma cell-derived exosomes promote phenotype switching in primary melanocytes through paracrine/autocrine signaling. We found that the mitogen-activated protein kinase (MAPK) signaling pathway was activated during the exosome-mediated epithelial-to-mesenchymal transition (EMT)-resembling process, which promotes metastasis. Let-7i, an miRNA modulator of EMT, was also involved in this process. We further defined two other miRNA modulators of EMT (miR-191 and let-7a) in serum exosomes for differentiating stage I melanoma patients from non-melanoma subjects. These results provide the first strong molecular evidence that melanoma cell-derived exosomes promote the EMT-resembling process in the tumor microenvironment. Thus, novel strategies targeting EMT and modulating the tumor microenvironment may emerge as important approaches for the treatment of metastatic melanoma. PMID:27063098

  2. Sporadic naturally occurring melanoma in dogs as a preclinical model for human melanoma.

    Science.gov (United States)

    Simpson, R Mark; Bastian, Boris C; Michael, Helen T; Webster, Joshua D; Prasad, Manju L; Conway, Catherine M; Prieto, Victor M; Gary, Joy M; Goldschmidt, Michael H; Esplin, D Glen; Smedley, Rebecca C; Piris, Adriano; Meuten, Donald J; Kiupel, Matti; Lee, Chyi-Chia R; Ward, Jerrold M; Dwyer, Jennifer E; Davis, Barbara J; Anver, Miriam R; Molinolo, Alfredo A; Hoover, Shelley B; Rodriguez-Canales, Jaime; Hewitt, Stephen M

    2014-01-01

    Melanoma represents a significant malignancy in humans and dogs. Different from genetically engineered models, sporadic canine melanocytic neoplasms share several characteristics with human disease that could make dogs a more relevant preclinical model. Canine melanomas rarely arise in sun-exposed sites. Most occur in the oral cavity, with a subset having intra-epithelial malignant melanocytes mimicking the in situ component of human mucosal melanoma. The spectrum of canine melanocytic neoplasia includes benign lesions with some analogy to nevi, as well as invasive primary melanoma, and widespread metastasis. Growing evidence of distinct subtypes in humans, differing in somatic and predisposing germ-line genetic alterations, cell of origin, epidemiology, relationship to ultraviolet radiation and progression from benign to malignant tumors, may also exist in dogs. Canine and human mucosal melanomas appear to harbor BRAF, NRAS, and c-kit mutations uncommonly, compared with human cutaneous melanomas, although both species share AKT and MAPK signaling activation. We conclude that there is significant overlap in the clinical and histopathological features of canine and human mucosal melanomas. This represents opportunity to explore canine oral cavity melanoma as a preclinical model. © 2013 The Authors. Pigment Cell & Melanoma Research published by John Wiley & Sons Ltd.

  3. Satellite in transit metastases in rapidly fatal conjunctival melanoma: implications for angiotropism and extravascular migratory metastasis (description of a murine model for conjunctival melanoma).

    Science.gov (United States)

    Barnhill, Raymond L; Lemaitre, Stéphanie; Lévy-Gabrielle, Christine; Rodrigues, Manuel; Desjardins, Laurence; Dendale, Rémi; Vincent-Salomon, Anne; Roman-Roman, Sergio; Lugassy, Claire; Cassoux, Nathalie

    2016-02-01

    Little information is currently available concerning loco-regional metastases such as satellite and in transit metastases and their natural history in conjunctival melanoma as compared to cutaneous melanoma. Angiotropism, a marker of extravascular migration of melanoma cells along vascular channels, often appears responsible for microscopic satellite, satellite and in transit metastases development in cutaneous melanoma. In addition, diffuse tissue microscopic satellites are correlated with widespread melanoma dissemination and death. Herein we report rapid conjunctival melanoma progression and a fatal outcome in four of five patients following recurrence as satellite in transit metastases. Five patients aged 31, 60, 63, 56, and 67 years developed primary conjunctival melanoma, histologically characterised by tumour thicknesses of 4, 4, 1.1, 3, and 2 mm. Two or more conjunctival melanomas manifested ulceration, significant mitotic rates, necrosis, angiotropism, and intralesional transformation. The conjunctival melanoma recurred in a matter of months as one or more discrete satellite in transit lesions in the vicinity of the primary melanoma. Histological examination revealed well-defined micronodules containing atypical melanocytes in the subepithelial connective tissue stroma. All lesions were extravascular and most appeared angiotropic. Four of five patients subsequently developed parotid or other loco-regional nodal disease and rapidly ensuing widespread metastases and death. The time course from diagnosis to the demise of the patients averaged about 13 (range 7-20) months. Our findings suggest that satellite in transit metastases constitute an important new risk marker for possible rapid metastatic disease progression and death in patients with conjunctival melanoma. This finding appears to take on even greater significance if such lesions develop rapidly, i.e., in a matter of weeks or months following diagnosis of primary conjunctival melanoma, and if the

  4. Epidermotropic metastatic melanoma with perilesional depigmentation in an Indian male

    Directory of Open Access Journals (Sweden)

    Bhavana Doshi

    2013-01-01

    Full Text Available Melanoma is a rare form of cutaneous malignancy encountered in the dark skin population. Epidermotropic metastatic melanoma is a rare form of cutaneous metastatic melanoma which can mimic primary melanoma on histopathology. Hence its differentiation is of immense prognostic importance. The occurrence of rim of depigmentation around the primary cutaneous melanoma has previously been reported to portend a bad prognosis. The occurrence of vitiligo like lesions in patients with metastatic melanoma in comparison has a better prognosis. However the occurrence of depigmentation around the secondaries is rare and its importance is not well known. Hence we wish to report a case of epidermotropic metastatic melanoma with perilesional depigmentation in a 78 year old Indian male.

  5. Melanoma survivorship: research opportunities.

    Science.gov (United States)

    Oliveria, Susan A; Hay, Jennifer L; Geller, Alan C; Heneghan, Maureen K; McCabe, Mary S; Halpern, Allan C

    2007-03-01

    The rising incidence and mortality rates of melanoma, the most fatal form of skin cancer, are among the greatest increases of all preventable cancers over the past decade. However, because of recent advances in early detection, secondary prevention efforts, and treatment, the number of melanoma survivors is increasing. Little research has been conducted on melanoma survivors and important opportunities exist for research in this understudied population. Here, we outline the important research opportunities related to the study of melanoma survivorship and summarize the paucity of literature currently available. A computerized literature search was performed of the MEDLINE database of the National Library of Medicine from 1966-2005. The scope of the search was limited to those studies published in English. The search was conducted using the following MeSH headings: melanoma, neoplasms, skin neoplasms, survival, and survival rate. The reference lists of relevant book chapters and review articles were further reviewed, and printed materials from recent scientific meetings addressing this topic were obtained. Several factors that affect melanoma survivors warrant further study, including: physiologic long-term effects; psychosocial, behavioral, and cognitive factors; demographic characteristics; surveillance practices; recurrences, secondary primaries, and other cancers; family members of survivors; and economic issues, access to health care/life insurance. Understanding recurrence and second primary cancer risk, psychosocial and cognitive characteristics, behaviors, surveillance patterns, economic sequelae, and family issues of melanoma survivors is important from a public health standpoint to promote the health and well-being of this cohort. Melanoma is an understudied cancer, and the incidence and mortality of this disease are increasing. Describing the long term burden of this cancer and identifying factors that contribute to them will facilitate efforts to develop

  6. The impact of surgery on survival of patients with cutaneous melanoma: revisiting the role of primary tumor excision margins.

    Science.gov (United States)

    Mocellin, Simone; Pasquali, Sandro; Nitti, Donato

    2011-02-01

    To quantify the impact of excision margins on disease-specific survival of patients with primary cutaneous melanoma. Current guidelines recommend narrow margins for the treatment of primary melanoma, although available evidence on this subject is not unequivocal and not always appropriately analyzed. A systematic review of randomized controlled trials (RCT) addressing the issue of wide versus narrow excision margins was performed. Meta-analysis methods for time-to-event data were used to extract hazard ratios(HR) and their 95% confidence intervals (CI) from eligible studies, and ultimately to estimate the summary effect of excision margins on patients' survival. The 5 eligible RCT enrolled a total of 3295 patients who were allocated to wide (3-5 cm) or narrow (1-2 cm) excision of their primary tumor. The data of locoregional disease-free (LDFS), disease-free (DFS),disease-specific (DSS), and overall (OS) survival were available for 3, 5, 3, and 5 RCT, respectively. The meta-analysis suggested that narrow margins might be associated with an increased risk of both locoregional disease recurrence (HR: 1.30, CI: 1.07-1.57; P = 0.01) and death by disease (HR: 1.28, CI:1.07-1.53, P = 0.01). As regards DFS, the borderline disadvantage (HR:1.13, CI: 0.995-1.28; P = 0.06) becomes significant when considering RCT that enrolled patients with thicker melanoma (HR: 1.19, CI: 1.02-1.39, P =0.03). When death by any cause (OS) was analyzed, no risk difference was found. The lack of DSS data from all the available RCT does not allow to draw definitive conclusions. However, current evidence appears sufficient to question the common belief that narrow excision margins are as safe as wide margins in the management of primary melanoma, that calls for further investigation in this field.

  7. Biatrial Cardiac Metastases in a Patient with Uterine Cervix Malignant Melanoma

    Directory of Open Access Journals (Sweden)

    Caglayan Geredeli

    2015-01-01

    Full Text Available Primary malignant melanomas of uterine cervix are quite rarely seen neoplasms, and long-life prognosis of patients with this disease is poor. Immunohistochemical methods and exclusion of other primary melanoma sites are used to confirm the diagnosis. As with other melanomas, cervix malignant melanomas may also cause cardiac metastases. Cardiac metastases are among rarely seen but more commonly encountered cases, compared to primary cardiac tumors. Here, we present a case of biatrial cardiac metastases in a 73-year-old patient with uterine cervix malignant melanomas. The patient underwent echocardiography, cardiac magnetic resonance imaging, and computed tomography. Our report shows the importance of advanced diagnostic techniques, such as cardiac magnetic resonance, not only for the detection of cardiac masses, but for a better anatomic definition and tissue characterization. Although the cases of malignant melanomas leading to multiple cardiac metastasis were reported in literature, the metastatic concurrence of malignant melanomas in both right and left atriums is quite rarely encountered as metastatic malignant melanomas. Also, another intriguing point in our case is that the primary lesion of our case was stemmed from uterine cervix, but not skin.

  8. Canine oral melanoma.

    Science.gov (United States)

    Bergman, Philip J

    2007-05-01

    Melanoma is the most common oral malignancy in the dog. Oral and/or mucosal melanoma has been routinely considered an extremely malignant tumor with a high degree of local invasiveness and high metastatic propensity. Primary tumor size has been found to be extremely prognostic. The World Health Organization staging scheme for dogs with oral melanoma is based on size, with stage I = or = 4cm tumor and/or lymph node metastasis, and stage IV = distant metastasis. Median survival times for dogs with oral melanoma treated with surgery are approximately 17 to 18, 5 to 6, and 3 months with stage I, II, and III disease, respectively. Significant negative prognostic factors include stage, size, evidence of metastasis, and a variety of histologic criteria. Standardized treatments such as surgery, coarse-fractionation radiation therapy, and chemotherapy have afforded minimal to modest stage-dependent clinical benefits and death is usually due to systemic metastasis. Numerous immunotherapeutic strategies have been employed to date with limited clinical efficacy; however, the use of xenogeneic DNA vaccines may represent a leap forward in clinical efficacy. Oral melanoma is a spontaneous syngeneic cancer occurring in outbred, immunocompetent dogs and appears to be a more clinically faithful therapeutic model for human melanoma; further use of canine melanoma as a therapeutic model for human melanoma is strongly encouraged. In addition, the development of an expanded but clinically relevant staging system incorporating the aforementioned prognostic factors is also strongly encouraged.

  9. Implementing Curriculum-Embedded Formative Assessment in Primary School Science Classrooms

    Science.gov (United States)

    Hondrich, Annika Lena; Hertel, Silke; Adl-Amini, Katja; Klieme, Eckhard

    2016-01-01

    The implementation of formative assessment strategies is challenging for teachers. We evaluated teachers' implementation fidelity of a curriculum-embedded formative assessment programme for primary school science education, investigating both material-supported, direct application and subsequent transfer. Furthermore, the relationship between…

  10. Primary Oral Malignant Melanoma - A Case Report and Review of Literature

    Directory of Open Access Journals (Sweden)

    R Sathawane

    2005-01-01

    Malignant melanoma (MM is a neoplasm of melanocytic origin that arises from a benign melanocytic lesion or de novo from melanocytes within otherwise normal mucosa or skin. It is one of most biologically unpredictable and deadly of all human neoplasms. It is third most common skin cancer, and accounts for 5% of all tumours. Although it comprises 1.3% of all cancers, MM of oral cavity accounts for only 0.2 to 8% of all reported melanomas. The mucosal melanoma tends to appear at a higher stage and is much aggressive than its cutaneous counterpart. The prognosis of oral melanoma is extremely poor, until recently less than 29% of affected patients survived for 5 years or more.

  11. Primary Tr1 cells from metastatic melanoma eliminate tumor-promoting macrophages through granzyme B- and perforin-dependent mechanisms.

    Science.gov (United States)

    Yan, Hongxia; Zhang, Ping; Kong, Xue; Hou, Xianglian; Zhao, Li; Li, Tianhang; Yuan, Xiaozhou; Fu, Hongjun

    2017-04-01

    In malignant melanoma, tumor-associated macrophages play multiple roles in promoting tumor growth, such as inducing the transformation of melanocytes under ultraviolet irradiation, increasing angiogenesis in melanomas, and suppressing antitumor immunity. Because granzyme B- and perforin-expressing Tr1 cells could specifically eliminate antigen-presenting cells of myeloid origin, we examined whether Tr1 cells in melanoma could eliminate tumor-promoting macrophages and how the interaction between Tr1 cells and macrophages could affect the growth of melanoma cells. Tr1 cells were characterized by high interleukin 10 secretion and low Foxp3 expression and were enriched in the CD4 + CD49b + LAG-3 + T-cell fraction. Macrophages derived from peripheral blood monocytes in the presence of modified melanoma-conditioned media demonstrated tumor-promoting capacity, exemplified by improving the proliferation of cocultured A375 malignant melanoma cells. But when primary Tr1 cells were present in the macrophage-A375 coculture, the growth of A375 cells was abrogated. The conventional CD25 + Treg cells, however, were unable to inhibit macrophage-mediated increase in tumor cell growth. Further analyses showed that Tr1 cells did not directly eliminate A375 cells, but mediated the killing of tumor-promoting macrophages through the secretion of granzyme B and perforin. The tumor-infiltrating interleukin 10 + Foxp3 - CD4 + T cells expressed very low levels of granzyme B and perforin, possibly suggested the downregulation of Tr1 cytotoxic capacity in melanoma tumors. Together, these data demonstrated an antitumor function of Tr1 cells through the elimination of tumor-promoting macrophages, which was not shared by conventional Tregs.

  12. Nucleoli cytomorphology in cutaneous melanoma cells - a new prognostic approach to an old concept.

    Science.gov (United States)

    Donizy, Piotr; Biecek, Przemyslaw; Halon, Agnieszka; Maciejczyk, Adam; Matkowski, Rafal

    2017-12-29

    The nucleolus is an organelle that is an ultrastructural element of the cell nucleus observed in H&E staining as a roundish body stained with eosin due to its high protein content. Changes in the nucleoli cytomorphology were one of the first histopathological characteristics of malignant tumors. The aim of this study was to assess the relationship between the cytomorphological characteristics of nucleoli and detailed clinicopathological parameters of melanoma patients. Moreover, we analyzed the correlation between cytomorphological parameters of nucleoli and immunoreactivity of selected proteins responsible for, among others, regulation of epithelial-mesenchymal transition (SPARC, N-cadherin), cell adhesion and motility (ALCAM, ADAM-10), mitotic divisions (PLK1), cellular survival (FOXP1) and the functioning of Golgi apparatus (GOLPH3, GP73). Three characteristics of nucleoli - presence, size and number - of cancer cells were assessed in H&E-stained slides of 96 formalin-fixed paraffin-embedded primary cutaneous melanoma tissue specimens. The results were correlated with classical clinicopathological features and patient survival. Immunohistochemical analysis of the above mentioned proteins was described in details in previous studies. Higher prevalence and size of nucleoli were associated with thicker and mitogenic tumors. All three nucleolar characteristics were related to the presence of ulceration. Moreover, microsatellitosis was strongly correlated with the presence of macronucleoli and polynucleolization (presence of two or more nucleoli). Lack of immunologic response manifested as no TILs in primary tumor was associated with high prevalence of melanoma cells with distinct nucleoli. Interestingly, in nodular melanoma a higher percentage of melanoma cells with prominent nucleoli was observed. In Kaplan-Meier analysis, increased prevalence and amount, but not size of nucleoli, were connected with shorter cancer-specific and disease-free survival. (1) High

  13. Survival According to BRAF-V600 Tumor Mutations – An Analysis of 437 Patients with Primary Melanoma

    Science.gov (United States)

    Meckbach, Diana; Bauer, Jürgen; Pflugfelder, Annette; Meier, Friedegund; Busch, Christian; Eigentler, Thomas K.; Capper, David; von Deimling, Andreas; Mittelbronn, Michel; Perner, Sven; Ikenberg, Kristian; Hantschke, Markus; Büttner, Petra; Garbe, Claus; Weide, Benjamin

    2014-01-01

    The prognostic impact of BRAF-V600 tumor mutations in stage I/II melanoma patients has not yet been analyzed in detail. We investigated primary tumors of 437 patients diagnosed between 1989 and 2006 by Sanger sequencing. Mutations were detected in 38.7% of patients and were associated with age, histological subtype as well as mitotic rate. The mutational rate was 36.7% in patients with disease-free course and 51.7% in those with subsequent distant metastasis (p = 0.031). No difference in overall survival (p = 0.119) but a trend for worse distant-metastasis-free survival (p = 0.061) was observed in BRAF mutant compared to BRAF wild-type patients. Independent prognostic factors for overall survival were tumor thickness, mitotic rate and ulceration. An interesting significant prognostic impact was observed in patients with tumor thickness of 1 mm or less, with the mutation present in 6 of 7 patients dying from melanoma. In conclusion, no significant survival differences were found according to BRAF-V600 tumor mutations in patients with primary melanoma but an increasing impact of the mutational status was observed in the subgroup of patients with tumor thickness of 1 mm or less. A potential role of the mutational status as a prognostic factor especially in this subgroup needs to be investigated in larger studies. PMID:24475086

  14. DMBT1 expression distinguishes anorectal from cutaneous melanoma

    DEFF Research Database (Denmark)

    Helmke, Burkhard Maria; Renner, Marcus; Poustka, Annemarie

    2009-01-01

    tumours 1 (DMBT1) in cases of primary anorectal malignant melanoma and CM. METHODS AND RESULTS: Expression analyses of classical immunohistochemical markers (S100, HMB45, Melan A and MiTF) and of the protein DMBT1 were carried out in 27 cases of primary anorectal malignant melanoma and 26 cases of CM. All...

  15. Protocol for the melatools skin self-monitoring trial: a phase II randomised controlled trial of an intervention for primary care patients at higher risk of melanoma.

    Science.gov (United States)

    Mills, Katie; Emery, Jon; Lantaff, Rebecca; Radford, Michael; Pannebakker, Merel; Hall, Per; Burrows, Nigel; Williams, Kate; Saunders, Catherine L; Murchie, Peter; Walter, Fiona M

    2017-11-28

    Melanoma is the fifth most common cancer in the UK. Incidence rates have quadrupled over the last 30 years and continue to rise, especially among younger people. As routine screening of the general population is not currently recommended in the UK, a focus on secondary prevention through early detection and prompt treatment in individuals at increased risk of melanoma could make an important contribution to improve melanoma outcomes. This paper describes the protocol for a phase II, multisite, randomised controlled trial, in the primary care setting, for patients at increased risk of melanoma. A skin self-monitoring (SSM) smartphone 'App' was used to improve symptom appraisal and encourage help seeking in primary care, thereby promoting early presentation with skin changes suspicious of melanoma. We aim to recruit 200 participants from general practice waiting rooms in the East of England. Eligible patients are those identified at higher melanoma risk (using a real-time risk assessment tool), without a personal history of melanoma, aged 18 to 75 years. Participants will be invited to a primary care nurse consultation, and randomised to the intervention group (standard written advice on skin cancer detection and sun protection, loading of an SSM 'App' onto the participant's smartphone and instructions on use including self-monitoring reminders) or control group (standard written advice alone). The primary outcomes are consultation rates for changes to a pigmented skin lesion, and the patient interval (time from first noticing a skin change to consultation). Secondary outcomes include patient sun protection behaviours, psychosocial outcomes, and measures of trial feasibility and acceptability. NHS ethical approval has been obtained from Cambridgeshire and Hertfordshire research ethics committee (REC reference 16/EE/0248). The findings from the MelaTools SSM Trial will be disseminated widely through peer-reviewed publications and scientific conferences. ISCTRN16061621

  16. Metastatic breast disease from cutaneous malignant melanoma.

    Science.gov (United States)

    Moschetta, Marco; Telegrafo, Michele; Lucarelli, Nicola Maria; Martino, Gianluigi; Rella, Leonarda; Stabile Ianora, Amato Antonio; Angelelli, Giuseppe

    2014-01-01

    Malignant melanoma is one of the most rapidly increasing cancer in the world. Breast metastases from melanoma are uncommon but could reflect a widespread disease. We report a case of malignant widespread melanoma presenting with bilateral breast nodules in a 39 year-old pre-menopausal Caucasian woman with an history of cutaneous melanoma of the trunk. Breast clinical examination revealed the presence of a hard and mobile lump located on the left breast. Ultrasound detected two bilateral nodules corresponding to oval opacities with well-defined edges and without calcifications or architectural distortion on mammography. Fine needle aspiration cytology performed on both breast nodules confirmed that the breast lesions were metastases from primary cutaneous malignant melanoma. A total-body CT examination detected brain, lung and abdominal lymph nodes metastases. The breast represents an uncommon site of metastatic disease from extra-mammary tumors. Imaging features of breast metastases from melanoma usually do not allow a differential diagnosis with breast primary tumors. Breast metastases may be asymptomatic or palpable as dense and well-circumscribed nodules. Breast metastases indicate a widespread disease and should lead to avoid aggressive surgical procedures because of the poor prognosis of patients affected by metastatic melanoma. The detection of bilateral breast metastases from melanoma is highly suggestive of metastatic multi-organ disease and could be useful to address the therapeutic approach. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

  17. Uveal melanoma: Estimating prognosis

    Directory of Open Access Journals (Sweden)

    Swathi Kaliki

    2015-01-01

    Full Text Available Uveal melanoma is the most common primary malignant tumor of the eye in adults, predominantly found in Caucasians. Local tumor control of uveal melanoma is excellent, yet this malignancy is associated with relatively high mortality secondary to metastasis. Various clinical, histopathological, cytogenetic features and gene expression features help in estimating the prognosis of uveal melanoma. The clinical features associated with poor prognosis in patients with uveal melanoma include older age at presentation, male gender, larger tumor basal diameter and thickness, ciliary body location, diffuse tumor configuration, association with ocular/oculodermal melanocytosis, extraocular tumor extension, and advanced tumor staging by American Joint Committee on Cancer classification. Histopathological features suggestive of poor prognosis include epithelioid cell type, high mitotic activity, higher values of mean diameter of ten largest nucleoli, higher microvascular density, extravascular matrix patterns, tumor-infiltrating lymphocytes, tumor-infiltrating macrophages, higher expression of insulin-like growth factor-1 receptor, and higher expression of human leukocyte antigen Class I and II. Monosomy 3, 1p loss, 6q loss, and 8q and those classified as Class II by gene expression are predictive of poor prognosis of uveal melanoma. In this review, we discuss the prognostic factors of uveal melanoma. A database search was performed on PubMed, using the terms "uvea," "iris," "ciliary body," "choroid," "melanoma," "uveal melanoma" and "prognosis," "metastasis," "genetic testing," "gene expression profiling." Relevant English language articles were extracted, reviewed, and referenced appropriately.

  18. Lifetime prevalence of non-melanoma and melanoma skin cancer in Australian recreational and competitive surfers.

    Science.gov (United States)

    Climstein, Mike; Furness, James; Hing, Wayne; Walsh, Joe

    2016-07-01

    Surfing is one of the most popular outdoor aquatic activities in Australia with an estimated 2.7 million recreational surfers; however, Australia has long been recognized as having the highest incidence of melanoma in the world, and it is the most common type of cancer in young Australians. The aim of this study was to investigate the lifetime prevalence of non-melanoma [basal cell carcinoma (BCC), squamous cell carcinoma (SCC)] and melanoma skin cancers in Australian recreational and competitive surfers. Australian surfers were invited to complete an online surveillance survey to determine the lifetime prevalence of non-melanoma and melanoma skin cancers. A total of 1348 surfers (56.9% recreational) participated in this study, of which 184 surfers reported a skin cancer (competitive n = 96, recreational n = 87). Of non-melanoma and melanoma cancers reported, BCC was the most common (6.8%), followed by melanoma (1.4%) and SCC (0.6%). The relative risk was higher (P well as significantly (P surf are advised to regularly utilize sun protection strategies (avoid peak ultraviolet radiation (10 am-3 pm), rashvest, hat and sunscreen) and primary care physicians are recommended to regularly screen their patients who surf. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  19. Non-melanoma Skin Cancer in Canada Chapter 2: Primary Prevention of Non-melanoma Skin Cancer.

    Science.gov (United States)

    Barber, Kirk; Searles, Gordon E; Vender, Ronald; Teoh, Hwee; Ashkenas, John

    2015-01-01

    Non-melanoma skin cancer (NMSC), including basal and squamous cell carcinoma (BCC and SCC), represents the most common malignancy. To provide guidance to Canadian health care practitioners regarding primary prevention of NMSC. Structured literature searches were conducted, using search terms including prevention, sunscreen, and sun prevention factor. All recommendations concern guidance that physicians should regularly discuss with their patients to help establish photoprotection habits. The GRADE system was used to assign strength to each recommendation. Ultraviolet exposure is the major modifiable risk factor for NMSC. Aspects of photoprotection, including effective sunscreen use and avoidance of both the midday sun and artificial tanning, are discussed. Several widespread misunderstandings that undermine responsible public health measures related to sun safety are addressed. Photoprotection represents both an individual priority and a public health imperative. By providing accurate information during routine patient visits, physicians reinforce the need for ongoing skin cancer prevention. © The Author(s) 2015.

  20. GPNMB expression in uveal melanoma: a potential for targeted therapy.

    Science.gov (United States)

    Williams, Michelle D; Esmaeli, Bita; Soheili, Aydin; Simantov, Ronit; Gombos, Dan S; Bedikian, Agop Y; Hwu, Patrick

    2010-06-01

    Uveal melanoma is an aggressive disease without effective adjuvant therapy for metastases. Despite genomic differences between cutaneous and uveal melanomas, therapies based on shared biological factors could be effective against both tumor types. High expression of glycoprotein-NMB (GPNMB) in cutaneous melanomas led to the development of CDX-011 (glembatumumab vedotin), a fully human monoclonal antibody against the extracellular domain of GPNMB conjugated to the cytotoxic microtubule toxin monomethylauristatin E. Ongoing phase II trials suggest that CDX-011 has activity against advanced cutaneous melanomas. To determine the potential role of CDX-011 in uveal melanomas, we studied their GPNMB expression. Paraffin-embedded tissues from 22 uveal melanomas treated by enucleation from 2004-2007 at one institution were evaluated immunohistochemically for expression of GPNMB using biotinylated CDX-011 (unconjugated) antibody. Melanoma cells were evaluated for percentage and intensity of expression. Spectral imaging was used in one case with high melanin content. Clinical data were reviewed. Twelve women and 10 men with a median age of 58.7 years (range: 28-83 years) were included. Eighteen of 21 tumors evaluated immunohistochemically (85.7%) expressed GPNMB in 10-90% of tumor cells with variable intensity (5 tumors, 1+; 11, 2+; and 2, 3+). Eleven of 18 tumors (61.1%) expressed GPNMB in >or=50% of cells. Spectral imaging showed diffuse CDX-011 (unconjugated) reactivity in the remaining case. Uveal melanoma, like cutaneous melanoma, commonly expresses GPNMB. Ongoing clinical trials of CDX-011 should be extended to patients with metastatic uveal melanoma to determine potential efficacy in this subset of patients with melanoma.

  1. Similar survival of patients with multiple versus single primary melanomas based on Utah Surveillance, Epidemiology, and End Results data (1973-2011).

    Science.gov (United States)

    Grossman, Douglas; Farnham, James M; Hyngstrom, John; Klapperich, Marki E; Secrest, Aaron M; Empey, Sarah; Bowen, Glen M; Wada, David; Andtbacka, Robert H I; Grossmann, Kenneth; Bowles, Tawnya L; Cannon-Albright, Lisa A

    2018-03-01

    Survival data are mixed comparing patients with multiple primary melanomas (MPM) to those with single primary melanomas (SPM). We compared MPM versus SPM patient survival using a matching method that avoids potential biases associated with other analytic approaches. Records of 14,138 individuals obtained from the Surveillance, Epidemiology, and End Results registry of all melanomas diagnosed or treated in Utah between 1973 and 2011 were reviewed. A single matched control patient was selected randomly from the SPM cohort for each MPM patient, with the restriction that they survived at least as long as the interval between the first and second diagnoses for the matched MPM patient. Survival curves (n = 887 for both MPM and SPM groups) without covariates showed a significant survival disadvantage for MPM patients (chi-squared 39.29, P < .001). However, a multivariate Cox proportional hazards model showed no significant survival difference (hazard ratio 1.07, P = .55). Restricting the multivariate analysis to invasive melanomas also showed no significant survival difference (hazard ratio 0.99, P = .96). Breslow depth, ulceration status, and specific cause of death were not available for all patients. Patients with MPM had similar survival times as patients with SPM. Copyright © 2018 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

  2. Malignant melanoma in children: imaging spectrum

    International Nuclear Information System (INIS)

    Kaste, S.C.; Pappo, Alberto S.; Jenkins, J.J. III; Pratt, C.B.

    1996-01-01

    Objective. The objective of this study was to investigate the role of diagnostic imaging in detecting unsuspected metastatic disease in children with malignant melanoma. This has not been well studied previously. Materials and methods. We correlated imaging findings of 33 children diagnosed with melanoma with the level of invasion and clinical stage of disease. Results. Clinically undetectable metastases were identified in eight patients (25 %), four of whom had multiple metastases. All eight patients had deep lesions (Clark's level IV or V) or unknown primary sites of disease. Conclusion. Children with thick melanomas and those with unknown site of primary tumors are at increased risk of having clinically unsuspected metastases and should undergo CT of the chest, abdomen, and local-regional nodal basins at diagnosis to determine disease extent. (orig.). With 8 figs

  3. Primary melanoma of the esophagus treated with esophagectomy. Clinical Cases

    International Nuclear Information System (INIS)

    Butte, Jean M; Visscher, Alvaro; De la Fuente, Hernan; Meneses, Manuel; Carrasco, Ana Maria; Amaral, Horacio; Waugh, Enrique

    2010-01-01

    Esophageal melanomas correspond to 0.1 to 0.2% of esophageal tumors. We report two patients with the disease. The first patient is a 51 year-old woman pre-sentingwith dysphagia and weight loss. An upper gastrointestinal endoscopy showed a polypoid ulcerated lesion in the middle third of the esophagus. The pathological study of the biopsy disclosed a malignant melanoma. The patient was subjected to an esophagectomy with a satisfactory postoperative evolution. Four months later, liver metastases were detected and the patient died eleven months after the operation. The second patient is a 59 year-old mole that consulted by dysphagia. An endoscopy showed a pigmented esophageal lesion whose pathological diagnosis was a malignant melanoma. The patient was subjected to an esophagectomy and sixteen months after surgery there was no evidence of relaps

  4. Growth inhibitory activity of Ankaferd hemostat on primary melanoma cells and cell lines

    Directory of Open Access Journals (Sweden)

    Seyhan Turk

    2017-02-01

    Full Text Available Objective: Ankaferd hemostat is the first topical hemostatic agent about the red blood cell–fibrinogen relations tested in the clinical trials. Ankaferd hemostat consists of standardized plant extracts including Alpinia officinarum, Glycyrrhiza glabra, Thymus vulgaris, Urtica dioica, and Vitis vinifera. The aim of this study was to determine the effect of Ankaferd hemostat on viability of melanoma cell lines. Methods: Dissimilar melanoma cell lines and primary cells were used in this study. These cells were treated with different concentrations of Ankaferd hemostat to assess the impact of different dosages of the drug. All cells treated with different concentrations were incubated for different time intervals. After the data had been obtained, one-tailed T-test was used to determine whether the Ankaferd hemostat would have any significant inhibitory impact on cell growth. Results: We demonstrated in this study that cells treated with Ankaferd hemostat showed a significant decrease in cell viability compared to control groups. The cells showed different resistances against Ankaferd hemostat which depended on the dosage applied and the time treated cells had been incubated. We also demonstrated an inverse relationship between the concentration of the drug and the incubation time on one hand and the viability of the cells on the other hand, that is, increasing the concentration of the drug and the incubation time had a negative impact on cell viability. Conclusion: The findings in our study contribute to our knowledge about the anticancer impact of Ankaferd hemostat on different melanoma cells.

  5. Chromosome 7 Aneusomy. A Marker for Metastatic Melanoma?

    Directory of Open Access Journals (Sweden)

    Martin Udart

    2001-01-01

    Full Text Available Receptor tyrosine kinases such as the epidermal growth factor receptor (EGFR play an important role in a variety of malignant neoplasias, making the search for aberrations in the relevant chromosomes an important issue. Differential expression of the EGFR gene was investigated by reverse transcriptase (RT-PCR on tissue samples of normal skin, nevi, primary melanomas, and melanoma metastases. The EGFR gene is located on chromosome 7p12.3-p12.1. To determine the number of chromosomes 7 in cell nuclei of the mentioned tissue samples we performed fluorescence in situ hybridization (FISH on touch preparations, using a DNA probe that hybridizes specifically to the centromeric region of chromosome 7. Additionally, chromosome 7 number in interphase nuclei was determined in short-term primary cell cultures of nevi, primary melanomas, and metastases. The highest EGFR gene expression frequency was found in melanoma metastases. By FISH we detected the highest fraction of cell nuclei with more than two chromosomes 7 in the group of metastases. Our results suggest that overexpression of the EGFR gene might play an important role in metastasis of malignant melanoma. This is well reflected by polysomy 7, possibly accounting for an increased EGFRgene copy number.

  6. Primary Malignant Melanoma of the Gingiva: A Case Report and Review of Literature

    Directory of Open Access Journals (Sweden)

    Niti Singhal

    2011-01-01

    In contrast to cutaneous melanoma, the mucosal melanomas have an aggressive vertical growth phase. Different cell types, like spindled, plasmacytoid, and epithelioid may be observed. The treatment of choice is complete excision with adequate negative margins. The role of radiotherapy is not clearly defined since malignant melanoma is relatively insensitive to radiation. The prognosis for mucosal melanoma is generally quite poor because of its tendency to invade and cause early hematogenous metastasis. Nodal involvement reduces survival time and multiple local recurrences are the most common cause of treatment failure.

  7. Analysis of T cell receptor alpha beta variability in lymphocytes infiltrating melanoma primary tumours and metastatic lesions

    DEFF Research Database (Denmark)

    Schøller, J; thor Straten, P; Jakobsen, Annette Birck

    1994-01-01

    The T cell receptor (TCR) alpha beta variable (V) gene family usage of tumour-infiltrating lymphocytes (TIL) in four different primary human malignant melanomas and their corresponding metastatic lesions was characterized using a recently developed method based on the reverse-transcription-couple......The T cell receptor (TCR) alpha beta variable (V) gene family usage of tumour-infiltrating lymphocytes (TIL) in four different primary human malignant melanomas and their corresponding metastatic lesions was characterized using a recently developed method based on the reverse...... usage of the TCR V gene families V alpha 4, V alpha 5, V alpha 22 and V beta 8, whereas the V beta 3 gene family appeared to be expressed together with HLA-A1. Other highly expressed V gene families, apparently not restricted to either HLA-A1 or -A2, were V alpha 1 (expressed in three of four primary...... tumours) and V alpha 21 (expressed in two of four tumours). We found no evidence suggesting any correlations between the haplotypes HLA-A1 and -A2 and preferential V gene family expression in the metastatic lesions, and the only common feature was V alpha 8, which was found to be highly expressed in two...

  8. Sentinel lymph node biopsy in local recurrence of cutaneous melanoma

    International Nuclear Information System (INIS)

    Junqueira, G. Jr.; Bodanese, B.; Boff, M.F.; Espindola, M.B.; Haack, R.L.; Frigeri, C.D.L.

    2004-01-01

    Full text: Locally recurrent disease in patients with melanoma is usually defined as cutaneous or subcutaneous arising within 5 cm of the primary site after complete excision of the primary lesion. It may represent residual disease not excised with the primary tumor or the outgrowth of the satellite lesions, which are common with melanoma. Lymphatic mapping and sentinel lymph node (SLN) biopsy is highly accurate in staging nodal basins at risk of regional metastases in primary melanoma patients and identifies those who may benefit from earlier lymphadenectomy. Our purpose was to evaluate the efficacy of sentinel lymph node mapping and biopsy in local recurrence of cutaneous melanoma when the primary lesion was less than 1.0mm thick. Three patients with local recurrence of cutaneous melanoma underwent sentinel lymph node mapping and biopsy. All patients underwent preoperative lymphoscintigraphy to identify the lymphatic basin and the site of the sentinel node. All patients subsequently underwent intra-operative lymphatic mapping and selective lymph node biopsy with vital blue dye and hand-held gamma probe. Excised SLN were analysed by conventional histological staining (H and E) and immunohistochemical staining. In all patients the lymphatic mapping and sentinel lymph node biopsy was successful. The SLN biopsy was negative in two patients and positive in one who underwent therapeutic lymph node dissection. Our results indicate that the SLN mapping and biopsy is also possible in patients having local recurrence of cutaneous melanoma. Although long-term results are not available, early results are promising. (author)

  9. Primary mediastinal melanoma presenting as superior vena cava syndrome: A case study

    Directory of Open Access Journals (Sweden)

    Ann C Gaffey

    2016-03-01

    Full Text Available The rates of melanoma have increased over the past 30 years. Malignant melanoma most commonly occurs in the skin with secondary involvement of other organs. Here, we present an extremely rare case of malignant melanoma of the mediastinum with presentation of superior vena cava syndrome without clinical evidence of extrathoracic disease. The incidence of this clinical presentation is uncommon, resulting in only a handful of case reports in the literature. [Arch Clin Exp Surg 2016; 5(1.000: 56-58

  10. Highly Adaptive Primary Mirror Having Embedded Actuators, Sensors, and Neural Control, Phase II

    Data.gov (United States)

    National Aeronautics and Space Administration — Xinetics has demonstrated the technology required to fabricate a self-compensating highly adaptive silicon carbide primary mirror system having embedded actuators,...

  11. The relationship between MDM2 expression and tumor thickness and invasion in primary cutaneous malignant melanoma

    Directory of Open Access Journals (Sweden)

    Parvin Rajabi

    2012-01-01

    Full Text Available Background: Malignant melanoma is the most invasive cutaneous tumor which is associated with an incredibly high mortality rate. The most reliable histological factors associated with melanoma prognosis are tumor thickness- measured by the Breslow index- and invasion depth- measured by Clark level. Murine double minute 2 (MDM2 gene inhibits p53-dependent apoptosis. An increase in MDM2 expression has been found in many tumors. This study aimed to investigate MDM2 expression and its correlation with tumor thickness and invasion level in malignant melanoma. Materials and Methods: This study evaluated paraffin blocks from 43 randomly selected patients with primary cutaneous melanoma who referred to the main university pathology center in Isfahan, Iran. MDM2 expression rate was assessed via immunohistochemical techniques and hematoxylin and eosin staining to determine tumor thickness and invasion level. Correlations between MDM2 expression and tumor thickness and invasion were analyzed using Spearman′s correlation coefficient in SPSS 17 . Results: The mean age of patients was 61.2 ± 15 years. Men and women constituted 55.8% and 44.2% of the participants, respectively. The rate of MDM2 positivity was 28.9%. MDM2 expression was directly associated with tumor thickness (r = 0.425; p = 0.002 and weakly with invasion level (r = 0.343; p = 0.01. Conclusions: Despite the low MDM2 expression rate observed in this study, direct relationships between MDM2 positivity and tumor thickness and invasion level were identified. MDM2 expression can thus be suggested as a potential new predictive prognostic factor.

  12. Two unusual cases of brain metastases from lung primary malignant melanoma

    International Nuclear Information System (INIS)

    Rodríguez, A.; Mañana, G.; Panuncio, A.; Rodríguez, R.; Roldán, G.; Sosa, A.

    2004-01-01

    Start with two cases of brain metastases from lung melanoma are presented who were diagnosed in the Neuropathology Laboratory of the Department of Anatomy Pathology, Institute of Neurology, Hospital de Clinicas, Montevideo, emphasizing the pathological diagnostic criteria and their evolution clinic. Both patients presented at the time of the initial consultation injuries amelánica respectively pigmented single brain. In both cases ruled by the morphology and the use of complementary techniques metastasis carcinoma. The main differential diagnosis of these lesions is whether is a primitive brain tumor, pigmented or not, or of a secondary tumor melanin: metastatic malignant melanoma. In both cases the patients had been studied one being in an unresectable lung injury, and in the other showed a single pulmonary nodule was resected in its entirety. the pulmonary lesions were for malignant melanoma, one with ample pigment and the other for the most part amelánico, with few areas retained pigment. He studied dermatologist, discarded the presence of a cutaneous malignant melanoma primitive. Other locations were also excluded

  13. The evaluaton of prevalence rate of p53 antigen expression in cutaneous malignant melanoma and it′s relation to tumor thickness

    Directory of Open Access Journals (Sweden)

    Faghihi Gita

    2005-01-01

    Full Text Available P53 tumor suppressor gene mutation is one of the most common genetic alteration in human malignancies. This study was done to determine the prevalence of the P53 antigen expression by sex, age, type of melanoma, thickness of the lesion and site of the antigen expression either cytoplasmic or nuclear. Paraffin embeded block of 50 patients (45 primary and metastaticwith documented diagnosis of melanoma deparaffinized and immuno stained with DO-7 monoclonal antibody. The lesions were divided depending on the degree of the staining as follow: 1. no staining, 2. mild (less than 10%, 3. moderate (10%-50% staining, 4. severe (more than 50%. Fifty four percent of evaluated patients were female and 46% were male. Forty percent of lesions were graded as no staining, 36% of lesions showed mild staining, 14% moderate and 10% severe staining site of expression was excusively in the cytoplasm. There was no meaningful statistical deference between severity of staining and the age group, sex, type and thickness of melanoma. (p value was 0.532, 0.488, 0.626, 0.954 respectively.

  14. Characterization of long noncoding RNA and messenger RNA signatures in melanoma tumorigenesis and metastasis.

    Directory of Open Access Journals (Sweden)

    Siqi Wang

    Full Text Available The incidence of melanoma, the most aggressive and life-threatening form of skin cancer, has significantly risen over recent decades. Therefore, it is essential to identify the mechanisms that underlie melanoma tumorigenesis and metastasis and to explore novel and effective melanoma treatment strategies. Accumulating evidence s uggests that aberrantly expressed long noncoding RNAs (lncRNAs have vital functions in multiple cancers. However, lncRNA functions in melanoma tumorigenesis and metastasis remain unclear. In this study, we investigated lncRNA and messenger RNA (mRNA expression profiles in primary melanomas, metastatic melanomas and normal skin samples from the Gene Expression Omnibus database. We used GSE15605 as the training set (n = 74 and GSE7553 as the validation set (n = 58. In three comparisons (primary melanoma versus normal skin, metastatic melanoma versus normal skin, and metastatic melanoma versus primary melanoma, 178, 295 and 48 lncRNAs and 847, 1758, and 295 mRNAs were aberrantly expressed, respectively. We performed Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses to examine the differentially expressed mRNAs, and potential core lncRNAs were predicted by lncRNA-mRNA co-expression networks. Based on our results, 15 lncRNAs and 144 mRNAs were significantly associated with melanoma tumorigenesis and metastasis. A subsequent analysis suggested a critical role for a five-lncRNA signature during melanoma tumorigenesis and metastasis. Low expression of U47924.27 was significantly associated with decreased survival of patients with melanoma. To the best of our knowledge, this study is the first to explore the expression patterns of lncRNAs and mRNAs during melanoma tumorigenesis and metastasis by re-annotating microarray data from the Gene Expression Omnibus (GEO microarray dataset. These findings reveal potential roles for lncRNAs during melanoma tumorigenesis and metastasis and provide a rich candidate

  15. Stereological estimates of nuclear volume in thin malignant melanomas

    DEFF Research Database (Denmark)

    Björnhagen, V; Månsson-Brahme, E; Lindholm, J

    1998-01-01

    melanomas were individually compared with 33 thin non-metastasizing melanomas after individual matching of cases with one or two randomly chosen controls for site of primary tumour, tumour thickness, level of invasion, tumour regression and follow-up. Conditional logistic regression analysis showed...

  16. Germline TERT promoter mutations are rare in familial melanoma

    DEFF Research Database (Denmark)

    Harland, Mark; Petljak, Mia; Robles-Espinoza, Carla Daniela

    2016-01-01

    Germline CDKN2A mutations occur in 40 % of 3-or-more case melanoma families while mutations of CDK4, BAP1, and genes involved in telomere function (ACD, TERF2IP, POT1), have also been implicated in melanomagenesis. Mutation of the promoter of the telomerase reverse transcriptase (TERT) gene (c.-57...... T>G variant) has been reported in one family. We tested for the TERT promoter variant in 675 multicase families wild-type for the known high penetrance familial melanoma genes, 1863 UK population-based melanoma cases and 529 controls. Germline lymphocyte telomere length was estimated in carriers....... The c.-57 T>G TERT promoter variant was identified in one 7-case family with multiple primaries and early age of onset (earliest, 15 years) but not among population cases or controls. One family member had multiple primary melanomas, basal cell carcinomas and a bladder tumour. The blood leukocyte...

  17. Management of uveal tract melanoma: A comprehensive review

    International Nuclear Information System (INIS)

    Kapoor, A.; Kumar, H.S.; Beniwal, V.; Beniwal, S.; Mathur, H.

    2016-01-01

    Uveal tract melanoma is the most common primary intraocular malignancy in adults, accounting for about 5–10% of all the melanomas. Since there are no lymphatic vessels in the eye, uveal melanoma can only spread hematogenously leading to liver metastasis. A wide variety of treatment modalities are available for its management, leading to dilemma in selecting the appropriate therapy. This article reviews the diagnostic and therapeutic modalities available and thus, can help to individualize the treatment plan for each patient

  18. In-depth characterization of microRNA transcriptome in melanoma.

    Directory of Open Access Journals (Sweden)

    James Kozubek

    Full Text Available The full repertoire of human microRNAs (miRNAs that could distinguish common (benign nevi from cutaneous (malignant melanomas remains to be established. In an effort to gain further insight into the role of miRNAs in melanoma, we applied Illumina next-generation sequencing (NGS platform to carry out an in-depth analysis of miRNA transcriptome in biopsies of nevi, thick primary (>4.0 mm and metastatic melanomas with matched normal skin in parallel to melanocytes and melanoma cell lines (both primary and metastatic (n=28. From this data representing 698 known miRNAs, we defined a set of top-40 list, which properly classified normal from cancer; also confirming 23 (58% previously discovered miRNAs while introducing an additional 17 (42% known and top-15 putative novel candidate miRNAs deregulated during melanoma progression. Surprisingly, the miRNA signature distinguishing specimens of melanoma from nevus was significantly different than that of melanoma cell lines from melanocytes. Among the top list, miR-203, miR-204-5p, miR-205-5p, miR-211-5p, miR-23b-3p, miR-26a-5p and miR-26b-5p were decreased in melanomas vs. nevi. In a validation cohort (n=101, we verified the NGS results by qRT-PCR and showed that receiver-operating characteristic curves for miR-211-5p expression accurately discriminated invasive melanoma (AUC=0.933, melanoma in situ (AUC=0.933 and dysplastic (atypical nevi (AUC=0.951 from common nevi. Target prediction analysis of co-transcribed miRNAs showed a cooperative regulation of key elements in the MAPK signaling pathway. Furthermore, we found extensive sequence variations (isomiRs and other non-coding small RNAs revealing a complex melanoma transcriptome. Deep-sequencing small RNAs directly from clinically defined specimens provides a robust strategy to improve melanoma diagnostics.

  19. Growth of melanoma brain tumors monitored by photoacoustic microscopy

    Science.gov (United States)

    Staley, Jacob; Grogan, Patrick; Samadi, Abbas K.; Cui, Huizhong; Cohen, Mark S.; Yang, Xinmai

    2010-07-01

    Melanoma is a primary malignancy that is known to metastasize to the brain and often causes death. The ability to image the growth of brain melanoma in vivo can provide new insights into its evolution and response to therapies. In our study, we use a reflection mode photoacoustic microscopy (PAM) system to detect the growth of melanoma brain tumor in a small animal model. The melanoma tumor cells are implanted in the brain of a mouse at the beginning of the test. Then, PAM is used to scan the region of implantation in the mouse brain, and the growth of the melanoma is monitored until the death of the animal. It is demonstrated that PAM is capable of detecting and monitoring the brain melanoma growth noninvasively in vivo.

  20. Metastatic malignant subungal melanoma: Importance of FNAC

    Directory of Open Access Journals (Sweden)

    Radhika Punshi Nandwani

    2014-01-01

    Full Text Available Subungual melanoma is a rare type of skin cancer. It is an uncommon form of acral lentiginous melanoma. Approximately 85% of cases are misdiagnosed initially, and it is generally associated with a poor prognosis. Herein, we describe a case of metastatic subungal melanoma to the axillary lymph node in a 45-year-old male. Diagnosis of metastasis was made based on cytology, where the clinicians were guided to search for primary. This case report highlights the role of fine-needle aspiration cytology (FNAC in the diagnosis of this entity to draw the attention of the reader to the possible underreporting of melanoma because of a variant that evades diagnosis and our reluctance to think about its existence.

  1. Missing an opportunity: the embedded nature of weight management in primary care.

    Science.gov (United States)

    Asselin, J; Osunlana, A M; Ogunleye, A A; Sharma, A M; Campbell-Scherer, D

    2015-12-01

    The 5As Team study was designed to create, implement and evaluate a flexible intervention to improve the quality and quantity of weight management visits in primary care. The objective of this portion of the study was to explore how primary care providers incorporate weight management in their practice. 5AsT is a randomized controlled trial (RCT) on the implementation of a 6-month 5 As Team (5AsT) intervention designed to operationalize the 5As of obesity management in primary care. Data for the qualitative portion of the study presented here included semi-structured interviews with 29 multidisciplinary team providers and field notes of intervention sessions. Thematic analysis was undertaken. A key pattern that emerged from the data was that healthcare providers usually do not address obesity as a primary focus for a visit. Rather, obesity is embedded in a wide range of primary care encounters for other conditions. Implications were it can take extra time to discuss weight, it can be inappropriate to bring up weight as a topic, and treating risk factors and root causes of obesity have indirect benefits to patient weight management. Our findings have implications for obesity treatment approaches and tools that assume a discreet weight management visit. The embedded nature of obesity management in primary care can be harnessed to leverage multiple opportunities for asking and assessing root causes of obesity, and working longitudinally towards individual health goals. © 2015 The Authors. Clinical Obesity published by John Wiley & Sons Ltd on behalf of World Obesity.

  2. Severe sunburn and subsequent risk of primary cutaneous malignant melanoma in scotland.

    Science.gov (United States)

    MacKie, R. M.; Aitchison, T.

    1982-01-01

    A case-control study of occupational and recreational sun exposure, Mediterranean and other sun-exposed holidays, tanning history and history of isolated episodes of severe sunburn has been carried out on 113 patients with cutaneous malignant melanoma and 113 age- and sex-matched controls. Social class and skin type were also considered in the analysis of the data which involved the use of conditional multiple logistic regression. A highly significant increase in the history of severe sunburn was recorded in melanoma patients of both sexes in the 5-year period preceding presentation with their tumour. Higher social class and negative history of recreational sun exposure were also significantly increased in patients by comparison with controls. In the male group severe sunburn, lack of occupational sun exposure and higher social class were significant factors while in the female group only severe sunburn was significantly increased in the melanoma patients. This study thus provides evidence to suggest that short intense episodes of UV exposure resulting in burning may be one of the aetiological factors involved in subsequent development of melanoma. PMID:7150488

  3. Management of uveal tract melanoma: A comprehensive review

    Directory of Open Access Journals (Sweden)

    Akhil Kapoor

    2016-06-01

    Full Text Available Uveal tract melanoma is the most common primary intraocular malignancy in adults, accounting for about 5–10% of all the melanomas. Since there are no lymphatic vessels in the eye, uveal melanoma can only spread hematogenously leading to liver metastasis. A wide variety of treatment modalities are available for its management, leading to dilemma in selecting the appropriate therapy. This article reviews the diagnostic and therapeutic modalities available and thus, can help to individualize the treatment plan for each patient.

  4. Melanoma genetics

    DEFF Research Database (Denmark)

    Read, Jazlyn; Wadt, Karin A W; Hayward, Nicholas K

    2015-01-01

    Approximately 10% of melanoma cases report a relative affected with melanoma, and a positive family history is associated with an increased risk of developing melanoma. Although the majority of genetic alterations associated with melanoma development are somatic, the underlying presence of herita......Approximately 10% of melanoma cases report a relative affected with melanoma, and a positive family history is associated with an increased risk of developing melanoma. Although the majority of genetic alterations associated with melanoma development are somatic, the underlying presence...... in a combined total of approximately 50% of familial melanoma cases, the underlying genetic basis is unexplained for the remainder of high-density melanoma families. Aside from the possibility of extremely rare mutations in a few additional high penetrance genes yet to be discovered, this suggests a likely...... polygenic component to susceptibility, and a unique level of personal melanoma risk influenced by multiple low-risk alleles and genetic modifiers. In addition to conferring a risk of cutaneous melanoma, some 'melanoma' predisposition genes have been linked to other cancers, with cancer clustering observed...

  5. Impact of sentinel lymphadenectomy on survival in a murine model of melanoma.

    Science.gov (United States)

    Rebhun, Robert B; Lazar, Alexander J F; Fidler, Isaiah J; Gershenwald, Jeffrey E

    2008-01-01

    Lymphatic mapping and sentinel lymph node biopsy-also termed sentinel lymphadenectomy (SL)-has become a standard of care for patients with primary invasive cutaneous melanoma. This technique has been shown to provide accurate information about the disease status of the regional lymph node basins at risk for metastasis, provide prognostic information, and provide durable regional lymph node control. The potential survival benefit afforded to patients undergoing SL is controversial. Central to this controversy is whether metastasis to regional lymph nodes occurs independent of or prior to widespread hematogenous dissemination. A related area of uncertainty is whether tumor cells residing within regional lymph nodes have increased metastatic potential. We have used a murine model of primary invasive cutaneous melanoma based on injection of B16-BL6 melanoma cells into the pinna to address two questions: (1) does SL plus wide excision of the primary tumor result in a survival advantage over wide excision alone; and (2) do melanoma cells growing within lymph nodes produce a higher incidence of hematogenous metastases than do cells growing at the primary tumor site? We found that SL significantly improved the survival of mice with small primary tumors. We found no difference in the incidence of lung metastases produced by B16-BL6 melanoma cells growing exclusively within regional lymph nodes and cells growing within the pinna.

  6. Meningeal Melanomas Associated With Transforming Ota Nevus to Malignant Melanoma: A Case Report

    Directory of Open Access Journals (Sweden)

    Seyed-Mohammad Fereshtehnejad

    2010-11-01

    Full Text Available Intracranial invasion of cellular blue nevus (CBN from the skin is extremely rare and such a condition with malignant transformation is even rarer.A case of meningeal melanoma with malignant transformation which was derived from an Ota   nevus is presented in this report.   A21-year-old man with a neurocutaneous syndrome since childhood was referred with headache and mild left hemiparesia. CT scan and MRI demonstrated intracranial lesions and conjunctival biopsy leads to the pathologic diagnosis of blue nevus.Thereafter his parietal lesion was operated by craniotomy with total gross excision.On histopathological examination, diagnosis of malignant melanoma was confirmed.Approximately 2 months after radiotherapy and chemotherapy, he afflicted to diplopia and blurred vision on the leftside due to enlargement of orbital and cavernous sinus lesion. Following one year follow-up,he was survived and thrived with diffuse leptomeningeal nodular enhancement in favor of melanoma dissemination.Primary intracranial melanomas are though rare, but it should be suspected especially in the presence of periorbital blue nevus or nevus of Ota. Moreover, although CBN is considered benign, scalp or periorbital CBN has the potential for intracranial invasion and malignant ransformation.

  7. [Acute dyspnea in malignant melanoma].

    Science.gov (United States)

    Franzen, A M; Günzel, T

    2011-09-01

    Metastases to the larynx are rare. The current article presents the case of a 75-year-old patient with a history of shortness of breath due to a supraglottic exophytic lesion that was identified as a metastasis of a cutaneous melanoma treated 2.5 years previously. As a result of our medline analysis we found approximately 30 cases of metastatic melanoma to the larynx published to date. Primary tumors are always cutaneous in origin and spread over the whole integument of trunk and extremities. The time interval between diagnosis of the primary and the laryngeal metastasis is often several years. In most reports a supraglottic exophytic, red coloured lesion is described. Diagnosis can only be proven by histological examination. Laryngeal metastasis is usually an indication of tumor dissemination and always has a fatal prognosis.

  8. Use of support services in a sample of patients with high-risk primary melanomas in urban, regional and rural Queensland.

    Science.gov (United States)

    von Schuckmann, Lena A; Smithers, Bernhard M; Khosrotehrani, Kiarash; Beesley, Vanessa L; van der Pols, Jolieke C; Hughes, Maria B; Green, Adele C

    2017-06-01

    To characterise use of support services in patients diagnosed with high-risk primary melanoma by their location of residence. In a cross-sectional study of 787 patients with histologically-confirmed clinical stage 1B-2 melanoma, we estimated odds ratios (ORs) using regression models to assess the association of support service use with residence in rural, regional or urban areas. We also evaluated demographic and clinical correlates of support service use. Among 113 rural patients, 33 (29%) used support services around time of diagnosis compared to 88 (39%) of 224 regional participants and 164 of 448 (37%) urban participants. Regional participants more commonly used support services compared to rural participants (OR 1.84; CI 1.09-3.10), but there was no association with urban versus rural residence (OR 1.32; CI 0.82-2.13). As well, females (OR 1.58; CI 1.15-2.18), those <65 years (OR 1.96; CI 1.42-2.71), or with higher education (OR 2.30; CI 1.53-3.44), or those with T-stage 4B (OR 2.69; CI 1.36-5.32) were more likely to use support services than other patients. Use of support services is lower among rural patients and other sub-groups of primary melanoma patients who have poorer prognoses than others. Implications for public health: Appropriate triage to support services is required for rural and other vulnerable patient groups to ensure optimal patient care. © 2017 The Authors.

  9. Oral malignant melanoma: a rare case with unusual clinical ...

    African Journals Online (AJOL)

    Primary Oral malignant melanoma is a rare tumor with an indigent prognosis. This is a case report of 47-year-old Sudanese female diagnosed as Oral malignant melanoma of the mandible with an unusual pattern of growth and clinical presentation. Furthermore, a possibility of intraosseous origin is suggested. Pan African ...

  10. BAP1 has a survival role in cutaneous melanoma.

    Science.gov (United States)

    Kumar, Raj; Taylor, Michael; Miao, Benchun; Ji, Zhenyu; Njauw, Jenny C-N; Jönsson, Göran; Frederick, Dennie T; Tsao, Hensin

    2015-04-01

    Although the pattern of BAP1 inactivation in ocular melanoma specimens and in the BAP1 cutaneous melanoma (CM)/ocular melanoma predisposition syndrome suggests a tumor suppressor function, the specific role of this gene in the pathogenesis of CM is not fully understood. We thus set out to characterize BAP1 in CM and discovered an unexpected pro-survival effect of this protein. Tissue and cell lines analysis showed that BAP1 expression was maintained, rather than lost, in primary melanomas compared with nevi and normal skin. Genetic depletion of BAP1 in melanoma cells reduced proliferation and colony-forming capability, induced apoptosis, and inhibited melanoma tumor growth in vivo. On the molecular level, suppression of BAP1 led to a concomitant drop in the protein levels of survivin, a member of anti-apoptotic proteins and a known mediator of melanoma survival. Restoration of survivin in melanoma cells partially rescued the growth-retarding effects of BAP1 loss. In contrast to melanoma cells, stable overexpression of BAP1 into immortalized but non-transformed melanocytes did suppress proliferation and reduce survivin. Taken together, these studies demonstrate that BAP1 may have a growth-sustaining role in melanoma cells, but that its impact on ubiquitination underpins a complex physiology, which is context and cell dependent.

  11. BAP1 PLAYS A SURVIVAL ROLE IN CUTANEOUS MELANOMA

    Science.gov (United States)

    Kumar, Raj; Taylor, Michael; Miao, Benchun; Ji, Zhenyu; Njauw, Jenny Ching-Ni; Jönsson, Göran; Frederick, Dennie Tompers; Tsao, Hensin

    2014-01-01

    Although the pattern of BAP1 inactivation in ocular melanoma specimens and in the BAP1 cutaneous/ocular melanoma (CM/OM) predisposition syndrome suggests a tumor suppressor function, the specific role of this gene in the pathogenesis of cutaneous melanoma is not fully understood. We thus set out to characterize BAP1 in cutaneous melanoma and discovered an unexpected pro-survival effect of this protein. Tissue and cell lines analysis showed that BAP1 expression was maintained, rather than lost, in primary melanomas compared to nevi and normal skin. Genetic depletion of BAP1 in melanoma cells reduced proliferation and colony forming capability, induced apoptosis and inhibited melanoma tumor growth in vivo. On the molecular level, suppression of BAP1 led to a concomitant drop in the protein levels of survivin a member of anti-apoptotic proteins and a known mediator of melanoma survival. Restoration of survivin in melanoma cells partially rescued the growth-retarding effects of BAP1 loss. In contrast to melanoma cells, stable overexpression of BAP1 into immortalized but non-transformed melanocytes did suppress proliferation and reduce survivin. Taken together, these studies demonstrate that BAP1 may play a growth-sustaining role in melanoma cells, but that its impact on ubiquitination underpins a complex physiology which is context and cell dependent. PMID:25521456

  12. Balloon Cell Urethral Melanoma: Differential Diagnosis and Management

    Directory of Open Access Journals (Sweden)

    M. McComiskey

    2015-01-01

    Full Text Available Introduction. Primary malignant melanoma of the urethra is a rare tumour (0.2% of all melanomas that most commonly affects the meatus and distal urethra and is three times more common in women than men. Case. A 76-year-old lady presented with vaginal pain and discharge. On examination, a 4 cm mass was noted in the vagina and biopsy confirmed melanoma of a balloon type. Preoperative CT showed no distant metastases and an MRI scan of the pelvis demonstrated no associated lymphadenopathy. She underwent anterior exenterative surgery and vaginectomy also. Histology confirmed a urethral nodular malignant melanoma. Discussion. First-line treatment of melanoma is often surgical. Adjuvant treatment including chemotherapy, radiotherapy, or immunotherapy has also been reported. Even with aggressive management, malignant melanoma of the urogenital tract generally has a poor prognosis. Recurrence rates are high and the mean period between diagnosis and recurrence is 12.5 months. A 5-year survival rate of less than 20% has been reported in balloon cell melanomas along with nearly 20% developing local recurrence. Conclusion. To the best of our knowledge, this case is the first report of balloon cell melanoma arising in the urethra. The presentation and surgical management has been described and a literature review provided.

  13. Seven Non-melanoma Features to Rule Out Facial Melanoma

    Directory of Open Access Journals (Sweden)

    Philipp Tschandl

    2017-08-01

    Full Text Available Facial melanoma is difficult to diagnose and dermatoscopic features are often subtle. Dermatoscopic non-melanoma patterns may have a comparable diagnostic value. In this pilot study, facial lesions were collected retrospectively, resulting in a case set of 339 melanomas and 308 non-melanomas. Lesions were evaluated for the prevalence (> 50% of lesional surface of 7 dermatoscopic non-melanoma features: scales, white follicles, erythema/reticular vessels, reticular and/or curved lines/fingerprints, structureless brown colour, sharp demarcation, and classic criteria of seborrhoeic keratosis. Melanomas had a lower number of non-melanoma patterns (p < 0.001. Scoring a lesion suspicious when no prevalent non-melanoma pattern is found resulted in a sensitivity of 88.5% and a specificity of 66.9% for the diagnosis of melanoma. Specificity was higher for solar lentigo (78.8% and seborrhoeic keratosis (74.3% and lower for actinic keratosis (61.4% and lichenoid keratosis (25.6%. Evaluation of prevalent non-melanoma patterns can provide slightly lower sensitivity and higher specificity in detecting facial melanoma compared with already known malignant features.

  14. Proteomic Analysis of Laser Microdissected Melanoma Cells from Skin Organ Cultures

    Science.gov (United States)

    Hood, Brian L.; Grahovac, Jelena; Flint, Melanie S.; Sun, Mai; Charro, Nuno; Becker, Dorothea; Wells, Alan; Conrads, Thomas P

    2010-01-01

    Gaining insights into the molecular events that govern the progression from melanoma in situ to advanced melanoma, and understanding how the local microenvironment at the melanoma site influences this progression, are two clinically pivotal aspects that to date are largely unexplored. In an effort to identify key regulators of the crosstalk between melanoma cells and the melanoma-skin microenvironment, primary and metastatic human melanoma cells were seeded into skin organ cultures (SOCs), and grown for two weeks. Melanoma cells were recovered from SOCs by laser microdissection and whole-cell tryptic digests analyzed by nanoflow liquid chromatography-tandem mass spectrometry with an LTQ-Orbitrap. The differential protein abundances were calculated by spectral counting, the results of which provides evidence that cell-matrix and cell-adhesion molecules that are upregulated in the presence of these melanoma cells recapitulate proteomic data obtained from comparative analysis of human biopsies of invasive melanoma and a tissue sample of adjacent, non-involved skin. This concordance demonstrates the value of SOCs for conducting proteomic investigations of the melanoma microenvironment. PMID:20459140

  15. Establishment and characterization of human uveal malignant melanoma xenografts in nude mice

    DEFF Research Database (Denmark)

    Heegaard, S; Spang-Thomsen, M; Prause, J U

    2003-01-01

    the characteristic properties of malignant melanoma. However, the transplanted cells demonstrated vimentin reactivity, whereas the primary tumour cells were negative for vimentin. It can be concluded that a new experimental model of malignant uveal melanoma with tumours that were easy to observe and access...... model. Tumour tissue blocks (2 x 2 x 2 mm) from enucleated eyes with choroidal malignant melanoma were transplanted subcutaneously into the flanks of nude mice. The growing tumours were measured and serially transplanted. The tumour samples were investigated by histology, immunohistochemistry....... The transplanted tumour cells were epithelioid and slightly larger than the primary tumour cells and had prominent nucleoli. However, the transplanted tumour retained a morphological appearance similar to that of the primary tumour. Immunohistochemical examinations demonstrated that the cells preserved...

  16. Choroidal melanoma

    International Nuclear Information System (INIS)

    Hernandez Quesada, Flora

    2013-01-01

    A useful and practical guide is developed to better track to the uveal melanoma, due to its highly malignant character. Melanoma of the uveal tract (choroid, iris, ciliary body) has been the intraocular tumor most frequent in adults. The biopsy has been inaccessible, due to its location; therefore, the diagnostic should be based on clinical examination and the correct utilization of the diagnostic procedures (ultrasound, fluorescent angiography, computed axial tomography and magnetic resonance). The cases are diagnosed in the histological examination of the operatory piece post-enucleation for other causes. Epidemiological research has been key to determine the associated factors and better to understand the mechanisms of onset of the disease. Anatomopathological studies of choroidal melanoma have permitted to know the natural history of the disease. The decrease of the visual acuity, pain or inflammation are presented as a defect in the visual field. Different techniques to diagnose the disease are explained. Ultrasound in mode A and B, computed axial tomography and magnetic resonance are the diagnostic method of election. Ultrasound has been the primary method of diagnostic, giving the size and vascularisation, useful in tracking, when they are treated in shape conservatively, showing changes in echogenicity and less vascularisation as good response to treatment. The treatments of choroidal melanoma are specified. The correct interpretation of the clinical symptoms and early utilization of diagnostic imaging methods, have permitted to establish the adequate therapeutic and to avoid local and distant metastasis. The uveal melanoma, depending on their size and location, traditionally has been treated by enucleation. Data from the literature and authors, have promoted the conservation of the ocular globe, depending on the size of the tumor. Transpupillary thermotherapy has been an available alternative for small tumors in Costa Rica and level of social security

  17. Sinclair swine melanoma

    International Nuclear Information System (INIS)

    Hook, R.R.; Berkelhammer, J.; Hamby, C.V.

