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Sample records for human malignant melanomas

  1. Intercellular crosstalk in human malignant melanoma

    Czech Academy of Sciences Publication Activity Database

    Dvořánková, Barbora; Szabo, Pavol; Kodet, O.; Strnad, Hynek; Kolář, Michal; Lacina, L.; Krejčí, E.; Nanka, O.; Sedo, A.; Smetana, K.

    2017-01-01

    Roč. 254, č. 3 (2017), s. 1143-1150 ISSN 0033-183X R&D Projects: GA ČR GA16-05534S; GA MŠk(CZ) LQ1604; GA MŠk(CZ) ED1.1.00/02.0109 Grant - others:GA MŠk(CZ) LM2015042 Institutional support: RVO:68378050 Keywords : Melanocyte * Melanoma cells * Melanoma ecosystem * cancer -associated fibroblast * Keratinocyte * Cytokine Impact factor: 2.870, year: 2016

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

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    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.

  3. Basic and clinical aspects of malignant melanoma

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    Nathanson, L. (Health Sciences Center, State Univ. of New York at Stony Brook, Stony Brook, NY (US))

    1987-01-01

    This book contains the following 10 chapters: The role of oncogenes in the pathogenesis of malignant melanoma; Laminin and fibronectin modulate the metastatic activity of melanoma cells; Structure, function and biosynthesis of ganglioside antigens associated with human tumors derived from the neuroectoderm; Epidemiology of ocular melanoma; Malignant melanoma: Prognostic factors; Endocrine influences on the natural history of human malignant melanoma; Psychosocial factors associated with prognostic indicators, progression, psychophysiology, and tumor-host response in cutaneous malignant melanoma; Central nervous system metastases in malignant melanoma; Interferon trials in the management of malignant melanoma and other neoplasms: an overview; and The treatment of malignant melanoma by fast neutrons.

  4. Malignant Melanoma

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    Eshini Perera

    2013-12-01

    Full Text Available Melanomas are a major cause of premature death from cancer. The gradual decrease in rates of morbidity and mortality has occurred as a result of public health campaigns and improved rates of early diagnosis. Survival of melanoma has increased to over 90%. Management of melanoma involves a number of components: excision, tumor staging, re-excision with negative margins, adjuvant therapies (chemo, radiation or surgery, treatment of stage IV disease, follow-up examination for metastasis, lifestyle modification and counseling. Sentinel lymph node status is an important prognostic factor for survival in patients with a melanoma >1 mm. However, sentinel lymph node biopsies have received partial support due to the limited data regarding the survival advantage of complete lymph node dissection when a micrometastasis is detected in the lymph nodes. Functional mutations in the mitogen-activated pathways are commonly detected in melanomas and these influence the growth control. Therapies that target these pathways are rapidly emerging, and are being shown to increase survival rates in patients. Access to these newer agents can be gained by participation in clinical trials after referral to a multidisciplinary team for staging and re-excision of the scar.

  5. Primary ovarian malignant melanoma

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    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.

  6. Expression of lumican, a small leucine-rich proteoglycan with antitumour activity, in human malignant melanoma.

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    Brézillon, S; Venteo, L; Ramont, L; D'Onofrio, M-F; Perreau, C; Pluot, M; Maquart, F-X; Wegrowski, Y

    2007-07-01

    The family of small leucine-rich proteoglycans (SLRPs), which includes decorin, lumican, biglycan and fibromodulin, constitutes an abundant component of the skin extracellular matrix. We previously demonstrated that human lumican inhibits melanoma growth and progression in a mouse experimental model, by regulating cell migration, proliferation and apoptosis. The aim of this study was to investigate the expression of lumican and decorin in human malignant melanoma and adjacent peritumoral tissue, to understand better their role in the control of growth and invasion of human melanoma. Expression of both proteoglycans was studied by immunohistochemistry using specific antibodies in 34 malignant melanomas, 12 Hutchinson's melanotic freckles and 4 cutaneous metastatic melanomas. We showed that lumican and decorin are located in the dermis and in the peritumoral stroma of malignant melanoma, but are not found in melanoma cells or dense tumour tissue. In the healthy dermis, distant from the tumour, the increasing ratio of lumican to decorin was inversely correlated with the proliferation of the tumour cells (P = 0.035). The comparison of the level of expression of lumican protein in superficial vs. nodular subtypes of malignant melanomas showed a decrease of lumican but not decorin in the peritumoral stroma of nodular subtypes. In the peritumoral stroma, the level of expression of lumican but not decorin decreased significantly (P = 0.016) with increasing Clark levels. In addition, immunocytochemical and reverse transcription PCR analyses of malignant melanoma cell lines (A-375, HT-144) and of MRC-5 and dermal fibroblasts from healthy donors in vitro confirmed that dermal fibroblasts are responsible for lumican and decorin synthesis in skin. CONCLUSIONS. Lumican may regulate vertical progression of human malignant melanoma, but further study is necessary to clarify the antitumour mechanism and the downstream signal transduction pathways involved.

  7. Regulated Expression of Vascular Cell Adhesion Molecule-1 in Human Malignant Melanoma

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    Jonjic, Nives; Martìn-Padura, Inés; Pollicino, Teresa; Bernasconi, Sergio; Jílek, Petr; Bigotti, Aldo; Mortarini, Roberta; Anichini, Andrea; Parmiani, Giorgio; Colotta, Francesco; Dejana, Elisabetta; Mantovani, Alberto; Natali, Pier Giorgio

    1992-01-01

    Expression of the endothelial adhesion molecule VCAM-1 was studied in human malignant melanoma lines by flow cytometry. Clones 2/4 and 2/14(derived from the same lesion) had appreciable levels of VCAM-1 expression, whereas clone 2/21 and thelines A2058, Mel24, and A375 were negative. Clone 2/14 was selected for further analysis. Exposure to tumor necrosis factor (TNF) markedly augmented VCAM-1 on melanoma cells. Surface VCAM-1 was associated with expression of specific transcripts that were augmented by TNF. Analysis by reverse transcriptase and polymerase chain reaction using appropriate primers revealed that TNF-stimulated melanoma cells expressed both 7 and 6 immunoglobulin domain transcripts with predominance of the longer species. Tumor necrosis factor-stimulated melanoma cells bound more VLA-4-expressing cells (melanoma and monocytes) than resting tumor cells and anti-VCAM-1 monoclonal antibodies significantly inhibited binding, thus suggesting that surface VCAM-1 on melanoma is functional. Analysis of melanoma tissue sections demonstrated that VCAM-1 is not a marker of transformation of melanocytes because it can be detected in benign nevi. Although, unlike ICAM-1, VCAM-1 is not correlated with tumor progression, its expression in a fraction of primary melanomas indicates that it may play a role in regulating host immune response and homotypic interactions in some malignant melanomas ImagesFigure 2Figure 3Figure 5 PMID:1281617

  8. Malignant Melanoma of the Foot

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    ... page. Please enable Javascript in your browser. Malignant Melanoma of the Foot What Is Malignant Melanoma? Melanoma is a cancer that begins in the ... people of all age groups, even the young. Melanoma in the Foot Melanoma that occurs in the ...

  9. Cutavirus in Cutaneous Malignant Melanoma

    DEFF Research Database (Denmark)

    Mollerup, Sarah; Fridholm, Helena; Vinner, Lasse

    2017-01-01

    A novel human protoparvovirus related to human bufavirus and preliminarily named cutavirus has been discovered. We detected cutavirus in a sample of cutaneous malignant melanoma by using viral enrichment and high-throughput sequencing. The role of cutaviruses in cutaneous cancers remains to be in......A novel human protoparvovirus related to human bufavirus and preliminarily named cutavirus has been discovered. We detected cutavirus in a sample of cutaneous malignant melanoma by using viral enrichment and high-throughput sequencing. The role of cutaviruses in cutaneous cancers remains...

  10. [Establishment of nude mice liver metastatic model of human primary malignant melanoma of the small intestine].

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    Tuo, Shuai; Zhang, Ning; Liu, Qiu-Zhen

    2008-07-01

    To provide ideal animal models for exploring pathogenesis and experimental therapy of primary malignant melanoma of the small intestine. The histologically intact primary and liver metastatic fragments derived from surgical specimens of one patient with metastatic malignant melanoma of the small intestine were orthotopically implanted in the small intestinal mucous layer of nude mice. The take rate, invasion and liver metastasis were observed. Morphology (light microscopy, electron microscopy), immunophenotype analysis, flow cytometry and karyotype analysis were applied for the original human tumors and the transplanted tumors. The primary and liver metastatic fragments of malignant melanoma of the small intestine were successfully implanted in nude mice. After continuous passages in nude mice,an orthotopic model of human primary malignant melanoma of the small intestine(from the primary focus)in nude mice (termed HSIM-0501) and a liver metastatic model of human primary malignant melanoma of the small intestine (from the liver metastatic focus) in nude mice (termed HSIM-0502) were established. Histological examination of transplanted tumors revealed high-grade melanoma. S-100 protein and HMB45 were positive. Massive melanin granules and melanin complex were seen in cytoplasm of tumor cells.Chromosomal modal number was between 55 and 59. DNA index (DI) was 1.49-1.61, representing heteroploid. HSIM-0501 and HSIM-0502 were maintained for 25 and 27 passages in nude mice respectively. Three hundred and seventeen nude mice were used for transplantation. Both the take rate after transplantation and resuscitation rate of liquid nitrogen cryopreservation were 100%. HSIM-0501 exhibited 46.2% liver metastasis and 36.7% lymph node metastases. In HSIM-0502, both liver and lymph node metastases were 100%.The transplanted tumors autonomically and invasively grew in the small intestines of nude mice and hematogenous metastasis, lymph node metastasis and celiac planting metastasis

  11. Anoxia-Induced Up-Regulation of Interleukin-8 in Human Malignant Melanoma

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    Kunz, Manfred; Hartmann, Anke; Flory, Egbert; Toksoy, Atiye; Koczan, Dirk; Thiesen, Hans-Jürgen; Mukaida, Nafoumi; Neumann, Manfred; Rapp, Ulf Rüdiger; Bröcker, Eva-Bettina; Gillitzer, Reinhard

    1999-01-01

    Besides its proinflammatory properties, interleukin-8 (IL-8) has been suggested as an important promoter for melanoma growth. To study the role of IL-8 in melanoma biology, we determined the in vivo expression of IL-8 mRNA by in situ hybridization in primary melanoma lesions and metastases. High levels of melanoma cell-associated IL-8-specific transcripts were exclusively detected in close vicinity of necrotic/hypoxic areas of melanoma metastases, whereas both in primary melanomas and in non-necrotic metastases IL-8 expression was low or absent. To analyze further the up-regulation of IL-8 mRNA expression in necrotic/hypoxic tumor areas, human melanoma cell lines of different aggressiveness exposed to severe hypoxic stress (anoxia) were used as an in vitro model. Anoxia induced IL-8 mRNA and protein expression in the highly aggressive/metastatic cell lines MV3 and BLM but not in the low aggressive cell lines IF6 and 530. As shown by IL-8 promoter-dependent reporter gene analysis and mRNA stability assays, elevated mRNA levels in melanoma cells were due to both enhanced transcriptional activation and enhanced IL-8 mRNA stability. Interestingly, transcriptional activation was abolished by mutations in the AP-1 and the NF-κB-like binding motifs, indicating that both sites are critical for IL-8 induction. Concomitantly, anoxia induced an enhanced binding activity of AP-1 and NF-κB transcription factors only in the highly aggressive cells. From our in vitro and in vivo data we suggest that anoxia-induced regulation of IL-8 might be a characteristic feature of aggressive tumor cells, thus indicating that IL-8 might play a critical role for tumor progression in human malignant melanoma. PMID:10487833

  12. [Pregnancy and malignant melanoma].

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    Pankova, T; Stoikov, S; Nikolova, M

    2010-01-01

    The authors review on a rare pregnancy accompanying disease--Melanoma malignum. After the definition are presented the epidemiology, etiology, pathogenesis, pathomorphology, clinical forms, diagnosis, differential diagnosis, treatment and prevention. Described are the effects of the pregnancy on this malignant disease and the impact of it during the pregnancy.

  13. Proliferation kinetics of a human malignant melanoma serially grown in nude mice

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    Spang-Thomsen, M; Vindeløv, L L

    1984-01-01

    The technique of labelled mitoses and flow cytometric DNA analysis were used to determine the proliferation kinetics of a human malignant melanoma grown in nude mice. The effect of tumour volume and of long-term serial transplantation on the kinetic parameters was investigated. The results showed...... that the cell loss factor, which was the dominant factor in the growth of this melanoma, increased from 52 to 69% with increasing tumour size, whereas the calculated growth fraction showed no systematic changes. The cell generation time increased from 34 to 44 hr with tumour size, mainly due to a prolongation...

  14. Simulants of malignant melanoma

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    Gérald E. Piérard

    2015-08-01

    Full Text Available During the recent period, dermoscopy has yielded improvement in the early disclosure of various atypical melanocytic neoplasms (AMN of the skin. Beyond this clinical procedure, AMN histopathology remains mandatory for establishing their precise diagnosis. Of note, panels of experts in AMN merely report moderate agreement in various puzzling cases. Divergences in opinion and misdiagnosis are likely increased when histopathological criteria are not fine-tuned and when facing a diversity of AMN types. Furthermore, some AMN have been differently named in the literature including atypical Spitz tumor, metastasizing Spitz tumor, borderline and intermediate melanocytic tumor, malignant Spitz nevus, pigmented epithelioid melanocytoma or animal-type melanoma. Some acronyms have been further suggested such as MELTUMP (after melanocytic tumor of uncertain malignant potential and STUMP (after Spitzoid melanocytic tumor of uncertain malignant potential. In this review, such AMN at the exclusion of cutaneous malignant melanoma (MM variants, are grouped under the tentative broad heading skin melanocytoma. Such set of AMN frequently follows an indolent course, although they exhibit atypical and sometimes worrisome patterns or cytological atypia. Rare cases of skin melanocytomas progress to loco regional clusters of lesions (agminate melanocytomas, and even to regional lymph nodes. At times, the distinction between a skin melanocytoma and MM remains puzzling. However, multipronged immunohistochemistry and emerging molecular biology help profiling any malignancy risk if present.

  15. Human telomerase RNA component expression in Spitz nevi, common melanocytic nevi, and malignant melanomas.

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    Guttman-Yassky, Emma; Bergman, Reuven; Manov, Lena; Sprecher, Eli; Shaefer, Yan; Kerner, Hedviga

    2002-07-01

    Telomerase is a ribonucleoprotein DNA polymerase that is capable of synthesizing telomeres onto the ends of chromosomes. The cumulative loss of telomerase activity is believed to be associated with cell senescence. Telomerase activity has been shown to be higher in malignant melanomas than in common melanocytic nevi. The aim of the present study was to elucidate the pattern of expression of the human telomerase RNA (hTER) component in routinely processed specimens of Spitz nevi, malignant melanomas, and ordinary melanocytic nevi. Ten specimens of each type of tumor were studied, using an in situ hybridization technique. All three types of tumors demonstrated moderate to high intensities of hTER expression, usually in more than half of the tumor cells, and the majority of the studied lesions in each group did not show stratification of staining. The hTER component was also detected in the epidermis, sweat glands, and pilosebaceous units. hTER levels do not necessarily correlate with the level of telomerase activity, and the level and pattern of hTER expression are not useful as an adjunct to the histologic differential diagnosis of Spitz nevi from melanocytic nevi and malignant melanomas.

  16. RARE METASTASES OF MALIGNANT MELANOMA

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    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. Immunohistochemical expression of the glucose transporters Glut-1 and Glut-3 in human malignant melanomas and benign melanocytic lesions

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    Parente Paola

    2008-09-01

    Full Text Available Abstract Background Reported data indicate that cancer cells have increased rates of glucose metabolism, as determined by 18FDG-PET imaging in patients with malignancies. The results of many studies have demonstrated that the expression of glucose transporters, especially Glut-1, is increased in a variety of malignancies. This study was undertaken to assess the differential expression of Glut-1 and Glut-3 by benign and malignant melanocytic lesions. Methods Immunohistochemical staining for Glut-1 and Glut-3 was performed on paraffin-embedded tissue sections prepared from melanocytic nevi (12 cases, Spitz nevi (12 cases and primary cutaneous malignant melanomas (20 cases. Results We observed immunoreactivity for Glut-1 in all melanocytic nevi, 9 of the 12 Spitz nevi and in 9 of the 20 malignant melanomas, whereas Glut-3 was expressed in all the melanocytic lesions, both benign and malignant. Conclusion These findings indicate that the glucose transporters Glut-1 and Glut-3 play a role in the glucose metabolism of melanocytic cells. Glut-1 was present in the majority of benign nevi, whereas its expression was downregulated in 55% of malignant melanomas. Our results suggest that glucose transporter Glut-1 expression can significantly discriminate between human malignant melanoma and benign melanocytic nevi, and support the idea that additional mechanisms other than Glut-1 may contribute to glucose uptake in melanomas.

  18. Toxicogenomics of A375 human malignant melanoma cells treated with arbutin.

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    Cheng, Sun-Long; Liu, Rosa Huang; Sheu, Jin-Nan; Chen, Shui-Tein; Sinchaikul, Supachok; Tsay, Gregory Jiazer

    2007-01-01

    Although arbutin is a natural product and widely used as an ingredient in skin care products, its effect on the gene expression level of human skin with malignant melanoma cells is rarely reported. We aim to investigate the genotoxic effect of arbutin on the differential gene expression profiling in A375 human malignant melanoma cells through its effect on tumorigenesis and related side-effect. The DNA microarray analysis provided the differential gene expression pattern of arbutin-treated A375 cells with the significant changes of 324 differentially expressed genes, containing 88 up-regulated genes and 236 down-regulated genes. The gene ontology of differentially expressed genes was classified as belonging to cellular component, molecular function and biological process. In addition, four down-regulated genes of AKT1, CLECSF7, FGFR3, and LRP6 served as candidate genes and correlated to suppress the biological processes in the cell cycle of cancer progression and in the downstream signaling pathways of malignancy of melanocytic tumorigenesis.

  19. [Malignant melanoma : Current status].

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    Winkler, J K; Buder-Bakhaya, K; Dimitrakopoulou-Strauss, A; Enk, A; Hassel, J C

    2017-10-01

    The incidence of malignant melanoma is continuously increasing. The prognosis of metastatic disease is still limited. Until a few years ago palliative chemotherapy with a limited response rate was the standard treatment for metastatic melanoma. Immunotherapy and targeted therapy provide new treatment options. Immune checkpoint inhibitors have significantly improved the prognosis. Regional lymph node sonography, computed tomography (CT) of the neck, chest and abdomen and brain magnetic resonance imaging (MRI) are routinely used. As an alternative to CT scans 18 F fluorodeoxyglucose positron emission tomography (FDG-PET) may be used. Immunotherapy provides the chance of long-term disease control in metastatic melanoma. Ipilimumab may provide long-term tumor control in approximately 20% of patients. Median overall survival of approximately 2 years is achieved during therapy with anti-programmed cell death (PD) 1 antibodies. For combined therapy of ipilimumab and nivolumab a response rate of almost 60% is achieved and 2‑year survival is also approximately 60%. The range of immune-mediated side effects demands particular consideration. For response evaluation immune-related response criteria were defined. Furthermore, immunotherapeutic approaches, such as talimogene laherparepvec (T-VEC), which is a modified herpes virus can be used for intralesional injection. An individual definition of the appropriate therapy for each patient is of particular importance. In the context of modern therapy regimens close patient monitoring is crucial.

  20. Withania somnifera Root Extract Has Potent Cytotoxic Effect against Human Malignant Melanoma Cells.

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    Babli Halder

    Full Text Available In Ayurveda, Withania somnifera is commonly known as Ashwagandha, its roots are specifically used in medicinal and clinical applications. It possesses numerous therapeutic actions which include anti-inflammatory, sedative, hypnotic and narcotic. Extracts from this plant have been reported for its anticancer properties. In this study we evaluated for the first time, the cytotoxic effect of Withania root extract on human malignant melanoma A375 cells. The crude extract of Withania was tested for cytotoxicity against A375 cells by MTT assay. Cell morphology of treated A375 cells was visualized through phase contrast as well as fluorescence microscopy. Agarose gel electrophoresis was used to check DNA fragmentation of the crude extract treated cells. Crude extract of Withania root has the potency to reduce viable cell count in dose as well as time dependent manner. Morphological change of the A375 cells was also observed in treated groups in comparison to untreated or vehicle treated control. Apoptotic body and nuclear blebbing were observed in DAPI stained treated cells under fluorescence microscope. A ladder of fragmented DNA was noticed in treated cells. Thus it might be said that the crude water extract of Withania somnifera has potent cytotoxic effect on human malignant melanoma A375 cells.

  1. Withania somnifera Root Extract Has Potent Cytotoxic Effect against Human Malignant Melanoma Cells.

    Science.gov (United States)

    Halder, Babli; Singh, Shruti; Thakur, Suman S

    2015-01-01

    In Ayurveda, Withania somnifera is commonly known as Ashwagandha, its roots are specifically used in medicinal and clinical applications. It possesses numerous therapeutic actions which include anti-inflammatory, sedative, hypnotic and narcotic. Extracts from this plant have been reported for its anticancer properties. In this study we evaluated for the first time, the cytotoxic effect of Withania root extract on human malignant melanoma A375 cells. The crude extract of Withania was tested for cytotoxicity against A375 cells by MTT assay. Cell morphology of treated A375 cells was visualized through phase contrast as well as fluorescence microscopy. Agarose gel electrophoresis was used to check DNA fragmentation of the crude extract treated cells. Crude extract of Withania root has the potency to reduce viable cell count in dose as well as time dependent manner. Morphological change of the A375 cells was also observed in treated groups in comparison to untreated or vehicle treated control. Apoptotic body and nuclear blebbing were observed in DAPI stained treated cells under fluorescence microscope. A ladder of fragmented DNA was noticed in treated cells. Thus it might be said that the crude water extract of Withania somnifera has potent cytotoxic effect on human malignant melanoma A375 cells.

  2. c-RET molecule in malignant melanoma from oncogenic RET-carrying transgenic mice and human cell lines.

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    Yuichiro Ohshima

    Full Text Available Malignant melanoma is one of the most aggressive cancers and its incidence worldwide has been increasing at a greater rate than that of any other cancer. We previously reported that constitutively activated RFP-RET-carrying transgenic mice (RET-mice spontaneously develop malignant melanoma. In this study, we showed that expression levels of intrinsic c-Ret, glial cell line-derived neurotrophic factor (Gdnf and Gdnf receptor alpha 1 (Gfra1 transcripts in malignant melanomas from RET-transgenic mice were significantly upregulated compared with those in benign melanocytic tumors. These results suggest that not only introduced oncogenic RET but also intrinsic c-Ret/Gdnf are involved in murine melanomagenesis in RET-mice. We then showed that c-RET and GDNF transcript expression levels in human malignant melanoma cell lines (HM3KO and MNT-1 were higher than those in primary cultured normal human epithelial melanocytes (NHEM, while GFRa1 transcript expression levels were comparable among NHEM, HM3KO and MNT-1. We next showed c-RET and GFRa1 protein expression in HM3KO cells and GDNF-mediated increased levels of their phosphorylated c-RET tyrosine kinase and signal transduction molecules (ERK and AKT sited potentially downstream of c-RET. Taken together with the finding of augmented proliferation of HM3KO cells after GDNF stimulation, our results suggest that GDNF-mediated c-RET kinase activation is associated with the pathogenesis of malignant melanoma.

  3. Metastatic malignant melanoma affecting stomach

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    Jamal Eivazi-Ziaei

    2014-01-01

    Full Text Available Malignant melanoma has been reported to affect all organs of the human body with the metastasis. Stomach metastases are quite rare in cases of the most commonly reported primaries including, melanoma and breast, and lung carcinomas. This report involves, a 56-year-old man suffering from melanoma of the lower extremity that developed into gastric, pulmonary, and brain metastases. The patient who experienced epigastric pain with suspicious melanoma was referred to undergo endoscopy. A black and white ulcer with dimensions of 1 × 1.5 cm and a mass of 1 × 2 cm mass were found at D1 and lesser curvature. Physical examination revealed a 2 × 3 cm black lesion at his right heel. Pathologic examination provided multiple pieces of creamy soft-tissue measuring 0.3 × 0.2 × 0.1 cm showing pigmented tumor cells in lamina propria. Staining biopsy samples with anti-HMB-45 and Fontana demonstrated a higher degree of positivity in tumor cells. The patient was admitted to the hospital, but unfortunately his general conditions were deteriorated and he developed convulsion and deceased four days after admission.

  4. Nivolumab: Immunotherapy in Malignant Melanoma.

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    Bayless, Heather; Schneider, Susan

    2015-08-01

    Although patients diagnosed with melanoma that is confined to the skin have a five-year survival rate of 98%, this number drops to 16% with widely metastatic disease. Melanoma rates have been steadily increasing since the 1970s, but cytotoxic chemotherapy generally prolongs survival by about four months. Nivolumab is an effective immunotherapy agent. This article discusses the use of nivolumab for metastatic melanoma. Clinical trial and early postmarketing data were reviewed. In clinical trials, patients with advanced melanoma experienced partial sustained responses to nivolumab, a new targeted immunotherapy agent, for more than one year. Nivolumab helps the immune system mobilize lymphocytes that have been inactivated by melanoma cells, enhancing the body's ability to recognize the cancer as abnormal. Compared to conventional chemotherapy, nivolumab has been shown to greatly improve survival in widespread, inoperable malignant melanoma. Oncology nurses will administer, monitor, and educate patients about nivolumab.

  5. Oncolysis of malignant human melanoma tumors by Coxsackieviruses A13, A15 and A18

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    Barry Richard D

    2011-01-01

    Full Text Available Abstract Many RNA viruses are displaying great promise in the field of oncolytic virotherapy. Previously, we reported that the picornavirus Coxsackievirus A21 (CVA21 possessed potent oncolytic activity against cultured malignant melanoma cells and melanoma xenografts in mice. In the present study, we demonstrate that three additional Group A Coxsackieviruses; Coxsackievirus A13 (CVA13, Coxsackievirus A15 (CVA15 and Coxsackievirus A18 (CVA18, also have similar oncolytic activity against malignant melanoma. Each of the viruses grew quickly to high titers in cancer cells expressing ICAM-1 and intratumoral injection of preformed subcutaneous SK-Mel-28 xenografts in mice with CVA13, CVA15 and CVA18 resulted in significant tumor volume reduction. As preexisting immunity could potentially hinder oncolytic virotherapy, sera from stage IV melanoma patients and normal controls were tested for levels of protective antibody against the panel of oncolytic Coxsackieviruses. Serum neutralization assays revealed that 3 of 21 subjects possessed low levels of anti-CVA21 antibodies, while protective antibodies for CVA13, CVA15 and CVA18 were not detected in any sample. Serum from individuals who were seropositive for CVA21 failed to exhibit cross-neutralization of CVA13, CVA15 and CVA18. From these studies it can be concluded that the administration of CVA13, CVA15 or CVA18 could be employed as a potential multivalent oncolytic therapy against malignant melanoma.

  6. Malignant Melanoma and Melanocortin 1 Receptor

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    Rosenkranz, A. A.; Slastnikova, T. A.; Durymanov, M. O.; Sobolev, A. S.

    2013-01-01

    The conventional chemotherapeutic treatment of malignant melanoma still remains poorly efficient in most cases. Thus the use of specific features of these tumors for development of new therapeutic modalities is highly needed. Melanocortin receptor-1 (MC1R) overexpression on the cell surface of the vast majority of human melanomas, making MC1R a valuable marker of these tumors, is one of these features. Naturally, MC1R plays a key role in skin protection against damaging ultraviolet radiation ...

  7. 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

    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...

  8. Selective growth inhibition of a human malignant melanoma cell line by sesame oil in vitro.

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    Smith, D E; Salerno, J W

    1992-06-01

    Ayurveda, an ancient and comprehensive system of natural medicine, recommends regular topical application to the skin of sesame oil, above all other oils, as a health-promoting procedure. We examined the effect of sesame oil and several other vegetable oils and their major component fatty acids on the proliferation rate of human normal and malignant melanocytes growing at similar rates in serum-free media. We found that sesame and safflower oils, both of which contain large amounts of linoleate in triglyceride form, selectively inhibited malignant melanoma growth over normal melanocytes whereas coconut, olive and mineral oils, which contain little or no linoleate as triglyceride, did not. These oils were tested at a range of 10-300 micrograms/ml. We found that of the fatty acids tested, only linoleic acid was selectively inhibitory while palmitic and oleic were not. These fatty acids were tested in the range of 3-100 micrograms/ml. These results suggest that certain vegetable oils rich in linoleic acid, such as the sesame oil, recommended for topical use by Ayurveda, may contain selective antineoplastic properties which are similar to those demonstrated for essential polyunsaturated fatty acids and their metabolites. This suggests that whole vegetable oils may have potential clinical usefulness.

  9. Anoxia-induced up-regulation of interleukin-8 in human malignant melanoma. A potential mechanism for high tumor aggressiveness.

    Science.gov (United States)

    Kunz, M; Hartmann, A; Flory, E; Toksoy, A; Koczan, D; Thiesen, H J; Mukaida, N; Neumann, M; Rapp, U R; Bröcker, E B; Gillitzer, R

    1999-09-01

    Besides its proinflammatory properties, interleukin-8 (IL-8) has been suggested as an important promoter for melanoma growth. To study the role of IL-8 in melanoma biology, we determined the in vivo expression of IL-8 mRNA by in situ hybridization in primary melanoma lesions and metastases. High levels of melanoma cell-associated IL-8-specific transcripts were exclusively detected in close vicinity of necrotic/hypoxic areas of melanoma metastases, whereas both in primary melanomas and in non-necrotic metastases IL-8 expression was low or absent. To analyze further the up-regulation of IL-8 mRNA expression in necrotic/hypoxic tumor areas, human melanoma cell lines of different aggressiveness exposed to severe hypoxic stress (anoxia) were used as an in vitro model. Anoxia induced IL-8 mRNA and protein expression in the highly aggressive/metastatic cell lines MV3 and BLM but not in the low aggressive cell lines IF6 and 530. As shown by IL-8 promoter-dependent reporter gene analysis and mRNA stability assays, elevated mRNA levels in melanoma cells were due to both enhanced transcriptional activation and enhanced IL-8 mRNA stability. Interestingly, transcriptional activation was abolished by mutations in the AP-1 and the NF-kappaB-like binding motifs, indicating that both sites are critical for IL-8 induction. Concomitantly, anoxia induced an enhanced binding activity of AP-1 and NF-kappaB transcription factors only in the highly aggressive cells. From our in vitro and in vivo data we suggest that anoxia-induced regulation of IL-8 might be a characteristic feature of aggressive tumor cells, thus indicating that IL-8 might play a critical role for tumor progression in human malignant melanoma.

  10. Malignant melanoma (non-metastatic).

    Science.gov (United States)

    Savage, Philip

    2007-06-01

    The incidence of malignant melanoma has increased over the past 25 years in the UK, but death rates have remained fairly constant. Five-year survival ranges from 20% to 95% depending on disease stage. Risks are greater in white populations and in people with higher numbers of skin naevi. We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of interventions to prevent malignant melanoma? Is there an optimal surgical margin for the primary excision of melanoma? What are the effects of elective lymph node dissection in people with malignant melanoma with clinically uninvolved lymph nodes? What are the effects of sentinel lymph node biopsy in people with malignant melanoma with clinically uninvolved lymph nodes? What are the effects of adjuvant treatment for malignant melanoma? We searched: Medline, Embase, The Cochrane Library and other important databases up to October 2006 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). We found 30 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. In this systematic review we present information relating to the effectiveness and safety of the following interventions: adjuvant vaccines; elective lymph node dissection; low-, intermediate-, and high-dose adjuvant interferon alfa; sentinel lymph node biopsy; suncreens; surveillance for early recurrence; and wide excisions.

  11. Blood supply to human malignant melanoma xenografts in the mouse dorsal window chamber : Abstract

    OpenAIRE

    Øye, Kathrine Sørestrand

    2006-01-01

    The effectiveness of non-surgical treatments is depending on the oxygenation status of the tumor. The oxygenation status is determined in part by whether the bloodsupply is arterial or venous in origin, if the blood is distributed homogenously troughout the tumornetwork, and if there is fluctuations in the bloodstream. We have looked at some of these parameters for the malignant melanoma xenographt, using the mouse dorsal window chamber and a fluorecent cell line. We have also developed a tec...

  12. Proteomics analysis of A375 human malignant melanoma cells in response to arbutin treatment.

    Science.gov (United States)

    Nawarak, Jiraporn; Huang-Liu, Rosa; Kao, Shao-Hsuan; Liao, Hsien-Hua; Sinchaikul, Supachok; Chen, Shui-Tein; Cheng, Sun-Long

    2009-02-01

    Although the toxicogenomics of A375 human malignant melanoma cells treated with arbutin have been elucidated using DNA microarray, the proteomics of the cellular response to this compound are still poorly understood. In this study, we performed proteomic analyses to investigate the anticancer effect of arbutin on the protein expression profile in A375 cells. After treatment with arbutin (8 microg/ml) for 24, 48 and 72 h, the proteomic profiles of control and arbutin-treated A375 cells were compared, and 26 differentially expressed proteins (7 upregulated and 19 downregulated proteins) were identified by MALDI-Q-TOF MS and MS/MS. Among these proteins, 13 isoforms of six identical proteins were observed. Bioinformatic tools were used to search for protein function and to predict protein interactions. The interaction network of 14 differentially expressed proteins was found to be correlated with the downstream regulation of p53 tumor suppressor and cell apoptosis. In addition, three upregulated proteins (14-3-3G, VDAC-1 and p53) and five downregulated proteins (ENPL, ENOA, IMDH2, PRDX1 and VIME) in arbutin-treated A375 cells were validated by RT-PCR analysis. These proteins were found to play important roles in the suppression of cancer development.

  13. Human malignant melanoma-derived progestagen-associated endometrial protein immunosuppresses T lymphocytes in vitro.

    Directory of Open Access Journals (Sweden)

    Suping Ren

    Full Text Available Progestagen-associated endometrial protein (PAEP is a glycoprotein of the lipocalin family that acts as a negative regulator of T cell receptor-mediated activation. However, the function of tumor-derived PAEP on the human immune system in the tumor microenvironment is unknown. PAEP is highly expressed in intermediate and thick primary melanomas (Breslow's 2.5mm or greater and metastatic melanomas, correlating with its expression in daughter cell lines established in vitro. The current study investigates the role of melanoma cell-secreted PAEP protein in regulating T cell function. Upon the enrichment of CD3+, CD4+ and CD8+ T cells from human peripheral blood mononuclear cells, each subset was then mixed with either melanoma-derived PAEP protein or PAEP-poor supernatant of gene-silenced tumor cells. IL-2 and IFN-γ secretion of CD4+ T cells significantly decreased with the addition of PAEP-rich supernatant. And the addition of PAEP-positive cell supernatant to activated lymphocytes significantly inhibited lymphocyte proliferation and cytotoxic T cell activity, while increasing lymphocyte apoptosis. Our result suggests that melanoma cell-secreted PAEP protein immunosuppresses the activation, proliferation and cytotoxicity of T lymphocytes, which might partially explain the mechanism of immune tolerance induced by melanoma cells within the tumor microenvironment.

  14. Isolated Pancreatic Metastasis from Malignant Melanoma: Is ...

    African Journals Online (AJOL)

    Pancreatic metastatic tumors are uncommon and account for less than 2% of all pancreatic carcinomas.[1] Renal-cell cancer, colorectal cancer, melanoma and sarcoma are the most common sites of primary malignancy.[1] Around one-third of patients with malignant melanoma develop metastases.[2] Metastatic melanoma ...

  15. Malignant melanoma in a cow

    OpenAIRE

    Mesarić M.; Zadnik T.; Cerne Manca

    2002-01-01

    A malignant melanoma located in the area of the ocular orbit and maxillary sinus of a 2,5 year old, female Brown Swiss cow is described. Complete clinical examination of the cow was performed and blood samples were taken for haematological analyses. According to the unfavorable prognosis, the cow was submitted for necropsy. After necropsy representative sections of tissue were sampled for gross and micro histopathology. Selected sections of tissue were stained with hematoxylin and eosin. Clin...

  16. 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....

  17. Antiproliferative Activity of Double Point Modified Analogs of 1,25-Dihydroxyvitamin D2 Against Human Malignant Melanoma Cell Lines

    Directory of Open Access Journals (Sweden)

    Anna Piotrowska

    2016-01-01

    Full Text Available Vitamin D is a lipid soluble steroid hormone with pleiotropic biological properties, including regulation of cell proliferation, differentiation and apoptosis. As to these desirable anticancer actions, 1,25-dihydroxyvitamins D and analogs have been reported to inhibit the proliferation and to induce differentiation of a wide variety of cancer cell types, including human malignant melanoma. However, there is a need for novel and more efficacious vitamin D analogs, and how best to design such is still an open issue. A series of double point modified (DPM analogs of 1,25-dihydroxyvitamin D2 (1,25(OH2D2 induced differentiation of the vitamin D receptor (VDR positive A375 and VDR negative SK-MEL 188b human malignant melanoma cell lines. Surprisingly, the dose of 1,25(OH2D2 required to inhibit the proliferation of the A375 melanoma cell line by was several fold lower than that required in the case of 1,25(OH2D3. To evaluate the impact of the modification in the side chain (additional 22-hydroxyl and in the A-ring (5,6-trans modification, the regular side-chain of vitamin D2 or D3 was retained in the structure of our analogs. As expected, 5,6-trans modification was advantageous to enhancing the anti-proliferative activity of analogs, but not as a single point modification (SPM. Very unexpectedly, the additional 22-hydroxyl in the side-chain reduced significantly the anti-proliferative activity of both the natural and 5,6-trans series analogs. Finally, an induction of pigmentation in melanoma SK-MEL 188b cells was observed to sensitized cells to the effect of vitamin D analogs.

  18. Changes of proliferation kinetics after X-irradiation of a human malignant melanoma grown in nude mice

    DEFF Research Database (Denmark)

    Spang-Thomsen, M; Vindeløv, L L

    1984-01-01

    A human malignant melanoma grown in nude mice was exposed to single-dose X-irradiation and the effect on the proliferation kinetics was investigated by two methods. Flow cytometric DNA analysis was performed on tumour tissue obtained by sequential fine-needle aspirations after the treatment...... to monitor the initial cell cycle distribution changes. The technique of labelled mitoses was used to examine the kinetics of the tumours during regrowth. The results showed that the treatment initially induced a partial synchronization of small fractions of cells accumulated in the G2 phase of the cell...

  19. 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

  20. Theranostics of Malignant Melanoma with 64CuCl2

    OpenAIRE

    Qin, Chunxia; Liu, Hongguang; Chen, Kai; Hu, Xiang; Ma, Xiaowei; Lan, Xiaoli; Zhang, Yongxue; Cheng, Zhen

    2014-01-01

    Human copper transporter 1 (CTR1) is overexpressed in a variety of cancers. This study aimed to evaluate the use of 64CuCI2 as a theranostic agent for PET and radionuclide therapy of malignant melanoma.

  1. Malignant melanoma (non-metastatic)

    OpenAIRE

    Savage, Philip

    2007-01-01

    The incidence of malignant melanoma has increased over the past 25 years in the UK, but death rates have remained fairly constant. Five year survival ranges from 20% to 95% depending on disease stage. Risks are greater in white populations and in people with higher numbers of skin naevi.Prognosis depends on depth of tumour, ulceration, and number of lymph nodes involved. Survival may be better in women compared with men, and for lesions on the limbs compared with the trunk.Lesions can recu...

  2. Melanocytoma-like melanoma may be the missing link between benign and malignant uveal melanocytic lesions in humans and dogs: a comparative study.

    Science.gov (United States)

    Zoroquiain, Pablo; Mayo-Goldberg, Erin; Alghamdi, Sarah; Alhumaid, Sulaiman; Perlmann, Eduardo; Barros, Paulo; Mayo, Nancy; Burnier, Miguel N

    2016-12-01

    The cutoff presented in the current classification of canine melanocytic lesions by Wilcock and Pfeiffer is based on the clinical outcome rather than morphological concepts. Classification of tumors based on morphology or molecular signatures is the key to identifying new therapies or prognostic factors. Therefore, the aim of this study was to analyze morphological findings in canine melanocytic lesions based on classic malignant morphologic principles of neoplasia and to compare these features with human uveal melanoma (HUM) samples. In total, 64 canine and 111 human morphologically malignant melanocytic lesions were classified into two groups (melanocytoma-like or classic melanoma) based on the presence or absence of M cells, respectively. Histopathological characteristics were compared between the two groups using the χ-test, t-test, and multivariate discriminant analysis. Among the 64 canine tumors, 28 (43.7%) were classic and 36 (56.3%) were melanocytoma-like melanomas. Smaller tumor size, a higher degree of pigmentation, and lower mitotic activity distinguished melanocytoma-like from classic tumors with an accuracy of 100% for melanocytoma-like lesions. From the human series, only one case showed melanocytoma-like features and had a low risk for metastasis characteristics. Canine uveal melanoma showed a morphological spectrum with features similar to the HUM counterpart (classic melanoma) and overlapped features between uveal melanoma and melanocytoma (melanocytoma-like melanoma). Recognition that the subgroup of melanocytoma-like melanoma may represent the missing link between benign and malignant lesions could help explain the progression of uveal melanoma in dogs; these findings can potentially be translated to HUM.

  3. Wnt interaction and extracellular release of prominin-1/CD133 in human malignant melanoma cells

    Energy Technology Data Exchange (ETDEWEB)

    Rappa, Germana [Cancer Research Program, Roseman University of Health Sciences, 10530 Discovery Drive. Las Vegas, NV 89135 (United States); College of Pharmacy, Roseman University of Health Sciences, Henderson, NV 89104 (United States); Mercapide, Javier; Anzanello, Fabio [Cancer Research Program, Roseman University of Health Sciences, 10530 Discovery Drive. Las Vegas, NV 89135 (United States); Le, Thuc T. [Nevada Cancer Institute, Las Vegas, NV 89135 (United States); Johlfs, Mary G. [Cancer Research Program, Roseman University of Health Sciences, 10530 Discovery Drive. Las Vegas, NV 89135 (United States); Center for Diabetes and Obesity Prevention, Treatment, Research and Education, Roseman University of Health Sciences, Henderson, NV 89104 (United States); Fiscus, Ronald R. [Cancer Research Program, Roseman University of Health Sciences, 10530 Discovery Drive. Las Vegas, NV 89135 (United States); College of Pharmacy, Roseman University of Health Sciences, Henderson, NV 89104 (United States); Center for Diabetes and Obesity Prevention, Treatment, Research and Education, Roseman University of Health Sciences, Henderson, NV 89104 (United States); Wilsch-Bräuninger, Michaela [Max-Planck-Institute of Molecular Cell Biology and Genetics, Pfotenhauerstr. 108, 01307 Dresden (Germany); Corbeil, Denis [Tissue Engineering Laboratories (BIOTEC) and DFG Research Center and Cluster of Excellence for Regenerative Therapies Dresden (CRTD), Technische Universität Dresden, Tatzberg 47–49, 01307 Dresden, Germany Technische Universitat Dresden, Dresden (Germany); Lorico, Aurelio, E-mail: alorico@roseman.edu [Cancer Research Program, Roseman University of Health Sciences, 10530 Discovery Drive. Las Vegas, NV 89135 (United States); College of Pharmacy, Roseman University of Health Sciences, Henderson, NV 89104 (United States)

    2013-04-01

    Prominin-1 (CD133) is the first identified gene of a novel class of pentaspan membrane glycoproteins. It is expressed by various epithelial and non-epithelial cells, and notably by stem and cancer stem cells. In non-cancerous cells such as neuro-epithelial and hematopoietic stem cells, prominin-1 is selectively concentrated in plasma membrane protrusions, and released into the extracellular milieu in association with small vesicles. Previously, we demonstrated that prominin-1 contributes to melanoma cells pro-metastatic properties and suggested that it may constitute a molecular target to prevent prominin-1-expressing melanomas from colonizing and growing in lymph nodes and distant organs. Here, we report that three distinct pools of prominin-1 co-exist in cultures of human FEMX-I metastatic melanoma. Morphologically, in addition to the plasma membrane localization, prominin-1 is found within the intracellular compartments, (e.g., Golgi apparatus) and in association with extracellular membrane vesicles. The latter prominin-1–positive structures appeared in three sizes (small, ≤40 nm; intermediates ∼40–80 nm, and large, >80 nm). Functionally, the down-regulation of prominin-1 in FEMX-I cells resulted in a significant reduction of number of lipid droplets as observed by coherent anti-Stokes Raman scattering image analysis and Oil red O staining, and surprisingly in a decrease in the nuclear localization of beta-catenin, a surrogate marker of Wnt activation. Moreover, the T-cell factor/lymphoid enhancer factor (TCF/LEF) promoter activity was 2 to 4 times higher in parental than in prominin-1-knockdown cells. Collectively, our results point to Wnt signaling and/or release of prominin-1–containing membrane vesicles as mediators of the pro-metastatic activity of prominin-1 in FEMX-I melanoma. - Highlights: ► First report of release of prominin-1–containing microvesicles from cancer cells. ► Pro-metastatic role of prominin-1–containing microvesicles in

  4. The common Scandinavian human leucocyte antigen ancestral haplotype 62.1 as prognostic factor in patients with advanced malignant melanoma.

    Science.gov (United States)

    Helgadottir, Hildur; Andersson, Emilia; Villabona, Lisa; Kanter, Lena; van der Zanden, Henk; Haasnoot, Geert W; Seliger, Barbara; Bergfeldt, Kjell; Hansson, Johan; Ragnarsson-Olding, Boel; Kiessling, Rolf; Masucci, Giuseppe Valentino

    2009-10-01

    We have previously demonstrated an association of the human leukocyte antigen (HLA), HLA-A2 allele with ovarian and prostate cancer mortality as well as a segregation of the ancestral HLA haplotype (AHH) 62.1 [(A2) B15 Cw3 DRB1*04] in patients with stage III-IV serous ovarian cancer. The objective of the present study was to determine the role of the HLA phenotype on the prognosis in stage III-IV malignant melanoma patients. A cohort of metastatic malignant melanoma patients (n = 91), in stage III (n = 26) or IV (n = 65) were analysed for HLA-A, -B, -Cw and -DRB1 types by PCR/sequence-specific primer method. The frequencies of HLA alleles in the patients were compared to that of healthy Swedish bone marrow donors. The effect of HLA types on prognosis was defined by Kaplan-Meier and Cox analysis. The presence of the AHH 62.1 in clinical stage IV patients was significantly and independently associated with the worst survival rate recorded from the appearance of metastasis (HR = 2.14; CI = 1.02-4.4; P = 0.04). In contrast, the period from the primary diagnosis to metastasis was the longest in patients with this haplotype (HR = 0.40; CI = 0.17-0.90; P = 0.02). Melanoma patients in our cohort with 62.1 AHH which is associated with autoimmune diseases have an initial strong anti-tumour control with longer metastasis-free period. These patients have rapid progression after the appearance of metastasis, responding poorly to chemo- or/and immunotherapy. This apparently paradoxical clinical process could be due to the interplay between tumour clones escape and immune surveillance ending up with a rapid disease progression.

  5. Thigmotropism of Malignant Melanoma Cells

    Directory of Open Access Journals (Sweden)

    Pascale Quatresooz

    2012-01-01

    Full Text Available During malignant melanoma (MM progression including incipient metastasis, neoplastic cells follow some specific migration paths inside the skin. In particular, they progress along the dermoepidermal basement membrane, the hair follicles, the sweat gland apparatus, nerves, and the near perivascular space. These features evoke the thigmotropism phenomenon defined as a contact-sensing growth of cells. This process is likely connected to modulation in cell tensegrity (control of the cell shape. These specifically located paucicellular aggregates of MM cells do not appear to be involved in the tumorigenic growth phase, but rather they participate in the so-called “accretive” growth model. These MM cell collections are often part of the primary neoplasm, but they may, however, correspond to MM micrometastases and predict further local overt metastasis spread.

  6. primary malignant amelanotic melanoma arising from a vitiligo patch ...

    African Journals Online (AJOL)

    2014-05-05

    May 5, 2014 ... nevus, achromic patches on melanoma scars, depigmentation of injection site after immunotherapy and depigmentation associated with regressing malignant melanoma. The association of vitiligo with regressing melanoma has been widely reported in literature, however primary melanoma presenting.

  7. [Molecular classification and markers of malignant melanoma].

    Science.gov (United States)

    Tímár, József; Hársing, Judit; Somlai, Beáta

    2013-06-01

    Pathological classification of malignant melanoma did not change in the past decade, it was just completed with UV-induced skin alterations. A new feature, however, is the establishment of molecular classification of melanoma indicating that beside the most frequent genetic alterations (BRAF, NRAS, CKIT mutations) there is a wide variety of rare molecular subclasses. Unfortunately, none of these genetic alterations can be used to discriminate benign lesions from malignant ones. The frequently used "melanoma" markers are mostly melanosomal markers, therefore they are not helpful for this diagnostic purpose either. More recently, novel FISH kits have been developed analyzing characteristic copy number alterations specific for malignant melanoma. Though melanosomal markers are helpful in differencial diagnostics, the presence of normal melanocytes in various tissues (lymph nodes, intestine or brain) requires application of molecular techniques when melanoma metastasis is in question.

  8. Cutaneous Malignant Melanoma in a Cat

    OpenAIRE

    Karakurum, Mehmet Çağrı; Pekcan, Zeynep; Özmen, Özlem

    2009-01-01

    Melanomlar melanosit ve melanoblastların benign veya malign tümörleridir. Malign melanom kedilerde oldukça nadir gözlenen bir tümördür. Bu vaka takdiminde 16 yaşlı bir kedide kutanöz malign melonoma’nın klinik ve histopatolojik bulguları bildirilmiştir. Bu, aynı zamanda, Türkiye’de bir kedide bildirilen ilk kutanöz malign melanoma vakasıdır. Melanomas are neoplasia of melanocytes and melanoblasts which may in benign or malign character. Malign melanoma is typically considered as a rare neo...

  9. Intraoral malignant melanoma | Babburi | Nigerian Medical Journal

    African Journals Online (AJOL)

    Primary oral mucosal melanoma is a rare aggressive neoplasm and accounts for only 0.2‑8% of all reported melanomas. It is a malignant neoplasm of melanocytes that may arise from a benign melanocytic lesion or de novo from melanocytes within normal skin or mucosa. It is considered to be the most deadly and ...

  10. Angiogenic and Metastatic Determinants of Malignant Melanoma

    NARCIS (Netherlands)

    A. Mooppilmadham Das (Asha)

    2015-01-01

    markdownabstractCutaneous melanoma or malignant melanoma of the skin is a highly metastatic disease, with an increasing rate of incidence, poor prognosis and high resistance to therapeutic intervention. Although early diagnosis and surgical resection of the primary lesion could significantly improve

  11. Isolated Pancreatic Metastasis from Malignant Melanoma: Is ...

    African Journals Online (AJOL)

    Isolated pancreatic metastasis from malignant melanoma (IPMMM) is rare because most melanoma patients already have a widespread disease at diagnosis. No adjuvant systemic treatment is known to be effi cient in this setting. Experience with pancreatic resection for IPMMM is limited and controversial. We report here ...

  12. Primary malignant melanoma of aryepiglottic fold | Chhabra | Ghana ...

    African Journals Online (AJOL)

    Background: Primary malignant melanoma rarely arises from noncutaneous tissues that contain melanocytes. Head and neck mucosal melanomas account for 0.7% to 3.8% of all melanomas. Here we report a case of primary malignant melanoma of aryepiglottic fold. Result: Here we reported a case of primary malignant ...

  13. Tattoo pigment mimicking metastatic malignant melanoma.

    Science.gov (United States)

    Anderson, L L; Cardone, J S; McCollough, M L; Grabski, W J

    1996-01-01

    The benefits of elective lymph node dissection (ELND) in the treatment of melanoma remain controversial, however, it may be beneficial in some patients. Tattoo pigment from decorative tattoos may migrate to the regional lymph nodes. In patients who develop malignant melanoma and who have been tattooed, this pigment may clinically mimic metastatic disease. We wish to alert clinicians that pigment from tattoos may migrate to the regional lymph nodes. In the unusual instance of a tattooed patient who develops malignant melanoma, when undergoing ELND, surgeons should rely on histologic confirmation of metastatic disease before altering operative plans. ELND for malignant melanoma, in a patient with a history of decorative tattoos that had been removed by dermabrasion, was performed. Black lymph nodes that clinically resembled metastatic disease were identified. Subsequent histologic examination revealed normal lymph node architecture with a heavy collection of black pigment. Mass spectrophotometry showed this pigment to be consistent with tattoo dye. A patient who had undergone dermabrasion for removal of decorative tattoos developed malignant melanoma in the same extremity. Clinically suspicious black lymph nodes were identified during ELND. Histologic examination did not reveal metastatic disease. Additional therapy was not considered intra- or postoperatively even though the clinical suspicion of metastatic disease was high. The patient was not subjected to any unnecessary emotional or physical distress pending histologic confirmation. Tattoo pigment in the lymph nodes may clinically mimic metastatic melanoma. Histologic confirmation of metastatic disease should always be obtained before additional therapy is considered.

  14. Metastatic malignant melanoma of the gastrointestinal tract.

    Science.gov (United States)

    Liang, Kelly V; Sanderson, Schuyler O; Nowakowski, Grzegorz S; Arora, Amindra S

    2006-04-01

    Malignant melanoma is one of the most common malignancies to metastasize to the gastrointestinal (GI) tract. Metastases to the GI tract can present at the time of primary diagnosis or decades later as the first sign of recurrence. Symptoms may include abdominal pain, dysphagia, small bowel obstruction, hematemesis, and melena. We report 2 cases of malignant melanoma metastatic to the GI tract, followed by a review of the literature. The first case is a 72-year-old man who underwent resection of superficial spreading melanoma on his back 13 years previously who presented with dysphagia. A biopsy specimen of a mucosal fold in a gastric fundus noted during endoscopy was taken and revealed metastatic malignant melanoma, which was resected 1 month later. Three weeks later, the patient was found to have an ulcerated jejunal metastatic melanoma mass, which was also resected. The second case is a 63-year-old man with an ocular melanoma involving the chorold of the left eye that had been diagnosed 4 years previously, which had been excised several times, who presented with anorexia, dizziness, and fatigue. He was found to have cerebellar and stomach metastases. He underwent adjuvant radiation therapy, chemotherapy, and surgical resection of the gastric melanoma metastasis. In patients with a history of melanoma, a high index of suspicion for metastasis must be maintained if they present with seemingly unrelated symptoms. Diagnosis requires careful inspection of the mucosa for metastatic lesions and biopsy with special immunohistochemical stains. Management may include surgical resection, chemotherapy, immunotherapy, observation, or enrollment in clinical trials. Prognosis is poor, with a median survival of 4 to 6 months.

  15. Screening for metastatic malignant melanoma of the uvea revisited

    DEFF Research Database (Denmark)

    Eskelin, Sebastian; Pyrhönen, Seppo; Summanen, Paula

    1999-01-01

    ophthalmology, malignant uveal melanoma, metastasis, liver, screening, ultrasonography, X-ray, lactate dehydrogenase, alkaline phosphatase, aminotransferases......ophthalmology, malignant uveal melanoma, metastasis, liver, screening, ultrasonography, X-ray, lactate dehydrogenase, alkaline phosphatase, aminotransferases...

  16. Visual Screening for Malignant Melanoma

    Science.gov (United States)

    Losina, Elena; Walensky, Rochelle P.; Geller, Alan; Beddingfield, Frederick C.; Wolf, Lindsey L.; Gilchrest, Barbara A.; Freedberg, Kenneth A.

    2008-01-01

    Objective To evaluate the cost-effectiveness of various melanoma screening strategies proposed in the United States. Design We developed a computer simulation Markov model to evaluate alternative melanoma screening strategies. Participants Hypothetical cohort of the general population and siblings of patients with melanoma. Intervention We considered the following 4 strategies: background screening only, and screening 1 time, every 2 years, and annually, all beginning at age 50 years. Prevalence, incidence, and mortality data were taken from the Surveillance, Epidemiology, and End Results Program. Sibling risk, recurrence rates, and treatment costs were taken from the literature. Main Outcome Measures Outcomes included life expectancy, quality-adjusted life expectancy, and lifetime costs. Cost-effectiveness ratios were in dollars per quality-adjusted life year ($/QALY) gained. Results In the general population, screening 1 time, every 2 years, and annually saved 1.6, 4.4, and 5.2 QALYs per 1000 persons screened, with incremental cost-effectiveness ratios of $10 100/QALY, $80 700/QALY, and $586 800/QALY, respectively. In siblings of patients with melanoma (relative risk, 2.24 compared with the general population), 1-time, every-2-years, and annual screenings saved 3.6, 9.8, and 11.4 QALYs per 1000 persons screened, with incremental cost-effectiveness ratios of $4000/QALY, $35 500/QALY, and $257 800/QALY, respectively. In higher risk siblings of patients with melanoma (relative risk, 5.56), screening was more cost-effective. Results were most sensitive to screening cost, melanoma progression rate, and specificity of visual screening. Conclusions One-time melanoma screening of the general population older than 50 years is very cost-effective compared with other cancer screening programs in the United States. Screening every 2 years in siblings of patients with melanoma is also cost-effective. PMID:17224538

  17. Molecular testing in malignant melanoma.

    Science.gov (United States)

    Grossmann, Allie H; Grossmann, Kenneth F; Wallander, Michelle L

    2012-06-01

    Molecular testing of cancers to determine therapeutic eligibility is now standard of care and has changed the practice of pathology. Recent advances in the treatment of metastatic melanoma with BRAF and KIT inhibitors have increased the demand for molecular testing in melanoma. Furthermore, rapid progress is being made in determining potential new targets, mechanisms of resistance, and developing additional rationally designed therapies. The likely consequence will be a significant expansion of molecular testing for melanoma to include an array of multiple signaling intermediates. Currently, routine testing is mostly limited to BRAF and KIT. Mutations in these genes generally occur in a distinct group of melanoma subsets though, and with the numerous techniques available for mutation analysis, decisions about testing can be complex. The purpose of this review is to provide an overview of clinically relevant mutations which currently guide systemic therapy in Stage IV melanoma, how these molecular events vary with melanoma subtype and primary site of origin, and practical recommendations for testing. Copyright © 2012 Wiley Periodicals, Inc.

  18. Malignant melanoma at a scientific laboratory

    Energy Technology Data Exchange (ETDEWEB)

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

    1985-11-15

    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.

  19. Ascorbic acid, but not dehydroascorbic acid increases intracellular vitamin C content to decrease Hypoxia Inducible Factor -1 alpha activity and reduce malignant potential in human melanoma.

    Science.gov (United States)

    Fischer, Adam P; Miles, Sarah L

    2017-02-01

    Accumulation of hypoxia inducible factor-1 alpha (HIF-1α) in malignant tissue is known to contribute to oncogenic progression and is inversely associated with patient survival. Ascorbic acid (AA) depletion in malignant tissue may contribute to aberrant normoxic activity of HIF-1α. While AA supplementation has been shown to attenuate HIF-1α function in malignant melanoma, the use of dehydroascorbic acid (DHA) as a therapeutic means to increase intracellular AA and modulate HIF-1α function is yet to be evaluated. Here we compared the ability of AA and DHA to increase intracellular vitamin C content and decrease the malignant potential of human melanoma by reducing the activity of HIF-1α. HIF-1α protein accumulation was evaluated by western blot and transcriptional activity was evaluated by reporter gene assay using a HIF-1 HRE-luciferase plasmid. Protein expressions and subcellular localizations of vitamin C transporters were evaluated by western blot and confocal imaging. Intracellular vitamin C content following AA, ascorbate 2-phosphate (A2P), or DHA supplementation was determined using a vitamin C assay. Malignant potential was accessed using a 3D spheroid Matrigel invasion assay. Data was analyzed by One or Two-way ANOVA with Tukey's multiple comparisons test as appropriate with pascorbic acid as an adjuvant cancer therapy remains under investigated. While AA and A2P were capable of modulating HIF-1α protein accumulation/activity, DHA supplementation resulted in minimal intracellular vitamin C activity with decreased ability to inhibit HIF-1α activity and malignant potential in advanced melanoma. Restoring AA dependent regulation of HIF-1α in malignant cells may prove beneficial in reducing chemotherapy resistance and improving treatment outcomes. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  20. Metastatic Malignant Melanoma of Parotid Gland with a Regressed Primary Tumor

    National Research Council Canada - National Science Library

    Kılıçkaya, M. Mustafa; Aynali, Giray; Ceyhan, Ali Murat; Çiriş, Metin

    2016-01-01

    .... Nevertheless, some malignant melanomas may metastasize and subsequently regress. Therefore, it may not be possible to observe a metastatic malignant melanoma and its primary melanoma simultaneously...

  1. Necrotic and apoptotic cell death of human malignant melanoma cells following photodynamic therapy using an amphiphilic photosensitizer, ATX-S10(Na).

    Science.gov (United States)

    Nagata, Satoshi; Obana, Akira; Gohto, Yuko; Nakajima, Susumu

    2003-01-01

    To investigate the phototoxic effect on and cell death modes of human malignant melanoma cells following photodynamic therapy (PDT) using ATX-S10(Na), an amphiphilic photosensitizer. Cultured human malignant melanoma cells were incubated in a medium containing various concentrations of ATX-S10(Na) and irradiated with a 670 nm wavelength diode laser. Phototoxicity was analyzed by a 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium inner salt (MTS) assay, and cell death modes were investigated by fluorescence microscopy using a Hoechst 33342-propidium iodide double-staining method as well as by static gel electrophoresis. The subcellular localization of ATX-S10(Na) and mitochondrial destabilization following PDT were observed by fluorescence microscopy. Higher phototoxicity was obtained with higher dye and/or laser doses. Most of the dead cells appeared apoptotic with dye and irradiation doses that induced less than 70% cytotoxicity. In contrast, most of them appeared necrotic with doses that induced 99% cytotoxicity. Cells receiving PDT showed disturbances of mitochondrial trans-membrane potential, although the primary site of ATX-S10(Na) accumulation was in lysosomes. ATX-S10(Na) has a phototoxic effect on malignant melanoma cells and, therefore, potential as a photosensitizing agent for PDT designed to kill these cells. Apoptotic pathways may be activated via mitochondrial destabilization following the damage of lysosomes by PDT. Further study, including investigation of therapeutic efficacy in vivo, is warranted. Copyright 2003 Wiley-Liss, Inc.

  2. Complete regression of primary malignant melanoma.

    Science.gov (United States)

    Emanuel, Patrick O; Mannion, Meghan; Phelps, Robert G

    2008-04-01

    Over the years, histopathologic studies to determine the nature and significance of regression in malignant melanoma have yielded different results. At least in part, this most likely reflects differences in the definition of what constitutes regression. Although partial regression is relatively common, complete regression is rare. It has been said that complete regression of a primary lesion is associated with metastatic disease, but the evidence for this is largely anecdotal-the literature contains only case reports and small series. We found 2 cases of complete regression in our dermatopathology database. Metastatic disease was identified in both cases; in 1 case, the suspicion of melanoma was raised on the initial biopsy and subsequent workup revealed lymph node metastasis. These cases illustrate the histologic features of a completely regressed primary melanoma and add credence to the theory that completely regressed melanoma is associated with a poor outcome.

  3. Metastatic malignant melanoma. Successfull treatment with ipilimumab

    NARCIS (Netherlands)

    Jansen, T.J.G.; Bruch-Gerharz, D.; Reifenberger, J.; Schulte, K.W.

    2013-01-01

    A 73-year-old man, in whom 26 years ago a malignant melanoma with cervical lymph node metastases of the right retroauricular region was diagnosed, developed BRAF V600E-negative distant metastases, which progressed during both monochemotherapy and polychemotherapy. Therefore he was started on

  4. Infarcted Tarsal Pyogenic Granuloma Simulating Malignant Melanoma.

    Science.gov (United States)

    Charles, Norman C; Kahn, Jonathan B

    The authors describe a rapidly enlarging, pedunculated brown tarsal lesion in a 34-year-old man with a history of chalazia. Following excision, histopathologic analysis showed the features of a necrotic pyogenic granuloma. This unique case expands the differential diagnosis of conjunctival malignant melanoma.

  5. Metastatic Malignant Melanoma Mimicking Benign Breast Cysts

    OpenAIRE

    Marius Lund-Iversen; Olav Inge Håskjold; Hiep Phuc Dong; Aasmund Berner

    2011-01-01

    Benign cysts are one of the most common mass-occupying lesions of the breast and are often investigated with triple diagnostic trial (clinical examination, radiology, and cytology). Malignant melanoma is one of medicine's imitators, and metastatic disease can mimic cysts. Thorough investigation of any breast mass is essential to clarify its nature.

  6. PRIMARY MALIGNANT MELANOMA OF ARYEPIGLOTTIC FOLD

    African Journals Online (AJOL)

    2015-12-01

    Dec 1, 2015 ... This can be helpful in development of effective adjuvant immunotherapy for the treatment of melano- mas.1,3. Patients with primary malignant melanoma of the lar- ynx usually present with complaints of hoarseness of voice and sore throat. If the size of tumor increases and obstructs the lumen of larynx, ...

  7. TANGO is a tumor suppressor of malignant melanoma.

    Science.gov (United States)

    Arndt, Stephanie; Bosserhoff, Anja K

    2006-12-15

    The TANGO gene was originally identified as a new family member of the melanoma inhibitory activity gene family. The gene codes for a 14 kDa protein of so far unknown function. In our study we revealed that TANGO was downregulated or lost in 9 melanoma cell lines when compared to normal melanocytes and in most of the 8 tumor samples analyzed. The losses were associated with advanced stage of the disease. These results were confirmed in situ by immunohistochemistry on 10 paraffin-embedded sections of human malignant melanoma primary tumors and melanoma skin metastases. A small reduction of TANGO was also seen in different benign and atypical nevi when compared to normal skin. For functional analysis of TANGO we evaluated TANGO re-expressing melanoma cell clones and antisense TANGO cell clones with a complete loss of TANGO. Functional assays with TANGO transfected or treated cell lines revealed that TANGO expression reduces motility, whereas reduction of TANGO enhances migration. Our studies, therefore, indicate that reduction of TANGO expression contributes to tumor progression. These results taken together provide the first indications for a tumor suppressor role of TANGO gene in human malignant melanoma. Copyright 2006 Wiley-Liss, Inc.

  8. Up-regulation of hepatoma-derived growth factor facilitates tumor progression in malignant melanoma [corrected].

    Directory of Open Access Journals (Sweden)

    Han-En Tsai

    Full Text Available Cutaneous malignant melanoma is the fastest increasing malignancy in humans. Hepatoma-derived growth factor (HDGF is a novel growth factor identified from human hepatoma cell line. HDGF overexpression is correlated with poor prognosis in various types of cancer including melanoma. However, the underlying mechanism of HDGF overexpression in developing melanoma remains unclear. In this study, human melanoma cell lines (A375, A2058, MEL-RM and MM200 showed higher levels of HDGF gene expression, whereas human epidermal melanocytes (HEMn expressed less. Exogenous application of HDGF stimulated colony formation and invasion of human melanoma cells. Moreover, HDGF overexpression stimulated the degree of invasion and colony formation of B16-F10 melanoma cells whereas HDGF knockdown exerted opposite effects in vitro. To evaluate the effects of HDGF on tumour growth and metastasis in vivo, syngeneic mouse melanoma and metastatic melanoma models were performed by manipulating the gene expression of HDGF in melanoma cells. It was found that mice injected with HDGF-overexpressing melanoma cells had greater tumour growth and higher metastatic capability. In contrast, mice implanted with HDGF-depleted melanoma cells exhibited reduced tumor burden and lung metastasis. Histological analysis of excised tumors revealed higher degree of cell proliferation and neovascularization in HDGF-overexpressing melanoma. The present study provides evidence that HDGF promotes tumor progression of melanoma and targeting HDGF may constitute a novel strategy for the treatment of melanoma.

  9. Approach to Malign Melanoma in Anorectal Area

    Directory of Open Access Journals (Sweden)

    Huseyin Pulat

    2014-12-01

    Full Text Available Aim: Anorectal malign melanoma comprise 0.2-1 % of all malign melanoma. They are extremely aggressive. Most patients are lost beacuse of incurable systemic illness. In our study, we aim to evaluate the results of surgical and oncological follow-up of our patients that we operated because of anorectal malign melanoma. Material and Method: Our 4 patients operated because of anorectal malign melanoma between October 2008 and April 2013 were analysed. The patients were analysed in terms of demographic datas, complaint and its time, physical examination and imaging findings, treatment procedure, local recurrence or presence of metastasis and follow-up results.Results: Our study group comprised 4 people (2 men and 2 women with the mean age of 64,2 years. The main complaint was rectal bleeding. The avarage complaint duration was 7.5 months. In all patients, anorectal mass was detected after physical examination and imaging studies. Biopsies of the mass were reported to be consistent with malign melanoma. With the further studies, one patient was detected to have metastasis in liver. Abdominoperineal resection was applied to one patient after wide local excision and to three patients during the first aplication. The avarage follow-up time was 19,25 months. The avarage diameter of tumor was 3,9 cm. One patient was applied lymph node dissection because of recurrence in iliac region. The avarage stay time at hospital of the patients who had no postoperative problems was 9,7 days. During follow-up time, three of the patients died because of common metastasis. A patient followed regularly is still continuing his life without illness in his postoperative 22nd month. Discussion: Anorectal malign melanoma is a rare, with a bad prognosis and a late diagnosed entity as it has a similarity with benign illnesses which are mostly seen in anorectal area in terms of clinical symptoma. To correct the prognosis of the illness, the suitable surgery and adjuvant treatment

  10. Biomarkers as Key Contributors in Treating Malignant Melanoma Metastases

    Directory of Open Access Journals (Sweden)

    Camila Ferreira de Souza

    2012-01-01

    Full Text Available Melanoma is a human neurocristopathy associated with developmental defects in the neural crest-derived epidermal melanocytes. At the present time, at least three hypotheses were identified that may explain melanoma aetiology, as follows: (1 a model of linear progression from differentiated melanocytes to metastatic cancer cells (2 a model involving the appearance of melanoma stem-like cells, and (3 an epigenetic progenitor model of cancer. Treating metastatic melanoma is one of the most serious challenges in the 21st century. This is justified because of a subpopulation of cells presenting a remarkable molecular heterogeneity, which is able to explain the drug resistance and the growing mortality rates worldwide. Fortunately, there are now evidences sustaining the importance of genetic, epigenetic, and metabolomic alterations as biomarkers for classification, staging, and better management of melanoma patients. To illustrate some fascinating insights in this field, the genes BRAFV600E and CTLA4 have been recognized as bona fide targets to benefit melanoma patients. Our research attempts to carefully evaluate data from the literature in order to highlight the link between a molecular disease model and the key contribution of biomarkers in treating malignant melanoma metastases.

  11. Ocular metastasis of cutaneous malignant melanoma.

    Science.gov (United States)

    Ullah, Tehseena; Gurwood, Andrew S; Myers, Marc D

    2009-10-01

    Metastatic melanoma to the eye and orbit are rare. Patients at greatest risk often have disseminated metastases in the setting of advanced disease. Because the prognosis for orbital metastatic disease is poor, emphasis must be placed on early detection and prevention. Although cutaneous malignancies include basal cell carcinoma, squamous cell carcinoma, sebaceous cell carcinoma, and malignant melanoma, the majority of cases that result in metastasis, ocular morbidity, and mortality are from sebaceous cell carcinoma and malignant melanoma. A 72-year-old white woman presented emergently with a chief complaint of sudden, painless vision loss in her left eye of 2 weeks' duration. Her best-corrected visual acuities measured 20/30 in the right eye and 20/400 in the left eye with no improvement on refraction. Her systemic medical history was significant for the diagnosis of a cutaneous malignant melanoma. Examination of the left eye found grade II disc edema with all other posterior pole and peripheral structures intact and unremarkable. Magnetic resonance imaging confirmed the diagnosis of metastatic lesions involving structures of the left orbit ultimately causing reduced visual ability. The patient opted to avoid aggressive care and "hope for the best." Denying significant medical intervention, the woman lived in hospice where she died 6 months later. The primary care optometric setting, by the way a patient's visual symptoms present or the appearance of fundus abnormalities, can offer the capability of first detection and referral for the discovery of metastatic lesions. Although orbital metastasis is considered a terminal finding in these cases, timely diagnosis enables, while limited, the best options for management.

  12. [Malignant melanoma (review of 68 cases)].

    Science.gov (United States)

    Sittart, J A; Valente, N Y; Stevale, J N

    1986-01-01

    A clinica pathologic revision was performed about 68 patients with malignant melanoma of the Hospital dos Servidores Publicos do Estado de São Paulo. The authors had checked the data concerning to color, age and sex of the patients, localisation, clinical aspect of the lesions and clinical evolution of the cases. They made comments on the histopathology related to Clark's levels, the depth of tumors (Breslow), solar elastosis and inflammatory infiltrate, in relation with the clinical evolution of the cases.

  13. Metastatic Malignant Melanoma Presenting as an Appendiceal Mucocele

    Directory of Open Access Journals (Sweden)

    A. A. Alduaij

    2011-01-01

    Full Text Available Melanoma metastatic to the appendix is extremely rare. Here we describe a case of a 31-year-old female from Bolivia with a remote history of metastatic malignant melanoma first diagnosed as a cutaneous malignant melanoma ten years prior to this presentation. The patient was being followed for a mucocele which on resection was found to be metastatic melanoma. “Mucocele” is a generic diagnosis that warrants further characterization and treatment.

  14. Novel ZnO:Ag nanocomposites induce significant oxidative stress in human fibroblast malignant melanoma (Ht144 cells

    Directory of Open Access Journals (Sweden)

    Syeda Arooj

    2015-02-01

    Full Text Available The use of photoactive nanoparticles (NPs such as zinc oxide (ZnO and its nanocomposites has become a promising anticancer strategy. However, ZnO has a low photocatalytic decomposition rate and the incorporation of metal ions such as silver (Ag improves their activity. Here different formulations of ZnO:Ag (1, 3, 5, 10, 20 and 30% Ag were synthesized by a simple co-precipitation method and characterized by powder X-ray diffraction, scanning electron microscopy, Rutherford back scattering and diffuse reflectance spectroscopy for their structure, morphology, composition and optical band gap. The NPs were investigated with regard to their different photocatalytic cytotoxic effects in human malignant melanoma (HT144 and normal (HCEC cells. The ZnO:Ag nanocomposites killed cancer cells more efficiently than normal cells under daylight exposure. Nanocomposites having higher Ag content (10, 20 and 30% were more toxic compared to low Ag content (1, 3 and 5%. For HT144, under daylight exposure, the IC50 values were ZnO:Ag (10%: 23.37 μg/mL, ZnO:Ag (20%: 19.95 μg/mL, and ZnO:Ag (30%: 15.78 μg/mL. ZnO:Ag (30% was toxic to HT144 (IC50: 23.34 μg/mL in dark as well. The three nanocomposites were further analyzed with regard to their ability to generate reactive oxygen species (ROS and induce lipid peroxidation. The particles led to an increase in levels of ROS at cytotoxic concentrations, but only HT144 showed strongly induced MDA level. Finally, NPs were investigated for the ROS species they generated in vitro. A highly significant increase of 1O2 in the samples exposed to daylight was observed. Hydroxyl radical species, HO•, were also generated to a lesser extent. Thus, the incorporation of Ag into ZnO NPs significantly improves their photo-oxidation capabilities. ZnO:Ag nanocomposites could provide a new therapeutic option to selectively target cancer cells.

  15. Primary retroperitoneal melanoma presented in a rare extracutaneous site for malignant melanoma

    Directory of Open Access Journals (Sweden)

    Mohamed Alsharedi

    2016-10-01

    Full Text Available Malignant melanoma, as the name implies, is a malignant tumor of melanocytes, found in the skin, eyes, meningeal lining and the mucosal epithelium of the aero-digestive and genitourinary tracts. Malignant melanoma is typically skin malignancy, which rarely presents at extracutaneous site. Here we present a rare case of primary retroperitoneal melanoma and review the findings in comparison with other cases described in literature.

  16. Malignant melanoma clinically masquerading vascular tumor: A diagnostic dilemma

    Directory of Open Access Journals (Sweden)

    Samiksha Pradhan

    2015-01-01

    Full Text Available Malignant melanoma is an invasive neoplasm of the skin, whose incidence is reported to be rising among Indians. We hereby present a unique case of unilateral, multiple, asymptomatic, pigmented, nodular lesions over the lower limb; resembling vascular tumor, revealing itself as malignant melanoma only on histopathology. To the best of our knowledge, such a unique presentation of malignant melanoma has not yet been reported from the Indian subcontinent.

  17. Malignant Melanoma of the Oral Cavity

    Directory of Open Access Journals (Sweden)

    M.S. Hashemi Pour

    2007-03-01

    Full Text Available Oral malignant melanoma (OMM accounts for 5% of all oral malignancies. It is a rare aggressive neoplasm usually found on the hard palate and gingiva. The etiology is unknown, but tobacco and chronic irritation are suggested as probable causative factors.Over 30% of the cases have been reported to arise from pre-existing pigmented lesions.A biopsy is required to establish the diagnosis and the treatment of choice is surgery which may be affected by several factors such as size of the lesion and anatomic location. Despite aggressive resection and adjuvant treatments such as chemotherapy and immunotherapy, the five-year survival rate of this malignancy is poor.

  18. 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...

  19. Geometric cutaneous melanoma: a helpful clinical sign of malignancy?

    Science.gov (United States)

    Morris, Andrew D; Gee, Bruce C; Millard, Leslie G

    2003-08-01

    Malignant melanomas change shape in a random pattern, with ovoid, crescentic, or nodular shapes seen most frequently. We have observed a number of malignant melanomas that have presented with a geometric, angular shape and have noted that pigmented lesions with this configuration are often found to be malignant. We present 20 patients with malignant melanoma whose lesion displayed a geometric, angular shape. Before excision for formal histopathology, all lesions were scored using the seven-point checklist and ABCDE systems and were divided into low-risk or significant risk of melanoma. Five different geometric shapes were observed. Depending on the scoring system employed, 20% to 40% of the geometric melanomas were considered to be of low risk of malignancy. The development of geometrical angular patterns in a malignant melanoma may represent a morphologic growth pattern that can be used as a clinical risk sign. Even apparently benign low-risk lesions with a geometric shape may pose a significant risk of malignant melanoma. By definition, the majority of lesions that are morphologically geometric are symmetrical in shape, which is more in favor of a benign diagnosis. This may increase the likelihood that early cutaneous melanomas with a geometric shape may be missed. Any pigmented lesion with a geometric configuration should raise the clinician's suspicion of malignancy even if considered otherwise to be of low risk by the standard melanoma checklists.

  20. Toward automated detection of malignant melanoma

    Science.gov (United States)

    Huang, Billy; Gareau, Daniel S.

    2009-02-01

    In vivo reflectance confocal microscopy shows promise for the early detection of malignant melanoma (MM). Two hallmarks of MM have been identified: the presence of pagetoid melanocytes in the epidermis and the breakdown of the dermal papillae. For detection of MM, these features must be identified qualitatively by the clinician and qualitatively through automated pattern recognition. A machine vision algorithm was developed for automated detection. The algorithm detected pagetoid melanocytes and breakdown of the dermal/epidermal junction in a pre-selected set of five MMs and five benign nevi for correct diagnosis.

  1. Oral malignant melanoma: A rare case report and review

    Directory of Open Access Journals (Sweden)

    Mangala Rakaraddi

    2011-01-01

    Full Text Available Primary malignant melanoma is only rarely found in oral cavity (estimated between 0.2 and 8-0% of all melanomas and occurs approximately four times more frequently in oral mucosa of the upper jaw, usually on the palate, alveolar gingiva and melanoma of mandibular gingiva is extremely rare. The peak age of diagnosis of melanoma is between 55 and 65 years. A biopsy is required to confirm the diagnosis. Here, we present a rare case of malignant melanoma of mandibular gingiva in a 64-year-old female patient which is confirmed by histopathology.

  2. 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......Stereological estimation of nuclear volume was performed in a case control study of 72 malignant melanomas, thickness melanomas due to too sparse cellularity. Thus, 21 thin metastasizing...... no significant differences in nuclear volume between metastasizing and non-metastasizing thin malignant melanomas....

  3. Malignant melanoma of the oral cavity: A review of literature

    Directory of Open Access Journals (Sweden)

    Hashemi Pour M

    2008-01-01

    Full Text Available Oral malignant melanoma is a rare aggressive neoplasm of the middle age. This malignancy commonly affects male subjects and is more frequently seen at the level of the hard palate and gingiva. At present, the clinicopathological classification of oral melanoma is not yet clearly outlined; consequently, the skin form is often taken as a reference. In many cases (up to 30%, the diagnosis of melanoma is made on lesions, which have evolved from the pre-existing pigmented lesions. The poor prognosis of oral melanomas requires that pigmented lesions of undetermined origin be routinely biopsied. The surgical approach, combined with the chemotherapeutic one, is the first choice treatment. The purpose of this study is to review literature that has been published about malignant melanoma of the oral cavity. Materials and Methods: Thirty-eight published articles and 8 textbooks related to oral malignant melanoma and been published in the last two decades are reviewed. Conclusion: The review of literature in the field of malignant melanoma of the oral cavity show that this malignancy might be different from cutaneous malignant melanomas, and new criteria for diagnosis and therapy should be considered for this disease. Physicians and dentists who treat problems of the oral cavity should be aware of the need for early diagnosis of oral melanomas and performing biopsies of doubtful pigmented lesions.

  4. Penetration of dacarbazine and its active metabolite 5-aminoimidazole-4-carboxamide into cutaneous metastases of human malignant melanoma.

    Science.gov (United States)

    Joukhadar, C; Klein, N; Mader, R M; Schrolnberger, C; Rizovski, B; Heere-Ress, E; Pehamberger, H; Strauchmann, N; Jansen, B; Müller, M

    2001-10-15

    Dacarbazine has been on the market for approximately 3 decades but remains the most effective single agent available for the therapy of metastatic malignant melanoma (MMM). Most MMMs, however, respond poorly to dacarbazine therapy. Apart from tumor resistance at a molecular level, several studies support the notion that therapeutic failure in tumor therapy also might be attributed to an impaired transcapillary drug transfer. On the basis of this hypothesis, the authors measured intratumor transcapillary transfer rates of dacarbazine and its active metabolite 5-aminoimidazole-4-carboxamide (AIC) by in vivo microdialysis after intravenous administration of dacarbazine at doses of 200 mg/m(2) to 1000 mg/m(2) (n = 7) in patients suffering from MMM. For all doses, area under the concentration curve (AUC) values for dacarbazine and AIC were not significantly different between plasma and tumor interstitium with AUC(tumor)/AUC(plasma) ratios of 0.97 +/- 0.08 (mean +/- standard error of the mean) for dacarbazine and 0.76 +/- 0.22 for AIC. AUC(0-240) values for dacarbazine and AIC measured in plasma correlated closely with corresponding AUC(0-240)values measured in the interstitium of MMMs with values of r(s) = 0.82 (P = 0.042) and r(s) = 0.90 (P = 0.037), respectively. The results of this study indicate favorable tumor penetration characteristics of dacarbazine and its active metabolite AIC. The relative lack of response to antineoplastic therapy with dacarbazine, thus might be explained by resistance of melanoma cells at a molecular level rather than by an inability of dacarbazine and AIC to penetrate into the interstitium of MMM. Copyright 2001 American Cancer Society.

  5. UVB: suscetibilidade no melanoma maligno UVB: susceptibility in malignant melanoma

    Directory of Open Access Journals (Sweden)

    Nilton Nasser

    2010-12-01

    Full Text Available FUNDAMENTOS: Está bem definido que a radiação ultravioleta provoca depleção imunológica na pele, permitindo o desenvolvimento de tumores cutâneos malignos. A maioria dos pacientes de cânceres da pele não melanomas são considerados UVB-suscetíveis. OBJETIVOS: Estudar a UVB-suscetibilidade nos pacientes com melanoma maligno e se este é um fator de risco para o desenvolvimento desse câncer. MÉTODOS: Foram selecionados 88 voluntários divididos em dois grupos: grupo-controle saudável (n=61 e grupo de portadores de melanoma (n=27, todos identificados de acordo com os critérios: tipo histológico, nível de invasão, fotótipos de pele, sexo e idade. A suscetibilidade à radiação ultravioleta B (UVB foi medida pela reação de hipersensibilidade ao contato com o difenciprone nos voluntários sensibilizados em áreas previamente irradiadas. RESULTADOS: A suscetibilidade à radiação UVB foi de 81,5% nos pacientes com melanoma maligno e de 31,2% no grupo-controle. O risco de um indivíduo desenvolver o melanoma maligno foi 9,7 vezes maior do que nos indivíduos UVB-resistentes. CONCLUSÕES: A UVB-suscetibilidade pode ser considerada um fator de risco importante para o desenvolvimento do melanoma maligno.BACKGROUND: It is well established that UV radiation provokes an immunological depletion in the skin, enabling the development of malignant cutaneous tumors. Most nonmelanoma skin cancer patients are considered to be UVB-susceptible. OBJECTIVE: To study the behavior of UVB- susceptibility in malignant melanoma (MM patients and whether this is a risk factor to the development of MM. METHODS: Eighty-eight volunteers were selected and divided into two groups: healthy control group (n = 61 and MM group (n = 27, which were identified according to the following clinical criteria: histopathological type, level of invasion, skin phototype, sex and age. Susceptibility to ultraviolet B (UVB radiation was measured by the onset of a contact

  6. Unusual occurrence of primary malignant melanoma of the nasal cavity

    Directory of Open Access Journals (Sweden)

    Madhu Kumar

    2016-01-01

    Full Text Available Malignant melanoma of nasal cavity is an extremely rare tumor with an incidence rate of 0.67% among all malignant melanomas. Melanomas are tumors arising from melanocytes that are neuroectodermal cells located in the basal layers of skin, skin adnexa, uveal tract, and occasionally in mucosal membranes. We report a case of malignant melanoma of nasal cavity in a 60-year-old female for its rare occurrence. These tumors have poor prognosis owing to high rates of locoregional recurrence and distant metastasis. We report this case without the symptom of epistaxis because of its rarity.