    1986-01-01

    Sinclair(S-1) miniature swine spontaneously develop melanomas which have many biologic and histologic features in common with human superficial spreading melanoma. Host control of this neoplasm was indicated by the high incidence of spontaneous regression, a decrease in tumor development with age and a decrease in progressive growth of the tumor as age of tumor development increases. Immunologic mechanisms were implicated in host control by histologic observation of a mononuclear inflammatory infiltration of tumors which lead to depigmentation and fibrosis. In vitro immunologic studies revealed that leukocytes from melanoma swine were sensitized specifically to a tumor associated antigen like substance present in extracts of cutaneous melanomas and cultured swine melanoma cells and that melanoma swine leukocytes were cytotoxic for swine melanoma cells. Furthermore, these studies suggested the existence of a common cross reactive, melanoma associated antigen shared by human and swine melanomas. Antigenic analyses of swine melanomas with mouse monoclonal antibodies developed to a single swine melanoma cell culture and with rabbit antisera developed to pooled extracts of cutaneous melanomas demonstrated the presence of tumor associated antigens in swine melanoma cell culture and cutaneous melanomas. The failure of mouse monoclonal antibodies to detect antigens in cutaneous melanoma extracts and the failure of rabbit antisera to detect antigens in melanoma cell culture extracts suggested a differential in antigen expression between swine melanoma cells grown in vitro and in vivo

  18. Differential diagnosis in primary and metastatic cutaneous melanoma by FT-Raman spectroscopy Diagnóstico diferencial no melanoma primário e metastático por espectroscopia FT-Raman

    Directory of Open Access Journals (Sweden)

    Andrea Fernandes de Oliveira

    2010-10-01

    Full Text Available PURPOSE: To qualify the FT-Raman spectral data of primary and metastatic cutaneous melanoma in order to obtain a differential diagnosis. METHODS: Ten normal human skin samples without any clinical or histopathological alterations, ten cutaneous melanoma fragments, and nine lymph node metastasis samples were used; 105, 140 and 126 spectra were obtained respectively. Each sample was divided into 2 or 3 fragments of approximately 2 mm³ and positioned in the Raman spectrometer sample holder in order to obtain the spectra; a monochrome laser light Nd:YAG at 1064 nm was used to excite the inelastic effect. RESULTS: To differentiate the three histopathological groups according to their characteristics extracted from the spectra, data discriminative analysis was undertaken. Phenylalanine, DNA, and Amide-I spectral variables stood out in the differentiation of the three groups. The percentages of correctly classified groups based on Phenylalanine, DNA, and Amide-I spectral features was 93.1%. CONCLUSION: FT-Raman spectroscopy is capable of differentiating melanoma from its metastasis, as well as from normal skin.OBJETIVO: Qualificar os dados espectrais FT-Raman do melanoma cutâneo primário e metastático e assim realizar o diagnóstico diferencial. MÉTODOS: Foram utilizadas amostras de 10 fragmentos de pele sem alterações clínicas ou histopatológicas, 10 de melanomas cutâneos e 9 de metástases linfonodais; 105, 140 and 126 espectros foram obtidos respectivamente. Cada amostra foi dividida em 2 ou 3 frações de 2 mm³ e posicionada no porta amostras do espectrômetro Raman para obtenção dos espectros, por meio da excitação do espalhamento inelástico pelo laser de Nd:YAG em 1064 nm incididos na amostra. RESULTADOS: Para diferenciar os três grupos formados de acordo com as características fornecidas pelos espectros, realizamos a análise discriminante dos dados. As variáveis espectrais Fenilalanina, DNA e Amida-I se destacaram na

  19. Ultraviolet-radiation-induced inflammation promotes angiotropism and metastasis in melanoma

    Science.gov (United States)

    Bald, Tobias; Quast, Thomas; Landsberg, Jennifer; Rogava, Meri; Glodde, Nicole; Lopez-Ramos, Dorys; Kohlmeyer, Judith; Riesenberg, Stefanie; van den Boorn-Konijnenberg, Debby; Hömig-Hölzel, Cornelia; Reuten, Raphael; Schadow, Benjamin; Weighardt, Heike; Wenzel, Daniela; Helfrich, Iris; Schadendorf, Dirk; Bloch, Wilhelm; Bianchi, Marco E.; Lugassy, Claire; Barnhill, Raymond L.; Koch, Manuel; Fleischmann, Bernd K.; Förster, Irmgard; Kastenmüller, Wolfgang; Kolanus, Waldemar; Hölzel, Michael; Gaffal, Evelyn; Tüting, Thomas

    2014-03-01

    Intermittent intense ultraviolet (UV) exposure represents an important aetiological factor in the development of malignant melanoma. The ability of UV radiation to cause tumour-initiating DNA mutations in melanocytes is now firmly established, but how the microenvironmental effects of UV radiation influence melanoma pathogenesis is not fully understood. Here we report that repetitive UV exposure of primary cutaneous melanomas in a genetically engineered mouse model promotes metastatic progression, independent of its tumour-initiating effects. UV irradiation enhanced the expansion of tumour cells along abluminal blood vessel surfaces and increased the number of lung metastases. This effect depended on the recruitment and activation of neutrophils, initiated by the release of high mobility group box 1 (HMGB1) from UV-damaged epidermal keratinocytes and driven by Toll-like receptor 4 (TLR4). The UV-induced neutrophilic inflammatory response stimulated angiogenesis and promoted the ability of melanoma cells to migrate towards endothelial cells and use selective motility cues on their surfaces. Our results not only reveal how UV irradiation of epidermal keratinocytes is sensed by the innate immune system, but also show that the resulting inflammatory response catalyses reciprocal melanoma-endothelial cell interactions leading to perivascular invasion, a phenomenon originally described as angiotropism in human melanomas by histopathologists. Angiotropism represents a hitherto underappreciated mechanism of metastasis that also increases the likelihood of intravasation and haematogenous dissemination. Consistent with our findings, ulcerated primary human melanomas with abundant neutrophils and reactive angiogenesis frequently show angiotropism and a high risk for metastases. Our work indicates that targeting the inflammation-induced phenotypic plasticity of melanoma cells and their association with endothelial cells represent rational strategies to specifically interfere

  20. Shared care in the follow-up of early-stage melanoma: a qualitative study of Australian melanoma clinicians’ perspectives and models of care

    Directory of Open Access Journals (Sweden)

    Rychetnik Lucie

    2012-12-01

    Full Text Available Abstract Background Patients with early stage melanoma have high survival rates but require long-term follow-up to detect recurrences and/or new primary tumours. Shared care between melanoma specialists and general practitioners is an increasingly important approach to meeting the needs of a growing population of melanoma survivors. Methods In-depth qualitative study based on semi-structured interviews with 16 clinicians (surgical oncologists, dermatologists and melanoma unit GPs who conduct post-treatment follow-up at two of Australia’s largest specialist referral melanoma treatment and diagnosis units. Interviews were recorded, transcribed and analysed to identify approaches to shared care in follow-up, variations in practice, and explanations of these. Results Melanoma unit clinicians utilised shared care in the follow-up of patients with early stage melanoma. Schedules were determined by patients’ clinical risk profiles. Final arrangements for delivery of those schedules (by whom and where were influenced by additional psychosocial, professional and organizational considerations. Four models of shared care were described: (a surgical oncologist alternating with dermatologist (in-house or local to patient; (b melanoma unit dermatologist and other local doctor (e.g. family physician; (c surgical oncologist and local doctor; or (d melanoma physician and local doctor. Conclusions These models of shared care offer alternative solutions to managing the requirements for long-term follow-up of a growing number of patients with stage I/II melanoma, and warrant further comparative evaluation of outcomes in clinical trials, with detailed cost/benefit analyses.

  1. High accuracy of family history of melanoma in Danish melanoma cases.

    Science.gov (United States)

    Wadt, Karin A W; Drzewiecki, Krzysztof T; Gerdes, Anne-Marie

    2015-12-01

    The incidence of melanoma in Denmark has immensely increased over the last 10 years making Denmark a high risk country for melanoma. In the last two decades multiple public campaigns have sought to increase the awareness of melanoma. Family history of melanoma is a known major risk factor but previous studies have shown that self-reported family history of melanoma is highly inaccurate. These studies are 15 years old and we wanted to examine if a higher awareness of melanoma has increased the accuracy of self-reported family history of melanoma. We examined the family history of 181 melanoma probands who reported 199 cases of melanoma in relatives, of which 135 cases where in first degree relatives. We confirmed the diagnosis of melanoma in 77% of all relatives, and in 83% of first degree relatives. In 181 probands we validated the negative family history of melanoma in 748 first degree relatives and found only 1 case of melanoma which was not reported in a 3 case melanoma family. Melanoma patients in Denmark report family history of melanoma in first and second degree relatives with a high level of accuracy with a true positive predictive value between 77 and 87%. In 99% of probands reporting a negative family history of melanoma in first degree relatives this information is correct. In clinical practice we recommend that melanoma diagnosis in relatives should be verified if possible, but even unverified reported melanoma cases in relatives should be included in the indication of genetic testing and assessment of melanoma risk in the family.

  2. Intratumor and Intertumor Heterogeneity in Melanoma

    Directory of Open Access Journals (Sweden)

    Tomasz M. Grzywa

    2017-12-01

    Full Text Available Melanoma is a cancer that exhibits one of the most aggressive and heterogeneous features. The incidence rate escalates. A high number of clones harboring various mutations contribute to an exceptional level of intratumor heterogeneity of melanoma. It also refers to metastases which may originate from different subclones of primary lesion. Such component of the neoplasm biology is termed intertumor and intratumor heterogeneity. These levels of tumor heterogeneity hinder accurate diagnosis and effective treatment. The increasing number of research on the topic reflects the need for understanding limitation or failure of contemporary therapies. Majority of analyses concentrate on mutations in cancer-related genes. Novel high-throughput techniques reveal even higher degree of variations within a lesion. Consolidation of theories and researches indicates new routes for treatment options such as targets for immunotherapy. The demand for personalized approach in melanoma treatment requires extensive knowledge on intratumor and intertumor heterogeneity on the level of genome, transcriptome/proteome, and epigenome. Thus, achievements in exploration of melanoma variety are described in details. Particularly, the issue of tumor heterogeneity or homogeneity given BRAF mutations is discussed.

  3. Treatment of Regional Metastatic Melanoma of Unknown Primary Origin

    Directory of Open Access Journals (Sweden)

    Elke J. A. H. van Beek

    2015-08-01

    Full Text Available (1 Background: The purpose of this retrospective study was to evaluate the recurrence and survival rates of metastatic melanoma of unknown primary origin (MUP, in order to further refine current recommendations for the surgical treatment; (2 Methods: Medical data of all MUP patients registered between 2000 and 2011, were analyzed. Seventy-eight patients were categorized in either lymph node (axilla, groin, head-and neck or subcutaneous MUP. Axillary node MUPs were generally treated with dissections of levels I-III, inguinal node MUPs with combined superficial and deep groin dissections, and head-and-neck node MUPs with neck dissections to various extents, based on lymph drainage patterns. Subcutaneous lesions were excised with 1–2 cm margins. The primary outcome was treatment outcomes in terms of (locoregional recurrence and survival rates; (3 Results: Lymph node MUP recurred regionally in 11% of patients, with an overall recurrence rate of 45%. In contrast, subcutaneous MUP recurred locally in 65% of patients with an overall recurrence rate of 78%. This latter group had a significantly shorter disease-free interval than patients with lymph node MUP (p = 0.000. In the entire study population, 5-year and 10-year overall survival rates were 56% and 47% respectively, with no differences observed between the various subgroups; (4 Conclusion: The relatively low regional recurrence rate after regional lymph node dissection (11% supports its current status as standard surgical treatment for lymph node MUP. Subcutaneous MUP, on the contrary, appears to recur both locally (65% and overall (78% at a significantly higher rate, suggesting a different biological behavior. However, wide local excision remains the best available option for this specific group.

  4. Ocular Melanoma

    Science.gov (United States)

    ... is Ocular Melanoma? Leer en Español: ¿Qué es el melanoma ocular? Written By: Daniel Porter Reviewed By: Robert H Janigian Jr MD Sep. 01, 2017 Ocular melanoma (melanoma in or around the eye) is a type of cancer that develops in the cells that produce pigment. ...

  5. Treatment and outcomes of anorectal melanoma.

    LENUS (Irish Health Repository)

    Heeney, Anna

    2012-02-01

    INTRODUCTION: anorectal melanoma is an uncommon disease constituting less than 3% of all melanomas. Due to its rarity, there are a lack of randomized control trials regarding appropriate management and current evidence is based mainly on retrospective studies. METHODS: in view of the controversial surgical treatment of anorectal melanoma, we review the most published literature in an attempt to elucidate its typical clinical features along with current thinking with respect to management approaches to this aggressive disease. Using the keywords "anorectal" and "malignant melanoma", a medline search of all articles in English was performed and the relevant articles procured. Additional references were retrieved by cross reference from key articles. RESULTS: anorectal melanoma affects the elderly with a slight preponderance for females. It commonly presents disguised as benign disease with local bleeding or suspicion for haemorrhoidal disease. There is no convincing evidence to indicate that radical resection of primary anorectal melanoma is associated with improvement in local control or survival, and local excision is an acceptable treatment option. CONCLUSION: optimum management depends on several factors and the therapeutic goals should be to lengthen survival and preserve quality-of-life. Given that wide local excision is a more limited intervention with comparable survival it should be considered as the initial treatment choice. Unfortunately prognosis for patients with this disease remains poor despite choice of treatment strategy with overall five year disease-free survival less than twenty percent in most studies.

  6. Melanoma Therapy with Rhenium-Cyclized Alpha Melanocyte Stimulating Hormone Peptide Analogs

    Energy Technology Data Exchange (ETDEWEB)

    Thomas P Quinn

    2005-11-22

    Malignant melanoma is the 6th most commonly diagnosed cancer with increasing incidence in the United States. It is estimated that 54,200 cases of malignant melanoma will be newly diagnosed and 7,600 cases of death will occur in the United States in the year 2003 (1). At the present time, more than 1.3% of Americans will develop malignant melanoma during their lifetime (2). The average survival for patients with metastatic melanoma is about 6-9 months (3). Moreover, metastatic melanoma deposits are resistant to conventional chemotherapy and external beam radiation therapy (3). Systematic chemotherapy is the primary therapeutic approach to treat patients with metastatic melanoma. Dacarbazine is the only single chemotherapy agent approved by FDA for metastatic melanoma treatment (5). However, the response rate to Dacarbazine is only approximately 20% (6). Therefore, there is a great need to develop novel treatment approaches for metastatic melanoma. The global goal of this research program is the rational design, characterization and validation of melanoma imaging and therapeutic radiopharmaceuticals. Significant progress has been made in the design and characterization of metal-cyclized radiolabeled alpha-melanocyte stimulating hormone peptides. Therapy studies with {sup 188}Re-CCMSH demonstrated the therapeutic efficacy of the receptor-targeted treatment in murine and human melanoma bearing mice (previous progress report). Dosimetry calculations, based on biodistribution data, indicated that a significant dose was delivered to the tumor. However, {sup 188}Re is a very energetic beta-particle emitter. The longer-range beta-particles theoretically would be better for larger tumors. In the treatment of melanoma, the larger primary tumor is usually surgically removed leaving metastatic disease as the focus of targeted radiotherapy. Isotopes with lower beta-energies and/or shorter particle lengths should be better suited for targeting metastases. The {sup 177}Lu

  7. Clinical, Histopathological and Cytogenetic Prognosticators in Uveal Melanoma - A Comprehensive Review.

    Science.gov (United States)

    Berus, Tomasz; Halon, Agnieszka; Markiewicz, Anna; Orlowska-Heitzman, Jolanta; Romanowska-Dixon, Bozena; Donizy, Piotr

    2017-12-01

    Uveal melanoma is the most prevalent primary intraocular cancer in adults. Although it accounts for only 5% of all melanomas, it is responsible for 13% of deaths due to this type of cancer. A wide variety of therapeutic options of primary tumor is available and progress in its management is noticeable. The fact still remains, however, that almost half of patients develop metastases which may be due to practically undetectable cancer spread present as early as at diagnosis of the primary focus. Metastatic disease is uniformly fatal despite systemic therapy. Prediction of metastasis is crucial for prognosis. It also allows targeting of emerging new therapeutic methods to the appropriate group of patients. The Authors reviewed literature concerning epidemiology and etiopathogenesis of uveal melanoma, and its clinical, histopathological and cytogenetic prognosticators. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  8. Downregulation of miR-125b in metastatic cutaneous malignant melanoma.

    Science.gov (United States)

    Glud, Martin; Rossing, Maria; Hother, Christoffer; Holst, Line; Hastrup, Nina; Nielsen, Finn C; Gniadecki, Robert; Drzewiecki, Krzysztof T

    2010-12-01

    This study aimed to identify microRNA species involved in the earliest metastatic event in cutaneous malignant melanoma (MM). Samples from 28 patients with MM [stage T2 (tumor), M0 (distant metastasis)] were grouped by the presence of micrometastasis in the sentinel lymph nodes (N0/N1). Melanoma cells were harvested from primary, cutaneous MM tumors by laser-capture microdissection, and microRNA expression profiles were obtained by the microarray technique. Results were validated by quantitative reverse transcription PCR. We found that miR-125b was downregulated in the primary cutaneous melanomas that produced early metastases (T2, N1, M0) compared with the sentinel lymph node-negative (T2, N0, M0) melanomas. MiR-125b has earlier been found to be downregulated in other tumor types and in atypic naevi compared with the common acquired naevi. In conclusion, miR-125b may be involved in an early progression of cutaneous MM.

  9. Sun protection and skin self-examination in melanoma survivors.

    Science.gov (United States)

    Mujumdar, Urvi J; Hay, Jennifer L; Monroe-Hinds, Yvette C; Hummer, Amanda J; Begg, Colin B; Wilcox, Homer B; Oliveria, Susan A; Berwick, Marianne

    2009-10-01

    Patients diagnosed with melanoma are at risk for developing recurrent and second primary disease. Skin self-examination (SSE) and sun protection are standard clinical recommendations to minimize risk. In this study we examined performance of these behaviors in individuals with melanoma drawn from the general population. Potential participants (N=148) with a first primary melanoma diagnosed in 2000 were identified through a population-based cancer registry in New Jersey, USA. One hundred and fifteen individuals participated in a 30 min telephone interview concerning behavioral adherence with SSE and sun protection, self-efficacy for performing these behaviors, and perceived risk of developing another skin cancer. We utilized logistic regression to estimate potential associations of demographic, medical, and psychosocial factors with SSE and sun protection, respectively. Seventeen percent of subjects reported performing comprehensive SSE at least once every two months and 23% engaged in regular sun protection. Utilization of SSE was related to the presence of moles (OR=4.2, 95% CI: 1.1-15) and higher SSE self-efficacy (OR=14.4, 95% CI: 1.9-112). Regular sun protection was related to older age (>60 years; OR=3.3, 95% CI: 1.3-8.7), being female (OR=2.8, 95% CI: 1.1-7.3), and higher sun protection self-efficacy (OR=5.0, 95% CI: 1.4-18). These factors remained significant in multivariate models. In this group of primary melanoma survivors, the rates of SSE and sun protection are comparable to, but do not exceed, general population estimates. This study provides justification for further research to address barriers to prevention and control behaviors in melanoma survivors.

  10. Transformation of a Silent Adrencorticotrophic Pituitary Tumor Into Central Nervous System Melanoma

    Directory of Open Access Journals (Sweden)

    Brandon A. Miller MD, PhD

    2013-06-01

    Full Text Available Silent adrenocorticotrophic pituitary adenomas are nonfunctioning pituitary adenomas that express adrenocorticotrophic hormone (ACTH but do not cause the clinical or laboratory features of hypercortisolemia. Primary central nervous system (CNS melanoma is well documented, but rarely originates in the sellar region or pituitary gland. Here we report transformation of an aggressive silent adrenocorticotrophic pituitary adenoma that transformed into CNS melanoma and review other presentations of pituitary melanoma. A 37-year-old woman initially presented with apoplexy and an invasive nonfunctioning pituitary macroadenoma for which she underwent transphenoidal surgery. The patient underwent 3 subsequent surgeries as the tumor continued to progress. Pathology from the first 3 operations showed pituitary adenoma or carcinoma. Pathology from the final surgery showed melanoma and the magnetic resonance imaging characteristics of the tumor had changed to become consistent with CNS melanoma. Dermatologic and ophthalmologic examinations did not identify cutaneous or ocular melanoma. The patient’s disease progressed despite aggressive surgical, medical and radiologic treatment. To our knowledge, this is the first report demonstrating transformation of a primary pituitary tumor into melanoma. The mechanism of tumor transformation is unclear, but it is possible that a mutation in the original ACTH-producing tumor lead to increased cleavage of pro-opiomelanocortin or ACTH into α-melanocyte-stimulating hormone, which in turn stimulated the expression of microopthalmia transcription factor, leading to melanocytic phenotype transformation.

  11. Primary melanoma lung purposely clinico pathologic considerations of a clinical case

    International Nuclear Information System (INIS)

    Rodríguez, R.; Roldán, G.; Sosa, A.; Mañana, G.; Rodríguez, A.; Panuncio, A.

    2004-01-01

    Introduction: There are few reports of primary malignant melanomas (M M) of visceral organs, general case of metastatic cutaneous and ocular M M regression suffering go unnoticed or diagnosis. Cases of lung primary melanomas (MPP) that meet the clinico pathologic to be considered as such criteria constitute about 0.01% lung tumors and are published as individual case analysis is impossible series of patients. These criteria are under constant review, constituting a field permanent controversial.Materials and method: A case review of the clinical literature on the most relevant of MPP clinico pathological aspects is performed. Case: This is a patient (Pt), 58 years old, smoker, who consults for elements progressive intracranial hypertension installation without other symptoms to note. the Computed tomography (CT) of the skull shows an expansive process only right temporal. Radiography and CT of the chest then show a right parahiliar single nodule without liver involvement without mediastinal symphadenopathy. Flexible bronchoscopy and bronchial brushing are negative. With the proposition that it is a bearer of a lung carcinoma with second only symptomatic brain macroscopically complete resection is performed head injury. The pathology reports that metastasis is a M M. Is discarded the presence of other injuries, especially to skin and eye. Receive brain radiotherapy and a right lower lobectomy whose analysis confirms that this is a M M is performed and that no there are other lesions in the resected lobe. Analyzed the cost / benefit profile indication treatment (t to) with systemic disease in the absence of other obvious injuries continues regular clinical exams. Remained asymptomatic for 5 months relapsing to brain level no new lesions in the lungs. The p te refuses to receive palliative systemic t to reaching, to the presentation of this work, a survival of 11 months. Discussion: Within the clinical criteria that state that is an MPP, the absence of a history of

  12. Communication about melanoma and risk reduction after melanoma diagnosis.

    Science.gov (United States)

    Rodríguez, Vivian M; Berwick, Marianne; Hay, Jennifer L

    2017-12-01

    Melanoma patients are advised to perform regular risk-reduction practices, including sun protection as well as skin self-examinations (SSEs) and physician-led examinations. Melanoma-specific communication regarding family risk and screening may promote such behaviors. To this end, associations between patients' melanoma-specific communication and risk reduction were examined. Melanoma patients (N = 169) drawn from a population-based cancer registry reported their current risk-reduction practices, perceived risk of future melanoma, and communication with physicians and relatives about melanoma risk and screening. Patients were, on average, 56 years old and 6.7 years' post diagnosis; 51% were male, 93% reported "fair/very fair" skin color, 75% completed at least some college, and 22% reported a family history of melanoma. Patients reported varying levels of regular (always/nearly always) sun protection: sunscreen use (79%), shade seeking (60%), hat use (54%), and long-sleeve shirt use (30%). Only 28% performed thorough SSE regularly, whereas 92% reported undergoing physician-led skin examinations within the past year. Participants who were female, younger, and had a higher perceived risk of future melanoma were more likely to report past communication. In adjusted analyses, communication remained uniquely associated with increased sunscreen use and SSE. Encouraging melanoma patients to have a more active role in discussions concerning melanoma risk and screening with relatives and physicians alike may be a useful strategy to promote 2 key risk-reduction practices post melanoma diagnosis and treatment. Future research is needed to identify additional strategies to improve comprehensive risk reduction in long-term melanoma patients. Copyright © 2016 John Wiley & Sons, Ltd.

  13. Expression of VEGF(xxx)b, the inhibitory isoforms of VEGF, in malignant melanoma.

    Science.gov (United States)

    Pritchard-Jones, R O; Dunn, D B A; Qiu, Y; Varey, A H R; Orlando, A; Rigby, H; Harper, S J; Bates, D O

    2007-07-16

    Malignant melanoma is the most lethal of the skin cancers and the UK incidence is rising faster than that of any other cancer. Angiogenesis - the growth of new vessels from preexisting vasculature - is an absolute requirement for tumour survival and progression beyond a few hundred microns in diameter. We previously described a class of anti-angiogenic isoforms of VEGF, VEGF(xxx)b, that inhibit tumour growth in animal models, and are downregulated in some cancers, but have not been investigated in melanoma. To determine whether VEGF(xxx)b expression was altered in melanoma, PCR and immunohistochemistry of archived human tumour samples were used. In normal epidermis and in a proportion of melanoma samples, VEGF(xxx)b staining was seen. Some melanomas had much weaker staining. Subsequent examination revealed that expression was significantly reduced in primary melanoma samples (both horizontal and vertical growth phases) from patients who subsequently developed tumour metastasis compared with those who did not (analysis of variance (ANOVA) Pxxx)b expression appears to predict metastatic spread in patients with primary melanoma. These results suggest that there is a switch in splicing as part of the metastatic process, from anti-angiogenic to pro-angiogenic VEGF isoforms. This may form part of a wider metastatic splicing phenotype.

  14. Primary malignant melanoma of the vagina with repeated local recurrences and brain metastasis

    Directory of Open Access Journals (Sweden)

    Li-Te Lin

    2011-08-01

    Full Text Available Malignant melanoma of the vagina, a very rare malignancy, has a notoriously aggressive behavior associated with a high risk of local recurrence and distant metastasis. At present, there are various treatment options for this disease but no standard guideline. We describe a case of a 54-year-old woman with a locally advanced melanoma of the vagina, who underwent radical surgery, biochemotherapy with interferon-α-2b, chemotherapy, radiotherapy, and repeat excision of local recurrent lesions and brain metastasis. In conclusion, malignant melanoma of the vagina has a high risk for local recurrence. Repeated local excision followed by biochemotherapy is a tolerable treatment.

  15. High accuracy of family history of melanoma in Danish melanoma cases

    DEFF Research Database (Denmark)

    Wadt, Karin A W; Drzewiecki, Krzysztof T; Gerdes, Anne-Marie

    2015-01-01

    The incidence of melanoma in Denmark has immensely increased over the last 10 years making Denmark a high risk country for melanoma. In the last two decades multiple public campaigns have sought to increase the awareness of melanoma. Family history of melanoma is a known major risk factor...... but previous studies have shown that self-reported family history of melanoma is highly inaccurate. These studies are 15 years old and we wanted to examine if a higher awareness of melanoma has increased the accuracy of self-reported family history of melanoma. We examined the family history of 181 melanoma...

  16. Intralesional and metastatic heterogeneity in malignant melanomas demonstrated by stereologic estimates of nuclear volume

    DEFF Research Database (Denmark)

    Sørensen, Flemming Brandt; Erlandsen, M

    1990-01-01

    Regional variability of nuclear 3-dimensional size can be estimated objectively using point-sampled intercepts obtained from different, defined zones within individual neoplasms. In the present study, stereologic estimates of the volume-weighted mean nuclear volume, nuclear vv, within peripheral...... on average larger in the peripheral zones of primary melanomas, than nuclear vv in central zones (2p = 6.7 x 10(-4), whereas no zonal differences were demonstrated in metastatic lesions (2p = 0.21). A marked intraindividual variation was demonstrated between primary and corresponding secondary melanomas (2p...... melanomas showed large interindividual variation. This finding emphasizes that unbiased estimates of nuclear vv are robust to regional heterogeneity of nuclear volume and thus suitable for purposes of objective, quantitative malignancy grading of melanomas....

  17. Role of key-regulator genes in melanoma susceptibility and pathogenesis among patients from South Italy

    International Nuclear Information System (INIS)

    Casula, Milena; Sini, MariaCristina; Palomba, Grazia; The Italian Melanoma Intergroup; Palmieri, Giuseppe; Muggiano, Antonio; Cossu, Antonio; Budroni, Mario; Caracò, Corrado; Ascierto, Paolo A; Pagani, Elena; Stanganelli, Ignazio; Canzanella, Sergio

    2009-01-01

    Several genetic alterations have been demonstrated to contribute to the development and progression of melanoma. In this study, we further investigated the impact of key-regulator genes in susceptibility and pathogenesis of such a disease. A large series (N = 846) of sporadic and familial cases originating from South Italy was screened for germline mutations in p16 CDKN2A , BRCA2, and MC1R genes by DHPLC analysis and automated DNA sequencing. Paired primary melanomas and lymph node metastases from same patients (N = 35) as well as melanoma cell lines (N = 18) were analyzed for somatic mutations in NRAS, BRAF, and p16 CDKN2A genes. For melanoma susceptibility, investigations at germline level indicated that p16 CDKN2A was exclusively mutated in 16/545 (2.9%) non-Sardinian patients, whereas BRCA2 germline mutations were observed in 4/91 (4.4%) patients from North Sardinia only. Two MC1R germline variants, Arg151Cys and Asp294His, were significantly associated with melanoma in Sardinia. Regarding genetic events involved in melanoma pathogenesis at somatic level, mutually-exclusive mutations of NRAS and BRAF genes were observed at quite same rate (about two thirds) in cultured and in vivo melanomas (either primary or metastatic lesions). Conversely, p16 CDKN2A gene alterations were observed at increased rates moving from primary to metastatic melanomas and melanoma cell lines. Activation of the ERK gene product was demonstrated to be consistently induced by a combination of molecular alterations (NRAS/BRAF mutations and p16 CDKN2A silencing). Our findings further clarified that: a) mutation prevalence in melanoma susceptibility genes may vary within each specific geographical area; b) multiple molecular events are accumulating during melanomagenesis

  18. Malignant melanoma of the oral cavity: Report of two cases

    Directory of Open Access Journals (Sweden)

    Anita Munde

    2014-01-01

    Full Text Available Primary malignant melanoma is a rare and aggressive neoplasm that originates from the proliferation of melanocytes. Although, it comprises 1.3% of all cancers, malignant melanoma of the oral cavity accounts for only 0.2-8% of all reported melanomas and occurs approximately 4 times more frequently in the oral mucosa of the upper jaw, usually on the palate or alveolar gingivae. Most of the mucosal melanomas are usually asymptomatic in early stages, and presents as pigmented patch or a mass delaying the diagnosis until symptoms of swelling, ulceration, bleeding, or loosening of teeth are noted. The prognosis is extremely poor, especially in advanced stages. Therefore, any pigmented lesion of undetermined origin should always be biopsied. We herewith report of two cases of oral malignant melanoma in a 60 and 75-year-old female.

  19. Vitamin D and melanoma: state of the art and possible therapeutic uses.

    Science.gov (United States)

    Paolino, Giovanni; Moliterni, Elisa; Corsetti, Paola; Didona, Dario; Bottoni, Ugo; Calvieri, Stefano; Mattozzi, Carlo

    2017-12-15

    Despite the presence of several studies in literature, the real connection between vitamin D serological levels, vitamin D receptor and melanoma remains unclear, probably because of the complex correlation between vitamin D and melanoma. Indeed, UV radiations are not reported as the main risk factor for melanoma in non-sun-exposed, while systemic immunosuppression, anatomical and physiological features may contribute to malignancy. Therefore, the correlation between melanoma cells in sun- exposed areas and vitamin D, as well as vitamin D receptor could be different from the one in melanoma of sun-shielded sites. These differences may also explain the controversial results reported in the literature regarding the correlation between melanoma and vitamin D, as well as the different outcomes in melanoma patients treated with vitamin D as adjuvant therapy. The aim of this review is to highlight the most recent findings about vitamin D and melanoma, focusing on the anatomic site of the primary tumor as well as on the possible therapeutic uses of vitamin D in melanoma patients.

  20. Genetic Background of Iris Melanomas and Iris Melanocytic Tumors of Uncertain Malignant Potential.

    Science.gov (United States)

    van Poppelen, Natasha M; Vaarwater, Jolanda; Mudhar, Hardeep S; Sisley, Karen; Rennie, Ian G; Rundle, Paul; Brands, Tom; van den Bosch, Quincy C C; Mensink, Hanneke W; de Klein, Annelies; Kiliç, Emine; Verdijk, Robert M

    2018-01-19

    Uveal melanoma (UM) is the most common primary intraocular malignancy in adults. Iris melanoma comprises 4% to 10% of all UMs and has a lower mortality rate. The genetic changes in iris melanoma are not as well characterized as ciliary body or choroidal melanoma. The aim of this study was to gain more insight into the genetic background of iris melanoma and iris nevi. Multicenter, retrospective case series. Patients diagnosed with iris melanoma or iris nevi who underwent surgical intervention as primary or secondary treatment. Next-generation sequencing of GNAQ, GNA11, EIF1AX, SF3B1, BAP1, NRAS, BRAF, PTEN, c-Kit, TP53, and TERT was performed on 30 iris melanomas and 7 iris nevi. Copy number status was detected using single nucleotide polymorphisms (SNPs) included in the next-generation sequencing (NGS) panel, SNP array, or fluorescent in situ hybridization. BAP1 immunohistochemistry was performed on all samples. Mutation and copy number status were analyzed. Results of BAP1 immunohistochemistry were used for survival analysis. In 26 of the 30 iris melanoma and all iris nevi, at least 1 mutation was identified. Multiple mutations were detected in 23 iris melanoma and 5 nevi, as well as mutations in GNAQ and GNA11. Furthermore, 13 of 30 BAP1, 5 of 30 EIF1AX, and 2 of 30 SF3B1 mutations were identified in iris melanoma. No correlation between BAP1 status and disease-free survival was found. The iris nevi showed 1 EIF1AX and 3 BAP1 mutations. Two of the nevi, with a BAP1 mutation, were histologically borderline malignant. Mutations in NRAS, BRAF, PTEN, c-KIT, and TP53 were detected in 6 iris melanomas and 4 iris nevi. Mutations that are often found in uveal and cutaneous melanoma were identified in this cohort of iris melanomas and iris nevi. Therefore, iris melanomas harbor a molecular profile comparable to both choroidal melanoma and cutaneous melanoma. These findings may offer adjuvant targeted therapies for iris melanoma. There was no prognostic significance of

  1. Familial melanoma associated with dominant ultraviolet radiation sensitivity

    International Nuclear Information System (INIS)

    Ramsay, R.G.; Chen, P.; Imray, F.P.; Kidson, C.; Lavin, M.F.; Hockey, A.

    1982-01-01

    Sensitivity to ultraviolet radiation was studied in lymphoblastoid cell lines derived from 32 members of two families with histories of multiple primary melanomas in several generations. As assayed by colony formation in agar or by trypan blue exclusion following irradiation, cellular sensitivity showed a bimodal distribution. All persons with melanoma or multiple moles were in the sensitive group, while some family members exhibited responses similar to those of controls. Cells from four cases of sporadic melanoma showed normal levels of sensitivity. The data are consistent with a dominantly inherited ultraviolet light sensitivity associated with these examples of familial melanoma. Spontaneous and ultraviolet light-induced sister chromatid exchange frequencies were similar to those in control cell lines. No defect in excision repair was detected in any of the above cell lines, but the sensitive group showed postirradiation inhibition of DNA replication intermediate between controls and an excision-deficient xeroderma pigmentosum cell line

  2. Malignant melanomas of the meninges (MR and CT)

    International Nuclear Information System (INIS)

    Schuknecht, B.; Nadjmi, M.; Mueller, J.

    1990-01-01

    Malignant melanoma of the meninges is a rare neoplasm derived from melanocytes of the cranial or spinal meninges. Histologically classified as grade IV tumours, malignant melanoma may present either as a diffuse meningeal neoplasm, first described by Virchow in 1859, or as a circumscribed tumour attached to the meninges. Although diagnosis is rarely established prior to surgery or autopsy, MR and CT may provide indispensable information probably leading to earlier diagnosis. In 4 patients, diagnosis of a primary meningeal melanoma was based on MR and CT findings and histology. Histology was obtained in 3 cases by surgery, in one patient by autopsy and showed a melanotic and an amelanotic malignant melanoma in 2 patients each. Autopsy was carried out in 3 cases after survival of 4, 5, and 18 months; in a single case, the follow-up period is almost 3 years. (orig.) [de

  3. [A case of pulmonary malignant melanoma mimicking lung abscess].

    Science.gov (United States)

    Mochizuki, Hideaki; Chikui, Emiko; Tokumaru, Aya; Kato, Takayuki; Arai, Tomio; Takahashi, Hideki

    2011-06-01

    An 84-year-old man was admitted with paresis of the right lower limb. Hemorrhagic lesions were demonstrated in the left frontoparietal lobe and cerebellum by cranial computed tomography (CT) and magnetic resonance imaging (MRI). Chest CT revealed an ill-defined mass measuring 4 x 6 cm in the left lower lobe of the lung, although bronchoscopic examination failed to obtain pathological diagnosis. Clinical diagnosis of primary lung cancer with multiple brain metastases was made, and he underwent whole brain radiotherapy. The pulmonary and cerebral lesions mimicked abscesses during his clinical course, and he died of respiratory failure due to bilateral pneumonia three months after admission. Autopsy revealed that both the pulmonary and brain lesions were malignant melanomas, but no other melanoma lesions could be identified despite meticulous investigation. Although malignant melanoma with an unknown primary site is rare in Japan, careful evaluation of the CT and MRI findings might be the key to correct diagnosis in this case.

  4. Intratumor and Intertumor Heterogeneity in Melanoma.

    Science.gov (United States)

    Grzywa, Tomasz M; Paskal, Wiktor; Włodarski, Paweł K

    2017-12-01

    Melanoma is a cancer that exhibits one of the most aggressive and heterogeneous features. The incidence rate escalates. A high number of clones harboring various mutations contribute to an exceptional level of intratumor heterogeneity of melanoma. It also refers to metastases which may originate from different subclones of primary lesion. Such component of the neoplasm biology is termed intertumor and intratumor heterogeneity. These levels of tumor heterogeneity hinder accurate diagnosis and effective treatment. The increasing number of research on the topic reflects the need for understanding limitation or failure of contemporary therapies. Majority of analyses concentrate on mutations in cancer-related genes. Novel high-throughput techniques reveal even higher degree of variations within a lesion. Consolidation of theories and researches indicates new routes for treatment options such as targets for immunotherapy. The demand for personalized approach in melanoma treatment requires extensive knowledge on intratumor and intertumor heterogeneity on the level of genome, transcriptome/proteome, and epigenome. Thus, achievements in exploration of melanoma variety are described in details. Particularly, the issue of tumor heterogeneity or homogeneity given BRAF mutations is discussed. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  5. Primary Sinonasal Malignant Melanoma: Effect of Clinical and Histopathologic Prognostic Factors on Survival

    Directory of Open Access Journals (Sweden)

    Sercan Göde

    2017-06-01

    Full Text Available Background: Mucosal melanoma is a rare malignancy arising from melanocytes of the mucosal surfaces. The pattern and frequency of oncogenic mutations and histopathological biomarkers have a role on distinct tumour behaviour and survival. Aims: To assess the rate of C-KIT positivity and its effect on survival of surgically treated sinonasal malignant melanoma patients with other histopathological biomarkers and clinical features. Study Design: Retrospective cross-sectional study. Methods: Seventeen sinonasal malignant melanoma patients with a mean age of 65.41 (39-86 years were included. Overall survival and disease-specific survival rates were calculated. The impact of age, gender, stage and extent of the disease, type of surgery, and adjuvant therapies were also taken into consideration. The effect of mitotic index, pigmentation, S100, HMB-45, Melan-A and C-KIT on survival were evaluated. Results: Median tumour size was 20 mm (interquartile range=27.5 mm. Pigmentation was present in 7 (41.2% cases. Median number of mitoses per millimetre squared was 11 (interquartile range=13. Melan A was positive in 7 (41.2% patients, ulceration was present in 6 cases (35.3%, and necrosis was present in (47.1% 8 cases. Six patients (35.3% were positive for S100, 14 (82.4% specimens stained positive for HMB-45 and C-KIT (CD117 was positive in 9 cases (52.9%. Three patients (16.7% developed distant metastasis. Five year overall and disease free survival rates were 61.4% and 43.8%, respectively. Conclusion: Although C-KIT positive sinonasal malignant melanoma patients (52.9% can be candidates for targeted tumour therapies, the studied clinical or histopathological features along with C-KIT seem to have no significant effect on survival in a small group of patients with sinonasal malignant melanoma

  6. Multidisciplinary management of very advanced stage III and IV melanoma: Proof-of-principle.

    Science.gov (United States)

    Gutman, Haim; Ben-Ami, Eytan; Shapira-Frommer, Roni; Schachter, Jacob

    2012-08-01

    Patients with potentially resectable advanced stage III and IV melanoma are a selected subgroup that gain maximal advantage if treated in a melanoma center. Surgery combined with chemo/chemobiotherapy may yield durable remission and long-term palliation. Thirty-seven non-randomly selected patients underwent systemic therapy with the aim of consolidating treatment by surgery. Data were collected prospectively, and analyzed retrospectively. The median follow-up from diagnosis was 50 (3-307) months and 15 (1-156) months when calculated from the last intervention. Twenty-two males and 15 females, with a median age at diagnosis of 44 (20-71) years, with 13 trunk, 13 extremity, 3 head and neck and 8 unknown primary melanomas were included. There were 17 stage III and 20 stage IV patients with a median Breslow thickness of 3.7 (0.45-26) mm. Chemo/chemobiotherapy achieved 7 clinical complete responses (cCRs), 28 partial responses (PRs) and 2 instances of stable disease. Six of the 7 cCRs were operated on, securing pathological complete response in 5 and PR in one. Four of these five and the PR patient still have no evidence of disease (NED). Twenty-one of 30 PR patients were rendered NED by surgery; 14 of these 21 patients succumbed to melanoma, and one is alive with stable disease. Overall, 11 of 37 patients have not succumbed to melanoma, with a median of 72 (14-156) months survival following the last intervention. Of the eight patients with unknown primary melanomas, five have not succumbed to melanoma, with a median of 89 (30-156) months survival following the last intervention. Patients with marginally resectable stage III and IV melanoma have a significant 30% chance, according to this series, for durable remission if treated by a multidisciplinary team in a melanoma center using induction chemobiotherapy and surgery. Results are more favorable for patients with an unknown primary lesion. In view of the currently approved new effective treatments for melanoma, this

  7. Periostin Is a Key Niche Component for Wound Metastasis of Melanoma.

    Directory of Open Access Journals (Sweden)

    Keitaro Fukuda

    Full Text Available Tissue injury promotes metastasis of several human cancers, although factors associated with wound healing that attract circulating tumor cells have remained unknown. Here, we examined the primary and metastatic lesions that appeared 1 month after trauma in a patient with acral lentiginous melanoma. The levels of mRNA for periostin (POSTN, type 1 collagen, and fibronectin were significantly increased in the metastatic lesion relative to the primary lesion. The increase of these extracellular matrix proteins at the wound site was reproduced in a mouse model of wound healing, with the upregulation of Postn mRNA persisting the longest. POSTN was expressed in the region surrounding melanoma cell nests in metastatic lesions of both wounded mice and the patient. POSTN attenuated the cell adhesion and promoted the migration of melanoma cells without affecting their proliferation in vitro. In the mouse model, the wound site as well as subcutaneously injected osteoblasts that secrete large amounts of POSTN invited the metastasis of remotely-transplanted melanoma cells on the sites. Osteoblasts with suppression of POSTN by shRNA showed a greatly reduced ability to promote such metastasis. Our results suggest that POSTN is a key factor in promoting melanoma cell metastasis to wound sites by providing a premetastatic niche.

  8. Study of melanoma invasion by FTIR spectroscopy

    Science.gov (United States)

    Yang, Y.; Sulé-Suso, J.; Sockalingum, G. D.

    2008-02-01

    Compared to other forms of skin cancer, a malignant melanoma has a high risk of spreading to other parts of the body. Melanoma invasion is a complex process involving changes in cell-extracellular matrix (ECM) interaction and cell-cell interactions. To fully understand the factors which control the invasion process, a human skin model system was reconstructed. HBL (a commercially available cell line) melanoma cells were seeded on a skin model with and without the presence of keratinocytes and/or fibroblasts. After 14 days culture, the skin specimens were fixed, parafin embedded and cut into 7 µm sections. The de-parafinised sections were investigated by synchrotron Fourier transformed infrared (FTIR) microspectroscopy to study skin cell invasion behaviour. The advantage of using FTIR is its ability to obtain the fingerprint information of the invading cells in terms of protein secondary structure in comparison to non-invading cells and the concentration of the enzyme (matrix-metalloproteinase) which digests protein matrix, near the invading cells. With aid of the spectral mapping images, it is possible to pinpoint the cells in non-invasion and invasion area and analyse the respective spectra. It has been observed that the protein bands in cells and matrix shifted between non-invasive and invasive cells in the reconstructed skin model. We hypothesise that by careful analysis of the FTIR data and validation by other models, FTIR studies can reveal information on which type of cells and proteins are involved in melanoma invasion. Thus, it is possible to trace the cell invasion path by mapping the spectra along the interface of cell layer and matrix body by FTIR spectroscopy.

  9. IQGAP1 is an oncogenic target in canine melanoma.

    Directory of Open Access Journals (Sweden)

    Becky H Lee

    Full Text Available Canine oral mucosal melanoma is an aggressive malignant neoplasm and is characterized by local infiltration and a high metastatic potential. The disease progression is similar to that of human oral melanomas. Whereas human cutaneous melanoma is primarily driven by activating mutations in Braf (60% or Nras (20%, human mucosal melanoma harbors these mutations much less frequently. This makes therapeutic targeting and research modeling of the oral form potentially different from that of the cutaneous form in humans. Similarly, research has found only rare Nras mutations and no activating Braf mutations in canine oral melanomas, but they are still reliant on MAPK signaling. IQGAP1 is a signaling scaffold that regulates oncogenic ERK1/2 MAPK signaling in human Ras- and Raf- driven cancers, including melanomas. To investigate whether IQGAP1 is a potential target in canine melanoma, we examined the expression and localization of IQGAP1 in primary canine melanomas and canine oral melanoma cell lines obtained from the University of California-Davis. Using CRISPR/Cas9 knockout of IQGAP1, we examined effects on downstream ERK1/2 pathway activity and assayed proliferation of cell lines when treated with a peptide that blocks the interaction between IQGAP1 and ERK1/2. We observed that canine IQGAP1 is expressed and localizes to a similar extent in both human and canine melanoma by qPCR, Western blot, and immunofluorescence. Deletion of IQGAP1 reduces MAPK pathway activation in cell lines, similar to effects seen in human BrafV600E cell lines. Additionally, we demonstrated reduced proliferation when these cells are treated with a blocking peptide in vitro.

  10. Expression of Estrogen Receptor Alpha in Malignant Melanoma

    Directory of Open Access Journals (Sweden)

    Parvin Rajabi

    2017-01-01

    Full Text Available Background: Features of malignant melanoma (MM vary in the different geographic regions of the world. This may be attributable to environmental, ethnic, and genetic factors. The aim of this study was to determine the expression of estrogen receptor alpha (ER-α in MM in Isfahan, Iran. Materials and Methods: This study was planned as a descriptive, analytical, cross-sectional investigation. During this study, paraffin-embedded tissue blocks of patients with a histopathologic diagnosis of MM was studied for ER-α using immunohistochemistry (IHC. Results: In this study, 38 patients (female/male; 20/18 with a definite diagnosis of malignant cutaneous melanoma and mean age of 52.4 ± 11.2 years were investigated. Using envision IHC staining, there were not any cases with ER-α expression. Conclusion: In confirmation to the most previous studies, expression of ER-α was negative in MM. It is recommended to investigate the expression of estrogen receptor beta and other markers in MM.

  11. Comprehensive expression profiling of tumor cell lines identifies molecular signatures of melanoma progression.

    Directory of Open Access Journals (Sweden)

    Byungwoo Ryu

    2007-07-01

    Full Text Available Gene expression profiling has revolutionized our ability to molecularly classify primary human tumors and significantly enhanced the development of novel tumor markers and therapies; however, progress in the diagnosis and treatment of melanoma over the past 3 decades has been limited, and there is currently no approved therapy that significantly extends lifespan in patients with advanced disease. Profiling studies of melanoma to date have been inconsistent due to the heterogeneous nature of this malignancy and the limited availability of informative tissue specimens from early stages of disease.In order to gain an improved understanding of the molecular basis of melanoma progression, we have compared gene expression profiles from a series of melanoma cell lines representing discrete stages of malignant progression that recapitulate critical characteristics of the primary lesions from which they were derived. Here we describe the unsupervised hierarchical clustering of profiling data from melanoma cell lines and melanocytes. This clustering identifies two distinctive molecular subclasses of melanoma segregating aggressive metastatic tumor cell lines from less-aggressive primary tumor cell lines. Further analysis of expression signatures associated with melanoma progression using functional annotations categorized these transcripts into three classes of genes: 1 Upregulation of activators of cell cycle progression, DNA replication and repair (CDCA2, NCAPH, NCAPG, NCAPG2, PBK, NUSAP1, BIRC5, ESCO2, HELLS, MELK, GINS1, GINS4, RAD54L, TYMS, and DHFR, 2 Loss of genes associated with cellular adhesion and melanocyte differentiation (CDH3, CDH1, c-KIT, PAX3, CITED1/MSG-1, TYR, MELANA, MC1R, and OCA2, 3 Upregulation of genes associated with resistance to apoptosis (BIRC5/survivin. While these broad classes of transcripts have previously been implicated in the progression of melanoma and other malignancies, the specific genes identified within each class

  12. Sequential Acral Lentiginous Melanomas of the Foot

    Directory of Open Access Journals (Sweden)

    Jiro Uehara

    2010-12-01

    Full Text Available A 64-year-old Japanese woman had a lightly brown-blackish pigmented macule (1.2 cm in diameter on the left sole of her foot. She received surgical excision following a diagnosis of acral lentiginous melanoma (ALM, which was confirmed histopathologically. One month after the operation, a second melanoma lesion was noticed adjacent to the grafted site. Histopathologically, the two lesions had no continuity, but HMB-45 and cyclin D1 double-positive cells were detected not only on aggregates of atypical melanocytes but also on single cells near the cutting edge of the first lesion. The unique occurrence of a sequential lesion of a primary melanoma might be caused by stimulated subclinical field cells during the wound healing process following the initial operation. This case warrants further investigation to establish the appropriate surgical margin of ALM lesions.

  13. Management of advanced melanoma

    International Nuclear Information System (INIS)

    Nathanson, L.

    1986-01-01

    This book presents papers on the subject of management of advanced melanoma. The topics covered are: non-investigational cytotoxic agents; high-dosage chemotherapy in antologous bone marrow transplantation; Radiotherapy of melanomas; hyperthermia; ureal melanoma; surgical treatment of recurrent a metastatic melanoma; role of interferons in management of melanoma and molecular genetics of melanoma

  14. Platelet-Derived Growth Factor-Receptor α Strongly Inhibits Melanoma Growth In Vitro and In Vivo

    Directory of Open Access Journals (Sweden)

    Debora Faraone

    2009-08-01

    Full Text Available Cutaneous melanoma is the most aggressive skin cancer; it is highly metastatic and responds poorly to current therapies. The expression of platelet-derived growth factor receptors (PDGF-Rs is reported to be reduced in metastatic melanoma compared with benign nevi or normal skin; we then hypothesized that PDGF-Rα may control growth of melanoma cells. We show here that melanoma cells overexpressing PDGF-Rα respond to serum with a significantly lower proliferation compared with that of controls. Apoptosis, cell cycle arrest, pRb dephosphorylation, and DNA synthesis inhibition were also observed in cells overexpressing PDGF-Rα. Proliferation was rescued by PDGF-Rα inhibitors, allowing to exclude nonspecific toxic effects and indicating that PDGF-Rα mediates autocrine antiproliferation signals in melanoma cells. Accordingly, PDGF-Rα was found to mediate staurosporine cytotoxicity. A protein array-based analysis of the mitogen-activated protein kinase pathway revealed that melanoma cells overexpressing PDGF-Rα show a strong reduction of c-Jun phosphorylated in serine 63 and of protein phosphatase 2A/Bα and a marked increase of p38γ, mitogen-activated protein kinase kinase 3, and signal regulatory protein α1 protein expression. In a mouse model of primary melanoma growth, infection with the Ad-vector overexpressing PDGF-Rα reached a significant 70% inhibition of primary melanoma growth (P < .001 and a similar inhibition of tumor angiogenesis. All together, these data demonstrate that PDGF-Rα strongly impairs melanoma growth likely through autocrine mechanisms and indicate a novel endogenous mechanism involved in melanoma control.

  15. Characterization of individuals at high risk of developing melanoma in Latin America: bases for genetic counseling in melanoma.

    Science.gov (United States)

    Puig, Susana; Potrony, Miriam; Cuellar, Francisco; Puig-Butille, Joan Anton; Carrera, Cristina; Aguilera, Paula; Nagore, Eduardo; Garcia-Casado, Zaida; Requena, Celia; Kumar, Rajiv; Landman, Gilles; Costa Soares de Sá, Bianca; Gargantini Rezze, Gisele; Facure, Luciana; de Avila, Alexandre Leon Ribeiro; Achatz, Maria Isabel; Carraro, Dirce Maria; Duprat Neto, João Pedreira; Grazziotin, Thais C; Bonamigo, Renan R; Rey, Maria Carolina W; Balestrini, Claudia; Morales, Enrique; Molgo, Montserrat; Bakos, Renato Marchiori; Ashton-Prolla, Patricia; Giugliani, Roberto; Larre Borges, Alejandra; Barquet, Virginia; Pérez, Javiera; Martínez, Miguel; Cabo, Horacio; Cohen Sabban, Emilia; Latorre, Clara; Carlos-Ortega, Blanca; Salas-Alanis, Julio C; Gonzalez, Roger; Olazaran, Zulema; Malvehy, Josep; Badenas, Celia

    2016-07-01

    CDKN2A is the main high-risk melanoma-susceptibility gene, but it has been poorly assessed in Latin America. We sought to analyze CDKN2A and MC1R in patients from Latin America with familial and sporadic multiple primary melanoma (SMP) and compare the data with those for patients from Spain to establish bases for melanoma genetic counseling in Latin America. CDKN2A and MC1R were sequenced in 186 Latin American patients from Argentina, Brazil, Chile, Mexico, and Uruguay, and in 904 Spanish patients. Clinical and phenotypic data were obtained. Overall, 24 and 14% of melanoma-prone families in Latin America and Spain, respectively, had mutations in CDKN2A. Latin American families had CDKN2A mutations more frequently (P = 0.014) than Spanish ones. Of patients with SMP, 10% of those from Latin America and 8.5% of those from Spain had mutations in CDKN2A (P = 0.623). The most recurrent CDKN2A mutations were c.-34G>T and p.G101W. Latin American patients had fairer hair (P = 0.016) and skin (P < 0.001) and a higher prevalence of MC1R variants (P = 0.003) compared with Spanish patients. The inclusion criteria for genetic counseling of melanoma in Latin America may be the same criteria used in Spain, as suggested in areas with low to medium incidence, SMP with at least two melanomas, or families with at least two cases among first- or second-degree relatives.Genet Med 18 7, 727-736.

  16. Pregnancy and melanoma.

    Science.gov (United States)

    Driscoll, Marcia S; Martires, Kathryn; Bieber, Amy Kalowitz; Pomeranz, Miriam Keltz; Grant-Kels, Jane M; Stein, Jennifer A

    2016-10-01

    Malignant melanoma is the most common malignancy during pregnancy, and is diagnosed during childbearing age in approximately one-third of women diagnosed with melanoma. The impact of hormonal changes during pregnancy and from iatrogenic hormones on melanoma is controversial. Women undergo immunologic changes during pregnancy that may decrease tumor surveillance. In addition, hormone receptors are found on some melanomas. In spite of these observations, the preponderance of evidence does not support a poorer prognosis for pregnancy-associated melanomas. There is also a lack of evidence that oral contraceptives or hormone replacement therapy worsens melanoma prognosis. Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

  17. Pulse-mediated chemotherapy enhances local control and survival in a spontaneous canine model of primary mucosal melanoma.

    Science.gov (United States)

    Spugnini, Enrico P; Dragonetti, Emanuele; Vincenzi, Bruno; Onori, Nicoletta; Citro, Gennaro; Baldi, Alfonso

    2006-02-01

    Mucosal melanomas account for 1% of all malignant melanomas in humans. Treatment options include surgery, chemotherapy, immunotherapy and radiation therapy; however, local recurrence and distant dissemination are still frequent. We treated locally aggressive spontaneous canine oral melanomas that, because of their advanced stage, were not treatable with conventional strategies. A cohort of 10 dogs with oral melanoma was enrolled over a 4-year period. The dogs received two sessions of local bleomycin, followed by the application of trains of biphasic pulses. The treatment was well tolerated and resulted in an overall response rate of 80% with 50% long-term control. Of interest, only one of the dogs died of metastatic disease, and four of the long-term survivors showed a vitiligo-like discoloration at the site of treatment, potentially suggesting a recruitment of the immune system by the therapy. Further studies are needed to characterize this approach and to determine its suitability for head and neck mucosal melanoma.

  18. Multifocal amelanotic conjunctival melanoma and acquired melanosis sine pigmento.

    Science.gov (United States)

    Paridaens, A D; McCartney, A C; Hungerford, J L

    1992-03-01

    Clinical and histopathological features of four cases of multifocal amelanotic malignant melanoma of the conjunctiva in association with 'acquired melanosis sine pigmento' are reported. The absence of conjunctival pigmentation in this extremely rare combination of lesions prevented early diagnosis and clinical monitoring. As a result orbital exenteration was required in three cases. This multicentric non-pigmented variety of conjunctival malignant melanoma tends to present later than pigmented forms and may require exenteration of the orbit as a primary procedure.

  19. SOLAR RADIATION AS A RISK FACTOR FOR CUTANEOUS MELANOMA: REVIEW

    Directory of Open Access Journals (Sweden)

    Marianna Pesce

    2013-04-01

    Full Text Available Melanoma is a particularly aggressive type of skin cancer, and its incidence has been increasing steadily since the 1970s. In this article we have reviewed the main risk factors for this disease in particular: sun exposure, the use of tanning beds or sunlamps and skin phototype. We also mention the importance of primary prevention in subjects at risk to reduce the onset of cutaneous melanoma.

  20. Treatment of cutaneous melanoma: current approaches and future prospects

    International Nuclear Information System (INIS)

    Algazi, Alain P; Soon, Christopher W; Daud, Adil I

    2010-01-01

    Melanoma is the most aggressive and deadly type of skin cancer. Surgical resection with or without lymph node sampling is the standard of care for primary cutaneous melanoma. Adjuvant therapy decisions may be informed by careful consideration of prognostic factors. High-dose adjuvant interferon alpha-2b increases disease-free survival and may modestly improve overall survival. Less toxic alternatives for adjuvant therapy are currently under study. External beam radiation therapy is an option for nodal beds where the risk of local recurrence is very high. In-transit melanoma metastases may be treated locally with surgery, immunotherapy, radiation, or heated limb perfusion. For metastatic melanoma, the options include chemotherapy or immunotherapy; targeted anti-BRAF and anti-KIT therapy is under active investigation. Standard chemotherapy yields objective tumor responses in approximately 10%–20% of patients, and sustained remissions are uncommon. Immunotherapy with high-dose interleukin-2 yields objective tumor responses in a minority of patients; however, some of these responses may be durable. Identification of activating mutations of BRAF, NRAS, c-KIT, and GNAQ in distinct clinical subtypes of melanoma suggest that these are molecularly distinct. Emerging data from clinical trials suggest that substantial improvements in the standard of care for melanoma may be possible

  1. Prevalence of variations in melanoma susceptibility genes among Slovenian melanoma families

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    Besic Nikola

    2008-09-01

    Full Text Available Abstract Background Two high-risk genes have been implicated in the development of CM (cutaneous melanoma. Germline mutations of the CDKN2A gene are found in CDK4 gene reported to date. Beside those high penetrance genes, certain allelic variants of the MC1R gene modify the risk of developing the disease. The aims of our study were: to determine the prevalence of germline CDKN2A mutations and variants in members of families with familial CM and in patients with multiple primary CM; to search for possible CDK4 mutations, and to determine the frequency of variations in the MC1R gene. Methods From January 2001 until January 2007, 64 individuals were included in the study. The group included 28 patients and 7 healthy relatives belonging to 25 families, 26 patients with multiple primary tumors and 3 children with CM. Additionally 54 healthy individuals were included as a control group. Mutations and variants of the melanoma susceptibility genes were identified by direct sequencing. Results Seven families with CDKN2A mutations were discovered (7/25 or 28.0%. The L94Q mutation found in one family had not been previously reported in other populations. The D84N variant, with possible biological impact, was discovered in the case of patient without family history but with multiple primary CM. Only one mutation carrier was found in the control group. Further analysis revealed that c.540C>T heterozygous carriers were more common in the group of CM patients and their healthy relatives (11/64 vs. 2/54. One p14ARF variant was discovered in the control group and no mutations of the CDK4 gene were found. Most frequently found variants of the MC1R gene were T314T, V60L, V92M, R151C, R160W and R163Q with frequencies slightly higher in the group of patients and their relatives than in the group of controls, but the difference was statistically insignificant. Conclusion The present study has shown high prevalence of p16INK4A mutations in Slovenian population of

  2. Genetic variations of patients with familial or multiple melanoma in Southern Brazil.

    Science.gov (United States)

    Grazziotin, T C; Rey, M C W; Bica, C G; Pinto, L A; Bonamigo, R R; Puig-Butille, J A; Cuellar, F; Puig, S

    2013-02-01

    Patients with familial melanoma or multiple primary melanoma represent a high-risk population to hereditary melanoma. Mutations in susceptibility genes, such as CDKN2A, CDK4 and MC1R, have been associated with the development of melanoma. The purpose of this study was to determine the genotypic background of patients with familial and/or multiple melanoma in southern Brazil. This study analysed 33 cases (5 patients with multiple primary melanoma and 28 patients from families with at least two well documented cases) and 29 controls. Genomic analysis of CDKN2A and CDK4 genes by PCR-SSCP analysis and sequencing and direct sequencing of MC1R were performed in all individuals. No functional mutations in CDKN2A or CDK4 were detected in the 62 individuals. Infrequent variants in polymorphic loci of CDKN2A gene were identified in 15 participants (24.2%) and 24/33 (72.8%) cases and 19/27 (70.4%) controls reported at least one infrequent variant in MC1R (P = 0.372). Furthermore, a non-significant tendency towards an association between melanoma risk and MC1R variants G274A and C451T and a non-significant linear tendency to the number of infrequent high-risk variants in MC1R were observed. These results suggest that in southern Brazilian population, CDKN2A or CDK4 germinal alterations may have a weaker influence than previously thought and environmental risk factors may play a central role in melanoma susceptibility. However, considering the tendency observed for gene MC1R, low-penetrance genes may be a relevant aetiological factor in southern Brazil with fair skin population and high sunlight exposure. © 2012 The Authors. Journal of the European Academy of Dermatology and Venereology © 2012 European Academy of Dermatology and Venereology.

  3. One Step Melanoma Surgery for Patient with Thick Primary Melanomas: "To Break the Rules, You Must First Master Them!"

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    Georgi Tchernev

    2018-02-01

    CONCLUSIONS: In this case remains unclear the following question: For what reason a preoperative high - frequent ultrasonography (HFUS is not recommended to be used as it will allow only one surgical excision with the elimination of a tumour with a safety field of 2cm in all directions? The enigma about the obstacles preventing such a rational optimisation of the current diagnostic and therapeutic algorithm in patients with melanomas remains unresolved. One step surgery for cutaneous melanoma is widely used in many countries although it continues to be considered as a matter of dispute for some experts. Once again, by a clinical case and the following analysis, we would like to focus the attention of the dermatosurgical community on this crucial and highly significant problem. Innovations are very often resulting from the simplicity of logic, which unfortunately is not always accepted appropriately.

  4. Aberrant Cx43 Expression and Mislocalization in Metastatic Human Melanomas.

    Science.gov (United States)

    Alaga, Katanya C; Crawford, Melissa; Dagnino, Lina; Laird, Dale W

    2017-01-01

    At present, it is unclear if melanocytes contain Cx43 gap junctions and whether Cx43 expression is regulated in melanoma onset and progression. To this end, we cultured pure populations of mouse melanocytes and found that they had no detectable Cx43 and exhibited an inability for dye transfer indicating they were devoid of functional gap junctions. Given the evidence that melanomas acquire the expression of other connexin isoforms during tumor progression, we assessed if Cx43 was also expressed and assembled into gap junctions at any stage of human melanoma onset and progression to distant metastases. Nearly all primary melanomas within the epidermis lacked Cx43. In contrast, nodal metastases expressed low levels of Cx43 which was markedly higher in distant metastases that had invaded vital organs. Importantly, in all stages of melanoma progression, Cx43 could be detected in intracellular compartments but was rarely assembled into gap junctions indicative of functional gap junction channels. Overall, these studies suggest that melanocytes do not form Cx43 homocellular gap junctions and even though Cx43 levels increase during melanoma progression, this connexin rarely assembles into gap junction structures.

  5. Uveal Melanoma Cell Lines: Where do they come from? (An American Ophthalmological Society Thesis).

    Science.gov (United States)

    Jager, Martine J; Magner, J Antonio Bermudez; Ksander, Bruce R; Dubovy, Sander R

    2016-08-01

    To determine whether some of the most often used uveal melanoma cell lines resemble their original tumor. Analysis of the literature, patient charts, histopathology, mutations, chromosome status, HLA type, and expression of melanocyte markers on cell lines and their primary tumors. We examined five cell lines and the primary tumors from which they were derived. Four of the five examined primary tumors were unusual: one occupied the orbit, two were recurrences after prior irradiation, and one developed in an eye with a nevus of Ota. One cell line did not contain the GNA11 mutation, but it was present in the primary tumor. Three of the primary tumors had monosomy 3 (two of these lacked BAP1 expression); however, all five cell lines showed disomy 3 and BAP1 expression. All of the cell lines had gain of 8q. Two cell lines lacked expression of melanocyte markers, although these were present in the corresponding primary tumor. All cell lines could be traced back to their original uveal melanoma. Four of the five primary tumors were unusual. Cell lines often differed from their primary tumor in chromosome status and melanocyte markers. However, their specific chromosome aberrations and capacity to continue proliferation characterize them as uveal melanoma cell lines.

  6. Advances in Immunotherapy for Melanoma: A Comprehensive Review

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    Carmen Rodríguez-Cerdeira

    2017-01-01

    Full Text Available Melanomas are tumors originating from melanocytes and tend to show early metastasis secondary to the loss of cellular adhesion in the primary tumor, resulting in high mortality rates. Cancer-specific active immunotherapy is an experimental form of treatment that stimulates the immune system to recognize antigens on the surface of cancer cells. Current experimental approaches in immunotherapy include vaccines, biochemotherapy, and the transfer of adoptive T cells and dendritic cells. Several types of vaccines, including peptide, viral, and dendritic cell vaccines, are currently under investigation for the treatment of melanoma. These treatments have the same goal as drugs that are already used to stimulate the proliferation of T lymphocytes in order to destroy tumor cells; however, immunotherapies aim to selectively attack the tumor cells of each patient. In this comprehensive review, we describe recent advancements in the development of immunotherapies for melanoma, with a specific focus on the identification of neoantigens for the prediction of their elicited immune responses. This review is expected to provide important insights into the future of immunotherapy for melanoma.

  7. Investigation for the extended application of melanoma Boron Neutron Capture Therapy

    International Nuclear Information System (INIS)

    Mishima, Yutaka

    1991-11-01

    This issue is the Part B of the Progress Report (III) which includes our latest research results focusing mainly on the successful treatment of the first human melanoma patient who had metastasis in the scalp region. We also include the subsequent clinical treatment of various types of human primary melanoma lesions and the additional basic investigations necessary to perform the treatment. (J.P.N.)

  8. Cytomorphology of cervicovaginal melanoma: ThinPrep versus conventional Papanicolaou tests.

    Science.gov (United States)

    Setia, Namrata; Goulart, Robert A; Leiman, Gladywn; Otis, Christopher N; Modem, Rukmini; Pantanowtiz, Liron

    2010-12-31

    Primary cervicovaginal melanoma is a rare malignancy associated with a high risk of recurrence. Prior studies discussing the cytomorphology of cervicovaginal melanoma have been based primarily on review of conventional Papanicolaou (Pap) smears. The aim of this study was to evaluate cervicovaginal melanomas identified in liquid-based Pap tests, in comparison with features seen on conventional Pap smear preparation. Cases of cervicovaginal melanoma identified on Pap tests with concurrent or subsequent histopathologic confirmation were collected from the Baystate Medical Center cytopathology files and personal archives of the authors over a total period of 34 years. All cytopathology (n = 6) and the available histology slides (n = 5) were reviewed. Cases were analyzed regarding clinical, histopathologic and cytomorphological findings. A total of six cases with invasive cervicovaginal melanoma diagnosed on Pap tests were identified. Most patients were postmenopausal with contact bleeding, correlating with surface ulceration (identified in biopsy/excision material in 5/5 cases). Most cases had deeply invasive tumors (5/5: modified Breslow's thickness > 5 mm and Chung's level of invasion IV/V). Pap tests included four ThinPrep and two conventional smears. Overall, ThinPrep Pap tests exhibited a higher ratio of tumor cells to background squamous cells. While all Pap tests were bloodstained, tumor diathesis was prominent only within conventional smears. Melanoma cells were present both as clusters and scattered single cells in each Pap test type. Both the preparations contained epithelioid tumor cells, whereas spindled tumor cells were seen in only two ThinPrep cases. Prominent nucleoli and binucleation of tumor cells were seen in both the preparations. Melanin pigment was identified in only ThinPrep (3/4) cases and nuclear pseudo-inclusions in one conventional Pap smear. Cell blocks were made in three ThinPrep cases and immunocytochemistry (S-100, HMB45, Melan

  9. Assessing the clinical utility of measuring Insulin-like Growth Factor Binding Proteins in tissues and sera of melanoma patients

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    Buckley Michael T

    2008-11-01

    Full Text Available Abstract Background Different Insulin-like Growth Factor Binding Proteins (IGFBPs have been investigated as potential biomarkers in several types of tumors. In this study, we examined both IGFBP-3 and -4 levels in tissues and sera of melanoma patients representing different stages of melanoma progression. Methods The study cohort consisted of 132 melanoma patients (primary, n = 72; metastatic, n = 60; 64 Male, 68 Female; Median Age = 56 prospectively enrolled in the New York University School of Medicine Interdisciplinary Melanoma Cooperative Group (NYU IMCG between August 2002 and December 2006. We assessed tumor-expression and circulating sera levels of IGFBP-3 and -4 using immunohistochemistry and ELISA assays. Correlations with clinicopathologic parameters were examined using Wilcoxon rank-sum tests and Spearman-rank correlation coefficients. Results Median IGFBP-4 tumor expression was significantly greater in primary versus metastatic patients (70% versus 10%, p = 0.01 A trend for greater median IGFBP-3 sera concentration was observed in metastatic versus primary patients (4.9 μg/ml vs. 3.4 μg/ml, respectively, p = 0.09. However, sera levels fell within a normal range for IGFBP-3. Neither IGFBP-3 nor -4 correlated with survival in this subset of patients. Conclusion Decreased IGFBP-4 tumor expression might be a step in the progression from primary to metastatic melanoma. Our data lend support to a recently-described novel tumor suppressor role of secreting IGFBPs in melanoma. However, data do not support the clinical utility of measuring levels of IGFBP-3 and -4 in sera of melanoma patients.