  7. Primary Malignant Amelanotic Melanoma Arising From a Vitiligo ...

    African Journals Online (AJOL)

    Skin cancer is rare in people of African origin while vitiligo occurs worldwide. The occurrence of primary malignant melanoma and vitiligo together is very rare. We present a rare case of primary malignant amelanotic melanoma arising from a depigmented patch of a patient with vitiligo. It was completely excised and followed ...

  8. Primary oral malignant melanoma - A case report | Kumar | Nigerian ...

    African Journals Online (AJOL)

    This paper reports a case of a 42year old woman with primary malignant melanoma at a rare site, the left retromolar region involving the left side of the mandible, up to level IV ipsilateral cervical lymph nodes. The patient was treated ... should be biopsied. Keywords: Malignant melanoma, palate, maxilla, gingiva, oral cavity ...

  9. Metastatic Malignant Melanoma in an alpaca (Vicugna pacos)

    Science.gov (United States)

    Malignant melanoma in a 7-year old, intact male alpaca with a chronic, non-healing wound on the left nares, weight loss and inappetance is described. Malignant melanoma was diagnosed in punch biopsy specimens from a mass on the maxilla associated with the non-healing wound and from a mass in the su...

  10. 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 ...

  11. Malignant Melanoma Presenting as Superior Mediastinal Mass without Extrathoracic Primary Melanoma

    Energy Technology Data Exchange (ETDEWEB)

    You, Myung Won; Sung, Dong Wook; Lee, Young Kyung [Dept. of Diagnostic Radiology, Kyung Hee University Hospital, Seoul (Korea, Republic of)

    2013-03-15

    Malignant melanoma most commonly occurs in the skin, and other organs are secondarily involved. Malignant melanoma presenting in the mediastinum without an extrathoracic primary is very rare. Authors report a case of malignant melanoma of the superior mediastinum without clinical history of extrathoracic malignant melanoma primarily and discuss its radiologic findings. CT shows lobulated heterogenous enhanced mass. Magnetic resonance shows mild hyperintense mass on T1 and T2-weighted images contained focal hemorrhage and necrosis, and invasion to neural foramen. In addition, positron emission tomography/computed tomography shows high standard uptake values uptake of the mass.

  12. Stereological estimates of nuclear volume in thin malignant melanomas

    DEFF Research Database (Denmark)

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

    1998-01-01

    Stereological estimation of nuclear volume was performed in a case control study of 72 malignant melanomas, thickness measurements could be performed in only 57 thin melanomas due to too sparse cellularity. Thus, 21 thin metastasizing...... 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...

  13. Malignant melanoma as second malignant neoplasm in long-term childhood cancer survivors: A systematic review

    NARCIS (Netherlands)

    Braam, Katja I.; Overbeek, Annelies; Kaspers, Gertjan J. L.; Ronckers, Cecile M.; Schouten-van Meeteren, Annette Y. N.; van Dulmen-den Broeder, Eline; Veening, Margreet A.

    2012-01-01

    This systematic review provides information on malignant melanoma as second malignant neoplasm (SMN) after childhood cancer and evaluates its risk factors. Study reports describing incidences of SMN and malignant melanoma as SMN in a population of childhood cancer survivors (CCS) were included. Of

  14. Treatment with levodopa and risk for malignant melanoma

    DEFF Research Database (Denmark)

    Olsen, Jørgen H; Tangerud, Karina; Wermuth, Lene

    2007-01-01

    A large follow-up study in Denmark of 14,088 patients in whom Parkinson's disease was diagnosed at hospital showed a twofold higher incidence of malignant melanoma in these patients than in the general population. In a nested case-control study of 45 patients with malignant melanoma, 97 patients...... melanoma in a subgroup of patients with a probable diagnosis of idiopathic Parkinson's disease as compared with other patients. There was apparently no effect of levodopa on the risk for malignant melanoma as indicated by an odds ratio of 1.0 (95% confidence interval, 0.8-1.3) per 1,000 g cumulative intake...... of the drug. We conclude that the increased rate of malignant melanoma observed in patients treated at hospital for Parkinson's disease is restricted to those with idiopathic Parkinson's disease, however, unrelated to the treatment with levodopa. (c) 2007 Movement Disorder Society....

  15. Expression of heat shock protein 105 and 70 in malignant melanoma and benign melanocytic nevi.

    Science.gov (United States)

    Park, Hye-Sang; Park, Chan-Hyuk; Choi, Bo-Ra; Lim, Mi-Sun; Heo, Su-Hak; Kim, Cheol-Hann; Kang, Sang-Gue; Whang, Kyu U; Cho, Moon K

    2009-05-01

    Heat shock proteins (HSPs) restore immature proteins or denatured proteins, thus protecting cells. Also, the expression of some HSPs is elevated substantially in malignant tumors, but the expression of HSPs in association with melanoma has yet to be studied. Therefore, we examined the expression patterns of HSP 70 and 105 in melanoma, benign melanocytic nevi and normal human skin. Two specimens of malignant melanoma, two of benign melanocytic nevi and six of normal human skin were analyzed using Western blot analysis for expression of HSP 70 and 105. In another set, 16 specimens of malignant melanoma, 24 of benign melanocytic nevi and eight of normal human skin were analyzed for the expression of HSP 105 using immunohistochemical studies. The Western blot analysis showed that HSP 70 was overexpressed in all three types. But, the HSP 105 was hardly expressed in normal human skin and benign melanocytic nevi. However, in malignant melanoma, the HSP 105 was overexpressed, and immunohistochemical examination of HSP 105 showed a result similar to that of Western blot analysis. In our study, HSP 105 is thought to be a more relevant tumor-associated antigen in malignant melanoma than is HSP 70.

  16. [Regression in malignant melanoma. Definition, etiopathogenesis, morphology and differential diagnosis].

    Science.gov (United States)

    Paredes, B E

    2007-11-01

    Malignant melanoma is a neoplasm that more often tends to undergo regression. Clinically, variation in color is perhaps the most important hallmark of primary cutaneous melanoma. The change in color to white, off-white, blue-white and gray-white is a sign of (spontaneous) regression in malignant melanoma. Histopathologically the process starts with a dense lichenoid infiltrate of lymphocytes, and ends with fibrosis and/or melanosis within a thickened papillary dermis. The dense infiltrate of lymphocytes permeates the thin melanoma and destroys the atypical melanocytes in the epidermis and the papillary dermis. A key concern is how to define regression in a reproducible way. Using the following definition, a statistically significant risk of metastases can be demonstrated in thin melanomas (50%): "fibroplasia with an absence of epidermal and dermal involvement by melanoma cells, but allowing for (lentiginous) single-cell proliferation of atypical melanocytes along the dermo-epidermal junction".

  17. 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.

  18. Oral malignant melanoma: A silent killer?

    Science.gov (United States)

    Padhye, Ashvini; D’souza, Jovita

    2011-01-01

    Oral malignant melanomas are extremely rare lesions and occur commonly in the maxillary gingiva more frequently on the palate with fewer incidences in the mandibular gingiva. Though these lesions are biologically aggressive, they often go unnoticed since they are clinically asymptomatic in the early stages and usually present merely as a hyperpigmented patch on the gingival surface. These lesions if diagnosed at an early in situ stage are potentially curable and definitely have a better prognosis, but unfortunately as they are clinically asymptomatic, it results in delayed diagnosis thus making the prognosis extremely poor. This paper presents the case of a patient who visited our department with the complaint of darkened patches on the gums and his concern was purely aesthetic. There were no symptoms associated with the hyperpigmented lesions and hence the patient did not approach us earlier. When the lesions grew larger and were unsightly, the patient has seeked dental advice. Histopathologic investigation confirmed the diagnosis as ‘Oral Malignant Melanoma’. Though aggressive therapy was instilled immediately, unfortunately, the patient succumbed to death within a few months after diagnosis as the lesion was highly invasive. Due to the biologically aggressive but clinically silent nature of progression of the lesion, the importance of maintaining a high index of suspicion and early detection and diagnosis for any pigmented gingival lesions cannot be overemphasised. Diagnosis must be based on thorough detailed history and valid histologic evidence. PMID:22368374

  19. Apparent absence of a benign precursor lesion: Implications for the pathogenesis of malignant melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Ross, P.M. (Rockefeller Univ., New York, NY (USA))

    1989-09-01

    This review relates concepts derived from the study of chemically induced skin cancer in animal models to the pathogenesis of malignant melanoma in humans. Most chemically induced experimental cancers in animals, including melanomas in rodents, arise within a benign precursor lesion. The initiation-promotion-progression sequence is a central concept in animal models for carcinogenesis. Many human melanomas appear to arise from epidermal melanocytes, with no associated precursor lesion. This article considers why there is no apparent precursor in many human melanomas and the consequences of this absence. Melanocyte physiology and factors that govern escape from defenses such as DNA repair, local tissue environment, and immunity presumably influence melanocyte conversion to melanoma. These factors may determine the absence of a precursor lesion in primary melanomas. In addition, it is possible that some human melanomas arise by cellular mechanisms different from those causing cancer in rodent models. Both molecular and prospective clinical studies will be required to explain this apparent paradox in the pathogenesis of melanoma. A similar approach may help to explain the origin of basal cell carcinoma and perhaps other human cancers that appear to arise directly from normal cells. From a clinical point of view, the absence of an identifiable, benign precursor lesion requires even greater emphasis on melanoma prevention. Research on mechanisms of ultraviolet carcinogenesis indicates that appropriate postexposure treatments may be useful in preventing long-term consequences of sunburn, including melanoma. 69 references.

  20. Malignant melanoma of the tongue following low-dose radiation

    Energy Technology Data Exchange (ETDEWEB)

    Kalemeris, G.C.; Rosenfeld, L.; Gray, G.F. Jr.; Glick, A.D.

    1985-03-01

    A 47-year-old man had a spindly malignant melanoma of the tongue many years after low-dose radiation therapy for lichen planus. To our knowledge, only 12 melanomas of the tongue have been reported previously, and in none of these was radiation documented.

  1. Morphological Patterns Of Malignant Melanoma In Benin-City, South ...

    African Journals Online (AJOL)

    Materials and Methods: Data of surgical biopsies from the skin received at the department of Histopathology, over a twenty-five year period (January 1982 to ... and foot region. Nodular melanoma constituted first majority variant accounting for 36.3%. Malignant melanoma in advanced stages IV and V was the most common ...

  2. Primary Malignant Melanoma of the Female Genital Tract

    Directory of Open Access Journals (Sweden)

    Tayfun Gungor

    2009-06-01

    Conclusion: Although malignant melanoma of the female genital tract is uncommon, elderly women should undergo regular gynecologic examinations and suspicious pigmented lesions should be biopsied. The use of immunohistochemical assays could markedly improve diagnosis. However, the prognosis for these tumors is poor, regardless of the treatment delivered, and they are associated with a high rate of recurrence and low long-term survival. Surgery is the best available treatment for controlling and potentially curing malignant melanomas.

  3. Amelanotic malignant melanoma of the perineum: a case report.

    Science.gov (United States)

    Zamurovic, M; Soldo, V; Cutura, N; Perisic, Z

    2013-01-01

    The case of a patient diagnosed and surgically treated for amelanotic malignant melanoma of the perineum, accompanied by several local relapses, metastases to iliac-femoral lymph nodes, and distant metastases to both lungs is presented. Survival, up to date, equals 12 years. Amelanotic malignant melanomas are very rare tumors. Perineal and perianal localization of these tumors is especially rare. References cite about 500 cases with survival limited to between six months and one year after diagnosis..

  4. Screening for reducing morbidity and mortality in malignant melanoma

    DEFF Research Database (Denmark)

    Johansson, Minna; Brodersen, John; Gøtzsche, Peter C.

    2016-01-01

    This is the protocol for a review and there is no abstract. The objectives are as follows: To assess the effects on morbidity and mortality of screening for malignant melanoma in the general population.......This is the protocol for a review and there is no abstract. The objectives are as follows: To assess the effects on morbidity and mortality of screening for malignant melanoma in the general population....

  5. Malignant melanoma. Current status; Malignes Melanom. Aktueller Stand

    Energy Technology Data Exchange (ETDEWEB)

    Winkler, J.K.; Buder-Bakhaya, K.; Enk, A.; Hassel, J.C. [Universitaetshautklinik, Nationales Centrum fuer Tumorerkrankungen, Heidelberg (Germany); Dimitrakopoulou-Strauss, A. [Deutsches Krebsforschungszentrum, Klinische Kooperationseinheit Nuklearmedizin, Heidelberg (Germany)

    2017-10-15

    The incidence of malignant melanoma is continuously increasing. The prognosis of metastatic disease is still limited. Until a few years ago palliative chemotherapy with a limited response rate was the standard treatment for metastatic melanoma. Immunotherapy and targeted therapy provide new treatment options. Immune checkpoint inhibitors have significantly improved the prognosis. Regional lymph node sonography, computed tomography (CT) of the neck, chest and abdomen and brain magnetic resonance imaging (MRI) are routinely used. As an alternative to CT scans 18 F fluorodeoxyglucose positron emission tomography (FDG-PET) may be used. Immunotherapy provides the chance of long-term disease control in metastatic melanoma. Ipilimumab may provide long-term tumor control in approximately 20% of patients. Median overall survival of approximately 2 years is achieved during therapy with anti-programmed cell death (PD) 1 antibodies. For combined therapy of ipilimumab and nivolumab a response rate of almost 60% is achieved and 2-year survival is also approximately 60%. The range of immune-mediated side effects demands particular consideration. For response evaluation immune-related response criteria were defined. Furthermore, immunotherapeutic approaches, such as talimogene laherparepvec (T-VEC), which is a modified herpes virus can be used for intralesional injection. An individual definition of the appropriate therapy for each patient is of particular importance. In the context of modern therapy regimens close patient monitoring is crucial. (orig.) [German] Die Inzidenz des Melanoms steigt stetig an. Die Prognose bei metastasierter Erkrankung ist weiterhin limitiert. Bis vor wenigen Jahren war eine palliative Chemotherapie mit begrenzten Ansprechraten Standardtherapie des metastasierten Melanoms. Immuntherapie und zielgerichtete Therapien stellen neue Behandlungsoptionen dar. Insbesondere Immuncheckpointinhibitoren haben die Prognose verbessert. Routinemaessig werden die

  6. miR-137 inhibits glutamine catabolism and growth of malignant melanoma by targeting glutaminase.

    Science.gov (United States)

    Luan, Wenkang; Zhou, Zhou; Zhu, Yan; Xia, Yun; Wang, Jinlong; Xu, Bin

    2018-01-01

    Glutamine catabolism is considered to be an important metabolic pathway for cancer cells. Glutaminase (GLS) is the important rate-limiting enzyme of glutamine catabolism. miR-137 functions as a tumor suppressor in many human malignant tumors. However, the role and molecular mechanism of miR-137 and GLS in malignant melanoma has not been reported. In this study, we showed that miR-137 was decreased in melanoma tissue, and the low miR-137 level and high GLS expression are independent risk factor in melanoma. miR-137 suppressed the proliferation and glutamine catabolism of melanoma cells. GLS is crucial for glutamine catabolism and growth of malignant melanoma. We also demonstrated that miR-137 acts as a tumor suppressor in melanoma by targeting GLS. This result elucidates a new mechanism for miR-137 in melanoma development and provides a survival indicator and potential therapeutic target for melanoma patients. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Phase I study of GC1008 (fresolimumab: a human anti-transforming growth factor-beta (TGFβ monoclonal antibody in patients with advanced malignant melanoma or renal cell carcinoma.

    Directory of Open Access Journals (Sweden)

    John C Morris

    Full Text Available In advanced cancers, transforming growth factor-beta (TGFβ promotes tumor growth and metastases and suppresses host antitumor immunity. GC1008 is a human anti-TGFβ monoclonal antibody that neutralizes all isoforms of TGFβ. Here, the safety and activity of GC1008 was evaluated in patients with advanced malignant melanoma and renal cell carcinoma.In this multi-center phase I trial, cohorts of patients with previously treated malignant melanoma or renal cell carcinoma received intravenous GC1008 at 0.1, 0.3, 1, 3, 10, or 15 mg/kg on days 0, 28, 42, and 56. Patients achieving at least stable disease were eligible to receive Extended Treatment consisting of 4 doses of GC1008 every 2 weeks for up to 2 additional courses. Pharmacokinetic and exploratory biomarker assessments were performed.Twenty-nine patients, 28 with malignant melanoma and 1 with renal cell carcinoma, were enrolled and treated, 22 in the dose-escalation part and 7 in a safety cohort expansion. No dose-limiting toxicity was observed, and the maximum dose, 15 mg/kg, was determined to be safe. The development of reversible cutaneous keratoacanthomas/squamous-cell carcinomas (4 patients and hyperkeratosis was the major adverse event observed. One malignant melanoma patient achieved a partial response, and six had stable disease with a median progression-free survival of 24 weeks for these 7 patients (range, 16.4-44.4 weeks.GC1008 had no dose-limiting toxicity up to 15 mg/kg. In patients with advanced malignant melanoma and renal cell carcinoma, multiple doses of GC1008 demonstrated acceptable safety and preliminary evidence of antitumor activity, warranting further studies of single agent and combination treatments.Clinicaltrials.gov NCT00356460.

  8. A new treatment for human malignant melanoma targeting L-type amino acid transporter 1 (LAT1): A pilot study in a canine model

    Energy Technology Data Exchange (ETDEWEB)

    Fukumoto, Shinya; Hanazono, Kiwamu [Veterinary Internal Medicine, Department of Small Animal Clinical Sciences, School of Veterinary Medicine, Rakuno Gakuen University, Ebetsu, Hokkaido 069-8501 (Japan); Fu, Dah-Renn; Endo, Yoshifumi; Kadosawa, Tsuyoshi [Veterinary Oncology, Department of Small Animal Clinical Sciences, School of Veterinary Medicine, Rakuno Gakuen University, Ebetsu, Hokkaido 069-8501 (Japan); Iwano, Hidetomo [Veterinary Biochemistry, Department of Basic Veterinary Medicine, School of Veterinary Medicine, Rakuno Gakuen University, Ebetsu, Hokkaido 069-8501 (Japan); Uchide, Tsuyoshi, E-mail: uchide@rakuno.ac.jp [Veterinary Internal Medicine, Department of Small Animal Clinical Sciences, School of Veterinary Medicine, Rakuno Gakuen University, Ebetsu, Hokkaido 069-8501 (Japan)

    2013-09-13

    Highlights: •LAT1 is highly expressed in tumors but at low levels in normal tissues. •We examine LAT1 expression and function in malignant melanoma (MM). •LAT1 expression in MM tissues and cell lines is higher than those in normal tissues. •LAT1 selective inhibitors inhibit amino acid uptake and cell growth in MM cells. •New chemotherapeutic protocols including LAT1 inhibitors are effective for treatment. -- Abstract: L-type amino acid transporter 1 (LAT1), an isoform of amino acid transport system L, transports branched or aromatic amino acids essential for fundamental cellular activities such as cellular growth, proliferation and maintenance. This amino acid transporter recently has received attention because of its preferential and up-regulated expression in a variety of human tumors in contrast to its limited distribution and low-level expression in normal tissues. In this study, we explored the feasibility of using LAT1 inhibitor as a new therapeutic agent for human malignant melanomas (MM) using canine spontaneous MM as a model for human MM. A comparative study of LAT expression was performed in 48 normal tissues, 25 MM tissues and five cell lines established from MM. The study observed LAT1 mRNA levels from MM tissues and cell lines that were significantly (P < 0.01) higher than in normal tissues. Additionally, MM with distant metastasis showed a higher expression than those without distant metastasis. Functional analysis of LAT1 was performed on one of the five cell lines, CMeC-1. [{sup 3}H]L-Leucine uptake and cellular growth activities in CMeC-1 were inhibited in a dose-dependent manner by selective LAT1 inhibitors (2-amino-2-norbornane-carboxylic acid, BCH and melphalan, LPM). Inhibitory growth activities of various conventional anti-cancer drugs, including carboplatin, cyclophosphamide, dacarbazine, doxorubicin, mitoxantrone, nimustine, vinblastine and vincristine, were significantly (P < 0.05) enhanced by combination use with BCH or LPM

  9. Epidemiological aspects of cutaneous malignant melanoma (review).

    Science.gov (United States)

    Serraino, D; Fratino, L; Gianni, W; Campisi, C; Pietropaolo, M; Trimarco, G; Marigliano, V

    1998-01-01

    There is an increasing interest in the etiology of cutaneous malignant melanoma (CMM). Once considered a rare tumour, CMM is now the fourth commonest cancer in Australia and New Zeland, the tenth in the Usa, Canada and Scandinavia and the eighteenth in Great Britain. The growing scientific concern on the urgent need to highlight the cause/s of CMM is well documented by the large number of well-designed and well-conducted epidemiological studies reported in the last two decades. Such studies facilitated testing of many etiological hypotheses derived from earlier descriptive investigations and contributed to significant progress in understanding the etiology of such disease. The quantification of the extent to which the increases in CMM incidence and mortality rates are related to new lifestyles and to new patterns of exposure to potential carcinogenetic agents is essential in order to establish an appropriate preventive strategy. In population of mainly European origin a substantial proportion of the increased incidence of CMM is attributable to steady change from predominantly occupational to predominantly recreational exposure to solar radiation. Therefore the present review puts particular emphasis on exposure to sunlight as well as to artificial ultraviolet light, as modifiable causes of CMM. Incidence and mortality data and other potential risk factors for the development of CMM will also be briefly reviewed.

  10. Metastatic Malignant Melanoma of Parotid Gland with a Regressed Primary Tumor

    Directory of Open Access Journals (Sweden)

    M. Mustafa Kılıçkaya

    2016-01-01

    Full Text Available Malignant melanoma of the parotid gland is often metastatic and mainly originates from malignant melanomas in the head and neck. Nevertheless, some malignant melanomas may metastasize and subsequently regress. Therefore, it may not be possible to observe a metastatic malignant melanoma and its primary melanoma simultaneously. The investigation of a patient’s old photographs may help in the detection of preexisting and regressed pigmented lesions in the facial and neck regions.

  11. 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.

  12. MicroRNAs in the pathogenesis of malignant melanoma

    DEFF Research Database (Denmark)

    Glud, M; Gniadecki, R

    2013-01-01

    Cutaneous malignant melanoma is the most aggressive and lethal form of skin cancer. Over the past decades, its incidence has been increasing by 3-8% per year in western countries while mortality has stabilized. Melanoma is a heterogenous disease and can be subclassified based on distinct clinical...... characteristics, histopathological features and mutation patterns within NRAS and BRAF genes. Recent data indicate that microRNAs (miRNAs) are involved in the pathogenesis of malignant melanoma. MiRNAs are small, non-coding, regulatory RNA molecules expressed in a tissue and cell specific manner and are known...... to play a crucial role in cell homeostasis and carcinogenesis. MiRNAs might prove to be powerful cancer biomarkers and future therapeutic targets. In this review, we focused on the miRNA involvement in four molecular pathways known to be deregulated in malignant melanoma, including the RAS...

  13. Primary malignant melanoma of the vagina: a case report

    Energy Technology Data Exchange (ETDEWEB)

    Jang, Ji Young; Kim, Do Kang; Lee, Eun Hee [College of Medicine, Catholic Univ., Seoul (Korea, Republic of); Kim, Jun Sang [College of Medicine, Chungnam National Univ., Daejeon (Korea, Republic of)

    2003-09-01

    A primary malignant melanoma of the vagina is a very rare gynecological malignant tumor. Its clinical behavior is more aggressive than that of cutaneous and vulvar melanomas. We present a case of a large sized primary melanoma of the lower third of the vagina, with a cervical lesion, in a 58-year-old postmenopausal woman. The patient was treated with conventional external radiation therapy and intracavitary radiotherapy (lCR), without surgical treatment. Although the primary lesion showed a partial response, the patient died of extensive metastases, which were found 4.5 months after the initial diagnosis. We suggest that shortening the treatment period, such as hypofractionated radiation therapy and surgical removal, and various systemic therapies for preventing early distant metastasis, are appropriate treatments for a primary malignant melanoma of the vagina, with a large tumor size.

  14. Ability to self-detect malignant melanoma decreases with age

    DEFF Research Database (Denmark)

    Trolle, L; Henrik-Nielsen, R; Gniadecki, R

    2011-01-01

    The prognosis of malignant melanoma depends on the thickness of the tumour. In this study, we analysed the trends in Breslow thickness in 63 patients referred to our institution, a tertiary dermatology referral centre. The mean thickness of melanoma was 0.31 mm, which was lower than the national...... average of 1.10 mm. There was a significant trend towards increased melanoma thickness with increasing age, with a rate of 0.24 mm (95% CI 0.12-0.37) for each additional 10 years of age above the age of 20 years. This trend was only apparent in cases of self-diagnosed melanomas; the thickness of tumours...... diagnosed by a dermatologist did not show any dependence on patient age. As the mortality from melanoma increases with age, this study suggests that dermatologists should include older people in screening programmes for melanoma....

  15. 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.

  16. Changes in expression of putative antigens encoded by pigment genes in mouse melanomas at different stages of malignant progression.

    OpenAIRE

    Orlow, S J; Hearing, V. J.; Sakai, C.; Urabe, K; Zhou, B K; Silvers, W. K.; Mintz, B

    1995-01-01

    Cutaneous melanomas of Tyr-SV40E transgenic mice (mice whose transgene consists of the tyrosinase promoter fused to the coding regions of simian virus 40 early genes) strikingly resemble human melanomas in their development and progression. Unlike human melanomas, the mouse tumors all arise in genetically identical individuals, thereby better enabling expression of specific genes to be characterized in relation to advancing malignancy. The products of pigment genes are of particular interest ...

  17. miR-137 suppresses tumor growth of malignant melanoma by targeting aurora kinase A

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Xiao; Zhang, Haiping [Department of Dermatology and Venereal Disease, Xuanwu Hospital, Capital Medical University, Beijing 100053 (China); Lian, Shi [Department of Dermatology and Venereal Disease, Capital Medical University, Beijing 100069 (China); Zhu, Wei, E-mail: zhuwei_2020@163.com [Department of Dermatology and Venereal Disease, Xuanwu Hospital, Capital Medical University, Beijing 100053 (China)

    2016-07-01

    As an oncogene, aurora kinase A (AURKA) is overexpressed in various types of human cancers. However, the expression and roles of AURKA in malignant melanoma are largely unknown. In this study, a miR-137-AURKA axis was revealed to regulate melanoma growth. We found a significant increase in levels of AURKA in melanoma. Both genetic knockdown and pharmacologic inhibition of AURKA decreased tumor cell growth in vitro and in vivo. Further found that miR-137 reduced AURKA expression through interaction with its 3′ untranslated region (3′UTR) and that miR-137 was negatively correlated with AURKA expression in melanoma specimens. Overexpression of miR-137 decreased cell proliferation and colony formation in vitro. Notably, re-expression of AURKA significantly rescued miR-137-mediated suppression of cell growth and clonality. In summary, these results reveal that miR-137 functions as a tumor suppressor by targeting AURKA, providing new insights into investigation of therapeutic strategies against malignant melanoma. -- Highlights: •First reported overexpression of AURKA in melanoma. •Targeting AURKA inhibits melanoma growth in vitro and in vivo. •Further found miR-137 suppressed cell growth by binding to AURKA 3′UTR. •Re-expression of AURKA rescued miR-137-mediated suppression. •miR-137-AURKA axis may be potential therapeutic targets of melanoma.

  18. SOX10 expression in malignant melanoma, carcinoma, and normal tissues.

    Science.gov (United States)

    Mohamed, Amr; Gonzalez, Raul S; Lawson, Diane; Wang, Jason; Cohen, Cynthia

    2013-12-01

    Sry-related HMg-Box gene 10 (SOX10) is a nuclear transcription factor that plays an important role in melanocytic cell differentiation. It has been shown to be a sensitive marker of melanoma including spindle and desmoplastic subtypes. We assessed its frequency of expression in melanoma, carcinoma, benign nevi, and non-neoplastic tissues with routine immunohistochemistry for SOX10. The 109 primary melanoma included 49 epithelioid, 19 spindle cell, 22 desmoplastic, and 19 mixed spindle cell/desmoplastic melanoma. All primary, except 8 desmoplastic melanoma, and 11 metastatic melanoma were strongly and diffusely nuclear SOX10-positive. Six desmoplastic melanoma had ≤10% cells positive, and 2 were benign nevi, 18 dysplastic nevi, 68 non-neoplastic and benign skins, and all 56 non-neoplastic breast tissue were SOX10-positive. The sensitivity and specificity for SOX10 in the diagnosis of melanoma are 1.0 and 0.93, respectively; the positive and negative predictive values are 0.87 and 1.0, respectively. SOX10 is a sensitive, specific marker for melanoma. As benign nevi also express SOX10, it cannot be used to differentiate between benign and malignant pigmented skin lesions. Only a small number of breast carcinoma (12%), and breast lobules, express SOX10; no carcinoma of the ovary, endometrium, lung, or colon expressed SOX10.

  19. Mobile phones and malignant melanoma of the eye

    OpenAIRE

    Johansen, C; Boice, J D; McLaughlin, J K; Christensen, H C; Olsen, J H

    2002-01-01

    Recently a four-fold increase in the risk of malignant melanoma of the eye was associated with the use of radiofrequency transmitting devices, including mobile phones in Germany. We contrasted the incidence rates of this rare cancer with the number of mobile phone subscribers in Denmark. We observed no increasing trend in the incidence rate of melanoma, which was in sharp contrast to the exponentially increasing number of mobile phone subscribers starting in the early 1980s. Our study provide...

  20. Malignant melanoma of the penis and urethra: one case report

    OpenAIRE

    Li, Yunxiang; Yuan, Haichao; Wang, Anguo; Zhang, Zongping; Wu, Ji; Wei, Qiang

    2014-01-01

    We present a case of a patient with malignant melanoma of the glans penis and urethra, which was found in a 53-year-old man with nonhealing ulcerative penile lesion and bilateral, clinically palpable inguinal lymphadenopathies at diagnosis. A diagnostic biopsy showed the characteristics of a melanoma. We treated the patient with total penectomy and bilateral inguinal lymph node dissection. After surgery, chemotherapy with bleomycin, vincristine and cisplatin and immunotherapy with thymosin in...

  1. Unexpected pulmonary hypertensive crisis after surgery for ocular malignant melanoma.

    Science.gov (United States)

    Sato, Kaori; Saji, Tsutomu; Kaneko, Taku; Takahashi, Kei; Sugi, Kaoru

    2014-11-24

    To report a case of unexpected pulmonary hypertensive crisis caused by endothelin release from melanoma cells after surgery for choroidal melanoma. A 56-year-old man suddenly developed dyspnea after resection of choroidal melanoma. Worsening hypoxia required intensive treatment, including percutaneous cardiopulmonary support, after which a series of tests were immediately performed. The tentative diagnosis was idiopathic pulmonary arterial hypertension. Previous studies noted a significant association between melanoma and endothelin (ET)-1. We hypothesized that a substantial amount of ET-1 had been released from malignant melanoma cells during resection, thus triggering the pulmonary hypertensive crisis in our patient. The patient fully recovered after intensive treatment and administration of the endothelin receptor antagonist bosentan. The success of bosentan treatment, along with the extremely high level of ET-1 on pathologic analysis, confirmed our hypothesis regarding the increase in plasma ET-1 level. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. Female Urethral Malignant Melanoma With Vesical Invasion: A Case Report

    Directory of Open Access Journals (Sweden)

    Alpaslan Akbas

    2010-02-01

    Full Text Available We report a 75-year-old female with a primary urethral malignant melanoma. A mass protruding from inside the urethra was detected on physical examination. Abdominopelvic magnetic resonance imaging revealed a mass extending from the urethra with dimensions of 4 × 2 cm, and periurethral heterogenous fatty planes consistent with infiltration. The histopathologic examination was consistent with HMB45(+ malignant melanoma. We performed cystourethrectomy and bilateral inguinal and pelvic lymphadenectomy in one session. The pathology report revealed primary malignant melanoma of the urethra invading the inferior bladder wall. The patient received no adjuvant therapy because of cardiopulmonary morbidities and the presence of multiple pulmonary metastases. The patient eventually died 13 months after surgery.

  3. Vaginal Primary Malignant Melanoma: A Rare and Aggressive Tumor

    Directory of Open Access Journals (Sweden)

    Georgios Androutsopoulos

    2013-01-01

    Full Text Available Vaginal primary malignant melanoma is a rare and very aggressive tumor. It most commonly occurs in postmenopausal women, with a mean age of 57 years. Our patient is an 80-year-old, postmenopausal Greek woman presented with a complaint of abnormal vaginal bleeding. On gynecologic examination there was a pigmented, raised, ulcerated, and irregular lesion  cm in the upper third of anterior vaginal wall. She underwent a wide local excision of the lesion. The histopathology revealed vaginal primary malignant melanoma with ulceration and no clear surgical margins. She denied any additional surgical interventions and underwent to postoperative adjuvant radiotherapy. Follow up 5 months after initial diagnosis revealed no evidence of local recurrence or distant metastasis. The prognosis of vaginal primary malignant melanoma is very poor despite treatment modality, because most of the cases are diagnosed at advanced stage. Particularly patients with no clear surgical margins and tumor size >3 cm needed postoperative adjuvant radiotherapy.

  4. Spontaneous regression of metastases from malignant melanoma: a case report

    DEFF Research Database (Denmark)

    Kalialis, Louise V; Drzewiecki, Krzysztof T; Mohammadi, Mahin

    2008-01-01

    A case of a 61-year-old male with widespread metastatic melanoma is presented 5 years after complete spontaneous cure. Spontaneous regression occurred in cutaneous, pulmonary, hepatic and cerebral metastases. A review of the literature reveals seven cases of regression of cerebral metastases......; this report is the first to document complete spontaneous regression of cerebral metastases from malignant melanoma by means of computed tomography scans. Spontaneous regression is defined as the partial or complete disappearance of a malignant tumour in the absence of all treatment or in the presence...... of therapy, which is considered inadequate to exert a significant influence on neoplastic disease. The incidence of spontaneous regression of metastases from malignant melanoma is approximately one per 400 patients, and possible mechanisms include immunologic, endocrine, inflammatory and tumour nutritional...

  5. 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

    CONTEXT: Pathologists may encounter problems in the differential diagnosis of malignant melanoma, spindle and epithelioid neoplasms of peripheral nerves, and fibrohistiocytic tumors. Tyrosinase has been demonstrated to be a sensitive marker for melanoma. OBJECTIVE: To determine the specificity...... 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...

  6. Silencing of Peroxiredoxin 2 and aberrant methylation of 33 CpG islands in putative promoter regions in human malignant melanomas.

    Science.gov (United States)

    Furuta, Junichi; Nobeyama, Yoshimasa; Umebayashi, Yoshihiro; Otsuka, Fujio; Kikuchi, Kanako; Ushijima, Toshikazu

    2006-06-15

    Aberrant methylation of promoter CpG islands (CGI) is involved in silencing of tumor suppressor genes and is also a potential cancer biomarker. Here, to identify CGIs aberrantly methylated in human melanomas, we did a genome-wide search using methylation-sensitive representational difference analysis. CGIs in putative promoter regions of 34 genes (ABHD9, BARHL1, CLIC5, CNNM1, COL2A1, CPT1C, DDIT4L, DERL3, DHRS3, DPYS, EFEMP2, FAM62C, FAM78A, FLJ33790, GBX2, GPR10, GPRASP1, HOXA9, HOXD11, HOXD12, HOXD13, p14ARF, PAX6, PRDX2, PTPRG, RASD1, RAX, REC8L1, SLC27A3, TGFB2, TLX2, TMEM22, TMEM30B, and UNC5C) were found to be methylated in at least 1 of 13 melanoma cell lines but not in two cultured normal melanocytes. Among these genes, Peroxiredoxin 2 (PRDX2) was expressed in normal melanocytes, and its expression was lost in melanomas with methylation. The loss of expression was restored by treatment of melanomas with a demethylating agent 5-aza-2'-deoxycytidine. In surgical melanoma specimens, methylation of PRDX2 was detected in 3 of 36 (8%). Furthermore, immunohistochemical analysis of PRDX2 showed that disappearance of immunoreactivity tends to associate with its methylation. PRDX2 was recently reported to be a negative regulator of platelet-derived growth factor signaling, and its silencing was suggested to be involved in melanomas. On the other hand, 12 CGIs were methylated in >or=9 of the 13 melanoma cell lines and are considered as candidate melanoma biomarkers.

  7. Clinicopathological features and pituitary homeobox 1 gene expression in the progression and prognosis of cutaneous malignant melanoma

    Directory of Open Access Journals (Sweden)

    Figen Barut

    2016-10-01

    Full Text Available The evidence that PITX1 (pituitary homeobox 1 is a significant tumor suppressor in human cancer remains largely circumstantial, but it clearly warrants further study as little is known about the tumor-inhibitory roles of PITX1 in cutaneous malignant melanoma. The aims of this study were to investigate PITX1 gene expression in patients with cutaneous malignant melanoma and to evaluate its potential relevance to clinicopathological characteristics and tumor cell proliferation. Clinicopathological findings of patients with cutaneous malignant melanoma were analyzed retrospectively. PITX1 and Ki-67 expression were detected by immunohistochemistry in malignant melanoma and healthy tissue samples from each patient. Labeling indices were calculated based on PITX1 gene and Ki-67 expression. The correlation between PITX1and Ki-67 expressions was analyzed in cutaneous malignant melanoma cases. The relationship between PITX1 expression intensity and clinicopathological characteristics was also analyzed. PITX1 expression was observed in all (100% normal healthy skin tissue samples. In addition, PITX1 expression was found in 56 (80% and was absent in 14 (20% of the 70 cutaneous malignant melanoma cases. Ki-67 positive expression was only detected in the 14 (20% PITX1-negative cases. PITX1-positive tumor cells were observed on the surface, but Ki-67 positive tumor cells were observed in deeper zones of the tumor nests. PITX1 expression was downregulated in human cutaneous malignant melanoma lesions compared with healthy skin tissue, but Ki-67 expression was upregulated in concordance with the progression of cutaneous malignant melanoma. PITX1 expression may be involved in tumor progression and is a potential tumor suppressor gene and prognostic marker for cutaneous malignant melanoma.

  8. Multidisciplinary approach to patient with malignant melanoma.

    Science.gov (United States)

    Scarpati, Giuseppina Della Vittoria; Fusciello, Celeste; Sabbatino, Francesco; Ferrone, Soldano; Caponigro, Francesco; Perri, Francesco; Carlomagno, Chiara; Pepe, Stefano

    2013-07-01

    The incidence of melanoma is rapidly increasing worldwide and the prognosis of patients with metastatic disease is still poor, with a median survival of 8-9 months and a 3-year overall survival (OS) rate less than 15% [1,2]. A complete surgical excision is the main treatment for primary cutaneous melanoma [3], but controversies about the extension of excision margins still remain [4]. Sentinel lymph node biopsy (SLNB) provides important prognostic and staging data by the identification of regional node-negative patients who would not benefit from a complete nodal dissection. However, there is no consensus in the definition of melanoma thickness to enforce the execution of the SLNB [5]. To date, Interferon-α (IFN-α)is the only approved adjuvant treatment after surgical excision of high-risk melanoma, but its indication remains still controversial [2,6].

  9. 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.

  10. Raf inhibitor stabilizes receptor for the type I interferon but inhibits its anti-proliferative effects in human malignant melanoma cells.

    Science.gov (United States)

    Kumar, K G Suresh; Liu, Jianghuai; Li, Ying; Yu, Duonan; Thomas-Tikhonenko, Andrei; Herlyn, Meenhard; Fuchs, Serge Y

    2007-09-01

    Interferon alpha (IFNalpha) is widely used in treatment of malignant melanoma patients. This cytokine acts on cells by engaging Type I IFN receptor consisting of two subunits, (IFNAR1 and IFNAR2) followed by activation of Janus kinases (Jak). Levels of IFNAR1 (regulated via degradation mediated by the betaTrcp E3 ubiquitin ligase) and IFNalpha signaling were reduced in 1205Lu melanoma cell line that harbors activated BRAF and exhibits high levels of betaTrcp ubiquitin ligase. Expression of stabilized IFNAR1 in melanoma cells decreased their tumorigenicity. Furthermore, RNAi-mediated BRAF knockdown and pharmacologic inhibition of either Raf or MEK1 decreased levels of betaTrcp and stabilized IFNAR1. However, despite causing stabilization of IFNAR1, Raf inhibitor BAY 43-9006 interfered with cellular responses to IFNalpha most likely due to its ability to directly inhibit Jak activity. We discuss the implications of this result for combination therapy with BAY 43-9006 and IFNalpha in melanoma patients.

  11. THE STUDY OF MECHANISMS OF PHOTOINDUCED APOPTOSIS IN THE SKIN MALIGNANT MELANOMA CELL MODEL

    Directory of Open Access Journals (Sweden)

    M. L. Gelfond

    2016-01-01

    Full Text Available The results of the experimental study of immune response of human skin malignant melanoma cells Mel 226 on photodynamic exposure are represented in the article. Photoinduced apoptosis of skin malignant melanoma was studied in vitro. The study showed that irradiation with the agent fotoditazin at dose of 0.5–2.5 µg/ml (6 and 10 min exposure 30 min before irradiation; irradiation parameters: wavelength of 662 nm, total light dose from 40 to 60 J/cm2 induced early apoptosis. The increase of the time of laser irradiation significantly accelerates the conversion of photosensitized tumor cells from early to late apoptosis.

  12. Serotonin and ionizing radiation synergistically affect proliferation and adhesion molecule expression of malignant melanoma cells.

    Science.gov (United States)

    Müller, Kerstin; Gilbertz, Klaus-Peter; Meineke, Viktor

    2012-11-01

    Mast cells are key effectors of the immune system and are involved in a variety of physiological and pathophysiological processes. Dermal mast cells have been demonstrated to degranulate as a consequence of ionizing radiation exposure. Mast cells accumulate at the periphery of skin tumours including malignant melanoma. Melanoma cells thus represent a potential target for the action of mediators released from irradiated mast cells. In this study, we evaluated the effects of serotonin and ionizing radiation on the proliferation and the adhesion molecule expression of malignant melanoma cells. Human mast cells (HMC-1) were examined for serotonin release after irradiation using an enzyme-linked immunosorbent assay (ELISA). Protein expression of serotonin receptors and adhesion molecules on human melanoma cells (IPC-298) was investigated by flow cytometry. Cell attachment to fibronectin was determined by an adhesion assay. Proliferation and cell cycle kinetics were analysed by proliferation assay and 5-bromodeoxyuridine (BrdU)/DNA dual parameter flow cytometry, respectively. Ionizing radiation exposure resulted in serotonin release by HMC-1 cells. Expression of serotonin receptors was detected on IPC-298 cells. Serotonin enhanced the radiation-induced reduction in melanoma cell proliferation. Serotonin and ionizing radiation synergistically increased the expression of adhesion molecules on melanoma cells and improved cell adhesion to fibronectin. The up-regulation of cellular adhesion molecule expression was attenuated by inhibitors to phosphatidylinositol 3-kinase, mitogen-activated protein (MAP) ERK kinase and protein kinase C. Our data suggest that serotonin released from irradiated dermal mast cells modulates the radiation response of human melanoma cells. We postulate that radiation-induced mast cell degranulation and mediator release have a great impact on malignant melanoma cell development. Copyright © 2012 Japanese Society for Investigative Dermatology

  13. [Molecular-target therapy for advanced malignant melanoma].

    Science.gov (United States)

    Takahashi, Shunji

    2013-01-01

    Malignant melanoma is insensitive to chemotherapy, and standard therapy for metastatic melanoma has been dacarbazine for years. Molecular abnormalities of malignant melanoma, mainly of MAP kinase signals such as BRAF mutation, have been clarified, and molecular target therapy for melanoma has been developed recently. Vemurafenib, an inhibitor for mutated BRAF, has shown its efficacy for the first time, with response rate of more than 50%, and an overall improvement in survival compared with dacarbazine in a phase III study. Skin toxicities including squamous cell carcinoma, are the most severe adverse events. Another BRAF inhibitor, dabrafenib, and a MEK inhibitor, trametinib, have shown excellent efficacy in clinical studies. Melanoma also has high immunogenicity, and cytokines or cell immunotherapy have shown some efficacy. Recently, the importance of immune checkpoints which adjust T-cell activation, such as the cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), -B7 or the programmed cell death protein-1(PD1)-PD1 ligand(PDL1), have been clarified. Targeting those immune checkpoints is expected to be effective for enhancing tumor immunity. CTLA-4 antibody ipilimumab has been reported to improve overall survival in two phase III studies. Major adverse events were autoimmune response such as colitis, eruption, liver dysfunction and endocrineopathies. Antibodies to PD1 or PDL1 have shown a higher response rate than those of ipilimumab, and seem to accompany fewer autoimmune responses in phase I studies. These two types of targeting therapy are expected to be standard therapies for melanoma.

  14. Ensemble approach for differentiation of malignant melanoma

    Science.gov (United States)

    Rastgoo, Mojdeh; Morel, Olivier; Marzani, Franck; Garcia, Rafael

    2015-04-01

    Melanoma is the deadliest type of skin cancer, yet it is the most treatable kind depending on its early diagnosis. The early prognosis of melanoma is a challenging task for both clinicians and dermatologists. Due to the importance of early diagnosis and in order to assist the dermatologists, we propose an automated framework based on ensemble learning methods and dermoscopy images to differentiate melanoma from dysplastic and benign lesions. The evaluation of our framework on the recent and public dermoscopy benchmark (PH2 dataset) indicates the potential of proposed method. Our evaluation, using only global features, revealed that ensembles such as random forest perform better than single learner. Using random forest ensemble and combination of color and texture features, our framework achieved the highest sensitivity of 94% and specificity of 92%.

  15. Radiosensitization by fullerene-C60 dissolved in squalene on human malignant melanoma through lipid peroxidation and enhanced mitochondrial membrane potential

    Science.gov (United States)

    Kato, Shinya; Kimura, Masatsugu; Miwa, Nobuhiko

    2014-04-01

    We examined fullerene-C60 dissolved in squalene (C60/Sqe) for the ability to potentiate the radiosensitization under X-ray irradiation on human malignant melanoma HMV-II cells, which were treated with C60/Sqe and thereafter irradiated with X-ray. The cell proliferation for C60/Sqe was inhibited more markedly than for Sqe alone. Meanwhile, cell proliferation was almost unaltered for C60/squalane (Sqa) or Sqa, a hydrogenated form of Sqe, as compared to no-additive control. Thus radiosensitization of C60/Sqe is attributed to peroxidation of unsaturated bonds of squalene by X-ray-excited C60 in contrast to squalane. The fluorescence images of HMV-II cells stained with Rhodamine123, an indicator for mitochondrial membrane potential, were monitored for 6 h after X-ray irradiation. C60/Sqe obviously exhibited more augmented fluorescence intensity on perinuclear region of HMV-II cells than Sqe alone. TBARS assay showed that the lipid peroxidation level as malondialdehyde-equivalent increased by combination of C60/Sqe and X-ray dose-dependently on X-ray doses. C60/Sqe exhibited lipid peroxidation more markedly by 1.2-fold than Sqe alone. Thus the level of lipid peroxidation of squalene was sufficiently higher in C60/Sqe than in Sqe in the absence of C60 under X-ray irradiation, suggesting the combination of C60/Sqe and X-ray irradiation induced radiosensitization on HMV-II cells by peroxidation of absorbed Sqe in mitochondrial membrane via oxidative stress mediated by fullerene-C60.

  16. Malignant melanoma of the vagina: a report of 2 cases

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Ok Bae; Kim, Jin Hee; Jung, Young Yeon; Cho, Chi Heum; Choi, Tae Jin [Dongsan Medical Center, School of Medicine, Keimyung University, Daegu (Korea, Republic of)

    2005-06-15

    Primary malignant melanoma of the vagina is an extremely rare genital neoplasm occurring mainly in postmenopausal women. It has a worse prognosis than cutaneous melanomas, because of the high rate of locoregional recurrences and rapid systemic dissemination. In the past, radical surgical extirpation as the primary management had been recommended to improve loco-regional control, and possibly overall survival. However, the prognosis was poor in spite of such a radical approach. Recently, more conservative treatment such as wide local excision combined with adjuvant high-dose fraction radiotherapy seems to have promising results. Primary radiation therapy could be served as an alternative to surgery for patients with lesion less than 3 cm in diameter. We report 2 cases of primary vaginal malignant melanoma treated with radiotherapy.

  17. Malignant melanoma in an area of chronic radiodermatitis. Case report

    Energy Technology Data Exchange (ETDEWEB)

    Shono, Yoshitaka [Matsuyama Red Cross Hospital (Japan); Nakanishi, Hideki; Hashimoto, Ichiro

    2000-02-01

    This is a case report of malignant melanoma that occurred in an area of chronic radiodermatitis on the sole of the foot. A 55-year-old woman was irradiated for corns on the soles of both feet in 1967. Dermatoplasty was performed for hyperkeratosis of the sole of the right foot in 1988, but a tumor developed on the right heel in 1998, and grew larger. The histological findings suggested malignant melanoma, and the tumor including the periosteum, was removed. The patient was treated with four cycles of adjuvant chemotherapy (dacarbazine, nimustine hydrochloride, and vincristine), and no signs of recurrence one year after surgery. Based on a review of the literature, there appears to be little relation between melanoma and irradiation, and this is only the second case ever reported in Japan. (K.H.)

  18. CT of malignant choroidal melanoma - morphology and perfusion characteristics

    Energy Technology Data Exchange (ETDEWEB)

    Heller, M.; Hagemann, J.; Jend, H.H.; Guthoff, R.

    1982-03-01

    The computed tomographic morphology of malignant choroidal melanoma and its perfusion characteristics are described. Thirty-three static and serial CT examinations made on 29 patients with choroidal melanoma, three with pseudotumors of the macula and one with choroidal metastasis revealed the choroidal melanoma to be usually a hyperdense, markedly perfused tumor, while the non-contrast, diagnostically undifferentiable pseudotumors and the choroidal metastasis, revealed no significant change in density after the administration of contrast material. Density values or perfusion characteristics of choroidal melanoma that are outside of the normal range are a result of secondary changes within the immediate surroundings of the tumor, such as detachment of the retina, tumor-induced glaucoma, or tumor necrosis.

  19. The magic of numbers: malignant melanoma between science and pseudoscience.

    Science.gov (United States)

    Weyers, Wolfgang

    2011-06-01

    In 2009, a new system for staging and classification of malignant melanoma has been proposed by the American Joint Committee on Cancer (AJCC). The AJCC recommends that staging of primary melanoma be based on 3 criteria, namely, thickness, ulceration, and mitotic rate, the latter substituting Clark levels in the previous classification. In melanomas measuring ≤1 mm in thickness, ulceration or finding of single mitotic figure in the dermis defines stage T1b. According to the AJCC, sentinel lymph node dissection should be considered for those melanomas because of a significantly impaired prognosis. As with other prognostic parameters, however, assessment of mitotic rate, with one mitotic figure being the cutoff point, is highly unreliable, and statistics based on such data lack validity. Despite the large database being employed, they may be pseudoscience rather than science.

  20. An amelanotic malignant melanoma masquerading as hypergranulation tissue.

    Science.gov (United States)

    Cahill, S; Cryer, J R; Otter, S J; Ramesar, K

    2009-01-01

    We report a case of amelanotic malignant melanoma occurring in the nail sulcus of the hallux, which on initial presentation was mistaken for hypergranulation tissue due to an in-growing toenail. We highlight the importance of this differential diagnosis as such lesions can have serious sequelae.

  1. ORIGINAL ARTICLE Malignant melanoma in a Nigerian tertiary ...

    African Journals Online (AJOL)

    Test

    adjuvant chemotherapy. Table 1. Patterns of presentation in malignant melanoma. *Excision .... trauma, exposure to agricultural chemicals, presence of pre-existing moles on the sole and high total body naevus ... the only adjuvant treatment given to our patients. This methylating agent is the reference agent of choice in ...

  2. Extra nodal growth as a prognostic factor in malignant melanoma

    NARCIS (Netherlands)

    Koopal, SA; Tiebosch, ATMG; Daryanani, D; Plukker, JTM; Hoekstra, HJ

    Aim. Extra nodal growth (ENG) in lymph-node metastases may be an additional. indicator for poor prognosis and increased Loco-regional recurrence in patients with a cutaneous malignant melanoma (CMM). Most studies analyzing prognostic factors tack a proper definition or description of the

  3. Malignant melanoma in a Nigerian tertiary hospital | Emegoakor ...

    African Journals Online (AJOL)

    Background: Malignant melanoma is a neoplasm of melanocytes which usually arises from the skin and other parts of the body where melanocytes exist. The incidence is low in black Africa and occurs mostly in the extremities. Surgery is the main stay of treatment for localised disease. Methodology: A 5-year retrospective ...

  4. Malignant Melanoma in an Albino | Efem | Sudan Journal of Medical ...

    African Journals Online (AJOL)

    Oculocutaneous albinism is a rare autosomal recessive disorder characterised by generalised depigmentation, photophobia, decreased visual acuity, and nystagmus. Malignant melanoma is rare in patients with albinism. We report a case of a large advanced fumigating tumour on the right forearm of a male Nigerian albino ...

  5. Socioeconomic status and cutaneous malignant melanoma in Northern Europe

    DEFF Research Database (Denmark)

    Idorn, L W; Wulf, H C

    2014-01-01

    Socioeconomic status (SES) is associated with cutaneous malignant melanoma (CMM), also in Northern Europe despite equal access to health care. SES per se is not responsible for this association which must be ascribed to important risk factors for CMM such as intermittent UVR exposure, and screening...

  6. Pattern of cutaneous malignant melanoma in Zaria, Nigeria ...

    African Journals Online (AJOL)

    The histopathological patterns of distribution, presence of dark brown melanin pigments, nucleolar appearance and Clark's histological grading were studied. The data was analysed and tabulated into frequency tables. Results: Fifty four cases of cutaneous malignant melanoma were reviewed. The over all male: female sex ...

  7. Psychoeducational intervention for patients with cutaneous malignant melanoma

    DEFF Research Database (Denmark)

    Boesen, Ellen H; Ross, Lone; Frederiksen, Kirsten

    2005-01-01

    PURPOSE: In 1993, a randomized intervention study among patients with malignant melanoma showed a significant decrease in psychological distress and increased coping capacity 6 months after the intervention and enhanced survival 6 years later. We applied a similar intervention with a few modifica......PURPOSE: In 1993, a randomized intervention study among patients with malignant melanoma showed a significant decrease in psychological distress and increased coping capacity 6 months after the intervention and enhanced survival 6 years later. We applied a similar intervention with a few...... modifications in a randomized controlled trial among Danish patients with malignant melanoma and evaluated results on immediate and long-term effects on psychological distress and coping capacity. PATIENTS AND METHODS: A total of 262 patients with primary cutaneous malignant melanoma were randomly assigned...... to the control or intervention group. Patients in the intervention group were offered six weekly sessions of 2 hours of psychoeducation, consisting of health education, enhancement of problem-solving skills, stress management, and psychological support. The participants were assessed at baseline before random...

  8. Caffeine Intake, Coffee Consumption, and Risk of Cutaneous Malignant Melanoma.

    Science.gov (United States)

    Wu, Shaowei; Han, Jiali; Song, Fengju; Cho, Eunyoung; Gao, Xiang; Hunter, David J; Qureshi, Abrar A

    2015-11-01

    Caffeine has been shown to prevent ultraviolet radiation-induced carcinogenesis and to inhibit growth of melanoma cells in experimental studies. We evaluated the association among caffeine intake, coffee consumption, and melanoma risk among three large cohort studies. The analysis used data from 89,220 women in the Nurses' Health Study II (1991-2009), 74,666 women in the Nurses' Health Study (1980-2008), and 39,424 men in the Health Professionals Follow-up Study (1986-2008). We used Cox proportional hazards models to estimate the hazard ratios (HR) with 95% confidence intervals (CIs) of melanoma associated with dietary intakes. We documented 2,254 melanoma cases over 4 million person-years of follow-up. After adjustment for other risk factors, higher total caffeine intake was associated with a lower risk of melanoma (≥393 mg/day vs. caffeinated coffee consumption, whereas no association was found for decaffeinated coffee consumption and melanoma risk. Increasing caffeine intake and caffeinated coffee consumption is associated with decreased risk of cutaneous malignant melanomas.

  9. Malignant melanoma revealed by testicular metastasi.

    Directory of Open Access Journals (Sweden)

    Marie Dusaud

    2015-01-01

    Due to rapid disease progression and high mortality rate within a short interval, a complete staging looking for other secondary locations must be done and a multidisciplinary care and palliative involvement must also be initiated in the context of metastatic melanoma.

  10. Malignant melanoma in teenagers and young adults.

    Science.gov (United States)

    Kolandijan, Nathalie A; Wei, Caimiao; Burke, Anahit; Bedikian, Agop Y

    2014-10-01

    This study compares the natural history and treatment outcomes of cutaneous melanoma in teenagers and young adults to determine if exclusion of teenagers from investigative trials is justified. This is a chart review of patients between the ages of 13 and 40 years treated at The University of Texas MD Anderson Cancer Center for melanoma. Data related to the natural history and treatment outcomes were collected. Statistical tools were used to compare characteristics between teenagers and young adults. Cox proportional hazard models were utilized to examine the association between age group and overall survival. Of the 476 patients, 109 were teenagers and 367 were young adults. Both groups had comparable disease stage, pathology, and rates of metastasis. Initial disease stage and pathology significantly influenced survival. Sixty-six of 452 patients with skin melanoma developed metastasis. Teenagers survived better than young adults from diagnosis of the skin primary and after development of systemic metastasis. Teenagers tolerated and benefited from interleukin-2-based systemic therapy and targeted therapies as well as the young adults. Because of the similarities in natural history and treatment outcomes between teenage and young adult patients, it is recommended that teenage patients be officially enrolled on adult melanoma therapeutic trials.

  11. [Sentinel lymph node in malignant melanoma].

    Science.gov (United States)

    Salas, Carmen; Pérez, Natividad

    2004-06-01

    The authors describe the technique called sentry ganglion, the ganglion which has the highest risk of receiving neoplastic cells and towards which a primary tumor directs its metastasis. The authors explain the procedure for carrying out a biopsy on this ganglion and its warnings regarding different neoplasias and specifically regarding melanoma.

  12. [Malignant Melanoma - from Classical Histology towards Molecular Genetic Testing].

    Science.gov (United States)

    Ryška, A; Horký, O; Berkovcová, J; Tichá, I; Kalinová, M; Matějčková, M; Bóday, Á; Drábek, J; Martínek, P; Šimová, J; Sieglová, K; Vošmiková, H

    Malignant melanoma is - in comparison with other skin tumors - a relatively rare malignant neoplasm with highly aggressive biologic behavior and variable prognosis. Recent data in pathology and molecular diagnostics indicate that malignant melanoma is in fact not a single entity but a group of different neoplasms with variable etiopathogenesis, biologic behavior and prognosis. New therapeutic options using targeted treatment blocking MAPK signaling pathway require testing of BRAF gene mutation status. This helps to select patients with highest probability of benefit from this treatment. This article summarizes information on the correlation of morphological findings with genetic changes, discusses the representation of individual genetic types in various morphological subgroups and deals with the newly proposed genetic classification of melanoma and the current possibilities, pitfalls and challenges in BRAF testing of malignant melanoma. It also describes the current testing situation in the Czech Republic - the methods used, the representation of BRAF mutations in the tested population and the future of testing. It also shows the limitations of the BRAF and MEK targeted treatment concept resulting from the heterogeneity of the tumor population. Mechanisms of acquired resistance to MAPK pathway inhibitors, possibilities of their detection, and issues of combination of targeted therapy and immunotherapy are discussed.Key words: malignant melanoma - BRAF - mutation - molecular targeted therapy - tumor microenvironment - tumor heterogeneity This work was supported by projects PROGRES Q40/11, BBMRICZ LM2015089, SVV 260398 and GACR 17-10331S. The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.Submitted: 28. 3. 2017Accepted: 16. 5. 2017.

  13. Clear cell melanoma: a cutaneous clear cell malignancy.

    Science.gov (United States)

    Pletneva, Maria A; Andea, Aleodor; Palanisamy, Nallasivam; Betz, Bryan L; Carskadon, Shannon; Wang, Min; Patel, Rajiv M; Fullen, Douglas R; Harms, Paul W

    2014-10-01

    Clear cell melanoma is a rare clear cell malignancy. Accurate diagnosis of clear cell melanoma requires integration of immunohistochemical and morphologic findings, with molecular studies to rule out clear cell sarcoma. The differential diagnosis includes melanoma, carcinoma, perivascular epithelioid cell tumor, and epidermotropic clear cell sarcoma. We use a case of a lesion on the helix of an 86-year-old man as an example. Histologic examination revealed an ulcerated clear cell malignant tumor. Tumor cell cytoplasm contained periodic acid-Schiff-positive, diastase-sensitive glycogen. Tumor cells showed positive labeling for S100, HMB-45, and Melan-A, and negative labeling for cytokeratins, p63, and smooth muscle actin. Molecular studies demonstrated BRAF V600E mutation, copy gains at the 6p25 (RREB1) and 11q13 (CCND1) loci, and absence of EWSR1-ATF1 fusion. These findings supported a diagnosis of clear cell melanoma. The rare pure clear cell morphology occurs due to accumulation of intracytoplasmic glycogen. We review the differential diagnosis of clear cell melanoma and describe the utility of immunohistochemical and molecular studies in confirming this diagnosis.

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

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    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.

  15. Malignant melanocytic neoplasm of pancreas with liver metastasis: Is it malignant melanoma or clear cell sarcoma?

    Science.gov (United States)

    Kodiatte, Thomas Alex; George, Sam Varghese; Chacko, Raju Titus; Ramakrishna, Banumathi

    2017-01-01

    Malignant melanocytic neoplasm, usually seen in soft tissues, is rare in a visceral location and presents as a diagnostic dilemma. We present a case of pancreatic malignant melanocytic neoplasm with liver metastasis. A 58-year-old man presented with left upper abdominal swelling and loss of appetite. Imaging revealed a large mass arising from the pancreatic tail, and this was diagnosed as malignant neoplasm with melanocytic differentiation on biopsy with the possible differentials of malignant melanoma, clear cell sarcoma (CCS), and perivascular epithelioid cell neoplasm. The patient underwent distal pancreatectomy and splenectomy for the same. Follow-up imaging 6 months later showed a metastatic liver lesion, for which he also underwent a liver resection. BRAF mutational analysis was found to be negative. Both CCS and malignant melanoma have similar morphological features and melanocytic differentiation, but each harbors a distinct genetic background. Differentiation of both has diagnostic and therapeutic implications.

  16. 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.

  17. Vitamin D status and risk for malignant cutaneous melanoma: recent advances.

    Science.gov (United States)

    Ombra, Maria N; Paliogiannis, Panagiotis; Doneddu, Valentina; Sini, Maria C; Colombino, Maria; Rozzo, Carla; Stanganelli, Ignazio; Tanda, Francesco; Cossu, Antonio; Palmieri, Giuseppe

    2017-11-01

    Cutaneous malignant melanoma, whose incidence is increasing steadily worldwide, is the result of complex interactions between individual genetic factors and environmental risk factors. Ultraviolet radiation represents the most important environmental risk factor for the development of skin cancers, including melanoma. Sun exposure and early sunburn during childhood are the principal causes of cutaneous melanoma insurgence in adults, with double the risk relative to a nonexposed population. Consequently, ultraviolet protection has long been recognized as an important measure to prevent such a malignancy. Biological and epidemiological data suggest that vitamin D status could affect the risk of cancer and play a role in cancer prevention by exerting antiproliferative effects. Solar radiations are critical for vitamin D synthesis in humans; however, uncontrolled and intensive sun exposure is dangerous to skin health and may contribute toward the development of cutaneous malignant melanoma. An optimum balance between sun protection and exposure is thus advocated. Additional research is required to confirm the preventive role of vitamin D in melanoma incidence or a positive influence on patient outcome.

  18. Malignant melanoma of the stomach presenting in a woman: a case report

    Directory of Open Access Journals (Sweden)

    Aslan İlknur

    2011-03-01

    Full Text Available Abstract Introduction Malignant melanoma is reported to metastasize to all organs of the human body. Although it is common for it to metastasize to the gastrointestinal tract, a melanoma located primarily in the gastric mucosa is an uncommon tumor. Gastrointestinal metastases are rarely diagnosed before death with radiological and endoscopic techniques. Case presentation In this case report the clinical course and treatment of a woman with melanoma of the stomach, without any other detectable primary lesion, is presented and discussed. A 55-year-old Turkish woman presented to our clinic with complaints of muscle pain and bone pain in the left side of her chest. During an upper gastrointestinal system endoscopy, dark cherry-colored, light elevated, round-shaped lesions were taken from her gastric fundus and from the first part of her duodenum. Biopsies from these samples were determined to be malignant melanoma by the pathologist. Conclusion Metastatic malignant melanoma cases should be examined through endoscopy for gastrointestinal metastases.

  19. Oncolytic virotherapy including Rigvir and standard therapies in malignant melanoma.

    Science.gov (United States)

    Babiker, Hani M; Riaz, Irbaz Bin; Husnain, Muhammad; Borad, Mitesh J

    2017-01-01

    The treatment of metastatic melanoma has evolved from an era where interferon and chemotherapy were the mainstay of treatments to an era where immunotherapy has become the frontline. Ipilimumab (IgG1 CTLA-4 inhibitor), nivolumab (IgG4 PD-1 inhibitor), pembrolizumab (IgG4 PD-1 inhibitor) and nivolumab combined with ipilimumab have become first-line therapies in patients with metastatic melanoma. In addition, the high prevalence of BRAF mutations in melanoma has led to the discovery and approval of targeted molecules, such as vemurafenib (BRAF kinase inhibitor) and trametinib (MEK inhibitor), as they yielded improved responses and survival in malignant melanoma patients. This is certainly a burgeoning time in immunotherapy drug development, and the aforementioned efforts along with the recent US Food and Drug Administration approval of talimogene laherparepvec (T-VEC), a recombinant oncolytic herpes virus, have paved the way to exploring the role of additional oncolytic viruses, such as the echovirus Rigvir, as new and innovative treatment modalities in patients with melanoma. Herein, we discuss the current standard of care treatment in melanoma with an emphasis on immunotherapy and oncolytic viruses in development.

  20. 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.

  1. 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.

  2. Relationship Between LAPTM4B Gene Polymorphism and Susceptibility of Malignant Melanoma in Chinese Patients

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    Meng Zhang

    2014-10-01

    Full Text Available Lysosomal-associated protein transmembrane 4 beta (LAPTM4B is known as an oncogene associated with many human malignant tumors. There are two alleles of the gene, LAPTM4B*1 and LAPTM4B*2. Previous studies have shown that LAPTM4B polymorphism contributes to the risk of many cancers. This case-control study was to investigate the relationship between LAPTM4B gene polymorphism and susceptibility of malignant melanoma. The genotypes of LAPTM4B were determined in 617 control subjects and 220 patients with malignant melanoma by utilizing polymerase chain reaction based on specific primers. The genotypic distribution of LAPTM4B and Hardy–Weinberg equilibrium were analyzed by χ2 test. Odds ratio and 95% confidence interval was calculated by unconditional logistic regression. The distributions of LAPTM4B genotypes were significantly different between melanoma patients (45.9% for *1/1, 46.4% for *1/2 and 7.7 for *2/2 and controls (54.5% for *1/1, 39.9% for *1/2 and 5.7 for *2/2. LAPTM4B *1/2 and LAPTM4B *2/2 had a 1.396-fold and 1.619-fold higher risk for melanoma occurrence than *1/1, and subjects with LAPTM4B*2 have a 1.308-fold higher risk than LAPTM4B*1 carriers. No association between LAPTM4B genotypes and gender, age, subtype, Clark level of invasion, Breslow thickness, ulceration, clinical stage, and C-KIT, BRAF gene mutation status was observed. LAPTM4B*2 is associated with the high risk of malignant melanoma and carrying LAPTM4B *2 may be a susceptible factor to Chinese melanoma patients.

  3. Temozolomide and cisplatin in avdanced malignant melanoma.

    Science.gov (United States)

    Daponte, Antonio; Ascierto, Paolo Antonio; Gravina, Adriano; Melucci, Mariateresa; Scala, Stefania; Ottaiano, Alessandro; Simeone, Ester; Palmieris, Giuseppe; Comella, Giuseppe

    2005-01-01

    Temozolomide (TMZ) is an oral alkylating agent; it produces DNA methyl adducts, which are removed by the DNA repair enzyme AGAT. In vitro studies suggest that CDDP may enhance the antitumor activity of TMZ due to the ability of cisplatin (CDDP) to down-regulate AGAT activity. In a previous phase I study, the combination of TMZ and CDDP was tested, and the recommended dose for each drug was defined. On the basis of these results, we designed a phase II study to evaluate the activity and safety profile of the TMZ-CDDP association in patients with advanced melanoma. From March 2001 to March 2002, 37 patients with metastatic melanoma, not amenable to surgery, were enrolled in this study. All eligible patients were treated with the combination of CDDP 75 mg/m2 i.v. d 1, TMZ 200 mg/m2 p.o. days 1-5 recycled every 4 weeks. Interferon alpha2b (IFN alpha2b) was administered at the end of chemotherapy to responsive patients at the dose of 5 M.I. U s.c. 3 times a week for 1 year. A total of 174 courses were administered, with a median number of 4 courses/patient (range 1-10). After chemotherapy, 9 CRs and 9 PRs were observed for an overall response rate of 48.6% (95% C.I., 31.9%-65.6%). One of 5 patients with initial brain metastases showed a complete response to the therapy. Five out of 9 CR patients were still with no evidence of recurrence, ranging from 28+ to 82+ weeks. The median survival time was 48 weeks. The schedule was well tolerated, with the most frequent adverse events reported being nausea and vomiting (59%), alopecia (14%) and fatigue (11%), all well controlled by supportive therapy. Haemotological toxicities were mild to moderate. Side-effects attributable to IFN alpha2b were also mild and manageable. The combination of TMZ and CDDP seems to be active in untreated patients with advanced melanoma. Absence of recurrence in the majority (5/9; 56%) of CR patients seems to indicate that IFN may act on the duration of the response to chemotherapy. The schedule was

  4. Symptomatic malignant melanoma presenting as multiple gastrointestinal polyps.

    Science.gov (United States)

    Casey, Shauna; Dvorkin, Lee; Alsanjari, Nazar; Dezso, Balazs

    2011-03-03

    We report on a 66-year-old man with a past medical history of gout who presented to his general practitioner (GP) in July 2009 with a history of nausea and intermittent diarrhoea. He had lost 6 kg in weight over 6 months. His GP found he was anaemic and referred him to a gastrointestinal outpatient clinic. He went on to have a gastroscopy and colonoscopy, which revealed multiple polyps in the stomach, duodenum and colon. Histology revealed that all the polyps were malignant melanoma. He had no known history of malignant melanoma. A staging CT scan revealed multiple lung metastases and he was referred for palliative care. The patient died 4 months after diagnosis.

  5. Malignant Melanoma of Nose and Paranasal Sinuses: 2 Case Reports

    Directory of Open Access Journals (Sweden)

    Sanjeev Bhagat

    2010-04-01

    Full Text Available Malignant melanoma is one of the rare and highly aggressive diseases of the sinonasal cavity. High index of suspicion is required for diagnosis as the patient usually presents with non specific signs and symptoms. In the natural course of the disease, higher rate of loco regional recurrences and distant metastasis are seen making the overall prognosis of disease very poor. In reviewing the various treatment modalities used in the past, surgical resection of the tumour with postoperative radiotherapy is preferred one. Advances in surgery, radiotherapy and chemotherapy don’t have any impact on improved survival, which remains poor in this disease. We report two cases of malignant melanoma, which were treated at our institute.

  6. Stereotactic radiosurgery in intraocular malignant melanoma--retrospective study.

    Science.gov (United States)

    Furdova, Alena; Sramka, Miron; Chorvath, Martin; Kralik, Gabriel; Krasnik, Vladimir; Krcova, Ivana; Waczulikova, Iveta

    2014-01-01

    One day session linear accelerator based stereotactic radiosurgery of intraocular malignant melanoma is a method of "conservative" attitude to treat posterior uveal melanoma. Retrospective clinic-based study of patients with posterior uveal melanoma in stage T2/T3 who underwent stereotactic radiosurgery at linear accelerator in period 2001-2011. Immobilization of the affected eye was achieved by mechanical fixation to the stereotactic Leibinger frame. The stereotactic treatment planning after fusion of computed tomography and magnetic resonance imaging was optimized according to the critical structures (lenses, optic nerves, chiasm). In group of 96 patients with posterior uveal melanoma treated with one day session stereotactic radiosurgery, patient age ranged from 25 to 80 years with a median of 54 years. Median tumor volume at baseline was 0.6 cm(3) (with range from 0.2 to 1.0 cm(3)). Median maximal dose applied was 49.0 Gy (range from 37.0 to 52.0 Gy). Secondary enucleation was necessary in 11 patients (11.5%) due to complications like irradiation neuropathy and secondary glaucoma. Tumor local control was successful in 95% of patients in 3 years interval after stereotactic radiosurgery and in 85% of patients in 5 years interval after stereotactic radiosurgery. One step LINAC based stereotactic radiosurgery with a single dose 35.0 Gy is one of treatment options to treat T2 or T3 stage posterior uveal melanoma.

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

    Directory of Open Access Journals (Sweden)

    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.

  8. Oncolytic virotherapy including Rigvir and standard therapies in malignant melanoma

    Directory of Open Access Journals (Sweden)

    Babiker HM

    2017-02-01

    Full Text Available Hani M Babiker,1 Irbaz Bin Riaz,2 Muhammad Husnain,2 Mitesh J Borad3,4 1University of Arizona Cancer Center, 2Department of Internal Medicine, University of Arizona, Tucson, 3Division of Hematology-Oncology, Mayo Clinic Cancer Center, Scottsdale, AZ, 4Department of Molecular Medicine, Center for Individualized Medicine, Mayo Clinic, Rochester, MN, USA Abstract: The treatment of metastatic melanoma has evolved from an era where interferon and chemotherapy were the mainstay of treatments to an era where immunotherapy has become the frontline. Ipilimumab (IgG1 CTLA-4 inhibitor, nivolumab (IgG4 PD-1 inhibitor, pembrolizumab (IgG4 PD-1 inhibitor and nivolumab combined with ipilimumab have become first-line therapies in patients with metastatic melanoma. In addition, the high prevalence of BRAF mutations in melanoma has led to the discovery and approval of targeted molecules, such as vemurafenib (BRAF kinase inhibitor and trametinib (MEK inhibitor, as they yielded improved responses and survival in malignant melanoma patients. This is certainly a burgeoning time in immunotherapy drug development, and the aforementioned efforts along with the recent US Food and Drug Administration approval of talimogene laherparepvec (T-VEC, a recombinant oncolytic herpes virus, have paved the way to exploring the role of additional oncolytic viruses, such as the echovirus Rigvir, as new and innovative treatment modalities in patients with melanoma. Herein, we discuss the current standard of care treatment in melanoma with an emphasis on immunotherapy and oncolytic viruses in development. Keywords: melanoma, virotherapy, Rigvir

  9. Gamma-Secretase/Notch Signalling Pathway Inhibitor RO4929097 in Treating Patients With Stage IV Melanoma

    Science.gov (United States)

    2016-05-06

    Acral Lentiginous Malignant Melanoma; Lentigo Maligna Malignant Melanoma; Nodular Malignant Melanoma; Recurrent Melanoma; Solar Radiation-related Skin Melanoma; Stage IV Melanoma; Superficial Spreading Malignant Melanoma

  10. Obesity and melanoma: could fat be fueling malignancy?

    Science.gov (United States)

    Clement, Emily; Lazar, Ikrame; Muller, Catherine; Nieto, Laurence

    2017-05-01

    Over the last decade, it has become increasingly clear that adipose tissue, and particularly adipocytes, contributes to tumor progression. Obesity, an ever-increasing worldwide phenomenon, exacerbates this effect. The influence of obesity on melanoma remains poorly studied, although recent data do underline an association between the two diseases in both humans and murine models. Herein, we review the impact of obesity on melanoma incidence and progression and discuss the underlying mechanisms known to be involved. Adipose tissue favors the proliferation and aggressiveness of melanoma cells through a direct dialog, mediated by soluble factors and by exosomes, and through remodeling of the tumor microenvironment. This knowledge could, in the future, help to design new personalized therapeutic options for obese melanoma patients. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  11. The miRNA machinery in primary cutaneous malignant melanoma, cutaneous malignant melanoma metastases and benign melanocytic nevi.

    Science.gov (United States)

    Sand, Michael; Skrygan, Marina; Georgas, Dimitrios; Sand, Daniel; Gambichler, Thilo; Altmeyer, Peter; Bechara, Falk G

    2012-10-01

    Although several studies have shown a dysregulation of microRNA (miRNA) expression profiles in cutaneous melanoma, there has been little research on the miRNA machinery itself. In this study, we investigated the mRNA expression profiles of different miRNA machinery components in primary cutaneous malignant melanoma (PCMM), cutaneous malignant melanoma metastases (CMMM) and benign melanocytic nevi (BMN). Patients with PCMM (n = 7), CMMM (n = 6) and BMN (n = 7) were included in the study. Punch biopsies were harvested from the centers of tumors (lesional) and from BMN (control). In contrast to previous reports exploring specific clusters of miRNAs in PCMM, the present study investigates mRNA expression levels of Dicer, Drosha, Exp5, DGCR8 and the RISC components PACT, argonaute-1, argonaute-2, TARBP1, TARBP2, MTDH and SND1, which were detected by TaqMan real-time reverse transcription polymerase chain reaction (RT-PCR). Argonaute-1, TARBP2 and SND1 expression levels were significantly higher in BMN compared to PCMM (p  0.05). The results of this study show that the miRNA machinery components argonaute-1, TARBP2 and SND1 are dysregulated in PCMM and CMMM compared to BMN and may play a role in the process of malignant transformation.

  12. Robot-assisted anterior pelvic exenteration in vulvovaginal malignant melanoma.

    Science.gov (United States)

    Kim, Se Ik; Lee, Seungmee; Jeong, Chang Wook; Kim, Hee Seung

    2017-12-21

    Melanomas of the vulva and vagina are rare, and surgery is the gold standard of treatment [1, 2]. Since recent studies have reported pelvic exenteration by using robotic surgical system [3, 4], we showed the surgical procedures of robot-assisted anterior pelvic exenteration (rAPE) with ileal conduit urinary diversion for vulvovaginal malignant melanoma. A 55-year-old woman who received vaginal wall resection due to vaginal malignant melanoma 8months before was referred. Multiple biopsies of pigmented lesions on the vulva, vagina, and urethral orifice confirmed the recurrence, whereas preoperative image studies revealed no abnormal findings. Thus, we performed rAPE with ileal conduit urinary diversion. First, we performed robot-assisted bilateral inguinal and pelvic lymphadenectomy. Thereafter, we conducted en bloc resection of the bladder, uterus, vagina, and vulva through abdominal and perineal approaches (Fig. 1): Under the 4-arm robotic surgical system, prevesical space was developed and laterally dissected along the undersurface of pubic bone, to the level of levator ani muscles. Bilateral infudibulopelvic ligaments, uterine arteries and parametrium, uterosacral ligaments, and pubovesical ligaments were ligated and resected. During the wide local excision of the vulva, the rectovaginal space was dissected along the posterior vaginal wall. En bloc specimen was successfully delivered. Finally, the ileal conduit urinary diversion was performed. Total operative time was 4.5h excluding set-up and docking times of the robotic surgical system. The pathologic report ascertained clear resection margin and no lymph node involvement. rAPE with ileal conduit urinary diversion for treatment of vulvovaginal malignant melanoma is feasible (Fig. 1). Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Immunological correlates of treatment and response in stage IV malignant melanoma patients treated with Ipilimumab

    DEFF Research Database (Denmark)

    Bjoern, Jon; Juul Nitschke, Nikolaj; Zeeberg Iversen, Trine

    2016-01-01

    ABSTRACT: Introduction: Ipilimumab is effective in the treatment of metastatic malignant melanoma, but few biomarkers reliably predict treatment response. Methods: Patients were treated with Ipilimumab for metastatic malignant melanoma. Blood and serum samples were collected before and during...... to increased ALC, T cell count and T cell activation in malignant melanoma patients responding to treatment. A high baseline frequency of myeloid-derived suppressor cells and high levels of IL6 is associated with a reduced chance of responding to therapy....

  14. 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.

  15. Sun exposure before and after a diagnosis of cutaneous malignant melanoma

    DEFF Research Database (Denmark)

    Idorn, L W; Philipsen, P A; Wulf, H C

    2011-01-01

    Previous studies on ultraviolet radiation (UVR) exposure before and after a diagnosis of cutaneous malignant melanoma (CMM) have been based primarily on questionnaires. Objective measures are needed....

  16. Improving early recognition of malignant melanomas by digital image analysis in dermatoscopy.

    Science.gov (United States)

    Horsch, A; Stolz, W; Neiss, A; Abmayr, W; Pompl, R; Bernklau, A; Bunk, W; Dersch, D R; Glässl, A; Schiffner, R; Morfill, G

    1997-01-01

    The malignant melanoma (MM) is the most dangerous human skin disease. The incidence increased dramatically during the last years. The only chance for the patient is an early recognition and excision of the MM. The best diagnostic method for this is skin surface microscopy or dermatoscopy. Its use, however, requires much expertise. In order to support learning and using the method, a computer-based dermatoscopy workstation is being developed. Among others, new complexity measures are used for the image analysis.

  17. 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.

  18. Serial or Parallel Metastasis of Cutaneous Melanoma? A Study of the German Central Malignant Melanoma Registry.

    Science.gov (United States)

    Gassenmaier, Maximilian; Eigentler, Thomas Kurt; Keim, Ulrike; Goebeler, Matthias; Fiedler, Eckhard; Schuler, Gerold; Leiter, Ulrike; Weide, Benjamin; Grischke, Eva-Maria; Martus, Peter; Garbe, Claus

    2017-12-01

    For more than a century the Halstedian hypothesis of contiguous metastasis from the primary tumor through the lymphatics to distant sites shaped lymph node surgery for melanoma. We challenge this dogma of serial metastatic dissemination. A single-center series of 2,299 patients with cutaneous metastatic melanoma was investigated to analyze overall survival and distant metastasis-free survival of stage IV patients with or without primary lymphatic metastasis. Results were then compared with those of 2,134 patients from three independent centers of the German Central Malignant Melanoma Registry. A multivariate binary logistic regression model was used to identify risk factors for the initial metastatic pathway. Distant metastasis-free survival (hazard ratio = 1.02; 95% confidence interval = 0.91-1.14; P = 0.76) and overall survival (HR = 1.09; 95% CI = 0.96-1.23; P = 0.177) did not differ between stage IV patients with primary hematogenous or primary lymphatic metastasis. Melanoma localization was the only significant risk factor for the initial metastatic pathway. These findings indicate that regional and distant metastases originate from the primary tumor itself in a rather parallel than serial fashion and could explain the lack of survival benefit associated with immediate complete lymph node dissection in sentinel lymph node-positive melanoma patients. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  19. A PRELIMARY APPROACH FOR THE AUTOMATED RECOGNITION OF MALIGNANT MELANOMA

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    Ezzeddine Zagrouba

    2011-05-01

    Full Text Available In this work, we are motivated by the desire to classify skin lesions as malignants or benigns from color photographic slides of the lesions. Thus, we use color images of skin lesions, image processing techniques and artificial neural network classifier to distinguish melanoma from benign pigmented lesions. As the first step of the data set analysis, a preprocessing sequence is implemented to remove noise and undesired structures from the color image. Second, an automated segmentation approach localizes suspicious lesion regions by region growing after a preliminary step based on fuzzy sets. Then, we rely on quantitative image analysis to measure a series of candidate attributes hoped to contain enough information to differentiate melanomas from benign lesions. At last, the selected features are supplied to an artificial neural network for classification of tumor lesion as malignant or benign. For a preliminary balanced training/testing set, our approach is able to obtain 79.1% of correct classification of malignant and benign lesions on real skin lesion images.

  20. 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.

  1. Primary malignant esophageal melanoma arising from localized benign melanocytosis.

    Science.gov (United States)

    Maroy, Bernard; Baylac, Francois

    2013-04-01

    A heavy drinker and smoker had a normal UGI-endoscopy in 1996. In 1999, a repeat examination disclosed distal esophageal benign melanocytosis, typical, macro- and microscopically. Endoscopic and microscopic features were stable in 2002 and 2004. In 2007, dysphagia prompted an endoscopy, which disclosed a poorly differentiated epidermoid carcinoma at 19 cm and black nodules of the cardia with a microscopy typical of malignant melanoma, uT3N1 at EUS. Radiochemotherapy led to an 8-month improvement, which did not prevent death one year after diagnosis. Copyright © 2012. Published by Elsevier Masson SAS.

  2. 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

    Mucosal melanomas constitute 1.3% of all melanomas and they may develop in any mucosal membrane. Conjunctival melanomas (0.5/million/year) and melanomas in the sinonasal cavity (0.5/million/year) are the most common, followed by anorectal melanomas (0.4/million/year) and melanomas in the oral cav...

  3. Orbital malignant melanoma associated with nevus of Ota

    Directory of Open Access Journals (Sweden)

    Cherungottil V Radhadevi

    2013-01-01

    Full Text Available Nevus of Ota (oculodermal melanosis is a dermal melanocytic hamartoma with bluish hyperpigmentation along the first and second branches of the trigeminal nerve. Extracutaneous involvement, especially ocular, has been reported. A 45-year-old male presented with malignant melanoma of the left orbit in association with nevus of Ota. Being locally invasive, a modified exenteration with frontal flap repair was done on left eye. Adjuvant chemotherapy was given after wound healing. All pigmented lesions of the eye require close monitoring to help in the early diagnosis. Since malignant transformation has been reported in oculodermal melanosis, close follow-up and patient education will facilitate early diagnosis and prompt management. This case is reported for its rarity and unusual presentation.