  10. AMPK promotes survival of c-Myc-positive melanoma cells by suppressing oxidative stress.

    Science.gov (United States)

    Kfoury, Alain; Armaro, Marzia; Collodet, Caterina; Sordet-Dessimoz, Jessica; Giner, Maria Pilar; Christen, Stefan; Moco, Sofia; Leleu, Marion; de Leval, Laurence; Koch, Ute; Trumpp, Andreas; Sakamoto, Kei; Beermann, Friedrich; Radtke, Freddy

    2018-03-01

    Although c-Myc is essential for melanocyte development, its role in cutaneous melanoma, the most aggressive skin cancer, is only partly understood. Here we used the Nras Q61K INK4a -/- mouse melanoma model to show that c-Myc is essential for tumor initiation, maintenance, and metastasis. c-Myc-expressing melanoma cells were preferentially found at metastatic sites, correlated with increased tumor aggressiveness and high tumor initiation potential. Abrogation of c-Myc caused apoptosis in primary murine and human melanoma cells. Mechanistically, c-Myc-positive melanoma cells activated and became dependent on the metabolic energy sensor AMP-activated protein kinase (AMPK), a metabolic checkpoint kinase that plays an important role in energy and redox homeostasis under stress conditions. AMPK pathway inhibition caused apoptosis of c-Myc-expressing melanoma cells, while AMPK activation protected against cell death of c-Myc-depleted melanoma cells through suppression of oxidative stress. Furthermore, TCGA database analysis of early-stage human melanoma samples revealed an inverse correlation between C-MYC and patient survival, suggesting that C-MYC expression levels could serve as a prognostic marker for early-stage disease. © 2018 The Authors.

  11. Growth Inhibition of Re-Challenge B16 Melanoma Transplant by Conjugates of Melanogenesis Substrate and Magnetite Nanoparticles as the Basis for Developing Melanoma-Targeted Chemo-Thermo-Immunotherapy

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    Tomoaki Takada

    2009-01-01

    Full Text Available Melanogenesis substrate, N-propionyl-cysteaminylphenol (NPrCAP, is selectively incorporated into melanoma cells and inhibits their growth by producing cytotoxic free radicals. Magnetite nanoparticles also disintegrate cancer cells and generate heat shock protein (HSP upon exposure to an alternating magnetic field (AMF. This study tested if a chemo-thermo-immunotherapy (CTI therapy strategy can be developed for better management of melanoma by conjugating NPrCAP on the surface of magnetite nanoparticles (NPrCAP/M. We examined the feasibility of this approach in B16 mouse melanoma and evaluated the impact of exposure temperature, frequency, and interval on the inhibition of re-challenged melanoma growth. The therapeutic protocol against the primary transplanted tumor with or without AMF exposure once a day every other day for a total of three treatments not only inhibited the growth of the primary transplant but also prevented the growth of the secondary, re-challenge transplant. The heat-generated therapeutic effect was more significant at a temperature of 43∘C than either 41∘C or 46∘C. NPrCAP/M with AMF exposure, instead of control magnetite alone or without AMF exposure, resulted in the most significant growth inhibition of the re-challenge tumor and increased the life span of the mice. HSP70 production was greatest at 43∘C compared to that with 41∘C or 46∘C. CD+T cells were infiltrated at the site of the re-challenge melanoma transplant.

  12. MMP-9 immunohistochemical expression is correlated with histologic grade in feline diffuse iris melanoma

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    Laura Nordio

    2018-06-01

    Full Text Available Feline diffuse iris melanoma (FDIM is the most common primary intraocular neoplasm in cats. It is usually a malignant tumor, even if slowly progressive, thus representing an unique spontaneous model of the aggressive, although rare, human iris melanoma. In cats, the extent of the tumor within the eye, expressed as histological grade, is considered a good predictor of survival. In the context of the neoplastic cells-tumor microenvironment interaction, Matrix Metalloproteinase-9 (MMP-9 is an endopeptidase able to digest the extracellular matrix with involvement in tumor invasion . MMP-9 expression has been positively correlated with metastasizing behavior in human posterior uveal melanoma. The present study investigates the expression of MMP-9 in a caseload of formalin-fixed paraffin-embedded FDIMs in relation to the histological grade  and mitotic index (MI (threshold=7/10 hpf. Sixty-one samples of FDIM evaluated on light microscopy (Fig. 1 were selected (grade I n=22, grade II n=20, grade III n=19. Immunohistochemical staining with standard ABC method was performed using a mouse anti-MMP-9 antibody. Results were semi-quantitatively scored and compared by Mann-Whitney U test. MMP-9 was expressed in 59,1% grade I FDIM, 90,0% grade II and 80,0% grade III. Tumors with MMP-9 expression in more than 50% of neoplastic cells were 13,6% in grade I cases, 40,0% in grade II and 36,8% in grade III. MMP-9 was expressed in 71,4% of FDIM with MI≤7 and 92,3% of FDIM with MI>7. MMP-9 expression differed significantly between grade I and the other two grades, and between groups with low and high MI. In conclusion, intense expression of MMP-9 seems to correlate with the histological aggressiveness of FDIM.

  13. Burden of Melanoma

    NARCIS (Netherlands)

    C. Holterhues (Cynthia)

    2011-01-01

    markdownabstract__Abstract__ Melanoma is a type of skin cancer that arises from melanocytes. More than 95% of all melanomas occur in the skin, but rarely in the pigmented cells of the eye, meninges or mucosa. This thesis will only regard the invasive cutaneous malignant melanomas.

  14. Improving outcomes in patients with melanoma: strategies to ensure an early diagnosis

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    Voss RK

    2015-11-01

    Full Text Available Rachel K Voss,1 Tessa N Woods,1 Kate D Cromwell,1 Kelly C Nelson,2 Janice N Cormier1 1Department of Surgical Oncology, 2Department of Dermatology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA Abstract: Patients with thin, low-risk melanomas have an excellent long-term prognosis and higher quality of life than those who are diagnosed at later stages. From an economic standpoint, treatment of early stage melanoma consumes a fraction of the health care resources needed to treat advanced disease. Consequently, early diagnosis of melanoma is in the best interest of patients, payers, and health care systems. This review describes strategies to ensure that patients receive an early diagnosis through interventions ranging from better utilization of primary care clinics, to in vivo diagnostic technologies, to new “apps” available in the market. Strategies for screening those at high risk due to age, male sex, skin type, nevi, genetic mutations, or family history are discussed. Despite progress in identifying those at high risk for melanoma, there remains a lack of general consensus worldwide for best screening practices. Strategies to ensure early diagnosis of recurrent disease in those with a prior melanoma diagnosis are also reviewed. Variations in recurrence surveillance practices by type of provider and country are featured, with evidence demonstrating that various imaging studies, including ultrasound, computed tomography, positron emission tomography, and magnetic resonance imaging, provide only minimal gains in life expectancy, even for those with more advanced (stage III disease. Because the majority of melanomas are attributable to ultraviolet radiation in the form of sunlight, primary prevention strategies, including sunscreen use and behavioral interventions, are reviewed. Recent international government regulation of tanning beds is described, as well as issues surrounding the continued use artificial ultraviolet

  15. Malignant melanoma misdiagnosed as diabetic foot ulcer: A case report.

    Science.gov (United States)

    Gao, Wei; Chen, Dawei; Ran, Xingwu

    2017-07-01

    Acral lentiginous melanoma (AML) does not exhibit the classic signs of malignant melanoma. ALM is frequently misdiagnosed because of its unusual sites and atypical clinical morphologies, which lead to poor prognosis. A female patient aged 78 years was presented to our center with two ulcers on her right foot. Diabetic foot ulcer was considered as the primary diagnosis. The ulcers failed to improve after 2 weeks' therapy. An incisional biopsy of the lesion revealed malignant melanoma. The patient received wide excision, skin grafting as well as biotherapy. The lesion was healed and no other metastasis has been founded until now. Clinicians must maintain a high level of suspicion in distinguishing malignant melanoma from other more benign skin lesions of the foot. The need for early biopsy of ulcer, even when clinical suspicion is low, can not be overemphasized. Only in this way can we reduce misdiagnosis rate and improve survival rate in patients with foot ulcer.

  16. Melanomas: radiobiology and role of radiation therapy

    International Nuclear Information System (INIS)

    Peschel, Richard E.

    1995-01-01

    Purpose/Objective: This course will review the radiobiology of malignant melanoma (MM) and the clinical use of radiation therapy for metastatic melanoma and selected primary sites. The course will emphasize the scientific principles underlying the clinical treatment of MM. Introduction: The incidence of malignant melanoma has one of the fastest growth rates in the world. In 1991, there were 32,000 cases and 7,000 deaths from MM in the United States. By the year 2000, one of every 90 Americans will develop MM. Wide local excision is the treatment of choice for Stage I-II cutaneous MM. Five-year survival rates depend on (a) sex: female-63%, male-40%; (b) tumor thickness: t 4 mm-25%; (c) location: extremity-60%, trunk-41%; and (d) regional lymph node status: negative-77%, positive-31%. Despite adequate surgery, 45-50% of all MM patients will develop metastatic disease. Radiobiology: Both the multi-target model: S = 1-(1-e-D/Do)n and the linear quadratic mode: -In(S) = alpha x D + beta x D2 predict a possible benefit for high dose per fraction (> 400 cGy) radiation therapy for some MM cell lines. The extrapolation number (n) varies from 1-100 for MM compared to other mammalian cells with n=2-4. The alpha/beta ratios for a variety of MM cell lines vary from 1 to 33. Other radiobiologic factors (repair of potentially lethal damage, hypoxia, reoxygenation, and repopulation) predict a wide variety of clinical responses to different time-dose prescriptions including high dose per fraction (> 400 cGy), low dose per fraction (200-300 cGy), or b.i.d. therapy. Based on a review of the radiobiology of MM, no single therapeutic strategy emerges which could be expected to be successful for all tumors. Time-Dose Prescriptions: A review of the retrospective and prospective clinical trials evaluating various time-dose prescriptions for MM reveals: (1) MM is a radiosensitive tumor over a wide range of diverse time-dose prescriptions; and (2) The high clinical response rates to a

  17. Validation of an NGS mutation detection panel for melanoma.

    Science.gov (United States)

    Reiman, Anne; Kikuchi, Hugh; Scocchia, Daniela; Smith, Peter; Tsang, Yee Wah; Snead, David; Cree, Ian A

    2017-02-22

    Knowledge of the genotype of melanoma is important to guide patient management. Identification of mutations in BRAF and c-KIT lead directly to targeted treatment, but it is also helpful to know if there are driver oncogene mutations in NRAS, GNAQ or GNA11 as these patients may benefit from alternative strategies such as immunotherapy. While polymerase chain reaction (PCR) methods are often used to detect BRAF mutations, next generation sequencing (NGS) is able to determine all of the necessary information on several genes at once, with potential advantages in turnaround time. We describe here an Ampliseq hotspot panel for melanoma for use with the IonTorrent Personal Genome Machine (PGM) which covers the mutations currently of most clinical interest. We have validated this in 151 cases of skin and uveal melanoma from our files, and correlated the data with PCR based assessment of BRAF status. There was excellent agreement, with few discrepancies, though NGS does have greater coverage and picks up some mutations that would be missed by PCR. However, these are often rare and of unknown significance for treatment. PCR methods are rapid, less time-consuming and less expensive than NGS, and could be used as triage for patients requiring more extensive diagnostic workup. The NGS panel described here is suitable for clinical use with formalin-fixed paraffin-embedded (FFPE) samples.

  18. Fear of new or recurrent melanoma after treatment for localised melanoma.

    Science.gov (United States)

    Bell, Katy J L; Mehta, Yachna; Turner, Robin M; Morton, Rachael L; Dieng, Mbathio; Saw, Robyn; Guitera, Pascale; McCaffery, Kirsten; Low, Donald; Low, Cynthia; Jenkins, Marisa; Irwig, Les; Webster, Angela C

    2017-11-01

    To estimate the amount of fear of new or recurrent melanoma among people treated for localised melanoma in an Australian specialist centre. We randomly selected 400 potential participants from all those treated for localised melanoma at the Melanoma Institute Australia during 2014 (n = 902). They were asked to complete an adapted version of the Fear of Cancer Recurrence Inventory (FCRI). We calculated summary statistics for demographics, clinical variables and total FCRI and subscale scores. Two hundred fifteen people (54%) completed the FCRI questionnaire. The overall mean severity subscale score was 15.0 (95% CI 14.0-16.1). A high proportion of participants had scores above a proposed threshold to screen for clinical fear of cancer recurrence (77% and 63% of participants with and without new or recurrent melanoma had severity subscale scores ≥13). Most participants also had scores above a threshold found to have high specificity for clinical fear of cancer recurrence (65% and 48% of participants with and without new or recurrent melanoma had severity subscale scores ≥16). The severity subscale appeared to discriminate well between groups with differing levels of risk of new or recurrent melanoma. There is a substantial amount of fear of new or recurrent melanoma among this population, despite most having a very good prognosis. Copyright © 2017 John Wiley & Sons, Ltd.

  19. Long-Term Metastatic Risk after Biopsy of Posterior Uveal Melanoma

    DEFF Research Database (Denmark)

    Bagger, Mette; Smidt-Nielsen, Isabel; Andersen, Mette K

    2018-01-01

    PURPOSE: Biopsy of posterior uveal melanoma continues to be intensely debated in terms of the clinical benefits and safety profile. Although several studies have reported a low frequency of ocular complications after tumor biopsy, the potential long-term risk of iatrogenic dissemination remains...... unresolved. The purpose of this study was to assess the risk of metastatic disease after biopsy of posterior uveal melanoma. DESIGN: Retrospective nationwide cohort study linking clinical and histopathologic records to pathology, cancer, and mortality registries. PARTICIPANTS: All patients with posterior...... uveal melanoma treated in Denmark between January 1985 and December 2016. METHODS: For each patient, we recorded detailed information on age, gender, tumor characteristics, and diagnostic and therapeutic measures, including tumor biopsy, if any, and the primary treating hospital. Absolute risk...

  20. Therapy for BRAFi-Resistant Melanomas: Is WNT5A the Answer?

    International Nuclear Information System (INIS)

    Prasad, Chandra Prakash; Mohapatra, Purusottam; Andersson, Tommy

    2015-01-01

    In recent years, scientists have advocated the use of targeted therapies in the form of drugs that modulate genes and proteins that are directly associated with cancer progression and metastasis. Malignant melanoma is a dreadful cancer type that has been associated with the rapid dissemination of primary tumors to multiple sites, including bone, brain, liver and lungs. The discovery that approximately 40%–50% of malignant melanomas contain a mutation in BRAF at codon 600 gave scientists a new approach to tackle this disease. However, clinical studies on patients have shown that although BRAFi (BRAF inhibitors) trigger early anti-tumor responses, the majority of patients later develop resistance to the therapy. Recent studies have shown that WNT5A plays a key role in enhancing the resistance of melanoma cells to BRAFi. The focus of the current review will be on melanoma development, signaling pathways important to acquired resistance to BRAFi, and why WNT5A inhibitors are attractive candidates to be included in combinatorial therapies for melanoma

  1. [X-ray computed tomographic aspects of benign primary cerebral melanomas. Apropos of 4 cases].

    Science.gov (United States)

    Adam, P; Alberge, Y; Espagno, C; Bouzigues, J Y

    1986-02-01

    Benign primitive melanomas are rare tumours usually involving the leptomeninges. Four cranial localizations are reported: 2 tumours of the foramen magnum, 1 of the cerebellopontine angle and 1 supratentorial. The clinical symptomatology is variable according to the level. Slow medullary compression is frequent. One can emphasize the special and difficult problem of foramen magnum tumours that present with a very variable clinical status frequently simulating a non surgical disease of the central nervous system. The benign and primitive appearance of these tumours is evocated by the slow and favourable evolution and by the absence of extraneurologic melanotic tumour. Our purpose is essentially to emphasize the radiological and particularly the computed tomographic (CT) findings poorly described in the literature. Benign melanomas have resemblance with meningiomas: osseous or meningeal relationship, homogeneity and high density. On the other hand the angiography shows poor vascularization. One can think that a tumor simulating a meningioma by CT but not by angiography is perhaps a benign melanoma. The special problem of the radiological diagnosis of foramen magnum tumours is evocated: Computed myelography, tridimensional imaging by NMR.

  2. Sentinel lymph node mapping and biopsy for melanoma in South Brazil

    International Nuclear Information System (INIS)

    Junqueira, G. Jr.; Bodanese, B.; Boff, M.F.; Espindola, M.B.; Haack, R.L.; Frigeri, C.D.L.

    2004-01-01

    Full text: The presence or absence of regional nodal metastases is one of the most important prognostic factors in the survival of patients with primary cutaneous melanoma. Unfortunately, the complications of lymphadenectomy can be significant. An approach that permits accurate staging of the regional nodes without complete lymphadenectomy is sentinel lymph node (SLN) biopsy. We reviewed the records of 107 patients with primary cutaneous melanoma who underwent lymphatic mapping and SLN biopsy from November 2000 to May 2003. In all patients the primary melanoma was at least 1.0 mm thick, if less than 1.0 mm, was at least Clark's level IV or ulcerated or demonstrated evidence of regression if the patient had no evidence of metastatic melanoma in regional lymph nodes and distant sites. All patients underwent preoperative lymphoscintigraphy to identify the lymphatic basin and the site of the sentinel node. All patients subsequently underwent intra-operative lymphatic mapping and selective lymph node biopsy with blue dye and hand-held gamma probe. Excised SLN were analyzed by conventional histological staining (H and E). Immuno-histochemical staining was also performed if the initial pathologic examination was negative. 107 patients (58 female) were subjected to sentinel node biopsy from November 2000 to May 2003. The primary tumor was in arm in 11.2%, legs in 29.9%, trunk in 53,3% and head and neck in 4.6% patients. 72.9% lesions were superficial spreading type and 49.5% were Clark's IV level. The sentinel node biopsy was positive in 13 (12.2%) patients. Our study thus suggests that SLN biopsy improves the accuracy of staging and provides valuable prognostic information to physicians to guide subsequent treatment decisions and facilitates early therapeutic lymph node dissection in patients having nodal metastases. (author)

  3. Genetic profiling of a rare condition: co-occurrence of albinism and multiple primary melanoma in a Caucasian family.

    Science.gov (United States)

    De Summa, Simona; Guida, Michele; Tommasi, Stefania; Strippoli, Sabino; Pellegrini, Cristina; Fargnoli, Maria Concetta; Pilato, Brunella; Natalicchio, Iole; Guida, Gabriella; Pinto, Rosamaria

    2017-05-02

    Multiple primary melanoma (MPM) is a rare condition, whose genetic basis has not yet been clarified. Only 8-12% of MPM are due to germline mutations of CDKN2A. However, other genes (POT1, BRCA1/2, MC1R, MGMT) have been demonstrated to be involved in predisposition to this pathology.To our knowledge, this is the first family study based on two siblings with the rare coexistence of MPM and oculocutaneous albinism (OCA), an autosomal recessive disease characterized by the absence or decrease in pigmentation in the skin, hair, and eyes.In this study, we evaluated genes involved in melanoma predisposition (CDKN2A, CDK4, MC1R, MITF, POT1, RB1, MGMT, BRCA1, BRCA2), pathogenesis (BRAF, NRAS, PIK3CA, KIT, PTEN), skin/hair pigmentation (MC1R, MITF) and in immune pathways (CTLA4) to individuate alterations able to explain the rare onset of MPM and OCA in indexes and the transmission in their pedigree.From the analysis of the pedigree, we were able to identify a "protective" haplotype with respect to MPM, including MGMT p.I174V alteration. The second generation offspring is under strict follow up as some of them have a higher risk of developing MPM according to our model.

  4. Melanoma in Buckinghamshire: Data from the Inception of the Skin Cancer Multidisciplinary Team

    International Nuclear Information System (INIS)

    Cubitt, J. J.; Khan, A. A.; Royston, E.; Rughani, M.; Budny, B. G.; Cubitt, J. J.; Middleton, M. R.

    2013-01-01

    Background. Melanoma incidence is increasing faster than any other cancer in the UK. The introduction of specialist skin cancer multidisciplinary teams intends to improve the provision of care to patients suffering from melanoma. This study aims to investigate the management and survival of patients diagnosed with melanoma around the time of inception of the regional skin cancer multidisciplinary team both to benchmark the service against published data and to enable future analysis of the impact of the specialisation of skin cancer care. Methods. All patients diagnosed with primary cutaneous melanoma between January 1, 2003 and December 3, 2005 were identified. Data on clinical and histopathological features, surgical procedures, complications, disease recurrence and 5-year survival were collected and analysed. Results. Two hundred and fourteen patients were included, 134 female and 80 males. Median Breslow thickness was 0.74 mm (0.7 mm female and 0.8 mm male). Overall 5-year survival was 88% (90% female and 85% male). Discussion. Melanoma incidence in Buckinghamshire is in keeping with published data. Basic demographics details concur with classic melanoma distribution and more recent trends, with increased percentage of superficial spreading and thin melanomas, leading to improved survival are reflected

  5. Association between dermoscopic and reflectance confocal microscopy features of cutaneous melanoma with BRAF mutational status.

    Science.gov (United States)

    Bombonato, C; Ribero, S; Pozzobon, F C; Puig-Butille, J A; Badenas, C; Carrera, C; Malvehy, J; Moscarella, E; Lallas, A; Piana, S; Puig, S; Argenziano, G; Longo, C

    2017-04-01

    Melanomas harbouring common genetic mutations might share certain morphological features detectable with dermoscopy and reflectance confocal microscopy. BRAF mutational status is crucial for the management of metastatic melanoma. To correlate the dermoscopic characteristics of primary cutaneous melanomas with BRAF mutational status. Furthermore, a subset of tumours has also been analysed for the presence of possible confocal features that might be linked with BRAF status. Retrospectively acquired dermoscopic and confocal images of patients with melanoma in tertiary referral academic centres: Skin Cancer Unit in Reggio Emilia and at the Melanoma Unit in Barcelona. Kruskal-Wallis test, logistic regressions, univariate and multivariate analyses have been performed to find dermoscopic and confocal features significantly correlated with BRAF mutational status. Dermoscopically, the presence of irregular peripheral streaks and ulceration were positive predictors of BRAF-mutated melanomas with a statistically significance value, while dotted vessels were more represented in wild-type melanomas. None of the evaluated reflectance confocal microscopy features were correlated with genetic profiling. Ulceration and irregular peripheral streaks represent dermoscopic feature indicative for BRAF-mutated melanoma, while dotted vessels are suggestive for wild-type melanoma. © 2016 European Academy of Dermatology and Venereology.

  6. Increased NY-ESO-1 Expression and Reduced Infiltrating CD3+ T Cells in Cutaneous Melanoma

    Directory of Open Access Journals (Sweden)

    Mara Giavina-Bianchi

    2015-01-01

    Full Text Available NY-ESO-1 is a cancer-testis antigen aberrantly expressed in melanomas, which may serve as a robust and specific target in immunotherapy. NY-ESO-1 antigen expression, tumor features, and the immune profile of tumor infiltrating lymphocytes were assessed in primary cutaneous melanoma. NY-ESO-1 protein was detected in 20% of invasive melanomas (16/79, rarely in in situ melanoma (1/10 and not in benign nevi (0/20. Marked intratumoral heterogeneity of NY-ESO-1 protein expression was observed. NY-ESO-1 expression was associated with increased primary tumor thickness (P=0.007 and inversely correlated with superficial spreading melanoma (P<0.02. NY-ESO-1 expression was also associated with reduced numbers and density of CD3+ tumor infiltrating lymphocytes (P=0.017. When NY-ESO-1 protein was expressed, CD3+ T cells were less diffusely infiltrating the tumor and were more often arranged in small clusters (P=0.010 or as isolated cells (P=0.002 than in large clusters of more than five lymphocytes. No correlation of NY-ESO-1 expression with gender, age, tumor site, ulceration, lymph node sentinel status, or survival was observed. NY-ESO-1 expression in melanoma was associated with tumor progression, including increased tumor thickness, and with reduced tumor infiltrating lymphocytes.

  7. Melanoma during pregnancy

    DEFF Research Database (Denmark)

    de Haan, Jorine; Lok, Christianne A; de Groot, Christianne J M

    2017-01-01

    The management of melanoma during pregnancy is challenging as maternal benefits and fetal risks need to be balanced. Here, we present an overview of the incidence, the demographic and clinical characteristics and the treatment modalities used. After analysis of obstetric, fetal and maternal outcome......, recommendations for clinical practice are provided. From the 'International Network on Cancer, Infertility and Pregnancy' database, pregnant patients with melanoma were identified and analysed. Sixty pregnancies were eligible for analysis. Fifty percent of the patients presented with advanced melanoma during...... pregnancy (14 stage III and 16 stage IV), and 27% were diagnosed with recurrent melanoma. Surgery was the main therapeutic strategy during pregnancy. Only four patients with advanced melanoma were treated during pregnancy with systemic therapy (n=1) or radiotherapy (n=3). Premature delivery was observed...

  8. Improved immunohistochemical evaluation of micrometastases in sentinel lymph nodes of cutaneous melanoma with 'MCW Melanoma Cocktail' – A mixture of monoclonal antibodies to MART-1, melan-A, and tyrosinase

    International Nuclear Information System (INIS)

    Shidham, Vinod B; Qi, Dan; Rao, R Nagarjun; Acker, Scott M; Chang, Chung-Che; Kampalath, Bal; Dawson, Glen; Machhi, Jinobya K; Komorowski, Richard A

    2003-01-01

    MART-1, Melan-A, and Tyrosinase have shown encouraging results for evaluation of melanoma micrometastases in sentinel lymph nodes, as compared to conventionally used S-100 protein and HMB-45. To achieve higher sensitivity, some studies recommend evaluation of three sections, each at intervals of 200 μ. This would mean, routine staining of three adjacent sections in each of the three clusters at intervals of 200 μ, requiring nine slides resulting in added expense. If a cocktail of these antibodies could be used, only one section would be required instead of three generating significant cost savings. We prepared a combination of monoclonal antibodies to these three immunomarkers in optimized dilutions (MART-1, clone M2-7C10, dilution 1:500; Melan-A, clone A103, dilution 1:100; and Tyrosinase, clone T311, dilution 1:50) and designated it as 'MCW melanoma cocktail'. Formalin-fixed paraffin-embedded tissue sections of sentinel lymph nodes from patients with cutaneous melanoma, without macro-metastases were evaluated with this cocktail. Melanoma micrometastases were easily detectable with the cocktail in 41 out of 188 slices (8/24 cases). The diagnostic accuracy amongst five pathologists did not show statistically significant difference. Out of 188 slices, 78 had adjacent sections immunostained individually with MART-1 and Melan-A during our previous study. Of these 78 slices, 21 were positive for melanoma micrometastases with MART-1 and Melan-A individually. However, the adjacent section of these slices immunostained with the cocktail detected metastases in four additional slices. Thus, MART-1 and Melan-A could not detect melanoma micrometastases individually in 16% (4/25) of slices positive with the cocktail. Benign capsular nevi were immunoreactive for the cocktail in 4.8% (9/188) slices. All 81 slices of negative test controls (sentinel lymph nodes of mammary carcinoma) were interpreted correctly as negative for melanoma micrometastases. The melanoma

  9. Sun behaviour after cutaneous malignant melanoma

    DEFF Research Database (Denmark)

    Idorn, L W; Datta, P; Heydenreich, J

    2013-01-01

    Background  It has been reported that patients with cutaneous malignant melanoma (CMM) can lower their risk of a second primary melanoma by limiting recreational sun exposure. Previous studies based on questionnaires and objective surrogate measurements indicate that before their diagnosis......, patients with CMM are exposed to higher ultraviolet radiation (UVR) doses than controls, followed by a reduction after diagnosis. Objectives  In a prospective, observational case-control study, we aimed to assess sun exposure after diagnosis of CMM by objective measurements to substantiate advice about sun...... months and 6 years before the start of the study. During a summer season participants filled in sun exposure diaries daily and wore personal electronic UVR dosimeters in a wristwatch that continuously measured time-stamped UVR doses in standard erythema dose. Results  The UVR dose of recently diagnosed...

  10. Melanoma of the Skin in the Danish Cancer Registry and the Danish Melanoma Database: A Validation Study.

    Science.gov (United States)

    Pedersen, Sidsel Arnspang; Schmidt, Sigrun Alba Johannesdottir; Klausen, Siri; Pottegård, Anton; Friis, Søren; Hölmich, Lisbet Rosenkrantz; Gaist, David

    2018-05-01

    The nationwide Danish Cancer Registry and the Danish Melanoma Database both record data on melanoma for purposes of monitoring, quality assurance, and research. However, the data quality of the Cancer Registry and the Melanoma Database has not been formally evaluated. We estimated the positive predictive value (PPV) of melanoma diagnosis for random samples of 200 patients from the Cancer Registry (n = 200) and the Melanoma Database (n = 200) during 2004-2014, using the Danish Pathology Registry as "gold standard" reference. We further validated tumor characteristics in the Cancer Registry and the Melanoma Database. Additionally, we estimated the PPV of in situ melanoma diagnoses in the Melanoma Database, and the sensitivity of melanoma diagnoses in 2004-2014. The PPVs of melanoma in the Cancer Registry and the Melanoma Database were 97% (95% CI = 94, 99) and 100%. The sensitivity was 90% in the Cancer Registry and 77% in the Melanoma Database. The PPV of in situ melanomas in the Melanoma Database was 97% and the sensitivity was 56%. In the Melanoma Database, we observed PPVs of ulceration of 75% and Breslow thickness of 96%. The PPV of histologic subtypes varied between 87% and 100% in the Cancer Registry and 93% and 100% in the Melanoma Database. The PPVs for anatomical localization were 83%-95% in the Cancer Registry and 93%-100% in the Melanoma Database. The data quality in both the Cancer Registry and the Melanoma Database is high, supporting their use in epidemiologic studies.

  11. Frequent Nuclear/Cytoplasmic Localization of β-Catenin without Exon 3 Mutations in Malignant Melanoma

    Science.gov (United States)

    Rimm, David L.; Caca, Karel; Hu, Gang; Harrison, Frank B.; Fearon, Eric R.

    1999-01-01

    β-Catenin has a critical role in E-cadherin-mediated cell-cell adhesion, and it also functions as a downstream signaling molecule in the wnt pathway. Mutations in the putative glycogen synthase kinase 3β phosphorylation sites near the β-catenin amino terminus have been found in some cancers and cancer cell lines. The mutations render β-catenin resistant to regulation by a complex containing the glycogen synthase kinase 3β, adenomatous polyposis coli, and axin proteins. As a result, β-catenin accumulates in the cytosol and nucleus and activates T-cell factor/lymphoid enhancing factor transcription factors. Previously, 6 of 27 melanoma cell lines were found to have β-catenin exon 3 mutations affecting the N-terminal phosphorylation sites (Rubinfeld B, Robbins P, Elgamil M, Albert I, Porfiri E, Polakis P: Stabilization of beta-catenin by genetic defects in melanoma cell lines. Science 1997, 275:1790–1792). To assess the role of β-catenin defects in primary melanomas, we undertook immunohistochemical and DNA sequencing studies in 65 melanoma specimens. Nuclear and/or cytoplasmic localization of β-catenin, a potential indicator of wnt pathway activation, was seen focally within roughly one third of the tumors, though a clonal somatic mutation in β-catenin was found in only one case (codon 45 Ser→Pro). Our findings demonstrate that β-catenin mutations are rare in primary melanoma, in contrast to the situation in melanoma cell lines. Nonetheless, activation of β-catenin, as indicated by its nuclear and/or cytoplasmic localization, appears to be frequent in melanoma, and in some cases, it may reflect focal and transient activation of the wnt pathway within the tumor. PMID:10027390

  12. Surgical Management and Prognostic Factors of Vulvovaginal Melanoma.

    Science.gov (United States)

    Ditto, Antonino; Bogani, Giorgio; Martinelli, Fabio; Di Donato, Violante; Laufer, Joel; Scasso, Santiago; Chiappa, Valentina; Signorelli, Mauro; Indini, Alice; Lorusso, Domenica; Raspagliesi, Francesco

    2016-07-01

    The aim of the study was to evaluate the surgical management and the role of different prognostic factors on survival outcomes of women affected by genital (i.e., vulvar and vaginal) melanoma. Data of patients undergoing primary surgical treatment for genital melanoma were evaluated in this retrospective study. Baseline, pathological, and postoperative variables were tested to identify prognostic factors. Five-year disease-free survival (DFS) and overall survival (OS) were analyzed using Kaplan-Meier and Cox proportional hazards models. Overall, 98 patients met the inclusion criteria. Sixty-seven (68%) and 31 (32%) patients in this study population were diagnosed with vulvar and vaginal melanoma, respectively. Median (range) DFS and OS were 12 (1-70) and 22 (1-70) months, respectively. Considering factors influencing DFS, we observed that at multivariate analysis, only vaginal localization (hazard ratio [HR] = 3.72; 95% CI = 1.05-13.2) and number of mitoses (HR = 1.24; 95% CI = 1.11-1.39) proved to be associated with worse DFS. Nodal status was the only independent factor influencing 5-year OS in patients with vulvar (HR = 1.76; 95% CI = 1.22-2.54; p = .002) and vaginal (HR = 3.65; 95% CI = 1.08-12.3; p = .03) melanoma. Genital melanomas are characterized by a poor prognosis. Number of mitoses and lymph node status are the main factors influencing survival. Surgery is the mainstay of treatment. A correct and prompt diagnosis is paramount.

  13. A novel recurrent mutation in MITF predisposes to familial and sporadic melanoma

    Science.gov (United States)

    Yokoyama, Satoru; Woods, Susan L.; Boyle, Glen M.; Aoude, Lauren G.; MacGregor, Stuart; Zismann, Victoria; Gartside, Michael; Cust, Anne E.; Haq, Rizwan; Harland, Mark; Taylor, John C.; Duffy, David L.; Holohan, Kelly; Dutton-Regester, Ken; Palmer, Jane M.; Bonazzi, Vanessa; Stark, Mitchell S.; Symmons, Judith; Law, Matthew H.; Schmidt, Christopher; Lanagan, Cathy; O’Connor, Linda; Holland, Elizabeth A.; Schmid, Helen; Maskiell, Judith A.; Jetann, Jodie; Ferguson, Megan; Jenkins, Mark A.; Kefford, Richard F.; Giles, Graham G.; Armstrong, Bruce K.; Aitken, Joanne F.; Hopper, John L.; Whiteman, David C.; Pharoah, Paul D.; Easton, Douglas F.; Dunning, Alison M.; Newton-Bishop, Julia A.; Montgomery, Grant W.; Martin, Nicholas G.; Mann, Graham J.; Bishop, D. Timothy; Tsao, Hensin; Trent, Jeffrey M.; Fisher, David E.; Hayward, Nicholas K.; Brown, Kevin M.

    2012-01-01

    So far, two familial melanoma genes have been identified, accounting for a minority of genetic risk in families. Mutations in CDKN2A account for approximately 40% of familial cases1, and predisposing mutations in CDK4 have been reported in a very small number of melanoma kindreds2. To identify other familial melanoma genes, here we conducted whole-genome sequencing of probands from several melanoma families, identifying one individual carrying a novel germline variant (coding DNA sequence c.G1075A; protein sequence p.E318K; rs149617956) in the melanoma-lineage-specific oncogene microphthalmia-associated transcription factor (MITF). Although the variant co-segregated with melanoma in some but not all cases in the family, linkage analysis of 31 families subsequently identified to carry the variant generated a log odds ratio (lod) score of 2.7 under a dominant model, indicating E318K as a possible intermediate risk variant. Consistent with this, the E318K variant was significantly associated with melanoma in a large Australian case–control sample. Likewise, it was similarly associated in an independent case–control sample from the United Kingdom. In the Australian sample, the variant allele was significantly over-represented in cases with a family history of melanoma, multiple primary melanomas, or both. The variant allele was also associated with increased naevus count and non-blue eye colour. Functional analysis of E318K showed that MITF encoded by the variant allele had impaired sumoylation and differentially regulated several MITF targets. These data indicate that MITF is a melanoma-predisposition gene and highlight the utility of whole-genome sequencing to identify novel rare variants associated with disease susceptibility. PMID:22080950

  14. Incidence of In Situ and Invasive Melanoma in Denmark From 1985 Through 2012

    DEFF Research Database (Denmark)

    Helvind, Neel Maria; Hölmich, Lisbet Rosenkrantz; Smith, Sigrun

    2015-01-01

    in melanoma incidence. Results may indicate the importance of secondary melanoma prevention in Denmark. Future efforts could intensify primary prevention aimed at young adults, adolescents, and children and maintain and target secondary prevention at the population older than 60 years........0% to -2.6%] in men and -3.4% [-4.0% to -2.8%] in women). More proximal tumor location occurred over time (P defined by codes...

  15. Cytokines and Growth Factors Expressed by Human Cutaneous Melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Elias, Elias G., E-mail: george.elias@medstar.net; Hasskamp, Joanne H.; Sharma, Bhuvnesh K. [Maryland Melanoma Center, Weinberg Cancer Institute, Franklin Square Hospital Center, Baltimore, MD (United States)

    2010-05-07

    Cytokines and growth factors have biologic effects that could stimulate tumor growth, invasion and angiogenesis. The incidence of 24 factors was investigated in 25 cultured human melanoma cell lines and in 62 fixed tissues at different stages of the disease. Over 80% of the human melanoma cell lines expressed TGF-β, IL-8, IL-6, VEGF, PDGF-AA and OPN. Significantly higher TGF-β, IGF-1 and IL-15 were determined in primary lesions compared to distant metastases by immunohistochemistry. Illustrating the complexity of the milieu of the tumor microenvironment, some of these factors may have to be considered in targeted therapy.

  16. Plasma 25-Hydroxyvitamin D and Risk of Non-Melanoma and Melanoma Skin Cancer

    DEFF Research Database (Denmark)

    Afzal, Shoaib; Nordestgaard, Børge G; Bojesen, Stig E

    2013-01-01

    Sun exposure is a major risk factor for skin cancer and is also an important source of vitamin D. We tested the hypothesis that elevated plasma 25-hydroxyvitamin D (25-OH-vitD) associates with increased risk of non-melanoma and melanoma skin cancer in the general population. We measured plasma 25......-OH-vitD in 10,060 white individuals from the Danish general population. During 28 years of follow-up, 590 individuals developed non-melanoma skin cancer and 78 developed melanoma skin cancer. Increasing 25-OH-vitD levels, by clinical categories or by seasonally adjusted tertiles, were associated...... with increasing cumulative incidence of non-melanoma skin cancer (trend P=2 × 10(-15) and P=3 × 10(-17)) and melanoma skin cancer (P=0.003 and P=0.001). Multivariable adjusted hazard ratios of non-melanoma skin cancer were 5.04 (95% confidence interval (CI): 2.78-9.16) for 25-OH-vitD 50 vs. 60 years, 25-OH...

  17. SOX2 regulates self-renewal and tumorigenicity of human melanoma-initiating cells.

    Science.gov (United States)

    Santini, R; Pietrobono, S; Pandolfi, S; Montagnani, V; D'Amico, M; Penachioni, J Y; Vinci, M C; Borgognoni, L; Stecca, B

    2014-09-18

    Melanoma is one of the most aggressive types of human cancer, characterized by enhanced heterogeneity and resistance to conventional therapy at advanced stages. We and others have previously shown that HEDGEHOG-GLI (HH-GLI) signaling is required for melanoma growth and for survival and expansion of melanoma-initiating cells (MICs). Recent reports indicate that HH-GLI signaling regulates a set of genes typically expressed in embryonic stem cells, including SOX2 (sex-determining region Y (SRY)-Box2). Here we address the function of SOX2 in human melanomas and MICs and its interaction with HH-GLI signaling. We find that SOX2 is highly expressed in melanoma stem cells. Knockdown of SOX2 sharply decreases self-renewal in melanoma spheres and in putative melanoma stem cells with high aldehyde dehydrogenase activity (ALDH(high)). Conversely, ectopic expression of SOX2 in melanoma cells enhances their self-renewal in vitro. SOX2 silencing also inhibits cell growth and induces apoptosis in melanoma cells. In addition, depletion of SOX2 progressively abrogates tumor growth and leads to a significant decrease in tumor-initiating capability of ALDH(high) MICs upon xenotransplantation, suggesting that SOX2 is required for tumor initiation and for continuous tumor growth. We show that SOX2 is regulated by HH signaling and that the transcription factors GLI1 and GLI2, the downstream effectors of HH-GLI signaling, bind to the proximal promoter region of SOX2 in primary melanoma cells. In functional studies, we find that SOX2 function is required for HH-induced melanoma cell growth and MIC self-renewal in vitro. Thus SOX2 is a critical factor for self-renewal and tumorigenicity of MICs and an important mediator of HH-GLI signaling in melanoma. These findings could provide the basis for novel therapeutic strategies based on the inhibition of SOX2 for the treatment of a subset of human melanomas.

  18. Matrix Metalloproteinase-9 (MMP-9 polymorphisms in patients with cutaneous malignant melanoma

    Directory of Open Access Journals (Sweden)

    Busam Klaus

    2007-03-01

    Full Text Available Abstract Background Cutaneous Malignant Melanoma causes over 75% of skin cancer-related deaths, and it is clear that many factors may contribute to the outcome. Matrix Metalloproteinases (MMPs play an important role in the degradation and remodeling of the extracellular matrix and basement membrane that, in turn, modulate cell division, migration and angiogenesis. Some polymorphisms are known to influence gene expression, protein activity, stability, and interactions, and they were shown to be associated with certain tumor phenotypes and cancer risk. Methods We tested seven polymorphisms within the MMP-9 gene in 1002 patients with melanoma in order to evaluate germline genetic variants and their association with progression and known risk factors of melanoma. The polymorphisms were selected based on previously published reports and their known or potential functional relevance using in-silico methods. Germline DNA was then genotyped using pyrosequencing, melting temperature profiles, heteroduplex analysis, and fragment size analysis. Results We found that reference alleles were present in higher frequency in patients who tend to sunburn, have family history of melanoma, higher melanoma stage, intransit metastasis and desmoplastic melanomas among others. However, after adjustment for age, sex, phenotypic index, moles, and freckles only Q279R, P574R and R668Q had significant associations with intransit metastasis, propensity to tan/sunburn and primary melanoma site. Conclusion This study does not provide strong evidence for further investigation into the role of the MMP-9 SNPs in melanoma progression.

  19. Malignant melanoma - a warning

    International Nuclear Information System (INIS)

    Volden, G.; Rajka, G.; Thune, P.; Falk, E.S.; Krogh, H.K.

    1990-01-01

    Incidence of malignant melonoma of the skin has risen rapidly during the last decades. Mortality rates are also rising, although not so much as incidence rates. There is strong evidence that exposure to sunlight is a major factor in the etiology of melanomas. There appears to be no direct cumulative dose-response relationship, except in the case of lentigo maligna melanoma. Episodes of sunburn among children and young individuals seem to be more important as an etiologic factor for melanoma than chronic exposure to the sun. Very high risk of melanoma exists in persons with dysplastic nevus syndrome. Persons with giant congenital nevi are also at increased risk. However, many melanomas arise de novo. The intension of the authors is to reduce mortality by screening families at risk, by early detection and treatment of melanomas, and by education. 15 refs., 2 tabs

  20. CD63 tetraspanin is a negative driver of epithelial-to-mesenchymal transition in human melanoma cells.

    Science.gov (United States)

    Lupia, Antonella; Peppicelli, Silvia; Witort, Ewa; Bianchini, Francesca; Carloni, Vinicio; Pimpinelli, Nicola; Urso, Carmelo; Borgognoni, Lorenzo; Capaccioli, Sergio; Calorini, Lido; Lulli, Matteo

    2014-12-01

    The CD63 tetraspanin is highly expressed in the early stages of melanoma and decreases in advanced lesions, suggesting it as a possible suppressor of tumor progression. We employed loss- and gain-of-gene-function approaches to investigate the role of CD63 in melanoma progression and acquisition of the epithelial-to-mesenchymal transition (EMT) program. We used two human melanoma cell lines derived from primary tumors and one primary human melanoma cell line isolated from a cutaneous metastasis, differing by levels of CD63 expression. CD63-silenced melanoma cells showed enhanced motility and invasiveness with downregulation of E-cadherin and upregulation of N-cadherin and Snail. In parallel experiments, transient and stable ectopic expression of CD63 resulted in a robust reduction of cell motility, invasiveness, and protease activities, which was proportional to the increase in CD63 protein level. Transfected cells overexpressing the highest level of CD63 when transplanted into immunodeficient mice showed a reduced incidence and rate of tumor growth. Moreover, these cells showed a reduction of N-cadherin, Vimentin, Zeb1, and a-SMA, and a significant resistance to undergo an EMT program both in basal condition and in the following stimulation with TGFβ. Thus, our results establish a previously unreported mechanistic link between the tetraspanin CD63 and EMT abrogation in melanoma.

  1. Intravital imaging reveals transient changes in pigment production and Brn2 expression during metastatic melanoma dissemination.

    Science.gov (United States)

    Pinner, Sophie; Jordan, Peter; Sharrock, Kirsty; Bazley, Laura; Collinson, Lucy; Marais, Richard; Bonvin, Elise; Goding, Colin; Sahai, Erik

    2009-10-15

    How melanoma acquire a metastatic phenotype is a key issue. One possible mechanism is that metastasis is driven by microenvironment-induced switching between noninvasive and invasive states. However, whether switching is a reversible or hierarchical process is not known and is difficult to assess by comparison of primary and metastatic tumors. We address this issue in a model of melanoma metastasis using a novel intravital imaging method for melanosomes combined with a reporter construct in which the Brn-2 promoter drives green fluorescent protein (GFP) expression. A subpopulation of cells containing little or no pigment and high levels of Brn2::GFP expression are motile in the primary tumor and enter the vasculature. Significantly, the less differentiated state of motile and intravasated cells is not maintained at secondary sites, implying switching between states as melanoma cells metastasize. We show that melanoma cells can switch in both directions between high- and low-pigment states. However, switching from Brn2::GFP high to low was greatly favored over the reverse direction. Microarray analysis of high- and low-pigment populations revealed that transforming growth factor (TGF)beta2 was up-regulated in the poorly pigmented cells. Furthermore, TGFbeta signaling induced hypopigmentation and increased cell motility. Thus, a subset of less differentiated cells exits the primary tumor but subsequently give rise to metastases that include a range of more differentiated and pigment-producing cells. These data show reversible phenotype switching during melanoma metastasis.

  2. Intracellular coexpression of CXC- and CC– chemokine receptors and their ligands in human melanoma cell lines and dynamic variations after xenotransplantation

    International Nuclear Information System (INIS)

    Pinto, Sandra; Martínez-Romero, Alicia; O’Connor, José-Enrique; Gil-Benso, Rosario; San-Miguel, Teresa; Terrádez, Liria; Monteagudo, Carlos; Callaghan, Robert C

    2014-01-01

    Chemokines have been implicated in tumor progression and metastasis. In melanoma, chemokine receptors have been implicated in organ selective metastasis by regulating processes such as chemoattraction, adhesion and survival. In this study we have analyzed, using flow cytometry, the systems formed by the chemokine receptors CXCR3, CXCR4, CXCR7, CCR7 and CCR10 and their ligands in thirteen human melanoma cell lines (five established from primary tumors and eight established from metastasis from different tissues). WM-115 and WM-266.4 melanoma cell lines (obtained from a primary and a metastatic melanoma respectively) were xenografted in nude mice and the tumors and cell lines derived from them were also analyzed. Our results show that the melanoma cell lines do not express or express in a low degree the chemokine receptors on their cell surface. However, melanoma cell lines show intracellular expression of all the aforementioned receptors and most of their respective ligands. When analyzing the xenografts and the cell lines obtained from them we found variations in the intracellular expression of chemokines and chemokine receptors that differed between the primary and metastatic cell lines. However, as well as in the original cell lines, minute or no expression of the chemokine receptors was observed at the cell surface. Coexpression of chemokine receptors and their ligands was found in human melanoma cell lines. However, this expression is intracellular and receptors are not found at the cell membrane nor chemokines are secreted to the cell medium. The levels of expressed chemokine receptors and their ligands show dynamic variations after xenotransplantation that differ depending on the origin of the cell line (from primary tumor or from metastasis)

  3. [Melanoma in organ transplant patients].

    Science.gov (United States)

    Lévêque, L; Dalac, S; Dompmartin, A; Louvet, S; Euvrard, S; Catteau, B; Hazan, M; Schollhamer, M; Aubin, F; Dreno, B; Daguin, P; Chevrant-Breton, J; Frances, C; Bismuth, M J; Tanter, Y; Lambert, D

    2000-02-01

    The incidence of cutaneous melanoma has rapidly increased in the white population over the last decades. It has been estimated that the incidence doubles world-wide every 10 years. Different risk factors have been identified, including immunosuppression. The aim of our study-was to determine the relative risk of developing melanoma in the organ transplant population and the clinical and histological features of their melanomas. This retrospective study was conducted with the collaboration of 9 University Hospital Centers: Besançon, Brest, Caen, Dijon, Lille, Lyon, Nantes, Paris (Pitié-Salpétrière) and Rennes. A questionnaire was sent to the different departments of dermatology of these hospitals to obtain information on patients who had presented a melanoma after a transplantation between 1971 and 1997. During this period, there were 12,477 organ transplant recipients in the transplantation units of these 9 hospitals. Average follow-up for these patients was about 5 years and the average duration of immunosuppressive therapy was about 4.5 years. Among 12,477 organ transplant recipients, we found 17 cases of melanoma but no data could be obtain on one case: 14 occurred in renal transplant recipients and 3 in cardiac transplant recipients. Clinical and histological data were only available in 16 patients. The average time between transplantation and diagnosis of melanoma was 63 months, but it was 5 times shorter for 2 patients who had a past history of melanoma before transplantation. Two patients had a mucosal melanoma; for the cutaneous melanomas, 2 appeared on Dubreuilh melanosis, 2 were in situ melanomas, 7 were superficial spreading melanomas and 3 were nodular melanomas. The histological review of 11 cutaneous melanomas revealed a precursor nevus in 6 cases and a weak or no stroma reaction in 7/7 cases. Complete excision of the melanoma was performed in all patients except one with anorectal melanoma. Four patients died of visceral metastasis within a mean

  4. Transcriptional dissection of melanoma identifies a high-risk subtype underlying TP53 family genes and epigenome deregulation

    Science.gov (United States)

    Badal, Brateil; Solovyov, Alexander; Di Cecilia, Serena; Chan, Joseph Minhow; Chang, Li-Wei; Iqbal, Ramiz; Aydin, Iraz T.; Rajan, Geena S.; Chen, Chen; Abbate, Franco; Arora, Kshitij S.; Tanne, Antoine; Gruber, Stephen B.; Johnson, Timothy M.; Fullen, Douglas R.; Phelps, Robert; Bhardwaj, Nina; Bernstein, Emily; Ting, David T.; Brunner, Georg; Schadt, Eric E.; Greenbaum, Benjamin D.; Celebi, Julide Tok

    2017-01-01

    BACKGROUND. Melanoma is a heterogeneous malignancy. We set out to identify the molecular underpinnings of high-risk melanomas, those that are likely to progress rapidly, metastasize, and result in poor outcomes. METHODS. We examined transcriptome changes from benign states to early-, intermediate-, and late-stage tumors using a set of 78 treatment-naive melanocytic tumors consisting of primary melanomas of the skin and benign melanocytic lesions. We utilized a next-generation sequencing platform that enabled a comprehensive analysis of protein-coding and -noncoding RNA transcripts. RESULTS. Gene expression changes unequivocally discriminated between benign and malignant states, and a dual epigenetic and immune signature emerged defining this transition. To our knowledge, we discovered previously unrecognized melanoma subtypes. A high-risk primary melanoma subset was distinguished by a 122-epigenetic gene signature (“epigenetic” cluster) and TP53 family gene deregulation (TP53, TP63, and TP73). This subtype associated with poor overall survival and showed enrichment of cell cycle genes. Noncoding repetitive element transcripts (LINEs, SINEs, and ERVs) that can result in immunostimulatory signals recapitulating a state of “viral mimicry” were significantly repressed. The high-risk subtype and its poor predictive characteristics were validated in several independent cohorts. Additionally, primary melanomas distinguished by specific immune signatures (“immune” clusters) were identified. CONCLUSION. The TP53 family of genes and genes regulating the epigenetic machinery demonstrate strong prognostic and biological relevance during progression of early disease. Gene expression profiling of protein-coding and -noncoding RNA transcripts may be a better predictor for disease course in melanoma. This study outlines the transcriptional interplay of the cancer cell’s epigenome with the immune milieu with potential for future therapeutic targeting. FUNDING

  5. Melanoma risk perception and prevention behavior among African-Americans: the minority melanoma paradox

    Directory of Open Access Journals (Sweden)

    Goldenberg A

    2015-08-01

    Full Text Available Alina Goldenberg,1 Igor Vujic,2,3 Martina Sanlorenzo,2,4 Susana Ortiz-Urda2 1Department of Internal Medicine/Dermatology, University of California, San Diego, 2Mt Zion Cancer Research Center, University of California San Francisco, San Francisco, CA, USA; 3Department of Dermatology, The Rudolfstiftung Hospital, Academic Teaching Hospital, Medical University Vienna, Vienna, Austria; 4Section of Dermatology, Department of Medical Sciences, University of Turin, Turin, Italy Introduction: Melanoma is the most deadly type of skin cancer with 75% of all skin cancer deaths within the US attributed to it. Risk factors for melanoma include ultraviolet exposure, genetic predisposition, and phenotypic characteristics (eg, fair skin and blond hair. Whites have a 27-fold higher incidence of melanoma than African-Americans (AA, but the 5-year survival is 17.8% lower for AA than Whites. It is reported continuously that AA have more advanced melanomas at diagnosis, and overall lower survival rates. This minority melanoma paradox is not well understood or studied. Objective: To explore further, the possible explanations for the difference in melanoma severity and survival in AA within the US. Methods: Qualitative review of the literature. Results: Lack of minority-targeted public education campaigns, low self-risk perception, low self-skin examinations, intrinsic virulence, vitamin D differences, and physician mistrust may play a role in the melanoma survival disparity among AA. Conclusion: Increases in public awareness of melanoma risk among AA through physician and media-guided education, higher index of suspicion among individuals and physicians, and policy changes can help to improve early detection and close the melanoma disparity gap in the future. Keywords: acral, advanced, African-American, disparity, melanoma, survival

  6. Transplantable Melanomas in Hamsters and Gerbils as Models for Human Melanoma. Sensitization in Melanoma Radiotherapy—From Animal Models to Clinical Trials

    Directory of Open Access Journals (Sweden)

    Martyna Śniegocka

    2018-04-01

    Full Text Available The focus of the present review is to investigate the role of melanin in the radioprotection of melanoma and attempts to sensitize tumors to radiation by inhibiting melanogenesis. Early studies showed radical scavenging, oxygen consumption and adsorption as mechanisms of melanin radioprotection. Experimental models of melanoma in hamsters and in gerbils are described as well as their use in biochemical and radiobiological studies, including a spontaneously metastasizing ocular model. Some results from in vitro studies on the inhibition of melanogenesis are presented as well as radio-chelation therapy in experimental and clinical settings. In contrast to cutaneous melanoma, uveal melanoma is very successfully treated with radiation, both using photon and proton beams. We point out that the presence or lack of melanin pigmentation should be considered, when choosing therapeutic options, and that both the experimental and clinical data suggest that melanin could be a target for radiosensitizing melanoma cells to increase efficacy of radiotherapy against melanoma.

  7. Humanistic burden of disease for patients with advanced melanoma in Canada.

    Science.gov (United States)

    Cheung, Winson Y; Bayliss, Martha S; White, Michelle K; Stroupe, Angela; Lovley, Andrew; King-Kallimanis, Bellinda L; Lasch, Kathryn

    2018-06-01

    Metastatic melanoma is a highly aggressive cancer, often striking in the prime of life. This study provides new information directly from advanced melanoma (stage III and IV) patients on how their disease impacts their health-related quality of life (HRQL). Twenty-nine in-depth, qualitative interviews were conducted with adult patients with advanced melanoma in Canada. A semi-structured interview guide was used. Interviews were transcribed verbatim and key concepts were identified using a grounded theory analytic approach. Many patients' journeys began with the startling diagnosis of an invasive disease and a vastly shortened life expectancy. By the time they reached an advanced stage of melanoma, these patients' overall functioning and quality of life had been greatly diminished by this quickly progressing cancer. The impact was described in terms of physical pain and disability, emotional distress, diminished interactions with friends and family, and burden on caregivers. Our findings provide evidence of signs, symptoms, and functional impacts of advanced melanoma. Signs and symptoms reported (physical, mental, and social) confirm and expand on those reported in the existing clinical literature. Primary care physicians should be better trained to identify melanomas early. Oncology care teams can improve on their current approaches for helping patients navigate treatment options, with information about ancillary services to mitigate disease impacts on HRQL, such as mental health and social supports, as well as employment or financial support services.

  8. Genetics of familial melanoma

    DEFF Research Database (Denmark)

    Aoude, Lauren G; Wadt, Karin A W; Pritchard, Antonia L

    2015-01-01

    Twenty years ago, the first familial melanoma susceptibility gene, CDKN2A, was identified. Two years later, another high-penetrance gene, CDK4, was found to be responsible for melanoma development in some families. Progress in identifying new familial melanoma genes was subsequently slow; however...

  9. Marginal and joint distributions of S100, HMB-45, and Melan-A across a large series of cutaneous melanomas.

    Science.gov (United States)

    Viray, Hollis; Bradley, William R; Schalper, Kurt A; Rimm, David L; Gould Rothberg, Bonnie E

    2013-08-01

    The distribution of the standard melanoma antibodies S100, HMB-45, and Melan-A has been extensively studied. Yet, the overlap in their expression is less well characterized. To determine the joint distributions of the classic melanoma markers and to determine if classification according to joint antigen expression has prognostic relevance. S100, HMB-45, and Melan-A were assayed by immunofluorescence-based immunohistochemistry on a large tissue microarray of 212 cutaneous melanoma primary tumors and 341 metastases. Positive expression for each antigen required display of immunoreactivity for at least 25% of melanoma cells. Marginal and joint distributions were determined across all markers. Bivariate associations with established clinicopathologic covariates and melanoma-specific survival analyses were conducted. Of 322 assayable melanomas, 295 (91.6%), 203 (63.0%), and 236 (73.3%) stained with S100, HMB-45, and Melan-A, respectively. Twenty-seven melanomas, representing a diverse set of histopathologic profiles, were S100 negative. Coexpression of all 3 antibodies was observed in 160 melanomas (49.7%). Intensity of endogenous melanin pigment did not confound immunolabeling. Among primary tumors, associations with clinicopathologic parameters revealed a significant relationship only between HMB-45 and microsatellitosis (P = .02). No significant differences among clinicopathologic criteria were observed across the HMB-45/Melan-A joint distribution categories. Neither marginal HMB-45 (P = .56) nor Melan-A (P = .81), or their joint distributions (P = .88), was associated with melanoma-specific survival. Comprehensive characterization of the marginal and joint distributions for S100, HMB-45, and Melan-A across a large series of cutaneous melanomas revealed diversity of expression across this group of antigens. However, these immunohistochemically defined subclasses of melanomas do not significantly differ according to clinicopathologic correlates or outcome.

  10. Sunburn, suntan and the risk of cutaneous malignant melanoma--The Western Canada Melanoma Study.

    Science.gov (United States)

    Elwood, J. M.; Gallagher, R. P.; Davison, J.; Hill, G. B.

    1985-01-01

    A comparison of interview data on 595 patients with newly incident cutaneous melanoma, excluding lentigo maligna melanoma and acral lentiginous melanoma, with data from comparison subjects drawn from the general population, showed that melanoma risk increased in association with the frequency and severity of past episodes of sunburn, and also that melanoma risk was higher in subjects who usually had a relatively mild degree of suntan compared to those with moderate or deep suntan in both winter and summer. The associations with sunburn and with suntan were independent. Melanoma risk is also increased in association with a tendency to burn easily and tan poorly and with pigmentation characteristics of light hair and skin colour, and history freckles; the associations with sunburn and suntan are no longer significant when these other factors are taken into account. This shows that pigmentation characteristics, and the usual skin reaction to sun, are more closely associated with melanoma risk than are sunburn and suntan histories. PMID:3978032

  11. Cure of malignant melanoma by single thermal neutron capture treatment using melanoma-seeking compounds

    International Nuclear Information System (INIS)

    Mishima, Yutaka; Ichihashi, Masamitsu; Nakanishi, Takafumi

    1985-01-01

    Since not only malignant melanomas but also many kinds of human cancers, for example thyroid cancer and squamous cell carcinoma, synthesize their specific protein, much attention has been paid to the establishment of selective thermal neutron capture treatment of malignant melanoma as a prototype of such cancer cells. This paper presents 10 B chlorpromazine compounds and 10 B 1 -para-boronophenylalanine ( 10 B 1 -BPA) as tumor-seeking 10 B compounds which themselves possess selective affinity for the specific metabolic activity of the target cancer cells. An overview of the following studies on the effects of 10 B 1 -BPA in the thermal neutron capture treatment of melanoma is provided: 1) in vitro studies on specific enhanced melanoma cell killing effects of 10 B 1 -BPA; 2) in vivo studies on therapeutic effects of 10 B 1 -BPA using melanoma-bearing hamsters; and 3) preclinical therapeutic experiments using spontaneously occurring malignant melanoma in Duroc pig skin, including experiments in which melanoma was successfully cured. (Namekawa, K.)

  12. Selective thermal neutron capture therapy of malignant melanoma using melanogenesis-seeking 10B-compounds

    International Nuclear Information System (INIS)

    Mishima, Yutaka

    1991-11-01

    This issue is the Part B of the Progress Report (III) which includes our latest research results focusing mainly on the successful treatment of the first human melanoma patient who had metastasis in the scalp region. We also include the subsequent clinical treatment of various types of human primary melanoma lesions and the additional basic investigations necessary to perform the treatment. (J.P.N.)

  13. Naturally occurring melanomas in dogs as models for non-UV pathways of human melanomas.

    Science.gov (United States)

    Gillard, Marc; Cadieu, Edouard; De Brito, Clotilde; Abadie, Jérôme; Vergier, Béatrice; Devauchelle, Patrick; Degorce, Frédérique; Dréano, Stephane; Primot, Aline; Dorso, Laetitia; Lagadic, Marie; Galibert, Francis; Hédan, Benoit; Galibert, Marie-Dominique; André, Catherine

    2014-01-01

    Spontaneously occurring melanomas are frequent in dogs. They appear at the same localizations as in humans, i.e. skin, mucosal sites, nail matrix and eyes. They display variable behaviors: tumors at oral localizations are more frequent and aggressive than at other anatomical sites. Interestingly, dog melanomas are associated with strong breed predispositions and overrepresentation of black-coated dogs. Epidemiological analysis of 2350 affected dogs showed that poodles are at high risk of developing oral melanoma, while schnauzers or Beauce shepherds mostly developped cutaneous melanoma. Clinical and histopathological analyses were performed on a cohort of 153 cases with a 4-yr follow-up. Histopathological characterization showed that most canine tumors are intradermal and homologous to human rare morphological melanomas types - 'nevocytoid type' and 'animal type'-. Tumor cDNA sequencing data, obtained from 95 dogs for six genes, relevant to human melanoma classification, detected somatic mutations in oral melanoma, in NRAS and PTEN genes, at human hotspot sites, but not in BRAF. Altogether, these findings support the relevance of the dog model for comparative oncology of melanomas, especially for the elucidation of non-UV induced pathways. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  14. Claudin11 Promoter Hypermethylation Is Frequent in Malignant Melanoma of the Skin, but Uncommon in Nevus Cell Nevi

    Energy Technology Data Exchange (ETDEWEB)

    Walesch, Sara K.; Richter, Antje M. [Institute for Genetics, Justus-Liebig-University Giessen, D-35392 Giessen (Germany); Helmbold, Peter [Department of Dermatology, University of Heidelberg, D-69120 Heidelberg (Germany); Dammann, Reinhard H., E-mail: reinhard.dammann@gen.bio.uni-giessen.de [Institute for Genetics, Justus-Liebig-University Giessen, D-35392 Giessen (Germany)

    2015-07-07

    Epigenetic inactivation of tumor-related genes is an important characteristic in the pathology of human cancers, including melanomagenesis. We analyzed the epigenetic inactivation of Claudin 11 (CLDN11) in malignant melanoma (MM) of the skin, including six melanoma cell lines, 39 primary melanoma, 41 metastases of MM and 52 nevus cell nevi (NCN). CLDN11 promoter hypermethylation was found in 19 out of 39 (49%) of the primary MM and in 21 out of 41 (51%) of the MM metastases, but only in eight out of 52 (15%) of NCN (p = 0.001 and p = 0.0003, respectively). Moreover, a significant increase in the methylation level of CLDN11 from primary melanomas to MM metastases was revealed (p = 0.003). Methylation of CLDN11 was significantly more frequent in skin metastases (79%) compared to brain metastases (31%; p = 0.007). CLDN11 methylation was also found in five out of six MM cell lines (83%) and its promoter hypermethylation correlated with a reduced expression. Treatment of MM cell lines with a DNA methylation inhibitor reactivated CLDN11 transcription by its promoter demethylation. In summary, CLDN11 proved to be an epigenetically inactivated tumor related gene in melanomagenesis, and analysis of CLDN11 methylation level represents a potential tool for assisting in the discrimination between malignant melanoma and nevus cell nevi.

  15. Cytokines and Growth Factors Expressed by Human Cutaneous Melanoma

    Directory of Open Access Journals (Sweden)

    Elias G. Elias

    2010-05-01

    Full Text Available Cytokines and growth factors have biologic effects that could stimulate tumor growth, invasion and angiogenesis. The incidence of 24 factors was investigated in 25 cultured human melanoma cell lines and in 62 fixed tissues at different stages of the disease. Over 80% of the human melanoma cell lines expressed TGF-β, IL-8, IL-6, VEGF, PDGF-AA and OPN. Significantly higher TGF-β, IGF-1 and IL-15 were determined in primary lesions compared to distant metastases by immunohistochemistry. Illustrating the complexity of the milieu of the tumor microenvironment, some of these factors may have to be considered in targeted therapy.

  16. Communication by mothers with breast cancer or melanoma with their children.

    Science.gov (United States)

    Gaber, Rikki; Desai, Sapna; Smith, Maureen; Eilers, Steve; Blatt, Hanz; Guevara, Yanina; Robinson, June K

    2013-08-08

    Communication of familial risk of breast cancer and melanoma has the potential to educate relatives about their risk, and may also motivate them to engage in prevention and early detection practices. With the Health Insurance Portability and Accountability Act (HIPAA) privacy laws, the patient often becomes the sole communicator of such risks to family members. This study surveys mothers diagnosed with either breast cancer or melanoma and their adult children about their family communication style, knowledge of increased risk, and early detection practices. In both cancer groups, most mothers alerted their children of the risk and need for early detection practices. Breast cancer mothers communicated risk and secondary prevention with early detection by breast self-examination and mammograms whereas the melanoma mothers communicated risk and primary prevention strategies like applying sunscreen and avoiding deliberate tanning. Open communication about health matters significantly increased the likelihood that children engaged in early detection and/or primary prevention behaviors. Examining the information conveyed to at-risk family members, and whether such information motivated them to engage in early detection/prevention behaviors, is key to guiding better cancer prevention communication between doctors and patients.

  17. Communication by Mothers with Breast Cancer or Melanoma with Their Children

    Directory of Open Access Journals (Sweden)

    June K. Robinson

    2013-08-01

    Full Text Available Communication of familial risk of breast cancer and melanoma has the potential to educate relatives about their risk, and may also motivate them to engage in prevention and early detection practices. With the Health Insurance Portability and Accountability Act (HIPAA privacy laws, the patient often becomes the sole communicator of such risks to family members. This study surveys mothers diagnosed with either breast cancer or melanoma and their adult children about their family communication style, knowledge of increased risk, and early detection practices. In both cancer groups, most mothers alerted their children of the risk and need for early detection practices. Breast cancer mothers communicated risk and secondary prevention with early detection by breast self-examination and mammograms whereas the melanoma mothers communicated risk and primary prevention strategies like applying sunscreen and avoiding deliberate tanning. Open communication about health matters significantly increased the likelihood that children engaged in early detection and/or primary prevention behaviors. Examining the information conveyed to at-risk family members, and whether such information motivated them to engage in early detection/prevention behaviors, is key to guiding better cancer prevention communication between doctors and patients.

  18. Increased UV-induced sister-chromatid exchange in cultured fibroblasts of first-degree relatives of melanoma patients

    International Nuclear Information System (INIS)

    Knees-Matzen, S.; Roser, M.; Reimers, U.; Ehlert, U.; Weichenthal, M.; Breitbart, E.W.; Ruediger, H.W.

    1991-01-01

    Cultured fibroblasts of 17 first-degree relatives of familial melanoma patients and six first-degree relatives of cutaneous melanoma (CMM) patients with multiple CMM primaries were tested for in vitro sensitivity to UV light. Fibroblasts of nine familial CMM patients with a known UV-sensitivity and 19 healthy probands served as a control. Sister chromatid exchange (SCE) was used as a parameter to detect UV-induced genotoxic damage. The authors found significantly (p less than 0.001) increased UV-induced SCE levels in familial melanoma patients, as well as in first-degree relatives of familial melanoma patients (p less than 0.001) after UV-A,B irradiation (375 J/m2), compared to the healthy probands without a family history of CMM. A significant (p less than 0.001) increase of UV-induced SCE was also observed in the relatives of CMM patients with multiple CMM primaries. In addition, the spontaneous SCE were significantly increased (p less than 0.05) in familial CMM patients. This study shows that increased UV sensitivity is a familial phenomenon. It is consistent with the concept of a genetic predisposition to CMM, which is based on increased UV sensitivity and may help to define groups with an elevated risk of developing cutaneous malignant melanoma

  19. Melanoma of the vulva and vagina: principles of staging and their relevance to management based on a clinicopathologic analysis of 85 cases.

    Science.gov (United States)

    Seifried, Susan; Haydu, Lauren E; Quinn, Michael J; Scolyer, Richard A; Stretch, Jonathan R; Thompson, John F

    2015-01-01

    Primary melanomas of the vulva and vagina are rare. As a result, it has been difficult to develop evidence-based guidelines for their management. By analyzing a large series of patients with vulval and vaginal melanomas, this study sought to document the most common presenting features, identify clinical and pathologic predictors of outcome, and provide management guidelines. A clinicopathologic analysis of 85 patients with primary melanomas of the vulva or vagina diagnosed and treated at Melanoma Institute Australia and associated units in Sydney, Australia, between 1960 and 2011 was performed. Predictors of disease-free and melanoma-specific survival (MSS) were determined. Patients with American Joint Committee on Cancer (AJCC) stage 0-II had a significantly better MSS (5Y MSS = 63.6 %, n = 59) compared with those with stage III disease (5Y MSS = 0 %, n = 12, p < 0.001). Tumor thickness, ulceration status, and pathologic clearance margin were significant predictors of MSS. Disease-free survival was predicted by these factors and additionally by tumor mitotic rate. The results of this study provide evidence to support the appropriateness of utilizing the AJCC (7th edition) cutaneous melanoma staging system for vulval and vaginal melanomas. Detection and removal of these melanomas at an early stage with pathologically confirmed clear margins confers the best chance of cure.