  4. Malignant melanoma and breast carcinoma: a bidirectional correlation.

    LENUS (Irish Health Repository)

    Ho, W L

    2009-03-05

    BACKGROUND: Epidemiologic and genetic studies have suggested a bidirectional association between breast carcinoma (BC) and malignant melanoma (MM). OBSERVATION: We present a series of patients with MM and BC detected in our department within a span of 6 months, raising concerns for the high associations between the two malignancies. This led us to match the concordance of the two tumours in the National Irish Cancer Registry. CONCLUSION: The national figures provide evidence of a link between BC and MM. We recommend increased awareness among clinicians leading to more detailed surveillance of both second primary tumours. All MM patients with a family history of BC should be referred to a breast clinic. Women above the age of 40 with MM should undergo annual mammography and those less than 40 may be better evaluated with a breast MRI. All breast cancer patients should be made aware of the significance of changing moles and those with suspicious lesions referred to a dermatologist for evaluation.

  5. Malignant melanoma and breast carcinoma: a bidirectional correlation.

    LENUS (Irish Health Repository)

    Ho, W L

    2012-02-01

    BACKGROUND: Epidemiologic and genetic studies have suggested a bidirectional association between breast carcinoma (BC) and malignant melanoma (MM). OBSERVATION: We present a series of patients with MM and BC detected in our department within a span of 6 months, raising concerns for the high associations between the two malignancies. This led us to match the concordance of the two tumours in the National Irish Cancer Registry. CONCLUSION: The national figures provide evidence of a link between BC and MM. We recommend increased awareness among clinicians leading to more detailed surveillance of both second primary tumours. All MM patients with a family history of BC should be referred to a breast clinic. Women above the age of 40 with MM should undergo annual mammography and those less than 40 may be better evaluated with a breast MRI. All breast cancer patients should be made aware of the significance of changing moles and those with suspicious lesions referred to a dermatologist for evaluation.

  6. Nevus of the Eyelid Margin Mimicking a Malignant Melanoma

    Directory of Open Access Journals (Sweden)

    A. Echchaoui

    2016-06-01

    Full Text Available Nevi are a benign skin lesions commonly found on the eyelid margin, these tumors are usually pigmented and have thickness. Nevi are not typically visible at birth; they appear during childhood and often exhibit a more rapid increase in pigmentation about the time of puberty. Most eyelid nevi can be diagnosed by clinical examination; suspicious lesions should be biopsied when rapid growth, loss of eyelashes or discoloration of the nevus is noted. Eyelid nevi require treatment if malignant transformation and/or cosmetically bothersome to the patient. We report a case of a 37-year-old female patient exhibited a single cutaneous tumor at the free margin of the lower left eyelid, she noticed a dark spot on their eyelid since childhood. It was a brown, fleshy, thickened, and nodular well-circumscribed exophytic mass, measuring 6 mm in diameter; its clinical appearance argued for a possible nodular melanoma. Excisional-biopsy was performed using a full-thickness pentagonal wedge excision technique. Histopathology showed that the lesion was a benign melanocytic nevocellular nevus. The post-operative courses were uneventful with excellent cosmetic and functional result. Preventive measures (cap, sunglasses... and regular monitoring of the lesion by assessing ABCDE criteria (asymmetry, irregular borders, multiple colors, diameter ≥ 6 mm, and enlargement remain necessary to detect and rule out a possible risk of malignant melanoma.

  7. Deadliest tumor of oral cavity: A rare case of intra oral malignant melanoma

    Directory of Open Access Journals (Sweden)

    Nunsavathu Purnachandrarao Naik

    2014-01-01

    Full Text Available Malignant melanoma is a rare tumor arising from the uncontrolled growth of melanocytes found in the basal layer of the epithelium. Although cutaneous malignant melanoma is the third most common malignancy of the skin, it accounts only for 3-5% of all dermal malignancies. Primary malignant melanoma of the oral mucosa is extremely rare, accounting for only 0.2-8% of all malignant melanomas. The incidence is slightly higher in males while others report a higher incidence in females. In the oral cavity, 80% of the cases occur in the maxilla with the prevalence of the hard palate or combined with the gingival or alveolar ridge. In this paper, we present a rare case of a 47-year-old female patient who reported with completely asymptomatic, pigmented growth in the maxillary anterior region.

  8. Survival after a psychoeducational intervention for patients with cutaneous malignant melanoma: a replication study

    DEFF Research Database (Denmark)

    Boesen, Ellen H; Boesen, Sidsel H; Frederiksen, Kirsten

    2007-01-01

    The results of a randomized, intervention study done in 1993 of psychoeducation for patients with early-stage malignant melanoma showed a beneficial effect on recurrence and survival 6 years after the intervention. In the present study, we replicated the study with 258 Danish patients with malign...... with malignant melanoma. We also compared recurrence and survival among the participants in the randomized study with 137 patients who refused to participate....

  9. 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.

  10. Characterization of ex vivo expanded tumor infiltrating lymphocytes from patients with malignant melanoma for clinical application

    DEFF Research Database (Denmark)

    Junker, Niels; Thor Straten, Per; Andersen, Mads Hald

    2011-01-01

    Clinical trials of adoptive transfer of autologous tumor infiltrating lymphocytes (TILs) to patients with advanced malignant melanoma have shown remarkable results with objective clinical responses in 50% of the treated patients. In order to initiate a clinical trial in melanoma, we have establis......Clinical trials of adoptive transfer of autologous tumor infiltrating lymphocytes (TILs) to patients with advanced malignant melanoma have shown remarkable results with objective clinical responses in 50% of the treated patients. In order to initiate a clinical trial in melanoma, we have...

  11. Fast Diagnostics of BRAF Mutations in Biopsies from Malignant Melanoma.

    Science.gov (United States)

    Huber, François; Lang, Hans Peter; Glatz, Katharina; Rimoldi, Donata; Meyer, Ernst; Gerber, Christoph

    2016-09-14

    According to the American skin cancer foundation, there are more new cases of skin cancer than the combined incidence of cancers of the breast, prostate, lung, and colon each year, and malignant melanoma represents its deadliest form. About 50% of all cases are characterized by a particular mutation BRAF(V600E) in the BRAF (Rapid Acceleration of Fibrosarcoma gene B) gene. Recently developed highly specific drugs are able to fight BRAF(V600E) mutated tumors but require diagnostic tools for fast and reliable mutation detection to warrant treatment efficiency. We completed a preliminary clinical trial applying cantilever array sensors to demonstrate identification of a BRAF(V600E) single-point mutation using total RNA obtained from biopsies of metastatic melanoma of diverse sources (surgical material either frozen or fixated with formalin and embedded in paraffin). The method is faster than the standard Sanger or pyrosequencing methods and comparably sensitive as next-generation sequencing. Processing time from biopsy to diagnosis is below 1 day and does not require PCR amplification, sequencing, and labels.

  12. Malignant melanoma in patients with hereditary nonpolyposis colorectal cancer.

    Science.gov (United States)

    Ponti, G; Losi, L; Pellacani, G; Wannesson, L; Cesinaro, A M; Venesio, T; Petti, C; Seidenari, S

    2008-07-01

    Malignant melanoma (MM) is the most aggressive skin cancer. Most MMs are sporadic, and in this setting an association with mismatch repair (MMR) gene mutations, typical of hereditary nonpolyposis colorectal cancer (HNPCC) tumours, has been proposed. To characterize clinically and/or by molecular biology the patients with MM belonging to a cohort of 60 kindreds with HNPCC. Methods Patients with HNPCC with a diagnosis of MM were studied by immunohistochemistry (IHC) on tumour tissue using antibodies to MLH1, MSH2, p16, beta-catenin and E-cadherin, and by direct sequencing of MMR genes on germline DNA, and BRAF and NRAS on somatic DNA extracted from MM. Nine cutaneous MMs were detected in the tumour spectrum of eight families with HNPCC. The median age at diagnosis was 46 years. In one HNPCC family the diagnosis of MM was made in two first-degree relatives fitting the clinical definition of familial melanoma. IHC and sequencing analysis showed an MSH2 mutation in one patient with MM. Dermatological surveillance should be recommended to families in which MM is diagnosed in at least one member, especially at a young age. The combination of MMR gene mutations and abnormalities of p16 or other molecular pathways is needed to induce melanocytic carcinogenesis in a familial setting as well as in sporadic MM.

  13. MALIGNANT TRANSFORMATION OF A CHOROIDAL NEVUS IN AN EYE TREATED FOR CHOROIDAL MELANOMA.

    Science.gov (United States)

    Fabian, Ido D; Arora, Amit K; Cohen, Victoria M L

    2017-01-01

    To report a case of a choroidal melanoma and a discrete choroidal nevus that has transformed into a malignant melanoma 5 years after initial diagnosis. Retrospective case report. A diffuse macular choroidal melanoma and a discrete choroidal nevus located superonasal to the optic disk were diagnosed in the right eye of a 63-year-old woman in 2009. The patient was treated by ruthenium plaque radiotherapy for the choroidal melanoma, which consequently flattened and scarred. On a routine eye check in 2014, the nevus was found to have been transformed into a choroidal melanoma. It was treated with ruthenium plaque radiotherapy. Although extremely rare, patients with a uveal melanoma can develop an additional discrete uveal melanoma. This case highlights the importance of monitoring benign choroidal nevi in patients with a history of choroidal melanoma.

  14. Workplace investigation of increased diagnosis of malignant melanoma among employees of Lawrence Livermore National Laboratory

    Energy Technology Data Exchange (ETDEWEB)

    Moore, D.H. II; Patterson, H.W.; Hatch, F.; Discher, D.; Schneider, J.S.; Bennett, D.

    1994-08-01

    Based on rates for the surrounding communities, the diagnosis rate of malignant melanoma for employees of Lawrence Livermore National Laboratory (LLNL) during 1972 to 1977 was three to four times higher than expected. In 1984 Austin and Reynolds concluded, as a result of a case-control study, that five occupational factors were {open_quotes}causally associated{close_quotes} with melanoma risk at LLNL. These factors were: (1) exposure to radioactive materials, (2) work at Site 300, (3) exposure to volatile photographic chemicals, (4) presence at the Pacific Test Site, and (5) chemist duties. Subsequent reviews of the Austin and Reynolds report concluded that the methods used were appropriate and correctly carried out. These reports did determine, however, that Austin and Reynolds` conclusion concerning a causal relationship between occupational factors and melanoma among employees was overstated. There is essentially no supporting evidence linking the occupational factors with melanoma from animal studies or human epidemiology. Our report summarizes the results of further investigation of potential occupational factors.

  15. Laser-induced autofluorescence spectroscopy of benign and dysplastic nevi and malignant melanoma

    Science.gov (United States)

    Troyanova, P.; Borisova, E.; Stoyanova, V.; Avramov, L.

    2006-09-01

    The easy and non-destructive fluorescence method for quantification of early changes in biological tissues improves the possibilities of the clinical research. Using endogenous and exogenous fluorophores one can achieve high accuracy in the determination of malignant melanoma lesions with wide clinical applications. The goals of this work were investigation of melanin-pigmented cutaneous lesions by the methods of laser-induced autofluorescence spectroscopy (LIAFS), using nitrogen laser (337 nm) as excitation source. All lesions investigated were excised and investigated histologically by standard methods and histological results were used for comparison with the spectra detected. In the cases of nevi and melanoma significant decrease of fluorescence intensity toward normal skin fluorescence, which correlated with the type of pigment lesion was observed. The results, obtained in this investigation of the different pigment lesions could be used for better comprehension of the skin optical properties. The fluorescence spectroscopy of the human skin is very prominent for early diagnosis and differentiation of cutaneous diseases.

  16. Automatic Detection of Malignant Melanoma using Macroscopic Images.

    Science.gov (United States)

    Ramezani, Maryam; Karimian, Alireza; Moallem, Payman

    2014-10-01

    In order to distinguish between benign and malignant types of pigmented skin lesions, computerized procedures have been developed for images taken by different equipment that the most available one of them is conventional digital cameras. In this research, a new procedure to detect malignant melanoma from benign pigmented lesions using macroscopic images is presented. The images are taken by conventional digital cameras with spatial resolution higher than one megapixel and by considering no constraints and special conditions during imaging. In the proposed procedure, new methods to weaken the effect of nonuniform illumination, correction of the effect of thick hairs and large glows on the lesion and also, a new threshold-based segmentation algorithm are presented. 187 features representing asymmetry, border irregularity, color variation, diameter and texture are extracted from the lesion area and after reducing the number of features using principal component analysis (PCA), lesions are determined as malignant or benign using support vector machine classifier. According to the dermatologist diagnosis, the proposed processing methods have the ability to detect lesions area with high accuracy. The evaluation measures of classification have indicated that 13 features extracted by PCA method lead to better results than all of the extracted features. These results led to an accuracy of 82.2%, sensitivity of 77% and specificity of 86.93%. The proposed method may help dermatologists to detect the malignant lesions in the primary stages due to the minimum constraints during imaging, the ease of usage by the public and nonexperts, and high accuracy in detection of the lesion type.

  17. 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.

  18. Molecular Biology and Genetic Mechanisms in the Progression of the Malignant Skin Melanoma.

    Science.gov (United States)

    Pejkova, Sofija; Dzokic, Gjorgje; Tudzarova-Gjorgova, Smilja; Panov, Sasho

    2016-11-01

    Malignant skin melanoma is a tumor deriving from transformed skin melanocytes as a result of complex interactions between genetic and environmental factors. This melanoma has a potential to metastasize early and very often it is resistant to the existing modalities of the systemic therapy. As in any other neoplasms, certain types of melanoma may skip certain stages of progression. The progression from one stage to another is accompanied by specific biological changes. Several key changes in the melanoma tumorogenesis influence the regulation of the cell proliferation and vitality, including the RAS-RAF-ERK, PI3K-AKT, and p16INK4/CDK4/RB pathways. A key role in the dissreguarity of the RAS-RAF-ERK (MAPK) pathway in the malignant melanoma development have been demonstrated by many studies. To date, the molecular genetic alterations during melanoma development have been partially known. In the pathogenesis of the malignant melanoma, there are mutations of various genes such as NRAS, BRAF, and PTEN and mutations and deletions of CDKN2A. In the past years, great advance has been made in the insights of the molecular aspects of the melanoma pathogenesis. However, this field yet poses a challenge to discover new details about the melanoma molecular characteristics. The research results are focused towards the improvement of the melanoma patients prognosis by introducing personalized targeted therapy.

  19. Use of integrative epigenetic and cytogenetic analyses to identify novel tumor-suppressor genes in malignant melanoma.

    Science.gov (United States)

    Mithani, Suhail K; Smith, Ian M; Califano, Joseph A

    2011-08-01

    The objective of this study was to identify novel tumor-suppressor genes in melanoma, using an integrative genomic approach. Data from: (i) earlier reports of DNA loss and gain in malignant melanoma accompanied by comparative genomic hybridization high-definition array data of the entire human genome; (ii) microarray expression data from melanoma-derived cell lines identifying genes with significantly increased expression due to methylation using a pharmacologic demethylating strategy; and (iii) publicly available RNA expression microarray data of primary tumors and benign nevi were integrated using statistical tools to define a population of candidate tumor-suppressor genes. Twenty-seven genes were identified in areas of deletion that demonstrated diminished expression in primary melanomas relative to benign nevi and were significantly increased in expression by 5-Aza treatment. Seven genes of these 27 genes demonstrated methylation and deletion in a validation cohort of 14 separate primary tumors. These were: CHRDL1, SFRP1, TMEM47, LPL, RARRES1, PLCXD1, and KOX15. All of these genes demonstrated growth-suppressive properties with transfection into melanoma-derived cell lines. Seven putative tumor-suppressor genes in malignant melanoma were identified using a novel integrative technique.

  20. Comparative microarray analysis of microRNA expression profiles in primary cutaneous malignant melanoma, cutaneous malignant melanoma metastases, and benign melanocytic nevi.

    Science.gov (United States)

    Sand, Michael; Skrygan, Marina; Sand, Daniel; Georgas, Dimitrios; Gambichler, Thilo; Hahn, Stephan A; Altmeyer, Peter; Bechara, Falk G

    2013-01-01

    Perturbations in microRNA (miRNA) expression profiles have been reported for cutaneous malignant melanoma (CMM) predominantly when examined in cell lines. Despite the rapidly growing number of newly discovered human miRNA sequences, the availability of up-to-date miRNA expression profiles for clinical samples of primary cutaneous malignant melanoma (PCMM), cutaneous malignant melanoma metastases (CMMM), and benign melanocytic nevi (BMN) is limited. Specimens excised from the center of tumors (lesional) from patients with PCMM (n=9), CMMM (n=4), or BMN (n=8) were obtained during surgery. An exploratory microarray analysis was performed by miRNA expression profiling based on Agilent platform screening for 1205 human miRNAs. The results from the microarray analysis were validated by TaqMan quantitative real-time polymerase chain reaction. In addition to several miRNAs previously known to be associated with CMM, 19 unidentified miRNA candidates were found to be dysregulated in CMM patient samples. Among the 19 novel miRNA candidates, the genes hsa-miR-22, hsa-miR-130b, hsa-miR-146b-5p, hsa-miR-223, hsa-miR-301a, hsa-miR-484, hsa-miR-663, hsa-miR-720, hsa-miR-1260, hsa-miR-1274a, hsa-miR-1274b, hsa-miR-3663-3p, hsa-miR-4281, and hsa-miR-4286 were upregulated, and the genes hsa-miR-24-1*, hsa-miR-26a, hsa-miR-4291, hsa-miR-4317, and hsa-miR-4324 were downregulated. The results of this study partially confirm previous CMM miRNA profiling studies identifying miRNAs that are dysregulated in CMM. However, we report several novel miRNA candidates in CMM tumors; these miRNA sequences require further validation and functional analysis to evaluate whether they play a role in the pathogenesis of CMM.

  1. Insitu analysis of the mononuclear cell infiltrate in primary malignant-melanoma of the skin

    NARCIS (Netherlands)

    Poppema, S.; Brocker, E. B.; de Leij, L; ter Brack, D; Visscher, T.; Macher, E; The, T. Hauw; Sorg, C

    Monoclonal antibodies, directed against functionally different lymphocyte subsets, were applied on frozen sections of primary malignant melanomas and benign nevi. Positive reaction was identified by means of an immunoperoxidase method. It was found that lymphocytic infiltrate underneath and in

  2. Lymph node dissection in patients with malignant melanoma is associated with high risk of morbidity

    DEFF Research Database (Denmark)

    Ul-Mulk, Jamshaid; Hölmich, Lisbet Rosenkrantz

    2012-01-01

    Malignant melanoma is one of the most rapidly increasing cancer types globally, and it is by far the most serious skin cancer. Patients with a melanoma ≥ 1 mm in Breslow thickness are offered sentinel node (SN) biopsy and subsequent radical lymph node dissection if the biopsy is positive...

  3. Radiculopathy due to malignant melanoma in the sacrum with unknown primary site.

    Science.gov (United States)

    Kakutani, Kenichiro; Doita, Minoru; Nishida, Kotaro; Miyamoto, Hiroshi; Kurosaka, Masahiro

    2008-09-01

    Melanoma is an interesting tumor, showing the appearance of metastasis without any trace of its primary lesion. To report a very rare case of malignant melanoma in the sacrum with unknown primary origin. The authors present a case of a 52-year-old man who was admitted with increasing lower back, left buttock, and left lower extremity pain, and dysuria. Plain radiograph, computed tomography scan, and magnetic resonance imaging revealed a destructive lesion in the sacrum and left ilium, which infiltrated the spinal canal and sacroiliac joint. The tumor cells were immunoreactive for HMB-45. The pathological diagnosis was malignant melanoma. No obvious primary malignant melanoma was detected on the skin surface, on the oral or anal mucosa, or in the fundus oculi. Following radiotherapy and chemotherapy, the severe buttock pain disappeared and the patient was able to walk without impediment. However the patient died nine months after initial diagnosis. Malignant melanoma in the sacrum with an unknown primary site, showing S1 radiculopathy is reported for the first time. The melanoma could have been a metastatic tumor of the sacrum, although the primary site was not detected. The incidence of primary melanoma is increasing faster than any other cancer. Thus treatment of patients with spinal metastasis of melanoma is an important challenge for orthopedic surgeons.

  4. Malignant melanoma of the skin in black South Africans: A 15-year ...

    African Journals Online (AJOL)

    128 documented deaths, 35 patients having died of melanoma within 1 year of presentation. Thirty patients survived for more than 3 years. Because of late presentation and the nature of the dis- ease, malignant melanoma has a very poor prognosis in black patients in South Africa. SAJS. Fig. 1. Gender/age breakdown of ...

  5. Utility of chest X-ray and abdominal ultrasound for stage III cutaneous malignant melanoma

    DEFF Research Database (Denmark)

    Breitenbauch, M. T. W.; Holm, J.; Rødgaard, J. C.

    2015-01-01

    Background: Current Danish Melanoma Guidelines suggest that stage III cutaneous malignant melanoma receive chest X-ray and abdominal ultrasound to exclude lung and liver metastases. The aim of this study was to examine the sensitivity, specificity, and negative predictive value of chest X-ray and...

  6. Segmental neurofibromatosis in association with a large congenital nevus and malignant melanoma.

    Science.gov (United States)

    Doherty, Sean D; George, Saira; Prieto, Victor G; Gershenwald, Jeffrey E; Duvic, Madeleine

    2006-12-10

    We describe a patient with segmental neurofibromatosis and a large congenital nevus who developed malignant melanoma in the same anatomic distribution. The overlapping presentation suggests a common etiologic link between neurofibromatosis and large congenital nevi and the possibility that neurofibromatosis increases the risk of melanoma with large congenital nevi.

  7. Does the sun play a role in the aetiology of malignant melanoma ...

    African Journals Online (AJOL)

    The role of the sun in the aetiology of malignant melanoma is controversial. In 1992 Schuster1 wrote provocatively, 'Despite the lack of evidence of a causal link between sun exposure and melanoma, fear has been used shamelessly to frighten people out of the sun and into pigmented lesion clinics.' He claimed that the ...

  8. Does the sun play a role in the aetiology of malignant melanoma ...

    African Journals Online (AJOL)

    and into pigmented lesion clinics.' He claimed that the main reason for the supposed increase in incidence of melanoma was that many lesions, previously regarded as benign, were being classified as malignant, and that melanomas were being invented not found. South African Medical Journal Vol. 97 (8) 2007: pp. 568- ...

  9. Diffuse Interstitial Infiltrative Lung Metastasis of Malignant Melanoma: a Case Report

    Energy Technology Data Exchange (ETDEWEB)

    Shin, Na young; Hong, Yoo Jin; Kim, Ah Hyun; Shim, Hyo Sub; Nam, Ji Eun; Lee, Hye Jeong; Kim, Myung Joon [Severance Hospital, Yonsei University College of Medicine, Seoul (Korea, Republic of)

    2011-04-15

    A diffuse interstitial infiltrative pattern of lung metastasis in a patient with malignant melanoma is rare and can be confused with benign conditions such as pulmonary edema or drug-induced pneumonitis. We experienced a case of diffuse interstitial infiltrative lung metastasis in malignant melanoma in a 37-year-old man. This case was confirmed by a transbronchial lung biopsy. We herein describe the findings on CT and positron emission tomography scan

  10. Differentiation of malignant melanoma from benign nevus using a novel genomic microarray with low specimen requirements.

    Science.gov (United States)

    Chandler, Wells M; Rowe, Leslie R; Florell, Scott R; Jahromi, Mona S; Schiffman, Joshua D; South, Sarah T

    2012-08-01

    Histologic examination of clinically suspicious melanocytic lesions is very sensitive and specific for the detection of malignant melanoma. Yet, the malignant potential of a small percentage of melanocytic lesions remains histologically uncertain. Molecular testing offers the potential to detect the genetic alterations that lead to malignant behavior without overt histologic evidence of malignancy. To differentiate benign melanocytic nevi from malignant melanoma and to predict the clinical course of melanocytic lesions with ambiguous histology using a novel genomic microarray. We applied a newly developed single-nucleotide polymorphism genomic microarray to formalin-fixed, paraffin-embedded melanocytic lesions to differentiate benign nevi (n  =  23) from malignant melanoma (n  =  30) and to predict the clinical course of a set of histologically ambiguous melanocytic lesions (n  =  11). For cases with unambiguous histology, there was excellent sensitivity and specificity for identifying malignant melanoma with this genomic microarray (89% sensitivity, 100% specificity). For cases with ambiguous histology, the performance of this genomic microarray was less impressive. Without microdissection and with quantities of DNA one-tenth what is required for more commonly used microarrays, this microarray can differentiate between malignant melanoma and benign melanocytic nevi. For histologically ambiguous lesions, longer clinical follow-up is needed to confidently determine the sensitivity and specificity of this microarray. Some of the previous technical hurdles to the clinical application of genomic microarray technology are being overcome, and the advantages over targeted fluorescence in situ hybridization assays currently in clinical use are becoming apparent.

  11. Involvement of ANXA5 and ILKAP in susceptibility to malignant melanoma.

    Directory of Open Access Journals (Sweden)

    Yoana Arroyo-Berdugo

    Full Text Available Single nucleotide-polymorphisms (SNPs are a source of diversity among human population, which may be responsible for the different individual susceptibility to diseases and/or response to drugs, among other phenotypic traits. Several low penetrance susceptibility genes associated with malignant melanoma (MM have been described, including genes related to pigmentation, DNA damage repair and oxidative stress pathways. In the present work, we conducted a candidate gene association study based on proteins and genes whose expression we had detected altered in melanoma cell lines as compared to normal melanocytes. The result was the selection of 88 loci and 384 SNPs, of which 314 fulfilled our quality criteria for a case-control association study. The SNP rs6854854 in ANXA5 was statistically significant after conservative Bonferroni correction when 464 melanoma patients and 400 controls were analyzed in a discovery Phase I. However, this finding could not be replicated in the validation phase, perhaps because the minor allele frequency of SNP rs6854854 varies depending on the geographical region considered. Additionally, a second SNP (rs6431588 located on ILKAP was found to be associated with melanoma after considering a combined set of 1,883 MM cases and 1,358 disease-free controls. The OR was 1.29 (95% CI 1.12-1.48; p-value = 4×10-4. Both SNPs, rs6854854 in ANXA5 and rs6431588 in ILKAP, show population structure, which, assuming that the Spanish population is not significantly structured, suggests a role of these loci on a specific genetic adaptation to different environmental conditions. Furthermore, the biological relevance of these genes in MM is supported by in vitro experiments, which show a decrease in the transcription levels of ANXA5 and ILKAP in melanoma cells compared to normal melanocytes.

  12. The epidemiology of cutaneous malignant melanoma in Nova Scotia

    Science.gov (United States)

    Howlett, Andrew L; Dewar, Ron AD; Morris, Steven F

    2006-01-01

    BACKGROUND: Since 1993, the annual increase in cutaneous malignant melanoma (MM) incidence has been one of the highest for all cancers registered in Canada, with the leading rate in Nova Scotia (NS). The purpose of the present study was to document the pathological and epidemiological data on MM cases found in NS. PATIENTS AND METHODS: All MM cases identified by the Nova Scotia Cancer Registry from January 1998 to December 2002 were evaluated. The five-year survival outlook, by major prognostic factors, was also determined. In addition, the annual incidence and mortality rates from 1972 to 2002 were computed. RESULTS: Between 1998 and 2002, 925 MM cases were recorded. The age-standardized incidence rate for males and females in this period was 19.2 and 16.1 per 100,000 respectively. Men 65 years of age or older had the highest age-specific rate. The most common MM had a Breslow’s depth of less than 1.0 mm (61.9%) and was Clark’s level II (34.9%). There was no significant seasonal variation noted in the time of diagnosis. Survival analyses indicated that sex, age, tumour location and thickness were significant independent predictors. Despite the increase in incidence, there have only been modest changes in the annual mortality rate. CONCLUSION: The incidence of MM in NS increases with age, and is nearly double for men 65 years of age or older, compared with women in the same age group. Thin melanomas on the extremities of young females have the best prognosis in NS, which is similar to other parts of the world. Incidence appears to be unrelated to season. Public health interventions are necessary to reduce the burden of this disease. PMID:19554137

  13. CHEK2*1100delC and risk of malignant melanoma

    DEFF Research Database (Denmark)

    Weischer, Maren; Heerfordt, Ida M; Bojesen, Stig E

    2012-01-01

    It is possible that reduced function of DNA repair and cell-cycle control genes increases the individual susceptibility to malignant melanoma. As CHEK2 is a cell-cycle master controller, we tested the hypothesis that heterozygosity for the frameshift alteration CHEK2*1100delC is associated...... with increased risk of malignant melanoma. First, we performed case-control studies of 1,152 Danish and 752 German individuals with malignant melanoma compared with 9,142 Danish and 3,718 German controls. Second, we performed a meta-analysis of CHEK2*1100delC and malignant melanoma, involving 2,619 cases and 17......,481 controls. Third, we examined the risk of malignant melanoma associated with CHEK2*1100delC heterozygosity in an analysis stratified for sun exposure, as well as for subtype and location on the body. The odds ratios for malignant melanoma for CHEK2(*)1100del heterozygotes compared with those for noncarriers...

  14. Vesicular Stomatitis Virus Variants Selectively Infect and Kill Human Melanomas but Not Normal Melanocytes

    Science.gov (United States)

    Wollmann, Guido; Davis, John N.; Bosenberg, Marcus W.

    2013-01-01

    Metastatic malignant melanoma remains one of the most therapeutically challenging forms of cancer. Here we test replication-competent vesicular stomatitis viruses (VSV) on 19 primary human melanoma samples and compare these infections with those of normal human melanocyte control cells. Even at a low viral concentration, we found a strong susceptibility to viral oncolysis in over 70% of melanomas. In contrast, melanocytes displayed strong resistance to virus infection and showed complete protection by interferon. Several recombinant VSVs were compared, and all infected and killed most melanomas with differences in the time course with increasing rates of melanoma infection, as follows: VSV-CT9-M51 VSV-M51 VSV-G/GFP VSV-rp30. VSV-rp30 sequencing revealed 2 nonsynonymous mutations at codon positions P126 and L223, both of which appear to be required for the enhanced phenotype. VSV-rp30 showed effective targeting and infection of multiple subcutaneous and intracranial melanoma xenografts in SCID mice after tail vein virus application. Sequence analysis of mutations in the melanomas used revealed that BRAF but not NRAS gene mutation status was predictive for enhanced susceptibility to infection. In mouse melanoma models with specific induced gene mutations including mutations of the Braf, Pten, and Cdkn2a genes, viral infection correlated with the extent of malignant transformation. Similar to human melanocytes, mouse melanocytes resisted VSV-rp30 infection. This study confirms the general susceptibility of the majority of human melanoma types for VSV-mediated oncolysis. PMID:23552414

  15. Vesicular stomatitis virus variants selectively infect and kill human melanomas but not normal melanocytes.

    Science.gov (United States)

    Wollmann, Guido; Davis, John N; Bosenberg, Marcus W; van den Pol, Anthony N

    2013-06-01

    Metastatic malignant melanoma remains one of the most therapeutically challenging forms of cancer. Here we test replication-competent vesicular stomatitis viruses (VSV) on 19 primary human melanoma samples and compare these infections with those of normal human melanocyte control cells. Even at a low viral concentration, we found a strong susceptibility to viral oncolysis in over 70% of melanomas. In contrast, melanocytes displayed strong resistance to virus infection and showed complete protection by interferon. Several recombinant VSVs were compared, and all infected and killed most melanomas with differences in the time course with increasing rates of melanoma infection, as follows: VSV-CT9-M51 VSV-M51 VSV-G/GFP VSV-rp30. VSV-rp30 sequencing revealed 2 nonsynonymous mutations at codon positions P126 and L223, both of which appear to be required for the enhanced phenotype. VSV-rp30 showed effective targeting and infection of multiple subcutaneous and intracranial melanoma xenografts in SCID mice after tail vein virus application. Sequence analysis of mutations in the melanomas used revealed that BRAF but not NRAS gene mutation status was predictive for enhanced susceptibility to infection. In mouse melanoma models with specific induced gene mutations including mutations of the Braf, Pten, and Cdkn2a genes, viral infection correlated with the extent of malignant transformation. Similar to human melanocytes, mouse melanocytes resisted VSV-rp30 infection. This study confirms the general susceptibility of the majority of human melanoma types for VSV-mediated oncolysis.

  16. Changes in expression of putative antigens encoded by pigment genes in mouse melanomas at different stages of malignant progression.

    Science.gov (United States)

    Orlow, S J; Hearing, V J; Sakai, C; Urabe, K; Zhou, B K; Silvers, W K; Mintz, B

    1995-10-24

    Cutaneous melanomas of Tyr-SV40E transgenic mice (mice whose transgene consists of the tyrosinase promoter fused to the coding regions of simian virus 40 early genes) strikingly resemble human melanomas in their development and progression. Unlike human melanomas, the mouse tumors all arise in genetically identical individuals, thereby better enabling expression of specific genes to be characterized in relation to advancing malignancy. The products of pigment genes are of particular interest because peptides derived from these proteins have been reported to function as autoantigens with immunotherapeutic potential in some melanoma patients. However, the diminished pigmentation characteristic of many advanced melanomas raises the possibility that some of the relevant products may no longer be expressed in the most malignant cells. We have therefore investigated the contributions of several pigment genes in melanotic vs. relatively amelanotic components of primary and metastatic mouse melanomas. The analyses reveal marked differences within and among tumors in levels of mRNAs and proteins encoded by the wild-type alleles at the albino, brown, slaty, and silver loci. Tyrosinase (the protein encoded by the albino locus) was most often either absent or undetectable as melanization declined. The protein encoded by the slaty locus (tyrosinase-related protein 2) was the only one of those tested that was clearly present in all the tumor samples. These results suggest that sole reliance on targeting tyrosinase-based antigens might selectively favor survival of more malignant cells, whereas targeting the ensemble of the antigens tested might contribute toward a more inclusive and effective antimelanoma strategy.

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

    DEFF Research Database (Denmark)

    Glud, Martin; Rossing, Maria; Hother, Christoffer

    2010-01-01

    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...... 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...

  18. Nivolumab in the treatment of malignant melanoma: review of the literature

    Directory of Open Access Journals (Sweden)

    Mashima E

    2015-08-01

    Full Text Available Emi Mashima, Akiha Inoue, Yumiko Sakuragi, Takashi Yamaguchi, Natsuko Sasaki, Yoko Hara, Daisuke Omoto, Shun Ohmori, Sanehito Haruyama, Yu Sawada, Manabu Yoshioka, Daisuke Nishio, Motonobu Nakamura Department of Dermatology, University of Occupational and Environmental Health, Kitakyushu, Japan Abstract: Nivolumab was developed as a monoclonal antibody against programmed death receptor-1, an immune checkpoint inhibitor which negatively regulates T-cell proliferation and activation. Intravenous administration of nivolumab was approved for the treatment of unresectable malignant melanoma in 2014 in Japan. When advanced melanoma patients were treated with nivolumab, median overall survival became longer. Overall survival rate was significantly better in nivolumab-treated melanoma patients than dacarbazine-treated melanoma patients. Nivolumab had an acceptable long-term tolerability profile, with 22% of patients experiencing grade 3 or 4 adverse events related to the drug. Therefore, nivolumab can become an alternative therapy for advanced malignant melanoma. Keywords: monoclonal antibody, PD-1, PD-L1

  19. 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.

  20. Ovarian metastasis of malignant melanoma: The first pediatric case

    Directory of Open Access Journals (Sweden)

    Yuko Araki

    2014-10-01

    Full Text Available We report a case of an 8-year-old girl with metastasis of malignant melanoma (MM to the ovary. She was initially diagnosed with cutaneous MM on the left buttock for which she underwent wide local excision, left inguinal/pelvic lymph node dissection, and subcutaneous injection of interferon beta. In spite of the treatment, she developed dissemination of MM to the liver, the bone, and the right ovary. All the lesions responded well to systemic chemotherapy (intravenous dacarbazine, except for the right ovarian tumor. She underwent an elective right salpingo-oophorectomy to avoid torsion or rupture of the tumor. However, she developed metastases to the contralateral ovary with peritoneal dissemination in 4 months. She received home palliative care and died at home 14 months after the last surgery. Ovarian metastasis of MM is a rare form of dissemination, and only 15 adult cases have ever been reported. Our patient is the first pediatric case. Since there is no standard of surgical indication for metastatic MM to the ovary, palliative resection can be an option for improving quality of life of a patient with this rare condition.

  1. Malign Melanoma: Risk Factors and Major Clinical Findings

    Directory of Open Access Journals (Sweden)

    Can Baykal

    2015-03-01

    Full Text Available Malignant melanoma (MM shows rapid increase in the incidence and it is the most common cause of death due to skin cancer. On the other hand, MM can completely be removed in patients noticing the lesions early and applying to physicians on time. Thus the life expectancy of these patients is not altered. Although MM can occur in every individual, it is more common in patients with some of the established risk factors such as fair skin, increased sun exposure, genetic basis (CDKN2A mutation, and existence of increased number of melanocytic nevi and/or dysplastic nevi. A specialized care of patients with risk factors and their regular follow-up is critical to lower the mortality and morbidity in MM. Early diagnosis of MM prevents metastasis and decreases mortality rate. Nowadays, there are many newly developed imaging methods to help the clinicians before biopsy. However, the suspicion of MM should initially be based upon major clinical findings of the lesion subject to changes during the evolution of the tumor. In this review, risk factors of MM will be summarized and clues for early diagnosis of this dangerous tumor will be discussed.

  2. Experience with Ruthenium /sup 106/-treatment of uveal malignant melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Laatikainen, L.; Tarkkanen, A.

    1987-01-01

    In 1981-1986, 25 eyes with malignant melanoma of the uvea were treated with beta irradiation using ruthenium/sup 106/ plaques. In 21 cases the tumour originated in the choriod, in 4 cases in the ciliary body. In 12 eyes it was within 3 mm from the optic disc or the fovea, and the mean height (+-SEM) was 5.2+-0.4 mm. Three eyes received two sets of irradiation with 1.1 - 1.7 years' interval. After a mean followup of 1.6 years (range 0,5 - 5.6) the tumour had decreased in size in 12, was unchanged in 6, and had progressed in 7 eyes, 4 of the latter were enucleated. In 3 patients metastases were diagnosed (2.0 -2.9 years after irradiation), and 1 patient has died (3.3 years after the first irradiation). Twelve eyes have retained useful vision (0.05 or better), but in some of them a tendency to deterioration was observed 3-5 years after treatment due to radiation maculopathy. Other causes of visual loss were the centrally located tumour itself, exudative detachment of the retina, and persistent vitreous haemorrhage.

  3. Dermatomyositis as a paraneoplastic syndrome of malignant melanoma or incidental coexistence?

    Directory of Open Access Journals (Sweden)

    Magdalena Krajewska

    2016-09-01

    Full Text Available Introduction . Dermatomyositis is a rare systemic disease of connective tissue characterized by inflammation of the muscles and the skin. Malignant melanoma is a cancer that begins in melanocytes in the skin, mucosa of the rectum, intestine, oral cavity, external genitalia or in the eyeball. Objective . Presentation of a patient with dermatomyositis as a possible paraneoplastic syndrome of malignant melanoma. Case report . We present a case of a 56-year-old woman who was referred to us due to erythematous skin lesions on the limbs, face, neck and upper chest. The patient also complained of progressive muscle pain and weakness of the shoulder and pelvic girdle as well as of dysphagia. The patient had a small ulcerative lesion on the right foot that was removed. Histopathological evaluation revealed malignant melanoma cells, which were also present in the sentinel lymph node. Conclusions. Screening in dermatomyositis patients should also be focused on melanoma, especially in cases with negative antibodies.

  4. Malignant Mucosal Melanoma in the Nasal Cavity: An Uncommon Cause of Epistaxis

    Directory of Open Access Journals (Sweden)

    Ru-Hsiao Lo

    2010-09-01

    Full Text Available Malignant mucosal melanoma of the nasal cavity is extremely rare. It is usually diagnosed in the elderly. We report a 78-year-old man who had symptoms of occasional episodes of epistaxis and blood-tinged sputum for about 1 month. Physical examination showed a dark-colored mass lesion over the left nasal cavity, and biopsy of it revealed malignant melanoma. Wide excision of the tumor was performed via endoscopic surgery, and adjuvant radiotherapy was also arranged. Diagnosis of malignant melanoma mainly depends on histochemistry and immunostain. Up to now, surgery offers the best chance for local tumor control. However, postoperative radiotherapy or chemotherapy is often needed because mucosal melanomas tend to have distant metastasis and local failure. Immunotherapy may play a role in improving outcome, but evidence is lacking.

  5. Targeting Histone Deacetylases in Malignant Melanoma: A Future Therapeutic Agent or Just Great Expectations?

    Science.gov (United States)

    Garmpis, Nikolaos; Damaskos, Christos; Garmpi, Anna; Dimitroulis, Dimitrios; Spartalis, Eleftherios; Margonis, Georgios-Antonios; Schizas, Dimitrios; Deskou, Irini; Doula, Chrysoula; Magkouti, Eleni; Andreatos, Nikolaos; Antoniou, Efstathios A; Nonni, Afroditi; Kontzoglou, Konstantinos; Mantas, Dimitrios

    2017-10-01

    Malignant melanoma is the most aggressive type of skin cancer, with increasing frequency and mortality. Melanoma is characterized by rapid proliferation and metastases. Malignant transformation of normal melanocytes is associated with imbalance between oncogenes' action and tumor suppressor genes. Mutations or inactivation of these genes plays an important role in the pathogenesis of malignant melanoma. Many target-specific agents improved progression-free survival but unfortunately metastatic melanoma remains incurable, so new therapeutic strategies are needed. The balance of histones' acetylation affects cell cycle progression, differentiation and apoptosis. Histone deacetylases (HDAC) are associated with different types of cancer. Histone deacetylase inhibitors (HDACI) are enzymes that inhibit the action of HDAC, resulting in block of tumor cell proliferation. A small number of these enzymes has been studied regarding their anticancer effects in melanoma. The purpose of this article was to review the therapeutic effect of HDACI against malignant melanoma, enlightening the molecular mechanisms of their action. The MEDLINE database was used. The keywords/ phrases were; HDACI, melanoma, targeted therapies for melanoma. Our final conclusions were based on studies that didn't refer solely to melanoma due to their wider experimental data. Thirty-two articles were selected from the total number of the search's results. Only English articles published until March 2017 were used. Molecules, such as valproid acid (VPA), LBH589, LAQ824 (dacinostat), vorinostat, tubacin, sirtinol and tx-527, suberoyl bis-hydroxamic acid (SBHA), depsipeptide and Trichostatin A (TSA) have shown promising antineoplastic effects against melanoma. HDACI represent a promising agent for targeted therapy. More trials are required. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  6. Malignant melanoma - a warning; How to reduce mortality. Malignt melanom - et varsko; Hvordan redusere doedeligheten

    Energy Technology Data Exchange (ETDEWEB)

    Volden, G. (University and Regional Hospital, Trondheim (Norway)); Rajka, G. (Rikshospitalet, Oslo (Norway)); Thune, P. (Ullevaal Sykehus, Oslo (Norway)); Falk, E.S. (University and Regional Hospital, Tromsoe (Norway)); Krogh, H.K. (Haukeland Sykehus, Bergen (Norway))

    1990-04-01

    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.

  7. Risk of malignant melanoma in men with prostate cancer. Nationwide, population-based cohort study

    DEFF Research Database (Denmark)

    Thomsen, Frederik B; Folkvaljon, Yasin; Garmo, Hans

    2016-01-01

    obtained from nationwide registers. Melanoma was diagnosed in 830/108,145 (0.78%) men with prostate cancer and in 3,699/556,792 (0.66%) prostate cancer-free men. In multivariable Cox regression models, men with prostate cancer had a significantly increased risk of melanoma (HR 1.18, 95% CI 1......An increased risk of malignant melanoma has been observed in men with prostate cancer. To assess potential shared risk factors and confounding factors, we analysed risk of melanoma in men with prostate cancer including information on tumor characteristics and demographics including socioeconomic...... status. In The Prostate Cancer data Base Sweden, risk of melanoma was assessed in a cohort of men with prostate cancer and in a comparison cohort of prostate-cancer free men. Data on prostate cancer risk category, melanoma stage, basal cell carcinoma, location of residency, and socioeconomic status were...

  8. Growth-Inhibitory and Antiangiogenic Activity of the MEK Inhibitor PD0325901 in Malignant Melanoma with or without BRAF Mutations

    Directory of Open Access Journals (Sweden)

    Ludovica Ciuffreda

    2009-08-01

    Full Text Available The Raf/MEK/ERK pathway is an importantmediator of tumor cell proliferation and angiogenesis. Here, weinvestigated the growth-inhibitory and antiangiogenic properties of PD0325901, a novel MEK inhibitor, in human melanoma cells. PD0325901 effects were determined in a panel of melanoma cell lines with different genetic aberrations. PD0325901 markedly inhibited ERK phosphorylation and growth of both BRAF mutant and wild-type melanoma cell lines, with IC50 in the nanomolar range even in the least responsive models. Growth inhibition was observed both in vitro and in vivo in xenograft models, regardless of BRAF mutation status, and was due to G1-phase cell cycle arrest and subsequent induction of apoptosis. Cell cycle (cyclin D1, c-Myc, and p27KIP1 and apoptosis (Bcl-2 and survivin regulators were modulated by PD0325901 at the protein level. Gene expression profiling revealed profound modulation of several genes involved in the negative control of MAPK signaling and melanoma cell differentiation, suggesting alternative, potentially relevant mechanisms of action. Finally, PD0325901 inhibited the production of the proangiogenic factors vascular endothelial growth factor and interleukin 8 at a transcriptional level. In conclusion, PD0325901 exerts potent growth-inhibitory, proapoptotic, and antiangiogenic activity in melanoma lines, regardless of their BRAF mutation status. Deeper understanding of the molecular mechanisms of action of MEK inhibitors will likely translate into more effective treatment strategies for patients experiencing malignant melanoma.

  9. Noninvasive, label-free, three-dimensional imaging of melanoma with confocal photothermal microscopy: Differentiate malignant melanoma from benign tumor tissue

    OpenAIRE

    Jinping He; Nan Wang; Hiromichi Tsurui; Masashi Kato; Machiko Iida; Takayoshi Kobayashi

    2016-01-01

    Skin cancer is one of the most common cancers. Melanoma accounts for less than 2% of skin cancer cases but causes a large majority of skin cancer deaths. Early detection of malignant melanoma remains the key factor in saving lives. However, the melanoma diagnosis is still clinically challenging. Here, we developed a confocal photothermal microscope for noninvasive, label-free, three-dimensional imaging of melanoma. The axial resolution of confocal photothermal microscope is ~3 times higher th...

  10. 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.

  11. Primary leptomeningeal malignant melanoma in posterior fossa and upper cervical canal: a case report

    Energy Technology Data Exchange (ETDEWEB)

    Cho, Kyu Ran; Kim, Jung Hyuk; Shin, Bong Kyung; Lee, Nam Joon [Korea Univ. Hospital, Seoul (Korea, Republic of)

    2001-11-01

    The term 'primary melanocytic neoplasm' covers a wide disease spectrum, from well differentiated meningeal melanocytoma to malignant melanoma, its most aggressive malignant counterpart. Previous reports have shown that due to the paramagnetic effect of melanin, melanocytic neoplasms show high signal intensity on T1-weighted images and very low signal intensity on T2-weighted images, with relatively homogeneous contrast enhancement. The differentiation of leptomeningeal malignant melanoma from benign melanocytoma is important because of their different prognosis but on the basis of imaging findings alone is difficult. Ultrastructural immunohistochemical analysis is a possible alternative. We report the imaging findings of rare primary malignant melanoma, revealed by noncontrast-enhanced CT as a high-density mass, and demonstrating high signal intensity on T1-weighted images, and very low signal intensity on T2WI, with relatively good contrast enhancement.

  12. Metastatic malignant melanoma representing a multiple mesenteric cystic tumor: a case report

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jong Lim; Woo, Ji Young [Kangnam Sacred Heart, College of Medicine, Hallym University, Seoul (Korea, Republic of)

    2008-05-15

    A metastatic malignant melanoma is a malignant tumor which can involve virtually every organ system. It has variable radiographic findings which mostly indicate solid masses in the mesentery. We report here on a case of a metastatic malignant melanoma, which is made up of multiple mesenteric cystic tumors that need to differentiate from the mesenteric cystic tumor. These include the cystic spindle cell tumor, cystic teratoma, cystic mesothelioma as well as the mesenteric cystic and the solid tumor, which in turn comprises the gastrointestinal stromal tumor, lymphoma and metastatic lesion. The metastatic malignant melanoma can offer a differential diagnosis when the image findings indicate multiple mesenteric cystic masses, multiple organic metastases, and subcutaneous nodules.

  13. A donor cornea with metastatic cells from a cutaneous malignant melanoma.

    Science.gov (United States)

    Campanelli, Marino; Mistò, Raffaela; Limongelli, Anna; Valente, Maria G; Cuttin, Maria S; D'Amato Tóthová, Jana

    2013-12-01

    To describe the case of a donor cornea that showed hematogenous metastatic spread of cutaneous melanoma to the sclerocorneal limbus. Corneal tissue obtained from a donor with cutaneous malignant melanoma was evaluated for endothelial cell density, corneal transparency, and epithelial morphology. Subsequently, hematoxylin and eosin staining and immunohistochemical characterization using S100, HMB45, Melan-A, and CD34 antibodies were performed on the corneal sections. The corneal tissue was transparent with high endothelial cell density; it was graded as being suitable for transplantation according to the current eye bank criteria. However, the aggressiveness of the donor's cancer and the diffuse melanosis of the sclera led to the suspicion of malignant melanoma metastasis to the cornea. Histochemical analysis of the corneoscleral rim showed small aggregates rich in pigmented cells that were localized in cleft-like structures in the sclera, at the sclerocorneal interface and in the peripheral avascular portion of the cornea. The aggregates were positive for the melanocytic tumor markers S100, HMB45, and Melan-A; the rims of the clefts expressed the panvascular CD34 antigen, which was suggestive of neovascularization. Corneal tissue from a donor with malignant cutaneous melanoma displayed neoplastic lesions of melanocytic origin that had spread from a primitive melanoma through hematogenous routes to the sclerocorneal limbus. On the basis of this finding, we believe that having a metastatic cutaneous malignant melanoma could in some cases be reviewed as an exclusionary criterion for undergoing cornea transplantation.

  14. [Cutaneous malignant melanoma; diagnostic procedures and their evaluation in diagnosing and mapping sentinel nodes].

    Science.gov (United States)

    Valsamaki, Pipitsa; Zanglis, Antonios; Gerali, Sophia

    2009-01-01

    Cutaneous malignant melanoma represents 4% of all the malignant neoplasms. Nevertheless, 79% of the fatal malignant skin diseases are attributed to melanoma. In melanoma patients, the most important prognostic factor is the regional lymph node invasion. The present article describes the classical diagnostic, staging and therapeutic strategies in melanoma patients. In the realm of cutaneous melanoma, pre-operative lymphoscintigraphy and the intra-operative gamma-probe detection, removal and biopsy of the sentinel lymph node(s), comprise convenient, procedures, virtually lacking morbidity. The definition of sentinel includes the first lymph node or nodes, draining the lymph from the primary lesion, thereby attributed with the highest probability of harbouring migrating metastatic cells. A sentinel lymph node negative for malignancy accurately "predicts" the absence of melanoma cell invasion in all the rest regional and distant lymphatic basins. The method aims in the best discrimination of high-risk patients, as candidates for selective lymphadenectomy, with or without adjunctive treatment. Radionuclide-guided lymphatic mapping and surgery is based on the phagocytosis of colloidal-based radiopharmaceuticals by the macrophages encountered in functional tumour-infiltrated sentinel nodes. The nuclear methods successfully add to the staging and the potential surgical treatment of the disease.

  15. Malignant melanoma mortality rates in Chile (1988-98).

    Science.gov (United States)

    Zemelman, Vivian; Garmendia, M L; Kirschbaum, A

    2002-02-01

    Malignant melanoma (MM) mortality has increased in the Caucasian population many fold over the past several decades. In this study, we analyzed the Chilean-specific, age-adjusted MM mortality rates per 100,000 population during the decade 1988-98 in order to establish changes in that period. We analyzed all death certificates from the Chilean Death Registry Office (1988-98) and retrieved the deaths attributed to MM. The data were categorized according to sex and age group. The annual age-adjusted and sex-specific rates of MM mortality per 100,000 population were calculated. Chilean MM mortality rates increased by 14% between 1988 and 1998. The relative risk for males vs. females was 1.3 with a tendency to rise, showing an increase of 30%. The relative risk of dying from MM in Chile increased linearly with age. An individual of 75 years or older had a 44.24 times greater risk of dying of MM than an individual in the 0-44-year age group. The rates in the > 75-year age group also showed a tendency to rise over the decade, with an increase of 64% (1988-98). The Chilean MM mortality rates are lower than the world standardized rates. The total Chilean MM mortality rates showed an increase over the decade 1988-98, mainly due to MM mortality in males. The MM mortality in Chilean females was lower than that in males, and was unchanged over the decade; this is in agreement with the results reported in other countries. This is one of the first studies of MM mortality in the Chilean population. The results are important when the geographic location of Chile is considered.

  16. Towards automatic detection of malignant melanoma by laser speckle

    Science.gov (United States)

    Lee, T. K.; Tchvialeva, L.; Lui, H.; Zeng, H.; McLean, D. I.

    2010-09-01

    The incidence of malignant melanoma (MM), the most aggressive and deadly form of skin cancer, has been increasing rapidly since the last few decades. Clinical differentiation between MM and pigmented benign skin lesions based on visual assessment can be challenging because some of benign lesions such as melanocytic lesions (ML) and seborrheic keratoses (SK) resemble MM. In this paper we introduce a novel, non-invasive, "optical biopsy" method based on laser speckle. Propagating inside the skin tissues, photons undergo optical path dispersion due to scattering. Therefore the emerging light loses the initial state of coherence, which influences the backscattered speckle pattern if the light optical path deviation in a tissue is comparable with the length of coherence. Speckle contrast is a measure of this decorrelation process. Histology shows that MM, ML, and SK have diverse morphology. We hypothesized that the morphological differences can be detected by polychromatic speckle, and the technique can be used to differentiate these lesions in vivo. In a study with 12 MMs, 24 MLs, and 37 SKs, we computed the speckle contrast related to their superficial skin region. The mean contrast of MM, ML and SK were 0.78 (standard error (SE) = 0.02, 0.63 (SE = 0.01), and 0.67 (SE = 0.01), respectively. Statistical test showed that there was a significant difference among the contrast of the three types of lesions (p < 0.001, Kruskal-Wallis), and intergroup pair-wise tests showed significant differences in distribution between all three groups. Potentially, speckle imaging can differentiate these lesions.

  17. Coffee consumption and the risk of malignant melanoma in the Norwegian Women and Cancer (NOWAC) Study.

    Science.gov (United States)

    Lukic, Marko; Jareid, Mie; Weiderpass, Elisabete; Braaten, Tonje

    2016-07-29

    Coffee contains biologically-active substances that suppress carcinogenesis in vivo, and coffee consumption has been associated with a lower risk of malignant melanoma. We studied the impact of total coffee consumption and of different brewing methods on the incidence of malignant melanoma in a prospective cohort of Norwegian women. We had baseline information on total coffee consumption and consumption of filtered, instant, and boiled coffee from self-administered questionnaires for 104,080 women in the Norwegian Women and Cancer (NOWAC) Study. We also had follow-up information collected 6-8 years after baseline. Multiple imputation was used to deal with missing data, and multivariable Cox regression models were used to calculate hazard ratios (HR) for malignant melanoma by consumption category of total, filtered, instant, and boiled coffee. During 1.7 million person-years of follow-up, 762 cases of malignant melanoma were diagnosed. Compared to light consumers of filtered coffee (≤1 cup/day), we found a statistically significant inverse association with low-moderate consumption (>1-3 cups/day, HR = 0.80; 95 % confidence interval [CI] 0.66-0.98) and high-moderate consumption of filtered coffee (>3-5 cups/day, HR = 0.77; 95 % CI 0.61-0.97) and melanoma risk (p trend = 0.02). We did not find a statistically significant association between total, instant, or boiled coffee consumption and the risk of malignant melanoma in any of the consumption categories. The data from the NOWAC Study indicate that a moderate intake of filtered coffee could reduce the risk of malignant melanoma.

  18. Correlations Between Cutaneous Malignant Melanoma and Other Cancers: An Ecological Study in Forty European Countries.

    Science.gov (United States)

    Serrano, Pablo Fernandez-Crehuet; Serrano, Jose Luis Fernandez-Crehuet; Allam, Mohamed Farouk; Navajas, Rafael Fernandez-Crehuet

    2016-01-01

    The presence of noncutaneous neoplasms does not seem to increase the risk of cutaneous malignant melanoma; however, it seems to be associated with the development of other hematological, brain, breast, uterine, and prostatic neoplasms. An ecological transversal study was conducted to study the geographic association between cutaneous malignant melanoma and 24 localizations of cancer in forty European countries. Cancer incidence rates were extracted from GLOBOCAN database of the International Agency for Research on Cancer. We analyzed the age-adjusted and gender-stratified incidence rates for different localizations of cancer in forty European countries and calculated their correlation using Pearson's correlation test. In males, significant correlations were found between cutaneous malignant melanoma with testicular cancer (r = 0.83 [95% confidence interval (CI): 0.68-0.89]), myeloma (r = 0.68 [95% CI: 0.46-0.81]), prostatic carcinoma (r = 0.66 [95% CI: 0.43-0.80]), and non-Hodgkin lymphoma (NHL) (r = 0.63 [95% CI: 0.39-0.78]). In females, significant correlations were found between cutaneous malignant melanoma with breast cancer (r = 0.80 [95% CI: 0.64-0.88]), colorectal cancer (r = 0.72 [95% CI: 0.52-0.83]), and NHL (r = 0.71 [95% CI: 0.50-0.83]). These correlations call to conduct new studies about the epidemiology of cancer in general and cutaneous malignant melanoma risk factors in particular.

  19. Prognostic significance of thymidylate synthase (TS) expression in cutaneous malignant melanoma.

    Science.gov (United States)

    Shimizu, A; Kaira, K; Yasuda, M; Asao, T; Ishikawa, O

    2016-01-01

    Thymidylate synthase (TS) plays an essential role in the pathogenesis and development of cancer, and TS-targeting agents have been widely used against different types of cancers. However, it remains still unclear whether or not TS is expressed in malignant melanoma. We conducted the clinicopathological study to investigate the prognostic significance of TS expression in cutaneous malignant melanoma. Ninety-nine patients with surgically resected cutaneous malignant melanoma were assessed. Tumor sections were stained by immunohistochemistry for TS, Ki-67, and microvessel density (MVD) determined by CD34. TS was positively expressed in 26% (26 out of 99). The expression of TS was significantly associated with T factor, cell proliferation (Ki-67) and MVD (CD34). By Spearman's rank test, TS expression was significantly correlated with Ki67 and CD34. By univariate analysis, ulceration, disease stage, TS, Ki-67 and CD34 had a significant relationship with survival. Multivariate analysis confirmed that TS was an independent prognostic factor for poor prognosis of cutaneous malignant melanoma. The positive expression of TS could be a useful marker for predicting poor prognosis in patients with cutaneous malignant melanoma, and TS-targeting agents may be worth trying for the treatment of this dismal disease.

  20. Correlations between cutaneous malignant melanoma and other cancers: An ecological study in forty European countries

    Directory of Open Access Journals (Sweden)

    Pablo Fernandez-Crehuet Serrano

    2016-01-01

    Full Text Available Background: The presence of noncutaneous neoplasms does not seem to increase the risk of cutaneous malignant melanoma; however, it seems to be associated with the development of other hematological, brain, breast, uterine, and prostatic neoplasms. An ecological transversal study was conducted to study the geographic association between cutaneous malignant melanoma and 24 localizations of cancer in forty European countries. Methods: Cancer incidence rates were extracted from GLOBOCAN database of the International Agency for Research on Cancer. We analyzed the age-adjusted and gender-stratified incidence rates for different localizations of cancer in forty European countries and calculated their correlation using Pearson′s correlation test. Results: In males, significant correlations were found between cutaneous malignant melanoma with testicular cancer (r = 0.83 [95% confidence interval (CI: 0.68-0.89], myeloma (r = 0.68 [95% CI: 0.46-0.81], prostatic carcinoma (r = 0.66 [95% CI: 0.43-0.80], and non-Hodgkin lymphoma (NHL (r = 0.63 [95% CI: 0.39-0.78]. In females, significant correlations were found between cutaneous malignant melanoma with breast cancer (r = 0.80 [95% CI: 0.64-0.88], colorectal cancer (r = 0.72 [95% CI: 0.52-0.83], and NHL (r = 0.71 [95% CI: 0.50-0.83]. Conclusions: These correlations call to conduct new studies about the epidemiology of cancer in general and cutaneous malignant melanoma risk factors in particular.

  1. SKI knockdown inhibits human melanoma tumor growth in vivo.

    Science.gov (United States)

    Chen, Dahu; Lin, Qiushi; Box, Neil; Roop, Dennis; Ishii, Shunsuke; Matsuzaki, Koichi; Fan, Tao; Hornyak, Thomas J; Reed, Jon A; Stavnezer, Ed; Timchenko, Nikolai A; Medrano, Estela E

    2009-12-01

    The SKI protein represses the TGF-beta tumor suppressor pathway by associating with the Smad transcription factors. SKI is upregulated in human malignant melanoma tumors in a disease-progression manner and its overexpression promotes proliferation and migration of melanoma cells in vitro. The mechanisms by which SKI antagonizes TGF-beta signaling in vivo have not been fully elucidated. Here we show that human melanoma cells in which endogenous SKI expression was knocked down by RNAi produced minimal orthotopic tumor xenograft nodules that displayed low mitotic rate and prominent apoptosis. These minute tumors exhibited critical signatures of active TGF-beta signaling including high levels of nuclear Smad3 and p21(Waf-1), which are not found in the parental melanomas. To understand how SKI promotes tumor growth we used gain- and loss-of-function approaches and found that simultaneously to blocking the TGF-beta-growth inhibitory pathway, SKI promotes the switch of Smad3 from tumor suppression to oncogenesis by favoring phosphorylations of the Smad3 linker region in melanoma cells but not in normal human melanocytes. In this context, SKI is required for preventing TGF-beta-mediated downregulation of the oncogenic protein c-MYC, and for inducing the plasminogen activator inhibitor-1, a mediator of tumor growth and angiogenesis. Together, the results indicate that SKI exploits multiple regulatory levels of the TGF-beta pathway and its deficiency restores TGF-beta tumor suppressor and apoptotic activities in spite of the likely presence of oncogenic mutations in melanoma tumors.

  2. Malignant melanoma mimicking giant cell variant of glioblastoma multiforme: a case report and review of literature.

    Science.gov (United States)

    Arcega, Ramir; Yong, William H; Xu, Haodong

    2015-01-01

    We present a case of metastatic malignant melanoma in a patient initially diagnosed with glioblastoma multiforme, giant cell variant. A forty year old female presented to our institution for a re-resection of a recurrent right parietal lobe mass, presumed to be recurrent glioblastoma multiforme. PET scan during preoperative evaluation revealed a 3 cm left lower lobe lung mass. Metastatic glioblastoma to lung was considered in the differential diagnosis. Resection of the brain mass revealed a highly pleomorphic giant and spindle cell lesion with an immunophenotype strongly supportive of melanoma. Immunostains for melanocytic markers were subsequently performed on the lung biopsy specimen, and demonstrated diffuse staining of the atypical cells, supporting the diagnosis of malignant melanoma in the lung. This case demonstrates the importance of considering melanoma in the differential in any tumor with high grade features.

  3. Radiculopathy due to malignant melanoma in the sacrum with unknown primary site

    OpenAIRE

    Kakutani, Kenichiro; Doita, Minoru; Nishida, Kotaro; Miyamoto, Hiroshi; Kurosaka, Masahiro

    2007-01-01

    Melanoma is an interesting tumor, showing the appearance of metastasis without any trace of its primary lesion. To report a very rare case of malignant melanoma in the sacrum with unknown primary origin. The authors present a case of a 52-year-old man who was admitted with increasing lower back, left buttock, and left lower extremity pain, and dysuria. Plain radiograph, computed tomography scan, and magnetic resonance imaging revealed a destructive lesion in the sacrum and left ilium, which i...

  4. 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...... 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....

  5. Malignant amelanotic melanoma of the pleura without primary skin lesion:an autopsy case report.

    Science.gov (United States)

    Ohata, Yuichiro; Haga, Takayuki; Ogata, Sho; Nakanishi, Kuniaki; Kawai, Toshiaki

    2009-12-01

    Melanoma metastasizing to the lungs is common, but primary pulmonary or pleural melanoma is extremely rare. We present an autopsy case of malignant melanoma of the pleura without primary skin lesion in a 49-year-old man. A mass found in the right chest was diagnosed as spindle cell sarcoma by antemortem fine-needle aspiration cytology. At autopsy, a yellow-white tumor located primarily in the right visceral pleura (diagnosed as an amelanotic melanoma) was found to have invaded into the right lung, right parietal pleura, and right diaphragm, and to have metastasized into the left lung and visceral pleura, thyroid, and left adrenal gland. No primary site was found. The tumor cells were positive for S100 and focally positive for HMB-45, but negative for other markers. Immuno-histochemical examination for S100 and HMB-45 would thus appear to be useful for the diagnosis of an amelanotic melanoma.

  6. [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.

  7. Primary malignant melanoma of uterine cervix with probable origin from benign cervical melanosis.

    Science.gov (United States)

    Singh, Nilanchali; Tripathi, Reva; Mala, Yedla Manikya

    2013-06-03

    We report a case of primary malignant melanoma of cervix which is a rare malignancy with only around 60 cases being reported. This patient presented with bleeding per vaginum. A large exophytic growth from cervix with black discolouration was seen. International Federation of Gynaecology and Obsterics (FIGO) staging was stage IIa. Histoimmunocytology confirmed the diagnosis of malignant melanoma of cervix. S-100 and HMB-45 are reliable markers for cervical melanomas. We attempted Wertheim's hysterectomy; but, due to extensive disease, paravescical and pararectal fossae could not be dissected and we had to perform type I hysterectomy. The patient was started on adjuvant chemotherapy with dacarbazine. Despite counselling, she refused a complete course of chemotherapy and died after 6 months. Radical surgery, chemotherapy and immunotherapy are the therapeutic modalities used. In bulky disease, neoadjuvant chemotherapy should be considered to reduce the tumour bulk and facilitate required surgery. Prognosis is poor and unpredictable.

  8. Metastatic Malignant Melanoma of the Inguinal Lymph Node with Unknown Primary Lesion

    Directory of Open Access Journals (Sweden)

    Sherif Ali Eltawansy

    2015-01-01

    Full Text Available Background. Malignant melanoma could present with metastasis with unknown primary (MUP and this happens in 2-3% according to the studies. Around 90% of melanomas have cutaneous origin, but still there are melanomas that could be found in visceral organs or lymph nodes with unknown primary site. Spontaneous regression of the primary site could be an explanation. Case Report. We report a 58-year-old Caucasian male who presented with a right sided swelling in the inguinal region. Surgery was performed and biopsy showed metastatic malignant melanoma. No cutaneous lesions were identified by history or physical examination. Work up could not detect the primary lesion and patient was started on radiotherapy and immunotherapy. Conclusion. We present a case of malignant melanoma of unknown primary presenting in an unusual place which is the inguinal lymph node. Theories try to explain the pathway of development of such tumors and one of the theories mentions that it could be a spontaneous regression of the primary cutaneous lesion. Another theory is that it could be from transformation of aberrant melanocyte within the lymph node. Prognosis is postulated to be better in this case than in melanoma with a known primary.

  9. RAGE-aptamer Attenuates the Growth and Liver Metastasis of Malignant Melanoma in Nude Mice.

    Science.gov (United States)

    Nakamura, Nobutaka; Matsui, Takanori; Ishibashi, Yuji; Sotokawauchi, Ami; Fukami, Kei; Higashimoto, Yuichiro; Yamagishi, Sho-Ichi

    2017-11-06

    Epidemiological studies have suggested the link between cumulative diabetic exposure and cancer. Interaction of advanced glycation end products (AGEs) with their receptor (RAGE) may contribute to the phenomenon. We examined here the effects of DNA aptamer raised against RAGE (RAGE-aptamer) on growth and liver metastasis of G361 melanoma in nude mice. Malignant melanoma cells were intradermally injected into the upper flank region of nude mice, which received continuous administration of RAGE-aptamer (38.4 pmol/day/g body weight) or vehicle intraperitoneally by an osmotic pump up to 42 days. RAGE-aptamer significantly reduced levels of 8-hydroxy-2'-deoxy-guanosine, AGEs, RAGE, proliferating nuclear antigen, cyclin D1, vascular endothelial growth factor (VEGF), monocyte chemoattractant protein-1 (MCP-1), and CD31 and Mac-3, respective markers of endothelial cells and macrophages in tumors of nude mice and suppressed the proliferation and liver metastasis of malignant melanoma. Furthermore, RAGE-aptamer attenuated the AGE-induced oxidative stress generation, proliferation, and VEGF and MCP-1 gene expression in both G361 melanoma cells and endothelial cells. The present findings suggest that RAGE-aptamer could attenuate melanoma growth and liver metastasis in nude mice by suppressing the tumor angiogenesis and macrophage infiltration via inhibition of the AGE-RAGE system. RAGE-aptamer may be a novel therapeutic tool for the treatment of malignant melanoma.

  10. Analysis of alpha-synuclein in malignant melanoma - development of a SRM quantification assay.

    Directory of Open Access Journals (Sweden)

    Charlotte Welinder

    Full Text Available Globally, malignant melanoma shows a steady increase in the incidence among cancer diseases. Malignant melanoma represents a cancer type where currently no biomarker or diagnostics is available to identify disease stage, progression of disease or personalized medicine treatment. The aim of this study was to assess the tissue expression of alpha-synuclein, a protein implicated in several disease processes, in metastatic tissues from malignant melanoma patients. A targeted Selected Reaction Monitoring (SRM assay was developed and utilized together with stable isotope labeling for the relative quantification of two target peptides of alpha-synuclein. Analysis of alpha-synuclein protein was then performed in ten metastatic tissue samples from the Lund Melanoma Biobank. The calibration curve using peak area ratio (heavy/light versus concentration ratios showed linear regression over three orders of magnitude, for both of the selected target peptide sequences. In support of the measurements of specific protein expression levels, we also observed significant correlation between the protein and mRNA levels of alpha-synuclein in these tissues. Investigating levels of tissue alpha-synuclein may add novel aspect to biomarker development in melanoma, help to understand disease mechanisms and ultimately contribute to discriminate melanoma patients with different prognosis.

  11. BRAF mutations in metastatic malignant melanoma: comparison of molecular analysis and immunohistochemical expression.

    Science.gov (United States)

    Ehsani, Laleh; Cohen, Cynthia; Fisher, Kevin E; Siddiqui, Momin T

    2014-10-01

    Melanoma is a complex genetic disease, and multiple genetic alterations have been reported to play a role during disease progression. The dysregulation of BRAF signaling has been shown to affect many molecules that promote the continual progression of melanoma. Oncogenic BRAF expression plays a vital role in promoting cell invasion and metastasis in melanoma. It is also associated with poor prognosis in metastatic melanoma. About 40% to 60% of cutaneous melanomas have BRAF mutations, and 90% of the mutations involve a specific substitution at codon 600 (BRAF V600E). In this study, we compared BRAF (V600E) mutation detection by molecular analysis with BRAF expression by immunohistochemical (IHC) analysis using 2 different antibodies. A total of 25 metastatic malignant melanomas were included in this study. 10 of the 25 (40%) cases were positive by molecular analysis using the COBAS 4800 BRAF V600 Real-time PCR assay, and 18 of the 25 (72%) cases were positive by IHC analysis with 2 different antibodies. All positive cases by molecular analysis were positive by both IHC stains (100%). No false negatives were obtained with either IHC stain. Eight of the 25 (32%) were false-positive by both IHC stains. This study demonstrates that IHC analysis is a very sensitive test for evaluation of BRAF mutations in metastatic malignant melanoma and may be useful as an initial screening test.

  12. FGF5 is expressed in melanoma and enhances malignancy in vitro and in vivo.

    Science.gov (United States)

    Ghassemi, Sara; Vejdovszky, Katharina; Sahin, Emine; Ratzinger, Lukas; Schelch, Karin; Mohr, Thomas; Peter-Vörösmarty, Barbara; Brankovic, Jelena; Lackner, Andreas; Leopoldi, Alexandra; Meindl, Diana; Pirker, Christine; Hegedus, Balazs; Marian, Brigitte; Holzmann, Klaus; Grasl-Kraupp, Bettina; Heffeter, Petra; Berger, Walter; Grusch, Michael

    2017-10-20

    Although FGF5 mRNA was previously found expressed in some melanoma cell lines in contrast to normal human melanocytes, neither its contribution to melanoma growth nor its expression in melanoma tissue has been investigated. Here we demonstrate that ectopic overexpression of FGF5 in human melanoma cells with low endogenous FGF5 expression increased clonogenicity and invasion but not short-term growth in vitro. Silencing of FGF5 in melanoma cells with high endogenous FGF5 expression had the opposite effect on clonogenicity. FGF overexpression led to increased signaling along the MAPK and NFAT axis but had no effect on STAT3 signaling. In an in vivo experiment in immunocompromised mice, human melanoma xenografts overexpressing FGF5 showed enhanced tumor growth, a higher Ki-67 proliferation index, decreased apoptosis and enhanced angiogenesis. Immunohistochemistry performed on a tissue microarray demonstrated FGF5 protein expression in more than 50% of samples of melanoma and benign nevi. These data suggest that FGF5 has oncogenic potential in melanoma cells and contributes to melanoma growth in a subset of patients. This highlights the importance of further evaluating FGF5 as potential biomarker and therapy target in melanoma.

  13. Coping with melanoma-related worry: a qualitative study of the experiences and support needs of patients with malignant melanoma.

    Science.gov (United States)

    Bird, Joanne; Coleman, Patricia; Danson, Sarah

    2015-04-01

    To explore the patients' experience of having malignant melanoma, their related support needs and the processes that lead to these needs being met. The number of patients attending surveillance clinics after a diagnosis of malignant melanoma is increasing. In the UK specialist nurses provide support to patients, but little evidence exists about the nature of patients' support needs or their experience of having melanoma. Melanoma has often been researched within general cancer studies, yet the support needs of melanoma patients may be different from those of patients with other skin cancers or tumour types. A Grounded Theory Approach was used to guide sampling, data collection and analysis. In-depth interviews were conducted with eleven patients who where purposively sampled. Transcripts were read several times, coded and categorised using the constant comparative method. Emergent categories were discussed with participants. Three emergent categories related to a core category of melanoma-related worry which formed a substantive theory about the strategies patients use to control this. Participants reported needing to have their concerns believed by others prior to and after diagnosis. They discussed discerning whom to share their concerns with depending upon who they felt would not perceive assisting them as being burdensome. They also sought ways to reassure themselves. Patients need to have their fear and worries acknowledged by others. This includes nurses, healthcare professionals and family members. Patients will also use self-examination and the absence of symptoms to reassure themselves. Nurses play key roles throughout the patient's care; therefore they need to be sensitive to the fact that patients may consider them a primary source of support. When teaching self-examination it is important that nurses discuss that this may ease worry and aid coping. © 2015 John Wiley & Sons Ltd.

  14. Beta-blocker usage after malignant melanoma diagnosis and survival: a population-based nested case-control study.

    Science.gov (United States)

    McCourt, C; Coleman, H G; Murray, L J; Cantwell, M M; Dolan, O; Powe, D G; Cardwell, C R

    2014-04-01

    Beta-blockers have potential antiangiogenic and antimigratory activity. Studies have demonstrated a survival benefit in patients with malignant melanoma treated with beta-blockers. To investigate the association between postdiagnostic beta-blocker usage and risk of melanoma-specific mortality in a population-based cohort of patients with malignant melanoma. Patients with incident malignant melanoma diagnosed between 1998 and 2010 were identified within the U.K. Clinical Practice Research Datalink and confirmed using cancer registry data. Patients with malignant melanoma with a melanoma-specific death (cases) recorded by the Office of National Statistics were matched on year of diagnosis, age and sex to four malignant melanoma controls (who lived at least as long after diagnosis as their matched case). A nested case-control approach was used to investigate the association between postdiagnostic beta-blocker usage and melanoma-specific death and all-cause mortality. Conditional logistic regression was applied to generate odds ratios (ORs) and 95% confidence intervals (CIs) for beta-blocker use determined from general practitioner prescribing. Beta-blocker medications were prescribed after malignant melanoma diagnosis to 20·2% of 242 patients who died from malignant melanoma (cases) and 20·3% of 886 matched controls. Consequently, there was no association between beta-blocker use postdiagnosis and cancer-specific death (OR 0·99, 95% CI 0·68-1·42), which did not markedly alter after adjustment for confounders including stage (OR 0·87, 95% CI 0·56-1·34). No significant associations were detected for individual beta-blocker types, by defined daily doses of use or for all-cause mortality. Contrary to some previous studies, beta-blocker use after malignant melanoma diagnosis was not associated with reduced risk of death from melanoma in this U.K. population-based study. © 2014 British Association of Dermatologists.

  15. Intraocular malignant melanoma of the choroid presenting as orbital cellulitis.

    Science.gov (United States)

    Nair, Akshay Gopinathan; Kaliki, Swathi; Ali, Mohammed Javed; Naik, Milind N; Vemuganti, Geeta K

    2014-06-01

    We report a case of choroidal melanoma with features suggestive of orbital cellulitis. A 24-year-old Asian Indian male presented with a 20-day history of sudden loss of vision in the right eye. Edematous eyelids with complete mechanical ptosis, complete ophthalmoplegia, gross proptosis accompanied by massive chemosis, and prolapse of the inferior forniceal conjunctiva were noted. He denied perception of light in the right eye. The left eye was unremarkable. B-scan ultrasonography of the right eye showed a large dome-shaped mass filling the posterior segment suggestive of choroidal melanoma. Computed tomography confirmed those findings and showed no extraocular tumor extension. The patient was conservatively treated with systemic steroids following which the inflammation subsided. He underwent enucleation of the right eye and a diagnosis of spindle A cell choroidal melanoma was confirmed by histopathological examination. Although rare, orbital cellulitis is one of the presenting features of choroidal melanoma. Uveal melanoma-associated orbital cellulitis can be well controlled with systemic steroids, does not always indicate extraocular tumor extension, and can occur in spindle A cell melanomas.

  16. 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.

  17. Time trends and latitude dependence of uveal and cutaneous malignant melanoma induced by solar radiation

    Energy Technology Data Exchange (ETDEWEB)

    Moan, J.; Setlow, R.; Cicarma, E.; Porojnicu, A. C.; Grant, W. B.; Juzeniene, A.

    2010-01-01

    In order to evaluate the role of solar radiation in uveal melanoma etiology, the time and latitude dependency of the incidence rates of this melanoma type were studied in comparison with those of cutaneous malignant melanoma (CMM). Norway and several other countries with Caucasian populations were included. There is a marked north - south gradient of the incidence rates of CMM in Norway, with three times higher rates in the south than in the north. No such gradient is found for uveal melanoma. Similar findings have been published for CMM in other Caucasian populations, with the exception of Europe as a whole. In most populations the ratios of uveal melanoma incidence rates to those of CMM tend to decrease with increasing CMM rates. This is also true for Europe, in spite of the fact that in this region there is an inverse latitude gradient of CMM, with higher rates in the north than in the south. In Norway the incidence rates of CMM have increased until about 1990 but have been constant, or even decreased (for young people) after that time, indicating constant or decreasing sun exposure. The uveal melanoma rates have been increasing after 1990. In most other populations the incidence rates of CMM have been increasing until recently while those of uveal melanoma have been decreasing. These data generally support the assumption that uveal melanomas are not generated by ultraviolet (UV) radiation and that solar UV, via its role in vitamin D photosynthesis, may have a protective effect.

  18. Obesity as a risk factor for malignant melanoma and non-melanoma skin cancer.

    Science.gov (United States)

    Karimi, K; Lindgren, T H; Koch, C A; Brodell, Robert T

    2016-09-01

    The dramatic increases in incidence of both obesity and many cancers including skin cancer emphasize the need to better understand the pathophysiology of both conditions and their connections. Melanoma is considered the fastest growing cancer and rates of non-melanoma skin cancer have also increased over the last decade. The molecular mechanisms underlying the association between obesity and skin cancer are not clearly understood but emerging evidence points to changes in the tumor microenvironment including aberrant cell signaling and genomic instability in the chronic inflammatory state many obese individuals experience. This article reviews the literature linking obesity to melanoma and non-melanoma skin cancer.

  19. Serum anti-BPAG1 auto-antibody is a novel marker for human melanoma.

    Directory of Open Access Journals (Sweden)

    Takashi Shimbo

    2010-05-01

    Full Text Available Malignant melanoma is one of the most aggressive types of tumor. Because malignant melanoma is difficult to treat once it has metastasized, early detection and treatment are essential. The search for reliable biomarkers of early-stage melanoma, therefore, has received much attention. By using a novel method of screening tumor antigens and their auto-antibodies, we identified bullous pemphigoid antigen 1 (BPAG1 as a melanoma antigen recognized by its auto-antibody. BPAG1 is an auto-antigen in the skin disease bullous pemphigoid (BP and anti-BPAG1 auto-antibodies are detectable in sera from BP patients and are used for BP diagnosis. However, BPAG1 has been viewed as predominantly a keratinocyte-associated protein and a relationship between BPAG1 expression and melanoma has not been previously reported. In the present study, we show that bpag1 is expressed in the mouse F10 melanoma cell line in vitro and F10 melanoma tumors in vivo and that BPAG1 is expressed in human melanoma cell lines (A375 and G361 and normal human melanocytes. Moreover, the levels of anti-BPAG1 auto-antibodies in the sera of melanoma patients were significantly higher than in the sera of healthy volunteers (p<0.01. Furthermore, anti-BPAG1 auto-antibodies were detected in melanoma patients at both early and advanced stages of disease. Here, we report anti-BPAG1 auto-antibodies as a promising marker for the diagnosis of melanoma, and we discuss the significance of the detection of such auto-antibodies in cancer biology and patients.

  20. Giant Congenital Melanocytic Naevus with Proliferative Nodules Mimicking Congenital Malignant Melanoma: A Case Report and Review of the Literature of Congenital Melanoma

    Directory of Open Access Journals (Sweden)

    Massimiliano Scalvenzi

    2013-01-01

    Full Text Available Congenital malignant melanoma (CMM is a rare condition that is defined as malignant melanoma recognized at birth. CMM may develop in utero in one of three ways: (1 transmission by metastasis through the placenta from a mother with melanoma; (2 primary melanoma arising within a giant congenital melanocytic naevus (GCMN; (3 primary de novo cutaneous CMM arising in utero. CMM can be confused clinically and histologically with benign proliferative melanocytic lesions such as giant congenital nevi. We describe the case of a patient presenting a GCMN with proliferative nodules, clinically and dermoscopically resembling a CMM, demonstrating the importance of caution in making a diagnosis of MM and highlighting the possibility that benign lesions as GCMN can mimic a malignant melanoma in this age group.

  1. The first attempt in local excision of anorectal malignant melanoma using transanal endoscopic microsurgery

    OpenAIRE

    Kong, Xiangyi; Liu, Qi; Lin, Guole; Zhao, Dachun; Qiu, Huizhong; Cui, Quancai

    2015-01-01

    Anorectal malignant melanoma (AMM) is an uncommon malignancy that is thought to arise from melanocytes in the mucosa around the anorectal junction. AMM is commonly misdiagnosed, and definitive preoperative diagnosis is often difficult. The prognosis of AMM is relatively poor. Although radical resection is required for AMM, there is still no consensus at this moment on which surgical approach is preferred. We herein report a rare case of AMM which was treated by transanal endoscopic microsurge...

  2. Long term outcome of boron neutron capture therapy for malignant melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Hiratsuka, J. [Kawasaki Medical School, Kurashiki, Okayama (Japan); Fukuda, H. [Tohoku Univ., Sendai (Japan); Kobayashi, T. [Kyoto Univ. (Japan); Yoshino, K. [Shinshu Univ., Matsumoto, Nagano (Japan); Honda, C.; Ichihashi, M. [Kobe Univ., Kobe, Hyogo (Japan); Mishima, Y. [Mishima Institute for Dermatological Research, Kobe, Hyogo (Japan)

    2000-10-01

    Eighteen patients with cutaneous malignant melanoma were treated by boron neutron capture therapy (BNCT) using {sup 10}B-BPA. Our aim was to assess the long term clinical outcome of BNCT on these patients. The target areas were 15 primary lesions and 5 metastatic lesions. The primary lesions were consisted of acral lentigious melanoma (ALM) in six patients, nodular melanoma (NM) in six and lentigo maligna melanoma (LMM) in three. The complete regression (CR) rates were 73% for the primary lesions, 20% for the metastatic lesions. The CR rates for the primary lesions according to melanoma type were 33% for NM and 100% for non-NM. None of the patients with CR showed local recurrence in the radiation field during follow up ranging from 5.5 to 10.6 years (mean 6.7 years). The five year cause specific survival rate was 92% in the cases without distant metastasis at the time of BNCT. BNCT proves to be a very useful therapeutic modality for the management of cutaneous malignant melanoma. (author)

  3. Malignant melanoma of the conjunctiva: a case report with examination of KIT and PDGFRA

    Directory of Open Access Journals (Sweden)

    Tadashi Terada

    2012-01-01

    Full Text Available Although many clinicopathological studies malignant melanoma of the conjunctiva have been reported, there are no studies of the expression and gene mutation of KIT and PDGFRA in melanoma of the conjunctiva. A 69-year-old Japanese woman consulted to our hospital because of black mass (0.7 x 0.7 x 0.6 cm in the conjunctive. A biopsy was taken. The biopsy showed malignant epithelioid cells with melanin deposition. Immunohistochemically, the tumor was positive for S100 protein, HMB45, p53, Ki-67 (labeling=30%, KIT and PDGFRA. The tumor was negative for cytokeratins (AE1/3 and CAM5.2. A genetic analysis using PCR-direct sequencing revealed no mutation of KIT gene (exons 9, 11, 13, and 17 and the PDGFRA gene (exons 12 and 18. The pathological diagnosis was conjunctival melanoma. Despite chemotherapy, the patient developed multiple metastases of melanoma, and died of melanoma 7 years after the biopsy. In conclusion, the author reported a case of melanoma of conjunctive expressing KIT and PDGFRA without gene mutations of KIT and PDGFRA.