  20. Primary malignant melanoma of the urinary bladder: clinical, morphological, and molecular analysis of five cases.

    Science.gov (United States)

    Karabulut, Yasemin Y; Erdogan, Seyda; Sayar, Hamide; Ergen, Ali; Ertoy Baydar, Dilek

    2016-12-01

    The aim of our study was to evaluate the clinical and morphological features of primary malignant melanomas of the urinary bladder. We obtained information on five such cases from three different institutions. These were three men and two women between 52 and 76 years of age. Three tumors presented with hematuria, one with dysuria, and one was discovered incidentally on imaging studies. All were invasive to muscularis propria on transuretral resections performed for diagnosis. Neoplastic cells showed variable patterns (large cell epithelioid, small cell diffuse, storiform, or mixed) in different tumors. Pigmentation was prominent in all except one case. Each case was labeled diffusely for S-100, HMB-45, and Melan-A. Pan-cytokeratin showed a perinuclear dot-like reaction in two tumors. Three cases showed the BRAF mutation in molecular studies. Two patients were already metastatic at the time of diagnosis. Two patients died, one is alive with disease after 15 months, and two patients are disease free at 1 and 5 years of surveillance.

  1. Monosomy 3 by chromogenic in situ hybridization (CISH) in Iranian patients with uveal melanoma.

    Science.gov (United States)

    Naseripour, Masood; Mehrazma, Mitra; Pourmatin, Rama; Kashkouli, Mohsen Bahmani; Sedaghat, Ahad; Gheytanchi, Elmira

    2015-01-01

    The aim of this study was to investigate the rate of monosomy 3 by CISH technique in Iranian patients with uveal melanoma (UM) and its correlation with clinical and histopathological features. Archival formalin fixed, paraffin-embedded material from 50 patients who had undergone enucleation for large uveal melanomas was obtained. Monosomy of chromosome 3 alteration by chromogenic in situ hybridization (CISH) was investigated. Clinical and histopathological features of tumors were collected. The patients had a mean age of 56.6±7.6 years. Mean basal diameter and thickness of tumors were 14.1 mm and 10.2 mm, respectively. Four patients (8%) were identified to harbor monosomy of chromosome 3. In the mean follow-up of 5.3 years (range, 3.2-9.5 y), only one case with monosomy 3 died of UM metastasis. The most common type of cellularity was mixed cell (86%). There was not any statistically significant correlation between monosomy of chromosome 3 and type of cellularity, ciliary body involvement, and largest basal diameter. The low rate of monosomy chromosome 3 and the consequent low rate of mortality may be indicative of good prognosis in Iranian patients with uveal melanoma.

  2. T-Cell Mediated Immune Responses Induced in ret Transgenic Mouse Model of Malignant Melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Abschuetz, Oliver [Skin Cancer Unit, German Cancer Research Center (DKFZ), Heidelberg and Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim, Ruprecht-Karl University of Heidelberg, Mannheim , Heidelberg 69120 (Germany); Osen, Wolfram [Division of Translational Immunology, German Cancer Center, Heidelberg 69120 (Germany); Frank, Kathrin [Skin Cancer Unit, German Cancer Research Center (DKFZ), Heidelberg and Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim, Ruprecht-Karl University of Heidelberg, Mannheim , Heidelberg 69120 (Germany); Kato, Masashi [Unit of Environmental Health Sciences, Department of Biomedical Sciences, College of Life and Health Sciences, Chubu University, Aichi 487-8501 (Japan); Schadendorf, Dirk [Department of Dermatology, University Hospital Essen, Essen 45122 (Germany); Umansky, Viktor, E-mail: v.umansky@dkfz.de [Skin Cancer Unit, German Cancer Research Center (DKFZ), Heidelberg and Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim, Ruprecht-Karl University of Heidelberg, Mannheim , Heidelberg 69120 (Germany)

    2012-04-26

    Poor response of human malignant melanoma to currently available treatments requires a development of innovative therapeutic strategies. Their evaluation should be based on animal models that resemble human melanoma with respect to genetics, histopathology and clinical features. Here we used a transgenic mouse model of spontaneous skin melanoma, in which the ret transgene is expressed in melanocytes under the control of metallothionein-I promoter. After a short latency, around 25% mice develop macroscopic skin melanoma metastasizing to lymph nodes, bone marrow, lungs and brain, whereas other transgenic mice showed only metastatic lesions without visible skin tumors. We found that tumor lesions expressed melanoma associated antigens (MAA) tyrosinase, tyrosinase related protein (TRP)-1, TRP-2 and gp100, which could be applied as targets for the immunotherapy. Upon peptide vaccination, ret transgenic mice without macroscopic melanomas were able to generate T cell responses not only against a strong model antigen ovalbumin but also against typical MAA TRP-2. Although mice bearing macroscopic primary tumors could also display an antigen-specific T cell reactivity, it was significantly down-regulated as compared to tumor-free transgenic mice or non-transgenic littermates. We suggest that ret transgenic mice could be used as a pre-clinical model for the evaluation of novel strategies of melanoma immunotherapy.

  3. Evaluation of variants of melanoma-associated antigen genes and mRNA transcripts in melanomas of dogs.

    Science.gov (United States)

    Stell, Anneliese J; Dobson, Jane M; Scase, Timothy J; Catchpole, Brian

    2009-12-01

    OBJECTIVE-To characterize variability in melanoma-associated antigen (MAA) genes and gene expression in melanomas of dogs. ANIMALS-18 dogs with malignant melanomas and 8 healthy control dogs. PROCEDURES-cDNA was prepared from malignant melanoma biopsy specimens and from pigmented oral mucocutaneous tissues of healthy control dogs. Genomic DNA was extracted from poorly pigmented melanomas. A PCR assay was performed by use of Melan-A, SILV, or tyrosinase-specific primers. RESULTS-Splice variants of Melan-A and SILV were identified in malignant melanomas and also in healthy pigmented tissues, whereas a tyrosinase splice variant was detected in melanoma tissues only. A short interspersed nuclear element (SINE) insertion mutation was identified in the SILV gene in 1 of 10 poorly pigmented melanomas. Six novel exonic single nucleotide polymorphisms (SNPs; 3 synonymous and 3 nonsynonymous) were detected in the tyrosinase gene, and 1 nonsynonymous exonic SNP was detected in the SILV gene. CONCLUSIONS AND CLINICAL RELEVANCE-Variants of MAA mRNA were detected in malignant melanoma tissues of dogs. The importance of MAA alternative transcripts expressed in melanomas and normal pigmented tissues was unclear, but they may have represented a means of regulating melanin synthesis. The tyrosinase splice variant was detected only in melanomas and could potentially be a tumor-specific target for immunotherapy. A SILV SINE insertion mutation was identified in a melanoma from a Great Dane, a breed known to carry this mutation (associated with merle coat color). The nonsynonymous SNPs detected in tyrosinase and SILV transcripts did not appear to affect tumor pigmentation.

  4. A study of melanoma in Eastern European migrants in Italy.

    Science.gov (United States)

    Astrua, Chiara; Fava, Paolo; Brizio, Matteo; Savoia, Paola

    2017-04-01

    Cancer survival rates are lower in Eastern Europe. To describe, based on a single-centre database in northern Italy, clinical, histopathological, and prognostic features of melanoma in a migrant population from Eastern Europe. We retrospectively analysed data from 18,190 consecutive foreign patients who visited our institution, with 49 cases of melanoma from Eastern Europe. The control group was represented by 1,003 Italian melanoma patients diagnosed and followed at our centre during the same time period. Patients from Eastern Europe were mainly females with lower median age, without significant differences regarding primary melanoma site, relative to the control group. Diagnosis was made at the place of birth in 30.6% and in our centre for the remainder. Median Breslow thickness was greater (p = 0.0178), and aggressive histotypes (p = 0.0017) and ulcerated melanomas (p = 0.002) were significantly over-represented, particularly when diagnosed in the patients' native country. Disease was more advanced at diagnosis (p = 0.0001), regardless of the place of initial diagnosis (51% had a progressive disease within one year which rose to 80% if diagnosed before admission to our centre), and the percentage of patients who died within one year was significantly higher (p = 0.022), relative to the control group. Our study shows a poor prognosis for melanoma patients diagnosed in Eastern Europe. Moreover, for migrant populations moving from Eastern to Western European countries, financial difficulties, poor social integration, and language barriers, with consequent late access to healthcare facilities, may account for a worse prognosis.

  5. Thick melanoma in Tuscany.

    Science.gov (United States)

    Chiarugi, Alessandra; Nardini, Paolo; Borgognoni, Lorenzo; Brandani, Paola; Gerlini, Gianni; Rubegni, Pietro; Lamberti, Arianna; Salvini, Camilla; Lo Scocco, Giovanni; Cecchi, Roberto; Sirna, Riccardo; Lorenzi, Stefano; Gattai, Riccardo; Battistini, Silvio; Crocetti, Emanuele

    2017-03-14

    The epidemiologic trends of cutaneous melanoma are similar in several countries with a Western-type life style, where there is a progressive increasing incidence and a low but not decreasing mor- tality, or somewhere an increase too, especially in the older age groups. Also in Tuscany there is a steady rise in incidence with prevalence of in situ and invasive thin melanomas, with also an increase of thick melanomas. It is necessary to reduce the frequency of thick melanomas to reduce specific mortality. The objective of the current survey has been to compare, in the Tuscany population, by a case- case study, thin and thick melanoma cases, trying to find out those personal and tumour characteristics which may help to customize preventive interventions. RESULTS The results confirmed the age and the lower edu- cation level are associated with a later detection. The habit to perform skin self-examination is resulted protec- tive forward thick melanoma and also the diagnosis by a doctor. The elements emerging from the survey allow to hypothesize a group of subjects resulting at higher risk for a late diagnosis, aged over 50 and carrier of a fewer constitutional and environmental risk factors: few total and few atypical nevi, and lower sun exposure and burning. It is assumable that a part of people did not be reached from messages of prevention because does not recognize oneself in the categories of people at risk for skin cancers described in educational cam- paigns. If we want to obtain better results on diagnosis of skin melanoma we have to think a new strategy. At least to think over the educational messages discriminating people more at risk of incidence of melanoma from people more at risk to die from melanoma, and to renewed active involvement of the Gen- eral Practitioners .

  6. [The related factors of head and neck mocosal melanoma with lymph node metastasis].

    Science.gov (United States)

    Yin, G F; Guo, W; Chen, X H; Huang, Z G

    2017-12-05

    Objective: To investigate the related factors of mucosal melanoma of head and neck with lymph node metastasis for early diagnosis and further treatments. Method: A retrospective analysis of 117 cases of head and neck mucosal malignant melanoma patients which received surgical treatment was performed. Eleven cases of patients with pathologically confirmed lymph node metastasis and 33 cases without lymph node metastasis (1∶3) were randomly selected to analyze. The related factors of lymph node metastasis of head and neck mucosal melanoma patients including age, gender, whether the existence of recurrence, bone invasion, lesion location were analyzed. The single factor and logistic regression analysis were performed, P difference was statistically significant. Result: The lymph node metastasis rate of head and neck mucosal melanoma was 9.40%(11/117), the single factor analysis showed that there were 3 factors to be associated with lymph node metastasis, which was recurrence ( P =0.0000), bone invasion ( P =0.001), primary position ( P =0.007). Recurrence ( P =0.021) was a risk factor for lymph node metastasis according to the Logistic regression analysis, and the impact of bone invasion ( P =0.487) and primary location ( P =0.367) remained to be further explored. Conclusion: The patients of head and neck mucosal melanoma with the presence of recurrent usually accompanied by a further progression of the disease, such as lymph node metastasis, so for recurrent patients should pay special attention to the situation of lymph node and choose the reasonable treatment. Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.

  7. Tumor-infiltrating CD8+ lymphocytes effect on clinical outcome of muco-cutaneous melanoma

    Directory of Open Access Journals (Sweden)

    Mahtab Rahbar

    2015-01-01

    Full Text Available Background: Recent data have changed our views of prognostic factors in cutaneous melanoma, while some newer methods have yielded better prognostic information. Tumor-infiltrating lymphocytes are believed to represent the immune reaction/response to melanoma cells which is often found in melanocytic cancer. Aim and Objective: We carried out an analysis, aiming to establish pooled estimates for clinical outcomes based on the presence of CD8+ T cell in melanocytic cancer. Materials and Methods: We have included 42 patients with primary cutaneous melanocytic cancer without preoperative treatments in our study. We next analyzed the proliferative activity of CD8+ T cells that infiltrated in tumor cell nests. The intratumoral and adjacent to invasive margin of tumor CD+ T-cell infiltration were analyzed which could also reflect antitumor immunity. Results: The total number of CD8+ cells especially adjacent to invasive margin of tumor was positively correlated with anatomical tumor thickness (P < .001 and not correlated with patient′s age and sex. The stage of tumor which is related to vascular-neural invasion, regional lymph nodes involvement and tumor thickness shows positive correlation with CD8+ infiltration in tumor (P < .004, P < .005, P < .001, respectively. Acral melanoma shows more CD8 lymphocytes infiltration and also recurrence rate of tumor (P < .005. Conclusion: We believe that CD8+ T-cell infiltration in primary cutaneous melanocytic cancer represents the immune reaction/response to melanoma which could be an important new therapy for melanoma although more research is needed on this treatment modality.

  8. Nevoid melanoma of the vagina: report of one case diagnosed on thin layer cytological preparations

    Directory of Open Access Journals (Sweden)

    Ascierto Paolo

    2007-01-01

    Full Text Available Abstract Background Primary melanoma of the vagina is an extremely rare neoplasm with approximately 250 reported cases in the world literature 1234. In its amelanotic variant this lesion may raise several differential diagnostic problems in cytological specimens 5. In this setting, the usage of thin layer cytopathological techniques (Liquid Based Preparations = LBP may enhance the diagnostic sensitivity by permitting immunocytochemical study without having to repeat the sampling procedure. The aim of this paper is to describe the cytomorphological presentation of primary vaginal melanoma on LBP since it has not previously been reported up to now, to our knowledge. Case presentation a 79-y-o female complaining of vulvar itching and yellowish vaginal discharge underwent a complete gynaecological evaluation during which a LBP cytological sample was taken from a suspicious whitish mass protruding into the vaginal lumen. A cytopathological diagnosis of amelanotic melanoma was rendered. The mass was radically excised and the patient was treated with α-Interferon. Conclusion amelanotic melanoma may be successfully diagnosed on LBP cytological preparations. Thin layer preparations may enhance the diagnostic cytomorphological clues to its diagnosis and may permit an adequate immunocytochemical characterization of the neoplasm.

  9. Nevoid melanoma of the vagina: report of one case diagnosed on thin layer cytological preparations.

    Science.gov (United States)

    Fulciniti, Franco; Ascierto, Paolo Antonio; Simeone, Ester; Bove, Patrizia; Losito, Simona; Russo, Serena; Gallo, Maria Stella; Greggi, Stefano

    2007-07-03

    Primary melanoma of the vagina is an extremely rare neoplasm with approximately 250 reported cases in the world literature 1234. In its amelanotic variant this lesion may raise several differential diagnostic problems in cytological specimens 5. In this setting, the usage of thin layer cytopathological techniques (Liquid Based Preparations = LBP) may enhance the diagnostic sensitivity by permitting immunocytochemical study without having to repeat the sampling procedure. The aim of this paper is to describe the cytomorphological presentation of primary vaginal melanoma on LBP since it has not previously been reported up to now, to our knowledge. a 79-y-o female complaining of vulvar itching and yellowish vaginal discharge underwent a complete gynaecological evaluation during which a LBP cytological sample was taken from a suspicious whitish mass protruding into the vaginal lumen. A cytopathological diagnosis of amelanotic melanoma was rendered. The mass was radically excised and the patient was treated with alpha-Interferon. amelanotic melanoma may be successfully diagnosed on LBP cytological preparations. Thin layer preparations may enhance the diagnostic cytomorphological clues to its diagnosis and may permit an adequate immunocytochemical characterization of the neoplasm.

  10. Breast metastasis from cutaneous malignant melanoma mimicking a breast cancer.

    Science.gov (United States)

    Maniglio, Marina; Capalbo, Emanuela; Viganò, Sara; Trecate, Giovanna; Scaperrotta, Gianfranco Paride; Panizza, Pietro

    2015-06-25

    Breast metastases are very uncommon, either from solid tumors or malignant melanoma. We present the case of a 42-year-old woman with a history of cutaneous melanoma of the shoulder excised 21 years ago. She presented with a palpable lump in the upper outer quadrant of the right breast. Ultrasound demonstrated a solid mass within a cystic lesion. A core biopsy was taken and first histology reported a poorly differentiated primary breast cancer suspected to be triple negative. MRI detected a satellite lesion in the same breast, a focus of suspected enhancement in the other breast, and the extramammary finding of an enhancing pulmonary lesion. Staging computed tomography detected widespread metastases to the lungs, brain, subcutaneous left shoulder, liver, pancreas, and hepatorenal recess. A core biopsy was taken from the left breast lesion and the previous slides were reviewed; histopathology and immunohistochemistry were in keeping with metastasis from melanoma. The possibility of a metastatic lesion to the breast should be taken into account in any patient presenting with a breast lump and a previous history of melanoma. Breast involvement cannot be considered an isolated finding, as it might be the first manifestation of widespread disease.

  11. Cutaneous melanoma in women

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    Mi Ryung Roh, MD

    2015-02-01

    Conclusions: The published findings on gender disparities in melanoma have yielded many advances in our understanding of this disease. Biological, environmental, and behavioral factors may explain the observed gender difference in melanoma incidence and outcome. Further research will enable us to learn more about melanoma pathogenesis, with the goal of offering better treatments and preventative advice to our patients.

  12. Animal type melanoma: a report of two cases

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    Mariângela Esther Alencar Marques

    2010-08-01

    Full Text Available Dificuldade potencial no diagnóstico histológico de melanomas é a dificuldade em reconhecer variantes pouco frequentes de melanoma. Entre elas, as mais desafiantes incluem exemplos de melanoma desmoplásico, melanoma nevoide, o chamado "melanoma de desvio mínimo", melanomas com proeminente síntese de pigmento ou "melanoma tipo animal" e o nevo azul maligno. Os autores descrevem dois casos de melanoma tipo animal e discute-se a importância do diagnóstico diferencial clinico-histopatológico nesses casos.A potential diagnostic pitfall in the histological assessment of melanomas is the difficulty in recognizing unusual melanoma variants. Among them, the most challenging examples comprise desmoplastic melanomas, nevoid melanomas, the so-called minimal-deviation melanoma, melanomas with prominent pigment synthesis or animal-type melanoma, and the malignant blue nevus. Two cases of animal type melanoma are reported and the importance of clinical-histopathological differential diagnosis is discussed.

  13. Tyrosinase expression in malignant melanoma, desmoplastic melanoma, and peripheral nerve tumors

    DEFF Research Database (Denmark)

    Boyle, Jenny L; Haupt, Helen M; Stern, Jere B

    2002-01-01

    of tyrosinase expression in the differential diagnosis of melanoma, desmoplastic melanoma, and peripheral nerve sheath tumors. DESIGN: Immunoreactivity for tyrosinase, HMB-45 (anti-gp100 protein), S100 protein, CD34, and vimentin was studied in 70 tumors, including 15 melanomas (5 desmoplastic, 4 amelanotic, 6...... at 121 degrees C. RESULTS: All melanomas demonstrated positive immunostaining for tyrosinase, HMB-45, and S100 protein. Immunoreactivity for HMB-45 was generally stronger than that for tyrosinase in amelanotic lesions and significantly stronger in 1 of the desmoplastic lesions. The 4 pigmented...... neurofibromas were focally positive for tyrosinase, but did not stain for HMB-45. The pigmented schwannoma was focally positive for both tyrosinase and HMB-45. The malignant peripheral nerve sheath tumors, dermatofibrosarcoma protuberans, and dermatofibromas were nonreactive for tyrosinase and HMB-45...

  14. Nestin is expressed in HMB-45 negative melanoma cells in dermal parts of nodular melanoma.

    Science.gov (United States)

    Kanoh, Maho; Amoh, Yasuyuki; Tanabe, Kenichi; Maejima, Hideki; Takasu, Hiroshi; Katsuoka, Kensei

    2010-06-01

    Nestin, a marker of neural stem cells, is expressed in the stem cells of the mouse hair follicle. The nestin-expressing hair follicle stem cells can differentiate into neurons, glia, keratocytes, smooth muscle cells and melanocytes in vitro. These pluripotent nestin-expressing stem cells are keratin 15 (K15)-negative, suggesting that they are in a relatively undifferentiated state. Recent studies suggest that the epithelial stem cells are important in tumorigenesis, and nestin expression is thought to be important in tumorigenesis. In the present study, we examined the expression of the hair follicle and neural stem cell marker nestin, as well as S-100 and HMB-45, in melanoma. Nestin immunoreactivity was observed in the HMB-45-negative melanoma cells in all five cases of amelanotic nodular melanomas. Moreover, nestin immunoreactivity was observed in the dermal parts in seven of 10 cases of melanotic nodular melanomas. Especially, nestin immunoreactivity was observed in the HMB-45-negative melanoma cells in the dermal parts of all 10 cases of HMB-45-negative amelanotic and melanotic nodular melanomas. On the other hand, nestin expression was negative in 10 of 12 cases of superficial spreading melanoma. These results suggest that nestin is an important marker of HMB-45-negative melanoma cells in the dermal parts of patients with nodular melanoma.

  15. A Case of Malignant Melanoma of the Uterine Cervix with Disseminated Metastases throughout the Vaginal Wall

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    Tomoko Noguchi

    2017-01-01

    Full Text Available Malignant melanoma (MM in the female genital tract accounts for less than 2% of all melanomas, and the vast majority associated occur in the vulva and vagina. Primary MM of the uterine cervix is extremely rare and its prognosis is very poor. We report a case of primary MM of the cervix with dissemination throughout the vaginal wall. A 66-year-old woman presented with postmenopausal bleeding. Gynecologic examination demonstrated a 2 cm polypoid blackish-pigmented tumor on the cervix with multiple small blackish-pigmented lesions throughout the vaginal wall. Cervical Pap smear cytology showed malignant melanoma. MRI and PET/CT did not detect any distant or lymph node metastases. She underwent radical hysterectomy, pelvic lymphadenectomy, and total vaginectomy. The pathological diagnosis was FIGO stage IIIA primary cervical MM. She received adjuvant chemotherapy with 6 courses of dacarbazine, but 6 months later, multiple lung metastases were detected. Despite 4 courses of anti-PD-1 antibody (nivolumab treatment, she died of the disease 13 months after surgery.

  16. Psychosocial care to patients with Malignant Melanoma

    DEFF Research Database (Denmark)

    Thorup, Charlotte Brun

    Psychosocial care to patients with Malignant Melanoma Intensions: The intension of this project is to link new knowledge with the nurses experience based knowledge within the psychosocial care to patients, who have been diagnosed with Malignant Melanoma (MM), thereby improving the care...... to elaborate the care to these patients. Method: In 2007 the nurses from our ward gained experience from the psychosocial care to these patients. These experiences are a starting point to the study of literature the group has made. A group of five nurses have from this literature study, substantiated...... the psychosocial perspective. Results: After the literature review, the psychosocial aspects have been divided into five main areas: 1. Diagnosis, hospitalisation, and treatment 2. The body with cancer 3. Psychological 4. Social 5. Existential/spiritual Primary results show that patients with MM in general respond...

  17. Interpretation of Melanoma Risk Feedback in First-Degree Relatives of Melanoma Patients

    International Nuclear Information System (INIS)

    Hay, J. L.; Baguer, C.; Li, Y.; Orlow, I.; Berwick, M.

    2012-01-01

    Little is known about how individuals might interpret brief genetic risk feedback. We examined interpretation and behavioral intentions (sun protection, skin screening) in melanoma first-degree relatives (FDRs) after exposure to brief prototypic melanoma risk feedback. Using a 3 by 2 experimental pre-post design where feedback type (high-risk mutation, gene environment, and nongenetic) and risk level (positive versus negative findings) were systematically varied, 139 melanoma FDRs were randomized to receive one of the six scenarios. All scenarios included an explicit reminder that melanoma family history increased their risk regardless of their feedback. The findings indicate main effects by risk level but not feedback type; positive findings led to heightened anticipated melanoma risk perceptions and anticipated behavioral intentions. Yet those who received negative findings often discounted their family melanoma history. As such, 25%, 30%, and 32% of those who received negative mutation, gene-environment, and nongenetic feedback, respectively, reported that their risk was similar to the general population. Given the frequency with which those who pursue genetic testing may receive negative feedback, attention is needed to identify ideal strategies to present negative genetic findings in contexts such as direct to consumer channels where extensive genetic counseling is not required.

  18. Radiation biology of malignant melanoma

    International Nuclear Information System (INIS)

    Rofstad, E.K.; Norwegian Cancer Society, Oslo)

    1986-01-01

    The survival curves for melanoma cells exposed to single radiation doses in vitro and the specific growth delays for melanoma xenografts irradiated with single doses in vivo were found to differ considerably among individual cell lines and tumours. In fact, the differences could be almost as large as the largest differences observed among cell lines and xenografts from tumours of different histology with very different clinical radiocurability. Moreover, radiobiologic parameters that may have significant influence on tumour response to fractionated irradiation, e.g. growth rate, hypoxic fraction, reoxygenation ability, PLD-repair capacity and contact repair capacity, were found to differ greatly in magnitude among individual melanomas. This review therefore concludes that malignant melanoma is a tumour type that is very heterogeneous in radioresponsiveness, i.e. malignant melanomas should no longer be considered to be radiation resistant in general. The values of the α/β ratio derived from cell survival curves for melanoma cells irradiated in vitro and melanoma xenografts irradiated in vivo were found to cover a wide range relative to those for acutely and late responding normal tissues. Although these α/β ratios are no more than estimates of the effective α/β ratios in a clinical situation, they still indicated that hyperfractionation may be beneficial in the treatment of some melanomas, whereas others may be more efficiently treated by use of conventional fractionation regimes, either based on 2 Gy or higher doses per fraction. Consequently, optimum radiation therapy of malignant melanoma will probably require an individualized treatment strategy. In vitro assays for prediction of radiocurability and choice of treatment strategy for individual melanoma patients seem therefore highly warranted. (orig.)

  19. Monitoring the systemic human memory B cell compartment of melanoma patients for anti-tumor IgG antibodies.

    Directory of Open Access Journals (Sweden)

    Amy E Gilbert

    Full Text Available Melanoma, a potentially lethal skin cancer, is widely thought to be immunogenic in nature. While there has been much focus on T cell-mediated immune responses, limited knowledge exists on the role of mature B cells. We describe an approach, including a cell-based ELISA, to evaluate mature IgG antibody responses to melanoma from human peripheral blood B cells. We observed a significant increase in antibody responses from melanoma patients (n = 10 to primary and metastatic melanoma cells compared to healthy volunteers (n = 10 (P<0.0001. Interestingly, we detected a significant reduction in antibody responses to melanoma with advancing disease stage in our patient cohort (n = 21 (P<0.0001. Overall, 28% of melanoma patient-derived B cell cultures (n = 1,800 compared to 2% of cultures from healthy controls (n = 600 produced antibodies that recognized melanoma cells. Lastly, a patient-derived melanoma-specific monoclonal antibody was selected for further study. This antibody effectively killed melanoma cells in vitro via antibody-mediated cellular cytotoxicity. These data demonstrate the presence of a mature systemic B cell response in melanoma patients, which is reduced with disease progression, adding to previous reports of tumor-reactive antibodies in patient sera, and suggesting the merit of future work to elucidate the clinical relevance of activating humoral immune responses to cancer.

  20. Monitoring the Systemic Human Memory B Cell Compartment of Melanoma Patients for Anti-Tumor IgG Antibodies

    Science.gov (United States)

    Gilbert, Amy E.; Karagiannis, Panagiotis; Dodev, Tihomir; Koers, Alexander; Lacy, Katie; Josephs, Debra H.; Takhar, Pooja; Geh, Jenny L. C.; Healy, Ciaran; Harries, Mark; Acland, Katharine M.; Rudman, Sarah M.; Beavil, Rebecca L.; Blower, Philip J.; Beavil, Andrew J.; Gould, Hannah J.; Spicer, James; Nestle, Frank O.; Karagiannis, Sophia N.

    2011-01-01

    Melanoma, a potentially lethal skin cancer, is widely thought to be immunogenic in nature. While there has been much focus on T cell-mediated immune responses, limited knowledge exists on the role of mature B cells. We describe an approach, including a cell-based ELISA, to evaluate mature IgG antibody responses to melanoma from human peripheral blood B cells. We observed a significant increase in antibody responses from melanoma patients (n = 10) to primary and metastatic melanoma cells compared to healthy volunteers (n = 10) (P<0.0001). Interestingly, we detected a significant reduction in antibody responses to melanoma with advancing disease stage in our patient cohort (n = 21) (P<0.0001). Overall, 28% of melanoma patient-derived B cell cultures (n = 1,800) compared to 2% of cultures from healthy controls (n = 600) produced antibodies that recognized melanoma cells. Lastly, a patient-derived melanoma-specific monoclonal antibody was selected for further study. This antibody effectively killed melanoma cells in vitro via antibody-mediated cellular cytotoxicity. These data demonstrate the presence of a mature systemic B cell response in melanoma patients, which is reduced with disease progression, adding to previous reports of tumor-reactive antibodies in patient sera, and suggesting the merit of future work to elucidate the clinical relevance of activating humoral immune responses to cancer. PMID:21559411

  1. Síndrome de cauda eqüina produzida por melanoma

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    J. Lamartine de Assis

    Full Text Available The authors present a case of melanoma of the cauda equina which evolved during two years, starting with pain in the lower extremities and becoming at length a cauda equina syndrome, with bilateral sciatic pain, motor and sensorial signs and bladder and rectal disturbances. The tumor was only partially removed, on account of its infiltrating character. The patient died eleven months later. He had X-ray therapy soon after the operation. Autopsy was not performed but considering the clinical data, the localization and the type of the tumor, authors believe it connected by a primary melanoma of the lombar leptomeninges. A brief review of the literature is made.

  2. Prognosis of patients with transected melanomas.

    Science.gov (United States)

    Martires, Kathryn J; Nandi, Tina; Honda, Kord; Cooper, Kevin D; Bordeaux, Jeremy S

    2013-04-01

    The management of melanoma is directly related to Breslow's depth. Biopsying melanomas in a fashion that transects the deep margin precludes an accurate measurement of the true depth. To examine the prognosis of melanomas transected along the deep margins, as well as cases where no residual melanoma was seen on re-excision after transection. Records from a cohort of patients at one institution were examined from 1996 through 2007. Patients were considered to have "transected" melanomas if tumor cells were present on the deep margin of the biopsy. Overall survival was determined. Seven hundred fourteen patients were examined. 171 (24%) of all melanomas were transected. 101(59%) of those lacked tumor cells on re-excision. Patients with transected melanomas were older (OR = 1.03, p < .001), and had higher Breslow's depths (OR = 1.21, p < .001) than those without transected tumors. Those with no residual melanoma after transection were younger (OR = 0.98, p = .010) and more likely to have no lymph node involvement (OR = 2.23, p = .037). Neither transection (p = .760), nor lack of residual melanoma on re-excision after transection (p = .793) influenced survival. A high number of melanomas are transected at diagnosis, many of which lack visible tumor. The original Breslow's depth of transected melanomas without residual tumor on re-excision accurately predicts survival and prognosis. © 2013 by the American Society for Dermatologic Surgery, Inc. Published by Wiley Periodicals, Inc.

  3. Genetics of uveal melanoma and cutaneous melanoma: two of a kind?

    NARCIS (Netherlands)

    T. van den Bosch (Thomas); E. Kiliç (Emine); A.D.A. Paridaens (Dion); J.E.M.M. de Klein (Annelies)

    2010-01-01

    textabstractCutaneous melanoma and uveal melanoma both derive from melanocytes but show remarkable differences in tumorigenesis, mode of metastatic spread, genetic alterations, and therapeutic response. In this review we discuss the differences and similarities along with the genetic research

  4. Is the identification of in-transit sentinel lymph nodes in malignant melanoma patients really necessary?

    International Nuclear Information System (INIS)

    Vidal-Sicart, Sergi; Pons, Francesca; Fuertes, Silvia; Ortega, Marisa; Vilalta, Antonio; Puig, Susana; Palou, Josep M.; Castel, Teresa; Rull, Ramon

    2004-01-01

    The sentinel lymph node (SLN) is the first node in a nodal basin to receive the direct lymphatic flow from a malignant melanoma. However, in some patients, lymphoscintigraphic study reveals the presence of lymphatic nodes in the area between the primary melanoma and the regional basin. These nodes are called ''in-transit nodes'' or ''interval nodes'' and, by definition, are also SLNs. The purpose of this study was to determine the incidence and location of in-transit SLNs in patients with malignant melanoma and to assess whether it is really necessary to harvest them. The evaluation involved 600 consecutive malignant melanoma patients. Lymphoscintigraphy was performed on the day before surgery following intradermal injection of 74-111 MBq of 99m Tc-nanocolloid in four doses around the primary melanoma or the biopsy scar. Dynamic and static images were obtained and revealed SLNs in 599 out of 600 patients. The SLN was intraoperatively identified with the aid of patent blue dye and a hand-held gamma probe. Lymphoscintigraphy showed in-transit SLNs in 59/599 patients (9.8%). During surgery, all these in-transit SLNs were harvested, with those in the popliteal and epitrochlear regions being the most difficult to identify and excise. Metastatic cell deposits were subsequently identified in ten (16.9%) of these in-transit SLNs. In conclusion, lymphoscintigraphy has a key role in the identification of in-transit SLNs. Although the incidence of these nodes is relatively low in malignant melanoma patients, such SLNs present metastatic deposits in a significant percentage of cases and therefore the identification of in-transit SLNs in these patients is really necessary. (orig.)

  5. A retrospective study comparing the accuracy of prehistology diagnosis and surgical excision of malignant melanomas by general practitioners and hospital specialists.

    Science.gov (United States)

    Bakhai, M; Hopster, D; Wakeel, R

    2010-01-01

    A retrospective study was carried out to compare the overall standard of surgical excision of malignant melanomas (MMs) between general practitioners (GPs) and hospital specialists before and after the introduction of the UK melanoma guidelines between 1989 and 2006. In total, 213 melanoma excision reports were examined and surgical excision margins recorded. The results showed a significant difference in the rate of adequate surgical excision margins (at all levels of Breslow thickness) between GPs and hospital specialists, with hospital specialists excising melanomas with safe surgical excision margins at a significantly higher rate compared with GPs. Since the introduction of the guidelines in 2002, GPs showed a significant improvement in the completeness of melanoma excision but remained poor at prehistology diagnosis and in particular at taking adequate excision margins. Implementation of the guidelines has not produced significant improvements in adequacy of excision margins in both primary and secondary care. The results show that hospital specialists maintained a high standard of prehistological diagnosis and completeness of excision throughout the time of the study, performing at a significantly higher standard compared with GPs. Our conclusions concur with the UK melanoma guidelines and the National Institute for Health and Clinical Excellence guidelines, which suggest that lesions suspicious for melanoma should be urgently referred to a dermatologist or plastic surgeon for surgical excision and should not be surgically excised in primary care, particularly if lesions have a Breslow thickness > 2 mm. We suggest that the new guidelines need to be more aggressively implemented in primary care and guidance introduced to improve the accuracy of diagnosis, with better training provided for GPs.

  6. Fisetin inhibits human melanoma cell invasion through promotion of mesenchymal to epithelial transition and by targeting MAPK and NFκB signaling pathways.

    Directory of Open Access Journals (Sweden)

    Harish Chandra Pal

    Full Text Available Malignant melanoma is responsible for approximately 75% of skin cancer-related deaths. BRAF plays an important role in regulating the mitogen-activated protein kinase (MAPK signaling cascade in melanoma with activating mutations in the serine/threonine kinase BRAF occurring in 60-70% of malignant melanomas. The BRAF-MEK-ERK (MAPK pathway is a key regulator of melanoma cell invasion. In addition, activation of NFκB via the MAPK pathway is regulated through MEK-induced activation of IKK. These pathways are potential targets for prevention and treatment of melanoma. In this study, we investigated the effect of fisetin, a phytochemical present in fruits and vegetables, on melanoma cell invasion and epithelial-mesenchymal transition, and delineated the underlying molecular mechanism. Treatment of multiple human malignant melanoma cell lines with fisetin (5-20 µM resulted in inhibition of cell invasion. BRAF mutated melanoma cells were more sensitive to fisetin treatment, and this was associated with a decrease in the phosphorylation of MEK1/2 and ERK1/2. In addition, fisetin inhibited the activation of IKK leading to a reduction in the activation of the NFκB signaling pathway. Treatment of cells with an inhibitor of MEK1/2 (PD98059 or of NFκB (caffeic acid phenethyl ester also reduced melanoma cell invasion. Furthermore, treatment of fisetin promoted mesenchymal to epithelial transition in melanoma cells, which was associated with a decrease in mesenchymal markers (N-cadherin, vimentin, snail and fibronectin and an increase in epithelial markers (E-cadherin and desmoglein. Employing three dimensional skin equivalents consisting of A375 cells admixed with normal human keratinocytes embedded onto a collagen-constricted fibroblast matrix, we found that treatment of fisetin reduced the invasive potential of melanoma cells into the dermis and increased the expression of E-cadherin with a concomitant decrease in vimentin. These results indicate that

  7. Fisetin Inhibits Human Melanoma Cell Invasion through Promotion of Mesenchymal to Epithelial Transition and by Targeting MAPK and NFκB Signaling Pathways

    Science.gov (United States)

    Pal, Harish Chandra; Sharma, Samriti; Strickland, Leah Ray; Katiyar, Santosh K.; Ballestas, Mary E.; Athar, Mohammad; Elmets, Craig A.; Afaq, Farrukh

    2014-01-01

    Malignant melanoma is responsible for approximately 75% of skin cancer-related deaths. BRAF plays an important role in regulating the mitogen-activated protein kinase (MAPK) signaling cascade in melanoma with activating mutations in the serine/threonine kinase BRAF occurring in 60–70% of malignant melanomas. The BRAF-MEK-ERK (MAPK) pathway is a key regulator of melanoma cell invasion. In addition, activation of NFκB via the MAPK pathway is regulated through MEK-induced activation of IKK. These pathways are potential targets for prevention and treatment of melanoma. In this study, we investigated the effect of fisetin, a phytochemical present in fruits and vegetables, on melanoma cell invasion and epithelial-mesenchymal transition, and delineated the underlying molecular mechanism. Treatment of multiple human malignant melanoma cell lines with fisetin (5–20 µM) resulted in inhibition of cell invasion. BRAF mutated melanoma cells were more sensitive to fisetin treatment, and this was associated with a decrease in the phosphorylation of MEK1/2 and ERK1/2. In addition, fisetin inhibited the activation of IKK leading to a reduction in the activation of the NFκB signaling pathway. Treatment of cells with an inhibitor of MEK1/2 (PD98059) or of NFκB (caffeic acid phenethyl ester) also reduced melanoma cell invasion. Furthermore, treatment of fisetin promoted mesenchymal to epithelial transition in melanoma cells, which was associated with a decrease in mesenchymal markers (N-cadherin, vimentin, snail and fibronectin) and an increase in epithelial markers (E-cadherin and desmoglein). Employing three dimensional skin equivalents consisting of A375 cells admixed with normal human keratinocytes embedded onto a collagen-constricted fibroblast matrix, we found that treatment of fisetin reduced the invasive potential of melanoma cells into the dermis and increased the expression of E-cadherin with a concomitant decrease in vimentin. These results indicate that fisetin

  8. Metastatic melanoma masquerading as a furuncle

    Directory of Open Access Journals (Sweden)

    Imran Aslam

    2017-10-01

    Full Text Available Melanoma metastasizes to the skin in about 10-17% of patients. Although there are reports of metastatic melanoma masquerading as panniculitis and erysipelas, it is very uncommon for it to present as an inflammatory skin lesion. When malignant melanoma cells invade the superficial dermal lymphatic vessels it can result in erythema, edema and induration of the overlying skin. This presentation can be problematic for clinicians if they do not suspect melanoma and choose not to biopsy the lesion. We report a case of an elderly man with a history of invasive melanoma who presented with a furuncle-like lesion that was found to be in-transit metastatic melanoma.

  9. Case-control study on uveal melanoma (RIFA: rational and design

    Directory of Open Access Journals (Sweden)

    Schmidt-Pokrzywniak Andrea

    2004-08-01

    Full Text Available Abstract Background Although a rare disease, uveal melanoma is the most common primary intraocular malignancy in adults, with an incidence rate of up to 1.0 per 100,000 persons per year in Europe. Only a few consistent risk factors have been identified for this disease. We present the study design of an ongoing incident case-control study on uveal melanoma (acronym: RIFA study that focuses on radiofrequency radiation as transmitted by radio sets and wireless telephones, occupational risk factors, phenotypical characteristics, and UV radiation. Methods/Design We conduct a case-control study to identify the role of different exposures in the development of uveal melanoma. The cases of uveal melanoma were identified at the Division of Ophthalmology, University of Essen, a referral centre for tumours of the eye. We recruit three control groups: population controls, controls sampled from those ophthalmologists who referred cases to the Division of Ophthalmology, University of Duisburg-Essen, and sibling controls. For each case the controls are matched on sex and age (five year groups, except for sibling controls. The data are collected from the study participants by short self-administered questionnaire and by telephone interview. During and at the end of the field phase, the data are quality-checked. To estimate the effect of exposures on uveal melanoma risk, we will use conditional logistic regression that accounts for the matching factors and allows to control for potential confounding.

  10. Cutaneous melanoma – guidelines for diagnostics and therapy in 2016

    Directory of Open Access Journals (Sweden)

    Piotr Rutkowski

    2016-02-01

    Full Text Available Dermoscopy is currently the standard method for clinical differential diagnosis of cutaneous melanoma and for qualifying a lesion for excisional biopsy. Full thickness excisional biopsy of suspicious melanomatous skin lesions likely to be diagnosed as early melanomas is crucial in establishing the diagnosis and defining prognostic factors. Early diagnosis and surgical removal of cutaneous melanoma not only improves patients’ prognosis but is also associated with approximately 90% likelihood of cure. The next steps in the therapeutic management of cutaneous melanoma following excisional biopsy are radical scar excision with adequate margins and sentinel lymph node biopsy. Radical lymph node dissection is recommended in the case of regional lymph node metastases. High-risk patients (lymph node involvement and/or ulcerated primary lesion should be advised to participate in prospective clinical trials on adjuvant therapy. Melanoma patients with distant metastases are still characterized by poor outcomes. In patients with metastatic disease testing for the presence of BRAF gene mutation is mandatory. Patients with metastatic disease should be considered for participation in clinical trials. Long-term survival is confined to a selected group of patients undergoing resection of isolated metastatic lesions. In systemic – mainly first-line – therapy of patients with BRAF V600 mutation the BRAF inhibitor vemurafenib or dabrafenib (preferentially in combination with a MEK inhibitor may be employed and independently of mutational status immunotherapy with anti-PD-1 antibodies (nivolumab or pembrolizumab and eventually ipilimumab (anti-CTLA4 antibody may be used.

  11. Systematic genomic and translational efficiency studies of uveal melanoma.

    Directory of Open Access Journals (Sweden)

    Chelsea Place Johnson

    Full Text Available To further our understanding of the somatic genetic basis of uveal melanoma, we sequenced the protein-coding regions of 52 primary tumors and 3 liver metastases together with paired normal DNA. Known recurrent mutations were identified in GNAQ, GNA11, BAP1, EIF1AX, and SF3B1. The role of mutated EIF1AX was tested using loss of function approaches including viability and translational efficiency assays. Knockdown of both wild type and mutant EIF1AX was lethal to uveal melanoma cells. We probed the function of N-terminal tail EIF1AX mutations by performing RNA sequencing of polysome-associated transcripts in cells expressing endogenous wild type or mutant EIF1AX. Ribosome occupancy of the global translational apparatus was sensitive to suppression of wild type but not mutant EIF1AX. Together, these studies suggest that cells expressing mutant EIF1AX may exhibit aberrant translational regulation, which may provide clonal selective advantage in the subset of uveal melanoma that harbors this mutation.

  12. Pediatric Melanoma and Drug Development

    Directory of Open Access Journals (Sweden)

    Klaus Rose

    2018-03-01

    Full Text Available Importance—Pediatric melanoma occurs, albeit rarely. Should patients be treated by today’s medical standards, or be subjected to medically unnecessary clinical studies? Observations—We identified international, industry-sponsored pediatric melanoma studies triggered by regulatory demands in www.clinicaltrials.gov and further pediatric melanoma studies demanded by European Union pediatric investigation plans. We retrieved related regulatory documents from the internet. We analyzed these studies for rationale and medical beneficence on the basis of physiology, pediatric clinical pharmacology and rationale. Regulatory authorities define children by chronological age, not physiologically. Newborns’ organs are immature but they develop and mature rapidly. Separate proof of efficacy in underage patients is justified formally/regulatorily but lacks medical sense. Children—especially post-puberty—and adults vis-a-vis medications are physiologically very similar. Two adolescent melanoma studies were terminated in 2016 because of waning recruitment, while five studies in pediatric melanoma and other solid tumors, triggered by European Union pediatric investigation plans, continue recruiting worldwide. Conclusions and Relevance—Regulatory-demanded pediatric melanoma studies are medically superfluous. Melanoma patients of all ages should be treated with effective combination treatment. Babies need special attention. Children need dose-finding and pharmacokinetic studies but adolescents metabolize and respond to drugs similarly to adults. Institutional Review Boards/ethics committees should suspend ongoing questionable pediatric melanoma studies and reject newly submitted questionable studies.

  13. Melanoma Surveillance in the US: The Economic Burden of Melanoma

    Centers for Disease Control (CDC) Podcasts

    This podcast accompanies the publication of a series of articles on melanoma surveillance in the United States, available in the November supplement edition of the Journal of the American Academy of Dermatology. Dr. Gery Guy, from the CDC’s Division of Cancer Prevention and Control, discusses the economic burden of melanoma.

  14. Nail apparatus melanoma: a diagnostic opportunity Melanoma do aparelho ungueal: uma oportunidade diagnóstica

    Directory of Open Access Journals (Sweden)

    Ana Maria Carreño

    2013-04-01

    Full Text Available Malignant Melanoma is a high mortality neoplasm. The involvement of the nail apparatus is rare, with only 2 out of 3 patients seeking medical attention as the result of recent nail melanocytic lesions. This results in late diagnosis and a prognosis worse than cutaneous melanoma. We report a female, presenting with ulcerative lesions with clinical and laboratory features compatible with leishmaniasis. On return after treatment initiation a longitudinal melanonychia was observed on her first right finger. Biopsy of the nail matrix was performed. Histopathology was compatible with melanoma in situ. Longitudinal melanonychia is not a specific sign for melanoma and it is important that the dermatologist should identify the suspect lesions correctly. The incidental diagnosis of nail melanoma in situ in our case significantly impacted the patient's survival.Melanoma Maligno é uma neoplasia de alta mortalidade, sendo raro o acometimento do aparelho ungueal. Apenas 2/3 dos pacientes procuram atendimento médico devido lesão melanocítica ungueal recente, tornando o diagnóstico tardio e com prognóstico pior que do melanoma cutâneo. Descreve-se um caso de paciente sexo feminino, apresentando lesões ulceradas com características clínico-laboratoriais compatíveis com leishmaniose tegumentar americana. No retorno após início do tratamento foi observada melanoníquia longitudinal no primeiro quirodáctilo direito. Realizada biópsia da matriz ungueal com histopatológico compatível com melanoma in situ. Melanoníquia longitudinal não é sinal específico de melanoma. A identificação das lesões suspeitas é importante tarefa dos dermatologistas. O diagnóstico incidental de melanoma ungueal in situ do caso relatado resultou em grande impacto na sobrevida da paciente.

  15. Effect of dabrafenib on melanoma cell lines harbouring the BRAFV600D/R mutations

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    Gentilcore Giusy

    2013-01-01

    Full Text Available Abstract Background Conventional therapeutic agents are largely unsatisfactory into the treatment of malignant melanoma. Recently, an innovative approach based on inhibitors of the mutated BRAF gene (which represents the most prevalent alteration in melanoma patients appears very promising from the clinical point of view. On this regard, a new compound, dabrafenib (GSK2118436, has been demonstrated to be effective in patients carrying the BRAFV600E/K mutations. We here tested dabrafenib for its capability to inhibit cell growth on primary melanoma cell lines, established from patients' tumour tissues and carrying the BRAFV600D/R mutations. Methods Three melanoma cell lines were tested: M257 wild-type BRAF, LCP BRAFV600R and WM266 BRAFV600D. The MTT assays were performed using standardized approaches. To evaluate the inhibition of MAPK pathway and the consequent inhibition of cellular proliferation, the phosphorylation of ERK was examined by Western Blot analysis performed on total protein extracts from cell lines after treatment with dabrafenib. Results Our experiments demonstrated an effective action of Dabrafenib (GSK2118436 and the inhibition of MAPK pathway in melanoma cell lines carrying BRAFV600D/R mutations. Conclusion These results could be helpful to enlarge the number of melanoma patients who may benefit of a more effective targeted treatment.

  16. Non-Metastatic Cutaneous Melanoma Induces Chronodisruption in Central and Peripheral Circadian Clocks.

    Science.gov (United States)

    de Assis, Leonardo Vinícius Monteiro; Moraes, Maria Nathália; Magalhães-Marques, Keila Karoline; Kinker, Gabriela Sarti; da Silveira Cruz-Machado, Sanseray; Castrucci, Ana Maria de Lauro

    2018-04-03

    The biological clock has received increasing interest due to its key role in regulating body homeostasis in a time-dependent manner. Cancer development and progression has been linked to a disrupted molecular clock; however, in melanoma, the role of the biological clock is largely unknown. We investigated the effects of the tumor on its micro- (TME) and macro-environments (TMaE) in a non-metastatic melanoma model. C57BL/6J mice were inoculated with murine B16-F10 melanoma cells and 2 weeks later the animals were euthanized every 6 h during 24 h. The presence of a localized tumor significantly impaired the biological clock of tumor-adjacent skin and affected the oscillatory expression of genes involved in light- and thermo-reception, proliferation, melanogenesis, and DNA repair. The expression of tumor molecular clock was significantly reduced compared to healthy skin but still displayed an oscillatory profile. We were able to cluster the affected genes using a human database and distinguish between primary melanoma and healthy skin. The molecular clocks of lungs and liver (common sites of metastasis), and the suprachiasmatic nucleus (SCN) were significantly affected by tumor presence, leading to chronodisruption in each organ. Taken altogether, the presence of non-metastatic melanoma significantly impairs the organism's biological clocks. We suggest that the clock alterations found in TME and TMaE could impact development, progression, and metastasis of melanoma; thus, making the molecular clock an interesting pharmacological target.

  17. Non-Metastatic Cutaneous Melanoma Induces Chronodisruption in Central and Peripheral Circadian Clocks

    Directory of Open Access Journals (Sweden)

    Leonardo Vinícius Monteiro de Assis

    2018-04-01

    Full Text Available The biological clock has received increasing interest due to its key role in regulating body homeostasis in a time-dependent manner. Cancer development and progression has been linked to a disrupted molecular clock; however, in melanoma, the role of the biological clock is largely unknown. We investigated the effects of the tumor on its micro- (TME and macro-environments (TMaE in a non-metastatic melanoma model. C57BL/6J mice were inoculated with murine B16-F10 melanoma cells and 2 weeks later the animals were euthanized every 6 h during 24 h. The presence of a localized tumor significantly impaired the biological clock of tumor-adjacent skin and affected the oscillatory expression of genes involved in light- and thermo-reception, proliferation, melanogenesis, and DNA repair. The expression of tumor molecular clock was significantly reduced compared to healthy skin but still displayed an oscillatory profile. We were able to cluster the affected genes using a human database and distinguish between primary melanoma and healthy skin. The molecular clocks of lungs and liver (common sites of metastasis, and the suprachiasmatic nucleus (SCN were significantly affected by tumor presence, leading to chronodisruption in each organ. Taken altogether, the presence of non-metastatic melanoma significantly impairs the organism’s biological clocks. We suggest that the clock alterations found in TME and TMaE could impact development, progression, and metastasis of melanoma; thus, making the molecular clock an interesting pharmacological target.

  18. Transcriptional regulation of epithelial-mesenchymal transition in melanoma

    International Nuclear Information System (INIS)

    Wels, C.

    2010-01-01

    The downregulation of epithelial markers followed by upregulation of mesenchymal characteristics is an important step in melanoma development. This process goes along with gains in cell proliferation and motility, depolarization and detachment from neighbouring cells, finally enabling melanoma cells to leave the primary site of tumor growth and to circulate through the blood or lymphatic system. The entirety of these events is referred to as epithelial-mesenchymal transition (EMT). Changes during EMT are accomplished by a set of transcription factors which share the same DNA binding site called E-box. These E-box binding transcription factors are subsumed as epithelial-mesenchymal transitions regulators (EMTRs). In this thesis, I studied the interplay of the zinc-finger transcription factors Slug and ZEB1 and the basic helix-loop-helix transcription factor Twist during melanoma progression. I demonstrate for the first time the direct and specific transcriptional upregulation of one EMTR, ZEB1, by another, Slug, using gene silencing and overexpression studies together with mobility shift and luciferase assays. The two transcription factors cooperate in repressing the epithelial adhesion molecule E-cadherin which is supposed to be a crucial step during early EMT. Further, they show additive effects in promoting detachment from neighbouring cells and cell migration. Conceptually, Slug and ZEB1 are supported by Twist, a transcription factor that might be less pivotal for E-cadherin repression but rather for inducing the expression of the mesenchymal marker N-cadherin, enabling adhesion to mesenchymal cells, thereby promoting migration and invasion of melanoma cells.Taken together, I provide a model of a hierarchical organization of EMT transcription factors, with Slug as a transcriptional activator of ZEB1, leading to cooperative effects on detachment and migration and, together with Twist, leading to EMT in melanoma. (author) [de

  19. Melanoma stem cells in experimental melanoma are killed by radioimmunotherapy

    International Nuclear Information System (INIS)

    Jandl, Thomas; Revskaya, Ekaterina; Jiang, Zewei; Harris, Matthew; Dorokhova, Olena; Tsukrov, Dina; Casadevall, Arturo; Dadachova, Ekaterina

    2013-01-01

    Introduction: In spite of recently approved B-RAF inhibitors and immunomodulating antibodies, metastatic melanoma has poor prognosis and novel treatments are needed. Melanoma stem cells (MSC) have been implicated in the resistance of this tumor to chemotherapy. Recently we demonstrated in a Phase I clinical trial in patients with metastatic melanoma that radioimmunotherapy (RIT) with 188-Rhenium( 188 Re)-6D2 antibody to melanin was a safe and effective modality. Here we investigated the interaction of MSC with RIT as a possible mechanism for RIT efficacy. Methods: Mice bearing A2058 melanoma xenografts were treated with either 1.5 mCi 188 Re-6D2 antibody, saline, unlabeled 6D2 antibody or 188 Re-labeled non-specific IgM. Results: On Day 28 post-treatment the tumor size in the RIT group was 4-times less than in controls (P < 0.001). The tumors were analyzed by immunohistochemistry and FACS for two MSC markers — chemoresistance mediator ABCB5 and H3K4 demethylase JARID1B. There were no significant differences between RIT and control groups in percentage of ABCB5 or JARID1B-positive cells in the tumor population. Our results demonstrate that unlike chemotherapy, which kills tumor cells but leaves behind MSC leading to recurrence, RIT kills MSC at the same rate as the rest of tumor cells. Conclusions: These results have two main implications for melanoma treatment and possibly other cancers. First, the susceptibility of ABCB5 + and JARID1B + cells to RIT in melanoma might be indicative of their susceptibility to antibody-targeted radiation in other cancers where they are present as well. Second, specifically targeting cancer stem cells with radiolabeled antibodies to ABCB5 or JARID1B might help to completely eradicate cancer stem cells in various cancers

  20. A challenging case of ocular melanoma.

    Science.gov (United States)

    Costache, Mariana; Dumitru, Adrian Vasile; Pătraşcu, Oana Maria; Popa-Cherecheanu, Daniela Alina; Bădilă, Patricia; Miu, Jeni Cătălina; Procop, Alexandru; Popa, Manuela; Tampa, Mircea Ştefan; Sajin, Maria; Simionescu, Olga; Cîrstoiu, Monica Mihaela

    2015-01-01

    Ocular melanoma is a rare malignancy found in clinical practice. In this paper, we present a case of highly aggressive ocular melanoma, which was surgically removed at the Department of Ophthalmology and diagnosed at the Department of Pathology, Emergency University Hospital, Bucharest, Romania, using conventional histopathological techniques. Uveal melanoma, a subset of ocular melanoma, has a distinct behavior in comparison to cutaneous melanoma and has a widely divergent prognosis. Approximately half of patients with ocular melanoma will develop metastatic disease, predominantly with hepatic, pulmonary or cerebral location, over a 10 to 15 years period. No systemic therapy was associated with an evident clinical outcome for patients with advanced disease and overall survival rate remains poor.

  1. Leukocyte infiltration and tumor cell plasticity are parameters of aggressiveness in primary cutaneous melanoma.

    NARCIS (Netherlands)

    Hillen, F.; Baeten, C.I.M.; Winkel, van de A.; Creytens, D.; Schaft, van der D.W.J.; Winnepenninckx, V.; Griffioen, A.W.

    2008-01-01

    Various clinical and experimental observations detected an immunological host defense in cutaneous melanoma. In order to investigate the prognostic value of leukocyte effector mechanisms, we examined the presence of different subsets of leukocytes in tumor samples of 58 patients diagnosed with

  2. Oral malignant melanoma: A case report of an unusual clinical and histologic presentation

    Directory of Open Access Journals (Sweden)

    Uzma Iqbal Belgaumi

    2013-01-01

    Full Text Available Malignant melanoma is a potentially aggressive tumor of melanocytic origin. Primary oral malignant melanoma is a rare neoplasm, accounting for 0.5% of all oral malignancies. The present case occurred in a 60-year-old female patient, as a pedunculated growth involving the palate and alveolar ridge and histologically showing a desmoplastic differentiation. The article discusses the distinct clinico-pathologic presentation of this case and emphasizes on the need to identify and report such cases for further understanding of their biologic behavior.

  3. Radiopharmaceuticals targeting melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Pham, T.Q.; Berghofer, P.; Liu, X.; Greguric, I.; Dikic, B.; Ballantyne, P.; Mattner, F.; Nguyen, V.; Loc' h, C.; Katsifis, A. [Radiopharmaceuticals Research Institute, Australian Nuclear Science and Technology Organisation, Menai, N.S.W., Sydney (Australia)

    2008-02-15

    Melanoma is one of the most aggressive cancers known with a high rate of mortality and increasing global incidence. So, the development of radiopharmaceuticals for either diagnostic or therapeutic purposes could make enormous contributions to melanoma patient health care. We have been studying melanoma tumours through several targeting mechanisms including melanin or specific receptor based radiopharmaceuticals Structure activity studies indicate that the substitution patterns on radioiodinated benzamides significantly influence the uptake mechanism from melanin to sigma-receptor binding. Furthermore, the position of the iodine as well as the presence of key functional groups and substituents has resulted in compounds with varying degrees of activity uptake and retention in tumours. From these results, a novel molecule 2-(2-(4-(4-iodo benzyl)piperazin-1-yl)-2-oxo-ethyl)isoindoline- 1,3-dione (M.E.L.037) was synthesized, labelled with iodine-123 and evaluated for application in melanoma tumour scintigraphy and radiotherapy. The tumour imaging potential of {sup 123}IM.E.L.037 was studied in vivo in C.57 B.L./ 6 J female mice bearing the B.16 F.0. murine melanoma tumour and in BALB/c nude mice bearing the A.375 human amelanotic melanoma tumour by biodistribution, competition studies and by SPECT imaging. {sup 123}I-M.E.L.037 exhibited high and rapid uptake in the B.16 F.0 melanoma tumour at 1 h (13 % I.D./g) increasing with time to reach 25 % I.D./g at 6 h. A significant uptake was also observed in the eyes (2% I.D., at 3-6 h p.i.) of black mice. No uptake was observed in the tumour or in the eyes of nude mice bearing the A.375 tumour. Due to high uptake and long retention in the tumour and rapid body clearance, standardized uptake values(S.U.V.) of {sup 123}I-M.E.L.037 were 30 and 60, at 24 and 48 h p.i.,respectively. SPECT imaging of mice bearing the B.16 melanoma indicated the radioactivity was predominately located in the tumour followed by the eyes, while no

  4. Pediatric melanoma: incidence, treatment, and prognosis

    Directory of Open Access Journals (Sweden)

    Saiyed FK

    2017-04-01

    Full Text Available Faiez K Saiyed,1 Emma C Hamilton,1 Mary T Austin,1,2 1Department of Pediatric Surgery, McGovern Medical School, 2Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA Abstract: The purpose of this review is to outline recent advancements in diagnosis, treatment, and prevention of pediatric melanoma. Despite the recent decline in incidence, it continues to be the deadliest form of skin cancer in children and adolescents. Pediatric melanoma presents differently from adult melanoma; thus, the traditional asymmetry, border irregularity, color variegation, diameter >6 mm, and evolution (ABCDE criteria have been modified to include features unique to pediatric melanoma (amelanotic, bleeding/bump, color uniformity, de novo/any diameter, evolution of mole. Surgical and medical management of pediatric melanoma continues to derive guidelines from adult melanoma treatment. However, more drug trials are being conducted to determine the specific impact of drug combinations on pediatric patients. Alongside medical and surgical treatment, prevention is a central component of battling the incidence, as ultraviolet (UV-related mutations play a central role in the vast majority of pediatric melanoma cases. Aggressive prevention measures targeting sun safety and tanning bed usage have shown positive sun-safety behavior trends, as well as the potential to decrease melanomas that manifest later in life. As research into the field of pediatric melanoma continues to expand, a prevention paradigm needs to continue on a community-wide level. Keywords: melanoma, pediatric, adolescent, childhood

  5. Combining molecular and immunohistochemical analyses of key drivers in primary melanomas: interplay between germline and somatic variations.

    Science.gov (United States)

    Bruno, William; Martinuzzi, Claudia; Dalmasso, Bruna; Andreotti, Virginia; Pastorino, Lorenza; Cabiddu, Francesco; Gualco, Marina; Spagnolo, Francesco; Ballestrero, Alberto; Queirolo, Paola; Grillo, Federica; Mastracci, Luca; Ghiorzo, Paola

    2018-01-19

    Due to the high mutational somatic burden of Cutaneous Malignant Melanoma (CMM) a thorough profiling of the driver mutations and their interplay is necessary to explain the timing of tumorigenesis or for the identification of actionable genetic events. The aim of this study was to establish the mutation rate of some of the key drivers in melanoma tumorigenesis combining molecular analyses and/or immunohistochemistry in 93 primary CMMs from an Italian cohort also characterized for germline status, and to investigate an interplay between germline and somatic variants. BRAF mutations were present in 68% of cases, while CDKN2A germline mutations were found in 16 % and p16 loss in tissue was found in 63%. TERT promoter somatic mutations were detected in 38% of cases while the TERT -245T>C polymorphism was found in 51% of cases. NRAS mutations were found in 39% of BRAF negative or undetermined cases. NF1 was expressed in all cases analysed. MC1R variations were both considered as a dichotomous variable or scored. While a positive, although not significant association between CDKN2A germline mutations, but not MC1R variants, and BRAF somatic mutation was found, we did not observe other associations between germline and somatic events. A yet undescribed inverse correlation between TERT -245T>C polymorphism and the presence of BRAF mutation was found. It is possible to hypothesize that -245T>C polymorphism could be included in those genotypes which may influence the occurrence of BRAF mutations. Further studies are needed to investigate the role of -245T>C polymorphism as a germline predictor of BRAF somatic mutation status.

  6. Induction of arginosuccinate synthetase (ASS) expression affects the antiproliferative activity of arginine deiminase (ADI) in melanoma cells.

    Science.gov (United States)

    Manca, Antonella; Sini, Maria Cristina; Izzo, Francesco; Ascierto, Paolo A; Tatangelo, Fabiana; Botti, Gerardo; Gentilcore, Giusy; Capone, Marilena; Mozzillo, Nicola; Rozzo, Carla; Cossu, Antonio; Tanda, Francesco; Palmieri, Giuseppe

    2011-06-01

    Arginine deiminase (ADI), an arginine-degrading enzyme, has been used in the treatment of tumours sensitive to arginine deprivation, such as malignant melanoma (MM) and hepatocellular carcinoma (HCC). Endogenous production of arginine is mainly dependent on activity of ornithine transcarbamylase (OTC) and argininosuccinate synthetase (ASS) enzymes. We evaluated the effect of ADI treatment on OTC and ASS expression in a series of melanoma cell lines. Twenty-five primary melanoma cell lines and normal fibroblasts as controls underwent cell proliferation assays and Western blot analyses in the presence or absence of ADI. Tissue sections from primary MMs (N = 20) and HCCs (N = 20) were investigated by immunohistochemistry for ASS expression. Overall, 21/25 (84%) MM cell lines presented a cell growth inhibition by ADI treatment; none of them presented constitutive detectable levels of the ASS protein. However, 7/21 (33%) ADI-sensitive melanoma cell lines presented markedly increased expression levels of the ASS protein following ADI treatment, with a significantly higher IC50 median value. Growth was not inhibited and the IC50 was not reached among the remaining 4/25 (16%) MM cell lines; all of them showed constitutive ASS expression. The OTC protein was found expressed in all melanoma cell lines before and after the ADI treatment. Lack of ASS immunostaining was observed in all analyzed in vivo specimens. Our findings suggest that response to ADI treatment in melanoma is significantly correlated with the ability of cells to express ASS either constitutively at basal level (inducing drug resistance) or after the treatment (reducing sensitivity to ADI).

  7. Immunohistochemical Analysis of Collagen IV and Laminin Expression in Spontaneous Melanoma Regression in the Melanoma-Bearing Libechov Minipig

    International Nuclear Information System (INIS)

    Planska, Daniela; Burocziova, Monika; Strnadel, Jan; Horak, Vratislav

    2015-01-01

    Spontaneous regression (SR) of human melanoma is a rare, well-documented phenomenon that is not still fully understood. Its detailed study cannot be performed in patients due to ethical reasons. Using the Melanoma-bearing Libechov Minipig (MeLiM) animals of various ages (from 3 weeks to 8 months) we implemented a long-term monitoring of melanoma growth and SR. We focused on immunohistochemical detection of two important extracellular matrix proteins, collagen IV and laminin, which are associated with cancer. We showed that SR of melanoma is a highly dynamic process. The expression of collagen IV and laminin correlated with changes in population of melanoma cells. Tumours of 3-week-old animals consisted primarily of melanoma cells with a granular expression of collagen IV and laminin around them. Thereafter, melanoma cells were gradually destroyed and tumour tissue was rebuilt into the connective tissue. Collagen IV expression slightly increased in tumours of 10-week-old pigs showing extracellular fibrous appearance. In tumours of older animals, areas lacking melanoma cells demonstrated a low expression and areas still containing melanoma cells a high expression of both proteins. We considered the age of 10 weeks as a turning point in the transition between tumour growth and SR of the MeLiM melanoma

  8. Radiation therapy of malignant melanoma: Experience with high individual treatment doses

    International Nuclear Information System (INIS)

    Habermalz, H.J.; Fischer, J.J.

    1984-01-01

    Melanoma is a complex tumor, metastasizes early both by lymphatic and blood vessels, and which may invoke a significant host ''immune,'' response. One can imagine a number of potentially useful roles for an effective radiation therapy regimen: 1. Treatment of the primary lesion. For small lesions located on the extremities, surgery may be simpler and obviate the risk of radiation failure. In other areas, e.g., head and neck, which may require more cosmetically or functionally debilitating surgery, a trial of radiation therapy may be worthwhile. 2. Preoperative radiation to the primary lesion before surgical resection in the hope of preventing tumor dissemination. 3. Prophylactic, local and regional lymph node radiation therapy. It has been popular in the past to remove malignant melanoma with wide local excision and dissection of adjacent node areas. It is still an open question whether some or any additional patients will be cured by the more vigorous local and extended treatment. Generally, those procedures have fallen into disfavor because of the associated morbidity. Presumably subclinical amounts of malignant melanoma could be sterilized with doses of radiation smaller than those necessary for bulk tumor. Wide field irradiation to the areas surrounding the primary lesion and the adjacent lymph nodes, to doses causing little morbidity, may well be worth clinical trial. 4. In combination with other forms of therapy, e.g., chemotherapy, immunotherapy, hyperthermia, to reduce the number of malignant cells in localized areas known to contain diseases. This may be particularly important prior to initiation of immunotherapy which may be much more effective in the absence of gross disease

  9. Molecular Classification of Melanoma

    Science.gov (United States)

    Tissue-based analyses of precursors, melanoma tumors and metastases within existing study populations to further understanding of the heterogeneity of melanoma and determine a predictive pattern of progression for dysplastic nevi.

  10. Melanoma screening: Informing public health policy with quantitative modelling.

    Directory of Open Access Journals (Sweden)

    Stephen Gilmore

    Full Text Available Australia and New Zealand share the highest incidence rates of melanoma worldwide. Despite the substantial increase in public and physician awareness of melanoma in Australia over the last 30 years-as a result of the introduction of publicly funded mass media campaigns that began in the early 1980s -mortality has steadily increased during this period. This increased mortality has led investigators to question the relative merits of primary versus secondary prevention; that is, sensible sun exposure practices versus early detection. Increased melanoma vigilance on the part of the public and among physicians has resulted in large increases in public health expenditure, primarily from screening costs and increased rates of office surgery. Has this attempt at secondary prevention been effective? Unfortunately epidemiologic studies addressing the causal relationship between the level of secondary prevention and mortality are prohibitively difficult to implement-it is currently unknown whether increased melanoma surveillance reduces mortality, and if so, whether such an approach is cost-effective. Here I address the issue of secondary prevention of melanoma with respect to incidence and mortality (and cost per life saved by developing a Markov model of melanoma epidemiology based on Australian incidence and mortality data. The advantages of developing a methodology that can determine constraint-based surveillance outcomes are twofold: first, it can address the issue of effectiveness; and second, it can quantify the trade-off between cost and utilisation of medical resources on one hand, and reduced morbidity and lives saved on the other. With respect to melanoma, implementing the model facilitates the quantitative determination of the relative effectiveness and trade-offs associated with different levels of secondary and tertiary prevention, both retrospectively and prospectively. For example, I show that the surveillance enhancement that began in

  11. PRIMARY ENDOPROSTHETIC REPLACEMENT OF THE ANOPHTHALMIC ORBIT IN PATIENTS WITH UVEAL MELANOMA: SIX-YEAR FOLLOW-UP RESULTS

    Directory of Open Access Journals (Sweden)

    A. A. Yarovoy

    2012-01-01

    Full Text Available A locomotor stump was formed in 36 patients (28 women and 8 men, by implanting an endoprosthesis for enucleation of the eyeball with uveal melanoma (UM. The indication for endoprosthesis implantation was no signs of extrabulbar growth. A modified 17–19 mm silicone implant covered with strips from a dura mater graft and medical mesh fabric was used as an orbital implant. The follow-up was 3 to 72 months (mean 32.5 months. All the patients achieved a satisfactory cosmetic effect. None patient was found to have a recurrent orbital tumor. Out of the complications, anterior implant surface denudation was noted in 4 patients. Two patients developed metastases. The absence of recurrent orbital UM at a 6-year follow-up enables primary endoprosthetic replacement of the orbit for UM to be regarded as a safe and reasonable method for patient cosmetic rehabilitation. 