  4. Histone variant H2A.Z.2 mediates proliferation and drug sensitivity of malignant melanoma

    Science.gov (United States)

    Vardabasso, Chiara; Gaspar-Maia, Alexandre; Hasson, Dan; Pünzeler, Sebastian; Valle-Garcia, David; Straub, Tobias; Keilhauer, Eva C.; Strub, Thomas; Dong, Joanna; Panda, Taniya; Chung, Chi-Yeh; Yao, Jonathan L.; Singh, Rajendra; Segura, Miguel F.; Fontanals-Cirera, Barbara; Verma, Amit; Mann, Matthias; Hernando, Eva; Hake, Sandra B.; Bernstein, Emily

    2015-01-01

    SUMMARY Histone variants are emerging as key regulatory molecules in cancer. Here we report a novel role for the H2A.Z isoform H2A.Z.2 as a driver of malignant melanoma. H2A.Z.2 is highly expressed in metastatic melanoma, correlates with decreased patient survival, and is required for cellular proliferation. Our integrated genomic analyses reveal that H2A.Z.2 controls the transcriptional output of E2F target genes in melanoma cells. These genes are highly expressed and display a distinct signature of H2A.Z occupancy. We identify BRD2 as an H2A.Z interacting protein, whose levels are also elevated in melanoma. We further demonstrate that H2A.Z.2 regulated genes are bound by BRD2 and E2F1 in a H2A.Z.2-dependent manner. Importantly, H2A.Z.2 deficiency sensitizes melanoma cells to chemotherapy and targeted therapies. Collectively, our findings implicate H2A.Z.2 as a mediator of cell proliferation and drug sensitivity in malignant melanoma, holding translational potential for novel therapeutic strategies. PMID:26051178

  5. A case of collision tumor or transdifferentiation between malignant melanoma and leiomyosarcoma.

    Science.gov (United States)

    Ul-Mulk, Jamshaid; Rasmussen, Helle; Breiting, Line; Siim, Elsebeth

    2012-01-01

    A 73-year-old woman was referred to the hospital due to a pigmented, asymptomatic nevus on her right arm that had changed in size and color. The histopathological examination showed a superficial spreading malignant melanoma, Clark level III, 2.26 mm in thickness. Two years later, the patient presented a 10 cm rapidly growing mass in her right axilla. The mass in the axilla measured 12.5΄9΄cm. It revealed a lymph node metastases with a tumor growth composed of two different contiguous morphological and immunohistochemical components, respectively, melanosomes and leiomyosarcoma. The combination of a melanocytic nevus with other tumor of epidermal or adnexal origin has been described before, but still the co-existence of two different neoplasms within a lesion is still uncommon. The most common combination is basal cell carcinoma and melanocytic nevus or one of them together with a seborrheic keratosis. There have also been occasional reports of rhabdomyosarcomatous differentiation. However, mesenchymal differentiation, and in this case leiomysarcoma, with formation of heterologous elements in melanocytic tumor is very rare. Another plausible explanation may be that malignant melanoma cells could have transdifferentiated into a leiomyosarcomatoid phenotype with resulting metastases of either type. Malignant melanomas have shown a wide variety of cytological changes and can mimic carcinomas, lymphomas, and sarcomas. Spindle cell melanomas commonly simulate spindle cell carcinomas. It has also been documented that desmoplastic melanomas can change into fibroblastic, Schwannian, and myofibroblastic differentiation.

  6. Aqueous immune mediators in malignant uveal melanomas in comparison to benign pigmented intraocular tumors.

    Science.gov (United States)

    Usui, Yoshihiko; Tsubota, Kinya; Agawa, Tsuyoshi; Ueda, Shunichiro; Umazume, Kazuhiko; Okunuki, Yoko; Kezuka, Takeshi; Yamakawa, Naoyuki; Goto, Hiroshi

    2017-02-01

    To examine the usefulness of measuring immune mediators in aqueous humor samples for differentiating malignant uveal melanoma from benign pigmented intraocular tumors. Thirteen eyes of 13 patients with uveal melanoma were studied, and 13 eyes of 13 patients with benign pigmented intraocular tumors served as controls. Undiluted samples of aqueous humor were collected, and a cytometric bead array was used to determine the aqueous humor concentrations of 35 immune mediators comprising 14 interleukins (IL), interferon-γ, interferon-γ-inducible protein-10, monocyte chemoattractant protein (MCP)-1, macrophage inflammatory protein (MIP)-1α, MIP-1β, regulated on activation normal T cell expressed and secreted, monokine induced by interferon-γ, basic fibroblast growth factor, Fas ligand, granzyme A, granzyme B, eotaxin, interferon-inducible T-cell alpha chemoattractant, fractalkine, granulocyte macrophage colony-stimulating factor, granulocyte colony-stimulating factor, vascular endothelial growth factor, angiogenin, tumor necrosis factor-α, lymphotoxin-α, and CD40L. Aqueous humor levels of angiogenin, IL-8, and MCP-1 were significantly higher in eyes with malignant melanoma than in those with benign tumors (p melanoma from benign pigmented intraocular tumors, and may be a useful adjunct to histomorphology, diagnostic imaging, and other biomarkers for the diagnosis and appropriate clinical management of malignant uveal melanoma.

  7. Delayed presentation of tattoo lymphadenopathy mimicking malignant melanoma lymphadenopathy.

    Science.gov (United States)

    Bordea, C; Latifaj, B; Jaffe, W

    2009-08-01

    Tattooing is a popular cosmetic practice and the technique has been adopted in breast reconstruction. Pigment injected intradermally is transported to lymph nodes leading to permanent pigmentation. Differential diagnosis between melanoma and tattoo pigmentation of lymph nodes is done microscopically. We present the case study of a patient who presented with palpable and pigmented axillary lymph nodes, 2 years after excision of melanoma and 20 years after tattooing. Intraoperative finding of enlarged, pigmented lymph nodes is not a certain sign of metastasis, as causes other then melanoma can lead to pigmented lymphadenopathy. The diagnostic and investigation process should start with history (including history of previous tattooing) and fine needle aspiration (FNA) of enlarged lymph node. If FNA is negative an open biopsy should be performed for confirmation of diagnosis before proceeding to completion lymphadenectomy.

  8. Mouse models in the study of malignant melanoma

    OpenAIRE

    Virós Usandizaga, Amaya

    2013-01-01

    Presentamos tres publicaciones que resumen la investigación de la propuesta doctoral en modelos de melanoma en ratón. En la primera publicación presentamos como la expresión del oncogén V600EBRAF en melanocitos de ratón adultos combinado con la expresión en queratinocitos adultos del mismo ratón de KITL logra traslocar los melanocitos de la dermis a la epidermis de los ratones. Sin embargo, la inclusión de melanocitos epidérmicos no logra generar un melanoma en el ratón que replique las carac...

  9. Malignant Melanoma in the Elderly: Different Regional Disease and Poorer Prognosis

    Directory of Open Access Journals (Sweden)

    James B. Macdonald, Amylou C. Dueck, Richard J. Gray, Nabil Wasif, David L. Swanson, Aleksandar Sekulic, Barbara A. Pockaj

    2011-01-01

    Full Text Available Purpose: Age is a poor prognostic factor in melanoma patients. Elderly melanoma patients have a different presentation and clinical course than younger patients. We evaluated the impact of age ≥70 years (yrs on the diagnosis and natural history of melanoma.Methods: Retrospective review of 610 patients with malignant melanoma entered into a prospective sentinel lymph node (SLN database, treated from June 1997 to June 2010. Disease characteristics and clinical outcomes were compared between patients ≥70 yrs vs. <70 yrs of age.Results: 237 patients (39% were ≥70 yrs. Elderly patients had a higher proportion of head and neck melanomas (34% vs. 20%, p<0.001, and greater mean tumor thickness (2.4mm vs. 1.8mm, p<0.001. A greater proportion of T3 or T4 melanoma was seen in the elderly (p<0.001 as well as a greater mean number of mitotic figures: 3.6/mm2 vs. 2.7/mm2 (p=0.005. Despite greater mean thickness, the incidence of SLN metastases was less in the ≥70 yrs group with T3/T4 melanomas (18% vs. 33%, p=0.02. The elderly had a higher rate of local and in-transit recurrences, 14.5% vs. 3.4% at 5 yrs (p<0.001. 5 yr disease-specific mortality and overall mortality were worse for those ≥70 yrs: 16% vs. 8% (p=0.004, and 30% vs. 12% (p<0.001, respectively.Conclusions: Elderly (≥70 yrs melanoma patients present with thicker melanomas and a higher mitotic rate but have fewer SLN metastases. Melanoma in the elderly is more common on the head and neck. Higher incidence of local/in-transit metastases is seen among the elderly. Five-year disease-specific mortality and overall mortality are both worse for these patients.

  10. 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...... be obtained objectively by point-sampled intercepts. Using this approach, the volume-weighted mean nuclear volume, nuclear vv, was estimated in ordinary histological sections from 34 primary cutaneous malignant melanomas and their corresponding 62 metastatic lesions. For comparison, DNA-indices (DI) were...... determined by flow cytometry in adjacent sections from the same paraffin-embedded tumours. Only a poor correlation was found between nuclear vv and DI (Kendall's tau = +0.21). The variability of nuclear vv among metastatic lesions was increased as compared to primary melanomas, whereas averaged mean values...

  11. Gastric and Rectal Metastases from Malignant Melanoma Presenting with Hypochromic Anemia and Treated with Immunotherapy

    Directory of Open Access Journals (Sweden)

    Pietro Genova

    2017-01-01

    Full Text Available The authors present a case of an 80-year-old Caucasian male with multiple gastric and rectal metastases from malignant melanoma presenting with hypochromic anemia as the sole symptom of disease without evidence of cutaneous and ocular tumor localization. The patient had a medical history positive for malignant lentigo melanoma of the occipital region of the scalp and early stage laryngeal squamous cell carcinoma and prostatic carcinoma treated with radiation therapy. The authors make some considerations on intestinal involvement by metastatic melanoma and discuss the choice of not treating with endoscopic procedures the gastric metastatic lesions most likely responsible for the clinical sign present at diagnosis. The patient was referred to clinical oncologists and received immunotherapy with ipilimumab and pembrolizumab.

  12. Blood flow velocity imaging of malignant melanoma by micro multipoint laser Doppler velocimetry

    Science.gov (United States)

    Ishida, H.; Andoh, T.; Akiguchi, S.; Shirakawa, H.; Kobayashi, D.; Kuraishi, Y.; Hachiga, T.

    2010-09-01

    We have developed a laser Doppler velocimeter to measure blood flow, the micromultipoint laser Doppler velocimeter (μ-MLDV). This equipment can measure absolute velocity and, based on this, can display the course of blood vessels. In this study, we attempted to perform blood flow velocity imaging of malignant melanoma transplanted to the mouse ear. We found that blood flow velocity of the formed blood vessels originating in the melanoma was much greater than that of the capillary vessels in normal skin. Furthermore, the form of the tumor was clearly visible from the blood flow velocity image. These experimental results suggest that μ-MLDV has potential as a diagnostic method for distinguishing benign nevi from malignant melanomas.

  13. Choroidal malignant melanoma with no extraocular extension presenting as orbital cellulitis.

    Science.gov (United States)

    Nalcaci, Serhad; Palamar, Melis; Yaman, Banu; Akalin, Taner; Mentes, Jale

    2016-10-01

    This report describes a patient with choroidal malignant melanoma presenting as orbital cellulitis without extraocular tumor extension. It is an interventional case report with histopathologic correlation. A 68-year-old male presented with a 3-day history of painful hyperemia and swelling in the right eye. The examination showed edematous eyelids, mechanical ptosis and chemosis with conjunctival injection. B-scan ultrasonography showed a mass with medium level echogenicity that filled the vitreous cavity. Magnetic resonance imaging showed a solid choroidal mass with hemorrhagic and inflammatory changes with no obvious extraocular extension. Due to these suggestive findings of choroidal melanoma the right eye was enucleated. A spindle cell choroidal melanoma including intense pigmentation and necrosis was confirmed by histopathological examination. Although rare; choroidal melanoma may present as orbital cellulitis, particularly when the tumor is necrotic.

  14. Malignant melanoma risk after exposure to fertility drugs: results from a large Danish cohort study

    DEFF Research Database (Denmark)

    Hannibal, C.G.; Jensen, A.; Sharif, H.

    2008-01-01

    OBJECTIVE: The aim was to examine the effects of fertility drugs on malignant melanoma risk using data from the largest cohort of infertile women to date. METHODS: A cohort of 54,362 women with infertility problems referred to Danish fertility clinics in the period 1963-1998 was established. A de...

  15. Loss-of-function mutations in filaggrin gene and malignant melanoma

    DEFF Research Database (Denmark)

    Thyssen, J P; Andersen, Y M F; Balslev, E

    2017-01-01

    aimed to investigate the association between FLG mutation status and the occurrence of malignant melanoma (MM) in Danish adults. METHODS: The prevalence of FLG mutations in a sample of MM biopsies was compared with a FLG-genotyped cohort from two general population studies. Pearson's chi...

  16. Positron emission tomography in the follow-up of cutaneous malignant melanoma patients

    DEFF Research Database (Denmark)

    Danielsen, Maria; Højgaard, Liselotte; Kjær, Andreas

    2014-01-01

    Cutaneous malignant melanoma (CMM) has a high risk of dissemination to regional lymph nodes and visceral organs. Recurrences are most frequently seen within the first 2-3 years after initial treatment, but these patients have a life-long risk of relapse. The prognosis is highly dependent on lymph...

  17. A case of collision tumor or transdifferentiation between malignant melanoma and leiomyosarcoma

    DEFF Research Database (Denmark)

    Ul-Mulk, Jamshaid; Rasmussen, Helle; Breiting, Line

    2012-01-01

    A 73-year-old woman was referred to the hospital due to a pigmented, asymptomatic nevus on her right arm that had changed in size and color. The histopathological examination showed a superficial spreading malignant melanoma, Clark level III, 2.26 mm in thickness. Two years later, the patient...

  18. Radiosensitivity of Human Melanoma Cell Lines

    Energy Technology Data Exchange (ETDEWEB)

    Bergoc, R. M.; Medina, V.; Cricco, G.; Mohamed, N.; Martin, G.; Nunez, M.; Croci, M.; Crescenti, E. J.; Rivera, E. S.

    2004-07-01

    Cutaneous melanoma is a skin cancer resulting from the malign transformation of skin-pigment cells, the melanocytes. The radiotherapy, alone or in combination with other treatment, is an important therapy for this disease. the objective of this paper was to determine in vitro the radiosensitivity of two human melanoma cell lines with different metastatic capability: WM35 and MI/15, and to study the effect of drugs on radiobiological parameters. The Survival Curves were adjusted to the mathematical Linear-quadratic model using GrapsPad Prism software. Cells were seeded in RPMI medium (3000-3500 cells/flask), in triplicate and irradiated 24 h later. The irradiation was performed using an IBL 437C H Type equipment (189 TBq, 7.7 Gy/min) calibrated with a TLD 700 dosimeter. The range of Doses covered from 0 to 10 Gy and the colonies formed were counted at day 7th post-irradiation. Results obtained were: for WM35, {alpha}=0.37{+-}0.07 Gy''-1 and {beta}=0.06{+-}0.02 Gy''-2, for M1/15m {alpha}=0.47{+-}0.03 Gy''-1 and {beta}=0.06{+-}0.01 Gy''-2. The {alpha}/{beta} values WM35: {alpha}/{beta} values WM35: {alpha}/{beta}=6.07 Gy and M1/15: {alpha}/{beta}{sub 7}.33 Gy were similar, independently of their metastatic capabillity and indicate that both lines exhibit high radioresistance. Microscopic observation of irradiated cells showed multinuclear cells with few morphologic changes non-compatible with apoptosis. By means of specific fluorescent dyes and flow cytometry analysis we determined the intracellular levels of the radicals superoxide and hydrogen peroxide and their modulation in response to ionizing radiation. The results showed a marked decreased in H{sub 2}O{sub 2} intracellular levels with a simultaneous increase in superoxide that will be part of a mechanism responsible for induction of cell radioresistance. This response triggered by irradiated cells could not be abrogated by different treatments like histamine or the

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

    Science.gov (United States)

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

    2004-07-01

    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.

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

    Energy Technology Data Exchange (ETDEWEB)

    Vidal-Sicart, Sergi; Pons, Francesca [Department of Nuclear Medicine, Hospital Clinic, University of Barcelona, Villarroel 170, 08036, Barcelona (Spain); Institut d' Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Barcelona (Spain); Fuertes, Silvia; Ortega, Marisa [Department of Nuclear Medicine, Hospital Clinic, University of Barcelona, Villarroel 170, 08036, Barcelona (Spain); Vilalta, Antonio; Puig, Susana; Palou, Josep M.; Castel, Teresa [Department of Dermatology, Hospital Clinic, University of Barcelona (Spain); Rull, Ramon [Department of Surgery, Hospital Clinic, University of Barcelona (Spain)

    2004-07-01

    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 {sup 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.)

  1. Microsatellite instability as a predictive factor for immunotherapy in malignant melanoma.

    Science.gov (United States)

    Kubecek, Ondrej; Trojanova, Petronela; Molnarova, Veronika; Kopecky, Jindrich

    2016-08-01

    Immunotherapy has attracted attention as a novel treatment modality for malignant melanoma. Although the use of immunotherapy in metastatic melanoma has shown promising results, there remains a lack of predictive biomarkers indicating treatment benefit from immunotherapy. There is growing evidence suggesting that microsatellite instability (MSI) as a product of DNA mismatch repair deficiency, may be one of possible predictive markers in malignant melanoma. It has been proposed that the immunogenicity of some tumors might be determined by mutational heterogeneity and could be the key to the success of immune therapies. This is also supported by the fact that tumors with the highest amount of somatic mutations, such as malignant melanoma have showed positive results with immune checkpoint inhibitors. There are promising data regarding the association between MSI status and immunogenicity from studies with colorectal cancer, where MSI is linked to improved prognosis compared to microsatellite stable cancers. MSI in colon cancer is linked to a significant increase of immunocompetent cells responsible for the antitumor activity - CD3(+), CD8(+), CD45RO(+), and T-bet(+) lymphocytes and decrease of inhibition factors such as Foxp3, IL-6, IL-17, and TGF-β. On the other hand, taking into account the progression-dependent accumulation of somatic mutations in MSI tumors and consequent high levels of neo-antigens, the possible drug resistance of MSI tumors to traditional treatment, and the presence of inhibition checkpoints within the MSI tumors, there is a solid rationale for the use of novel therapeutic strategies such as immunotherapy in MSI melanomas. We presume that the MSI phenotype in malignant melanoma might be helpful to identify patients, who would be more likely to profit from immunotherapy than from conventional therapy. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. Prediction of nonsentinel lymph node metastasis in malignant melanoma.

    Science.gov (United States)

    Cadili, Ali; Smylie, Michael; Danyluk, John; Dabbs, Kelly

    2009-06-15

    Sentinel lymph node biopsy (SLNB) is the standard at many institutions caring for melanoma patients. Patients with positive SLNB results are currently offered completion lymph node dissection (CLND) of the affected lymph node basin. This procedure entails considerable morbidity and is often applied to patients with shortened life expectancies. Because 80% of CLNDs yield no additional positive nodes and there is no proof that CLND leads to survival improvement, criteria are needed to limit this procedure to those most likely to harbor nonsentinel lymph node (SLN) metastases. A retrospective review of 349 cases of melanoma from January 1999 to April 2007 that underwent sentinel lymph node biopsy at a single institution was done. Statistical analysis was used to compare two subgroups of patients: a positive CLND group and a negative CLND group. These two groups were compared with regards to multiple variables related to patient demographics, primary tumor characteristics, and SLN tumor burden. Age and total size of SLN tumor deposit were the factors with the strongest correlation with CLND positivity. By applying a risk score model that uses the cutoff values of age 55 y and SLN tumor deposit of 5 mm, it is possible to predict CLND positivity in SLN-positive melanoma patients. The likelihood of CLND positivity in SLN-positive melanoma patients can be predicted from two criteria readily available: size of SLN tumor deposit and patient age.

  3. Spontaneous regression of metastases from malignant melanoma: a case report

    DEFF Research Database (Denmark)

    Kalialis, Louise V; Drzewiecki, Krzysztof T; Mohammadi, Mahin

    2008-01-01

    A case of a 61-year-old male with widespread metastatic melanoma is presented 5 years after complete spontaneous cure. Spontaneous regression occurred in cutaneous, pulmonary, hepatic and cerebral metastases. A review of the literature reveals seven cases of regression of cerebral metastases...

  4. Case Report - Malignant melanoma of the lung: A case report ...

    African Journals Online (AJOL)

    Primary melanoma of the lung is an extremely rare pathological entity and sparsely reported in the literature. A 68-year-old man was admitted with 3 months history of cough, sputum production, dyspnea, hemoptysis and chest pain. The chest radiography demonstrated bilateral mass lesion and thoracal computerized (CT) ...

  5. Asymptomatic brain metastases in patients with cutaneous metastatic malignant melanoma

    DEFF Research Database (Denmark)

    Zukauskaite, Ruta; Schmidt, Henrik; Asmussen, Jon Thor

    2013-01-01

    The aim of the study was to identify the frequency of asymptomatic brain metastases detected by computed tomography (CT) scans in patients with metastatic cutaneous melanoma referred to first-line systemic treatment. Between 1995 and 2009, 697 Danish patients were screened with a contrast...

  6. Follow-up schedules after treatment for malignant melanoma

    NARCIS (Netherlands)

    Francken, A. B.; Accortt, N. A.; Shaw, H. M.; Colman, M. H.; Wiener, M.; Soong, S. -J.; Hoekstra, H. J.; Thompson, J. F.

    2008-01-01

    Background: Existing follow-up guidelines after treatment for melanoma are based largely on dated literature and historical precedent. This study aimed to calculate recurrence rates and establish prognostic factors for recurrence to help redesign a follow-up schedule. Methods: Data were retrieved

  7. Radiation-induced malignant melanoma following radiation treatment for squamous cell carcinoma of the oral cavity - a case report and review of literature -

    Energy Technology Data Exchange (ETDEWEB)

    Shin, Young Ju; Yang, Koang Mo; Suh, Hyun Suk [Inje Univ. College of Medicine, Seoul (Korea, Republic of)

    1998-03-01

    Malignant melanoma of the oral cavity is rare, accounting for 1 to 8% of all malignant melanomas. The overall prognosis remains poor despite the available treatments such as radical surgery, adjuvant radiotherapy, chemotherapy and immunotherapy due to failure in early detection and tendency in early metastasis. The etiology of mucosal malignant melanoma remains unkown. However, there are few cases of malignant melanoma of the oral cavity reported in the literature, which might be related to preexisting melanosis and radiation treatment. A case with malignant melanoma developed on the same site after 6 years following irradiation for squamous cell carcinoma of the oral cavity is reported in this article.

  8. Biology of Human Cutaneous Melanoma

    Directory of Open Access Journals (Sweden)

    Bhuvnesh K. Sharma

    2010-03-01

    Full Text Available A review of the natural behavior of cutaneous melanoma, clinical and pathological factors, prognostic indicators, some basic research and the present and possible futuristic strategies in the management of this disease are presented. While surgery remains to be the most effective therapeutic approach in the management of early primary lesions, there is no standard adjuvant therapy after surgical resection, or for metastatic disease.

  9. Congenital Giant Melanocytic Nevus with Malignant Melanoma of the Pleura: Do Primary Pleural Melanomas Exist?

    Directory of Open Access Journals (Sweden)

    Brijesh Sharma

    2017-09-01

    Full Text Available Cases of primary pleural and bronchial melanoma have been described in the literature in the absence of melanocytic cells in the pleura and bronchi. We described a case of congenital giant melanocytic nevus that had a presentation suggestive of primary pleural melanoma. However, biopsy of a chest wall lesion confirmed the presence of another melanoma deposit in a subcutaneous swelling concealed within the congenital giant melanocytic nevus. Histopathology with immunohistochemistry results showed that the pleural and chest wall swelling were similar. The difficult clinical detection of the primary tumor contributes to the fact that 24% of cases of congenital giant melanocytic nevus receive a diagnosis of metastatic melanoma without identification of the primary site. We propose that it is probable that the entity “primary pleural melanoma” may, in fact, not exist. Instead, all such reported tumors in the pleura may actually be metastatic from an unknown, regressed, or missed primary site.

  10. The metastatic microenvironment: Claudin-1 suppresses the malignant phenotype of melanoma brain metastasis.

    Science.gov (United States)

    Izraely, Sivan; Sagi-Assif, Orit; Klein, Anat; Meshel, Tsipi; Ben-Menachem, Shlomit; Zaritsky, Assaf; Ehrlich, Marcelo; Prieto, Victor G; Bar-Eli, Menashe; Pirker, Christine; Berger, Walter; Nahmias, Clara; Couraud, Pierre-Olivier; Hoon, Dave S B; Witz, Isaac P

    2015-03-15

    Brain metastases occur frequently in melanoma patients with advanced disease whereby the prognosis is dismal. The underlying mechanisms of melanoma brain metastasis development are not well understood. Identification of molecular determinants regulating melanoma brain metastasis would advance the development of prevention and therapy strategies for this disease. Gene expression profiles of cutaneous and brain-metastasizing melanoma variants from three xenograft tumor models established in our laboratory revealed that expression of tight junction component CLDN1 was lower in the brain-metastasizing variants than in cutaneous variants from the same melanoma. The objective of our study was to determine the significance of CLDN1 downregulation/loss in metastatic melanoma and its role in melanoma brain metastasis. An immunohistochemical analysis of human cells of the melanocyte lineage indicated a significant CLDN1 downregulation in metastatic melanomas. Transduction of melanoma brain metastatic cells expressing low levels of CLDN1 with a CLDN1 retrovirus suppressed their metastatic phenotype. CLDN1-overexpressing melanoma cells expressed a lower ability to migrate and adhere to extracellular matrix, reduced tumor aggressiveness in nude mice and, most importantly, eliminated the formation of micrometastases in the brain. In sharp contrast, the ability of the CLDN1-overexpressing cells to form lung micrometastases was not impaired. CLDN1-mediated interactions between these cells and brain endothelial cells constitute the mechanism underlying these results. Taken together, we demonstrated that downregulation or loss of CLDN1 supports the formation of melanoma brain metastasis, and that CLDN1 expression could be a useful prognostic predictor for melanoma patients with a high risk of brain metastasis. © 2014 UICC.

  11. Intracranial Tumor Cell Migration and the Development of Multiple Brain Metastases in Malignant Melanoma

    Directory of Open Access Journals (Sweden)

    Trude G. Simonsen

    2016-06-01

    Full Text Available INTRODUCTION: A majority of patients with melanoma brain metastases develop multiple lesions, and these patients show particularly poor prognosis. To develop improved treatment strategies, detailed insights into the biology of melanoma brain metastases, and particularly the development of multiple lesions, are needed. The purpose of this preclinical investigation was to study melanoma cell migration within the brain after cell injection into a well-defined intracerebral site. METHODS: A-07, D-12, R-18, and U-25 human melanoma cells transfected with green fluorescent protein were injected stereotactically into the right cerebral hemisphere of nude mice. Moribund mice were killed and autopsied, and the brain was evaluated by fluorescence imaging or histological examination. RESULTS: Intracerebral inoculation of melanoma cells produced multiple lesions involving all regions of the brain, suggesting that the cells were able to migrate over substantial distances within the brain. Multiple modes of transport were identified, and all transport modes were observed in all four melanoma lines. Thus, the melanoma cells were passively transported via the flow of cerebrospinal fluid in the meninges and ventricles, they migrated actively along leptomeningeal and brain parenchymal blood vessels, and they migrated actively along the surfaces separating different brain compartments. CONCLUSION: Migration of melanoma cells after initial arrest, extravasation, and growth at a single location within the brain may contribute significantly to the development of multiple melanoma brain metastases.

  12. Expression of Glut-1 in Malignant Melanoma and Melanocytic Nevi: an Immunohistochemical Study of 400 Cases.

    Science.gov (United States)

    Důra, Miroslav; Němejcová, Kristýna; Jakša, Radek; Bártů, Michaela; Kodet, Ondřej; Tichá, Ivana; Michálková, Romana; Dundr, Pavel

    2017-11-11

    The glucose transporter-1 (Glut-1) is a cell membrane glycoprotein involved in glucose uptake. An increased expression of Glut-1 is an important cell adaptation mechanism against hypoxia. An upregulation of Glut-1 can be found in several types of malignant tumors, which are able to reprogram their metabolism from oxidative phosphorylation to aerobic glycolysis (Warburg effect). However, the data regarding melanocytic lesions is equivocal. We performed comprehensive immunohistochemical analysis of the Glut-1 expression in 225 malignant melanomas (MM) and 175 benign nevi. Only the membranous expression of Glut-1 was regarded as positive. The expression of Glut-1 (the cut-off for positivity was determined as H-score 15) was found in 69/225 malignant melanomas. The number of positive cases and the H-score of Glut-1 increased where there was a higher Breslow thickness (p Glut-1 is a common feature of a malignant melanoma but this type of expression is very rare in benign melanocytic nevi. Our results suggest that the membranous expression of Glut-1 can be used as a surrogate marker in the assessing of the biological nature of benign and malignant melanocytic lesions. However, despite its high specificity, the sensitivity of this marker is relatively low. Moreover, due to the fact that the increased expression of Glut-1 correlates with a shorter survival period (10-year disease free survival, recurrence free survival and metastasis free survival and MFS), it can be used as a prognostically adverse factor.

  13. Surface modification of MPEG-b-PCL-based nanoparticles via oxidative self-polymerization of dopamine for malignant melanoma therapy

    Science.gov (United States)

    Xiong, Wei; Peng, Lixia; Chen, Hongbo; Li, Qin

    2015-01-01

    To enhance the therapeutic effects of chemotherapy on malignant melanoma, paclitaxel (PTX)-loaded methoxy poly(ethylene glycol)-b-poly(ε-caprolactone) nanoparticles (MPEG-b-PCL NPs) that had their surfaces modified with polydopamine (PTX-loaded MPEG-b-PCL NPs@PDA) were prepared as drug vehicles. The block copolymer MPEG-b-PCL was synthesized by ring-opening polymerization and characterized by proton nuclear magnetic resonance spectroscopy and gel permeation chromatography. The PTX-loaded NPs were prepared by a modified nanoprecipitation technique. The PTX-loaded NPs and PTX-loaded NPs@PDA were characterized in terms of size and size distribution, zeta potential, surface morphology, drug encapsulation efficiency, and drug release. Confocal laser scanning microscopy showed that coumarin-6-loaded NPs@PDA could be internalized by human melanoma cell line A875 cells. The cellular uptake efficiency of NPs was greatly enhanced after PDA modification. The antitumor efficacy of the PTX-loaded NPs@PDA was investigated in vitro by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and in vivo by a xenograft tumor model. The PTX-loaded NPs@PDA could significantly inhibit tumor growth compared to Taxol® and precursor PTX-loaded NPs. All the results suggested that the PTX-loaded MPEG-b-PCL NPs that had their surfaces modified with PDA are promising nanocarriers for malignant melanoma therapy. PMID:25945046

  14. Exploratory use of docetaxel loaded acid-prepared mesoporous spheres for the treatment of malignant melanoma.

    Science.gov (United States)

    Kaiser, Sameer; MacPherson, Maximilian B; James, Ted A; Emery, Albert; Spiess, Page; van der Vliet, Albert; Landry, Christopher C; Shukla, Arti

    Five year survival for metastatic melanoma (MM) is very low at effectiveness of acid-prepared mesoporous spheres (APMS-TEG) in delivering chemotherapeutic agents at a lower effective dose than systemic administration. This study aims to assess the ability of the previously developed APMS-TEG particles to deliver therapeutic doses of docetaxel for the treatment of melanoma. In vitro experiments were performed to assess docetaxel loading onto APMS-TEG particles and release kinetics. Toxicity experiments were performed using docetaxel and docetaxel loaded APMS-TEG. The effect on cell growth was assessed using the MelJuSo, UACC903, and WM1205 melanoma cell lines. Docetaxel demonstrated statistically significant dose dependent reduction in growth of melanoma cells. In all three cell lines, doses of 1 nM were sufficient to produce statistically significant reduction in cell growth. Scanning electron micrographs demonstrate increased uptake of APMS-TEG particles by melanoma cells in the first 24 hours, with the majority within the first 4 hours. Unloaded APMS particles had no effect on the melanoma cells, demonstrating that the particles themselves are not toxic. APMS-TEG particles had a peak release of drug within the first hour, with equilibration thereafter. The 5, 10, and 20 nM loaded particles all had statistically significant reduction in cell growth than the control groups. The high potency against melanoma cells makes docetaxel a suitable choice for loading into APMS-TEG particles. Docetaxel loaded APMS-TEG particles demonstrate significant activity against malignant melanoma and thus offer an innovative approach to the treatment of metastatic melanoma.

  15. Stereological estimation of nuclear volume in benign melanocytic lesions and cutaneous malignant melanomas

    DEFF Research Database (Denmark)

    Sørensen, Flemming Brandt

    1989-01-01

    noninvasive melanocytic cutaneous tumors were investigated retrospectively. vV clearly distinguished between noninvasive (average vV = 122 microns 3) and invasive lesions (average vV = 246 microns 3). Most of the patients with malignant melanomas showing an overlap of nuclear vV with benign lesions had......V in melanocytic cutaneous tumors and to compare these with estimates of nuclear volume fraction and with traditional two-dimensional morphometric estimates of nuclear profile area, nuclear density, and mitotic index. Routinely processed, paraffin embedded tissue specimens from 47 malignant melanomas and 76...... a favorable prognosis. No significant differences in vV could be demonstrated among different noninvasive tumor types. Two-dimensional estimates only distinguished benign from malignant tumors with considerable overlap and with significantly varying influence from other factors among different benign lesional...

  16. 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

  17. Critical analysis of an oncolytic herpesvirus encoding granulocyte-macrophage colony stimulating factor for the treatment of malignant melanoma.

    Science.gov (United States)

    Hughes, Tasha; Coffin, Robert S; Lilley, Caroline E; Ponce, Rafael; Kaufman, Howard L

    2014-01-01

    Oncolytic viruses that selectively lyse tumor cells with minimal damage to normal cells are a new area of therapeutic development in oncology. An attenuated herpesvirus encoding the granulocyte-macrophage colony stimulating factor (GM-CSF), known as talimogene laherparepvec (T-VEC), has been identified as an attractive oncolytic virus for cancer therapy based on preclinical tumor studies and results from early-phase clinical trials and a large randomized Phase III study in melanoma. In this review, we discuss the basic biology of T-VEC, describe the role of GM-CSF as an immune adjuvant, summarize the preclinical data, and report the outcomes of published clinical trials using T-VEC. The emerging data suggest that T-VEC is a safe and potentially effective antitumor therapy in malignant melanoma and represents the first oncolytic virus to demonstrate therapeutic activity against human cancer in a randomized, controlled Phase III study.

  18. Computer-Aided Diagnosis of Micro-Malignant Melanoma Lesions Applying Support Vector Machines

    Directory of Open Access Journals (Sweden)

    Joanna Jaworek-Korjakowska

    2016-01-01

    Full Text Available Background. One of the fatal disorders causing death is malignant melanoma, the deadliest form of skin cancer. The aim of the modern dermatology is the early detection of skin cancer, which usually results in reducing the mortality rate and less extensive treatment. This paper presents a study on classification of melanoma in the early stage of development using SVMs as a useful technique for data classification. Method. In this paper an automatic algorithm for the classification of melanomas in their early stage, with a diameter under 5 mm, has been presented. The system contains the following steps: image enhancement, lesion segmentation, feature calculation and selection, and classification stage using SVMs. Results. The algorithm has been tested on 200 images including 70 melanomas and 130 benign lesions. The SVM classifier achieved sensitivity of 90% and specificity of 96%. The results indicate that the proposed approach captured most of the malignant cases and could provide reliable information for effective skin mole examination. Conclusions. Micro-melanomas due to the small size and low advancement of development create enormous difficulties during the diagnosis even for experts. The use of advanced equipment and sophisticated computer systems can help in the early diagnosis of skin lesions.

  19. 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.

  20. Boron neutron capture therapy for malignant melanoma: An experimental approach

    Energy Technology Data Exchange (ETDEWEB)

    Larsson, B.S.; Larsson, B.; Roberto, A. (Uppsala Univ. (Sweden))

    1989-07-01

    Previous studies have shown that some thioamides, e.g., thiouracil, are incorporated as false precursors into melanin during its synthesis. If boronated analogs of the thioamides share this property, the melanin of melanotic melanomas offers a possibility for specific tumoural uptake and retention of boron as a basis for neutron capture therapy. We report on the synthesis of boronated 1H-1,2,4-triazole-3-thiol (B-TZT), boronated 5-carboxy-2-thiouracil (B-CTU), and boronated 5-diethylaminomethyl-2-thiouracil (B-DEAMTU) and the localization of these substances in melanotic melanomas transplanted to mice. The distribution in the mice was studied by boron neutron capture radiography. B-TZT and B-CTU showed the highest tumour:normal tissue concentration ratios, with tumour:liver ratios of about 4 and tumour:muscle ratios of about 14; B-DEAMTU showed corresponding ratios of 1.4 and 5, respectively. The absolute concentration of boron in the tumours, however, was more than three times higher in the mice injected with B-TZT, compared with B-CTU. The results suggest that B-TZT may be the most promising compound of the three tested with regard to possible therapy of melanotic melanomas.

  1. Noninvasive, label-free, three-dimensional imaging of melanoma with confocal photothermal microscopy: Differentiate malignant melanoma from benign tumor tissue

    Science.gov (United States)

    He, Jinping; Wang, Nan; Tsurui, Hiromichi; Kato, Masashi; Iida, Machiko; Kobayashi, Takayoshi

    2016-07-01

    Skin cancer is one of the most common cancers. Melanoma accounts for less than 2% of skin cancer cases but causes a large majority of skin cancer deaths. Early detection of malignant melanoma remains the key factor in saving lives. However, the melanoma diagnosis is still clinically challenging. Here, we developed a confocal photothermal microscope for noninvasive, label-free, three-dimensional imaging of melanoma. The axial resolution of confocal photothermal microscope is ~3 times higher than that of commonly used photothermal microscope. Three-dimensional microscopic distribution of melanin in pigmented lesions of mouse skin is obtained directly with this setup. Classic morphometric and fractal analysis of sixteen 3D images (eight for benign melanoma and eight for malignant) showed a capability of pathology of melanoma: melanin density and size become larger during the melanoma growth, and the melanin distribution also becomes more chaotic and unregulated. The results suggested new options for monitoring the melanoma growth and also for the melanoma diagnosis.

  2. Epidemiology and genetic susceptibility of malignant melanoma in North Sardinia, Italy.

    Science.gov (United States)

    Cossu, Antonio; Casula, Milena; Cesaraccio, Rosaria; Lissia, Amelia; Colombino, Maria; Sini, Maria C; Budroni, Mario; Tanda, Francesco; Paliogiannis, Panagiotis; Palmieri, Giuseppe

    2017-05-01

    The aim of this report was to study the descriptive and genetic epidemiology of malignant melanoma in North Sardinia, Italy, in the period 1992-2011. Epidemiological data were obtained from the local tumor registry, which is part of the Italian Association for Tumor Registries. Among patients included in the North Sardinia tumor registry, 316 patients first evaluated for familial recurrence of melanoma were submitted to mutation analysis in CDKN2A and CDK4 genes. The overall number of cases registered was 532. The male-to-female ratio was 1 : 1 and the mean age was 56 years for men and 55 years for women. The standardized incidence rates were 4.9/100 000 and 4.4/100 000 and the standardized mortality rates were 1.7/100 000 and 1.3/100 000 for men and women, respectively. The relative 5-year survival was 77% for men and 79% for women. In our series, 24/316 (7.6%) patients had a familial occurrence of melanoma (presence of at least one additional family member affected). Among these, one variant (Gly23Asp), reported previously as a low-frequency disease-causing mutation, was detected by mutational screening in the p16 gene only. With the exception of polymorphisms, none of either the sporadic melanoma patients or healthy controls presented a germline mutation in candidate genes. An increase in incidence and a decrease in mortality rates of malignant melanoma were registered in North Sardinia, from 1992 to 2011, whereas survival was similar to that reported in recent international reports. The high-penetrance melanoma susceptibility genes (CDKN2A and CDK4) are not involved in predisposition to melanoma in North Sardinia.

  3. Diagnosing malignant melanoma in ambulatory care: a systematic review of clinical prediction rules

    Science.gov (United States)

    Harrington, Emma; Clyne, Barbara; Wesseling, Nieneke; Sandhu, Harkiran; Armstrong, Laura; Bennett, Holly; Fahey, Tom

    2017-01-01

    Objectives Malignant melanoma has high morbidity and mortality rates. Early diagnosis improves prognosis. Clinical prediction rules (CPRs) can be used to stratify patients with symptoms of suspected malignant melanoma to improve early diagnosis. We conducted a systematic review of CPRs for melanoma diagnosis in ambulatory care. Design Systematic review. Data sources A comprehensive search of PubMed, EMBASE, PROSPERO, CINAHL, the Cochrane Library and SCOPUS was conducted in May 2015, using combinations of keywords and medical subject headings (MeSH) terms. Study selection and data extraction Studies deriving and validating, validating or assessing the impact of a CPR for predicting melanoma diagnosis in ambulatory care were included. Data extraction and methodological quality assessment were guided by the CHARMS checklist. Results From 16 334 studies reviewed, 51 were included, validating the performance of 24 unique CPRs. Three impact analysis studies were identified. Five studies were set in primary care. The most commonly evaluated CPRs were the ABCD, more than one or uneven distribution of Colour, or a large (greater than 6 mm) Diameter (ABCD) dermoscopy rule (at a cut-point of >4.75; 8 studies; pooled sensitivity 0.85, 95% CI 0.73 to 0.93, specificity 0.72, 95% CI 0.65 to 0.78) and the 7-point dermoscopy checklist (at a cut-point of ≥1 recommending ruling in melanoma; 11 studies; pooled sensitivity 0.77, 95% CI 0.61 to 0.88, specificity 0.80, 95% CI 0.59 to 0.92). The methodological quality of studies varied. Conclusions At their recommended cut-points, the ABCD dermoscopy rule is more useful for ruling out melanoma than the 7-point dermoscopy checklist. A focus on impact analysis will help translate melanoma risk prediction rules into useful tools for clinical practice. PMID:28264830

  4. 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

    Background: The number of patients diagnosed with malignant melanoma (MM) has increased over several years. Despite early diagnosis of MM and therefore better prognosis, the number of FDG-PET/CT scans (PET/CT) seems to be increasing. This study aimed to describe all MM patients who were PET....../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...