  12. Safety of administering the canine melanoma DNA vaccine (Oncept) to cats with malignant melanoma - a retrospective study.

    Science.gov (United States)

    Sarbu, Luminita; Kitchell, Barbara E; Bergman, Philip J

    2017-02-01

    Objectives A xenogeneic human tyrosinase DNA vaccine was developed for treatment of dogs with oral malignant melanoma (Oncept; Merial). No studies have evaluated the safety or efficacy of this vaccine in cats. The purpose of this study was to evaluate the safety of the canine melanoma vaccine in cats diagnosed with melanoma. Methods Medical records were reviewed from cats diagnosed with malignant melanoma and treated with the canine melanoma DNA vaccine (Oncept). Data regarding signalment, melanoma location, treatments received, vaccine adverse effects and cause of death were collected. Results A total of 114 melanoma vaccines were administered to 24 cats. Seven cats (11.4%) had clinical adverse effects from a total of 13 vaccines classified as grade 1 or 2 based on the Veterinary Cooperative Oncology Group's common terminology criteria for adverse events v1.1. These included pain on vaccine administration, brief muscle fasciculation, transient inappetence, depression, nausea and mild increase in pigmentation at the injection site. Nineteen cats were deceased at study close. The most common cause of death was melanoma (14 cats). Hematological and biochemical changes were observed in six cats, five of which had concurrent disease or treatments that likely caused or greatly contributed to the laboratory abnormalities found. Therefore, these adverse events were considered unlikely to be caused by the melanoma vaccine. One cat had transient grade 1 hypoalbuminemia, which was possibly caused by the vaccination but not thoroughly evaluated. Conclusions and relevance The canine melanoma DNA vaccine can be safely administered to cats, with minimal risk of adverse effects.

  13. Expression and functions of galectin-7 in human and murine melanomas.

    Directory of Open Access Journals (Sweden)

    Katherine Biron-Pain

    Full Text Available The identification of galectin-7 as a p53-induced gene and its ability to induce apoptosis in many cell types support the hypothesis that galectin-7 has strong antitumor activity. This has been well documented in colon cancer. However, in some cases, such as breast cancer and lymphoma, its high expression level correlates with aggressive subtypes of cancer, suggesting that galectin-7 may have a dual role in cancer progression. In fact, in breast cancer, overexpression of galectin-7 alone is sufficient to promote metastasis to the bone and lung. In the present work, we investigated the expression and function of galectin-7 in melanoma. An analysis of datasets obtained from whole-genome profiling of human melanoma tissues revealed that galectin-7 mRNA was detected in more than 90% of biopsies of patients with nevi while its expression was more rarely found in biopsies collected from patients with malignant melanoma. This frequency, however, was likely due to the presence of normal epidermis tissues in biopsies, as shown our studies at the protein level by immunohistochemical analysis. Using the experimental melanoma B16F1 cell line, we found that melanoma cells can express galectin-7 at the primary tumor site and in lung metastasis. Moreover, we found that overexpression of galectin-7 increased the resistance of melanoma cells to apoptosis while inducing de novo egr-1 expression. Overexpression of galectin-7, however, was insufficient to modulate the growth of tumors induced by the subcutaneous injection of B16F1 cells. It also failed to modulate the dissemination of B16F1 cells to the lung.

  14. BRAF, KIT, NRAS, GNAQ and GNA11 mutation analysis in cutaneous melanomas in Turkish population

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    Ismail Yilmaz

    2015-01-01

    Full Text Available Background: KIT and mitogen-activated protein kinase cascade are important for melanomagenesis. In the present study, we analyzed the frequency of BRAF, NRAS, KIT, GNAQ and GNA11 gene mutations and investigated their association with clinicopathological features of melanomas in Turkish population. Materials and Methods: Forty-seven primary cutaneous melanomas were included in our study. Sanger sequencing method was used for mutation analysis in all cases. Results: Mean age was 62.1 (29-101 years. Female:male ratio was 17:30. Among 47 melanomas, 14 (29.8% BRAF, 10 (21.3% NRAS, 4 (8.5% KIT and 1(2.1% GNAQ gene mutations were detected. Two of the KIT mutations were found in acral lentiginous melanoma (ALM. In the head and neck region, mutation frequency was significantly lower than in other locations (P = 0.035. The only GNAQ gene mutation (p.Q209L was detected in a melanoma arising from blue nevus located on the scalp. None of the melanomas harbored NRAS exon 2, KIT exon 13/17/18, GNAQ exon 4 and GNA11 exon 4/5 mutations. Overall mutation frequency did not show significant difference between metastatic (8/14, 57.1% and nonmetastatic (18/33, 54.5% patients. We did not observe any significant association between mutation status and gender or age of various patients. Conclusions: Our results support that BRAF and NRAS gene mutations are common in cutaneous melanomas. The activating mutations of KIT gene are rare and especially seen in ALM. GNAQ and GNA11 mutations are infrequent in cutaneous melanomas and may be associated only with melanomas arising from blue nevus.

  15. A novel approach for the detection and genetic analysis of live melanoma circulating tumor cells.

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    Melody J Xu

    Full Text Available Circulating tumor cell (CTC detection and genetic analysis may complement currently available disease assessments in patients with melanoma to improve risk stratification and monitoring. We therefore sought to establish the feasibility of a telomerase-based assay for detecting and isolating live melanoma CTCs.The telomerase-based CTC assay utilizes an adenoviral vector that, in the presence of elevated human telomerase activity, drives the amplification of green fluorescent protein. Tumor cells are then identified via an image processing system. The protocol was tested on melanoma cells in culture or spiked into control blood, and on samples from patients with metastatic melanoma. Genetic analysis of the isolated melanoma CTCs was then performed for BRAF mutation status.The adenoviral vector was effective for all melanoma cell lines tested with sensitivity of 88.7% (95%CI 85.6-90.4% and specificity of 99.9% (95%CI 99.8-99.9%. In a pilot trial of patients with metastatic disease, CTCs were identified in 9 of 10 patients, with a mean of 6.0 CTCs/mL. At a cutoff of 1.1 CTCs/mL, the telomerase-based assay exhibits test performance of 90.0% sensitivity and 91.7% specificity. BRAF mutation analysis of melanoma cells isolated from culture or spiked control blood, or from pilot patient samples was found to match the known BRAF mutation status of the cell lines and primary tumors.To our knowledge, this is the first report of a telomerase-based assay effective for detecting and isolating live melanoma CTCs. These promising findings support further studies, including towards integrating into the management of patients with melanoma receiving multimodality therapy.

  16. Regulation of cell cycle checkpoint kinase WEE1 by miR-195 in malignant melanoma.

    Science.gov (United States)

    Bhattacharya, A; Schmitz, U; Wolkenhauer, O; Schönherr, M; Raatz, Y; Kunz, M

    2013-06-27

    WEE1 kinase has been described as a major gate keeper at the G2 cell cycle checkpoint and to be involved in tumour progression in different malignant tumours. Here we analysed the expression levels of WEE1 in a series of melanoma patient samples and melanoma cell lines using immunoblotting, quantitative real-time PCR and immunohistochemistry. WEE1 expression was significantly downregulated in patient samples of metastatic origin as compared with primary melanomas and in melanoma cell lines of high aggressiveness as compared with cell lines of low aggressiveness. Moreover, there was an inverse correlation between the expression of WEE1 and WEE1-targeting microRNA miR-195. Further analyses showed that transfection of melanoma cell lines with miR-195 indeed reduced WEE1 mRNA and protein expression in these cells. Reporter gene analysis confirmed direct targeting of the WEE1 3' untranslated region (3'UTR) by miR-195. Overexpression of miR-195 in SK-Mel-28 melanoma cells was accompanied by WEE1 reduction and significantly reduced stress-induced G2-M cell cycle arrest, which could be restored by stable overexpression of WEE1. Moreover, miR-195 overexpression and WEE1 knockdown, respectively, increased melanoma cell proliferation. miR-195 overexpression also enhanced migration and invasiveness of melanoma cells. Taken together, the present study shows that WEE1 expression in malignant melanoma is directly regulated by miR-195. miR-195-mediated downregulation of WEE1 in metastatic lesions may help to overcome cell cycle arrest under stress conditions in the local tissue microenvironment to allow unrestricted growth of tumour cells.

  17. Lack of Radiation Maculopathy After Palladium-103 Plaque Radiotherapy for Iris Melanoma

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    Yousef, Yacoub A. [New York Eye Cancer Center, New York Eye and Ear Infirmary, and New York University School of Medicine, New York, NY (United States); Finger, Paul T., E-mail: pfinger@eyecancer.com [New York Eye Cancer Center, New York Eye and Ear Infirmary, and New York University School of Medicine, New York, NY (United States)

    2012-07-15

    Purpose: To report on the risk of radiation maculopathy for iris and iridociliary melanomas treated by {sup 103}Pd plaque radiotherapy. Methods and Materials: This is a retrospective clinical case series of 30 eyes in 30 patients with melanomas limited to the iris or invading the ciliary body. The main outcome measures included demographic information, laterality, tumor size, location, visual acuity, radiation dose, local control, retinal evaluation, and duration of follow-up. Results: Thirty patients were followed for a median 36 months (range, 12-90 months). Sixteen of 30 tumors (53%) were pure iris melanomas, and 14 (47%) were primary iris melanomas extending into the ciliary body. Radiation dosimetry showed that the median tumor apex dose was 85 Gy (range, 75-100 Gy), lens dose 43.5 Gy (range, 17.8-60 Gy), fovea dose 1.8 Gy (range, 1.3-5 Gy), and central optic disc dose 1.7 Gy (range, 1.3-4.7 Gy). Cataracts developed in 20 of the 28 phakic eyes (71.4%). No patient in this series developed radiation maculopathy or radiation optic neuropathy. Last best-corrected visual acuity was {>=}20/25 in 28 patients (93%) at a median 36 months' follow-up. Conclusion: Though visual acuities were transiently affected by radiation cataract, no radiation maculopathy or optic neuropathy has been noted after {sup 103}Pd treatment of iris and iridociliary melanomas.

  18. Immune cell-poor melanomas benefit from PD-1 blockade after targeted type I IFN activation.

    Science.gov (United States)

    Bald, Tobias; Landsberg, Jennifer; Lopez-Ramos, Dorys; Renn, Marcel; Glodde, Nicole; Jansen, Philipp; Gaffal, Evelyn; Steitz, Julia; Tolba, Rene; Kalinke, Ulrich; Limmer, Andreas; Jönsson, Göran; Hölzel, Michael; Tüting, Thomas

    2014-06-01

    Infiltration of human melanomas with cytotoxic immune cells correlates with spontaneous type I IFN activation and a favorable prognosis. Therapeutic blockade of immune-inhibitory receptors in patients with preexisting lymphocytic infiltrates prolongs survival, but new complementary strategies are needed to activate cellular antitumor immunity in immune cell-poor melanomas. Here, we show that primary melanomas in Hgf-Cdk4(R24C) mice, which imitate human immune cell-poor melanomas with a poor outcome, escape IFN-induced immune surveillance and editing. Peritumoral injections of immunostimulatory RNA initiated a cytotoxic inflammatory response in the tumor microenvironment and significantly impaired tumor growth. This critically required the coordinated induction of type I IFN responses by dendritic, myeloid, natural killer, and T cells. Importantly, antibody-mediated blockade of the IFN-induced immune-inhibitory interaction between PD-L1 and PD-1 receptors further prolonged the survival. These results highlight important interconnections between type I IFNs and immune-inhibitory receptors in melanoma pathogenesis, which serve as targets for combination immunotherapies. Using a genetically engineered mouse melanoma model, we demonstrate that targeted activation of the type I IFN system with immunostimulatory RNA in combination with blockade of immune-inhibitory receptors is a rational strategy to expose immune cell-poor tumors to cellular immune surveillance. ©2014 American Association for Cancer Research.

  19. Malignant melanoma at a scientific laboratory

    International Nuclear Information System (INIS)

    Shy, C.M.; Checkoway, H.; Marshall, E.G.

    1985-01-01

    The general consensus of the seven reviewers is that occupational exposures at Lawrence Livermore National Laboratory have not been established as a causal factor for the observed excess of malignant melanoma. Several observations support the impression that some or all of the observed melanoma excess may be attributable to intense surveillance and enhanced detection of early stage melanoma lesions. Since the incidence of melanomas among Laboratory employees has not diminished, an early harvesting effect is unlikely. This suggests the distinct possibility that localized, in situ melanomas that would normally not be detected are being reported, and that in the absence of this enhanced detection, many of these early stage lesions would show little or no clinical progression. This phenomenon would explain the continued high incidence of melanomas in the absence of a physical or chemical inciting cause. A key point in this reasoning is the issue of the rate of growth of early stage melanomas, and this point remains a key question for study. Even if the observed excess cannot be explained by detection bias, the reviewers agree that the Austin and Reynolds' study does not make a convincing case for occupational factors being a cause of the high melanoma incidence. 6 refs

  20. Do melanoma patients from Southern climates have a worse outcome than those from Northern climates?

    Science.gov (United States)

    Woodall, Charles E; Martin, Robert C G; Stromberg, Arnold J; Ginter, Brooke; Burton, Alison; Ross, Merrick I; Edwards, Michael J; McMasters, Kelly M; Scoggins, Charles R

    2009-08-01

    Sun exposure is known to cause melanoma; what is not known is whether patients from the Southern United States have a different profile of clinicopathologic factors and outcomes than those from the Northern United States. Data from a prospective, randomized trial on surgery for cutaneous melanoma were analyzed. All patients underwent wide excision and sentinel lymph node biopsy. Patients were categorized into two groups: Northern or Southern according to their state of residence. Clinicopathologic factors and outcomes were compared between groups. A total of 2025 patients were included in the analysis; 1214 (60%) were from Southern states. The median follow-up was 52 months. Despite significant differences in clinicopathologic features between groups on both univariate and multivariate analysis, two important factors, namely primary tumor thickness and ulceration were not different, nor was the rate of lymph node metastasis. Additionally, there were no differences in disease-free survival or overall survival between the two groups. Significant differences exist between primary melanomas based on geographic regions; however there are no differences in survival. Cumulative versus episodic sun exposure may play some role in these differences.

  1. Acute Truncal Lymphedema Secondary to Axillary Metastatic Melanoma Presenting Like Cellulitis

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    Shelley J. E. Hwang

    2017-01-01

    Full Text Available There are reported cases of diphencyprone used in treating cutaneous metastases of melanoma. Here, we report a patient with previous primary melanoma on his left back treated with surgical excision and lymphadenectomy, followed by radiotherapy for the recurrent tumor on the primary site. Despite radiotherapy and treatment with dabrafenib and trametinib, in-transit metastases have developed and topical diphencyprone was applied to these metastases. Six weeks later, the patient developed fever and a spreading erythematous tender indurated plaque covering the left side of the body including axillae, back, and flank, clinically suggestive of cellulitis. Systemic antibiotic therapy did not improve the condition and a biopsy showed sparse lymphocytic infiltrate. With the diagnosis of possible acute lymphedema, a CT scan was requested that showed significant axillary lymph node metastasis. The fever was considered secondary to dabrafenib and trametinib therapy. This case highlights that, in patients with lymphadenectomy, atypical forms of lymphedema on the body may appear. Truncal lymphedema is an infrequent event.

  2. Prediction of Non-sentinel Node Status in Patients with Melanoma and Positive Sentinel Node Biopsy: An Italian Melanoma Intergroup (IMI) Study.

    Science.gov (United States)

    Rossi, Carlo Riccardo; Mocellin, Simone; Campana, Luca Giovanni; Borgognoni, Lorenzo; Sestini, Serena; Giudice, Giuseppe; Caracò, Corrado; Cordova, Adriana; Solari, Nicola; Piazzalunga, Dario; Carcoforo, Paolo; Quaglino, Pietro; Caliendo, Virginia; Ribero, Simone

    2018-01-01

    Approximately 20% of melanoma patients harbor metastases in non-sentinel nodes (NSNs) after a positive sentinel node biopsy (SNB), and recent evidence questions the therapeutic benefit of completion lymph node dissection (CLND). We built a nomogram for prediction of NSN status in melanoma patients with positive SNB. Data on anthropometric and clinicopathological features of patients with cutaneous melanoma who underwent CLND after a positive SNB were collected from nine Italian centers. Multivariate logistic regression was utilized to identify predictors of NSN status in a training set, while model efficiency was validated in a validation set. Data were available for 1220 patients treated from 2000 through 2016. In the training set (n = 810), the risk of NSN involvement was higher when (1) the primary melanoma is thicker or (2) sited in the trunk/head and neck; (3) fewer nodes are excised and (4) more nodes are involved; and (5) the lymph node metastasis is larger or (6) is deeply located. The model showed high discrimination (area under the receiver operating characteristic curve 0.74, 95% confidence interval [CI] 0.70-0.79) and calibration (Brier score 0.16, 95% CI 0.15-0.17) performance in the validation set (n = 410). The nomogram including these six clinicopathological variables performed significantly better than five other previously published models in terms of both discrimination and calibration. Our nomogram could be useful for follow-up personalization in clinical practice, and for patient risk stratification while conducting clinical trials or analyzing their results.

  3. Membrane-type-3 matrix metalloproteinase (MT3-MMP functions as a matrix composition-dependent effector of melanoma cell invasion.

    Directory of Open Access Journals (Sweden)

    Olga Tatti

    Full Text Available In primary human melanoma, the membrane-type matrix metalloproteinase, MT3-MMP, is overexpressed in the most aggressive nodular-type tumors. Unlike MT1-MMP and MT2-MMP, which promote cell invasion through basement membranes and collagen type I-rich tissues, the function of MT3-MMP in tumor progression remains unclear. Here, we demonstrate that MT3-MMP inhibits MT1-MMP-driven melanoma cell invasion in three-dimensional collagen, while yielding an altered, yet MT1-MMP-dependent, form of expansive growth behavior that phenocopies the formation of nodular cell colonies. In melanoma cell lines originating from advanced primary or metastatic lesions, endogenous MT3-MMP expression was associated with limited collagen-invasive potential. In the cell lines with highest MT3-MMP expression relative to MT1-MMP, collagen-invasive activity was increased following stable MT3-MMP gene silencing. Consistently, MT3-MMP overexpression in cells derived from less advanced superficially spreading melanoma lesions, or in the MT3-MMP knockdown cells, reduced MT1-MMP-dependent collagen invasion. Rather than altering MT1-MMP transcription, MT3-MMP interacted with MT1-MMP in membrane complexes and reduced its cell surface expression. By contrast, as a potent fibrinolytic enzyme, MT3-MMP induced efficient invasion of the cells in fibrin, a provisional matrix component frequently found at tumor-host tissue interfaces and perivascular spaces of melanoma. Since MT3-MMP was significantly upregulated in biopsies of human melanoma metastases, these results identify MT3-MMP as a matrix-dependent modifier of the invasive tumor cell functions during melanoma progression.

  4. EMMPRIN/CD147 is an independent prognostic biomarker in cutaneous melanoma.

    Science.gov (United States)

    Caudron, Anne; Battistella, Maxime; Feugeas, Jean-Paul; Pages, Cécile; Basset-Seguin, Nicole; Mazouz Dorval, Sarra; Funck Brentano, Elisa; Sadoux, Aurélie; Podgorniak, Marie-Pierre; Menashi, Suzanne; Janin, Anne; Lebbé, Céleste; Mourah, Samia

    2016-08-01

    CD147 has been implicated in melanoma invasion and metastasis mainly through increasing metalloproteinase synthesis and regulating VEGF/VEGFR signalling. In this study, the prognostic value of CD147 expression was investigated in a cohort of 196 cutaneous melanomas including 136 consecutive primary malignant melanomas, 30 lymph nodes, 16 in-transit and 14 visceral metastases. A series of 10 normal skin, 10 blue nevi and 10 dermal nevi was used as control. CD147 expression was assessed by immunohistochemistry, and the association of its expression with the clinicopathological characteristics of patients and survival was evaluated using univariate and multivariate statistical analyses. Univariate analysis showed that high CD147 expression was significantly associated with metastatic potential and with a reduced overall survival (P CD147 expression level was correlated with histological factors which were associated with prognosis: Clark level, ulceration status and more particularly with Breslow index (r = 0.7, P CD147 expression level and ulceration status as predicting factors for metastasis and overall survival (P CD147 emerges as an important factor in the aggressive behaviour of melanoma and deserves further evaluation as an independent prognostic biomarker. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  5. Primary clear cell sarcoma of rib

    International Nuclear Information System (INIS)

    Hersekli, Murat Ali; Ozkoc, Gurkan; Akpinar, Sercan; Ozalay, Metin; Tandogan, Reha N.; Bircan, Sema; Tuncer, Ilhan

    2005-01-01

    Clear cell sarcoma (malignant melanoma of soft tissues) is a very rare soft tissue neoplasm. It generally arises in tendons and aponeuroses. Although metastasis of malignant melanoma to bone is not uncommon, primary clear cell sarcoma of bone is an extremely rare neoplasm. To our knowledge five cases have been reported in the English literature. We present a case of primary clear cell sarcoma of bone in a 28-year-old woman arising in the left ninth rib. We treated the patient with total excision of the mass and postoperative radiotherapy. The patient is alive and well without local recurrence or distant metastasis at 33 months after surgery. (orig.)

  6. Identification of an Immunogenic Subset of Metastatic Uveal Melanoma.

    Science.gov (United States)

    Rothermel, Luke D; Sabesan, Arvind C; Stephens, Daniel J; Chandran, Smita S; Paria, Biman C; Srivastava, Abhishek K; Somerville, Robert; Wunderlich, John R; Lee, Chyi-Chia R; Xi, Liqiang; Pham, Trinh H; Raffeld, Mark; Jailwala, Parthav; Kasoji, Manjula; Kammula, Udai S

    2016-05-01

    Uveal melanoma is a rare melanoma variant with no effective therapies once metastases develop. Although durable cancer regression can be achieved in metastatic cutaneous melanoma with immunotherapies that augment naturally existing antitumor T-cell responses, the role of these treatments for metastatic uveal melanoma remains unclear. We sought to define the relative immunogenicity of these two melanoma variants and determine whether endogenous antitumor immune responses exist against uveal melanoma. We surgically procured liver metastases from uveal melanoma (n = 16) and cutaneous melanoma (n = 35) patients and compared the attributes of their respective tumor cell populations and their infiltrating T cells (TIL) using clinical radiology, histopathology, immune assays, and whole-exomic sequencing. Despite having common melanocytic lineage, uveal melanoma and cutaneous melanoma metastases differed in their melanin content, tumor differentiation antigen expression, and somatic mutational profile. Immunologic analysis of TIL cultures expanded from these divergent forms of melanoma revealed cutaneous melanoma TIL were predominantly composed of CD8(+) T cells, whereas uveal melanoma TIL were CD4(+) dominant. Reactivity against autologous tumor was significantly greater in cutaneous melanoma TIL compared with uveal melanoma TIL. However, we identified TIL from a subset of uveal melanoma patients which had robust antitumor reactivity comparable in magnitude with cutaneous melanoma TIL. Interestingly, the absence of melanin pigmentation in the parental tumor strongly correlated with the generation of highly reactive uveal melanoma TIL. The discovery of this immunogenic group of uveal melanoma metastases should prompt clinical efforts to determine whether patients who harbor these unique tumors can benefit from immunotherapies that exploit endogenous antitumor T-cell populations. Clin Cancer Res; 22(9); 2237-49. ©2015 AACR. ©2015 American Association for Cancer Research.

  7. Sun Protection Practices and Sun Exposure among Children with a Parental History of Melanoma

    Science.gov (United States)

    Glenn, Beth A.; Lin, Tiffany; Chang, L. Cindy; Okada, Ashley; Wong, Weng Kee; Glanz, Karen; Bastani, Roshan

    2014-01-01

    Background First-degree relatives of melanoma survivors have a substantially higher lifetime risk for melanoma than individuals with no family history. Exposure to ultraviolet radiation is the primary modifiable risk factor for the disease. Reducing UV exposure through sun protection may be particularly important for children with a parental history of melanoma. Nonetheless, limited prior research has investigated sun protection practices and sun exposure among these children. Methods The California Cancer Registry was used to identify melanoma survivors eligible to participate in a survey to assess their children's sun protection practices and sun exposure. The survey was administered by mail, telephone, or web to Latino and non-Latino white melanoma survivors with at least one child (0–17 years; N = 324). Results Sun exposure was high and the rate of sunburn was equivalent to or higher than estimates from average risk populations. Use of sun protection was suboptimal. Latino children were less likely to wear sunscreen and hats and more likely to wear sunglasses, although these differences disappeared in adjusted analyses. Increasing age of the child was associated with lower sun protection and higher risk for sunburn whereas higher objective risk for melanoma predicted improved sun protection and a higher risk for sunburns. Perception of high barriers to sun protection was the strongest modifiable correlate of sun protection. Conclusions Interventions to improve sun protection and reduce sun exposure and sunburns in high risk children are needed. Impact Intervening in high risk populations may help reduce the burden of melanoma in the U.S. PMID:25587110

  8. Xeroderma pigmentosum genes and melanoma risk.

    Science.gov (United States)

    Paszkowska-Szczur, K; Scott, R J; Serrano-Fernandez, P; Mirecka, A; Gapska, P; Górski, B; Cybulski, C; Maleszka, R; Sulikowski, M; Nagay, L; Lubinski, J; Dębniak, T

    2013-09-01

    Xeroderma pigmentosum is a rare autosomal recessive disease that is associated with a severe deficiency in nucleotide excision repair. The presence of a distinct the nucleotide excision repair (NER) mutation signature in melanoma suggests that perturbations in this critical repair process are likely to be involved with disease risk. We hypothesized that persons with polymorphic NER gene(s) are likely to have reduced NER activity and are consequently at an increased risk of melanoma development. We assessed the association between 94 SNPs within seven XP genes (XPA-XPG) and the melanoma risk in the Polish population. We genotyped 714 unselected melanoma patients and 1,841 healthy adults to determine if there were any polymorphisms differentially represented in the disease group. We found that a significantly decreased risk of melanoma was associated with the Xeroderma pigmentosum complementation (XPC) rs2228000_CT genotype (odds ratio [OR] = 0.15; p Xeroderma pigmentosum group D (XPD) showed a modest association between two haplotypes and a decrease in melanoma risk. There were no major differences between the prevalence of the XP polymorphisms among young or older patients with melanoma. Linkage disequilibrium of XPC: rs2228001, G1475A, G2061A, rs2228000 and rs3731062 was found. The data from our study support the notion that only XPC and XPD genes are associated with melanoma susceptibility. Copyright © 2013 UICC.

  9. Amelanotic Esophageal Malignant Melanoma: Case Report and Short Review of the Literature

    Directory of Open Access Journals (Sweden)

    Michael Kranzfelder

    2008-07-01

    Full Text Available Malignant melanoma in the esophagus is a rare condition which has been described only occasionally in case reports or in larger series of patients with esophageal disease. We describe here the very rare case of a patient who presented initially with a 2-month history of dysphagia and weight loss which led to the endoscopic diagnosis of an unclear lesion in the distal esophagus. Biopsies were taken revealing positive immunohistochemical staining against HMB-45. As there were no signs of skin melanoma and there was an absence of pigmentation, a diagnosis of primary amelanotic malignant melanoma was made. Primary staging of the lesion was completed with computed tomography (CT, which revealed a locally advanced tumor with lymph node metastases at the lesser curvature of the stomach and celiac trunk. As there is still a lack of potential protocols for multimodal neoadjuvant treatment for this rare tumor entity, a palliative abdominothoracic esophagectomy with systemic lymphadenectomy and intrathoracic anastomosis was carried out. Due to an intraoperative R2 situation, clip marking was performed to allow postoperative radiotherapy. Two months postoperatively, the planning CT scan for radiotherapy revealed progression of the retroperitoneal tumor mass, which was enclosing the celiac trunk, renal vein, and superior mesenteric artery. Multiple new liver and lung metastases were also found. During the following weeks, the patient developed acute renal failure and was admitted for dialysis, and the planned radiotherapy was deferred. At the end of May 2007, 4 months after the primary diagnosis, the patient died due to acute renal failure.

  10. Identification of high-risk cutaneous melanoma tumors is improved when combining the online American Joint Committee on Cancer Individualized Melanoma Patient Outcome Prediction Tool with a 31-gene expression profile-based classification.

    Science.gov (United States)

    Ferris, Laura K; Farberg, Aaron S; Middlebrook, Brooke; Johnson, Clare E; Lassen, Natalie; Oelschlager, Kristen M; Maetzold, Derek J; Cook, Robert W; Rigel, Darrell S; Gerami, Pedram

    2017-05-01

    A significant proportion of patients with American Joint Committee on Cancer (AJCC)-defined early-stage cutaneous melanoma have disease recurrence and die. A 31-gene expression profile (GEP) that accurately assesses metastatic risk associated with primary cutaneous melanomas has been described. We sought to compare accuracy of the GEP in combination with risk determined using the web-based AJCC Individualized Melanoma Patient Outcome Prediction Tool. GEP results from 205 stage I/II cutaneous melanomas with sufficient clinical data for prognostication using the AJCC tool were classified as low (class 1) or high (class 2) risk. Two 5-year overall survival cutoffs (AJCC 79% and 68%), reflecting survival for patients with stage IIA or IIB disease, respectively, were assigned for binary AJCC risk. Cox univariate analysis revealed significant risk classification of distant metastasis-free and overall survival (hazard ratio range 3.2-9.4, P risk by GEP but low risk by AJCC. Specimens reflect tertiary care center referrals; more effective therapies have been approved for clinical use after accrual. The GEP provides valuable prognostic information and improves identification of high-risk melanomas when used together with the AJCC online prediction tool. Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

  11. The presence of dysplastic nevus remnants in malignant melanomas. A population-based study of 551 malignant melanomas.

    Science.gov (United States)

    Hastrup, N; Osterlind, A; Drzewiecki, K T; Hou-Jensen, K

    1991-08-01

    We examined 512 malignant melanomas, representing all newly diagnosed cutaneous malignant melanomas, excluding lentigo maligna melanomas, from the period October 1, 1982 to March 31, 1985 occurring in the region of eastern Denmark in patients aged 20-79 years for the presence of dysplastic nevus remnants. Criteria for the diagnosis of a dysplastic nevus remnant include all the following changes (a) lentiginous or epithelioid melanocyte hyperplasia, (b) cytologic melanocyte atypia, (c) eosinophilic fibroplasia, (d) lamellar fibroplasia, and (e) lymphocytic infiltration in the dermis. Dysplastic nevus remnants were found in association with 34 (7%) of the evaluable 512 malignant melanomas. Fourteen (41%) of the remnants were of compound nevus type. In nine (27%) of the remnants, atypia was pronounced. Most (62%) dysplastic nevus remnants were contiguous to thin superficial spreading melanomas. We conclude from this population-based study that about 7% of malignant melanomas arise in prior dysplastic nevi.

  12. Towards new therapeutic approaches for malignant melanoma.

    Science.gov (United States)

    Pacheco, Ivan; Buzea, Cristina; Tron, Victor

    2011-11-01

    Recent progress in understanding the molecular mechanisms of the initiation and progression of melanoma has created new opportunities for developing novel therapeutic modalities to manage this potentially lethal disease. Although at first glance, melanoma carcinogenesis appears to be a chaotic system, it is indeed, arguably, a deterministic multistep process involving sequential alterations of proto-oncogenes, tumour suppressors and miRNA genes. The scope of this article is to discuss the most recent and significant advances in melanoma molecular therapeutics. It is apparent that using single agents targeting solely individual melanoma pathways might be insufficient for long-term survival. However, the outstanding results on melanoma survival observed with novel selective inhibitors of B-RAF, such as PLX4032 give hope that melanoma can be cured. The fact that melanoma develops acquired resistance to PLX4032 emphasises the importance of simultaneously targeting several pathways. Because the most striking feature of melanoma is its unsurpassed ability to metastasise, it is important to implement newer systems for drug delivery adapted from research on stem cells and nanotechnology.

  13. Long-term Survival after Metastatic Childhood Melanoma

    DEFF Research Database (Denmark)

    Larsen, Anne Kristine; Bybjerg Jensen, Mette; Krag, Christen

    2014-01-01

    SUMMARY: Malignant melanoma in children is very rare and accounts for only 1-3% of all melanomas. A congenital melanocytic nevus depending on the size of the lesion is one of the risk factors for developing childhood melanoma because of the possible malignant transformation. Childhood malignant...... of malign melanoma must be in mind when evaluating a pigmented lesion in a pediatric patient. We present a case of a patient born with a congenital nevus diagnosed with metastatic childhood malignant scalp melanoma at the age of 6 years. The patient underwent surgical ablation and reconstruction and has...... survived 26 years without recurrence, thus representing an uplifting case of long-term survival of childhood melanoma....

  14. MelanomaDB: a Web Tool for Integrative Analysis of Melanoma Genomic Information to Identify Disease-Associated Molecular Pathways

    Directory of Open Access Journals (Sweden)

    Alexander Joseph Trevarton

    2013-07-01

    Full Text Available Despite on-going research, metastatic melanoma survival rates remain low and treatment options are limited. Researchers can now access a rapidly growing amount of molecular and clinical information about melanoma. This information is becoming difficult to assemble and interpret due to its dispersed nature, yet as it grows it becomes increasingly valuable for understanding melanoma. Integration of this information into a comprehensive resource to aid rational experimental design and patient stratification is needed. As an initial step in this direction, we have assembled a web-accessible melanoma database, MelanomaDB, which incorporates clinical and molecular data from publically available sources, which will be regularly updated as new information becomes available. This database allows complex links to be drawn between many different aspects of melanoma biology: genetic changes (e.g. mutations in individual melanomas revealed by DNA sequencing, associations between gene expression and patient survival, data concerning drug targets, biomarkers, druggability and clinical trials, as well as our own statistical analysis of relationships between molecular pathways and clinical parameters that have been produced using these data sets. The database is freely available at http://genesetdb.auckland.ac.nz/melanomadb/about.html . A subset of the information in the database can also be accessed through a freely available web application in the Illumina genomic cloud computing platform BaseSpace at http://www.biomatters.com/apps/melanoma-profiler-for-research . This illustrates dysregulation of specific signalling pathways, both across 310 exome-sequenced melanomas and in individual tumours and identifies novel features about the distribution of somatic variants in melanoma. We suggest that this database can provide a context in which to interpret the tumour molecular profiles of individual melanoma patients relative to biological information and available

  15. Embedded Solenoid Transformer for Power Conversion

    DEFF Research Database (Denmark)

    2015-01-01

    A resonant power converter for operation in the radio frequency range, preferably in the VHF, comprises at least one PCB-embedded transformer. The transformer is configured for radio frequency operation and comprises a printed circuit board defining a horizontal plane, the printed circuit board...... comprising at least two horizontal conductive layers separated by an isolating layer, a first embedded solenoid forming a primary winding of the transformer and a second embedded solenoid being arranged parallel to the first solenoid and forming a secondary winding of the transformer, wherein the first...

  16. When narrative medicine helps in the diagnosis of conjunctival melanoma – an exceptional case report [

    Directory of Open Access Journals (Sweden)

    Nunes, Ana Teresa

    2012-07-01

    Full Text Available [english] Introduction: Conjunctival melanoma is a relatively rare ocular malignancy with substantial associated morbidity and mortality. It can arise in previously unblemished and unpigmented regions (approximately 10% of cases, from a preexisting nevus (approximately 20% of cases, or from the flat, spreading pigmentation of primary acquired melanosis with atypia (60–70% of cases, actually called conjunctival melanocytic intraepithelial neoplasia (C-MIN with atypia (histopathologically more accurately term. Purpose: The authors describe an extremely rare case of malignant conjunctival melanoma, with a long evolution, in a young black woman. Results: Until now the patient has not shown any sign of relapse of this melanoma, after local excision.Conclusion: Conjunctival melanoma is a condition of concern because of its rarity and lethal potential. Advances in the understanding and management of this neoplasm have markedly reduced the mortality and possibly the morbidity associated with this malignancy. We observe that there are some cases of conjunctival melanoma that might be cured with only a local excision with posterior cryotherapy without more aggressive methods. The practice of narrative medicine brings new possibilities in the diagnosis and collection of classical history.

  17. Melanoma Surveillance in the US: Melanoma, Ultraviolet Radiation, and Socioeconomic Status

    Centers for Disease Control (CDC) Podcasts

    This podcast accompanies the publication of a series of articles on melanoma surveillance in the United States, available in the November supplement edition of the Journal of the American Academy of Dermatology. Chris Johnson, from the Cancer Data Registry of Idaho, discusses analyses examining the relationship between melanoma and two variables at the county level, ultraviolet radiation and socioeconomic status.

  18. Podoplanin Expression in Canine Melanoma.

    Science.gov (United States)

    Ogasawara, Satoshi; Honma, Ryusuke; Kaneko, Mika K; Fujii, Yuki; Kagawa, Yumiko; Konnai, Satoru; Kato, Yukinari

    2016-12-01

    A type I transmembrane protein, podoplanin (PDPN), is expressed in several normal cells such as lymphatic endothelial cells or pulmonary type I alveolar cells. We recently demonstrated that anticanine PDPN monoclonal antibody (mAb), PMab-38, recognizes canine PDPN of squamous cell carcinomas, but does not react with lymphatic endothelial cells. Herein, we investigated whether PMab-38 reacts with canine melanoma. PMab-38 reacted with 90% of melanoma cells (9/10 cases) using immunohistochemistry. Of interest, PMab-38 stained the lymphatic endothelial cells and cancer-associated fibroblasts in melanoma tissues, although it did not stain any lymphatic endothelial cells in normal tissues. PMab-38 could be useful for uncovering the function of PDPN in canine melanomas.

  19. Use of Oncept melanoma vaccine in 69 canine oral malignant melanomas in the UK.

    Science.gov (United States)

    Verganti, S; Berlato, D; Blackwood, L; Amores-Fuster, I; Polton, G A; Elders, R; Doyle, R; Taylor, A; Murphy, S

    2017-01-01

    Oral malignant melanomas carry a poor-to-guarded prognosis because of their local invasiveness and high metastatic propensity. The Oncept melanoma vaccine is licensed to treat dogs with stage II or III locally-controlled oral malignant melanoma and this retrospective study aimed to assess survival of affected dogs treated with the vaccine in the UK. Medical records of dogs with histopathologically-confirmed oral malignant melanoma that received the vaccine as part of their treatment were evaluated. Survival analyses for potential prognostic factors were performed. Sixty-nine dogs were included; 56 dogs, staged I to III, and with previous locoregional therapy, had a median survival time of 455 days (95% CI: 324 to 586 days). Based on Kaplan-Meier survival analysis with associated log-rank testing, no significant prognostic factors were identified for this population. Of the 13 patients with macroscopic disease treated with vaccine alone or in combination therapy, eight showed clinical response. Three patients with stage IV oral malignant melanoma survived 171, 178 and 288 days from diagnosis. Patients treated with the melanoma vaccine in our study had survival times similar to their counterparts receiving the vaccine in the USA. There were observed responses in patients with macroscopic disease and so the vaccine could be considered as palliative treatment in dogs with stage IV disease. © 2017 British Small Animal Veterinary Association.

  20. Methodology and Supporting Toolset Advancing Embedded Systems Quality

    DEFF Research Database (Denmark)

    Berger, Michael Stübert; Soler, José; Brewka, Lukasz Jerzy

    2013-01-01

    Software quality is of primary importance in the development of embedded systems that are often used in safety-critical applications. Moreover, as the life cycle of embedded products becomes increasingly tighter, productivity and quality are simultaneously required and closely interrelated towards...... delivering competitive products. In this context, the MODUS (Methodology and supporting toolset advancing embedded systems quality) project aims to provide a pragmatic and viable solution that will allow SMEs to substantially improve their positioning in the embedded-systems development market. This paper...... will describe the MODUS project with focus on the technical methodologies that will be developed advancing embedded system quality....

  1. Peptides in melanoma therapy.

    Science.gov (United States)

    Mocellin, Simone

    2012-01-01

    Peptides derived from tumor associated antigens can be utilized to elicit a therapeutically effective immune response against melanoma in experimental models. However, patient vaccination with peptides - although it is often followed by the induction of melanoma- specific T lymphocytes - is rarely associated with tumor response of clinical relevance. In this review I summarize the principles of peptide design as well as the results so far obtained in the clinical setting while treating cutaneous melanoma by means of this active immunotherapy strategy. I also discuss some immunological and methodological issues that might be helpful for the successful development of peptide-based vaccines.

  2. Involvement of ER stress and activation of apoptotic pathways in fisetin induced cytotoxicity in human melanoma.

    Science.gov (United States)

    Syed, Deeba N; Lall, Rahul K; Chamcheu, Jean Christopher; Haidar, Omar; Mukhtar, Hasan

    2014-12-01

    The prognosis of malignant melanoma remains poor in spite of recent advances in therapeutic strategies for the deadly disease. Fisetin, a dietary flavonoid is currently being investigated for its growth inhibitory properties in various cancer models. We previously showed that fisetin inhibited melanoma growth in vitro and in vivo. Here, we evaluated the molecular basis of fisetin induced cytotoxicity in metastatic human melanoma cells. Fisetin treatment induced endoplasmic reticulum (ER) stress in highly aggressive A375 and 451Lu human melanoma cells, as revealed by up-regulation of ER stress markers including IRE1α, XBP1s, ATF4 and GRP78. Time course analysis indicated that the ER stress was associated with activation of the extrinsic and intrinsic apoptotic pathways. Fisetin treated 2-D melanoma cultures displayed autophagic response concomitant with induction of apoptosis. Prolonged treatment (16days) with fisetin in a 3-D reconstituted melanoma model resulted in inhibition of melanoma progression with significant apoptosis, as evidenced by increased staining of cleaved Caspase-3 in the treated constructs. However, no difference in the expression of autophagic marker LC-3 was noted between treated and control groups. Fisetin treatment to 2-D melanoma cultures resulted in phosphorylation and activation of the multifunctional AMP-activated protein kinase (AMPK) involved in the regulation of diverse cellular processes, including autophagy and apoptosis. Silencing of AMPK failed to prevent cell death indicating that fisetin induced cytotoxicity is mediated through both AMPK-dependent and -independent mechanisms. Taken together, our studies confirm apoptosis as the primary mechanism through which fisetin inhibits melanoma cell growth and that activation of both extrinsic and intrinsic pathways contributes to fisetin induced cytotoxicity.

  3. [Elective lymph node dissection in malignant melanoma--status of color Doppler findings].

    Science.gov (United States)

    Omlor, G; Dill-Müller, D; Gross, G; Kautz, G; Schüder, G; Zaun, H; Feifel, G

    1996-01-01

    Since there is still a controversial discussion about the ELND in melanoma patients, the purpose of this prospective study was to optimize the indication concerning ELND by ultrasound examinations. 144 patients with primary melanomas were checked every 3 months after excision. Echomorphologic pattern and intranodal vascularisation in the color-flow Doppler modus provide essential information for differential diagnosis. We found 47 patients (32.6%) with suspicious ultrasound lesions. 50% of these patients had no pathological clinical findings, the histological findings of excised lymph nodes were positive in all cases. It must be emphasized, however, that the group with lymph node metastases included 12 patients with low-risk-melanomas (2 x Tis, 10 x T1 historical control group (141 patients), where ELND was performed routinely in high-risk-patients ( > T2), the incidence of ELND in our hospital decreased more than 50%; at the same time the percentage of detected lymph node metastases increased (twice).

  4. Linear Malignant Melanoma In Situ: Reports and Review of Cutaneous Malignancies Presenting as Linear Skin Cancer.

    Science.gov (United States)

    Cohen, Philip R

    2017-09-18

    Melanomas usually present as oval lesions in which the borders may be irregular. Other morphological features of melanoma include clinical asymmetry, variable color, diameter greater than 6 mm and evolving lesions. Two males whose melanoma in situ presented as linear skin lesions are described and cutaneous malignancies that may appear linear in morphology are summarized in this report. A medical literature search engine, PubMed, was used to search the following terms: cancer, cutaneous, in situ, linear, malignant, malignant melanoma, melanoma in situ, neoplasm, and skin. The 25 papers that were generated by the search and their references, were reviewed; 10 papers were selected for inclusion. The cancer of the skin typically presents as round lesions. However, basal cell carcinoma and squamous cell carcinoma may arise from primary skin conditions or benign skin neoplasms such as linear epidermal nevus and linear porokeratosis. In addition, linear tumors such as basal cell carcinoma can occur. The development of linear cutaneous neoplasms may occur secondary to skin tension line or embryonal growth patterns (as reflected by the lines of Langer and lines of Blaschko) or exogenous factors such as prior radiation therapy. Cutaneous neoplasms and specifically melanoma in situ can be added to the list of linear skin lesions.

  5. Immunoscintigraphy of malignant melanomas

    International Nuclear Information System (INIS)

    Nicol, L.; Sandron, A.; Herry, J.Y.; Chevrant-Breton, J.

    1990-01-01

    This work is part of a multicentric European evaluation of the monoclonal antibody 225.28s targeted against malignant melanoma and its metastases. Twenty-eight patients (12 males, 16 females, mean age: 53 yrs), who had initially been treated by resection of the primary tumour, were included in the study. Twenty-three of the 26 metastases more than 1 cm in diameter were visualized by immunoscintigraphy. The sensitivity of the procedure (88%) is limited however by the small size of the lesions and their depth, as well as by background noise caused by circulating antibodies. Immunoscintigraphy enables non-invasive investigation of the whole body and can detect lesions that other conventional complementary explorations fail to identify [fr

  6. Electron Paramagnetic Resonance Spectrometry and Imaging in Melanomas: Comparison between Pigmented and Nonpigmented Human Malignant Melanomas

    Directory of Open Access Journals (Sweden)

    Quentin Godechal

    2013-06-01

    Full Text Available It has been known for a long time that the melanin pigments present in normal skin, hair, and most of malignant melanomas can be detected by electron paramagnetic resonance (EPR spectrometry. In this study, we used EPR imaging as a tool to map the concentration of melanin inside ex vivo human pigmented and nonpigmented melanomas and correlated this cartography with anatomopathology. We obtained accurate mappings of the melanin inside pigmented human melanoma samples. The signal intensity observed on the EPR images correlated with the concentration of melanin within the tumors, visible on the histologic sections. In contrast, no EPR signal coming from melanin was observed from nonpigmented melanomas, therefore demonstrating the absence of EPR-detectable pigments inside these particular cases of skin cancer and the importance of pigmentation for further EPR imaging studies on melanoma.

  7. Lack of Radiation Maculopathy After Palladium-103 Plaque Radiotherapy for Iris Melanoma

    International Nuclear Information System (INIS)

    Yousef, Yacoub A.; Finger, Paul T.

    2012-01-01

    Purpose: To report on the risk of radiation maculopathy for iris and iridociliary melanomas treated by 103 Pd plaque radiotherapy. Methods and Materials: This is a retrospective clinical case series of 30 eyes in 30 patients with melanomas limited to the iris or invading the ciliary body. The main outcome measures included demographic information, laterality, tumor size, location, visual acuity, radiation dose, local control, retinal evaluation, and duration of follow-up. Results: Thirty patients were followed for a median 36 months (range, 12–90 months). Sixteen of 30 tumors (53%) were pure iris melanomas, and 14 (47%) were primary iris melanomas extending into the ciliary body. Radiation dosimetry showed that the median tumor apex dose was 85 Gy (range, 75–100 Gy), lens dose 43.5 Gy (range, 17.8–60 Gy), fovea dose 1.8 Gy (range, 1.3–5 Gy), and central optic disc dose 1.7 Gy (range, 1.3–4.7 Gy). Cataracts developed in 20 of the 28 phakic eyes (71.4%). No patient in this series developed radiation maculopathy or radiation optic neuropathy. Last best-corrected visual acuity was ≥20/25 in 28 patients (93%) at a median 36 months’ follow-up. Conclusion: Though visual acuities were transiently affected by radiation cataract, no radiation maculopathy or optic neuropathy has been noted after 103 Pd treatment of iris and iridociliary melanomas.

  8. Phenotypic and functional characteristics of blood natural killer cells from melanoma patients at different clinical stages.

    Directory of Open Access Journals (Sweden)

    Giulia Fregni

    Full Text Available Melanomas are aggressive skin tumors characterized by high metastatic potential. Immunotherapy is a valuable alternative for metastatic melanoma patients resistant to chemotherapy. Natural Killer (NK cells are efficient anti-tumor cytotoxic effectors. We previously showed that blood NK cells from stage IV metastatic melanoma patients display decreased NK receptors and that chemotherapy modifies the functional status of blood NK cells. To investigate the role of NK cells along melanoma progression, we have here studied NK cells from patients at different stages of the disease. First, we showed that ex vivo NK cells from certain stage III-IV patients displayed low degranulation potential. Using a dynamic label-free assay, we found that immunoselected IL-2 activated blood NK cells from patients efficiently lysed melanoma cells through NKp46 and NKG2D receptors, independently to the clinical stage. Moreover, the ex vivo phenotype of circulating NK cells from 33 patients (stage I to IV was extensively analyzed. NK cells from patients displayed higher variability in the percentages of Natural Cytotoxicity Receptors (NCR and Natural Killer Group 2D (NKG2D receptor expression compared to donor NK cells. The main defect was the decreased expression of NCR1 (NKp46 by NK cells from metastatic patients. Interestingly, we found a positive correlation between the NK cell percentages of NKp46 and the duration of stage IV in melanoma patients. Finally, we showed that NK cells infiltrated primary melanomas and displayed a predominant peritumoral distribution. These results are new arguments for the development of NK-based therapies in melanoma patients.

  9. [Primary pigmented breast adenocarcinoma in a male patient].

    Science.gov (United States)

    Dauendorffer, J-N; Pages, C; Abd Alsamad, I; Bagot, M; Fraitag, S

    2013-01-01

    Pigmented mammary tumours are rare. Herein, we report the third case of primary pigmented breast adenocarcinoma in a male patient with clinical mimicking of nodular melanoma of the nipple. A male patient presented with a pigmented nodule of the right nipple. Histological examination of the lesion showed dermal and subcutaneous adenocarcinomatous proliferation. The perilesional stroma contained melanin both inside and outside macrophages, leading us to conclude on primary pigmented breast adenocarcinoma clinically mimicking nodular melanoma of the nipple. Local production of melanin by neoplastic cells in the mammary carcinoma was postulated as the cause of hyperpigmentation of the tumour. Other possible causes are transfer of melanin from overlying melanocytes of the pigmented areolar epidermis to the underlying neoplastic cells, or melanin synthesis by intratumoral melanocytes migrating from the epidermis (which strikes us as the most convincing interpretation for the reported case). Breast adenocarcinoma is a rare tumour in men and may present clinically as a pigmented lesion of the nipple, resulting in the problem of differential diagnosis with primary or metastasised nodular melanoma. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

  10. Mistletoe in the treatment of malignant melanoma

    Directory of Open Access Journals (Sweden)

    Esin Sakallı Çetin

    2014-03-01

    Full Text Available Malignant melanoma is a malignant neoplasia drives from melanocytes. Malignant melanoma, the most causing death, is seen in the third place at skin cancer. Malignant melanoma shows intrinsic resistance to chemotherapeutic agents and variability in the course of the disease which are distinct features separating from other solid tumors. These features prevent the development and standardization of non-surgical treatment models of malignant melanoma. Although there is a large number of chemotherapeutic agents used in the treatment of metastatic malignant melanoma, it hasn’t been demonstrated the survival advantage of adjuvant treatment with chemotherapeutic agents. Because of the different clinical course of malignant melanoma, the disease is thought to be closely associated with immune system. Therefore, immunomodulatory therapy models were developed. Mistletoe stimulates the immune system by increasing the number and activity of dendritic cells, thus it has been shown to effect on tumor growth and metastasis of malignant melanoma patient. Outlined in this review are the recent developments in the understanding the role of mistletoe as a complementary therapy for malignant melanoma. J Clin Exp Invest 2014; 5 (1: 145-152

  11. A genome-wide shRNA screen identifies GAS1 as a novel melanoma metastasis suppressor gene.

    Science.gov (United States)

    Gobeil, Stephane; Zhu, Xiaochun; Doillon, Charles J; Green, Michael R

    2008-11-01

    Metastasis suppressor genes inhibit one or more steps required for metastasis without affecting primary tumor formation. Due to the complexity of the metastatic process, the development of experimental approaches for identifying genes involved in metastasis prevention has been challenging. Here we describe a genome-wide RNAi screening strategy to identify candidate metastasis suppressor genes. Following expression in weakly metastatic B16-F0 mouse melanoma cells, shRNAs were selected based upon enhanced satellite colony formation in a three-dimensional cell culture system and confirmed in a mouse experimental metastasis assay. Using this approach we discovered 22 genes whose knockdown increased metastasis without affecting primary tumor growth. We focused on one of these genes, Gas1 (Growth arrest-specific 1), because we found that it was substantially down-regulated in highly metastatic B16-F10 melanoma cells, which contributed to the high metastatic potential of this mouse cell line. We further demonstrated that Gas1 has all the expected properties of a melanoma tumor suppressor including: suppression of metastasis in a spontaneous metastasis assay, promotion of apoptosis following dissemination of cells to secondary sites, and frequent down-regulation in human melanoma metastasis-derived cell lines and metastatic tumor samples. Thus, we developed a genome-wide shRNA screening strategy that enables the discovery of new metastasis suppressor genes.

  12. Melanoma Surveillance in the US: The Economic Burden of Melanoma

    Centers for Disease Control (CDC) Podcasts

    2011-10-19

    This podcast accompanies the publication of a series of articles on melanoma surveillance in the United States, available in the November supplement edition of the Journal of the American Academy of Dermatology. Dr. Gery Guy, from the CDC’s Division of Cancer Prevention and Control, discusses the economic burden of melanoma.  Created: 10/19/2011 by National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP).   Date Released: 10/19/2011.

  13. Clinical significance of the molecular detection of melanoma cells circulating in the peripheral blood in melanoma patients.

    Science.gov (United States)

    Konstantopoulos, K; Psatha, M; Kalotychou, V; Frangia, N; Ioannovits, I; Meletis, I; Loukopoulos, D

    2001-06-01

    Blood circulating melanoma cells may be important for the spread of the disease. The current methods are not sensitive in detecting micro metastases. Tyrosinase mRNA can be detected in peripheral blood by a molecular test. As tyrosinase is expressed only in melanocytes and melanocytes normally do not circulate in the blood, the test may prove reliable in detecting circulating melanoma cells. we used a reverse-transcription polymerase chain reaction (RT-PCR) detecting tyrosinase mRNA in the blood. A prospective investigation in melanoma patients undergoing surgery was conducted; follow-up duration was 12 months. University Department Laboratory and Melanoma Clinic of a Tertiary Hospital. a total of 27 Greek patients with a diagnosis of malignant melanoma at different stages of the disease; 12 months follow-up after surgery. Samples form 12 healthy volunteers and 13 patients with chronic myelogenous leukemia served as controls. none. none. We detected mRNA tyrosinase in the peripheral blood in 16 out of 27 melanoma patients studied. No tyrosinase mRNA was detected in any of the 25 samples from the controls. Two of the 16 positive cases developed a metastasis within the next 12 months following testing. The other 14 positive cases remain metastasis free for this period, as also did the test negative cases. Detection of blood circulating melanoma cells by a RT-PCR technique, may be helpful in defining melanoma patients who are at risk for the spread of the disease.

  14. Umbilical melanoma: case report and review of anatomical and therapeutic aspects

    International Nuclear Information System (INIS)

    Brandao, Eduardo Miranda; Gomes, Alexandre Santos de Almeida; Ribeiro, Edilana Sa; Vilaca, Thiago Guimaraes; Macedo, Francisco Igor Bulcao de; Santos, Rogerio Luiz dos; Pernambuco Univ., Recife, PE

    2005-01-01

    Full text of publication follows: Background: Malignant melanoma corresponds to 5% of cutaneous neoplasias. However, umbilical melanoma is a rare occurrence, with only 13 cases reported on the literature. The purpose of this article is to present a case of umbilical primary melanoma, discuss the anatomy and lymphatic drainage of this region, and the therapeutic aspects. Clinical description: Three years ago, a 65 years-old white woman from Recife-PE, presented an umbilical pigmented nevus. It grew in size and one year ago the pigmentation increased. Examination showed depressed umbilical scarring completely filled by pigmented lesion with 1.5 cm, irregular borders and a depigmented area; no enlarged inguinal and axillary lymph nodes. Chest X-Ray, CT scan of abdomen and pelvis, and ultrasonography of groin and axillary lymphatic chains were normal. The pathological diagnosis after incisional biopsy was ulcerated malignant melanoma, without defining Breslow classification. Subsequently a complete excision of the lesion was performed; slide showed Breslow 8 mm and 1 mm of margin. Lymphoscintillography showed three left axillary lymph nodes. During surgical widening, the peritoneum seemed disease-free. Lymphatic mapping identified three lymph nodes, one of them not coloured by vital blue. All the lymph nodes were free of metastasis on histopathological and immunohistochemical examination. Discussion: Among the umbilical tumors, 80% are metastatic, the most common branch of which is the gastrointestinal tract. Melanoma is included in the other 20% corresponding to primary neoplasias of the umbilicus, which also include sarcomas, basal cell carcinomas and squamous cell carcinomas. From the embryological point of view, the umbilical scar can contain residues of several types of epithelial tissue of the gastrointestinal duct remaining from the omphalomesenteric duct. Anatomical aspects remain to be studied, such as the cylindrical form and the content within its thickness

  15. Clinical practice guidelines for the diagnosis and management of melanoma: melanomas that lack classical clinical features.

    Science.gov (United States)

    Mar, Victoria J; Chamberlain, Alex J; Kelly, John W; Murray, William K; Thompson, John F

    2017-10-16

    A Cancer Council Australia multidisciplinary working group is currently revising and updating the 2008 evidence-based clinical practice guidelines for the management of cutaneous melanoma. While there have been many recent improvements in treatment options for metastatic melanoma, early diagnosis remains critical to reducing mortality from the disease. Improved awareness of the atypical presentations of this common malignancy is required to achieve this. A chapter of the new guidelines was therefore developed to aid recognition of atypical melanomas. Main recommendations: Because thick, life-threatening melanomas may lack the more classical ABCD (asymmetry, border irregularity, colour variegation, diameter > 6 mm) features of melanoma, a thorough history of the lesion with regard to change in morphology and growth over time is essential. Any lesion that is changing in morphology or growing over a period of more than one month should be excised or referred for prompt expert opinion. Changes in management as a result of the guidelines: These guidelines provide greater emphasis on improved recognition of the atypical presentations of melanoma, in particular nodular, desmoplastic and acral lentiginous subtypes, with particular awareness of hypomelanotic and amelanotic lesions.

  16. Brain Metastasis as Initial Manifestation of Melanoma (A Case Report

    Directory of Open Access Journals (Sweden)

    Vitorino Modesto Santos

    2016-06-01

    Full Text Available Background: Melanoma is a malignancy derived from the neural crest, constituted of melanocytes found in the basal layer of epidermis, with the main function of melanin production. Case: A 64-year-old woman was admitted with headache and dyslalia and reported some episodes of vertigo and falls in the last six months. A superficial red and dark skin discoloration in the scalp and a node in the right parotid gland were observed. Computed tomography of the brain showed nodular lesions in the left parietal and right temporal and occipital lobes with hemorrhagic features, in addition to mass effect. Furthermore, PET-CT images were suggestive of brain, lung, and adrenal metastasis. The patient evolved with intracranial hypertension and a neurosurgery was performed. Histopathological and immunohistochemistry studies revealed metastatic melanoma. Conclusions: She underwent schedules of radiation therapy and chemotherapy, but developed uncontrolled sepsis and died in spite of clinical management and intensive care support. Cutaneous primary site of this malignancy in the scalp was previously neglected; therefore, neurological disturbances were the initial manifestations of melanoma. Immunohistochemistry findings allowed ruling out the main differential hypotheses.

  17. Targeted Therapy for Melanoma

    International Nuclear Information System (INIS)

    Quinn, Thomas; Moore, Herbert

    2016-01-01

    The research project, entitled ''Targeted Therapy for Melanoma,'' was focused on investigating the use of kidney protection measures to lower the non-specific kidney uptake of the radiolabeled Pb-DOTA-ReCCMSH peptide. Previous published work demonstrated that the kidney exhibited the highest non-target tissue uptake of the "2"1"2"P"b"/"2"0"3Pb radiolabeled melanoma targeting peptide DOTA-ReCCMSH. The radiolabeled alpha-melanocyte stimulating hormone (α-MSH) peptide analog DOTA-Re(Arg"1"1)CCMSH, which binds the melanocortin-1 receptor over-expressed on melanoma tumor cells, has shown promise as a PRRT agent in pre-clinical studies. High tumor uptake of "2"1"2Pb labeled DOTA-Re(Arg"1"1)CCMSH resulted in tumor reduction or eradication in melanoma therapy studies. Of particular note was the 20-50% cure rate observed when melanoma mice were treated with alpha particle emitter "2"1"2Pb. However, as with most PRRT agents, high radiation doses to the kidneys where observed. To optimize tumor treatment efficacy and reduce nephrotoxicity, the tumor to kidney uptake ratio must be improved. Strategies to reduce kidney retention of the radiolabeled peptide, while not effecting tumor uptake and retention, can be broken into several categories including modification of the targeting peptide sequence and reducing proximal tubule reabsorption.

  18. Targeted Therapy for Melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Quinn, Thomas [Alphamed, Jackson, TN (United States); Moore, Herbert [Alphamed, Jackson, TN (United States)

    2016-12-05

    The research project, entitled ”Targeted Therapy for Melanoma,” was focused on investigating the use of kidney protection measures to lower the non-specific kidney uptake of the radiolabeled Pb-DOTA-ReCCMSH peptide. Previous published work demonstrated that the kidney exhibited the highest non-target tissue uptake of the 212Pb/203Pb radiolabeled melanoma targeting peptide DOTA-ReCCMSH. The radiolabeled alpha-melanocyte stimulating hormone (α-MSH) peptide analog DOTA-Re(Arg11)CCMSH, which binds the melanocortin-1 receptor over-expressed on melanoma tumor cells, has shown promise as a PRRT agent in pre-clinical studies. High tumor uptake of 212Pb labeled DOTA-Re(Arg11)CCMSH resulted in tumor reduction or eradication in melanoma therapy studies. Of particular note was the 20-50% cure rate observed when melanoma mice were treated with alpha particle emitter 212Pb. However, as with most PRRT agents, high radiation doses to the kidneys where observed. To optimize tumor treatment efficacy and reduce nephrotoxicity, the tumor to kidney uptake ratio must be improved. Strategies to reduce kidney retention of the radiolabeled peptide, while not effecting tumor uptake and retention, can be broken into several categories including modification of the targeting peptide sequence and reducing proximal tubule reabsorption.

  19. Laser radiation therapy of skin melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Wagner, R.I.; Kozlov, A.P.; Moskalik, K.G.

    1981-10-01

    Pulsed neodymium laser radiation was used for the treatment of 79 patients with cutaneous melanomas and 19 patients with melanoma metastases to the skin. The patients were followed up from 3 months up to 8 years. During this period local recurrences were detected in 2 cases. Out of 70 patients with cutaneous melanomas, who by the start of the treatment had no metastases in the regional lymph nodes or distant organs, metastases developed in 15 patients (21.4%). There are all reasons to consider pulsed laser radiation an effective means of treatment of some forms of skin melanoma.

  20. Melanoma

    Science.gov (United States)

    ... cancers in females aged 15 to 29 years old. Tanning-bed use contributes to this. Melanoma: Who ... Publications Connect With Us Contact Us Media contacts Advertising contacts AAD logo Advertising, marketing and sponsorships Legal ...

  1. Advanced Melanoma Facebook Live Event

    Science.gov (United States)

    In case you missed it, watch this recent Facebook Live event about the current state of research and treatment for advanced stage melanoma. To learn more, see our evidence-based information about skin cancer, including melanoma.

  2. Correlation between theoretical anatomical patterns of lymphatic drainage and lymphoscintigraphy findings during sentinel node detection in head and neck melanomas

    Energy Technology Data Exchange (ETDEWEB)

    Vidal, Monica; Ruiz, Diana Milena [Hospital Clinic de Barcelona, Nuclear Medicine Department, Barcelona (Spain); Vidal-Sicart, Sergi; Paredes, Pilar; Pons, Francesca [Hospital Clinic de Barcelona, Nuclear Medicine Department, Barcelona (Spain); Institut d' Investigacions Biomediques Agusti Pi i Sunyer (IDIBAPS), Barcelona (Spain); Torres, Ferran [Hospital Clinic Barcelona, Statistical of Biostatistics and Data Management Core Facility, IDIBAPS, Barcelona (Spain); Universitat Autonoma de Barcelona, Biostatistics Unit, Faculty of Medicine, Barcelona (Spain)

    2016-04-15

    In the diagnosis of head and neck melanoma, lymphatic drainage is complex and highly variable. As regional lymph node metastasis is one of the most important prognostic factors, lymphoscintigraphy can help map individual drainage patterns. The aim of this study was to compare the results of lymphoscintigraphy and sentinel lymph node (SLN) detection with theoretical anatomical patterns of lymphatic drainage based on the location of the primary tumour lesion in patients with head and neck melanoma. We also determined the percentage of discrepancies between our lymphoscintigraphy and the theoretical location of nodal drainage predicted by a large lymphoscintigraphic database, in order to explain recurrence and false-negative SLN biopsies. In this retrospective study of 152 patients with head and neck melanoma, the locations of the SLNs on lymphoscintigraphy and detected intraoperatively were compared with the lymphatic drainage predicted by on-line software based on a large melanoma database. All patients showed lymphatic drainage and in all patients at least one SLN was identified by lymphoscintigraphy. Of the 152 patients, 4 had a primary lesion in areas that were not described in the Sydney Melanoma Unit database, so agreement could only be evaluated in 148 patients. Agreement between lymphoscintigraphic findings and the theoretical lymphatic drainage predicted by the software was completely concordant in 119 of the 148 patients (80.4 %, 95 % CI 73.3 - 86 %). However, this concordance was partial (some concordant nodes and others not) in 18 patients (12.2 %, 95 % CI 7.8 - 18.4 %). Discordance was complete in 11 patients (7.4 %, 95 % CI 4.2 - 12.8 %). In melanoma of the head and neck there is a high correlation between lymphatic drainage found by lymphoscintigraphy and the predicted drainage pattern and basins provided by a large reference database. Due to unpredictable drainage, preoperative lymphoscintigraphy is essential to accurately detect the SLNs in head and

  3. Antitumoral, antioxidant, and antimelanogenesis potencies of Hawthorn, a potential natural agent in the treatment of melanoma.

    Science.gov (United States)

    Mustapha, Nadia; Mokdad-Bzéouich, Imèn; Maatouk, Mouna; Ghedira, Kamel; Hennebelle, Thierry; Chekir-Ghedira, Leila

    2016-06-01

    The lack of an efficient agent that does not have the disadvantage of low activity (kojic acid), high cytotoxicity, and mutagenicity (hydroquinone), poor skin penetration (arbutin), or low stability in formulation (glabridin) led us to continue our research on new antipigmentation/skin-lightening agents. Therefore, research of natural products that can modulate the metabolism of pigmentation is of great interest. Otherwise, malignant melanoma is one of the most aggressive forms of skin cancer, with high metastatic potential, and currently, there is no effective chemotherapy against invasive melanoma. Therefore, it is necessary to develop new drugs with potent activity and weak side effects against melanoma. The in-vitro anticancer effect of hawthorn was analyzed against B16F10 melanoma cells using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The effect of isolated compounds from hawthorn on melanogenesis in B16F10 melanoma cells was investigated by measuring the amounts of melanin and tyrosinase spectrophotometrically at 475 nm. Balb/c mice models inoculated with B16F10 mouse tumor cells were used to evaluate the in-vivo antitumoral potential of hawthorn by assessing its effect on the growth of transplanted tumors. The antioxidant potential of tested samples was evaluated in B16F10 and primary human keratinocyte cells using a cellular antioxidant activity assay. Hawthorn tested samples inhibited effectively the growth of melanoma cells in vitro. Furthermore, it appears that tested samples from hawthorn reduced melanogenesis by inhibiting the tyrosinase activity of B16F10 cells in a dose-dependent manner. In-vivo studies showed that hawthorn total oligomer flavonoids extract treatment at a dose of 150 mg/kg body weight for 21 days in implanted tumor mice resulted in significant inhibition of the tumor growth volume and weight. In addition, tested samples showed significant cellular antioxidant capacity against the reactive oxygen species

  4. AMP kinase-related kinase NUAK2 affects tumor growth, migration, and clinical outcome of human melanoma.

    Science.gov (United States)

    Namiki, Takeshi; Tanemura, Atsushi; Valencia, Julio C; Coelho, Sergio G; Passeron, Thierry; Kawaguchi, Masakazu; Vieira, Wilfred D; Ishikawa, Masashi; Nishijima, Wataru; Izumo, Toshiyuki; Kaneko, Yasuhiko; Katayama, Ichiro; Yamaguchi, Yuji; Yin, Lanlan; Polley, Eric C; Liu, Hongfang; Kawakami, Yutaka; Eishi, Yoshinobu; Takahashi, Eishi; Yokozeki, Hiroo; Hearing, Vincent J

    2011-04-19

    The identification of genes that participate in melanomagenesis should suggest strategies for developing therapeutic modalities. We used a public array comparative genomic hybridization (CGH) database and real-time quantitative PCR (qPCR) analyses to identify the AMP kinase (AMPK)-related kinase NUAK2 as a candidate gene for melanomagenesis, and we analyzed its functions in melanoma cells. Our analyses had identified a locus at 1q32 where genomic gain is strongly associated with tumor thickness, and we used real-time qPCR analyses and regression analyses to identify NUAK2 as a candidate gene at that locus. Associations of relapse-free survival and overall survival of 92 primary melanoma patients with NUAK2 expression measured using immunohistochemistry were investigated using Kaplan-Meier curves, log rank tests, and Cox regression models. Knockdown of NUAK2 induces senescence and reduces S-phase, decreases migration, and down-regulates expression of mammalian target of rapamycin (mTOR). In vivo analysis demonstrated that knockdown of NUAK2 suppresses melanoma tumor growth in mice. Survival analysis showed that the risk of relapse is greater in acral melanoma patients with high levels of NUAK2 expression than in acral melanoma patients with low levels of NUAK2 expression (hazard ratio = 3.88; 95% confidence interval = 1.44-10.50; P = 0.0075). These data demonstrate that NUAK2 expression is significantly associated with the oncogenic features of melanoma cells and with the survival of acral melanoma patients. NUAK2 may provide a drug target to suppress melanoma progression. This study further supports the importance of NUAK2 in cancer development and tumor progression, while AMPK has antioncogenic properties.

  5. Current management and novel agents for malignant melanoma

    Directory of Open Access Journals (Sweden)

    Lee Byung

    2012-02-01

    Full Text Available Abstract Advanced malignant melanoma remains a challenging cancer. Over the past year, there have been 3 agents approved for treatment of melanoma by Food and Drug Administration. These include pegylated interferon alpha-2b for stage III melanoma, vemurafenib for unresectable or metastatic melanoma with BRAF V600E mutation, and ipilimumab for treatment of unresectable or metastatic melanoma. This review will also update on the development of novel agents, including tyrosine kinase inhibitors and adoptive cellular therapy.

  6. A texture based pattern recognition approach to distinguish melanoma from non-melanoma cells in histopathological tissue microarray sections.

    Directory of Open Access Journals (Sweden)

    Elton Rexhepaj

    Full Text Available AIMS: Immunohistochemistry is a routine practice in clinical cancer diagnostics and also an established technology for tissue-based research regarding biomarker discovery efforts. Tedious manual assessment of immunohistochemically stained tissue needs to be fully automated to take full advantage of the potential for high throughput analyses enabled by tissue microarrays and digital pathology. Such automated tools also need to be reproducible for different experimental conditions and biomarker targets. In this study we present a novel supervised melanoma specific pattern recognition approach that is fully automated and quantitative. METHODS AND RESULTS: Melanoma samples were immunostained for the melanocyte specific target, Melan-A. Images representing immunostained melanoma tissue were then digitally processed to segment regions of interest, highlighting Melan-A positive and negative areas. Color deconvolution was applied to each region of interest to separate the channel containing the immunohistochemistry signal from the hematoxylin counterstaining channel. A support vector machine melanoma classification model was learned from a discovery melanoma patient cohort (n = 264 and subsequently validated on an independent cohort of melanoma patient tissue sample images (n = 157. CONCLUSION: Here we propose a novel method that takes advantage of utilizing an immuhistochemical marker highlighting melanocytes to fully automate the learning of a general melanoma cell classification model. The presented method can be applied on any protein of interest and thus provides a tool for quantification of immunohistochemistry-based protein expression in melanoma.

  7. Melanoma of the skin in the Danish Cancer Registry and the Danish Melanoma Database

    DEFF Research Database (Denmark)

    Pedersen, Sidsel Arnspang; Schmidt, Sigrun Alba Johannesdottir; Klausen, Siri

    2018-01-01

    estimated the positive predictive value (PPV) of melanoma diagnosis for random samples of 200 patients from the Cancer Registry (n=200) and the Melanoma Database (n=200) during 2004-2014, using the Danish Pathology Registry as 'gold-standard' reference. We further validated tumor characteristics...

  8. The patterns of melanoma presentation in Rijeka region.

    Science.gov (United States)

    Pavlović-Ružić, Ira; Jonjić, Nives; Zamolo, Gordana; Zuvić-Butorac, Marta; Katunarić, Miljenko; Pečanić, Sanja

    2013-01-01

    There is a global rising incidence of melanoma. For different reasons, the patterns of the incidence, appearance, gender, anatomical distribution and outcome vary among different geographic areas. Screening programs have led to better early detection of melanoma in Australia and some world areas. National Cancer Registry and practice data show the incidence in Croatia to be constantly rising. Despite public education programs about early detection, at clinical departments there are still many new advanced stage melanoma patients. We analyzed data on 157 patients treated and followed up for 10 years for T1b-T4aN0 skin melanoma. There was a difference in anatomical distribution of melanoma lesions in correlation with patient age (ANOVA test, F=3.51, p=0.009). A higher prevalence of shoulder melanoma was found in young people and of head/neck melanoma in the elderly (post-hoc Sheffe test, p=0.038). T4 lesions were more commonly found in men and T1 mainly in women (Pearson χ(2)-test, χ(2)=12.08, p=0.016). There was no difference in Clark level, but a significantly higher Breslow stage was found in men (t=-2.52, p=0.013). Men were much more prone to have head and neck, body and shoulder melanoma, whereas women had more melanoma on their legs and arms. Clark and Breslow levels were strongly correlated in leg melanoma; head localization showed no correlation at all. In conclusion, more attention should be devoted to improve the results in melanoma detection in men, especially considering the prevalence of body (back) and head/neck localizations, sometimes not readily accessible for visual detection. The pattern of distribution also pointed to the need for more attention to pay to shoulder melanoma in younger people.

  9. [Telomerase activity in uveal melanomas].

    Science.gov (United States)

    Rohrbach, J M; Riedinger, C; Wild, M; Partsch, M

    2000-05-01

    The maximum number of cell divisions of a certain cell population is genetically fixed so that aging cells become non-dividing (senescent) at least. This replicative life span, also known as "Hayflick limit", is probably defined by a "critical" length of the telomeres. Telomeres are special DNA-sequences located at the four ends of the chromosomes which are shortened with each cell cycle. Cells of most, but not all malignant tumours have been shown to reactivate the enzyme telomerase so that telomeres can be reconstructed, "Hayflick limit" can be overcome, and unlimited cell division can be established. This study was undertaken to elucidate whether telomerase reactivation is used by uveal melanoma cells. Fresh tumour tissue was removed from 10 untreated uveal melanomas after enucleation. Telomerase activity was determined using a PCR ELISA according to the Telomeric Repeat Amplification Protocol (TRAP). Normal tissue of the skin and the conjunctiva served as control. Telomerase activity was detectable in 90% of the investigated uveal melanomas. All control specimens were telomerase negative. Uveal melanoma growth seems to depend on telomerase reactivation. Thus, telomerase inhibition could offer a new principle for uveal melanoma therapy in the future.

  10. Oral Amelanotic Melanoma | Adisa | Annals of Ibadan Postgraduate ...

    African Journals Online (AJOL)

    Malignant melanomas of the mucosal regions of the head and neck are extremely rare neoplasms accounting for less than 1% of all melanomas. Approximately half of all head and neck melanomas occur in the oral cavity. Less than 2% of all melanomas lack pigmentation, in the oral mucosa however, up to 75% of cases ...

  11. In Vivo Imaging of Experimental Melanoma Tumors using the Novel Radiotracer 68Ga-NODAGA-Procainamide (PCA).

    Science.gov (United States)

    Kertész, István; Vida, András; Nagy, Gábor; Emri, Miklós; Farkas, Antal; Kis, Adrienn; Angyal, János; Dénes, Noémi; Szabó, Judit P; Kovács, Tünde; Bai, Péter; Trencsényi, György

    2017-01-01

    The most aggressive form of skin cancer is the malignant melanoma. Because of its high metastatic potential the early detection of primary melanoma tumors and metastases using non-invasive PET imaging determines the outcome of the disease. Previous studies have already shown that benzamide derivatives, such as procainamide (PCA) specifically bind to melanin pigment. The aim of this study was to synthesize and investigate the melanin specificity of the novel 68 Ga-labeled NODAGA-PCA molecule in vitro and in vivo using PET techniques. Procainamide (PCA) was conjugated with NODAGA chelator and was labeled with Ga-68 ( 68 Ga-NODAGA-PCA). The melanin specificity of 68 Ga-NODAGA-PCA was tested in vitro , ex vivo and in vivo using melanotic B16-F10 and amelanotic Melur melanoma cell lines. By subcutaneous and intravenous injection of melanoma cells tumor-bearing mice were prepared, on which biodistribution studies and small animal PET/CT scans were performed for 68 Ga-NODAGA-PCA and 18 FDG tracers. 68 Ga-NODAGA-PCA was produced with high specific activity (14.9±3.9 GBq/µmol) and with excellent radiochemical purity (98%PCA uptake of B16-F10 cells was significantly ( p ≤0.01) higher than Melur cells. Ex vivo biodistribution and in vivo PET/CT studies using subcutaneous and metastatic tumor models showed significantly ( p ≤0.01) higher 68 Ga-NODAGA-PCA uptake in B16-F10 primary tumors and lung metastases in comparison with amelanotic Melur tumors. In experiments where 18 FDG and 68 Ga-NODAGA-PCA uptake of B16-F10 tumors was compared, we found that the tumor-to-muscle (T/M) and tumor-to-lung (T/L) ratios were significantly ( p ≤0.05 and p ≤0.01) higher using 68 Ga-NODAGA-PCA than the 18 FDG accumulation. Our novel radiotracer 68 Ga-NODAGA-PCA showed specific binding to the melanin producing experimental melanoma tumors. Therefore, 68 Ga-NODAGA-PCA is a suitable diagnostic radiotracer for the detection of melanoma tumors and metastases in vivo .

  12. Lack of GNAQ and GNA11 germ-line mutations in familial melanoma pedigrees with uveal melanoma or blue nevi

    Directory of Open Access Journals (Sweden)

    Jason Ezra Hawkes

    2013-06-01

    Full Text Available Approximately 10% of melanoma cases are familial, but only 25-40% of familial melanoma cases can be attributed to germ-line mutations in the CDKN2A - the most significant high-risk melanoma susceptibility locus identified to date. The pathogenic mutation(s in most of the remaining familial melanoma pedigrees have not yet been identified. The most common mutations in nevi and sporadic melanoma are found in BRAF and NRAS, both of which result in constitutive activation of the MAPK pathway. However, these mutations are not found in uveal melanomas or the intradermal melanocytic proliferations known as blue nevi. Rather, multiple studies report a strong association between these lesions and somatic mutations in Guanine nucleotide-binding protein G(q subunit alpha (GNAQ, Guanine nucleotide-binding protein G(q subunit alpha-11 (GNA11 and BRCA1 associated protein-1 (BAP1. Recently, germ-line mutations in BAP1, the gene encoding a tumor suppressing deubiquitinating enzyme, have been associated with predisposition to a variety of cancers including uveal melanoma, but no studies have examined the association of germ-line mutations in GNAQ and GNA11 with uveal melanoma and blue nevi. We have now done so by sequencing exon 5 of both of these genes in 13 unique familial melanoma pedigrees, members of which have had either uveal or cutaneous melanoma and/or blue nevi. Germ-line DNA from a total of 22 individuals was used for sequencing; however no deleterious mutations were detected. Nevertheless, such candidate gene studies and the discovery of novel germ-line mutations associated with an increased MM susceptibility can lead to a better understanding of the pathways involved in melanocyte transformation, formulation of risk assessment, and the development of specific drug therapies.

  13. TAPIOCA MELANOMA OF THE IRIS

    NARCIS (Netherlands)

    DEKEIZER, RJW; OOSTERHUIS, JA; HOUTMAN, WA; DEWOLFFROUENDAAL, D

    Clinical identification of tapioca melanoma of the iris is important because its medical treatment may differ from that of other malignant iris melanomas. The characteristic iris nodules must be differentiated from granulomatous uveitis, metastases, and Lisch nodules (neurofibromatosis). We will

  14. Late prostatic metastasis of an uveal melanoma in a miniature Schnauzer dog.

    Science.gov (United States)

    Delgado, Esmeralda; Silva, João X; Pissarra, Hugo; Peleteiro, Maria C; Dubielzig, Richard R

    2016-07-01

    This manuscript describes a previously unreported clinical case of canine uveal melanoma in a miniature Schnauzer dog with an unusual location of metastasis (prostate) and delayed occurrence (3 years after primary tumor diagnosis and enucleation). Immunohistochemical labeling of both tumors with Melan A, Ki-67, and c-kit added some valuable information.

  15. [Multiple conjunctival malignant melanomas (author's transl)].

    Science.gov (United States)

    Haddad, R

    1979-04-01

    5 1/2 years after excision of pigmented malignant melanoma which apparently arose in a nevus of the paralimbal bulbar conjunctiva, this 42-year-old male presented himself with a nonpigmented mass of the lid margin which also proved to be a malignant melanoma. "Acquired melanosis sine pigmento" was considered as a site of origin, but histopathologically there is more evidence that this melanoma arose in a non-pigmented compound nevus.

  16. Germline mutations in candidate predisposition genes in individuals with cutaneous melanoma and at least two independent additional primary cancers.

    Science.gov (United States)

    Pritchard, Antonia L; Johansson, Peter A; Nathan, Vaishnavi; Howlie, Madeleine; Symmons, Judith; Palmer, Jane M; Hayward, Nicholas K

    2018-01-01

    While a number of autosomal dominant and autosomal recessive cancer syndromes have an associated spectrum of cancers, the prevalence and variety of cancer predisposition mutations in patients with multiple primary cancers have not been extensively investigated. An understanding of the variants predisposing to more than one cancer type could improve patient care, including screening and genetic counselling, as well as advancing the understanding of tumour development. A cohort of 57 patients ascertained due to their cutaneous melanoma (CM) diagnosis and with a history of two or more additional non-cutaneous independent primary cancer types were recruited for this study. Patient blood samples were assessed by whole exome or whole genome sequencing. We focussed on variants in 525 pre-selected genes, including 65 autosomal dominant and 31 autosomal recessive cancer predisposition genes, 116 genes involved in the DNA repair pathway, and 313 commonly somatically mutated in cancer. The same genes were analysed in exome sequence data from 1358 control individuals collected as part of non-cancer studies (UK10K). The identified variants were classified for pathogenicity using online databases, literature and in silico prediction tools. No known pathogenic autosomal dominant or previously described compound heterozygous mutations in autosomal recessive genes were observed in the multiple cancer cohort. Variants typically found somatically in haematological malignancies (in JAK1, JAK2, SF3B1, SRSF2, TET2 and TYK2) were present in lymphocyte DNA of patients with multiple primary cancers, all of whom had a history of haematological malignancy and cutaneous melanoma, as well as colorectal cancer and/or prostate cancer. Other potentially pathogenic variants were discovered in BUB1B, POLE2, ROS1 and DNMT3A. Compared to controls, multiple cancer cases had significantly more likely damaging mutations (nonsense, frameshift ins/del) in tumour suppressor and tyrosine kinase genes and

  17. Ocular melanoma and mammary mucinous carcinoma in an African lion.

    Science.gov (United States)

    Cagnini, Didier Q; Salgado, Breno S; Linardi, Juliana L; Grandi, Fabrizio; Rocha, Rafael M; Rocha, Noeme S; Teixeira, Carlos R; Del Piero, Fabio; Sequeira, Julio L

    2012-09-25

    Reports of neoplasms in Panthera species are increasing, but they are still an uncommon cause of disease and death in captive wild felids. The presence of two or more primary tumor in large felids is rarely reported, and there are no documented cases of ocular melanoma and mammary mucinous carcinoma in African lions. An ocular melanoma and a mammary mucinous carcinoma are described in an African lion (Panthera leo). The first tumour was histologically characterized by the presence of epithelioid and fusiform melanocytes, while the latter was composed of mucus-producing cells with an epithelial phenotype that contained periodic acid-Schiff (PAS) and Alcian blue staining mucins. Metastases of both tumor were identified in various organs and indirect immunohistochemistry was used to characterize them. Peribiliary cysts were observed in the liver. This is the first description of these tumor in African lions.

  18. Melanoma Cells Can Adopt the Phenotype of Stromal Fibroblasts and Macrophages by Spontaneous Cell Fusion in Vitro.

    Science.gov (United States)

    Kemény, Lajos V; Kurgyis, Zsuzsanna; Buknicz, Tünde; Groma, Gergely; Jakab, Ádám; Zänker, Kurt; Dittmar, Thomas; Kemény, Lajos; Németh, István B

    2016-06-02

    After the removal of primary cutaneous melanoma some patients develop local recurrences, even after having histologically tumor-free re-excision. A potential explanation behind this phenomenon is that tumor cells switch their phenotype, making their recognition via standard histopathological assessments extremely difficult. Tumor-stromal cell fusion has been proposed as a potential mechanism for tumor cells to acquire mesenchymal traits; therefore, we hypothesized that melanoma cells could acquire fibroblast- and macrophage-like phenotypes via cell fusion. We show that melanoma cells spontaneously fuse with human dermal fibroblasts and human peripheral blood monocytes in vitro. The hybrid cells' nuclei contain chromosomes from both parental cells and are indistinguishable from the parental fibroblasts or macrophages based on their morphology and immunophenotype, as they could lose the melanoma specific MART1 marker, but express the fibroblast marker smooth muscle actin or the macrophage marker CD68. Our results suggest that, by spontaneous cell fusion in vitro, tumor cells can adopt the morphology and immunophenotype of stromal cells while still carrying oncogenic, tumor-derived genetic information. Therefore, melanoma-stromal cell fusion might play a role in missing tumor cells by routine histopathological assessments.

  19. Uveal melanoma in the Saudi Arabian population: Two decades of management at the King Khaled Eye Specialist Hospital

    International Nuclear Information System (INIS)

    Alsuhaibani Adel H

    2009-01-01

    To present the experience of King Khaled Eye Specialist Hospital (KKESH) with uveal melanoma over the last two decades in a fashion similar to the result of the Collaborative Ocular Melanoma Study (COMS). Retrospective, non-comparative, interventional, case series. All patients were diagnosed with uveal melanoma at the King Khaled Eye Specialist Hospital (KKESH), Riyadh, Saudi Arabia from June 1983 to July 2005 and met the inclusion criteria of the COMS. A medical record review of clinical history, imaging studies, surgical procedures and treatment outcome was performed. Forty patients (24 males and 16 females) with uveal melanoma (average age 50 years; range 24-77 years) were included in the study; 28 (70%) were of Saudi Arabian descent and the remaining 12 (30%) patients were from neighboring Arab countries. Decreased vision was the main presenting complaint of 29 (72.5%) patients; the duration of this symptom was 3 months or more in 27 (67.5%) patients. The apical height of the tumor was 10 mm or more in nine (22.5%) of the affected eyes and the largest basal dimension was more than 16 mm in nine (22.5%) of the affected eyes. The posterior border of the tumor was 1-2 mmfrom the optic disc in three (7.5%) affected eyes. Primary enucleation was performed for 33 (82.5%) eyes, episcleral radiation plaque therapy for six (15%) of the eyes and endo resection of the uveal melanoma in one (2.5%) eye. Adjunct external beam radiation therapy was performed in two (5%) orbits for extrascleral extension. The histopathological diagnosis was available for 34 (84%) eyes in which surgery had been performed (33 patients underwent primary enucleation and one patient underwent endo resection of the uveal melanoma); 24 (70.6%) eyes had spindle cell and the remaining 10 (29.4%) had epithelioid or mixed cell types. Evidence of extraocular tumor extension was found in three eyes. The average follow-up was 33.7 months with a median of 19 months (range 0.5 months to 10 years). Two (5

  20. Sarcoidosis in Melanoma Patients: Case Report and Literature Review

    Energy Technology Data Exchange (ETDEWEB)

    Beutler, Bryce D., E-mail: brycebeutler@hotmail.com [School of Allied Health Sciences, University of Nevada, Las Vegas, 1060 Wiegand Road, Encinitas, CA 92024 (United States); Cohen, Philip R., E-mail: brycebeutler@hotmail.com [Department of Dermatology, University of California San Diego, 10991 Twinleaf Court, San Diego, CA 92131 (United States)

    2015-06-15

    Sarcoidosis is a systemic inflammatory disease characterized by the development of noncaseating granulomas in multiple organ systems. Many hematologic malignancies and solid tumors, including melanoma, have been associated with sarcoidosis. We describe the clinical and pathologic findings of a 54-year-old man with melanoma-associated sarcoidosis. In addition, we not only review the literature describing characteristics of other melanoma patients with sarcoidosis, but also the features of melanoma patients with antineoplastic therapy-associated sarcoidosis. Sarcoidosis has been described in 80 melanoma patients; sufficient information for analysis was provided in 39 of these individuals. In 43.6% of individuals (17 out of 39), sarcoidosis was directly associated with melanoma; in 56.4% of oncologic patients (22 out of 39), sarcoidosis was induced by antineoplastic therapy that had been administered for the treatment of their metastatic melanoma. The discovery of melanoma preceded the development of sarcoidosis in 12 of the 17 (70.5%) individuals who did not receive systemic treatment. Pulmonary and/or cutaneous manifestations of sarcoidosis were common among both groups of patients. Most patients did not require treatment for sarcoidosis. Melanoma patients—either following antineoplastic therapy or without systemic treatment—may be at an increased risk to develop sarcoidosis. In antineoplastic therapy naive melanoma patients, a common etiologic factor—such as exposure to ultraviolet light—may play a role in their developing melanoma and sarcoidosis.

  1. Profiling of ABC transporters ABCB5, ABCF2 and nestin-positive stem cells in nevi, in situ and invasive melanoma.

    Science.gov (United States)

    Setia, Namrata; Abbas, Ossama; Sousa, Yessica; Garb, Jane L; Mahalingam, Meera

    2012-08-01

    Distinct ABCB5 forms and ABCF2, members of the ATP-binding cassette (ABC) superfamily of transporters, are normally expressed in various tissues and cells, and enhanced expression of both has been demonstrated in select cancers. In melanoma cell lines, gene expression profiling of ABC transporters has revealed enhanced expression of melanocyte-specific ABCB5 and ABCF2 proteins. Given this, our primary aim was to ascertain immunohistochemical expression of the ABC transporters ABCB5 and ABCF2 and, the stem cell marker, nestin in a spectrum of benign and malignant nevomelanocytic proliferations, including nevi (n=30), in situ (n=31) and invasive (n=24) primary cutaneous melanomas to assess their role in the stepwise development of malignancy. In addition, their expression was compared with established melanoma prognosticators to ascertain their utility as independent prognosticators. A semiquantitative scoring system was utilized by deriving a cumulative score (based on percentage positivity cells and intensity of expression) and statistical analyses was carried out using analysis of variance with linear contrasts. Mean cumulative score in nevi, in situ and invasive melanoma were as follows: 3.8, 4.4 and 5.3 for ABCB5, respectively (P1, after controlling for the presence of ulceration and mitotic activity, the expression of both proteins did not significantly correlate with known melanoma prognosticators. The gradual increase in the expression of ABCB5 from benign nevus to in situ to invasive melanoma suggests that it plays a role in melanomagenesis. On the basis of our findings, a prospective study with follow-up data is required to ascertain the utility of ABCB5 as a therapeutic target.

  2. GAB2 amplifications refine molecular classification of melanoma.

    Science.gov (United States)

    Chernoff, Karen A; Bordone, Lindsey; Horst, Basil; Simon, Katherine; Twadell, William; Lee, Keagan; Cohen, Jason A; Wang, Shuang; Silvers, David N; Brunner, Georg; Celebi, Julide Tok

    2009-07-01

    Gain-of-function mutations in BRAF, NRAS, or KIT are associated with distinct melanoma subtypes with KIT mutations and/or copy number changes frequently observed among melanomas arising from sun-protected sites, such as acral skin (palms, soles, and nail bed) and mucous membranes. GAB2 has recently been implicated in melanoma pathogenesis, and increased copy numbers are found in a subset of melanomas. We sought to determine the association of increased copy numbers of GAB2 among melanoma subtypes in the context of genetic alterations in BRAF, NRAS, and KIT. A total of 85 melanomas arising from sun-protected (n = 23) and sun-exposed sites (n = 62) were analyzed for copy number changes using array-based comparative genomic hybridization and for gain-of-function mutations in BRAF, NRAS, and KIT. GAB2 amplifications were found in 9% of the cases and were associated with melanomas arising from acral and mucosal sites (P = 0.005). Increased copy numbers of the KIT locus were observed in 6% of the cases. The overall mutation frequencies for BRAF and NRAS were 43.5% and 14%, respectively, and were mutually exclusive. Among the acral and mucosal melanomas studied, the genetic alteration frequency was 26% for GAB2, 13% for KIT, 30% for BRAF, and 4% for NRAS. Importantly, the majority of GAB2 amplifications occurred independent from genetic events in BRAF, NRAS, and KIT. GAB2 amplification is critical for melanomas arising from sun-protected sites. Genetic alterations in GAB2 will help refine the molecular classification of melanomas.

  3. Solitary Secondary Malignant Melanoma of Clavicle Two Years after Enuclation for Ocular Melanoma

    Directory of Open Access Journals (Sweden)

    Halil Tozum

    2013-01-01

    Full Text Available Solitary metastasis of uveal melanoma to bone is extremely rare and usually associated with other organ involvement. We present a rare case of an ocular melanoma patient presenting with solitary metastasis to the clavicle two years after enucleation, without any other organ involvement. In this report, we tried to present our treatment strategy for the solitary metastasis of bone.

  4. Management of anorectal melanoma: report of 17 cases and literature review.

    Science.gov (United States)

    Belbaraka, Rhizlane; Elharroudi, Tijani; Ismaili, Nabil; Fetohi, Mohammed; Tijami, Fouad; Jalil, Abdelouahed; Errihani, Hassan

    2012-03-01

    Primary anorectal melanoma is a rare and aggressive disease. It accounts for 0.5% of all rectal tumors. They are very agressive tumors with poor prognosis. The aim of this study is to report the clinical and evolutionary profile and therapeutical approach of these tumors. A retrospective study of 17 patients with anorectal melanoma diagnosed between January 1998 and December 2007 was performed. The signs and symptoms, diagnostic study, and surgical and medical treatments were analyzed. The average age was 58 years. Sex ratio was 12 men per five women. Patients had symptoms present for an average of 6 months. The most common symptom was rectal bleeding. According to Slingluff classification, five patients had stage I (localized tumor), four cases had stage II (regional nodes metastasis), and eight cases had stage III (distant metastasis). Seven patients have radical surgery. Only two patients received adjuvant immunotherapy. Eight patients received palliative chemotherapy based on dacarbazine or cisplatinum. The median survival was 8 months. Prognosis of anorectal melanoma is still very poor. However, some patients when treated by radical resection may experience long-term survival. The use of adjuvant immunotherapy needs large collaborative studies in view of the rarity of the tumor.

  5. LFA-1 and ICAM-1 expression induced during melanoma-endothelial cell co-culture favors the transendothelial migration of melanoma cell lines in vitro

    International Nuclear Information System (INIS)

    Ghislin, Stephanie; Obino, Dorian; Middendorp, Sandrine; Boggetto, Nicole; Alcaide-Loridan, Catherine; Deshayes, Frederique

    2012-01-01

    Patients with metastatic melanoma have a poor median rate of survival. It is therefore necessary to increase our knowledge about melanoma cell dissemination which includes extravasation, where cancer cells cross the endothelial barrier. Extravasation is well understood during travelling of white blood cells, and involves integrins such as LFA-1 (composed of two chains, CD11a and CD18) expressed by T cells, while ICAM-1 is induced during inflammation by endothelial cells. Although melanoma cell lines cross endothelial cell barriers, they do not express LFA-1. We therefore hypothesized that melanoma-endothelial cell co-culture might induce the LFA-1/ICAM ligand/receptor couple during melanoma transmigration. A transwell approach has been used as well as blocking antibodies against CD11a, CD18 and ICAM-1. Data were analyzed with an epifluorescence microscope. Fluorescence intensity was quantified with the ImageJ software. We show here that HUVEC-conditioned medium induce cell-surface expression of LFA-1 on melanoma cell lines. Similarly melanoma-conditioned medium activates ICAM-1 expression in endothelial cells. Accordingly blocking antibodies of ICAM-1, CD11a or CD18 strongly decrease melanoma transmigration. We therefore demonstrate that melanoma cells can cross endothelial monolayers in vitro due to the induction of ICAM-1 and LFA-1 occurring during the co-culture of melanoma and endothelial cells. Our data further suggest a role of LFA-1 and ICAM-1 in the formation of melanoma cell clumps enhancing tumor cell transmigration. Melanoma-endothelial cell co-culture induces LFA-1 and ICAM-1 expression, thereby favoring in vitro melanoma trans-migration

  6. LFA-1 and ICAM-1 expression induced during melanoma-endothelial cell co-culture favors the transendothelial migration of melanoma cell lines in vitro

    Directory of Open Access Journals (Sweden)

    Ghislin Stephanie

    2012-10-01

    Full Text Available Abstract Background Patients with metastatic melanoma have a poor median rate of survival. It is therefore necessary to increase our knowledge about melanoma cell dissemination which includes extravasation, where cancer cells cross the endothelial barrier. Extravasation is well understood during travelling of white blood cells, and involves integrins such as LFA-1 (composed of two chains, CD11a and CD18 expressed by T cells, while ICAM-1 is induced during inflammation by endothelial cells. Although melanoma cell lines cross endothelial cell barriers, they do not express LFA-1. We therefore hypothesized that melanoma-endothelial cell co-culture might induce the LFA-1/ICAM ligand/receptor couple during melanoma transmigration. Methods A transwell approach has been used as well as blocking antibodies against CD11a, CD18 and ICAM-1. Data were analyzed with an epifluorescence microscope. Fluorescence intensity was quantified with the ImageJ software. Results We show here that HUVEC-conditioned medium induce cell-surface expression of LFA-1 on melanoma cell lines. Similarly melanoma-conditioned medium activates ICAM-1 expression in endothelial cells. Accordingly blocking antibodies of ICAM-1, CD11a or CD18 strongly decrease melanoma transmigration. We therefore demonstrate that melanoma cells can cross endothelial monolayers in vitro due to the induction of ICAM-1 and LFA-1 occurring during the co-culture of melanoma and endothelial cells. Our data further suggest a role of LFA-1 and ICAM-1 in the formation of melanoma cell clumps enhancing tumor cell transmigration. Conclusion Melanoma-endothelial cell co-culture induces LFA-1 and ICAM-1 expression, thereby favoring in vitro melanoma trans-migration.

  7. Late prostatic metastasis of an uveal melanoma in a miniature Schnauzer dog

    OpenAIRE

    Delgado, Esmeralda; Silva, Jo?o X.; Pissarra, Hugo; Peleteiro, Maria C.; Dubielzig, Richard R.

    2016-01-01

    Key Clinical Message This manuscript describes a previously unreported clinical case of canine uveal melanoma in a miniature Schnauzer dog with an unusual location of metastasis (prostate) and delayed occurrence (3 years after primary tumor diagnosis and enucleation). Immunohistochemical labeling of both tumors with Melan A, Ki?67, and c?kit added some valuable information.

  8. Designing the role of the embedded care manager.

    Science.gov (United States)

    Hines, Patricia; Mercury, Marge

    2013-01-01

    : The role of the professional case manager is changing rapidly. Health reform has called upon the industry to ensure that care is delivered in an efficient, effective, and high-quality and low cost manner. As a means to achieve this objective, health plans and health systems are moving the care manager out of a centralized location within their organizations to "embedding" them into physician offices. This move enables the care manager to work alongside the primary care physicians and their high-risk patients. This article discusses the framework for designing and implementing an embedded care manager role into a physician practice. Key elements of the program are discussed. IMPLICATIONS FOR CARE MANAGEMENT:: Historically care management has played a foundational role in improving the quality of care for individuals and populations via the efficient and effective use of resources. Now with the goals of health care reform, a successful transition from a volume-based to value-based reimbursement system requires primary care physicians to welcome care managers into their practices to improve patient care, quality, and costs through care coordination across health care settings and populations. : As patient-centered medical homes and integrated delivery systems formulate their plans for population health management, their efforts have included embedding a care manager in the primary practice setting. Having care managers embedded at the physician offices increases their ability to collaborate with the physician and their staff in the implementation and monitoring care plans for their patients. : Implementing an embedded care manager into an existing physician's practice requires the following:Although the embedded care manager is a highly evolving role, physician groups are beginning to realize the benefits from their care management collaborations. Examples cited include improved outreach and coordination, patient adherence to care plans, and improved quality of life.

  9. Calibration and Stokes Imaging with Full Embedded Element Primary Beam Model for the Murchison Widefield Array

    Science.gov (United States)

    Sokolowski, M.; Colegate, T.; Sutinjo, A. T.; Ung, D.; Wayth, R.; Hurley-Walker, N.; Lenc, E.; Pindor, B.; Morgan, J.; Kaplan, D. L.; Bell, M. E.; Callingham, J. R.; Dwarakanath, K. S.; For, Bi-Qing; Gaensler, B. M.; Hancock, P. J.; Hindson, L.; Johnston-Hollitt, M.; Kapińska, A. D.; McKinley, B.; Offringa, A. R.; Procopio, P.; Staveley-Smith, L.; Wu, C.; Zheng, Q.

    2017-11-01

    The Murchison Widefield Array (MWA), located in Western Australia, is one of the low-frequency precursors of the international Square Kilometre Array (SKA) project. In addition to pursuing its own ambitious science programme, it is also a testbed for wide range of future SKA activities ranging from hardware, software to data analysis. The key science programmes for the MWA and SKA require very high dynamic ranges, which challenges calibration and imaging systems. Correct calibration of the instrument and accurate measurements of source flux densities and polarisations require precise characterisation of the telescope's primary beam. Recent results from the MWA GaLactic Extragalactic All-sky Murchison Widefield Array (GLEAM) survey show that the previously implemented Average Embedded Element (AEE) model still leaves residual polarisations errors of up to 10-20% in Stokes Q. We present a new simulation-based Full Embedded Element (FEE) model which is the most rigorous realisation yet of the MWA's primary beam model. It enables efficient calculation of the MWA beam response in arbitrary directions without necessity of spatial interpolation. In the new model, every dipole in the MWA tile (4 × 4 bow-tie dipoles) is simulated separately, taking into account all mutual coupling, ground screen, and soil effects, and therefore accounts for the different properties of the individual dipoles within a tile. We have applied the FEE beam model to GLEAM observations at 200-231 MHz and used false Stokes parameter leakage as a metric to compare the models. We have determined that the FEE model reduced the magnitude and declination-dependent behaviour of false polarisation in Stokes Q and V while retaining low levels of false polarisation in Stokes U.

  10. Alpha particles for treatment of disseminated melanoma

    International Nuclear Information System (INIS)

    Link, E.M.

    2010-01-01

    Invading melanoma spreads to local and unpredictable distant location at the early stages of its development. It is justifiable, therefore, to classify the disease as a systemic disorder. This requires a systemic treatment that reaches all melanoma cells irrespective of whether they are singly dispersed and in circulation or already forming solid tumours of various sizes. Targeted radiotherapy affects directly and selectively cancer cells provided an appropriate radionuclide and its carrier are chosen. Melanoma is a pigmented tumour. Methylene blue (MTB)) accumulates selectively in melanoma cells due to its exceptionally high affinity to melanin. MTB serves, therefore, as a carrier for radionuclides. 211 At-MTB has proved to be particularly effective in treating disseminated melanoma when administered systemically and, at the same time, non-toxic to normal non-pigmented and pigmented organs. (authors)

  11. The risk of melanoma in airline pilots and cabin crew: a meta-analysis.

    Science.gov (United States)

    Sanlorenzo, Martina; Wehner, Mackenzie R; Linos, Eleni; Kornak, John; Kainz, Wolfgang; Posch, Christian; Vujic, Igor; Johnston, Katia; Gho, Deborah; Monico, Gabriela; McGrath, James T; Osella-Abate, Simona; Quaglino, Pietro; Cleaver, James E; Ortiz-Urda, Susana

    2015-01-01

    Airline pilots and cabin crew are occupationally exposed to higher levels of cosmic and UV radiation than the general population, but their risk of developing melanoma is not yet established. To assess the risk of melanoma in pilots and airline crew. PubMed (1966 to October 30, 2013), Web of Science (1898 to January 27, 2014), and Scopus (1823 to January 27, 2014). All studies were included that reported a standardized incidence ratio (SIR), standardized mortality ratio (SMR), or data on expected and observed cases of melanoma or death caused by melanoma that could be used to calculate an SIR or SMR in any flight-based occupation. Primary random-effect meta-analyses were used to summarize SIR and SMR for melanoma in any flight-based occupation. Heterogeneity was assessed using the χ2 test and I2 statistic. To assess the potential bias of small studies, we used funnel plots, the Begg rank correlation test, and the Egger weighted linear regression test. Summary SIR and SMR of melanoma in pilots and cabin crew. Of the 3527 citations retrieved, 19 studies were included, with more than 266 431 participants. The overall summary SIR of participants in any flight-based occupation was 2.21 (95% CI, 1.76-2.77; P < .001; 14 records). The summary SIR for pilots was 2.22 (95% CI, 1.67-2.93; P = .001; 12 records). The summary SIR for cabin crew was 2.09 (95% CI, 1.67-2.62; P = .45; 2 records). The overall summary SMR of participants in any flight-based occupation was 1.42 (95% CI, 0.89-2.26; P = .002; 6 records). The summary SMR for pilots was 1.83 (95% CI, 1.27-2.63, P = .33; 4 records). The summary SMR for cabin crew was 0.90 (95% CI, 0.80-1.01; P = .97; 2 records). Pilots and cabin crew have approximately twice the incidence of melanoma compared with the general population. Further research on mechanisms and optimal occupational protection is needed.

  12. Melanoma Surveillance in the US: Melanoma, Ultraviolet Radiation, and Socioeconomic Status

    Centers for Disease Control (CDC) Podcasts

    2011-10-19

    This podcast accompanies the publication of a series of articles on melanoma surveillance in the United States, available in the November supplement edition of the Journal of the American Academy of Dermatology. Chris Johnson, from the Cancer Data Registry of Idaho, discusses analyses examining the relationship between melanoma and two variables at the county level, ultraviolet radiation and socioeconomic status.  Created: 10/19/2011 by National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP).   Date Released: 10/19/2011.

  13. PRIMARY CHOROIDAL MALIGNANT LYMPHOMA:REPORT OF A CASE AND REVIEW OF LITERATURE

    Directory of Open Access Journals (Sweden)

    F. Asadi Amoli

    2006-06-01

    Full Text Available Non-Hodgkin lymphoma (NHL is one of the masquerade syndromes of malignant melanoma that can occur with two main patterns of presentations in the eye: metastatic involvement of uveal tract, and primary involvement of retina. We report ophthalmic, imaging and histopathological findings in the first case diagnosed as primary choroidal NHL without central nervous system or systemic involvement. A 37-year-old woman presented with the complaint of severe visual loss in her right eye. Significant ocular finding included light perception of vision (LP, 2+ APD, 2+ cells in vitreous and intraocular pressure of 46 mmHg. Fundoscopic examination revealed exudative retinal detachment. Ocular echography showed choroidal thickening in addition to retinal detachment. MRI showed semilunar shape lesion in the posterior right globe suggesting choroidal melanoma. Systemic work-up could not reveal any underlying cause. The patient underwent enucleation with clinical suggestion of choroidal melanoma. Result of histological examination showed NHL (diffuse large Bcell type of choroid. Immunohistochemical staining showed negative staining for HMB-45 and CD3, positive staining for LCA, and CD20. Multiple periodic lumbar puncture, bone marrow biopsies and MRI were unremarkable. No recurrence of tumor in systemic work-up was noted during the 36-months follow-up. Primary choroidal NHL is one of the causes of generalized thickening of choroid and should be considered in differential diagnosis of malignant melanoma. It is recommended to perform fine needle biopsy before performing surgery in any patient who has had an atypical malignant melanoma. This is, so far as we know, the first case diagnosed as primary choroidal NHL.

  14. Outcomes of dogs undergoing radiotherapy for treatment of oral malignant melanoma: 111 cases (2006-2012).

    Science.gov (United States)

    Kawabe, Mifumi; Mori, Takashi; Ito, Yusuke; Murakami, Mami; Sakai, Hiroki; Yanai, Tokuma; Maruo, Kohji

    2015-11-15

    To evaluate the characteristics and outcomes of dogs with stage I, II, III, or IV oral malignant melanoma treated by various types of radiotherapy. Retrospective case series. 111 dogs. Medical records of dogs with oral malignant melanoma treated by radiotherapy (with or without adjunctive treatments) at a veterinary medical center between July 2006 and December 2012 were reviewed. Information regarding signalment, tumor location, disease stage, treatment protocols, adverse effects, and survival time were obtained from medical records and by telephone follow-up. Associations between variables of interest and outcome were analyzed. Dogs received orthovoltage x-ray (n = 68), megavoltage x-ray (39), or electron beam (4) radiotherapy. Adjunctive treatments included debulking surgery (n = 18), chemotherapy (39), or both (27). Median survival times for dogs with stage I, II, III, and IV melanoma were 758 days (n = 19), 278 days (24), 163 days (37), and 80 days (31), respectively, and differed significantly between dogs with stage I disease and those with all other disease stages. Among dogs with stage III melanoma, risk of death was significantly higher in those that received orthovoltage x-ray treatment than in those that received megavoltage x-ray treatment. Severe (primary or secondary) adverse effects were identified in 9 dogs. Median survival time was significantly longer for dogs with stage I oral malignant melanoma than for dogs with more advanced disease at the time of staging. The staging system used may be a useful tool for prognosis prediction in dogs undergoing similar treatment protocols for oral malignant melanomas.

  15. [Molecular and immunohistochemical diagnostics in melanoma].

    Science.gov (United States)

    Schilling, B; Griewank, K G

    2016-07-01

    To provide appropriate therapy and follow-up to patients with malignant melanoma, proper diagnostics are of critical importance. Targeted therapy of advanced melanoma is based on the molecular genetic analyses of tumor tissue. In addition, sequencing of genes and other genetic approaches can provide insight into the origin of melanocytic tumors and can aid in distinguishing benign from malignant lesions. In this regard, spizoid neoplasms remain a challenging entity. Aside from genetic analyses of tumor tissue, immunohistochemistry remains an essential tool in melanoma diagnostics and TNM classification. With new immunotherapies being approved for advanced melanoma, immunohistochemistry to determine PD-L1 expression has gained clinical interest. While PD-L1 expression is associated with response to PD-1 blockade, a substantial number of patients without PD-L1 expression can still experience tumor remission upon treatment. In this review, current and future developments in melanoma diagnostics with regard to molecular genetics and immunohistochemistry are summarized. The utilization of such analyses in clinical decision making is also discussed.

  16. Reflectance confocal microscopy features of thin versus thick melanomas.

    Science.gov (United States)

    Kardynal, Agnieszka; Olszewska, Małgorzata; de Carvalho, Nathalie; Walecka, Irena; Pellacani, Giovanni; Rudnicka, Lidia

    2018-01-24

    In vivo reflectance confocal microscopy (RCM) plays an increasingly important role in differential diagnosis of melanoma. The aim of the study was to assess typical confocal features of thin (≤1mm according to Breslow index) versus thick (>1mm) melanomas. 30 patients with histopathologically confirmed cutaneous melanoma were included in the study. Reflectance confocal microscopy was performed with Vivascope equipment prior to excision. Fifteen melanomas were thin (Breslow thickness ≤ 1mm) and 15 were thick melanomas (Breslow thickness >1mm). In the RCM examination, the following features were more frequently observed in thin compared to thick melanomas: edged papillae (26.7% vs 0%, p=0.032) and areas with honeycomb or cobblestone pattern (33.3% vs 6.7%, p=0.068). Both features are present in benign melanocytic lesions, so in melanoma are good prognostic factors. The group of thick melanomas compared to the group of thin melanomas in the RCM images presented with greater frequency of roundish cells (100% vs 40%, p=0.001), non-edged papillae (100% vs 60%, p=0.006), numerous pagetoid cells (73.3% vs 33.3%, p=0.028), numerous atypical cells at dermal-epidermal junction (53.3% vs 20%, p=0.058) and epidermal disarray (93.3% vs 66.7%, p=0.068). Non-invasive imaging methods helps in deepening of knowledge about the evolution and biology of melanoma. The most characteristic features for thin melanomas in confocal examination are: fragments of cobblestone or honeycomb pattern and edged papillae (as good prognostic factors). The features of thick melanomas in RCM examination are: roundish cells, non-edged papillae, numerous pagetoid cells at dermal-epidermal junction and epidermal disarray.

  17. Melanoma cells treated with GGTI and IFN-gamma allow murine vaccination and enhance cytotoxic response against human melanoma cells.

    Directory of Open Access Journals (Sweden)

    Guillaume Sarrabayrouse

    Full Text Available BACKGROUND: Suboptimal activation of T lymphocytes by melanoma cells is often due to the defective expression of class I major histocompatibility antigens (MHC-I and costimulatory molecules. We have previously shown that geranylgeranyl transferase inhibition (done with GGTI-298 stimulates anti-melanoma immune response through MHC-I and costimulatory molecule expression in the B16F10 murine model [1]. METHODOLOGY/PRINCIPAL FINDINGS: In this study, it is shown that vaccination with mIFN-gand GGTI-298 pretreated B16F10 cells induces a protection against untreated tumor growth and pulmonary metastases implantation. Furthermore, using a human melanoma model (LB1319-MEL, we demonstrated that in vitro treatment with hIFN-gamma and GGTI-298 led to the up regulation of MHC-I and a costimulatory molecule CD86 and down regulation of an inhibitory molecule PD-1L. Co-culture experiments with peripheral blood mononuclear cells (PBMC revealed that modifications induced by hIFN-gamma and GGTI-298 on the selected melanoma cells, enables the stimulation of lymphocytes from HLA compatible healthy donors. Indeed, as compared with untreated melanoma cells, pretreatment with hIFN-gamma and GGTI-298 together rendered the melanoma cells more efficient at inducing the: i activation of CD8 T lymphocytes (CD8+/CD69+; ii proliferation of tumor-specific CD8 T cells (MelanA-MART1/TCR+; iii secretion of hIFN-gamma; and iv anti-melanoma specific cytotoxic cells. CONCLUSIONS/SIGNIFICANCE: These data indicate that pharmacological treatment of melanoma cell lines with IFN-gamma and GGTI-298 stimulates their immunogenicity and could be a novel approach to produce tumor cells suitable for vaccination and for stimulation of anti-melanoma effector cells.

  18. Ambulatory Melanoma Care Patterns in the United States

    International Nuclear Information System (INIS)

    Ji, A. L.; Davis, S. A.; Feldman, S. R.; Fleischer, A. B.; Baze, M. R.; Feldman, S. R.; Feldman, S. R.; Fleischer, A. B.

    2013-01-01

    To examine trends in melanoma visits in the ambulatory care setting. Methods. Data from the National Ambulatory Medical Care Survey (NAMCS) from 1979 to 2010 were used to analyze melanoma visit characteristics including number of visits, age and gender of patients, and physician specialty. These data were compared to US Census population estimates during the same time period. Results. The overall rate of melanoma visits increased (ρ< 0.0001) at an apparently higher rate than the increase in population over this time. The age of patients with melanoma visits increased at approximately double the rate (0.47 year per interval year, ρ< 0.0001) of the population increase in age (0.23 year per interval year). There was a nonsignificant(ρ=0.19) decline in the proportion of female patients seen over the study interval. Lastly, ambulatory care has shifted towards dermatologists and other specialties managing melanoma patients and away from family/internal medicine physicians and general/plastic surgeons. Conclusions. The number and age of melanoma visits has increased over time with respect to the overall population, mirroring the increase in melanoma incidence over the past three decades. These trends highlight the need for further studies regarding melanoma management efficiency

  19. Activation of the MAPK pathway is a common event in uveal melanomas although it rarely occurs through mutation of BRAF or RAS.

    Science.gov (United States)

    Zuidervaart, W; van Nieuwpoort, F; Stark, M; Dijkman, R; Packer, L; Borgstein, A-M; Pavey, S; van der Velden, P; Out, C; Jager, M J; Hayward, N K; Gruis, N A

    2005-06-06

    In contrast to cutaneous melanoma, there is no evidence that BRAF mutations are involved in the activation of the mitogen-activated protein kinase (MAPK) pathway in uveal melanoma, although there is increasing evidence that this pathway is activated frequently in the latter tumours. In this study, we performed mutation analysis of the RAS and BRAF genes in a panel of 11 uveal melanoma cell lines and 19 primary uveal melanoma tumours. In addition, Western blot and immunohistochemical analyses were performed on downstream members of the MAPK pathway in order to assess the contribution of each of these components. No mutations were found in any of the three RAS gene family members and only one cell line carried a BRAF mutation (V599E). Despite this, mitogen-activated protein kinase/extracellular signal-regulated kinase kinase (MEK), ERK and ELK were constitutively activated in all samples. These data suggest that activation of the MAPK pathway is commonly involved in the development of uveal melanoma, but occurs through a mechanism different to that of cutaneous melanoma.

  20. Noscapine alters microtubule dynamics in living cells and inhibits the progression of melanoma.

    Science.gov (United States)

    Landen, Jaren W; Lang, Roland; McMahon, Steve J; Rusan, Nasser M; Yvon, Anne-Marie; Adams, Ashley W; Sorcinelli, Mia D; Campbell, Ross; Bonaccorsi, Paola; Ansel, John C; Archer, David R; Wadsworth, Patricia; Armstrong, Cheryl A; Joshi, Harish C

    2002-07-15

    Cellular microtubules, polymers of tubulin, alternate relentlessly between phases of growth and shortening. We now show that noscapine, a tubulin-binding agent, increases the time that cellular microtubules spend idle in a paused state. As a result, most mammalian cell types observed arrest in mitosis in the presence of noscapine. We demonstrate that noscapine-treated murine melanoma B16LS9 cells do not arrest in mitosis but rather become polyploid followed by cell death, whereas primary melanocytes reversibly arrest in mitosis and resume a normal cell cycle after noscapine removal. Furthermore, in a syngeneic murine model of established s.c. melanoma, noscapine treatment resulted in an 85% inhibition of tumor volume on day 17 when delivered by gavage compared with untreated animals (P melanoma progression by 83% on day 18 when delivered in drinking water (P melanoma cells through alterations in microtubule dynamics, with no detected toxicity to the host. Consequently, noscapine could be a valuable chemotherapeutic agent, alone or in combination, for the treatment of advanced melanoma.

  1. T-Cadherin Expression in Melanoma Cells Stimulates Stromal Cell Recruitment and Invasion by Regulating the Expression of Chemokines, Integrins and Adhesion Molecules

    Directory of Open Access Journals (Sweden)

    Kseniya A. Rubina

    2015-07-01

    Full Text Available T-cadherin is a glycosyl-phosphatidylinositol (GPI anchored member of the cadherin superfamily involved in the guidance of migrating cells. We have previously shown that in vivo T-cadherin overexpression leads to increased melanoma primary tumor growth due to the recruitment of mesenchymal stromal cells as well as the enhanced metastasis. Since tumor progression is highly dependent upon cell migration and invasion, the aim of the present study was to elucidate the mechanisms of T-cadherin participation in these processes. Herein we show that T-cadherin expression results in the increased invasive potential due to the upregulated expression of pro-oncogenic integrins, chemokines, adhesion molecules and extracellular matrix components. The detected increase in chemokine expression could be responsible for the stromal cell recruitment. At the same time our previous data demonstrated that T-cadherin expression inhibited neoangiogenesis in the primary tumors. We demonstrate molecules and reduction in pro-angiogenic factors. Thus, T-cadherin plays a dual role in melanoma growth and progression: T-cadherin expression results in anti-angiogenic effects in melanoma, however, this also stimulates transcription of genes responsible for migration and invasion of melanoma cells.

  2. Treatment with Ipilimumab: A Case Report of Complete Response in a Metastatic Malignant Melanoma Patient

    Directory of Open Access Journals (Sweden)

    Alfredo Addeo

    2013-05-01

    Full Text Available Introduction: Over the past year, 3 agents have been approved for the treatment of melanoma by the Food and Drug Administration. These include pegylated interferon α-2b for stage III melanoma, vemurafenib for unresectable or metastatic melanoma with BRAF V600E mutation, and ipilimumab for unresectable or metastatic melanoma. Case Presentation: We present here the case of a 65-year-old Caucasian male diagnosed with advanced melanoma in April 2011 and treated with ipilimumab (Yervoy®, a monoclonal antibody targeting cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4, as second-line treatment after progression with dacarbazine, for (wild-type BRAF metastatic melanoma. The patient was referred to us for several painful lumps on his right arm. A biopsy of one of them revealed melanoma. CT and PET scans did not show any other lesions or a primary site. The patient was started on first-line chemotherapy with dacarbazine 850 mg/m2 on day 1, every 3 weeks. After 3 cycles, the patient showed disease progression with an increase in size of the skin metastasis. Second-line treatment was started with ipilimumab 3 mg/kg on day 1, every 3 weeks. At the end of the treatment, after 4 cycles, we documented a complete clinical response with total resolution of the skin metastasis. At the time of writing this paper, our patient had finished his treatment more than 9 months earlier and is still in complete remission. Conclusion: This is a paradigmatic case where, despite extensive metastatic disease, treatment with ipilimumab has confirmed its efficacy. It is still an open question why only a minority of patients have such a remarkable response, and further trials are warranted to address this important question.

  3. Circulating Tyrosinase and MART-1 mRNA does not Independently Predict Relapse or Survival in Patients with AJCC Stage I–II Melanoma

    DEFF Research Database (Denmark)

    Schmidt, Henrik; Sørensen, Boe S; Sjoegren, Pia

    2006-01-01

    The detection of melanoma cells in peripheral blood has been proposed to select patients with a high risk of relapse. In this study, tyrosinase and melanoma antigen recognized by T cells 1 (MART-1) mRNA expression was evaluated in serial samples obtained before definitive surgery and during follow......-up in patients with American Joint Committee on Cancer stage I-II melanoma. Serial samples (n=2,262) were collected from 236 patients from 1997 to 2002. Analyses of the RNA samples were performed with a calibrated reverse transcriptase-PCR assay. Gender, age, primary tumor site, ulceration, thickness, Clark...

  4. Differentiating regressed melanoma from regressed lichenoid keratosis.

    Science.gov (United States)

    Chan, Aegean H; Shulman, Kenneth J; Lee, Bonnie A

    2017-04-01

    Distinguishing regressed lichen planus-like keratosis (LPLK) from regressed melanoma can be difficult on histopathologic examination, potentially resulting in mismanagement of patients. We aimed to identify histopathologic features by which regressed melanoma can be differentiated from regressed LPLK. Twenty actively inflamed LPLK, 12 LPLK with regression and 15 melanomas with regression were compared and evaluated by hematoxylin and eosin staining as well as Melan-A, microphthalmia transcription factor (MiTF) and cytokeratin (AE1/AE3) immunostaining. (1) A total of 40% of regressed melanomas showed complete or near complete loss of melanocytes within the epidermis with Melan-A and MiTF immunostaining, while 8% of regressed LPLK exhibited this finding. (2) Necrotic keratinocytes were seen in the epidermis in 33% regressed melanomas as opposed to all of the regressed LPLK. (3) A dense infiltrate of melanophages in the papillary dermis was seen in 40% of regressed melanomas, a feature not seen in regressed LPLK. In summary, our findings suggest that a complete or near complete loss of melanocytes within the epidermis strongly favors a regressed melanoma over a regressed LPLK. In addition, necrotic epidermal keratinocytes and the presence of a dense band-like distribution of dermal melanophages can be helpful in differentiating these lesions. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  5. Ocular melanoma and mammary mucinous carcinoma in an African lion

    Directory of Open Access Journals (Sweden)

    Cagnini Didier Q

    2012-09-01

    Full Text Available Abstract Background Reports of neoplasms in Panthera species are increasing, but they are still an uncommon cause of disease and death in captive wild felids. The presence of two or more primary tumor in large felids is rarely reported, and there are no documented cases of ocular melanoma and mammary mucinous carcinoma in African lions. Case presentation An ocular melanoma and a mammary mucinous carcinoma are described in an African lion (Panthera leo. The first tumour was histologically characterized by the presence of epithelioid and fusiform melanocytes, while the latter was composed of mucus-producing cells with an epithelial phenotype that contained periodic acid-Schiff (PAS and Alcian blue staining mucins. Metastases of both tumor were identified in various organs and indirect immunohistochemistry was used to characterize them. Peribiliary cysts were observed in the liver. Conclusions This is the first description of these tumor in African lions.

  6. Stereotactic Radiofrequency Ablation for Metastatic Melanoma to the Liver

    Energy Technology Data Exchange (ETDEWEB)

    Bale, Reto, E-mail: reto.bale@i-med.ac.at; Schullian, Peter [Medical University Innsbruck, Department of Radiology, Section of Interventional Oncology - Microinvasive Therapy (SIP) (Austria); Schmuth, Matthias [Medical University Innsbruck, Department of Dermatology (Austria); Widmann, Gerlig; Jaschke, Werner [Medical University Innsbruck, Department of Radiology, Section of Interventional Oncology - Microinvasive Therapy (SIP) (Austria); Weinlich, Georg [Medical University Innsbruck, Department of Dermatology (Austria)

    2016-08-15

    PurposeTo evaluate the outcome of patients with melanoma liver metastasis treated with stereotactic radiofrequency ablation (SRFA).Material and MethodFollowing IRB approval, a retrospective evaluation of the treatment of 20 patients with 75 melanoma liver metastases was performed.ResultsA median number of 2 lesions (range 1–14) per patient with a median size of 1.7 cm (range 0.5–14.5 cm) were treated. 67 lesions were <3 cm (89.3 %) and 8 lesions were >3 cm (10.7 %). Per patient a median of 1 ablation session was performed (range: 1–4) totaling 34 sessions. There were no procedure-related deaths and all major complications (n = 3) could be easily treated by pleural drainages. The primary and secondary success rates were 89.3 and 93.3 %, respectively. The overall local recurrence rate was 13.3 %. Four of ten local recurrences were re-treated successfully by SRFA. During follow-up, 9/20 patients developed extrahepatic metastatic disease and 10/20 had liver recurrence at any location. The median OS from the date of SRFA was 19.3 months, with an OS of 64, 41, and 17 % at 1, 3, and 5 years, with no significant difference for patients with cutaneous and ocular melanoma. The median DFS after SRFA for all 20 patients was 9.5 months, with 37, 9, and 0 % at 1, 3, and 5 years.ConclusionsDue to the high local curative potential and the promising long-term survival rates associated with minimal morbidity and mortality, radiofrequency ablation seems to be an attractive alternative to resection in patients with melanoma liver metastases.

  7. 2-cm versus 4-cm surgical excision margins for primary cutaneous melanoma thicker than 2 mm: a randomised, multicentre trial

    DEFF Research Database (Denmark)

    Gillgren, Peter; Drzewiecki, Krzysztof T; Niin, Marianne

    2011-01-01

    Optimum surgical resection margins for patients with clinical stage IIA-C cutaneous melanoma thicker than 2 mm are controversial. The aim of the study was to test whether survival was different for a wide local excision margin of 2 cm compared with a 4-cm excision margin.......Optimum surgical resection margins for patients with clinical stage IIA-C cutaneous melanoma thicker than 2 mm are controversial. The aim of the study was to test whether survival was different for a wide local excision margin of 2 cm compared with a 4-cm excision margin....

  8. Contemporary Management of Early-Stage Melanoma: A Systematic Review.

    Science.gov (United States)

    Rosko, Andrew J; Vankoevering, Kyle K; McLean, Scott A; Johnson, Timothy M; Moyer, Jeffrey S

    2017-05-01

    The incidence of melanoma is increasing, with 76 380 new cases of invasive melanoma and 68 480 new cases of melanoma in situ expected in 2016. To review the contemporary management of early-stage melanoma. We searched PubMed, MEDLINE, and the Cochrane Database of Systematic Reviews databases from January 1, 2011, to May 1, 2016, yielding 966 articles. We focused our search on early-stage (melanoma in situ, stage I, and stage II) cutaneous melanoma. After excluding articles, 41 articles were manually reviewed. A review of the bibliographies of selected articles generated additional references. While the majority of recent advances have been in the treatment of advanced melanoma, surgical excision with margins based on the presence and depth of invasion continues to be the cornerstone of management. Sentinel lymph node biopsy plays a central role in the staging and treatment of melanoma. Accurate diagnosis and adequate surgical excision are critical in reducing local recurrences and improving outcomes. Sentinel lymph node biopsy is useful in staging the regional nodal basin and guiding treatment in appropriately selected patients.

  9. Expression and prognostic value of putative cancer stem cell markers CD117 and CD15 in choroidal and ciliary body melanoma.

    Science.gov (United States)

    Lukenda, Adrian; Dotlic, Snjezana; Vukojevic, Nenad; Saric, Borna; Vranic, Semir; Zarkovic, Kamelija

    2016-03-01

    The aim of the present study was to immunohistochemically investigate the expression and prognostic significance of putative cancer stem cell markers CD117 (c-kit), CD34, CD20 and CD15 in a cohort of patients with primary choroidal and ciliary body melanoma. The immunohistochemical expression of these markers was evaluated using 3,3'-diaminobenzidine tetrahydrochloride (DAB) and 3-amino-9-ethylcarbazole (AEC) chromogens on paraffin-embedded tissue samples from 40 patients who underwent enucleation in the period from 1985 through 2000. Thirty-one patients had adequate tissue specimens for the analysis. CD117 overexpression was observed in 12 of the 31 samples (39%) when AEC chromogen was used and in 14 of 26 (54%) samples when DAB was used. CD15 positivity was seen in three out of 30 (10%) samples with AEC and in six out of 26 (23%) samples with DAB. CD20 and CD34 exhibited no positivity in the tested samples. During the average follow-up time of 8.7 years (range 0.5-22 years), 17 patients (55%) died due to metastatic disease. The Kaplan-Meier plots showed a significantly shorter overall and disease-free survival in CD117-positive patients when the AEC chromogen was used. CD15 expression was not associated with patients' survival. In multivariate analysis, patients expressing the CD117 AEC had 4.13 times higher risk of lethal outcome in comparison with CD117 AEC negative patients. Our retrospective cohort study has for the first time demonstrated a small proportion of CD15-positive uveal melanomas. CD117 AEC overexpression was associated with a worse outcome in patients with choroidal and ciliary body melanoma. Further studies should confirm the validity of these observations and their potential for targeted treatment modalities. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  10. Safety, immunogenicity, and early evidence of antitumor response with the use of the vaccine formulation NeuGcGM3 / VSSPs in patients with advanced melanoma

    International Nuclear Information System (INIS)

    Osorio Rodríguez, Marta de la Caridad

    2014-01-01

    Introduction. Melanoma is now considered an epidemic around the world. Its high lethality, constitutes a serious problem despite the continuous pharmacological and technological advances. NeuGcGM3/VSSP is a vaccine formulation containing ganglioside NeuGcGM3 incorporated in the acting of Neisseria meningitidis. It may be a choice therapeutic given this ganglioside in primary melanoma expression and immunogenicity and safety demonstrated by this vaccine in advanced breast cancer. This study evaluated the safety, immunogenicity and the anti-tumor response in patients with advanced melanoma to manage it via IM or SC. Material and methods: The expression of ganglioside in primary melanomas and its metastases was identified by immunohistochemical methods with the AcM 14F7 (anti-NGCGM3). 2 clinical trials Phase Ib/IIa escalation of doses with NeuGcGM3 /VSSP were conducted in patients with melanoma Advanced IM and SC routes. Safety and anti-tumour response were evaluated with the CTC and RECIST criteria. The statistical analysis was performed with the SPSS statistical package. Results: NeuGcGM3 is expressed in primary tumors and the studied lymph nodes metastases. NeuGcGM3/VSSP was safely managed by the SC and IM, roads without limiting toxicity. Immunogenic with IgM and IgG isotype antibody response resulted in 75% patients. There was anti-tumoral response in 38.5% with increase in median SV mainly associated with anti-tumor response. The appearance of vitiligo and the response of antibodies against other not present in the vaccine formulation gangliosides may be considered a manifestation of immune restoration. Conclusions. NeuGcGM3/VSSP managed IM and SC in patients with advanced melanoma was safe, immunogenic and antitumor activity associated with overall survival advantage. (author)

  11. Melanoma patients' disease-specific knowledge, information preference, and appreciation of educational YouTube videos for self-inspection.

    Science.gov (United States)

    Damude, S; Hoekstra-Weebers, J E H M; van Leeuwen, B L; Hoekstra, H J

    2017-08-01

    Informing and educating melanoma patients is important for early detection of a recurrence or second primary. This study aimed to investigate Dutch melanoma patients' disease-specific knowledge, and their opinions on information provision and the value of e-Health videos. All AJCC stage I-II melanoma patients in follow-up between March 2015 and March 2016 at a single melanoma center were invited to complete 19 online questions, addressing respondents' characteristics, knowledge on melanoma, and opinions on melanoma-specific information received and the educational YouTube videos. In total, 100 patients completed the survey (response = 52%); median age was 60 years and 51% were female. Breslow tumor thickness was unknown by 34% and incorrectly indicated by 19%, for presence of ulceration this was 33% and 11%, for mitosis 65% and 14%, and for AJCC stage 52% and 23%, respectively. Only 5% correctly reproduced all four tumor characteristics. Orally delivered information regarding warning signs, severity, treatment possibilities, and importance of self-inspection was clearest for patients, compared to information in the melanoma brochure. According to 77% of patients, YouTube videos regarding self-inspection of the skin and regional lymph nodes had additional value. Altogether, 63% preferred receiving information in multiple ways; 92% orally by their physician, 62% through videos, and 43% through brochures. Patients' melanoma-specific knowledge appears to be limited. There is an urgent need for further improvement of providing information and patient education. In addition to oral and written information, e-Health videos seem to be a convenient supplemental and easy accessible method for patient education. Copyright © 2017 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

  12. Combined-modality therapy for patients with regional nodal metastases from melanoma

    International Nuclear Information System (INIS)

    Ballo, Matthew T.; Ross, Merrick I.; Cormier, Janice N.; Myers, Jeffrey N.; Lee, Jeffrey E.; Gershenwald, Jeffrey E.; Hwu, Patrick; Zagars, Gunar K.

    2006-01-01

    Purpose: To evaluate the outcome and patterns of failure for patients with nodal metastases from melanoma treated with combined-modality therapy. Methods and Materials: Between 1983 and 2003, 466 patients with nodal metastases from melanoma were managed with lymphadenectomy and radiation, with or without systemic therapy. Surgery was a therapeutic procedure for clinically apparent nodal disease in 434 patients (regionally advanced nodal disease). Adjuvant radiation was generally delivered with a hypofractionated regimen. Adjuvant systemic therapy was delivered to 154 patients. Results: With a median follow-up of 4.2 years, 252 patients relapsed and 203 patients died of progressive disease. The actuarial 5-year disease-specific, disease-free, and distant metastasis-free survival rates were 49%, 42%, and 44%, respectively. By multivariate analysis, increasing number of involved lymph nodes and primary ulceration were associated with an inferior 5-year actuarial disease-specific and distant metastasis-free survival. Also, the number of involved lymph nodes was associated with the development of brain metastases, whereas thickness was associated with lung metastases, and primary ulceration was associated with liver metastases. The actuarial 5-year regional (in-basin) control rate for all patients was 89%, and on multivariate analysis there were no patient or disease characteristics associated with inferior regional control. The risk of lymphedema was highest for those patients with groin lymph node metastases. Conclusions: Although regional nodal disease can be satisfactorily controlled with lymphadenectomy and radiation, the risk of distant metastases and melanoma death remains high. A management approach to these patients that accounts for the competing risks of distant metastases, regional failure, and long-term toxicity is needed

  13. Importance of glycolysis and oxidative phosphorylation in advanced melanoma

    Directory of Open Access Journals (Sweden)

    Ho Jonhan

    2012-10-01

    Full Text Available Abstract Serum lactate dehydrogenase (LDH is a prognostic factor for patients with stage IV melanoma. To gain insights into the biology underlying this prognostic factor, we analyzed total serum LDH, serum LDH isoenzymes, and serum lactate in up to 49 patients with metastatic melanoma. Our data demonstrate that high serum LDH is associated with a significant increase in LDH isoenzymes 3 and 4, and a decrease in LDH isoenzymes 1 and 2. Since LDH isoenzymes play a role in both glycolysis and oxidative phosphorylation (OXPHOS, we subsequently determined using tissue microarray (TMA analysis that the levels of proteins associated with mitochondrial function, lactate metabolism, and regulators of glycolysis were all elevated in advanced melanomas compared with nevic melanocytes. To investigate whether in advanced melanoma, the glycolysis and OXPHOS pathways might be linked, we determined expression of the monocarboxylate transporters (MCT 1 and 4. Analysis of a nevus-to-melanoma progression TMA revealed that MCT4, and to a lesser extend MCT1, were elevated with progression to advanced melanoma. Further analysis of human melanoma specimens using the Seahorse XF24 extracellular flux analyzer indicated that metastatic melanoma tumors derived a large fraction of energy from OXPHOS. Taken together, these findings suggest that in stage IV melanomas with normal serum LDH, glycolysis and OXPHOS may provide metabolic symbiosis within the same tumor, whereas in stage IV melanomas with high serum LDH glycolysis is the principle source of energy.

  14. Subretinal lipid exudation associated with untreated choroidal melanoma

    Directory of Open Access Journals (Sweden)

    C K Minija

    2011-01-01

    Full Text Available Subretinal lipid exudation in an untreated choroidal melanoma is very rare. It is seen following plaque radiotherapy in choroidal melanoma. There is only one case report of untreated choroidal melanoma with massive lipid exudation in a patient with metastatic hypernephroma. We report here a rare case of untreated choroidal melanoma with lipid exudation. Subretinal exudation that is rarely seen following plaque brachytherapy was noted at the borders of this untreated tumor. Lipid exudation partially resolved following brachytherapy.

  15. Immunizing Patients With Metastatic Melanoma Using Recombinant Adenoviruses Encoding MART-1 or gp100 Melanoma Antigens

    Science.gov (United States)

    Rosenberg, Steven A.; Zhai, Yifan; Yang, James C.; Schwartzentruber, Douglas J.; Hwu, Patrick; Marincola, Francesco M.; Topalian, Suzanne L.; Restifo, Nicholas P.; Seipp, Claudia A.; Einhorn, Jan H.; Roberts, Bruce; White, Donald E.

    2008-01-01

    Background: The characterization of the genes encoding melanoma-associated antigens MART-1 or gp100, recognized by T cells, has opened new possibilities for the development of immunization strategies for patients with metastatic melanoma. With the use of recombinant adenoviruses expressing either MART-1 or gp100 to immunize patients with metastatic melanoma, we evaluated the safety, immunologic, and potential therapeutic aspects of these immunizations. Methods: In phase I studies, 54 patients received escalating doses (between 107 and 1011 plaque-forming units) of recombinant adenovirus encoding either MART-1 or gp100 melanoma antigen administered either alone or followed by the administration of interleukin 2 (IL-2). The immunologic impact of these immunizations on the development of cellular and antibody reactivity was assayed. Results: Recombinant adenoviruses expressing MART-1 or gp100 were safely administered. One of 16 patients with metastatic melanoma receiving the recombinant adenovirus MART-1 alone experienced a complete response. Other patients achieved objective responses, but they had received IL-2 along with an adenovirus, and their responses could be attributed to the cytokine. Immunologic assays showed no consistent immunization to the MART-1 or gp100 transgenes expressed by the recombinant adenoviruses. High levels of neutralizing antibody were found in the pretreatment sera of the patients. Conclusions: High doses of recombinant adenoviruses could be safely administered to cancer patients. High levels of neutralizing antibody present in patients' sera prior to treatment may have impaired the ability of these viruses to immunize patients against melanoma antigens. PMID:9862627

  16. Relato de um caso de melanoma de conjuntiva Conjuntival melanoma: a case report

    Directory of Open Access Journals (Sweden)

    Carlos Gustavo Leite Vieira

    2000-10-01

    Full Text Available Objetivo: Relatar um caso raro de melanoma de conjuntiva de longa evolução em paciente melanodérmica. Método: Análise de caso. Resultado: Até a presente data a paciente encontra-se bem sem evidências de recorrência da patologia em questão após excisão local. Conclusão: Observamos que mesmo sem a realização de crioterapia adjuvante ou medidas mais agressivas, existem alguns casos como esse que acabamos de relatar para o qual a excisão simples pode garantir a cura. Um aspecto importante deste relato é a importância do exame histopatológico de peças e fragmentos cirúrgicos removidos.Purpose: The authors describe a rare case of malignant conjunctival melanoma with a long evolution. Methods: A case report. Results: Until this time the patient does not show any sign of relapse of this melanoma, after local excision. Conclusion: Without cryotherapy or more agressive methods we observe that there are some cases of conjunctival melanoma that might be cured with only a local excision. An important aspect of this case is the relevance of the histopathologic analysis of the removed surgical fragments.

  17. Cartilaginous melanoma: case report and review of the literature Melanoma cartilagíneo: caso clínico e revisão da literatura

    Directory of Open Access Journals (Sweden)

    Parente Joana Devesa

    2013-06-01

    Full Text Available Malignant melanoma can present a variety of histopathological patterns. Cartilaginous change in the absence of osteogenic differentiation is extremely rare in malignant melanoma, being among the least frequent of the wide range of melanoma histologic patterns. We report a case of a 47-year-old woman with a subungual nodule on her right great toe for many years. Histopathological examination of the lesion led to a diagnosis of malignant melanoma with cartilaginous differentiation devoid of concomitant osseous areas. It would appear that this unusual form of melanoma has a predilection for acral location, particularly the subungual region. Malignant melanoma with chondroid stroma should therefore be considered in the differential diagnosis of cartilaginous lesions of the toes and fingers. Careful examination of the overlying epidermis and identification of an in situ component of melanoma may be necessary in order to establish the correct diagnosis.O melanoma maligno pode apresentar uma grande variedade de padrões histopatológicos. A presença de diferenciação cartilagínea, na ausência de diferenciação osteogénica, é extremamente rara no melanoma maligno. O melanoma cartilagíneo está entre os padrões histológicos menos frequentes. Relatamos um caso de uma doente do sexo feminino de 47 anos de idade com um nódulo subungueal no 1º dedo do pé direito com muitos anos de evolução. O exame histopatológico da lesão revelou melanoma cartilagíneo, sem áreas de diferenciação osteogénica. Esta variante de melanoma parece ter predileção pela extremidades, sobretudo pela região subungueal. Assim, o melanoma maligno com diferenciação condróide, deve ser tido em consideração no diagnóstico diferencial de lesões acrais cartilagíneas. A observação cuidadosa da epiderme e a identificação de um componente do melanoma in situ podem ser necessários para estabelecer um diagnóstico correto.

  18. Macrophage markers in serum and tumor have prognostic impact in American Joint Committee on Cancer stage I/II melanoma

    DEFF Research Database (Denmark)

    Jensen, Trine O.; Schmidt, Henrik; Møller, Holger John

    2009-01-01

    PURPOSE: To evaluate the prognostic role of soluble CD163 (sCD163) in serum and macrophage infiltration in primary melanomas from patients with American Joint Committee on Cancer (AJCC) stage I/II melanoma. The scavenger receptor CD163 is associated with anti-inflammatory macrophages...... melanomas from 190 patients were available for immunohistochemical analyzes of CD163(+) and CD68(+) macrophage infiltration. They were estimated semiquantitatively in three different tumor compartments: tumor nests, tumor stroma, and at the invasive front of the tumor. RESULTS: Serum sCD163 treated......, HR = 1.4; 95% CI, 1.1 to 1.8; P = .003). Melanomas with dense CD163(+) macrophage infiltration in tumor stroma and CD68(+) macrophage infiltration at the invasive front were associated with poor overall survival (CD163, HR = 2.7; 95% CI, 0.8 to 9.3; P = .11; and CD68, HR = 2.8; 95% CI, 1.2 to 6.8; P...

  19. Orbital invasion routes of non-melanoma skin cancers and survival outcomes.

    Science.gov (United States)

    Dundar, Yusuf; Cannon, Richard; Wiggins, Richard; Monroe, Marcus M; Buchmann, Luke O; Hunt, Jason P

    2018-02-21

    Overall non-melanoma head and neck skin cancer has a good prognosis; however, rarely patients have an aggressive variant which results in orbital invasion via perineural spread or direct extension. Despite these consequences, there are limited published studies defining this clinical entity. The main objectives of the current study are to describe orbital invasion patterns of non-melanoma head and neck skin cancers and their impact on survival. Retrospective case series from a tertiary-care, academic institution performed between 2004 and 2014. Demographic and tumour characteristics are reported as well as patterns of orbital invasion, types of treatments received, and survival outcomes. There were 17 consecutive patients with non-melanoma skin cancer and orbital invasion who met inclusion criteria. Average age at orbital invasion diagnosis was 70.8 years old. 76% were male. Mean follow-up time was 28.5 months. Of these patients, 71% had squamous cell carcinoma and 29% had basal cell carcinoma. Brow (41%) was the most common primary sub-site followed by cheek (23%) and temple (12%). 76% of patients had a history of prior treatment. The lateral orbital wall (41%) was the most common site of invasion, followed by the medial orbital wall (29%) and antero-superior invasion (23%). Age, histology, and location of orbital invasion were associated with disease-specific and overall survival. Orbital invasion for non-melanoma head and neck skin cancers creates a treatment dilemma and the patterns of invasion are described. In addition, the location of orbital invasion is associated with survival outcomes.

  20. The Role of Adenosine A2BR in Metastatic Melanoma

    Science.gov (United States)

    2017-07-01

    burden estimate or any other aspect of this collection of information, including suggestions for reducing this burden to Department of Defense...would like to interrogate the role of adenosine receptor (A2BR) in regulating primary tumor growth and metastasis in experimental models of melanoma...The positive control was a triple negative breast cancer cell line, E0771. To interrogate the role of A2BR in aiding tumor metastasis, we used VeCad

  1. Multiple Primary Cancers: Simultaneously Occurring Prostate ...

    African Journals Online (AJOL)

    2016-05-20

    May 20, 2016 ... occurring prostate cancer and other primary tumors-our experience and literature ..... thyroid cancers, pancreatic tumors, renal cancers, and melanoma. ... Hsing AW, Yeboah E, Biritwum R, Tettey Y, De Marzo AM,. Adjei A, et ...

  2. Immunotherapy for advanced melanoma: future directions.

    Science.gov (United States)

    Valpione, Sara; Campana, Luca G

    2016-02-01

    As calculated by the meta-analysis of Korn et al., the prognosis of metastatic melanoma in the pretarget and immunological therapy era was poor, with a median survival of 6.2 and a 1-year life expectancy of 25.5%. Nowadays, significant advances in melanoma treatment have been gained, and immunotherapy is one of the promising approaches to get to durable responses and survival improvement. The aim of the present review is to highlight the recent innovations in melanoma immunotherapy and to propose a critical perspective of the future directions of this enthralling oncology subspecialty.

  3. Desmoplastic malignant melanoma presenting as large lung mass.

    LENUS (Irish Health Repository)

    Al-Alao, Bassel Suffian

    2010-08-01

    We describe a case of successful minimally invasive thoracoscopic surgical resection of metastatic desmoplastic malignant melanoma replacing the entire right lower lobe of the lung, presenting 4 years after the initial complete resection of the primary scalp lesion. An 89-year-old man presented with a 6-month history of right-sided chest pain. A computed tomographic scan showed a large paravertebral mass with possibility of chest wall invasion. Core biopsy initially raised the suspicion of a schwannoma. We also discussed the atypical delayed presentation and misleading radiologic and histologic findings.

  4. Retrospective study of 338 canine oral melanomas with clinical, histologic, and immunohistochemical review of 129 cases.

    Science.gov (United States)

    Ramos-Vara, J A; Beissenherz, M E; Miller, M A; Johnson, G C; Pace, L W; Fard, A; Kottler, S J

    2000-11-01

    Diagnostic records from 338 canine oral melanomas in 338 dogs received at the Veterinary Medical Diagnostic Laboratory (1992-1999) were reviewed. Of these tumors, 122 plus an additional 7 metastatic melanomas of unknown origin were selected for clinical follow-up, histologic review, and immunohistochemistry. Chow Chow, Golden Retriever, and Pekingese/Poodle mix breeds were overrepresented, whereas Boxer and German Shepherd breeds were underrepresented. There was no gender predisposition and the average age at presentation was 11.4 years. Forty-nine dogs were euthanized due to recurrence or metastasis. The average postsurgical survival time was 173 days. The gingiva and the labial mucosa were the most common sites. Most tumors were composed of either polygonal cells (27 cases, 20.9%), spindle cells (44 cases, 34.1%), or a mixture of the two (polygonal and spindle) (54 cases, 41.9%). Clear cell (3 cases, 2.3%) and adenoid/papillary (1 case, 0.8%) patterns were uncommon. The metastases of 6/6 oral melanomas had morphologic and immunohistochemical features similar to those of the primary tumors. Immunohistochemically, Melan A was detected in 113/122 oral (92.6%) and 5/7 (71.9%) metastatic melanomas. Only 4/163 nonmelanocytic tumors were focally and weakly positive for Melan A. Antibodies against vimentin, S100 protein, and neuron-specific enolase stained 129 (100%), 98 (76%), and 115 (89.1%) of 129 melanomas, respectively. Antibodies against other melanocytic-associated antigens (tyrosinase, glycoprotein 100) did not yield adequate staining. We conclude that Melan A is a specific and sensitive marker for canine melanomas.

  5. Melanoma or Pseudo melanoma Change in a pigmented lesion after application of topical 5-Fluorouracil

    Science.gov (United States)

    2017-10-26

    2. REPORT TYPE 3. DATES COVERED (From - To) 10/26/2017 Poster 10/26/2017-10/29/2017 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Melanoma or Pseudo...melanoma? Change in a pigmented lesion after application of topical 5-Fluorouracil. 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d

  6. Preclinical targeted alpha therapy for melanoma, leukaemia, breast, prostate and colorectal cancers

    International Nuclear Information System (INIS)

    Allen, B.J.; Rizvi, S.; Li, Y.; Tian, Z.; University of Wollongong, NSW; Ranson, M.

    2000-01-01

    Full text: Targeted Alpha therapy (TAT) offers the potential to inhibit the growth of micro-metastases by selectively killing isolated and preangiogenic clusters of cancer cells. The alpha emitting radioisotopes Tb-149 and Bi-213 are produced by accelerator and generator respectively and are chelated to a cancer specific monoclonal antibody, peptide or protein to form the alpha-conjugates (AC) against melanoma, leukaemia, breast, prostate and colorectal cancers. These ACs are tested for stability, specificity and cytotoxicity in vitro and in vivo using several nude mouse models. The Australian TAT program began some 7 years at ANSTO but was still-born. Later, TAT had a second wind at St George Hospital, where collaborative research led to the investigation of Tb-149 as a new alpha emitting radionuclide. Subsequently, increased emphasis was placed on the Ac-225 generator to produce Bi-213. Although in-house funding was terminated in 1998, the project received its third wind with local fund raising in the Shire and a US grant in 1999, and continues to break new ground in the control of the above cancers. Stable alpha-ACs are produced which are highly specific and cytotoxic in vitro against melanoma, leukaemia, colorectal, breast and prostate cancers. Subcutaneous inoculation of 11.5 million cells into the flanks of nude mice causes tumours to grow in all mice. The tumour growth is compared with untreated controls, nonspecific AC and specific AC, for local (subcutaneous) and systemic (tail vein or intraperitoneal) injection models. Local TAT at 2 days post-inoculation completely prevents tumour formation for all cancers tested so far. Intra-lesional TAT can completely regress melanoma but is less successful for breast and prostate cancers. Systemic TAT inhibits the growth of melanoma xenografts and gives almost complete control of breast cancer tumour growth in the primary site and metastatic invasion of the lymph nodes. These results point to the application of local

  7. Immunohistochemical Expression of MCAM/CD146 in Canine Melanoma.

    Science.gov (United States)

    Abou Asa, S

    2017-07-01

    MCAM/CD146 (melanoma cell adhesion molecule/CD146) is a transmembrane immunoglobulin superfamily cell adhesion molecule involved in transendothelial migration and signal transduction. It is expressed in melanoma, squamous cell carcinoma, prostatic, ovarian, cervical and endometrial cancers and promotes tumour growth, angiogenesis and metastasis. Melanoma is the most common malignant oral tumour of dogs and also arises in the skin, nail bed and footpad. The aim of this study was to investigate the immunohistochemical expression of MCAM/CD146 in 51 canine melanomas, including oral, cutaneous and ocular tumours. Seventeen of the 51 (33.3%) cases were negative, eight (15.7%) were weakly positive, seven (13.7%) were moderately positive and 19 (37.3%) were strongly positive. MCAM/CD146 was expressed by both oral and cutaneous melanomas; however, the intensity and the extent of the immunoreactivity was higher in oral (P = 0.009) than in cutaneous tumours (P = 0.058). Most ocular melanomas did not express MCAM/CD146 (P = 0.256). Expression of MCAM/CD146 by canine melanomas may suggest the molecule as a target for treatment, especially in oral melanomas. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Sentinel lymph node biopsy: is it possible to reduce false negative rates by excluding patients with nodular melanoma?

    LENUS (Irish Health Repository)

    Corrigan, M A

    2012-02-03

    OBJECTIVE: The aim of this study was to review the outcome of sentinel lymph node biopsy (SLNB) in patients with melanoma and to delineate whether patients with nodular melanoma are more likely to develop nodal recurrence despite negative SLNB. METHODS: Consecutive patients with cutaneous melanoma undergoing SLNB were identified from a departmental database between 1997 and 2005. Factors including demographic data, site, histological subtype, depth and outcome were examined. RESULTS: Of 131 patients, 103 were node negative and eligible for study. The median age was 53 (16-82) years with 46 patients being male (45%) and 57 female (55%). Primary melanoma sites included lower limb (49; 48%), upper limb (29; 28%), head (12; 11%), trunk (7; 7%) and back (6; 6%). The median Breslow thickness was 2mm. Superficial spreading accounted for 43% of melanoma with nodular accounting for 42%. Median follow-up was 40 (3-90) months. Of 20 relapses, seven recurred in the same nodal basin, three were satellite recurrences, one recurred with both satellite and nodal lesions simultaneously, and nine experienced haematogenous spread. Of the eight patients who developed recurrence in the same nodal basin, four were of nodular histological subtype (p=NS). All of the three patients with satellite lesions had nodular melanoma histologically (p=0.02). When nodal and satellite recurrences were combined, eight of 11 were histologically nodular (p=0.01). CONCLUSIONS: This study indicates that lymphatic recurrence occurs more often in SLNB negative patients with nodular melanoma. Further evaluation of the inclusion criteria for sentinel node biopsy is warranted.

  9. Is it sufficient to repeat LINEAR accelerator stereotactic radiosurgery in choroidal melanoma?

    Science.gov (United States)

    Furdova, A; Horkovicova, K; Justusova, P; Sramka, M

    One day session LINAC based stereotactic radiosurgery (SRS) at LINAC accelerator is a method of "conservative" attitude to treat the intraocular malignant uveal melanoma. We used model Clinac 600 C/D Varian (system Aria, planning system Corvus version 6.2 verification IMRT OmniPro) with 6 MeV X by rigid immobilization of the eye to the Leibinger frame. The stereotactic treatment planning after fusion of CT and MRI was optimized according to the critical structures (lens, optic nerve, also lens and optic nerve at the contralateral side, chiasm). The first plan was compared and the best plan was applied for therapy at C LINAC accelerator. The planned therapeutic dose was 35.0 Gy by 99 % of DVH (dose volume histogram). In our clinical study in the group of 125 patients with posterior uveal melanoma treated with SRS, in 2 patients (1.6 %) was repeated SRS indicated. Patient age of the whole group ranged from 25 to 81 years with a median of 54 TD was 35.0 Gy. In 2 patients after 5 year interval after stereotactic radiosurgery for uveal melanoma stage T1, the tumor volume increased to 50 % of the primary tumor volume and repeated SRS was necessary. To find out the changes in melanoma characteristics after SRS in long term interval after irradiation is necessary to follow up the patient by an ophthalmologist regularly. One step LINAC based stereotactic radiosurgery with a single dose 35.0 Gy is one of treatment options to treat T1 to T3 stage posterior uveal melanoma and to preserve the eye globe. In some cases it is possible to repeat the SRS after more than 5 year interval (Fig. 8, Ref. 23).

  10. Current Research and Development of Chemotherapeutic Agents for Melanoma

    Directory of Open Access Journals (Sweden)

    Kyaw Minn Hsan

    2010-04-01

    Full Text Available Cutaneous malignant melanoma is the most lethal form of skin cancer and an increasingly common disease worldwide. It remains one of the most treatment-refractory malignancies. The current treatment options for patients with metastatic melanoma are limited and in most cases non-curative. This review focuses on conventional chemotherapeutic drugs for melanoma treatment, by a single or combinational agent approach, but also summarizes some potential novel phytoagents discovered from dietary vegetables or traditional herbal medicines as alternative options or future medicine for melanoma prevention. We explore the mode of actions of these natural phytoagents against metastatic melanoma.

  11. miR-125b induces cellular senescence in malignant melanoma

    DEFF Research Database (Denmark)

    Nyholm, Anne Marie; Lerche, Catharina M; Manfé, Valentina

    2014-01-01

    transfected melanoma cell line Mel-Juso and then investigated the effect of the presence of a stable overexpression of miR-125b on growth by western blotting, flow cytometry and β-galactosidase staining. The tumourogenicity of the transfected cells was tested using a murine model and the tumours were further...... examined with in-situ-hybridization. RESULTS: In primary human tumours and in lymph node metastases increased expression of miR-125b was found in single, large tumour cells with abundant cytoplasm. A stable overexpression of miR-125b in human melanoma cell line Mel-Juso resulted in a G0/G1 cell cycle block...... and emergence of large cells expressing senescence markers: senescence-associated beta-galactosidase, p21, p27 and p53. Mel-Juso cells overexpressing miR-125b were tumourigenic in mice, but the tumours exhibited higher level of cell senescence and decreased expression of proliferation markers, cyclin D1 and Ki...

  12. Characteristic findings of computed tomography in cerebral metastatic malignant melanomas

    International Nuclear Information System (INIS)

    Kukita, Chikashige; Nose, Tadao; Nakagawa, Kunio; Tomono, Yuji; Enomoto, Takao; Hashikawa, Masanori; Egashira, Taihei; Maki, Yutaka

    1986-01-01

    Four cases with metastatic cerebral melanoma were studied by means of computed tomography (CT). Two cases were male, and the other two were female, with an average age of 55 years. Their primary lesions were on the chest wall in two cases, around the calcaneus in one, and around the genitalia in one. All cases died within 6 months after the metastatic brain lesions were found. Necropsies were carried out in two cases. CT revealed high-density areas in all cases, and contrast studies showed an enhancement of the lesions, as has previously been reported. On the other hand, autopsied cases revealed neither fresh nor old intratumoral bleedings such as a scattered focus of hemosiderin. These findings suggest that the high-density tumoral shadows in CT are probably not intratumoral bleedings due to a bleeding tendency of the tumors, as some authors have previously supposed. We mentioned some other factors contributing to the high density of the melanoma on computed tomograms. (author)

  13. Mucosal malignant melanoma - a clinical, oncological, pathological and genetic survey

    DEFF Research Database (Denmark)

    Mikkelsen, Lauge H; Larsen, Ann-Cathrine; von Buchwald, Christian

    2016-01-01

    cavity (0.2/million/year). Anorectal melanoma occurs slightly more often in females, whereas oral melanoma has a male predilection. Mucosal melanoma most commonly develops in a patient's sixth or seventh decade of life, and no differences between races have been found except for sinonasal melanoma...

  14. Role of FDG-PET/CT in stage 1–4 malignant melanoma patients

    DEFF Research Database (Denmark)

    Eldon, Mai; Kjerkegaard, Ulrik Knap; Ørndrup, Mette Heisz

    2017-01-01

    /CT scanned in 2012 at a department of plastic surgery and to analyze the pattern of referral and outcome of PET/CT scans of these patients all back from early diagnosis of the patient in the period 2008–2012. Methods: All patients with MM stages 1–4 (AJCC stages) and melanoma of unknown primary (MUP) who...

  15. Efficient adenovector CD40 ligand immunotherapy of canine malignant melanoma.

    Science.gov (United States)

    von Euler, Henrik; Sadeghi, Arian; Carlsson, Björn; Rivera, Patricio; Loskog, Angelica; Segall, Thomas; Korsgren, Olle; Tötterman, Thomas H

    2008-05-01

    Cutaneous canine melanomas are usually benign in contrast to human malignant melanoma. However, the canine oropharyngeal, uveal, and mucocutaneous neoplasms are aggressive and have metastatic potential. Surgery and to a lesser extent radiotherapy and chemotherapy are widely adopted treatments but are seldom curative in advanced stages. The similarities between human and canine melanoma make spontaneous canine melanoma an excellent disease model for exploring novel therapies. Herein, we report the first 2 adenovector CD40L immunogene (AdCD40L) treatments of aggressive canine malignant melanoma. Case no. 1 was an advanced stage III oral melanoma that was cured from malignant melanoma with 2 intratumor AdCD40L injections before cytoreductive surgery. After treatment, the tumor tissue was infiltrated with T lymphocytes and B lymphocytes suggesting immune activation. This dog survived 401 days after the first round of gene therapy and was free of melanoma at autopsy. Case no. 2 had a conjunctival malignant melanoma with a rapid progression. This case was treated with 6 AdCD40L injections over 60 days. One hundred and twenty days after start of gene therapy and 60 days after the last injection, the tumor had regressed dramatically, and the dog had a minimal tumor mass and no signs of progression or metastasis. Our results indicate that AdCD40L immunogene therapy is beneficial in canine malignant melanoma and could be considered for human malignant melanoma as well.

  16. Melanoma costs: a dynamic model comparing estimated overall costs of various clinical stages.

    Science.gov (United States)

    Alexandrescu, Doru Traian

    2009-11-15

    The rapidly increasing incidence of melanoma occurs at the same time as an increase in general healthcare costs, particularly the expenses associated with cancer care. Previous cost estimates in melanoma have not utilized a dynamic model considering the evolution of the disease and have not integrated the multiple costs associated with different aspects of medical interventions and patient-related factors. Futhermore, previous calculations have not been updated to reflect the modern tendencies in healthcare costs. We designed a comprehensive model of expenses in melanoma that considers the dynamic costs generated by the natural progression of the disease, which produces costs associated with treatment, surveillance, loss of income, and terminal care. The complete range of initial clinical (TNM) stages of the disease and initial tumor stages were analyzed in this model and the total healthcare costs for the five years following melanoma presentation at each particular stage were calculated. We have observed dramatic incremental total costs associated with progressively higher initial stages of the disease, ranging from a total of $4,648.48 for in situ tumors to $159,808.17 for Stage IV melanoma. By stage, early lesions associate 30-55 percent of their costs for the treatment of the primary tumor, due to a low rate of recurrence (local, regional, or distant), which limits the need for additional interventions. For in situ melanoma, T1a, and T1b, surveillance is an important contributor to the medical costs, accounting for more than 25 percent of the total cost over 5 years. In contrast, late lesions incur a much larger proportion of their associated costs (up to 80-85%) from the diagnosis and treatment of metastatic disease because of the increased propensity of those lesions to disseminate. This cost increases with increasing tumor stage (from $2,442.17 for T1a to $6,678.00 for T4b). The most expensive items in the medical care of patients with melanoma consist of

  17. Sunnier European countries have lower melanoma mortality.

    Science.gov (United States)

    Shipman, A R; Clark, A B; Levell, N J

    2011-07-01

    Doubt has been cast on sunlight as the major causative factor for malignant melanoma. We performed statistical analysis of the average annual sunlight hours in 36 European capital cities compared with the country's melanoma mortality rate. A significant inverse proportionality was identified in both men and women, indicating that sun exposure is unlikely to be the strongest factor affecting mortality from malignant melanoma. © The Author(s). CED © 2011 British Association of Dermatologists.

  18. The Danish Melanoma Database

    DEFF Research Database (Denmark)

    Hölmich, Lisbet Rosenkrantz; Klausen, Siri; Spaun, Eva

    2016-01-01

    melanoma and 780 with in situ tumors were registered. The coverage is currently 93% compared with the Danish Pathology Register. MAIN VARIABLES: The main variables include demographic, clinical, and pathological characteristics, including Breslow's tumor thickness, ± ulceration, mitoses, and tumor...... studies are based on DMD data. CONCLUSION: DMD holds unique detailed information about tumor characteristics, the surgical treatment, and follow-up of Danish melanoma patients. Registration and monitoring is currently expanding to encompass even more clinical parameters to benefit both patient treatment...

  19. EMMPRIN promotes melanoma cells malignant properties through a HIF-2alpha mediated up-regulation of VEGF-receptor-2.

    Directory of Open Access Journals (Sweden)

    Faten Bougatef

    Full Text Available EMMPRIN's expression in melanoma tissue was reported to be predictive of poor prognosis. Here we demonstrate that EMMPRIN up-regulated VEGF receptor-2 (VEGFR-2 in two different primary melanoma cell lines and consequently increased migration and proliferation of these cells while inhibiting their apoptosis. SiRNA inhibition of VEGFR-2 expression abrogated these EMMPRIN effects. EMMPRIN regulation of VEGFR-2 was mediated through the over-expression of HIF-2alpha and its translocation to the nucleus where it forms heterodimers with HIF-1beta. These results were supported by an in vivo correlation between the expression of EMMPRIN with that of VEGFR-2 in human melanoma tissues as well as with the extent of HIF-2alpha localization in the nucleus. They demonstrate a novel mechanism by which EMMPRIN promotes tumor progression through HIF-2alpha/VEGFR-2 mediated mechanism, with an autocrine role in melanoma cell malignancy. The inhibition of EMMPRIN in cancer may thus simultaneously target both the VEGFR-2/VEGF system and the matrix degrading proteases to block tumor cell growth and invasion.

  20. T-Cadherin Expression in Melanoma Cells Stimulates Stromal Cell Recruitment and Invasion by Regulating the Expression of Chemokines, Integrins and Adhesion Molecules

    International Nuclear Information System (INIS)

    Rubina, Kseniya A.; Surkova, Ekaterina I.; Semina, Ekaterina V.; Sysoeva, Veronika Y.; Kalinina, Natalia I.; Poliakov, Alexei A.; Treshalina, Helena M.; Tkachuk, Vsevolod A.

    2015-01-01

    T-cadherin is a glycosyl-phosphatidylinositol (GPI) anchored member of the cadherin superfamily involved in the guidance of migrating cells. We have previously shown that in vivo T-cadherin overexpression leads to increased melanoma primary tumor growth due to the recruitment of mesenchymal stromal cells as well as the enhanced metastasis. Since tumor progression is highly dependent upon cell migration and invasion, the aim of the present study was to elucidate the mechanisms of T-cadherin participation in these processes. Herein we show that T-cadherin expression results in the increased invasive potential due to the upregulated expression of pro-oncogenic integrins, chemokines, adhesion molecules and extracellular matrix components. The detected increase in chemokine expression could be responsible for the stromal cell recruitment. At the same time our previous data demonstrated that T-cadherin expression inhibited neoangiogenesis in the primary tumors. We demonstrate that T-cadherin overexpression leads to the increase in the expression of anti-angiogenic molecules and reduction in pro-angiogenic factors. Thus, T-cadherin plays a dual role in melanoma growth and progression: T-cadherin expression results in anti-angiogenic effects in melanoma, however, this also stimulates transcription of genes responsible for migration and invasion of melanoma cells

  1. T-Cadherin Expression in Melanoma Cells Stimulates Stromal Cell Recruitment and Invasion by Regulating the Expression of Chemokines, Integrins and Adhesion Molecules

    Energy Technology Data Exchange (ETDEWEB)

    Rubina, Kseniya A., E-mail: rkseniya@mail.ru; Surkova, Ekaterina I.; Semina, Ekaterina V.; Sysoeva, Veronika Y.; Kalinina, Natalia I. [Department of Biochemistry and Molecular Medicine, Faculty of Medicine, M.V. Lomonosov Moscow State University, Lomonosovsky av., 31/5, Moscow 119192 (Russian Federation); Poliakov, Alexei A. [Division of Developmental Neurobiology, MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA (United Kingdom); Treshalina, Helena M. [Federal State Budgetary Scietific Institution «N.N. Blokhin Russian Cancer Research Center» (FSBSI “N.N.Blokhin RCRC”), Kashirskoe Shosse 24, Moscow 115478 (Russian Federation); Tkachuk, Vsevolod A. [Department of Biochemistry and Molecular Medicine, Faculty of Medicine, M.V. Lomonosov Moscow State University, Lomonosovsky av., 31/5, Moscow 119192 (Russian Federation)

    2015-07-21

    T-cadherin is a glycosyl-phosphatidylinositol (GPI) anchored member of the cadherin superfamily involved in the guidance of migrating cells. We have previously shown that in vivo T-cadherin overexpression leads to increased melanoma primary tumor growth due to the recruitment of mesenchymal stromal cells as well as the enhanced metastasis. Since tumor progression is highly dependent upon cell migration and invasion, the aim of the present study was to elucidate the mechanisms of T-cadherin participation in these processes. Herein we show that T-cadherin expression results in the increased invasive potential due to the upregulated expression of pro-oncogenic integrins, chemokines, adhesion molecules and extracellular matrix components. The detected increase in chemokine expression could be responsible for the stromal cell recruitment. At the same time our previous data demonstrated that T-cadherin expression inhibited neoangiogenesis in the primary tumors. We demonstrate that T-cadherin overexpression leads to the increase in the expression of anti-angiogenic molecules and reduction in pro-angiogenic factors. Thus, T-cadherin plays a dual role in melanoma growth and progression: T-cadherin expression results in anti-angiogenic effects in melanoma, however, this also stimulates transcription of genes responsible for migration and invasion of melanoma cells.

  2. Prevalence of left-sided melanomas in an Irish population.

    LENUS (Irish Health Repository)

    de Blacam, C

    2012-02-01

    BACKGROUND: A predominance of melanomas on the left side of the body has recently been described. No associations between tumour laterality and gender, age or anatomical site have been identified. AIM: The aim of this study was to investigate the prevalence of left-sided melanomas in an Irish population and to examine potential associations with various patient and tumour characteristics. METHODS: A retrospective chart review of patients with cutaneous melanoma who were treated over a 10-year period was carried out. Lateral distribution of melanoma on either side of the body was compared using chi(2) analysis and evaluated by gender, age group, anatomic location, histologic subtype and Breslow depth. RESULTS: More melanomas occurred on the left side (57%, P = 0.015), and this finding was particularly significant in females. For both genders combined, there were no statistically significant differences in laterality by age group, anatomic location, type of melanoma and Breslow depth. There were significantly more superficial spreading melanomas on the left side in both men and women. CONCLUSIONS: This study demonstrates a predominance of left-sided melanomas in Irish patients. While a number of demographic and molecular associations have been proposed, further research is required to fully explain this phenomenon.

  3. Prevalence of left-sided melanomas in an Irish population.

    LENUS (Irish Health Repository)

    de Blacam, C

    2011-04-17

    BACKGROUND: A predominance of melanomas on the left side of the body has recently been described. No associations between tumour laterality and gender, age or anatomical site have been identified. AIM: The aim of this study was to investigate the prevalence of left-sided melanomas in an Irish population and to examine potential associations with various patient and tumour characteristics. METHODS: A retrospective chart review of patients with cutaneous melanoma who were treated over a 10-year period was carried out. Lateral distribution of melanoma on either side of the body was compared using χ(2) analysis and evaluated by gender, age group, anatomic location, histologic subtype and Breslow depth. RESULTS: More melanomas occurred on the left side (57%, P = 0.015), and this finding was particularly significant in females. For both genders combined, there were no statistically significant differences in laterality by age group, anatomic location, type of melanoma and Breslow depth. There were significantly more superficial spreading melanomas on the left side in both men and women. CONCLUSIONS: This study demonstrates a predominance of left-sided melanomas in Irish patients. While a number of demographic and molecular associations have been proposed, further research is required to fully explain this phenomenon.

  4. Aberrant intermediate filament and synaptophysin expression is a frequent event in malignant melanoma: an immunohistochemical study of 73 cases.

    Science.gov (United States)

    Romano, Ryan C; Carter, Jodi M; Folpe, Andrew L

    2015-08-01

    Malignant melanomas are known to express vimentin, among other intermediate filaments. Though anomalous keratin expression by malignant melanoma has been reported, its frequency is not well-established and this phenomenon is not well-known. We have seen in consultation a number of malignant melanomas with anomalous expression of keratin, other intermediate filaments, or synaptophysin, and therefore studied a large group of primary and metastatic melanomas to determine the frequency of these events. About 73 cases of malignant melanoma (22 primaries and 51 metastases) from 71 patients (51 male, 20 female; mean 59 years, range 17-87 years) were retrieved from our archives. Prior diagnoses were confirmed by re-review of hematoxylin and eosin sections and relevant (e.g., S100 protein, HMB45, Melan-A, and tyrosinase) immunohistochemical studies. Available sections were immunostained for keratin (OSCAR and AE1/AE3 antibodies), desmin, neurofilament protein, glial fibrillary acidic protein, synaptophysin, and chromogranin A. Not all cases could be tested for all markers. Cases were predominantly epithelioid (48/73, 66%) or spindle cell/desmoplastic (25/73, 34%). S100 protein, Melan-A, HMB45, and tyrosinase were positive in 60/65 (92%), 34/64 (53%), 30/60 (50%), 25/48 (52%) of cases, respectively. All five S100-protein-negative cases expressed at least one of the other melanocytic markers: Melan-A (two of four, 50%), HMB45 (two of three, 67%), and tyrosinase (one of two, 50%). All cases expressed at least one melanocytic marker. Cases were positive for keratin (OSCAR, 17/61, 28%; AE1/AE3, 16/40, 40%), desmin (11/47, 24%), neurofilament protein (5/31, 16%), glial fibrillary acidic protein (3/32, 9%), and synaptophysin (10/34, 29%), typically only in a minority of cells. Chromogranin was negative (0/32, 0%). Altogether 9/73 cases (12%) showed expression of >1 intermediate filament. All S100-protein-negative melanomas showed anomalous intermediate filament expression (keratin

  5. The Abscopal Effect Associated With a Systemic Anti-melanoma Immune Response

    International Nuclear Information System (INIS)

    Stamell, Emily F.; Wolchok, Jedd D.; Gnjatic, Sacha; Lee, Nancy Y.; Brownell, Isaac

    2013-01-01

    The clearance of nonirradiated tumors after localized radiation therapy is known as the abscopal effect. Activation of an antitumor immune response has been proposed as a mechanism for the abscopal effect. Here we report a patient with metastatic melanoma who received palliative radiation to his primary tumor with subsequent clearance of all his nonirradiated in-transit metastases. Anti-MAGEA3 antibodies were found upon serological testing, demonstrating an association between the abscopal effect and a systemic antitumor immune response. A brain recurrence was then treated with a combination of stereotactic radiosurgery and immunotherapy with ipilimumab. The patient experienced a complete remission that included resolution of nodal metastases, with a concomitant increase in MAGEA3 titers and a new response to the cancer antigen PASD1. This case supports the immune hypothesis for the abscopal effect, and illustrates the potential of combining radiotherapy and immunotherapy in the treatment of melanoma.

  6. The Abscopal Effect Associated With a Systemic Anti-melanoma Immune Response

    Energy Technology Data Exchange (ETDEWEB)

    Stamell, Emily F. [Division of Dermatology, Department of Medicine, Albert Einstein College of Medicine, Bronx, New York (United States); Wolchok, Jedd D. [Melanoma and Sarcoma Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Ludwig Institute for Cancer Research, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Ludwig Center for Cancer Immunotherapy, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Weill-Cornell Medical College, New York, New York (United States); Gnjatic, Sacha [Ludwig Institute for Cancer Research, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Ludwig Center for Cancer Immunotherapy, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Lee, Nancy Y. [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Brownell, Isaac, E-mail: Isaac.brownell@nih.gov [Dermatology Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Dermatology Branch, National Cancer Institute, Bethesda, Maryland (United States)

    2013-02-01

    The clearance of nonirradiated tumors after localized radiation therapy is known as the abscopal effect. Activation of an antitumor immune response has been proposed as a mechanism for the abscopal effect. Here we report a patient with metastatic melanoma who received palliative radiation to his primary tumor with subsequent clearance of all his nonirradiated in-transit metastases. Anti-MAGEA3 antibodies were found upon serological testing, demonstrating an association between the abscopal effect and a systemic antitumor immune response. A brain recurrence was then treated with a combination of stereotactic radiosurgery and immunotherapy with ipilimumab. The patient experienced a complete remission that included resolution of nodal metastases, with a concomitant increase in MAGEA3 titers and a new response to the cancer antigen PASD1. This case supports the immune hypothesis for the abscopal effect, and illustrates the potential of combining radiotherapy and immunotherapy in the treatment of melanoma.

  7. Melanoma differentiation associated gene-7/interleukin-24 (mda-7/IL-24): Novel gene therapeutic for metastatic melanoma

    International Nuclear Information System (INIS)

    Fisher, Paul B.; Sarkar, Devanand; Lebedeva, Irina V.; Emdad, Luni; Gupta, Pankaj; Sauane, Moira; Su Zaozhong; Grant, Steven; Dent, Paul; Curiel, David T.; Senzer, Neil; Nemunaitis, John

    2007-01-01

    A potentially less toxic approach for cancer therapy comprises induction of tumor cells to lose growth potential irreversibly and terminally differentiate. Combining this scheme termed 'differentiation therapy of cancer' with subtraction hybridization to human melanoma cells resulted in the cloning of melanoma differentiation associated (mda) genes displaying elevated expression as a consequence of induction of terminal differentiation. One originally novel gene, mda-7, was found to display elevated expression in normal melanocytes and nevi with progressive loss of expression as a consequence of melanoma development and progression to metastasis. Based on structure, biochemical properties and chromosomal location, mda-7 has now been reclassified as interleukin (IL)-24, a member of the expanding IL-10 family of cytokines. In vitro cell culture and in vivo animal studies indicate that mda-7/IL-24 selectively induces programmed cell death (apoptosis) in multiple human cancers (including melanomas), without harming normal cells, and promotes profound anti-tumor activity in nude mice containing human tumor xenografts. Based on these remarkable properties, a Phase I clinical trial was conducted to test the safety of administration of mda-7/IL-24 by a replication incompetent adenovirus (Ad.mda-7; INGN 241) in patients with advanced solid cancers including melanoma. mda-7/IL-24 was found to be safe and to promote significant clinical activity, particularly in the context of patients with metastatic melanoma. These results provide an impetus for further clinical studies and document a central paradigm of cancer therapy, namely translation of basic science from the 'bench to the bedside.'

  8. Termoterapia transpupilar em melanoma maligno da coróide Transpupillary thermotherapy for malignant choroidal melanoma

    Directory of Open Access Journals (Sweden)

    Martha M. Motomo Chojniak

    2001-04-01

    ,63%, vitreite associada a tênues membranas vítreas em 1 paciente (9,09% e quemose associada a edema palpebral em 1 paciente (9,09%. Controle tumoral local com conservação do globo ocular foi observado durante este pequeno tempo de seguimento em 100% dos pacientes tratados. Por ocasião da "última revisão", 100% dos pacientes estavam vivos e sem doença metastática. Conclusão: Este estudo preliminar sugere que a termoterapia transpupilar apresenta-se como um método efetivo e seguro para o tratamento de selecionados melanomas pequenos da coróide. Para melhor avaliação é necessário tempo de seguimento prolongado.Purpose: Several methods have been used for treatment of choroidal melanoma. The purpose of this preliminary paper is to evaluate the effectiveness of transpupillary thermo- therapy (TTT as a primary treatment of small choroidal melanomas. Methods: This is a prospective nonrandomized study evaluating clinical aspects, tumor response, complications and visual outcome in patients presenting small choroidal melanomas (up to 4.0 mm thick and 12 mm base diameter treated with TTT over 810 nm laser diode applications. Results: There were 11 patients treated with trans-pupillary thermotherapy, all of them presenting pig-mented small choroidal melanomas. Growth previous to treatment was documented in 5 patients and risk factors for growth or metastatic disease was present in all the patients. After treatment the patients were followed for 3 to 8 months (mean 5.7 months. Three laser sessions were used in 5 pa-tients and 4 sessions in 6 patients. The lesions presented at the beginning of the treatment a mean thickness of 2.7 mm, with a mean larger base diameter of 7.8 mm. All the lesions responded to treatment and presented decrease of thickness and base diameters. After transpupillary thermotherapy, the lesions' mean thickness was 1.8 mm and the mean larger base diameter was 6.7 mm. The mean reduction in thickness was 0.9 mm and the mean decrease in larger base

  9. Poliosis circumscripta unmasking a scalp melanoma.

    Science.gov (United States)

    Yeo, L; Husain, E; Rajpara, S

    2015-12-01

    A 28-year-old man presented with a 1-year history of a localized patch of grey hair and an underlying darkly pigmented lesion on his right occipital area. Clinical appearance revealed poliosis overlying an asymmetrical plaque with variable degrees of brown pigmentation and white discolouration. Owing to the suspicious nature of the lesion, excision with a 2 mm margin was performed. Histology revealed an invasive melanoma with extensive regression and prominent involvement of multiple hair follicles. Scalp melanoma with associated poliosis is extremely rare, and has only been reported once in the literature to date. There have been two reports in the opthalmology literature regarding eyelash poliosis associated with orbital melanoma. The pathogenesis of poliosis still remains unclear. This is the second reported case of poliosis circmscripta unmasking a scalp melanoma, and highlights the importance of being vigilant when examining patients with poliosis of the scalp. © 2014 British Association of Dermatologists.

  10. Can Melan-A replace S-100 and HMB-45 in the evaluation of sentinel lymph nodes from patients with malignant melanoma?

    Science.gov (United States)

    Kucher, Cynthia; Zhang, Paul J; Acs, Geza; Roberts, Shelley; Xu, Xiaowei

    2006-09-01

    The sentinel lymph node (SLN) biopsy has become an increasingly important procedure used in the primary staging of malignant melanoma. However, micrometastases in a lymph node can be easily missed on routine H&E-stained sections. Therefore, S-100 and HMB-45 IHC stains are standardly performed on grossly negative SLNs for detection of metastatic melanoma. Each of these IHC markers, however, is not ideal. The authors investigated whether the newer IHC marker Melan-A would improve the detection of metastatic melanoma in SLN biopsies. Forty lymph nodes previously diagnosed with metastatic melanoma were retrospectively evaluated for S-100, HMB-45, and Melan-A expression. In addition, 42 SLN biopsies for metastatic melanoma detection were prospectively collected and evaluated for S-100, HMB-45, and Melan-A expression. All lymph nodes with metastatic melanoma from the retrospective study demonstrated S-100 reactivity. Five of the lymph nodes with metastatic melanoma from the retrospective study failed to express either HMB-45 or Melan-A, all of which displayed a desmoplastic morphology. One of the metastases positive for S-100 and HMB-45 failed to show reactivity with Melan-A (3%). The prospective study found 10 lymph nodes from 42 cases to be positive for metastatic melanoma, which were positive for S-100 (100%). Nine of the involved lymph nodes were positive for HMB-45(90%), and nine were positive for Melan-A (90%). Melan-A, although very specific, cannot replace the use of S-100 and HMB-45 for the detection of metastatic melanoma in SLNs. It can, however, substitute for HMB-45 with equally good results.

  11. Impact of Socioeconomic Status and Ethnicity on Melanoma Presentation and Recurrence in Caucasian Patients.

    Science.gov (United States)

    Salvaggio, Christine; Han, Sung Won; Martires, Kathryn; Robinson, Eric; Madankumar, Reshmi; Gumaste, Priyanka; Polsky, David; Stein, Jennifer; Berman, Russell; Shapiro, Richard; Zhong, Judy; Osman, Iman

    2016-01-01

    The impact of ethnicity and the socioeconomic status (SES) among Caucasians is not well studied. Here, we examine the impact of income on melanoma presentation and prognosis within a Caucasian cohort, accounting for ethnicity, as some reports suggest increased melanoma incidence in Ashkenazi Jewish (AJ) BRCA mutation carriers. We studied prospectively enrolled primary melanoma patients at New York University. SES data were estimated using United States' Census Bureau data and patient zip codes. We evaluated associations between ethnicity, SES, and baseline characteristics using the χ² test and multivariate logistic regression. We compared survival distributions using Kaplan-Meier curves, log-rank tests, and Cox proportional hazard ratios. Of the 1,339 enrolled patients, AJ represented 32% (n = 423). Apart from AJ being older at presentation (p < 0.001), no significant differences were observed in baseline characteristics between ethnic groups. Patients with a median household income (MHI) lower than the median of the cohort were significantly more likely to present with advanced stages (p < 0.001) compared to patients with a higher MHI. Shorter overall (p = 0.016) and post-recurrence survival (p = 0.042) was also observed in patients from lower-income households. Data suggest that disparities in melanoma presentation in Caucasians stratify according to income independent of ethnic background. © 2016 S. Karger AG, Basel.

  12. Malignant melanoma: A retrospective series from a regional cancer center in India

    Directory of Open Access Journals (Sweden)

    Sharma Kuldeep

    2009-01-01

    Full Text Available Purpose : To present our experience in treating malignant melanoma patients. Methods and Materials : All melanoma patients treated at the Department of Radiotherapy, All India Institute of Medical Sciences, New Delhi, India, from 1995 to 2007 were studied retrospectively. The endpoints were loco-regional recurrence, distant recurrence, recurrence-free survival (RFS, and duration of follow-up (DOFU. RFS and DOFU were analyzed with respect to the factors like age, sex, tissue of origin, site of disease, number of nodes, lymphadenopathy, ulceration, stage, and operability to find out any association. Results : Seventy-two patients were found evaluable with 40 males and 32 females (median age 46.5 years. Eye was the commonest primary site with visual disturbance as the commonest symptom. Overall, 87% of the lesions were single, with most of the nonocular lesions presenting in the advanced stage. During the disease course, regional lymphadenopathy and distant metastases were seen in 33% and 32% of cases, respectively. Highest incidence of lymphadenopathy was seen in skin lesions and in primaries from trunk and extremities. Of all treated patients, 47% achieved complete response, 18% partial response, and others had either stable or progressive disease. The median DOFU was 6.2 months. RFS was studied only in curatively treated cases with a median of 10 months. Operability at presentation was the only prognostic factor influencing DOFU. Conclusion : Malignant melanoma is an uncommon disease in India carrying a lot of morbidity due to late presentation. Its management is still not clear regarding the optimum use and schedule of treatment modalities. More prospective studies in the future are required to come to a definite conclusion.

  13. Immunoscintigraphy in ocular melanoma

    International Nuclear Information System (INIS)

    Scheidhauer, K.; Scober, O.; Scheidler, J.; Leinsinger, G.; Scheiffarth, O.; Riedel, K.; Schumacher, U.

    1990-01-01

    Immunoscintigraphy (IS) of malignant tumors has become an encouraging tool in nuclear medicine. Early diagnosis of small lesions is mandatory for successful cancer therapy generally. The scintigraphic detectability of small lesions ( 2 fragments of the anti-melanoma monoclonal antibody 225.28S; this antibody recognizes the high-molecular-weight melanoma-associated antigen. No adverse effects were observed. In terms of true positive results, Single Photon Emission CT proved to be superior compared to planar scans (81 versus 46 percent true positive results). (author). 30 refs

  14. Suppression of immune surveillance in melanoma [Immunotherapy of metastatic melanoma by reversal of immune suppression

    Energy Technology Data Exchange (ETDEWEB)

    Biggs, M. W. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Eiselein, J. E. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

    2001-06-01

    In this paper we develop the hypothesis that a significant fraction of patients with advanced melanoma can be successfully treated with immunotherapy. Reversal of antigen-specific immune suppression to melanoma polypeptide antigens is an essential, first step. We postulate the key regulation of CTL responses resides within the CD4+ T-lymphocytes and macrophage/dendritic cells. There is a pluri-potential cell within this regulatory arm that functions either as a Th1 cell or as a suppressor T-cell, Ths, depending on how antigen is presented. We have shown that poliovirus 1 Sabin will lyse human melanoma cells in tissue culture, and a special "vaccine" prepared from this lysis actively stimulates Ths cell function. The Ths arm of the regulatory system can be down-regulated with cyclophosphamide given 24 hours after the vaccine. The capacity to generate a CTL response is retained. The summary conclusion is that a phase 1 clinical trial in advanced melanoma using the special viral-tumor-lysate followed by cyclophosphamide, plus expanded autologous dendritic cells sensitized with the polypeptide epitopes captained in the viral-lysate will produce beneficial results.

  15. Germline BAP1 inactivation is preferentially associated with metastatic ocular melanoma and cutaneous-ocular melanoma families.

    Directory of Open Access Journals (Sweden)

    Ching-Ni Jenny Njauw

    Full Text Available BAP1 has been shown to be a target of both somatic alteration in high-risk ocular melanomas (OM and germline inactivation in a few individuals from cancer-prone families. These findings suggest that constitutional BAP1 changes may predispose individuals to metastatic OM and that familial permeation of deleterious alleles could delineate a new cancer syndrome.To characterize BAP1's contribution to melanoma risk, we sequenced BAP1 in a set of 100 patients with OM, including 50 metastatic OM cases and 50 matched non-metastatic OM controls, and 200 individuals with cutaneous melanoma (CM including 7 CM patients from CM-OM families and 193 CM patients from CM-non-OM kindreds.Germline BAP1 mutations were detected in 4/50 patients with metastatic OM and 0/50 cases of non-metastatic OM (8% vs. 0%, p = 0.059. Since 2/4 of the BAP1 carriers reported a family history of CM, we analyzed 200 additional hereditary CM patients and found mutations in 2/7 CM probands from CM-OM families and 1/193 probands from CM-non-OM kindreds (29% vs. 0.52%, p = .003. Germline mutations co-segregated with both CM and OM phenotypes and were associated with the presence of unique nevoid melanomas and highly atypical nevoid melanoma-like melanocytic proliferations (NEMMPs. Interestingly, 7/14 germline variants identified to date reside in C-terminus suggesting that the BRCA1 binding domain is important in cancer predisposition.Germline BAP1 mutations are associated with a more aggressive OM phenotype and a recurrent phenotypic complex of cutaneous/ocular melanoma, atypical melanocytic proliferations and other internal neoplasms (ie. COMMON syndrome, which could be a useful clinical marker for constitutive BAP1 inactivation.

  16. Metastasis of Ciliary Body Melanoma to the Contralateral Eye: A Case Report and Review of Uveal Melanoma Literature

    Directory of Open Access Journals (Sweden)

    Nouritza M. Torossian

    2015-01-01

    Full Text Available Many types of cancers metastasize to the eye. However, uveal melanoma metastasizing to the contralateral choroid is very rare. We report the case of a 68-year-old man with history of treated uveal melanoma of the right eye that developed metastasis to the liver and the choroid of the left eye. Ten years earlier, he was diagnosed to have uveal melanoma of the right eye and was initially treated with plaque radiotherapy. Two years later, upon progression of the disease in the right eye he had enucleation of the eye. We describe the patient’s clinical history, the diagnosis of recurrent disease in the contralateral eye, therapy of the left eye, and systemic metastasis. In addition, we reviewed the published medical literature and described the recent advances in the management of uveal melanoma.

  17. Assessment of PALB2 as a candidate melanoma susceptibility gene.

    Directory of Open Access Journals (Sweden)

    Lauren G Aoude

    Full Text Available Partner and localizer of BRCA2 (PALB2 interacts with BRCA2 to enable double strand break repair through homologous recombination. Similar to BRCA2, germline mutations in PALB2 have been shown to predispose to Fanconi anaemia as well as pancreatic and breast cancer. The PALB2/BRCA2 protein interaction, as well as the increased melanoma risk observed in families harbouring BRCA2 mutations, makes PALB2 a candidate for melanoma susceptibility. In order to assess PALB2 as a melanoma predisposition gene, we sequenced the entire protein-coding sequence of PALB2 in probands from 182 melanoma families lacking pathogenic mutations in known high penetrance melanoma susceptibility genes: CDKN2A, CDK4, and BAP1. In addition, we interrogated whole-genome and exome data from another 19 kindreds with a strong family history of melanoma for deleterious mutations in PALB2. Here we report a rare known deleterious PALB2 mutation (rs118203998 causing a premature truncation of the protein (p.Y1183X in an individual who had developed four different cancer types, including melanoma. Three other family members affected with melanoma did not carry the variant. Overall our data do not support a case for PALB2 being associated with melanoma predisposition.

  18. FOXP3 expression is modulated by TGF-β1/NOTCH1 pathway in human melanoma

    Science.gov (United States)

    Skarmoutsou, Eva; Bevelacqua, Valentina; D'Amico, Fabio; Russo, Angela; Spandidos, Demetrios A.; Scalisi, Aurora

    2018-01-01

    Forkhead box protein 3 (FOXP3) transcription factor is expressed by immune cells and several human cancers and is associated with tumor aggressiveness and unfavorable clinical outcomes. NOTCH and transforming growth factor-β (TGF-β) protumorigenic effects are mediated by FOXP3 expression in several cancer models; however, their interaction and role in melanoma is unknown. We investigated TGF-β-induced FOXP3 gene expression during NOTCH1 signaling inactivation. Primary (WM35) and metastatic melanoma (A375 and A2058) cell lines and normal melanocytes (NHEM) were used. FOXP3 subcellular distribution was evaluated by immuno cytochemical analysis. Gene expression levels were assessed by reverse transcription-quantitative polymerase chain reaction. Protein levels were assessed by western blot analysis. The γ-secretase inhibitor (GSI) was used for NOTCH1 inhibition and recombinant human (rh)TGF-β was used for melanoma cell stimulation. Cell proliferation and viability were respectively assessed by MTT and Trypan blue dye assays. FOXP3 mRNA and protein levels were progressively higher in WM35, A375 and A2058 cell lines compared to NHEM and their levels were further increased after stimulation with rh-TGF-β. TGF-β-mediated FOXP3 expression was mediated by NOTCH1 signaling. Inhibition of NOTCH1 with concomitant rh-TGF-β stimulation determined the reduction in gene expression and protein level of FOXP3. Finally, melanoma cell line proliferation and viability were reduced by NOTCH1 inhibition. The results show that nn increase in FOXP3 expression in metastatic melanoma cell lines is a potential marker of tumor aggressiveness and metastasis. NOTCH1 is a central mediator of TGF-β-mediated FOXP3 expression and NOTCH1 inhibition produces a significant reduction of melanoma cell proliferation and viability. PMID:29620159

  19. Isolated malignant melanoma metastasis to the pancreas

    DEFF Research Database (Denmark)

    Larsen, Anne K; Krag, Christen; Geertsen, Poul

    2013-01-01

    SUMMARY: Malignant melanomas rarely develop isolated pancreatic metastases. We describe a unique patient who is still alive 22 years following an isolated pancreatic melanoma metastasis, and we review the sparse literature in the field....

  20. The occurrence of non-melanoma malignant skin lesions and non-cutaneous squamous-cell carcinoma among metastatic melanoma patients: an observational cohort study in Denmark.

    Science.gov (United States)

    Li, Haojie; Pedersen, Lars; Nørgaard, Mette; Ulrichsen, Sinna P; Thygesen, Sandra K; Nelson, Jeanenne J

    2016-05-03

    Inhibitors of mutant BRAF are emerging as standard of care in patients with metastatic melanoma who carry relevant oncogenic mutations. However, BRAF inhibitors are found to induce cutaneous squamous cell carcinoma (cuSCC). Population-based background rates of cuSCC and non-cutaneous squamous cell carcinoma (non-cuSCC) in the metastatic melanoma population may contextualize safety signals from randomized clinical trials or the clinics. However, these background rates are lacking. We conducted a historical cohort study to evaluate the background rates of new-onset non-melanoma skin lesions and non-cuSCC among 2,814 metastatic malignant melanoma patients diagnosed in 1997-2010, identified through the Danish Cancer Registry and the National Pathology Registry. Patients were excluded if they had a history of cancer before the metastatic melanoma diagnosis, other than skin cancers. We determined the incidence of non-melanoma malignant skin lesions and non-cuSCC that occurred post metastatic melanoma diagnosis, censoring patients at death, emigration, or December 31, 2011 (end of study period), whichever came first. The median age at metastatic melanoma diagnosis was 64 years. Over 40% of patients died within one year of metastatic diagnosis and ~70% died within 5 years. The percentages of patients with prior history or prevalent disease at metastatic melanoma diagnosis included: 8.6% with cuSCC or basal cell carcinoma (BCC), 3.9% with actinic keratosis (AK), and 0.7% with Bowen's disease. No patients had past or current non-cuSCC per study exclusion criterion. The incidence of non-melanoma skin lesions during the 6 months post-metastatic melanoma diagnosis was as follows: BCC, 1.8% (42.5 per 1000 person-years [PY]); AK, 0.8% (18.6 per 1000 PY); cuSCC, 0.1% (1.7 per 1000 PY); Bowen's disease, 0.04% (0.8 per 1000 PY); and keratoacanthoma (KA), 0%. Non-cuSCC was observed in 3 patients (0.1%; 2.5 per 1000 PY) at 3 sites: bronchi, heart and lung. CuSCC and non-cuSCC were

  1. The occurrence of non-melanoma malignant skin lesions and non-cutaneous squamous-cell carcinoma among metastatic melanoma patients: an observational cohort study in Denmark

    International Nuclear Information System (INIS)

    Li, Haojie; Pedersen, Lars; Nørgaard, Mette; Ulrichsen, Sinna P.; Thygesen, Sandra K.; Nelson, Jeanenne J.

    2016-01-01

    Inhibitors of mutant BRAF are emerging as standard of care in patients with metastatic melanoma who carry relevant oncogenic mutations. However, BRAF inhibitors are found to induce cutaneous squamous cell carcinoma (cuSCC). Population-based background rates of cuSCC and non-cutaneous squamous cell carcinoma (non-cuSCC) in the metastatic melanoma population may contextualize safety signals from randomized clinical trials or the clinics. However, these background rates are lacking. We conducted a historical cohort study to evaluate the background rates of new-onset non-melanoma skin lesions and non-cuSCC among 2,814 metastatic malignant melanoma patients diagnosed in 1997–2010, identified through the Danish Cancer Registry and the National Pathology Registry. Patients were excluded if they had a history of cancer before the metastatic melanoma diagnosis, other than skin cancers. We determined the incidence of non-melanoma malignant skin lesions and non-cuSCC that occurred post metastatic melanoma diagnosis, censoring patients at death, emigration, or December 31, 2011 (end of study period), whichever came first. The median age at metastatic melanoma diagnosis was 64 years. Over 40 % of patients died within one year of metastatic diagnosis and ~70 % died within 5 years. The percentages of patients with prior history or prevalent disease at metastatic melanoma diagnosis included: 8.6 % with cuSCC or basal cell carcinoma (BCC), 3.9 % with actinic keratosis (AK), and 0.7 % with Bowen’s disease. No patients had past or current non-cuSCC per study exclusion criterion. The incidence of non-melanoma skin lesions during the 6 months post-metastatic melanoma diagnosis was as follows: BCC, 1.8 % (42.5 per 1000 person-years [PY]); AK, 0.8 % (18.6 per 1000 PY); cuSCC, 0.1 % (1.7 per 1000 PY); Bowen’s disease, 0.04 % (0.8 per 1000 PY); and keratoacanthoma (KA), 0 %. Non-cuSCC was observed in 3 patients (0.1 %; 2.5 per 1000 PY) at 3 sites: bronchi, heart and lung. CuSCC and

  2. Comparative study of angio genesis radiopharmaceuticals for melanoma detection; Estudo comparativo de radiofarmacos para angiogenese na deteccao de melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Oliveira, Erica Aparecida de

    2011-07-01

    Early diagnosis and treatment of melanoma, a cutaneous tumor with a serious prognosis, is extremely important for optimal clinical outcome. Phage display peptide libraries are a useful screening resource for identifying bioactive peptides that interact with cancer targets. The aim of this study was the evaluation of two technetium-99m tracers for angio genesis detection in melanoma model, using cyclic peguilated pentapeptide with RGD and NGR motifs conjugated with bifunctional chelator MAG3. The conjugated peptides (10 {mu}L of a {mu}g/{mu}L solution) were labeled with technetium-99m using a sodium tartrate buffer. Radiochemical evaluation was done by ITLC and confirmed by HPLC. Partition coefficient was determined and internalization assays were performed in two melanoma cells (B16F10 and SKMEL28). Biodistribution evaluation of the tracers was done in healthy animals at different times and also in mice bearing the tumor cells at 120 min post injection. Blocking studies were also conducted by co-injection of cold peptides. The conjugated showed the same profile in many evaluations. They were radiolabeled with high radiochemical purity (>97%). Both were hydrophilic, with preferential renal excretion. Tumor uptake was higher for human melanoma cells than for murinic melanoma cells, specially for {sup 99m}Tc-MAG3-PEG{sub 8}-c(RGDyK) (7.85{+-}{+-}2.34 %ID/g) at 120 min post injection. The performance of {sup 99m}Tc-MAG{sub 3}-PEG{sub 8}-c(RGDyk) was much better than NGR tracer concerning human melanoma uptake and might be considered in future investigations focusing radiotracers for melanoma diagnosis. (author)

  3. Melanoma NOS1 expression promotes dysfunctional IFN signaling.

    Science.gov (United States)

    Liu, Qiuzhen; Tomei, Sara; Ascierto, Maria Libera; De Giorgi, Valeria; Bedognetti, Davide; Dai, Cuilian; Uccellini, Lorenzo; Spivey, Tara; Pos, Zoltan; Thomas, Jaime; Reinboth, Jennifer; Murtas, Daniela; Zhang, Qianbing; Chouchane, Lotfi; Weiss, Geoffrey R; Slingluff, Craig L; Lee, Peter P; Rosenberg, Steven A; Alter, Harvey; Yao, Kaitai; Wang, Ena; Marincola, Francesco M

    2014-05-01

    In multiple forms of cancer, constitutive activation of type I IFN signaling is a critical consequence of immune surveillance against cancer; however, PBMCs isolated from cancer patients exhibit depressed STAT1 phosphorylation in response to IFN-α, suggesting IFN signaling dysfunction. Here, we demonstrated in a coculture system that melanoma cells differentially impairs the IFN-α response in PBMCs and that the inhibitory potential of a particular melanoma cell correlates with NOS1 expression. Comparison of gene transcription and array comparative genomic hybridization (aCGH) between melanoma cells from different patients indicated that suppression of IFN-α signaling correlates with an amplification of the NOS1 locus within segment 12q22-24. Evaluation of NOS1 levels in melanomas and IFN responsiveness of purified PBMCs from patients indicated a negative correlation between NOS1 expression in melanomas and the responsiveness of PBMCs to IFN-α. Furthermore, in an explorative study, NOS1 expression in melanoma metastases was negatively associated with patient response to adoptive T cell therapy. This study provides a link between cancer cell phenotype and IFN signal dysfunction in circulating immune cells.

  4. Addison's disease as a presentation of metastatic malignant melanoma.

    Science.gov (United States)

    Srinivasan, B; Patel, M; Ethunandan, M; Ilankovan, V

    2016-01-01

    Melanoma accounts for 5% of all skin cancers. The risk of metastasis is related to the thickness of the tumour, and can affect local, regional and distant sites. Adrenal metastasis from melanoma of the head and neck is uncommon and often asymptomatic. Addison's disease as a presentation of metastatic melanoma is extremely rare and we are unaware of previous reports in the world literature. We report a case of a patient with metastatic melanoma presenting with signs and symptoms of Addison's disease.

  5. Precision Medicine and PET/Computed Tomography in Melanoma.

    Science.gov (United States)

    Mena, Esther; Sanli, Yasemin; Marcus, Charles; Subramaniam, Rathan M

    2017-10-01

    Recent advances in genomic profiling and sequencing of melanoma have provided new insights into the development of the basis for molecular biology to more accurately subgroup patients with melanoma. The development of novel mutation-targeted and immunomodulation therapy as a major component of precision oncology has revolutionized the management and outcome of patients with metastatic melanoma. PET imaging plays an important role in noninvasively assessing the tumor biological behavior, to guide individualized treatment and assess response to therapy. This review summarizes the recent genomic discoveries in melanoma in the era of targeted therapy and their implications for functional PET imaging. Published by Elsevier Inc.

  6. Vemurafenib for the treatment of melanoma.

    LENUS (Irish Health Repository)

    Jordan, Emmet John

    2012-12-01

    Metastatic melanoma is an aggressive disease resistant to chemotherapy. Recent clinical trials have reported improved survival for two novel agents; ipilimumab, a humanized, IgG1 monoclonal antibody that blocks cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and vemurafenib , a BRAF (v-raf murine sarcoma viral oncogene homolog B1) inhibitor targeting an activating mutation in the serine-threonine-protein kinase BRAF gene. AREAS COVERED: The authors reviewed preclinical and clinical data examining the safety of vemurafenib in melanoma. MEDLINE and EMBASE were searched using the medical subject heading \\'vemurafenib\\' and the following text terms: melanoma, BRAF inhibition, vemurafenib. This review provides the reader with an overview of current data examining the efficacy and safety of vemurafenib in metastatic melanoma. EXPERT OPINION: Vemurafenib is an oral agent licensed for patients with BRAF V600E mutation-positive inoperable and metastatic melanoma. The most common adverse effects observed in Phase III clinical trials were dermatological events, arthralgia and fatigue. Specific dermatological toxicities included development of cutaneous squamous cell cancers and keratoacanthomas. Prolongation of the QT interval was also reported. Regular dermatological assessments and electrocardiograms are recommended. Ongoing trials are examining vemurafenib in both the adjuvant setting and metastatic setting in combination with ipilimumab and MEK inhibitors (mitogen-activated protein kinase\\/extracellular signal-regulated kinase). Understanding and overcoming mechanisms of resistance to BRAF inhibitors is the focus of ongoing research.

  7. Development, characterization, and photocytotoxicity assessment on human melanoma of chloroaluminum phthalocyanine nanocapsules

    Energy Technology Data Exchange (ETDEWEB)

    Siqueira-Moura, Marigilson P. [Departamento de Ciências Farmacêuticas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP), Universidade de São Paulo, Ribeirão Preto-SP (Brazil); Departamento de Química, Laboratório de Fotobiologia e Fotomedicina, Faculdade de Filosofia Ciências e Letras de Ribeirão Preto (FFCLRP), Universidade de São Paulo, Ribeirão Preto-SP (Brazil); Primo, Fernando L. [Departamento de Química, Laboratório de Fotobiologia e Fotomedicina, Faculdade de Filosofia Ciências e Letras de Ribeirão Preto (FFCLRP), Universidade de São Paulo, Ribeirão Preto-SP (Brazil); Espreafico, Enilza M. [Departamento de Biologia Celular e Molecular e Bioagentes Patogênicos, Faculdade de Medicina de Ribeirão Preto (FMRP), Universidade de São Paulo, Ribeirão Preto-SP (Brazil); Tedesco, Antonio C., E-mail: atedesco@usp.br [Departamento de Química, Laboratório de Fotobiologia e Fotomedicina, Faculdade de Filosofia Ciências e Letras de Ribeirão Preto (FFCLRP), Universidade de São Paulo, Ribeirão Preto-SP (Brazil)

    2013-04-01

    In this work we have developed nanocapsules containing chloroaluminum phthalocyanine (ClAlPc) and assessed their phototoxic action on WM1552C, WM278, and WM1617 human melanoma cell lines. The ClAlPc-loaded nanocapsules were prepared by the nanoprecipitation method and optimized by means of a 2{sup 3} full factorial design. The ClAlPc nanocapsules were characterized by particle size and distribution, zeta potential, morphology, encapsulation efficiency, singlet oxygen production, stability, and phototoxic action on melanoma cells. Both the development and optimization studies revealed that stable colloidal formulations could be obtained by using 1.75% (w/v) soybean lecithin, 1.25% (w/v) Poloxamer 188, 2.5% (v/v) soybean oil, and 0.75% (w/v) poly(D,L-lactide-co-glycolide). The nanocapsules had a mean diameter of 230 nm, homogeneous size distribution (polydispersity index < 0.3), and negative zeta potential (about − 30 mV). Their morphology was spherical, with evident polymer membrane coating droplet. The encapsulation efficiency was 70%, as expected for hydrophobic drugs, and the nanoencapsulated ClAlPc was able to produce high singlet oxygen quantum yield. ClAlPc nanocapsules exhibited good physical stability over a 12-month period. WM1552C primary melanoma cells were more sensitive (p < 0.05) to the phototoxic effect elicited by ClAlPc nanocapsules (0.3 μg ml{sup −1}) under light irradiation at 20 mJ cm{sup −2}. On the other hand, the cell survival percentage for all the melanoma cell lines treated with the highest light dose (150 mJ cm{sup −2}) was lower than 10%. In summary, ClAlPc nanoencapsulation could enable application of this hydrophobic photosensitizer in the treatment of malignant melanoma with the use of both low sensitizer drug concentration and light dose. - Highlights: ► Nanocapsules containing a hydrophobic metallophthalocyanine (ClAlPc) were developed. ► The colloidal formulations were characterized by their physicochemical parameters

  8. Born to be Alive: A Role for the BCL-2 Family in Melanoma Tumor Cell Survival, Apoptosis, and Treatment

    Energy Technology Data Exchange (ETDEWEB)

    Anvekar, Rina A.; Asciolla, James J.; Missert, Derek J.; Chipuk, Jerry E., E-mail: jerry.chipuk@mssm.edu [Department of Oncological Sciences, Mount Sinai School of Medicine, New York, NY (United States); Department of Dermatology, Mount Sinai School of Medicine, New York, NY (United States); The Tisch Cancer Institute, Mount Sinai Medical Center, New York, NY (United States)

    2011-10-13

    The global incidence of melanoma has dramatically increased during the recent decades, yet the advancement of primary and adjuvant therapies has not kept a similar pace. The development of melanoma is often centered on cellular signaling that hyper-activates survival pathways, while inducing a concomitant blockade to cell death. Aberrations in cell death signaling not only promote tumor survival and enhanced metastatic potential, but also create resistance to anti-tumor strategies. Chemotherapeutic agents target melanoma tumor cells by inducing a form of cell death called apoptosis, which is governed by the BCL-2 family of proteins. The BCL-2 family is comprised of anti-apoptotic proteins (e.g., BCL-2, BCL-xL, and MCL-1) and pro-apoptotic proteins (e.g., BAK, BAX, and BIM), and their coordinated regulation and function are essential for optimal responses to chemotherapeutics. Here we will discuss what is currently known about the mechanisms of BCL-2 family function with a focus on the signaling pathways that maintain melanoma tumor cell survival. Importantly, we will critically evaluate the literature regarding how chemotherapeutic strategies directly impact on BCL-2 family function and offer several suggestions for future regimens to target melanoma and enhance patient survival.

  9. Mutation analysis of genes that control the G1/S cell cycle in melanoma: TP53, CDKN1A, CDKN2A, and CDKN2B

    International Nuclear Information System (INIS)

    Soto, José Luis; Cabrera, Carmen M; Serrano, Salvio; López-Nevot, Miguel Ángel

    2005-01-01

    The role of genes involved in the control of progression from the G1 to the S phase of the cell cycle in melanoma tumors in not fully known. The aim of our study was to analyse mutations in TP53, CDKN1A, CDKN2A, and CDKN2B genes in melanoma tumors and melanoma cell lines We analysed 39 primary and metastatic melanomas and 9 melanoma cell lines by single-stranded conformational polymorphism (SSCP). The single-stranded technique showed heterozygous defects in the TP53 gene in 8 of 39 (20.5%) melanoma tumors: three new single point mutations in intronic sequences (introns 1 and 2) and exon 10, and three new single nucleotide polymorphisms located in introns 1 and 2 (C to T transition at position 11701 in intron 1; C insertion at position 11818 in intron 2; and C insertion at position 11875 in intron 2). One melanoma tumor exhibited two heterozygous alterations in the CDKN2A exon 1 one of which was novel (stop codon, and missense mutation). No defects were found in the remaining genes. These results suggest that these genes are involved in melanoma tumorigenesis, although they may be not the major targets. Other suppressor genes that may be informative of the mechanism of tumorigenesis in skin melanomas should be studied

  10. Health-related quality of life in melanoma patients: Impact of melanoma-related limb lymphoedema.

    Science.gov (United States)

    Gjorup, Caroline A; Groenvold, Mogens; Hendel, Helle W; Dahlstroem, Karin; Drzewiecki, Krzysztof T; Klausen, Tobias W; Hölmich, Lisbet R

    2017-11-01

    To explore health-related quality of life (HRQoL) in recurrence-free melanoma patients, with a focus on the association between melanoma-related limb lymphoedema and HRQoL. HRQoL was evaluated using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30), the breast cancer module (EORTC QLQ-BR23) subscales body image and future perspective, the Functional Assessment for Cancer Therapy-General subscale social/family well-being and the Hospital Anxiety and Depression Scale. Data were analysed using linear and ordinal logistic regression adjusting for age and gender. A total of 431 melanoma patients who had undergone wide local excision and axillary or inguinal sentinel lymph node biopsy (SLNB) and/or complete lymph node dissection (CLND) participated. No patients had had recurrence of the disease or had received adjuvant radiotherapy. The HRQoL scores improved with time after surgery. Melanoma-related limb lymphoedema was present in 109 patients (25%). Patients with lymphoedema had significantly worse HRQoL scores in the EORTC QLQ-C30 subscales global health status/quality of life, role and social functioning, fatigue, pain and financial difficulties, as well as in the QLQ-BR23 body image subscale. No associations were found between the limb affected (upper or lower limb), clinical stage of lymphoedema, duration of lymphoedema or type of surgery (SLNB or CLND) and HRQoL. We found an interaction with age and gender in the associations between lymphoedema and HRQoL: younger patients and women with lymphoedema had worse social functioning and women had significantly more impaired body image. The negative impact of melanoma-related limb lymphoedema on HRQoL emphasises the importance of developing strategies for increasing awareness and improving prevention and treatment of lymphoedema. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. BRAF inhibition is associated with enhanced melanoma antigen expression and a more favorable tumor microenvironment in patients with metastatic melanoma

    Science.gov (United States)

    Frederick, Dennie Tompers; Piris, Adriano; Cogdill, Alexandria P.; Cooper, Zachary A.; Lezcano, Cecilia; Ferrone, Cristina R.; Mitra, Devarati; Boni, Andrea; Newton, Lindsay P.; Liu, Chengwen; Peng, Weiyi; Sullivan, Ryan J; Lawrence, Donald P.; Hodi, F. Stephen; Overwijk, Willem W.; Lizée, Gregory; Murphy, George F.; Hwu, Patrick; Flaherty, Keith T.; Fisher, David E.; Wargo, Jennifer A.

    2013-01-01

    Purpose To evaluate the effects BRAF inhibition on the tumor microenvironment in patients with metastatic melanoma. Experimental Design Thirty-five biopsies were collected from 16 patients with metastatic melanoma pretreatment (day 0) and at 10-14 days after initiation of treatment with either BRAF inhibitor alone (vemurafenib) or BRAF + MEK inhibition (dabrafenib + trametinib), and were also taken at time of progression. Biopsies were analyzed for melanoma antigens, T cell markers, and immunomodulatory cytokines. Results Treatment with either BRAF inhibitor alone or BRAF + MEK inhibitor was associated with an increased expression of melanoma antigens and an increase in CD8+ T cell infiltrate. This was also associated with a decrease in immunosuppressive cytokines (IL-6 & IL-8) and an increase in markers of T cell cytotoxicity. Interestingly, expression of exhaustion markers TIM-3 and PD1 and the immunosuppressive ligand PDL1 were increased on treatment. A decrease in melanoma antigen expression and CD8 T cell infiltrate was noted at time of progression on BRAF inhibitor alone, and was reversed with combined BRAF and MEK inhibition. Conclusions Together, this data suggests that treatment with BRAF inhibition enhances melanoma antigen expression and facilitates T cell cytotoxicity and a more favorable tumor microenvironment, providing support for potential synergy of BRAF-targeted therapy and immunotherapy. Interestingly, markers of T cell exhaustion and the immunosuppressive ligand PDL1 are also increased with BRAF inhibition, further implying that immune checkpoint blockade may be critical in augmenting responses to BRAF-targeted therapy in patients with melanoma. PMID:23307859

  12. Predicting response to primary chemotherapy: gene expression profiling of paraffin-embedded core biopsy tissue.

    Science.gov (United States)

    Mina, Lida; Soule, Sharon E; Badve, Sunil; Baehner, Fredrick L; Baker, Joffre; Cronin, Maureen; Watson, Drew; Liu, Mei-Lan; Sledge, George W; Shak, Steve; Miller, Kathy D

    2007-06-01

    Primary chemotherapy provides an ideal opportunity to correlate gene expression with response to treatment. We used paraffin-embedded core biopsies from a completed phase II trial to identify genes that correlate with response to primary chemotherapy. Patients with newly diagnosed stage II or III breast cancer were treated with sequential doxorubicin 75 mg/M2 q2 wks x 3 and docetaxel 40 mg/M2 weekly x 6; treatment order was randomly assigned. Pretreatment core biopsy samples were interrogated for genes that might correlate with pathologic complete response (pCR). In addition to the individual genes, the correlation of the Oncotype DX Recurrence Score with pCR was examined. Of 70 patients enrolled in the parent trial, core biopsies samples with sufficient RNA for gene analyses were available from 45 patients; 9 (20%) had inflammatory breast cancer (IBC). Six (14%) patients achieved a pCR. Twenty-two of the 274 candidate genes assessed correlated with pCR (p < 0.05). Genes correlating with pCR could be grouped into three large clusters: angiogenesis-related genes, proliferation related genes, and invasion-related genes. Expression of estrogen receptor (ER)-related genes and Recurrence Score did not correlate with pCR. In an exploratory analysis we compared gene expression in IBC to non-inflammatory breast cancer; twenty-four (9%) of the genes were differentially expressed (p < 0.05), 5 were upregulated and 19 were downregulated in IBC. Gene expression analysis on core biopsy samples is feasible and identifies candidate genes that correlate with pCR to primary chemotherapy. Gene expression in IBC differs significantly from noninflammatory breast cancer.

  13. Targeting antisense mitochondrial ncRNAs inhibits murine melanoma tumor growth and metastasis through reduction in survival and invasion factors.

    Science.gov (United States)

    Lobos-González, Lorena; Silva, Verónica; Araya, Mariela; Restovic, Franko; Echenique, Javiera; Oliveira-Cruz, Luciana; Fitzpatrick, Christopher; Briones, Macarena; Villegas, Jaime; Villota, Claudio; Vidaurre, Soledad; Borgna, Vincenzo; Socias, Miguel; Valenzuela, Sebastián; Lopez, Constanza; Socias, Teresa; Varas, Manuel; Díaz, Jorge; Burzio, Luis O; Burzio, Verónica A

    2016-09-06

    We reported that knockdown of the antisense noncoding mitochondrial RNAs (ASncmtRNAs) induces apoptotic death of several human tumor cell lines, but not normal cells, suggesting this approach for selective therapy against different types of cancer. In order to translate these results to a preclinical scenario, we characterized the murine noncoding mitochondrial RNAs (ncmtRNAs) and performed in vivo knockdown in syngeneic murine melanoma models. Mouse ncmtRNAs display structures similar to the human counterparts, including long double-stranded regions arising from the presence of inverted repeats. Knockdown of ASncmtRNAs with specific antisense oligonucleotides (ASO) reduces murine melanoma B16F10 cell proliferation and induces apoptosis in vitro through downregulation of pro-survival and metastasis markers, particularly survivin. For in vivo studies, subcutaneous B16F10 melanoma tumors in C57BL/6 mice were treated systemically with specific and control antisense oligonucleotides (ASO). For metastasis studies, tumors were resected, followed by systemic administration of ASOs and the presence of metastatic nodules in lungs and liver was assessed. Treatment with specific ASO inhibited tumor growth and metastasis after primary tumor resection. In a metastasis-only assay, mice inoculated intravenously with cells and treated with the same ASO displayed reduced number and size of melanoma nodules in the lungs, compared to controls. Our results suggest that ASncmtRNAs could be potent targets for melanoma therapy. To our knowledge, the ASncmtRNAs are the first potential non-nuclear targets for melanoma therapy.

  14. Melanoma transition is frequently accompanied by a loss of cytoglobin expression in melanocytes: a novel expression site of cytoglobin.

    Directory of Open Access Journals (Sweden)

    Yoshihiko Fujita

    Full Text Available The tissue distribution and function of hemoglobin or myoglobin are well known; however, a newly found cytoglobin (CYGB, which also belongs to the globin family, remains to be characterized. To assess its expression in human malignancies, we sought to screen a number of cell lines originated from many tissues using northern blotting and real time PCR techniques. Unexpectedly, we found that several, but not all, melanoma cell lines expressed CYGB mRNA and protein at much higher levels than cells of other origins. Melanocytes, the primary origin of melanoma, also expressed CYGB at a high level. To verify these observations, immunostaining and immunoblotting using anti-CYGB antibody were also performed. Bisulfite-modified genomic sequencing revealed that several melanoma cell lines that abrogated CYGB expression were found to be epigenetically regulated by hypermethylation in the promoter region of CYGB gene. The RNA interference-mediated knockdown of the CYGB transcript in CYGB expression-positive melanoma cell lines resulted in increased proliferation in vitro and in vivo. Flow cytometric analysis using 2'-, 7'-dichlorofluorescein diacetate (DCFH-DA, an indicator of reactive oxygen species (ROS, revealed that the cellular ROS level may be involved in the proliferative effect of CYGB. Thus, CYGB appears to play a tumor suppressive role as a ROS regulator, and its epigenetic silencing, as observed in CYGB expression-negative melanoma cell lines, might function as an alternative pathway in the melanocyte-to-melanoma transition.

  15. A modified COMS plaque for iris melanoma

    Directory of Open Access Journals (Sweden)

    Daniel J. Scanderbeg

    2011-09-01

    Full Text Available Melanoma of the iris is a rare condition compared to posterior ocular tumors and in this case report we presenta 51-year-old female patient with diffuse iris melanoma. Traditional COMS (Collaborative Ocular Melanoma Studyplaques are used at our institution for radiation therapy, so a novel modification of the traditional plaque was requiredto allow better conformance with placement on the cornea. The usual silastic insert was machined to dimensions incompliance with the cornea, placed without incident, and treatment delivered with excellent patient tolerance of themodified plaque.

  16. Dermatoscopic Findings of Seborrheic Keratosis in Melanoma.

    Science.gov (United States)

    Brandão, Maria Luiza; Oliveira Lima, Cíntia Maria; Moura, Heloísa Helena; Ishida, Cleide; Campos-do-Carmo, Gabriella; Cuzzi, Tullia; Ramos-E-Silva, Marcia

    2016-06-01

    Cutaneous melanoma may in some instances be confused with seborrheic keratosis, which is a very common neoplasia, more often mistaken for actinic keratosis and verruca vulgaris. Melanoma may clinically resemble seborrheic keratosis and should be considered as its possible clinical simulator. We report a case of melanoma with dermatoscopic characteristics of seborrheic keratosis and emphasize the importance of the dermatoscopy algorithm in differentiating between a melanocytic and a non-melanocytic lesion, of the excisional biopsy for the establishment of the diagnosis of cutaneous tumors, and of the histopathologic examination in all surgically removed samples.

  17. Melanoma genetics and the development of rational therapeutics.

    Science.gov (United States)

    Chudnovsky, Yakov; Khavari, Paul A; Adams, Amy E

    2005-04-01

    Melanoma is a cancer of the neural crest-derived cells that provide pigmentation to skin and other tissues. Over the past 4 decades, the incidence of melanoma has increased more rapidly than that of any other malignancy in the United States. No current treatments substantially enhance patient survival once metastasis has occurred. This review focuses on recent insights into melanoma genetics and new therapeutic approaches being developed based on these advances.

  18. Podoplanin Expression in Canine Melanoma

    OpenAIRE

    Ogasawara, Satoshi; Honma, Ryusuke; Kaneko, Mika K.; Fujii, Yuki; Kagawa, Yumiko; Konnai, Satoru; Kato, Yukinari

    2016-01-01

    A type I transmembrane protein, podoplanin (PDPN), is expressed in several normal cells such as lymphatic endothelial cells or pulmonary type I alveolar cells. We recently demonstrated that anticanine PDPN monoclonal antibody (mAb), PMab-38, recognizes canine PDPN of squamous cell carcinomas, but does not react with lymphatic endothelial cells. Herein, we investigated whether PMab-38 reacts with canine melanoma. PMab-38 reacted with 90% of melanoma cells (9/10 cases) using immunohistochemistr...

  19. Survival analysis of patients with uveal melanoma after organ preserving and liquidation treatment

    Directory of Open Access Journals (Sweden)

    E. E. Grishina

    2018-01-01

    Full Text Available Rationale: Uveal melanoma is the most common primary malignancy of the eye.Aim: To evaluate survival in patients with uveal melanoma stratified according to the type of treatment and to identify factors significantly associated with their survival.Materials and methods: The study was performed on the data extracted from medical files and follow-up forms of patients with uveal melanoma seen in the Ophthalmological Clinical Hospital of the Department of Healthcare, Moscow, from 1977 to 2012. Analysis of survival was used to assess the life longevity of patients with uveal melanoma. The analysis was censored at January 2013, when vital status (dead or alive of all patients was assessed. The factors included into the study analysis, were those taken from the follow-up forms. The incidence of uveal melanoma in Moscow (2012 was 0.9 per 100,000 of the population, whereas its prevalence was 11.1 per 100,000.Results: 698 patients with uveal melanoma were included into the study, among them 260 (37% men (aged from 19 to 87 years, median age 60 years and 438 (63% women (aged from 18 to 93 years, median age 63 years; therefore, the proportion of women under the follow-up monitoring was by 26% higher than that of men. The liquidation treatment (mostly enucleation was performed in 358 (51% of the patients, whereas the organ preserving treatment in 340 (49%. At 5, 7, and 10 years of the follow-up, the disease-specific survival of patients with uveal melanoma after the organ preserving treatment (median survival has not been reached and after the liquidation treatment (median, 88 months were 89 ± 2, 83 ± 3, and 75 ± 4% versus 63 ± 3, 52 ± 4, and 47 ± 5%, respectively (р = 0.001. Overall survival and disease-specific survival of the patients after the liquidation treatment were significantly lower than in the patients after the organ-preserving treatment. According to multiple regression analysis, this was associated not with the type of

  20. lncRNA H19 predicts poor prognosis in patients with melanoma and regulates cell growth, invasion, migration and epithelial–mesenchymal transition in melanoma cells

    Directory of Open Access Journals (Sweden)

    Shi G

    2018-06-01

    Full Text Available Gaofeng Shi,1,2 Hu Li,2 Fengshan Gao,2 Qian Tan1 1Drum Tower Clinical Medical College of Nanjing Medical University, Nanjing, People’s Republic of China; 2Department of Plastic Surgery, the Affiliated Wuxi No 4 People’s Hospital of Jiangnan University, Wuxi, People’s Republic of China Introduction: Melanoma is a deadly malignancy and the poor prognosis of patients with advanced disease is relatively poor. Recent studies indicate that long non-coding RNAs are involved in the pathogenesis of malignant melanoma. This study aims to investigate the role of the long non-coding RNA H19 in melanoma and to explore the underlying molecular mechanisms. Materials and methods: The expression levels of H19 in clinical samples and melanoma cells were determined by quantitative real-time PCR. The cell growth and cell metastasis were assessed by Cell Counting Kit 8, cell invasion and wound healing assays. Cell apoptosis and cell cycle were determined by flow cytometry. Protein levels were determined by Western blotting assay. Results: H19 was highly expressed in melanoma tissues compared to normal adjacent skin tissues, and the tissue expression level of H19 from melanoma patients with metastasis was significantly higher than that from patients without distant metastasis. In addition, the high expression of H19 in melanoma tissues was associated with advanced tumor invasion and TNM stage, distal metastasis, lymph node metastasis and shorter overall survival in patients with melanoma. The in vitro functional assays showed that knockdown of H19 inhibited cell growth, invasion and migration and also induced cell apoptosis as well as G0/G1 arrest in melanoma cells. Further quantitative real-time PCR and Western blot experiments showed that knockdown of H19 differentially regulated the epithelial–mesenchymal transition (EMT-related gene expressions and reversed EMT in melanoma cell lines. Knockdown of H19 suppressed in vivo tumor growth and modulated the

  1. Targeted alpha therapy for melanoma : from bench to bedside

    International Nuclear Information System (INIS)

    Allen, B.J.; Rizvi, S.M.A.; Li, Y.; Tsui, W.; Douglas, S.; Raja, C.; Graham, P.; Smart, R.; Butler, P.; Kearsley, J.; Thompson, J.

    2001-01-01

    Full text: The control of metastatic melanoma remains an elusive objective. Targeted alpha therapy (TAT) offers a new approach to the control of micrometastases and regression of tumours. The alpha emitting immunoconjugate (AIC) against malignant melanoma has been prepared by chelating Bi-213 to the anti-melanoma antibody 9.2.27, and injected locally at 2 d post-inoculation of 1.5 million melanoma cells, or intralesionally into skin tumours. Human subjects receive 50μCi intralesional dose, escalating to 1 mCi. The clearances from the tumour, kidneys and bladder are monitored by a NaI detector that detects the 440 keV gamma ray. Blood samples and tumour photographs are taken at O. 2 and 4 weeks; tumours are excised at 4 weeks. Isolated cancer cells and preangiogenic cell clusters in mice can be eliminated with 25 μCi local AIC injection, and intra-lesional injections of 100 μCi are sufficient to completely regress melanomas with volumes up to 300 mm 3 without side-effects. Systemic TAT with a single administration is less effective with 100% growth delay of tumours observed, and ∼20% complete inhibition. The clinical TAT trial for recurrent subcutaneous melanoma has been approved by the NSW Radiation Advisory Committee and the SES Human Ethics Committee. In a world first phase 1 study, the first 5 subjects have been treated by intralesional injection, 3 at 50 μCi, and 2 at 150 μCi. All subjects having unchanged blood profiles at 2 and 4 weeks post-therapy. Tumour volumes appear little changed. However, histology of a 3 cm melanoma shows that almost complete cell kill occurred at 150 μCi, with only a few small cell clusters surviving. Local TAT inhibits tumourogenesis and intralesional TAT completely regresses melanoma in mice. Intralesional TAT for melanoma in human subjects is non-toxic so far and appears to be a promising modality. The ultimate objective is to apply systemic TAT for the control of melanoma micrometastases. Copyright (2001) Australasian

  2. Potential Role of Meiosis Proteins in Melanoma Chromosomal Instability

    International Nuclear Information System (INIS)

    Lindsey, S. F.; Byrnes, D. M.; Eller, M. S.; Rosa, A. M.; Dabas, N.; Escandon, J.; Grichnik, J. M.; Grichnik, J. M.; Grichnik, J. M.; Grichnik, J. M.

    2013-01-01

    Melanomas demonstrate chromosomal instability (CIN). In fact, CIN can be used to differentiate melanoma from benign nevi. The exact molecular mechanisms that drive CIN in melanoma have yet to be fully elucidated. Cancer/testis antigens are a unique group of germ cell proteins that are found to be primarily expressed in melanoma as compared to benign nevi. The abnormal expression of these germ cell proteins, normally expected only in the testis and ovaries, in somatic cells may lead to interference with normal cellular pathways. Germ cell proteins that may be particularly critical in CIN are meiosis proteins. Here, we review pathways unique to meiosis with a focus on how the aberrant expression of meiosis proteins in normal mitotic cells "meiomitosis"could impact chromosomal instability in melanoma and other cancers.

  3. Utility of whole-body (head-to-toe) PET/CT in the evaluation of melanoma and sarcoma patients.

    Science.gov (United States)

    Webb, Heather R; Latifi, Hamid R; Griffeth, Landis K

    2018-01-01

    The aim of this study was to assess the added benefit of whole-body (head-to-toes) PET/CT versus routine 'eyes-to-thighs' PET/CT of melanoma and sarcoma patients. We performed a retrospective review of consecutive whole-body PET/CT scans from January 2006 through December 2010 in patients with melanoma or sarcoma. PET abnormalities in the brain, distal thighs, and legs were recorded and clinical significance was assessed on the basis of pathology, imaging studies, and clinical follow-up. Patients with known primary lesions distal to the proximal femora were excluded as these patients would routinely undergo 'head-to-toe' PET/CT. We reviewed reports from 352 PET/CT examinations in 194 patients with melanoma and 75 PET/CT examinations in 44 patients with sarcoma. Melanoma: 13 patients had brain metastases on PET. In five of these patients, lesions were unknown, but all were in the setting of other metastatic disease. Twenty-seven patients had lower extremity metastases, all in the setting of other metastatic disease. No lower extremity metastases were found in the remaining 167 patients. Sarcoma: one patient had an isolated, unexpected brain metastasis. Six patients had leg metastases, but none were isolated. No lower extremity metastases were found in the remaining 38 patients. In patients with melanoma and sarcoma, inclusion of entire lower extremities adds little additional clinical value as detection of isolated, unexpected metastasis is rare. Brain imaging may add value as the presence of brain metastases alters clinical management. Overall, in patients with melanoma or sarcoma, whole-brain PET/CT imaging may be of value, but routine inclusion of the entire lower extremities adds little additional value.

  4. Immunotherapy of metastatic melanoma by reversal of immune suppression

    Energy Technology Data Exchange (ETDEWEB)

    Biggs, M.W.; Eiselein, J.E.

    1997-01-01

    Beginning with the observation that the human enteorvirus, Poliovirus Sabin 1, will lyse human melanoma cells in culture, clinical trials involving two patients with advance melanoma were performed. Parenteral injection of the viable Poliovirus into cutaneous melanoma metastases followed in 24 hours by oral administration of cyclophosphamide. The results of these two trials are described.

  5. Unilateral lichen planus pigmentosus mimicking acral lentiginous melanoma.

    Science.gov (United States)

    Bickle, Kelly; Smithberger, Erica; Lien, Mary H; Fenske, Neil Alan

    2010-07-01

    The authors report a case of a Latin American woman who developed progressive pigmentation primarily involving two digits of her right hand. She was scheduled for amputation based on a presumptive histologic diagnosis of melanoma with regression. Dermatology consultation with repeat biopsies disclosed a lichenoid tissue reaction with marked pigment incontinence and no evidence of melanoma. This report should prompt physicians to include lichen planus pigmentosus in the differential diagnosis of acral lentiginous melanoma.

  6. Balloon cell melanoma of the anal canal: A wolf in sheep′s clothing?

    Directory of Open Access Journals (Sweden)

    Munita Meenu Bal

    2013-01-01

    Full Text Available Balloon cell melanoma (BCM is a rare histologic variant of cutaneous malignant melanoma with exceptional reports of occurrences at non-cutaneous sites. Herein we present a case of primary amelanotic BCM of anal canal, a heretofore undescribed location. Histologically, the tumor was characterized by sheets of pale cells that bore striking resemblance to foamy macrophages. Presence of rare atypical mitoses confirmed the malignant nature of the cells. Neoplastic cells were immunoreactive for S100, Melan-A, and focally for HMB-45 while were negative for myogenic, gastrointestinal stromal tumor, epithelial and neuroendocrine markers. Resemblance to foamy macrophages, bland cytology and absence of pigment imparts this tumor a deceptively benign histological appearance making it prone to diagnostic pitfalls. Awareness of this rare entity and judicious employment of immunohistochemistry is imperative in segregating it from its diverse mimics.

  7. Communication Among Melanoma Family Members

    Science.gov (United States)

    Bowen, Deborah J; Albrecht, Terrance; Hay, Jennifer; Eggly, Susan; Harris-Wei, Julie; Meischke, Hendrika; Burke, Wylie

    2017-01-01

    Interventions to improve communication among family members may facilitate information flow about familial risk and preventive health behaviors. This is a secondary analysis of the effects of an interactive website intervention aimed at increasing communication frequency and agreement about health risk among melanoma families. Participants were family units, consisting of one family member with melanoma identified from a previous research study (the case) and an additional first degree relative and a parent of a child 0–17. Family triads were randomized to receive access to the website intervention or to serve as control families. Family communication frequency and agreement about melanoma prevention behaviors and beliefs were measured at baseline and again at one year post randomization. Intervention participants of all three types significantly increased the frequency of communication to their first degree relatives (Parents, siblings, children; range =14–18 percentage points; all pcommunication about cancer risk. PMID:28248624

  8. Role of Tc-99M(V) DMSA for imaging of ocular melanoma developing in graves' patients treated with radioiodine

    International Nuclear Information System (INIS)

    Bandopadhyaya, G.P.; Barai, S.; Bal, C.S.

    2004-01-01

    The melanoma originates from the melanocytes, which are embryologically derived from neural crest. The melanoma of choroids in adults is a very common type primary ocular malignancy, where the tyrosine, an immediate precursor common for both melanin and thyroid hormone synthesis is involved. The neurogenic origins of melanoma and medullary thyroid carcinoma have also been shown to have certain common metabolites, receptors and the receptor binding proteins. Several radiolabelled derivatives either in the form of melanin metabolites or melanin binding agents including receptors/ receptor-binding proteins like somatostatin, calcitonin and other monoclonal antibodies, protein receptors (S-100, myelin basic protein, Leu-7, glial fibrillary acidic protein, HMB-45) etc. have been tried to evaluate/diagnose melanoma, staging or post therapeutic effects. However their cost of production, tedious synthetic and radiolabelling processes and the availability of certain cyclotron produced isotopes were not favorable or patient friendly. Moreover post-therapeutic assessments in melanoma patients were not encouraging. Because of the chelating properties of Tc-99m (V) Dimercaptosuccinic acid with Calcium ion, uptake by neurogenic tumors including ocular retinoblastoma, medullary thyroid carcinoma, pituitary adenoma etc has been demonstrated. Since MTC and Melanoma have the common neural crest origin and producing some common metabolites, receptors/receptor proteins and at the same time Tc-99m (V) DMSA was used in pre and post therapeutic assessment of Medullary thyroid carcinoma extensively. We therefore decided to use Tc-99m (v) DMSA for the assessment of melanoma developed in thyrotoxicosis patients who underwent radioiodine therapy more than 15 years back. The DMSA kits were prepared locally and labeled with Tecnetium-99m at pentavalent state. After the quality control each patients were injected a dose of 10mCi of Tc-99m labeled DMSA.The whole body images were taken after two

  9. NRASQ61K mutated primary leptomeningeal melanoma in a child: case presentation and discussion on clinical and diagnostic implications

    International Nuclear Information System (INIS)

    Angelino, Giulia; De Pasquale, Maria Debora; De Sio, Luigi; Serra, Annalisa; Massimi, Luca; De Vito, Rita; Marrazzo, Antonio; Lancella, Laura; Carai, Andrea; Antonelli, Manila; Giangaspero, Felice; Gessi, Marco; Menchini, Laura; Scarciolla, Laura; Longo, Daniela; Mastronuzzi, Angela

    2016-01-01

    Primary melanocytic neoplasms are rare in the pediatric age. Among them, the pattern of neoplastic meningitis represents a peculiar diagnostic challenge since neuroradiological features may be subtle and cerebrospinal fluid analysis may not be informative. Clinical misdiagnosis of neoplastic meningitis with tuberculous meningitis has been described in few pediatric cases, leading to a significant delay in appropriate management of patients. We describe the case of a child with primary leptomeningeal melanoma (LMM) that was initially misdiagnosed with tuberculous meningitis. We review the clinical and molecular aspects of LMM and discuss on clinical and diagnostic implications. A 27-month-old girl with a 1-week history of vomiting with mild intermittent strabismus underwent Magnetic Resonance Imaging, showing diffuse brainstem and spinal leptomeningeal enhancement. Cerebrospinal fluid analysis was unremarkable. Antitubercular treatment was started without any improvement. A spinal intradural biopsy was suggestive for primary leptomeningeal melanomatosis. Chemotherapy was started, but general clinical conditions progressively worsened and patient died 11 months after diagnosis. Molecular investigations were performed post-mortem on tumor tissue and revealed absence of BRAF V600E , GNAQ Q209 and GNA11 Q209 mutations but the presence of a NRAS Q61K mutation. Our case adds some information to the limited experience of the literature, confirming the presence of the NRAS Q61K mutation in children with melanomatosis. To our knowledge, this is the first case of leptomeningeal melanocytic neoplasms (LMN) without associated skin lesions to harbor this mutation. Isolated LMN presentation might be insidious, mimicking tuberculous meningitis, and should be suspected if no definite diagnosis is possible or if antitubercular treatment does not result in dramatic clinical improvement. Leptomeningeal biopsy should be considered, not only to confirm diagnosis of LMN but also to study

  10. Frequency and characteristics of familial melanoma in Spain: the FAM-GEM-1 Study.

    Directory of Open Access Journals (Sweden)

    Iván Márquez-Rodas

    Full Text Available Familial history of melanoma is a well-known risk factor for the disease, and 7% melanoma patients were reported to have a family history of melanoma. Data relating to the frequency and clinical and pathological characteristics of both familial and non-familial melanoma in Spain have been published, but these only include patients from specific areas of Spain and do not represent the data for the whole of Spain.An observational study conducted by the Spanish Group of Melanoma (GEM analyzed the family history of patients diagnosed with melanoma between 2011 and 2013 in the dermatology and oncology departments.In all, 1047 patients were analyzed, and 69 (6.6% fulfilled criteria for classical familial melanoma (two or more first-degree relatives diagnosed with melanoma. Taking into account other risk factors for familial melanoma, such as multiple melanoma, pancreatic cancer in the family or second-degree relatives with melanoma, the number of patients fulfilling the criteria increased to 165 (15.8%. Using a univariate analysis, we determined that a Breslow index of less than 1 mm, negative mitosis, multiple melanoma, and a history of sunburns in childhood were more frequent in familial melanoma patients, but a multivariate analysis revealed no differences in any pathological or clinical factor between the two groups.Similar to that observed in other countries, familial melanoma accounts for 6.6% of melanoma diagnoses in Spain. Although no differences in the multivariate analysis were found, some better prognosis factors, such as Breslow index, seem more frequent in familial melanoma, which reflect a better early detection marker and/or a different biological behavior.

  11. The analysis of a case rate a skin melanoma in the Samara region for 1999-2009

    Directory of Open Access Journals (Sweden)

    Kozlov S.V.

    2011-06-01

    Full Text Available In article one of oncology problems — a skin melanoma is surveyed. The theme urgency proves to be true that annually the case rate of patients with an oncologic pathology is constantly enlarged. One of oncology problems still has a skin melanoma. The work purpose is studying of a case rate by a skin melanoma in large industrial area on an example of the Samara region over the last 10 years. In article one of oncology problems — a skin melanoma is surveyed. For the task in view decision following materials and methods were used: primary registration documentation for 11 years (1999-2009 About for the first time taped disease a skin melanoma, annual reports of the Samara regional clinical oncologic dispensary, annual statistical reports of the State statistical committee, bureau MSE annual reports. At processing and the forecast of results of research following statistical methods — an extrapolation method, model of linear regress were used. Reliability of the taped pattern of dynamics was defined by means of an error of regress with the subsequent definition t and p. The received results testify to growth of a case rate of all population of the Samara region at the expense of the senior age groups. According to the analysis the invalid population is more often is ill. Conclusions are drawn on appreciable influence on occurrence of this pathology occurring in an organism involutes processes, necessity of carrying out of sanitary-educational work, carrying out of additional profound inspection among the population with high level of a case rate

  12. Selenium for the Prevention of Cutaneous Melanoma

    Science.gov (United States)

    Cassidy, Pamela B.; Fain, Heidi D.; Cassidy, James P.; Tran, Sally M.; Moos, Philip J.; Boucher, Kenneth M.; Gerads, Russell; Florell, Scott R.; Grossman, Douglas; Leachman, Sancy A.

    2013-01-01

    The role of selenium (Se) supplementation in cancer prevention is controversial; effects often depend on the nutritional status of the subject and on the chemical form in which Se is provided. We used a combination of in vitro and in vivo models to study two unique therapeutic windows for intervention in the process of cutaneous melanomagenisis, and to examine the utility of two different chemical forms of Se for prevention and treatment of melanoma. We studied the effects of Se in vitro on UV-induced oxidative stress in melanocytes, and on apoptosis and cell cycle progression in melanoma cells. In vivo, we used the HGF transgenic mouse model of UV-induced melanoma to demonstrate that topical treatment with l-selenomethionine results in a significant delay in the time required for UV-induced melanoma development, but also increases the rate of growth of those tumors once they appear. In a second mouse model, we found that oral administration of high dose methylseleninic acid significantly decreases the size of human melanoma xenografts. Our findings suggest that modestly elevation of selenium levels in the skin might risk acceleration of growth of incipient tumors. Additionally, certain Se compounds administered at very high doses could have utility for the treatment of fully-malignant tumors or prevention of recurrence. PMID:23470450

  13. Synchronous high-risk melanoma and lymphoid neoplasia.

    LENUS (Irish Health Repository)

    Cahill, R A

    2012-02-03

    Large population-based studies have shown a significant association between melanoma and lymphoid neoplasia, particularly non-Hodgkin\\'s lymphoma (NHL) and chronic lymphocytic leukaemia (CLL), that is independent of any treatment received for the initial tumour. This study examines the presentation, diagnosis, treatment and progress of three patients who developed advanced melanoma concurrently with a lymphoid neoplasm (one NHL, two CLLs), in order to illustrate their association, discuss common aetiological factors and examine possible therapeutic options. As it is the melanoma rather than the lymphoid neoplasm that represents the bigger threat to overall survival, initial treatment should be targeted towards this cancer. However, because of the interplay between the diseases and the possible side-effects of the various treatments, the choice of adjuvant therapy requires careful consideration. Immunosuppression associated with chemotherapy may permit a more aggressive course for the melanoma, while locoregional radiotherapy is contraindicated following lymph node dissections. As immunotherapy is of benefit in the treatment of melanoma and has also been recently shown to be effective in the management of lymphoid neoplasia, we instituted interferon-alpha as adjuvant therapy for these patients, thereby utilizing a single agent to treat the dual pathologies. The three patients have now been followed-up for 6 months without evidence of disease recurrence or progression.

  14. Bioelectric Applications for Treatment of Melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Beebe, Stephen J., E-mail: sbeebe@odu.edu; Schoenbach, Karl H.; Heller, Richard [Frank Reidy Research Center for Bioelectrics/Old Dominion University 4211 Monarch Way, Suite 300, Norfolk, Virginia 23508 (United States)

    2010-09-27

    Two new cancer therapies apply bioelectric principles. These methods target tumor structures locally and function by applying millisecond electric fields to deliver plasmid DNA encoding cytokines using electrogene transfer (EGT) or by applying rapid rise-time nanosecond pulsed electric fields (nsPEFs). EGT has been used to locally deliver cytokines such as IL-12 to activate an immune response, resulting in bystander effects. NsPEFs locally induce apoptosis-like effects and affect vascular networks, both promoting tumor demise and restoration of normal vascular homeostasis. EGT with IL-12 is in melanoma clinical trials and nsPEFs are used in models with B16F10 melanoma in vitro and in mice. Applications of bioelectrics, using conventional electroporation and extensions of it, provide effective alternative therapies for melanoma.

  15. Bioelectric Applications for Treatment of Melanoma

    International Nuclear Information System (INIS)

    Beebe, Stephen J.; Schoenbach, Karl H.; Heller, Richard

    2010-01-01

    Two new cancer therapies apply bioelectric principles. These methods target tumor structures locally and function by applying millisecond electric fields to deliver plasmid DNA encoding cytokines using electrogene transfer (EGT) or by applying rapid rise-time nanosecond pulsed electric fields (nsPEFs). EGT has been used to locally deliver cytokines such as IL-12 to activate an immune response, resulting in bystander effects. NsPEFs locally induce apoptosis-like effects and affect vascular networks, both promoting tumor demise and restoration of normal vascular homeostasis. EGT with IL-12 is in melanoma clinical trials and nsPEFs are used in models with B16F10 melanoma in vitro and in mice. Applications of bioelectrics, using conventional electroporation and extensions of it, provide effective alternative therapies for melanoma

  16. Selumetinib in Combination With Dacarbazine in Patients With Metastatic Uveal Melanoma: A Phase III, Multicenter, Randomized Trial (SUMIT).

    Science.gov (United States)

    Carvajal, Richard D; Piperno-Neumann, Sophie; Kapiteijn, Ellen; Chapman, Paul B; Frank, Stephen; Joshua, Anthony M; Piulats, Josep M; Wolter, Pascal; Cocquyt, Veronique; Chmielowski, Bartosz; Evans, T R Jeffry; Gastaud, Lauris; Linette, Gerald; Berking, Carola; Schachter, Jacob; Rodrigues, Manuel J; Shoushtari, Alexander N; Clemett, Delyth; Ghiorghiu, Dana; Mariani, Gabriella; Spratt, Shirley; Lovick, Susan; Barker, Peter; Kilgour, Elaine; Lai, Zhongwu; Schwartz, Gary K; Nathan, Paul

    2018-04-20

    Purpose Uveal melanoma is the most common primary intraocular malignancy in adults with no effective systemic treatment option in the metastatic setting. Selumetinib (AZD6244, ARRY-142886) is an oral, potent, and selective MEK1/2 inhibitor with a short half-life, which demonstrated single-agent activity in patients with metastatic uveal melanoma in a randomized phase II trial. Methods The Selumetinib (AZD6244: ARRY-142886) (Hyd-Sulfate) in Metastatic Uveal Melanoma (SUMIT) study was a phase III, double-blind trial ( ClinicalTrial.gov identifier: NCT01974752) in which patients with metastatic uveal melanoma and no prior systemic therapy were randomly assigned (3:1) to selumetinib (75 mg twice daily) plus dacarbazine (1,000 mg/m 2 intravenously on day 1 of every 21-day cycle) or placebo plus dacarbazine. The primary end point was progression-free survival (PFS) by blinded independent central radiologic review. Secondary end points included overall survival and objective response rate. Results A total of 129 patients were randomly assigned to receive selumetinib plus dacarbazine (n = 97) or placebo plus dacarbazine (n = 32). In the selumetinib plus dacarbazine group, 82 patients (85%) experienced a PFS event, compared with 24 (75%) in the placebo plus dacarbazine group (median, 2.8 v 1.8 months); the hazard ratio for PFS was 0.78 (95% CI, 0.48 to 1.27; two-sided P = .32). The objective response rate was 3% with selumetinib plus dacarbazine and 0% with placebo plus dacarbazine (two-sided P = .36). At 37% maturity (n = 48 deaths), analysis of overall survival gave a hazard ratio of 0.75 (95% CI, 0.39 to 1.46; two-sided P = .40). The most frequently reported adverse events (selumetinib plus dacarbazine v placebo plus dacarbazine) were nausea (62% v 19%), rash (57% v 6%), fatigue (44% v 47%), diarrhea (44% v 22%), and peripheral edema (43% v 6%). Conclusion In patients with metastatic uveal melanoma, the combination of selumetinib plus dacarbazine had a tolerable safety

  17. Diagnosis of Malignant Melanoma of Skin Cancer Types

    Directory of Open Access Journals (Sweden)

    Abbas Hassin Alasadi

    2017-08-01

    Full Text Available Malignant melanoma is a kind of skin cancer that begins in melanocytes. It can influence on the skin only, or it may expand to the bones and organs. It is less common, but more serious and aggressive than other types of skin cancer. Malignant Melanoma can happen anywhere on the skin, but it is widespread in certain locations such as the legs in women, the back and chest in men, the face, the neck, mouth, eyes, and genitals. In this paper, a proposed algorithm is designed for diagnosing malignant melanoma types by using digital image processing techniques. The algorithm consists of four steps: preprocessing, separation, features extraction, and diagnosis. A neural network (NN used to diagnosis malignant melanoma types. The total accuracy of the neural network was 100% for training and 93% for testing. The evaluation of the algorithm is done by using sensitivity, specificity, and accuracy. The sensitivity of NN in diagnosing malignant melanoma types was 95.6%, while the specificity was 92.2% and the accuracy was 93.9%. The experimental results are acceptable.

  18. Histopathological study of malignant melanoma in highlanders ...

    African Journals Online (AJOL)

    Histopathological study of malignant melanoma in highlanders. AZ Mohammed, AN Manasseh, BM Mandong, ST Edino. Abstract. Background:Malignant melanoma is a fatal skin cancer that is curable when detected and treated early. Recent reports indicate a rising incidence globally. This study aims at identifying the ...

  19. Oral Malignant Melanoma in a Ferret ( Mustela putorius furo).

    Science.gov (United States)

    d'Ovidio, Dario; Rossi, Giacomo; Meomartino, Leonardo

    2016-06-01

    Oral malignant melanomas are one of the most common oral malignant neoplasms in dogs but are rare in other domesticated species. This case report describes the clinical manifestations and histological appearance of oral melanoma in a ferret ( Mustela putorius furo). To the authors' knowledge, this is the first published description of a clinical case and histopathological findings of oral melanoma in this species.

  20. Photodynamic therapy for melanoma: efficacy and immunologic effects

    Science.gov (United States)

    Avci, Pinar; Gupta, Gaurav K.; Kawakubo, Masayoshi; Hamblin, Michael R.

    2014-02-01

    Malignant melanoma is one of the fastest growing cancers and if it cannot be completely surgically removed the prognosis is bleak. Melanomas are known to be particularly resistant to both chemotherapy and radiotherapy. Various types of immunotherapy have however been investigated with mixed reports of success. Photodynamic therapy (PDT) has also been tested against melanoma, again with mixed effects as the melanin pigment is thought to act as both an optical shield and as an antioxidant. We have been investigating PDT against malignant melanoma in mouse models. We have compared B16F10 melanoma syngenic to C57BL/6 mice and S91 Cloudman melanoma syngenic to DBA2 mice. We have tested the hypothesis that S91 will respond better than B16 because of higher expression of immunocritical molecules such as MHC-1, tyrosinase, tyrosinase related protein-2 gp100, and intercellular adhesion molecule-1. Some of these molecules can act as tumor rejection antigens that can be recognized by antigen-specific cytotoxic CD8 T cells that have been stimulated by PDT. Moreover it is possible that DBA2 mice are intrinsically better able to mount an anti-tumor immune response than C57BL/6 mice. We are also studying intratumoral injection of photosensitzers such as benzoporphyrin monoacid ring A and comparing this route with the more usual route of intravenous administration.

  1. Inverse association between atopy and melanoma: A case-control study

    NARCIS (Netherlands)

    Marasigan, V. (Vivien); M.-A. Morren (Marie-Anne); J. Lambert; Medaer, K. (Karen); Fieuws, S. (Steffen); T.E.C. Nijsten (Tamar); Garmyn, M. (Marjan)

    2017-01-01

    textabstractHeightened cutaneous immune surveillance in atopic patients may inhibit development of melanoma. The aim of this study was to analyse the association between atopy and melanoma (development and outcome). A total of 188 cases of melanoma and 596 healthy controls were interviewed by

  2. Completion Dissection or Observation for Sentinel-Node Metastasis in Melanoma

    NARCIS (Netherlands)

    Faries, M. B.; Thompson, J. F.; Cochran, A. J.; Andtbacka, R. H.; Mozzillo, N; Zager, Jonathan S.; Jahkola, T.; Bowles, T. L.; Testori, Alessandro; Beitsch, P. D.; Hoekstra, H. J.; Moncrieff, M.; Ingvar, C.; Wouters, M. W. J. M.; Sabel, M. S.; Levine, E. A.; Agnese, D.; Henderson, M.; Dummer, R; Rossi, C. R.; Neves, R. I.; Trocha, S. D.; Wright, Sara F.; Byrd, D. R.; Matter, M.; Hsueh, E.; MacKenzie-Ross, A.; Johnson, B. D.; Terheyden, P.; Berger, A. C.; Huston, T. L.; Wayne, J. D.; Smithers, B. Mark; Neuman, H. B.; Schneebaum, S.; Gershenwald, Jeffrey E.; Ariyan, C. E.; Desai, D. C.; Jacobs, L.; McMasters, K. M.; Gesierich, A.; Hersey, P.; Bines, S. D.; Kane, Michael J.; Barth, R. J.; McKinnon, J. G.; Farma, J. M.; Schultz, B. E.; Vidal-Sicart, S.; Hoefer, R. A.; Lewis, David J. M.; Scheri, R.; Kelley, M. C.; Nieweg, O. E.; Noyes, R. D.; Hoon, D. S. B.; Wang, H. -J.; Elashoff, D. A.; Elashoff, R. M.

    2017-01-01

    BACKGROUND Sentinel-lymph-node biopsy is associated with increased melanoma-specific survival (i.e., survival until death from melanoma) among patients with node-positive intermediate-thickness melanomas (1.2 to 3.5 mm). The value of completion lymph-node dissection for patients with sentinel-node

  3. A case of malignant melanoma of the maxilla treated by adoptive immunotherapy after fast neutron therapy

    International Nuclear Information System (INIS)

    Morifuji, Masayo; Ohishi, Masamichi; Higuchi, Yoshinori; Ozeki, Satoru; Tashiro, Hideo

    1992-01-01

    A 77-year-old male patient with malignant melanoma was treated by fast neutron therapy and immunotherapy. Total dose of fast neutron applied to the primary lesion was 1905 cGy per 21 fractionation for 46 days. For adoptive immunotherapy, lymphocytes were collected from the peripheral blood drawn from the patient 2 days after the injection of cyclophosphamide. T cells were further purified by passing the lymphocytes through nylon wool. Cytotoxic T cells were induced by incubating the T cells mixed with allogeneic malignant melanoma cells and a small number of patient's adherent cells, and activated with recombinant interleukin-2 (γ IL-2). Our patient and the patient from whom stimulating melanoma cells were derived shared A locous 24 and B locous 51 of MHC class I antigens in common. Thus prepared cytotoxic T cells were inoculated to the patient via the maxillary artery, 3 to 4 times a week for one month. Total amount of cells transferred was 5.6 x 10 8 (97% lymphocytes). Primary lesion reduced markedly by the therapies. During adoptive immunotherapy, increase in natural killer cells and decrease in both suppressor/inducer T-cells and macrophages were observed. However, lung metastases appeared 3 months after adoptive immunotherapy. While the nonspecific immunotherapy (OK-432 injection) was being conducted thereafter, growth of the metastatic lesions of the lung was kept gentle but became obvious after the suspension of the treatment. (author)

  4. Kinome-wide transcriptional profiling of uveal melanoma reveals new vulnerabilities to targeted therapeutics.

    Science.gov (United States)

    Bailey, Fiona P; Clarke, Kim; Kalirai, Helen; Kenyani, Jenna; Shahidipour, Haleh; Falciani, Francesco; Coulson, Judy M; Sacco, Joseph J; Coupland, Sarah E; Eyers, Patrick A

    2018-03-01

    Metastatic uveal melanoma (UM) is invariably fatal, usually within a year of diagnosis. There are currently no effective therapies, and clinical studies employing kinase inhibitors have so far demonstrated limited success. This is despite common activating mutations in GNAQ/11 genes, which trigger signalling pathways that might predispose tumours to a variety of targeted drugs. In this study, we have profiled kinome expression network dynamics in various human ocular melanomas. We uncovered a shared transcriptional profile in human primary UM samples and across a variety of experimental cell-based models. The poor overall response of UM cells to FDA-approved kinase inhibitors contrasted with much higher sensitivity to the bromodomain inhibitor JQ1, a broad transcriptional repressor. Mechanistically, we identified a repressed FOXM1-dependent kinase subnetwork in JQ1-exposed cells that contained multiple cell cycle-regulated protein kinases. Consistently, we demonstrated vulnerability of UM cells to inhibitors of mitotic protein kinases within this network, including the investigational PLK1 inhibitor BI6727. We conclude that analysis of kinome-wide signalling network dynamics has the potential to reveal actionable drug targets and inhibitors of potential therapeutic benefit for UM patients. © 2017 The Authors. Pigment Cell & Melanoma Research Published by John Wiley & Sons.

  5. Prediction of melanoma metastasis by the Shields index based on lymphatic vessel density

    Directory of Open Access Journals (Sweden)

    Metcalfe Chris

    2010-05-01

    Full Text Available Abstract Background Melanoma usually presents as an initial skin lesion without evidence of metastasis. A significant proportion of patients develop subsequent local, regional or distant metastasis, sometimes many years after the initial lesion was removed. The current most effective staging method to identify early regional metastasis is sentinel lymph node biopsy (SLNB, which is invasive, not without morbidity and, while improving staging, may not improve overall survival. Lymphatic density, Breslow's thickness and the presence or absence of lymphatic invasion combined has been proposed to be a prognostic index of metastasis, by Shields et al in a patient group. Methods Here we undertook a retrospective analysis of 102 malignant melanomas from patients with more than five years follow-up to evaluate the Shields' index and compare with existing indicators. Results The Shields' index accurately predicted outcome in 90% of patients with metastases and 84% without metastases. For these, the Shields index was more predictive than thickness or lymphatic density. Alternate lymphatic measurement (hot spot analysis was also effective when combined into the Shields index in a cohort of 24 patients. Conclusions These results show the Shields index, a non-invasive analysis based on immunohistochemistry of lymphatics surrounding primary lesions that can accurately predict outcome, is a simple, useful prognostic tool in malignant melanoma.

  6. LOSS OF 5-HYDROXYMETHYLCYTOSINE IS AN EPIGENETIC HALLMARK OF MELANOMA

    Science.gov (United States)

    Lian, Christine Guo; Xu, Yufei; Ceol, Craig; Wu, Feizhen; Larson, Allison; Dresser, Karen; Xu, Wenji; Tan, Li; Hu, Yeguang; Zhan, Qian; Lee, Chung-wei; Hu, Di; Lian, Bill Q.; Kleffel, Sonja; Yang, Yijun; Neiswender, James; Khorasani, Abraham J.; Fang, Rui; Lezcano, Cecilia; Duncan, Lyn M.; Scolyer, Richard A.; Thompson, John F.; Kakavand, Hojabr; Houvras, Yariv; Zon, Leonard; Mihm, Martin C.; Kaiser, Ursula B.; Schatton, Tobias; Woda, Bruce A.; Murphy, George F.; Shi, Yujiang G.

    2013-01-01

    SUMMARY DNA methylation at the 5-position of cytosine (5-mC) is a key epigenetic mark critical for various biological and pathological processes. 5-mC can be converted to 5-hydroxymethylcytosine (5-hmC) by the Ten-Eleven Translocation (TET) family of DNA hydroxylases. Here we report that “loss of 5-hmC” is an epigenetic hallmark of melanoma with diagnostic and prognostic implications. Genome-wide mapping of 5-hmC reveals loss of 5-hmC landscape in the melanoma epigenome. We show that down-regulation of Isocitrate Dehydrogenase 2 (IDH2) and TET family enzymes is likely one of the mechanisms underlying 5-hmC loss in melanoma. Rebuilding the 5-hmC landscape in melanoma cells by reintroducing active TET2 or IDH2 suppresses melanoma growth and increases tumor-free survival in animal models. Thus, our study reveals a critical function of 5-hmC in melanoma development and directly links the IDH and TET activity-dependent epigenetic pathway to 5-hmC-mediated suppression of melanoma progression, suggesting a new strategy for epigenetic cancer therapy. PMID:22980977

  7. HTB140 melanoma cells under proton irradiation and/or alkylating agents

    Science.gov (United States)

    Korićanac, L.; Petrović, I.; Privitera, G.; Cuttone, G.; Ristić-Fira, A.

    2007-09-01

    Chemoresistance is a major problem in the treatment of malignant melanoma. The mainstay of treatment for melanoma is the DNA-alkylating agent dacarbazine (DTIC). Fotemustine (FM), a member of the chloroethylnitrosourea group of alkylating agents, has also demonstrated significant antitumor effects in malignant melanoma. However, the intrinsic and acquired resistance of melanoma limits the clinical application of these drugs. Melanomas are also extremely radioresistant. With the objective of enhancing growth inhibition of melanoma cells, combined treatments of FM or DTIC with proton irradiation have been investigated. These effects were studied on HTB140 melanoma cell viability and proliferation. Cells exposed to treatment with FM and protons have shown inhibition of cell growth and significant reduction of proliferation capacity compared to single irradiation or drug treatment. Treatment with DTIC and protons has shown improved growth inhibition compared to appropriate single drug treatment, while the effects of single proton irradiation have been the most pronounced.

  8. Ocular melanoma metastatic to skin: the value of HMB-45 staining.

    Science.gov (United States)

    Schwartz, Robert A; Kist, Joseph M; Thomas, Isabelle; Fernández, Geover; Cruz, Manuel A; Koziorynska, Ewa I; Lambert, W Clark

    2004-06-01

    Cutaneous metastatic disease is an important finding that may represent the first sign of systemic cancer, or, if already known, that may change tumor staging and thus dramatically altered therapeutic plans. Although cutaneous metastases are relatively frequent in patients with cutaneous melanoma, they are less so from ocular melanoma. To demonstrate the value of HMB-45, staining in the detection of ocular melanoma metastatic to skin. The immunohistochemical stain HMB-45 a monoclonal antibody directed against intact human melanoma cells, was employed on a skin biopsy specimen from a cutaneous tumor. HMB-45 staining was positive in the atypical hyperchromatic cells of the deep dermis. HMB-45 may be of value in the detection of ocular melanoma metastatic to skin. Cutaneous metastatic disease is a somewhat common and extremely important diagnosis. Although cutaneous metastases from cutaneous melanoma are relatively frequent, those from ocular melanomas are less so. Use of histochemical staining, especially the HMB-45 stain, allows confirmation of the diagnosis.

  9. Skin Cancer (Including Melanoma)—Patient Version

    Science.gov (United States)

    Skin cancer is the most common type of cancer. The main types of skin cancer are squamous cell carcinoma, basal cell carcinoma, and melanoma. Most deaths from skin cancer are caused by melanoma. Start here to find information on skin cancer treatment, causes and prevention, screening, research, and statistics.

  10. Ocular melanoma: Detection using iodine-123-iodoamphetamine and SPECT imaging

    International Nuclear Information System (INIS)

    Dewey, S.H.; Leonard, J.C.

    1990-01-01

    Uptake of iodine-123-iodoamphetamine has been demonstrated in malignant melanoma using planar imaging techniques and has been used to detect an ocular melanoma at 12 hr postinjection. Using SPECT technique, an ocular melanoma is identified in a 64-yr-old male at 1 hr postinjection

  11. Uptake in melanoma cells of N-(2-diethylaminoethyl)-2-iodobenzamide (BZA2), an imaging agent for melanoma staging: relation to pigmentation

    International Nuclear Information System (INIS)

    Mansard, Sandrine; Papon, Janine; Moreau, Marie-France; Miot-Noirault, Elisabeth; Labarre, Pierre; Bayle, Martine; Veyre, Annie; Madelmont, Jean-Claude; Moins, Nicole

    2005-01-01

    N-(2-diethylaminoethyl)-2-iodobenzamide (BZA 2 ) has been singled out as the most efficacious melanoma scintigraphy imaging agent. Our work was designed to assess the mechanisms of the specific affinity of the radioiodinated iodobenzamide for melanoma tissue. We studied the cellular uptake and retention of [ 125 I]-BZA 2 on various cell lines. In vitro, cellular [ 125 I]-BZA 2 uptake was related to the pigmentation status of the cells: higher in pigmented melanoma cell lines (M4 Beu, IPC 227, B 16) than in a nonpigmented one (M3 Dau) and nonmelanoma cell lines (MCF 7 and L 929). Two mechanisms were assessed: binding of the tracer to melanin or to sigma receptors of melanoma cells. First, the uptake of [ 125 I]-BZA 2 after melanogenesis stimulation by α-melanocyte-stimulating hormone and L-tyrosine increased in the B 16 melanoma cell line both in vitro and in vivo according to melanin concentration. Moreover, the binding of [ 125 I]-BZA 2 to synthetic melanin was dependent on melanin concentration and could be saturated. Second, no competition was evidenced on M4 Beu cells between [ 125 I]-BZA 2 and haloperidol, a sigma ligand, at concentrations ≤10 -6 M. We show that the specificity and sensibility of BZA 2 as a melanoma scintigraphic imaging agent are mostly due to interactions with melanic pigments

  12. WITHDRAWN: Systemic treatments for metastatic cutaneous melanoma.

    Science.gov (United States)

    Crosby, Tom; Fish, Reg; Coles, Bernadette; Mason, Malcolm

    2018-02-07

    Systemic therapies for metastatic cutaneous melanoma, the most aggressive of all skin cancers, remain disappointing. Few lasting remissions are achieved and the therapeutic aim remains one of palliation.Many agents are used alone or in combination with varying degrees of toxicity and cost. It is unclear whether evidence exists to support these complex regimens over best supportive care / placebo. To review the benefits from the use of systemic therapies in metastatic cutaneous melanoma compared to best supportive care/placebo, and to establish whether a 'standard' therapy exists which is superior to other treatments. Randomised controlled trials were identified from the MEDLINE, EMBASE and CCTR/CENTRAL databases. References, conference proceedings, and Science Citation Index/Scisearch were also used to locate trials. Cancer registries and trialists were also contacted. Randomised controlled trials of adults with histologically proven metastatic cutaneous melanoma in which systemic anti-cancer therapy was compared with placebo or supportive care. Study selection was performed by two independent reviewers. Data extraction forms were used for studies which appeared to meet the selection criteria and, where appropriate, full text articles were retrieved and reviewed independently. No randomised controlled trials were found comparing a systemic therapy with placebo or best supportive care in metastatic cutaneous melanoma. There is no evidence from randomised controlled clinical trials to show superiority of systemic therapy over best supportive care / placebo in the treatment of malignant cutaneous melanoma.Given that patients with metastatic melanoma frequently receive systemic therapy, it is our pragmatic view that a future systematic review could compare any systemic treatment, or combination of treatments, to single agent dacarbazine.

  13. Melanoma and tattoos: a case report and review of the literature.

    Science.gov (United States)

    Ricci, Francesco; Paradisi, Andrea; Maier, Stephanie Alissa; Kovacs, Maximilian; Podda, Maurizio; Peris, Ketty; Abeni, Damiano

    2018-02-01

    Malignant melanoma cases arising in tattoos have been increasingly described, however, there is no clear relationship between this practice and the development of cutaneous malignancies. We report a new case of melanoma in a dark-blue tattoo and we review all cases of melanoma reported in the medical literature from 1938 to date. Pubmed and Google Scholar were searched using the terms "melanoma tattoo", "tattoo skin tumour" and "ink melanoma". In most cases, the melanoma occurred on dark blue (10/30), black (8/30), or blue ink (3/30). The Breslow thickness at diagnosis was ≤1 mm in 13/30, 1-2 mm in 3/30, 2-4 mm in 2/30, >4 mm in 5/30, and Clark II in 2/30 (not available in 5/30). Both the incidence of melanoma and the number of tattoos have been increasing in recent years, but a possible carcinogenic effect of tattoos remains unproven. The spread of this decorative custom will make observation of melanoma in tattoos more frequent in dermatological practice, therefore these cases should be reported in national skin cancer registries.

  14. Characterisation of Human Keratinocytes by Measuring Cellular Repair Capacity of UVB-Induced DNA Damage and Monitoring of Cytogenetic Changes in Melanoma Cell Lines

    Energy Technology Data Exchange (ETDEWEB)

    Greinert, R.; Breibart, E.W.; Mitchell, D.; Smida, J.; Volkmer, B

    2000-07-01

    The molecular mechanisms for UV-induced photocarcinogenesis are far from being understood in detail, especially in the case of malignant melanoma of the skin. Nevertheless, it is known that deficiencies in cellular repair processes of UV-induced DNA damage (e.g. in the case of Xeroderma pigmentosum) represent important aetiological factors in the multistep development of skin cancer. The repair kinetics have therefore been studied of an established skin cell line (HaCaT), primary human keratinocytes, melanocytes and melanoma cell lines, using fluorescence microscopy and flow cytometry. Our data show a high degree of interindividual variability in cellular repair capacity for UV-induced DNA lesions, which might be due to individual differences in the degree of tolerable damage and/or the onsets of saturation of the enzymatic repair system. The cytogenetic analysis of melanoma cell lines, using spectral karyotyping (SKY) furthermore proves that malignant melanoma of the skin are characterised by high numbers of chromosomal aberrations. (author)

  15. Circulating tumor cells in melanoma patients.

    Directory of Open Access Journals (Sweden)

    Gary A Clawson

    Full Text Available Circulating tumor cells (CTCs are of recognized importance for diagnosis and prognosis of cancer patients. With melanoma, most studies do not show any clear relationship between CTC levels and stage of disease. Here, CTCs were enriched (∼400X from blood of melanoma patients using a simple centrifugation device (OncoQuick, and 4 melanocyte target RNAs (TYR, MLANA, MITF, and MIF were quantified using QPCR. Approximately one-third of melanoma patients had elevated MIF and MLANA transcripts (p<0.0001 and p<0.001, respectively compared with healthy controls. In contrast, healthy controls had uniformly higher levels of TYR and MITF than melanoma patients (p<0.0001. There was a marked shift of leukocytes into the CTC-enriched fractions (a 430% increase in RNA recovery, p<0.001, and no relationship between CTC levels and stage of disease was found. CTCs were captured on microfabricated filters and cultured. Captured melanoma CTCs were large cells, and consisted of 2 subpopulations, based on immunoreactivity. One subpopulation (∼50% stained for both pan-cytokeratin (KRT markers and the common leukocyte marker CD-45, whereas the second subpopulation stained for only KRT. Since similar cells are described in many cancers, we also examined blood from colorectal and pancreatic cancer patients. We observed analogous results, with most captured CTCs staining for both CD-45/KRT markers (and for the monocyte differentiation marker CD-14. Our results suggest that immature melanocyte-related cells (expressing TYR and MITF RNA may circulate in healthy controls, although they are not readily detectable without considerable enrichment. Further, as early-stage melanomas develop, immature melanocyte migration into the blood is somehow curtailed, whereas a significant proportion of patients develop elevated CTC levels (based on MIF and MLANA RNAs. The nature of the captured CTCs is consistent with literature describing leukocyte/macrophage-tumor cell fusion hybrids

  16. Deep sequencing of uveal melanoma identifies a recurrent mutation in PLCB4

    DEFF Research Database (Denmark)

    Johansson, Peter; Aoude, Lauren G; Wadt, Karin

    2016-01-01

    Next generation sequencing of uveal melanoma (UM) samples has identified a number of recurrent oncogenic or loss-of-function mutations in key driver genes including: GNAQ, GNA11, EIF1AX, SF3B1 and BAP1. To search for additional driver mutations in this tumor type we carried out whole......, instead, a BRCA mutation signature predominated. In addition to mutations in the known UM driver genes, we found a recurrent mutation in PLCB4 (c.G1888T, p.D630Y, NM_000933), which was validated using Sanger sequencing. The identical mutation was also found in published UM sequence data (1 of 56 tumors......-genome or whole-exome sequencing of 28 tumors or primary cell lines. These samples have a low mutation burden, with a mean of 10.6 protein changing mutations per sample (range 0 to 53). As expected for these sun-shielded melanomas the mutation spectrum was not consistent with an ultraviolet radiation signature...

  17. Melanoma in patients with chronic lymphocytic leukemia and non-Hodgkin lymphoma.

    Science.gov (United States)

    Famenini, Shannon; Martires, Kathryn J; Zhou, Hui; Xavier, Marin F; Wu, Jashin J

    2015-01-01

    The relationship between melanoma and chronic lymphocytic leukemia (CLL) or non-Hodgkin lymphoma (NHL) has been minimally investigated. The objective of this study was to examine the incidence of melanoma in patients with a history of CLL or NHL, and their associated mortality. Cohorts of Kaiser Permanente Southern California members with a history of CLL and NHL were identified. Age-adjusted incidence density rates of melanoma among patients with CLL or NHL were compared with rates of melanoma among the general population of Kaiser Permanente Southern California patients. The mortality of patients with melanoma was examined using Cox proportional hazards modeling. The age-adjusted incidence rate per 100,000 person-years for melanoma among patients with either CLL or NHL was 107 (95% confidence interval 84.4-129.6) versus 25.9 among the general population (95% confidence interval 84.4-129.6, P < .001). Patients with melanoma and a history of CLL or NHL had 2.46 greater odds of death compared with those without CLL or NHL (95% confidence interval 1.77-3.41). This study was retrospective in nature; the International Classification of Diseases, Ninth Revision codes used may contain diagnostic errors; and only overall survival was used in our analysis. Patients with a history of CLL or NHL have a higher incidence of melanoma. Patients with CLL or NHL who are subsequently given the diagnosis of melanoma have a higher mortality than patients with melanoma without a preceding diagnosis of CLL. Copyright © 2014 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

  18. Notch4 Signaling Induces a Mesenchymal–Epithelial–like Transition in Melanoma Cells to Suppress Malignant Behaviors

    Science.gov (United States)

    Rad, Ehsan Bonyadi; Hammerlindl, Heinz; Wels, Christian; Popper, Ulrich; Menon, Dinoop Ravindran; Breiteneder, Heimo; Kitzwoegerer, Melitta; Hafner, Christine; Herlyn, Meenhard; Bergler, Helmut; Schaider, Helmut

    2016-01-01

    The effects of Notch signaling are context-dependent and both oncogenic and tumor-suppressive functions have been described. Notch signaling in melanoma is considered oncogenic, but clinical trials testing Notch inhibition in this malignancy have not proved successful. Here, we report that expression of the constitutively active intracellular domain of Notch4 (N4ICD) in melanoma cells triggered a switch from a mesenchymal-like parental phenotype to an epithelial-like phenotype. The epithelial-like morphology was accompanied by strongly reduced invasive, migratory, and proliferative properties concomitant with the downregulation of epithelial–mesenchymal transition markers Snail2 (SNAI2), Twist1, vimentin (VIM), and MMP2 and the reexpression of E-cadherin (CDH1). The N4ICD-induced phenotypic switch also resulted in significantly reduced tumor growth in vivo. Immunohistochemical analysis of primary human melanomas and cutaneous metastases revealed a significant correlation between Notch4 and E-cadherin expression. Mechanistically, we demonstrate that N4ICD induced the expression of the transcription factors Hey1 and Hey2, which bound directly to the promoter regions of Snail2 and Twist1 and repressed gene transcription, as determined by EMSA and luciferase assays. Taken together, our findings indicate a role for Notch4 as a tumor suppressor in melanoma, uncovering a potential explanation for the poor clinical efficacy of Notch inhibitors observed in this setting. PMID:26801977

  19. Learning from mistakes: errors in approaches to melanoma and the urgent need for updated national guidelines.

    Science.gov (United States)

    Simionescu, Olga; Blum, Andreas; Grigore, Mariana; Costache, Mariana; Avram, Alina; Testori, Alessandro

    2016-09-01

    The tracking and identification of errors in the detection and follow-up of melanoma are important because there is huge potential to increase awareness about the most vulnerable aspects of diagnosis and treatment, and to improve both from the perspective of healthcare economics. The present study was designed to identify where errors occur and to propose a minimum set of rules for the routine guidance of any specialist in melanoma management. This report describes the evaluation of a unique series of 33 cases in which errors applying to many steps in the diagnosis and treatment of melanoma were detected. Cases were collected at two centers in Romania, one public and one private, as part of a process of obtaining patient-requested second opinions. A total of 166 errors were identified across the 33 patients, most of which were treatment errors. The errors fell into six categories: clinical diagnostic errors (36 errors among 30 patients); primary surgical errors (31 errors among 16 patients); pathology errors (24 errors among 17 patients); sentinel lymph node biopsy errors (13 errors among 13 patients); staging errors (17 errors among 13 patients); and treatment or management errors (45 errors among 33 patients). Based on the present results, we propose that in countries lacking national guidelines, clinicians should adhere to international evidence-based guidelines for the diagnosis and treatment of melanoma. © 2015 The International Society of Dermatology.

  20. Promoting early detection of melanoma during the mammography experience

    Directory of Open Access Journals (Sweden)

    A.K. Rzepecki, BS

    2017-12-01

    Full Text Available Background: Invasive melanoma, a lethal form of skin cancer, is the seventh most common cancer in women. Factors such as a history of indoor tanning or sunburn and a personal or family history of skin cancer increase a woman’s risk of developing a melanoma. Objective: Because the majority of melanomas occur in patients age 40 years or older, which is the age that is recommended for women to begin screening mammograms, the mammogram experience could be used to promote early detection of melanoma by introducing skin self-examinations (SSE to a population of women who are already invested in preventive health. Methods: This was a pilot and feasibility study that was designed to promote the early detection of melanoma among women who undergo a mammogram at the Lynn Sage Breast Center at the Northwestern Medicine/Prentice Women’s Hospital in Chicago, Illinois. The study was conducted in three phases: development of the materials, delivery of the program, and assessment of the program effectiveness. Results: Eighty six percent of women with scheduled mammogram appointments participated in the study (n = 560. Among these women, 68% noticed the SSE information in the changing rooms, 78% thought the information applied to them, and 68% identified with at least one of the risk factors for melanoma. Twenty percent of the patients checked their skin in the changing room, 13% noticed a concerning mole, and 60% of those women who noted a concerning lesion stated their intent to see a dermatologist for further evaluation. Conclusion: A large proportion of the women in our study had risk factors for developing a melanoma and noticed the SSE information in the screening center. Placing an intervention to encourage methods for the early detection of melanoma in an outpatient mammography environment is an effective strategy to increase awareness in a large proportion of at-risk women. Keywords: melanoma, skin self-examination, skin cancer screening