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

    OpenAIRE

    Noguchi, Tomoko; Ota, Nami; Mabuchi, Yasushi; Yagi, Shigetaka; Minami, Sawako; Okuhira, Hisako; Yamamoto, Yuki; Nakamura, Yasushi; Ino, Kazuhiko

    2017-01-01

    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 mult...

  6. Modelling the Future: System Dynamics in the Cutaneous Malignant Melanoma Care Pathway.

    Science.gov (United States)

    Claeson, Magdalena; Hallberg, Stefan; Holmström, Paul; Wennberg, Ann-Marie; Gonzalez, Helena; Paoli, John

    2016-02-01

    Incidence rates for cutaneous malignant melanoma are increasing worldwide. Estimates of the future number of melanoma cases are important for strategic planning of the care pathway. The aim of this study was to use system dynamics modelling to evaluate the long-term effects of changes in incidence, population growth and preventive interventions. Historical data on invasive melanoma cases in Western Sweden from 1990 to 2006 were obtained. Using computer simulation software, a model estimating the accumulated number of melanoma cases for 2014 to 2023 was developed. Five future scenarios were designed: stable incidence, business-as-usual, 25% reduced patient's delay, 50% reduced doctor's delay, and a combination of the last two, called improved overall secondary prevention. After 10 years, improved overall secondary prevention would have resulted in a 42% decrease in melanomas > 4 mm and a 10% increase in melanomas ≤ 1 mm, compared with business-as-usual. System dynamics is a valuable tool, which can help policymakers choose the preventive interventions with the greatest impact.

  7. Patients' Characteristics, Histopathological Findings, and Tumor Stage in Different Types of Malignant Melanoma: A Retrospective Multicenter Study.

    Science.gov (United States)

    Farahmand, Ali-Mohammad; Ehsani, Amir-Hoshang; Mirzaei, Mojtaba; Mohsenian, Maryam; Ghanadan, Alireza

    2017-05-01

    Cutaneous malignant melanoma (CMM) is currently the most fatal of skin cancers accounting for 50000 deaths annually. Five distinct melanomas are described histopathologically: superficial spreading, lentigo maligna, nodular, acral lentiginous and mucosal melanoma. The aim of this study was to investigate the characteristics of patients with various types of malignant melanoma and evaluate histopathological findings. In this retrospective study, we obtained our data from the records of 111 patients with melanoma. Biopsied specimens were collected and re-evaluated. Demographic information and histopathological findings were noted. SPSS 16 was used for analyzing data. Chi-square and one-way ANOVA was conducted for comparing categorical and numerical variables respectively. The mean age of patients was 59.33±14.68 years old. Most common melanoma type was acral lentiginous (40.5%), followed by nodular (35.1%) and mucosal (10.8%). The highest tumor thickness was viewed in nodular melanoma followed by mucosal melanoma. The highest rate of metastasis, microsatellitosis, perineural invasion and Clark level of the invasion were reported in nodular and acral lentiginous respectively. The most frequent rate of ulceration and vascular invasion was reported in mucosal melanoma. Distribution of melanoma types varies largely in different regions. Lack of classic presentations in some types necessitate specific public education about warning signs. Histopathological and pathological characteristics in melanoma can aid in better staging and management of the tumor.

  8. 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

  9. Phyllodes Tumor of the Breast With Malignant Melanoma Component: A Case Report.

    Science.gov (United States)

    Vergine, Marco; Guy, Catherine; Taylor, Mark R

    2015-09-01

    Phyllodes tumors of the breast display a wide variation in histological appearance and are classified into benign, borderline, and malignant categories based on a combination of histological parameters. These tumors may include a malignant heterologous component that is believed to originate through a process of multidirectional differentiation from a cancer stem cell. In these cases, the tumor is classified as a malignant phyllodes tumor. Among the heterologous elements that have been described in malignant phyllodes tumors are rhabdomyosarcoma, chondrosarcoma, osteosarcoma, liposarcoma and angiosarcoma. We present the first case of a phyllodes tumor with a malignant melanoma component in the breast of a 71-year-old lady, discussing the clinical implications of this diagnosis. © The Author(s) 2015.

  10. An independent validation of a gene expression signature to differentiate malignant melanoma from benign melanocytic nevi.

    Science.gov (United States)

    Clarke, Loren E; Flake, Darl D; Busam, Klaus; Cockerell, Clay; Helm, Klaus; McNiff, Jennifer; Reed, Jon; Tschen, Jaime; Kim, Jinah; Barnhill, Raymond; Elenitsas, Rosalie; Prieto, Victor G; Nelson, Jonathan; Kimbrell, Hillary; Kolquist, Kathryn A; Brown, Krystal L; Warf, M Bryan; Roa, Benjamin B; Wenstrup, Richard J

    2017-02-15

    Recently, a 23-gene signature was developed to produce a melanoma diagnostic score capable of differentiating malignant and benign melanocytic lesions. The primary objective of this study was to independently assess the ability of the gene signature to differentiate melanoma from benign nevi in clinically relevant lesions. A set of 1400 melanocytic lesions was selected from samples prospectively submitted for gene expression testing at a clinical laboratory. Each sample was tested and subjected to an independent histopathologic evaluation by 3 experienced dermatopathologists. A primary diagnosis (benign or malignant) was assigned to each sample, and diagnostic concordance among the 3 dermatopathologists was required for inclusion in analyses. The sensitivity and specificity of the score in differentiating benign and malignant melanocytic lesions were calculated to assess the association between the score and the pathologic diagnosis. The gene expression signature differentiated benign nevi from malignant melanoma with a sensitivity of 91.5% and a specificity of 92.5%. These results reflect the performance of the gene signature in a diverse array of samples encountered in routine clinical practice. Cancer 2017;123:617-628. © 2016 American Cancer Society. © 2016 Myriad Genetics, Inc. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society.

  11. Cytotoxic Activity of Oleocanthal Isolated from Virgin Olive Oil on Human Melanoma Cells.

    Science.gov (United States)

    Fogli, Stefano; Arena, Chiara; Carpi, Sara; Polini, Beatrice; Bertini, Simone; Digiacomo, Maria; Gado, Francesca; Saba, Alessandro; Saccomanni, Giuseppe; Breschi, Maria Cristina; Nieri, Paola; Manera, Clementina; Macchia, Marco

    2016-07-01

    Oleocanthal is one of the phenolic compounds of extra virgin olive oil with important anti-inflammatory properties. Although its potential anticancer activity has been reported, only limited evidence has been provided in cutaneous malignant melanoma. The present study is aimed at investigating the selective in vitro antiproliferative activity of oleocanthal against human malignant melanoma cells. Since oleocanthal is not commercially available, it was obtained as a pure standard by direct extraction and purification from extra virgin olive oil. Cell viability experiments carried out by WST-1 assay demonstrated that oleocanthal had a remarkable and selective activity for human melanoma cells versus normal dermal fibroblasts with IC50s in the low micromolar range of concentrations. Such an effect was paralleled by a significant inhibition of ERK1/2 and AKT phosphorylation and downregulation of Bcl-2 expression. These findings may suggest that extra virgin olive oil phenolic extract enriched in oleocanthal deserves further investigation in skin cancer.

  12. Imaging malignant melanoma with {sup 18}F-5-FPN

    Energy Technology Data Exchange (ETDEWEB)

    Feng, Hongyan; Xia, Xiaotian; Li, Chongjiao; Song, Yiling; Qin, Chunxia; Liu, Qingyao; Zhang, Yongxue; Lan, Xiaoli [Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology (China); Hubei Key Laboratory of Molecular Imaging (China)

    2016-01-15

    Radiolabelled benzamides are attractive candidates for targeting melanoma because they bind to melanin and exhibit high tumour uptake and retention. {sup 18}F-5-Fluoro-N-(2-[diethylamino]ethyl)picolinamide ({sup 18}F-5-FPN), a benzamide analogue, was prepared and its pharmacokinetics and binding affinity evaluated both in vitro and in vivo to assess its clinical potential in the diagnosis and staging of melanoma. {sup 18}F-5-FPN was prepared and purified. Its binding specificity was measured in vitro in two different melanoma cell lines, one pigmented (B16F10 cells) and one nonpigmented (A375m cells), and in vivo in mice xenografted with the same cell lines. Dynamic and static PET images using {sup 18}F-5-FPN were obtained in the tumour-bearing mice, and the static images were also compared with those acquired with {sup 18}F-FDG. PET imaging with {sup 18}F-5-FPN was also performed in B16F10 tumour-bearing mice with lung metastases. {sup 18}F-5-FPN was successfully prepared with radiochemical yields of 5 - 10 %. Binding of {sup 18}F-5-FPN to B16F10 cells was much higher than to A375m cells. On dynamic PET imaging B16F10 tumours were visible about 1 min after injection of the tracer, and the uptake gradually increased over time. {sup 18}F-5-FPN was rapidly excreted via the kidneys. B16F10 tumours were clearly visible on static images acquired 1 and 2 h after injection, with high uptake values of 24.34 ± 6.32 %ID/g and 16.63 ± 5.41 %ID/g, respectively, in the biodistribution study (five mice). However, there was no visible uptake by A375m tumours. {sup 18}F-5-FPN and {sup 18}F-FDG PET imaging were compared in B16F10 tumour xenografts, and the tumour-to-background ratio of {sup 18}F-5-FPN was ten times higher than that of {sup 18}F-FDG (35.22 ± 7.02 vs. 3.29 ± 0.53, five mice). {sup 18}F-5-FPN PET imaging also detected simulated lung metastases measuring 1 - 2 mm. {sup 18}F-5-FPN specifically targeted melanin in vitro and in vivo with high retention and affinity

  13. The Influence of HLA and KIR Genes on Malignant Melanoma Development and Progression.

    Science.gov (United States)

    Kandilarova, Snezhina Mihailova; Paschen, Annette; Mihaylova, Anastassia; Ivanova, Milena; Schadendorf, Dirk; Naumova, Elissaveta

    2016-12-01

    Many studies have described the role of killer immunoglobulin-like receptors (KIRs) and their cognate human leukocyte antigen (HLA) class I ligands in the immune protection against melanoma, but the effect of these markers on intra-individual variations in tumor development and progression has remained less clear. We performed KIR, HLA, and KIR/ligand analysis in 283 patients with malignant melanoma in order to evaluate their integrated influence on disease stage and progression. The patients were grouped according to AJCC staging, histological type of the primary tumor, progression, and survival rate. Analysis of HLA class I alleles revealed positive association of HLA-C*14 (Pc = 0.026, OR = 5.99) and negative association of HLA-C*02 (Pc = 0.026, OR = 0.43) with the disease. Decreased frequency of KIR2DS5 was observed in patients with rapid progression, as compared to those with slow progression. KIR BB genotype was prevalent in patients with metastasis (p = 0.004, OR = 0.025). KIR AA genotype was nearly twice as frequent in rapidly progressive cases, but without statistical relevance (p = 0.055, OR = 2.6). Significantly increased frequency of KIR2DL2 in the presence of C1 ligand (strong inhibition) was found in patients with AJCC III and IV, as compared to individuals with AJCC I stage (p = 0.045, OR = 1.93). In summary, our data imply that KIR/ligand gene content in patients could modulate the disease course towards unfavorable tumor behavior.

  14. CNS metastasis from malignant uveal melanoma: a clinical and histopathological characterisation

    DEFF Research Database (Denmark)

    Holfort, S K; Lindegaard, J; Isager, P

    2008-01-01

    AIM: To characterise uveal melanoma that has metastasised to the central nervous system (CNS). METHODS: Review of 2365 patients constituting all patients diagnosed as having primary uveal melanoma in Denmark during the period 1943-1997. All patients with malignant uveal melanoma and metastasis...... to the CNS were identified. For each patient, clinical and histopathological data were gathered. RESULTS: Sixteen patients with CNS metastasis were identified. The median age was 58 years. The majority of CNS metastases were located in the frontal and parietal lobes. Eleven patients had widespread metastases....... Five patients had exclusively metastasis to the CNS. The average time from diagnosis of primary tumour to symptoms of CNS metastasis was 91 months. The average time from the initial CNS symptoms to death was 20 months. All tumours were composed of either mixed or spindle cells. The average largest...

  15. MiR-219-5p Inhibits the Growth and Metastasis of Malignant Melanoma by Targeting BCL-2

    Directory of Open Access Journals (Sweden)

    Jianwen Long

    2017-01-01

    Full Text Available Malignant melanoma is a very dangerous tumor which is resistant to conventional therapy. MicroRNA exerts a vital function in promoting or inhibiting tumor development. The research has investigated the expression and function of miR-219-5p in melanoma. As a result, miR-219-5p expression was distinctly reduced in melanoma tissues and cell lines and was negatively correlated with Bcl-2 protein level in melanoma. Patients with low miR-219-5p level represented obviously a low overall survival in comparison with patients with high miR-219-5p level. The upregulation of miR-219-5p inhibited melanoma growth and metastasis and strengthened melanoma cells chemosensitivity by targeting Bcl-2. Therefore, the modulation of miR-219-5p expression may be a novel treatment strategy in melanoma.

  16. Oral malignant melanomas and other head and neck neoplasms in Danish dogs - data from the Danish Veterinary Cancer Registry

    Directory of Open Access Journals (Sweden)

    Kristensen Annemarie T

    2009-12-01

    Full Text Available Abstract Background Head and neck cancers (HNC are relatively common and often very serious diseases in both dogs and humans. Neoplasms originating in the head and neck region are a heterogeneous group. HNC often has an unfavourable prognosis and the proximity of the tissue structures renders extirpation of tumours with sufficient margins almost incompatible with preservation of functionality. In humans oral malignant melanoma (OMM is extremely rare, but represents a particular challenge since it is highly aggressive as is the canine counterpart, which thus may be of interest as a spontaneous animal model. Methods Canine cases entered in the Danish Veterinary Cancer Registry (DVCR from May 15th 2005 through February 29th 2008 were included in this study. Fisher's exact test was used to compare proportions of HNC in dogs and humans as well as proportions of surgically treated cases of OMM and squamous cell carcinomas (SCC. Also the proportions of benign and malignant neoplasms of different locations in dogs were compared using Fisher's exact test. Results A total of 1768 cases of neoplasias (679 malignant, 826 benign, 263 unknown were submitted. Of all neoplasias HNC accounted for 7.2% (n = 128. Of these, 64 (50% were malignant and 44 (34% benign. The most common types of malignant neoplasia were SCC (18; 28% of malignant, OMM (13; 20% of malignant, soft tissue sarcoma (11; 17% of malignant and adenocarcinoma (5; 11% of malignant. The most common types of benign neoplasms were adenoma (7; 16% of benign, polyps (6; 14% of benign and fibroma (5; 11% of benign. Conclusions In the current study, the proportion of neoplasia in the head and neck region in dogs in Denmark was similar to other canine studies and significantly more common than in humans with a large proportion of malignancies. Spontaneous HNC in dogs thus, may serve as a model for HNC in humans. Canine OMM is a spontaneous cancer in an outbred, immune-competent large mammal population and

  17. Influence of fast lymphatic drainage on metastatic spread in cutaneous malignant melanoma: a prospective feasibility study

    Energy Technology Data Exchange (ETDEWEB)

    Maza, Sofiane; Valencia, Ray; Geworski, Lilli; Sandrock, Dirk; Zander, Andreas; Munz, Dieter L. [Clinic for Nuclear Medicine, University Hospital Charite, Humboldt University of Berlin, Schumannstrasse 20-21, 10117, Berlin (Germany); Audring, Heike [Division of Dermatopathology, University Hospital Charite, Humboldt University of Berlin, Berlin (Germany); Draeger, Erik; Winter, Helmut; Sterry, Wolfram [Clinic for Dermatology, Venereology and Allergology, University Hospital Charite, Humboldt University of Berlin, Berlin (Germany)

    2003-04-01

    The concept of sentinel lymph node biopsy in cutaneous malignant melanoma is widely established. Preoperative cutaneous lymphoscintigraphic mapping is a reliable method for identifying the nodal basins at risk of metastases in melanomas. In this prospective study we investigated the correlation between the scintigraphic appearance time and the metastatic involvement of sentinel lymph nodes. In 276 malignant melanoma patients (137 women, 139 men; age 16-93 years), dynamic and static lymphoscintigraphy was performed after strict intracutaneous application of technetium-99m nanocolloid (40-150 MBq; 0.05 ml/deposit) around the tumour or biopsy scar. Analysis of dynamic scans primarily focussed on the appearance time of sentinel lymph nodes. Sentinel lymph node visualisation {<=}20 min post injection was defined as fast drainage, and visualisation >20 min as slow drainage. Fast lymphatic drainage was found in 236 patients, of whom 34 (14.4%) had sentinel lymph node metastases. Twenty-two patients showed hybrid (fast and slow) lymphatic drainage, and eight (36.4%) of them had sentinel lymph node metastases. Seven of the latter demonstrated fast lymphatic drainage, while one showed one positive sentinel lymph node with fast and another with slow drainage. The melanomas of 18 patients demonstrated exclusively slow lymphatic drainage, in all cases without sentinel lymph node metastases. This prospective study indicates that the scintigraphic appearance time of sentinel lymph nodes seems to be a clinically relevant factor for prediction of metastatic spread of cutaneous malignant melanoma. Larger numbers of patients need to be examined to truly assess the benefit of the scintigraphic appearance time compared with other predictors of sentinel lymph node tumour positivity. (orig.)

  18. Inguinal sentinel lymph node biopsy with only blue dye in lower extremity malignant melanoma

    Directory of Open Access Journals (Sweden)

    Omranipour R

    2008-06-01

    Full Text Available Background: Sentinel lymph node (SLN biopsy has become the standard of care in malignant melanoma, it is commonly identified by intradermal injection of both radiocolloid tracer and Patent Blue Dye (PBD around the tumor. This study aims to evaluate the efficacy of PBD in identifying inguinal SLN and also the accuracy of SLN mapping performed by peritumoral injection of PBD without combined radioisotope in malignant melanoma of lower extremity.Methods: Thirty consecutive patients with primary melanoma of lower exteremity who were referred to Cancer Institute of Tehran University of Medical Science between March 2003 to March 2006 were enrolled in this study. All patients had a preoperative pathologic diagnosis of malignant melanoma, median breslow thickness (range 1-4 mm and none had clinical or radiologic evidence of nodal involvement or distant metastases. At surgery PBD was injected around the lesion or scar of excisionl biopsy. Subsequently with a 5cm groin incision SLN Biopsy and complete lymph node dissection was done and all lymph nodes were sent for histopathologic examination. SLN examined by both hematoxylin-eosin and immunohistochemical staining.Results: SLN identification rate was 100%. No complication directly related to PBD injection was seen. Forty-eight sentinel lymph nodes and 195 non sentinel lymph nodes were harvested. Nineteen SLNS were found to be metastasic in 13 patients (47%. In these patients metastases were found in other inguinal lymph nodes.In the remaining 17 patients, both the SLN itself and the other removed nodes were negative for the metastatic involvement. Conclusions: Patent blue dye may be enough to identify superficial inguinal SLN in lower extremity melanoma.

  19. Neuropsychiatric complications associated with interferon - alpha -2b treatment of malignant melanoma.

    LENUS (Irish Health Repository)

    Enudi, W

    2012-02-01

    Several adverse effects have been associated with interferon alpha 2b treatment and neuropsychiatric effects have also been commonly reported. Psychosis and mood disorders have been described in the literature. This case report is of a 30 year old man with malignant melanoma stage 3a who was receiving adjuvant alpha 2b interferon and developed a manic episode two weeks post switching after one month of treatment on a high dose to a low dose. There was no previous psychiatric illness and no known family history of mental illness. This is in keeping with previous reports that mania has been observed in patients undergoing interferon treatment especially after significant dose-reduction or treatment breaks. Mania induced by interferon responds well to antimanic drugs .Since interferon alpha 2b is now commonly used in the treatment of malignant melanoma and other conditions, the need to be aware of its neuropsychiatric complications is essential.

  20. Neuropsychiatric complications associated with interferon - alpha -2b treatment of malignant melanoma.

    LENUS (Irish Health Repository)

    Enudi, W

    2009-08-01

    Several adverse effects have been associated with interferon alpha 2b treatment and neuropsychiatric effects have also been commonly reported. Psychosis and mood disorders have been described in the literature. This case report is of a 30 year old man with malignant melanoma stage 3a who was receiving adjuvant alpha 2b interferon and developed a manic episode two weeks post switching after one month of treatment on a high dose to a low dose. There was no previous psychiatric illness and no known family history of mental illness. This is in keeping with previous reports that mania has been observed in patients undergoing interferon treatment especially after significant dose-reduction or treatment breaks. Mania induced by interferon responds well to antimanic drugs .Since interferon alpha 2b is now commonly used in the treatment of malignant melanoma and other conditions, the need to be aware of its neuropsychiatric complications is essential.

  1. [Primary malignant melanoma of the vagina and treatment options: a case report].

    Science.gov (United States)

    Tsvetkov, Ch; Gorchev, G; Tomov, S; Hinkova, N; Nikolova, M; Veselinova, T

    2014-01-01

    To present and analyze the clinical characteristics, treatment, and treatment options for a patient with primary malignant melanoma of the vagina and review of literature. A 71-year-old patient with a history of vaginal bleeding caused by four tumor growths located in the vagina is presented. The size of each formation was about 2 cm. Three of them were located in the proximal two-thirds of the anterior wall of the vagina and one in the distal third. Excisional biopsy was performed of the lesion located near the entrance of the vagina. Histopathological examination revealed that it was a malignant melanoma of the vagina, which was confirmed immunohistochemically. After ruling out a tumor of an unknown primary site, the patient underwent radical hysterectomy type IV total vaginectomy and pelvic lymph node dissection. Hystological examination proved a clinically asymptomatic melanoma lesion of the uterine cervix. After surgery, the patient was given chemotherapy with Dacarbasine and monthly immunotherapy with BCG vaccine. The patient survived 21 months after surgery without developing a local relapse and died of distant metastases in the spine. Radical surgery for primary melanoma of the vagina is a secure way of achieving locoregional control of multifocal disease. The wide local excision can be used in unifocal lesions with security in achieving clean surgical margins.

  2. Melanoma

    Science.gov (United States)

    Melanoma is the most serious type of skin cancer. Often the first sign of melanoma is a change in the size, shape, color, or feel of a mole. Most melanomas have a black or black-blue area. Melanoma ...

  3. [Melanoma].

    Science.gov (United States)

    Saida, Toshiaki

    2006-10-01

    The definition of the TNM classification and staging system of malignant melanoma have been fundamentally revised. Moreover, several clinical guidelines for the management of this neoplasm were recently proposed. Advances in surgical procedures are excision of primary lesions with narrow margin and introduction of sentinel node biopsy, which contribute to maintain the good quality of life of patients. The significance of high-dose interferon-alpha as adjuvant therapy is still controversial. No effective chemotherapy or biotherapy has been established to date, however, interesting new findings were recently reported in the fields of immunotherapy and molecular targeting therapy.

  4. An Orbital Malignant Melanoma Arising in Cellular Blue Nevus in a Patient with Nevus of Ota

    OpenAIRE

    Buntinx-Krieg, Talayesa; Ouyang, Jie; Cartwright, Mont

    2016-01-01

    Melanomas arising from orbital melanocytic proliferations are exceedingly rare. Many questions remain regarding their development and malignant transformation. We report on a 45-year-old Caucasian woman with a nevus of Ota that presented with visual disturbances involving her right eye and was found to have a biopsy-proven cellular blue nevus in the orbital space. Five years later, she presented with proptosis and worsening symptoms. Biopsy at that time showed a cellular blue nevus with areas...

  5. Malignant melanoma mimicking giant cell variant of glioblastoma multiforme: A case report and review of literature

    OpenAIRE

    Arcega, R; Yong, WH; Xu, H

    2015-01-01

    We present a case of metastatic malignant melanoma in a patient initially diagnosed with glioblastoma multiforme, giant cell variant. A forty year old female presented to our institution for a re-resection of a recurrent right parietal lobe mass, presumed to be recurrent glioblastoma multiforme. PET scan during preoperative evaluation revealed a 3 cm left lower lobe lung mass. Metastatic glioblastoma to lung was considered in the differential diagnosis. Resection of the brain mass revealed a ...

  6. Nivolumab for the treatment of malignant melanoma in a patient with pre-existing myasthenia gravis

    OpenAIRE

    Maeda, Osamu; Yokota,Kenji; Atsuta, Naoki; Katsuno, Masahisa; Akiyama, Masashi; Ando, Yuichi

    2016-01-01

    ABSTRACT A 79-year-old man with lymph node recurrence of malignant melanoma received nivolumab, an anti-programmed death 1 (PD-1) monoclonal antibody. He had pre-existing ocular myasthenia gravis (MG) and a continued small amount of corticosteroid. Grade 3 creatine phosphokinase elevation appeared after two doses of nivolumab, and the treatment was postponed until it improved to grade 1. After three doses of nivolumab, he experienced diplopia and facial muscle weakness which were consistent w...

  7. Some Molecular and Clinical Aspects of Genetic Predisposition to Malignant Melanoma and Tumours of Various Site of Origin

    Directory of Open Access Journals (Sweden)

    Dębniak Tadeusz

    2007-06-01

    Full Text Available Abstract Based on epidemiological data we can assume that at least some malignant melanoma (MM and breast cancer cases can be caused by the same genetic factors. CDKN2A, which encodes the p16 protein, a cyclin-dependent kinase inhibitor suppressing cell proliferation, is regarded as a major melanoma susceptibility gene and the literature has also implicated this gene in predisposition to breast cancer. Genes also known to predispose to MM include XPD and MC1R. We studied CDKN2A/ARF, XPD and MC1R for their associations with melanoma and breast cancer risk in Polish patients and controls. We found that CDKN2A and ARF do not contribute significantly to either familial melanoma or malignant melanoma within the context of a cancer familial aggregation of disease with breast cancer. However, the common variant of the CDKN2A gene A148T, previously regarded as non-pathogenic, may predispose to malignant melanoma, early-onset breast cancer and lung cancer. Compound carriers of common XPD variants may be at slightly increased risk of breast cancer or late–onset malignant melanoma. Common recurrent variants of the MC1R gene (V60L, R151C, R163Q and R160W may predispose to malignant melanoma. In general, the establishment of surveillance protocols proposed as an option for carriers of common alterations in CDKN2A, XPD or MC1R variants requires additional studies. It is possible that missense variants of genes for which truncating mutations are clearly pathogenic may also be deleterious, but with reduced penetrance. This may be overlooked unless large numbers of patients and controls are studied. A registry that includes 2000 consecutive breast cancer cases, 3500 early onset breast cancer patients, 500 unselected malignant melanoma and over 700 colorectal cancer patients has been established in the International Hereditary Cancer Centre and can contribute to these types of large association studies.

  8. Guiding the Killer and Bringing in Accomplices: Bispecific Antibody Treatment for Malignant Melanoma.

    Science.gov (United States)

    Szegezdi, Eva; Leverkus, Martin

    2016-02-01

    Discovery of oncogene and immune checkpoint targeting has transformed melanoma therapy in the last 5 years. However, treatment of primary or secondary drug-resistant melanoma remains a challenge. Agents designed to activate the cell death machinery directly, for example by activating the death receptors expressed by melanoma cells, could break drug resistance, and they may achieve long-lasting therapeutic success. He et al. report their studies of an MCSPxDR5 bispecific, tetravalent antibody that can simultaneously target death receptor 5 (DR5, TRAIL-R2) and melanoma-associated chondroitin sulfate proteoglycan (MCSP). This antibody can exert strong and selective DR5-dependent cytotoxic activity against MCSP-expressing melanoma cells. Crosslinking of the antibody with Fcγ-receptors increased the cytotoxic potential further, without compromising its selectivity. This approach offers a novel immunotherapeutic tool via coupling of three cooperating processes: delivering the death receptor agonist to the malignant cell population, potent activation of DR5-mediated cell death signaling, and recruitment of Fcγ-receptor-carrying immune cells that can mount an immune response against the tumor cells. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  9. BCG-induced protection against malignant melanoma: possible immunospecific effect in a murine system.

    Science.gov (United States)

    Faraci, R P; Barone, J; Schour, L

    1975-02-01

    This report documents for the first time BCG-induced protection against a murine malignant melanoma. Adult Balb/C mice recieved 0.1-cm3 doses of BCG prior to intramuscular challenge with 1 x 10-6 S-91 melanoma cells. A 65% reduction in melanoma incidence was noted in BCG-pretreated mice. The possibility of specific protection induced by the BCG against the melanoma exists, since the BCG pretreatment did not protect against challenge with 1 x 10-5 mammary carcinoma cells or 1 x 10-4 MCA fibrosarcoma cells in the same strain of mice. Lack of immunogenicity was not a factor in the inability of the carcinoma and sarcoma to be inhibited by BCG. The strenght of the BCG-induced protection against the S-91 melanoma was demonstrated by significantly decreased tumor incidence following three different log challenge doses of the melanoma. However, reduction of the sarcoma challenge dose to as few as 10-2 cells administered to BCG pretreated mice did not result in decreased tumor incidence. It was further discovered that as few as two doses of 0.1 cm3 of BCG were sufficient to produce a 70% reduction in melanoma incidence compared with the incidence in control animals (P less than .001). Lymphocyte-mediated cytotoxicity studies paralleled the results of the in vivo experiments. Lymphocytes immune to each of the three tumors showed significant cytotoxicity against their respective tumor target cells (p less than .001), while the only tumor cells that lymphocytes from BCG-pretreated mice showed significant cytotoxicity against were S-91 target cells (p less than .01). Nonspecific cytotoxicity was not a factor in the effect of BCG-immune lymphocytes against S-91 target cells, since BCG-immune lymphocytes were not cytotoxic to Balb/C fibroblasts.

  10. Critical analysis of an oncolytic herpesvirus encoding granulocyte-macrophage colony stimulating factor for the treatment of malignant melanoma

    Directory of Open Access Journals (Sweden)

    Hughes T

    2014-01-01

    Full Text Available Tasha Hughes,1 Robert S Coffin,2 Caroline E Lilley,2 Rafael Ponce,2 Howard L Kaufman1 1Departments of General Surgery and Immunology and Microbiology, Rush University Medical Center, Chicago IL, 2BioVex, Inc, a subsidiary of Amgen, Inc, Sherman Oaks, CA, USA Abstract: Oncolytic viruses that selectively lyse tumor cells with minimal damage to normal cells are a new area of therapeutic development in oncology. An attenuated herpesvirus encoding the granulocyte-macrophage colony stimulating factor (GM-CSF, known as talimogene laherparepvec (T-VEC, has been identified as an attractive oncolytic virus for cancer therapy based on preclinical tumor studies and results from early-phase clinical trials and a large randomized Phase III study in melanoma. In this review, we discuss the basic biology of T-VEC, describe the role of GM-CSF as an immune adjuvant, summarize the preclinical data, and report the outcomes of published clinical trials using T-VEC. The emerging data suggest that T-VEC is a safe and potentially effective antitumor therapy in malignant melanoma and represents the first oncolytic virus to demonstrate therapeutic activity against human cancer in a randomized, controlled Phase III study. Keywords: granulocyte-macrophage colony stimulating factor, herpesvirus, melanoma, oncolytic virus, treatment

  11. 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

    Full Text Available Objetivo: Vários métodos vem sendo utilizados para o tratamento dos melanomas da coróide. A proposta deste trabalho preliminar é avaliar a eficácia da termoterapia transpupilar (TTT como tratamento primário de melanomas da coróide pequenos. Métodos: Foi realizado um trabalho prospectivo e não-randomizado para avaliar os aspectos clínicos, resposta do tumor, complicações e resultados visuais de pacientes portadores de melanomas da coróide pequenos (até 4,0 mm de espessura e 12 mm de diâmetro basal tratados por termoterapia transpupilar utilizando-se sucessivas aplicações de laser diodo contínuo de 810 nm. Resultados: Foram tratados 11 pacientes portadores de melanomas da coróide pequenos. O tumor era único e pigmentado em 100% dos casos. Crescimento documentado esteve presente em 5 pacientes (45,45% previamente ao tratamento e fatores de risco para crescimento ou metástase estavam presentes em todos os pacientes. O tempo de seguimento destes pacientes a partir do tratamento foi em média de 5,72 meses (3 - 8 meses. Foram utilizadas 3 sessões de laser em 5 pacientes (45,45% e 4 sessões em 6 pacientes (64,64%. As lesões apresentavam, por ocasião do diagnóstico, uma espessura média de 2,65 mm (1,85-3,86 mm, com maior diâmetro basal médio de 7,98 mm (4,2-11,33 mm. Após o tratamento, a espessura média foi de 1,83 mm (0,98-2,93 mm e o maior diâmetro basal médio foi de 6,59 mm (3,81 mm -10,67 mm. Das lesões tratadas, 100% apresentaram diminuição da altura e do máximo diâmetro basal, tendo sido a diminuição média da espessura de 0,89 mm e do máximo diâmetro basal de 1,39 mm. A acuidade visual manteve-se inalterada em 5 casos (45,45% e piorou após o tratamento em 6 casos (54,54%. Ocorreram complicações em 9 casos, tendo sido considerada complicação grave 1 caso de descolamento parcial da retina (9,09%; as outras complicações foram consideradas leves: pequenas hemorragias intra-retinianas em 7 pacientes (63

  12. A functional screen identifies specific microRNAs capable of inhibiting human melanoma cell viability.

    Directory of Open Access Journals (Sweden)

    Jos B Poell

    Full Text Available Malignant melanoma is an aggressive form of skin cancer with poor prognosis. Despite improvements in awareness and prevention of this disease, its incidence is rapidly increasing. MicroRNAs (miRNAs are a class of small RNA molecules that regulate cellular processes by repressing messenger RNAs (mRNAs with partially complementary target sites. Several miRNAs have already been shown to attenuate cancer phenotypes, by limiting proliferation, invasiveness, tumor angiogenesis, and stemness. Here, we employed a genome-scale lentiviral human miRNA expression library to systematically survey which miRNAs are able to decrease A375 melanoma cell viability. We highlight the strongest inhibitors of melanoma cell proliferation, including the miR-15/16, miR-141/200a and miR-96/182 families of miRNAs and miR-203. Ectopic expression of these miRNAs resulted in long-term inhibition of melanoma cell expansion, both in vitro and in vivo. We show specifically miR-16, miR-497, miR-96 and miR-182 are efficient effectors when introduced as synthetic miRNAs in several melanoma cell lines. Our study provides a comprehensive interrogation of miRNAs that interfere with melanoma cell proliferation and viability, and offers a selection of miRNAs that are especially promising candidates for application in melanoma therapy.

  13. Recent advances and developments in the antitumor effect of the HVJ envelope vector on malignant melanoma: from the bench to clinical application.

    Science.gov (United States)

    Tanemura, A; Kiyohara, E; Katayama, I; Kaneda, Y

    2013-11-01

    Inactivated Sendai virus particles (hemagglutinating virus of Japan envelope; HVJ-E) are considered to be safe and efficient non-viral vectors used for drug delivery, since they can incorporate DNA, RNA, proteins and drugs. We have recently found that HVJ-E has a novel antitumor immune effect using a colon cancer model. HVJ-E has also been shown to have both direct and immune-mediated indirect actions against malignancy. Intratumoral injection of an inactivated HVJ-E solution significantly reduced the tumor volume and prevented spontaneous lung metastasis, leading to an increased overall survival in C57/BL6 mice transplanted with B16/BL6 mouse melanoma cells, and even in immunodeficient mice transplanted with Mewo human melanoma cells. No severe adverse effects including laboratory data abnormalities or anaphylactic reactions were observed. The comprehensive mechanism(s) underlying the immunological effects of HVJ-E appear to include not only enhanced effector T cell- and/or natural killer (NK) cell-mediated immunity, but also rescue from regulatory T cell (Treg)-mediated immunosuppression, presumably through the interleukin-6 secretion from dendritic cells stimulated by HVJ-E. Since a protocol for a clinical study of HVJ-E in malignant melanoma was approved in 2009 by the ethics committee of Osaka University and of the Medical Center for Translational Research in Osaka University Hospital, a phase I/IIa study for advanced malignant melanoma patients was just started. In this review, we show several favorable results regarding the antitumor effects of HVJ-E and describe the novel mechanism underlying this tumor immune response. Since we are conducting a phase I/IIa clinical trial using HVJ-E in advanced melanoma patients on the basis of preclinical results, detailed clinical information and immune-monitoring data are also introduced. The development of new therapeutic modalities for advanced melanoma patients is urgently needed, and we hope that HVJ-E may provide

  14. Melanoma maligno anaplásico em um eqüino Anaplastic malignant melanoma in a horse

    Directory of Open Access Journals (Sweden)

    Daniel Ricardo Rissi

    2008-10-01

    Full Text Available Descreve-se um caso de melanoma maligno anaplásico em uma égua Crioula, tordilha, com 10 anos de idade, com histórico clínico de apatia, perda de peso progressiva, febre, anorexia e dispnéia. Múltiplas massas pigmentadas e não-pigmentadas, bem delimitadas ou infiltrativas, foram observadas no tecido subcutâneo e em vários órgãos. Histologicamente o neoplasma era composto de populações de células fusiformes, redondas ou poliédricas e, menos freqüentemente, de células multinucleadas e "células em anel de sinete". O diagnóstico foi realizado com base nos achados clinicopatológicos e confirmado pela microscopia eletrônica de transmissão.A case of anaplastic malignant melanoma in a 10-year-old gray mare is described. Clinical signs included depression, progressive weight loss, fever, anorexia, and dyspnea. Multiple circumscribed or infiltrative, pigmented, and non-pigmented tumors were observed in subcutaneous tissue and in several organs. Histological examination revealed a marked variation in neoplastic cell population, which was composed by spindle, round, polyhedrical, and less frequently, multinucleated or signet ring cells. The diagnostic was based up on clinical and pathological findings, and confirmed by transmission electronic microscopy.

  15. 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.

  16. Sentinel node biopsy (SNB) in malignant melanoma as same day procedure vs delayed procedure

    DEFF Research Database (Denmark)

    Rødgaard, Jes Christian; Kramer, Stine; Stolle, Lars B

    2013-01-01

    The aim of this study was to compare a delayed sentinel node biopsy (dSNB) procedure with a same-day procedure (sSNB) in malignant melanoma. In March 2012, Aarhus University Hospital went from the dSNB to the sSNB procedure defined by lymphoscintigraphy (LS) and sentinel node biopsy (SNB) performed...... malignant melanoma thickness >1 mm, Clark level IV/V, and ulcus or unknown thickness of the melanoma. All patients underwent re-excision and SNB at the same time. Pathological evaluation was not changed in the observation periods; however, the LS procedures varied. Only a minor turnover among the surgeons...... of hospitalisation days differed significantly, with 1.94 days in dSNB and 0.49 days in sSNB. Rates of complications at the site of the SNB procedure were similar. No differences in disease-free survival (DFS) or overall survival (OS) were recorded. SNB does not increase the overall survival. It is, therefore...

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    Noguchi, Tomoko; Ota, Nami; Mabuchi, Yasushi; Yagi, Shigetaka; Minami, Sawako; Okuhira, Hisako; Yamamoto, Yuki; Nakamura, Yasushi; Ino, Kazuhiko

    2017-01-01

    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.

  19. Formaldehyde solutions in simulated sweat increase human melanoma but not normal human keratinocyte cells proliferation.

    Science.gov (United States)

    Rizzi, M; Cravello, B; Tonello, S; Renò, F

    2016-12-01

    Our skin is in close contact with clothes most of the time thus risking potentially noxious chemicals contact. One of the potentially harmful manufacturing by-products that can be released by textiles when sweating is formaldehyde, used as an anti-crease treatment. As it is known to be carcinogenic to humans and a potent skin sensitizer, the aim of this study was to investigate its effects on both normal human keratinocytes (HaCaT cells) and on a highly invasive malignant melanoma cell line (SK-MEL-28) in order to contribute to the definition of safety cut-off to be applied to the production processes. Formaldehyde concentrations below the commonly accepted limits (10-50μM) were obtained by diluting formaldehyde in simulated sweat (UNI EN ISO 105-E04). The effects on cell proliferation were evaluated by cell counting, while ERK pathway activation was evaluated by western blot. Low concentrations of formaldehyde (10μM) in both acidic and alkaline simulated sweat were able to increase malignant melanoma cell proliferation, while not affecting normal keratinocytes. Melanoma proliferation increase was greater in acidic (pH=5.5) than in alkaline (pH=8) conditions. Moreover, formaldehyde stimulation was able to induce ERK pathway activation. The data obtained suggest the need for an even increasing attention to the potentially harmful effects of textile manufacturing by-products. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. [Psychological aspects of immunotherapies in the treatment of malignant melanoma].

    Science.gov (United States)

    Kovács, Péter; Pánczél, Gitta; Melegh, Krisztina; Balatoni, Tímea; Pörneczy, Edit; Lõrincz, Lenke; Czirbesz, Kata; Gorka, Eszter; Liszkay, Gabriella

    2016-03-02

    Psychological problems may arise in connection with oncomedical treatments in three ways: 1. acute and/or 2. chronic ways, as well as 3. co-morbid psychiatric diseases that already exist must also be taken into account. Immunotherapies have the most common and also clinically relevant psychological side effects. Fatigue, anhedonia, social isolation, psychomotor slowness is reported during treatment. Anti-CTLA-4 antibody (ipilimumab) immunotherapy can present one of the most modern opportunities for adequate treatment for patients having distant metastasis or unresectable tumour. In relation to immunotherapies, acute psychological side effects (acute stress) emerging during treatments develop in a way that can mostly be linked to environmental factors, e.g. notification of diagnosis, hospitalisation, progression, deterioration in quality of life, imminent dates of control. Crisis is a temporary and threatening condition that endangers psychological balance. In such conditions, enhanced psychological vulnerability must be taken into account and doctors play a key role in the rapid recognition of the condition. Chronic psychological problems, which may arise from the depressogenic effect of the applied treatment or originated from a pre-melanoma psychiatric condition, may exceed the diagnostic and psychotherapeutic competences of a clinical psychologist. Even in case of a well-defined depressogenic biological mechanism such as the activation of the pro-inflammatory cytokine pathway, positive environmental effects can reduce symptoms and thus increase compliance. Side effects can be treated successfully using psychotherapeutic methods and/or psychiatric medicines. The application of routinely used complex psychosocial screening packages can provide the easiest method to identify worsening psychological condition during immunotherapy and give rapid feedback to the oncologist and the patient. Team work is of particular importance in a situation like this as it requires

  1. Single sternal metastasis due to malignant melanoma with unexpected long-term survival: a case report

    Directory of Open Access Journals (Sweden)

    Gogakos AS

    2016-01-01

    Full Text Available Apostolos S Gogakos,1 Dimitrios Paliouras,1 Christos Asteriou,1 Thomas Rallis,1 Achilleas Lazopoulos,1 Fotios Chatzinikolaou,2 Athanassios Zissimopoulos,3 Drosos Tsavlis,4 Katerina Tsirgogianni,4 Konstantinos Zarogoulidis,4 Konstantinos Porpodis,4 Kosmas Tsakiridis,5 Georgia Pitsiou,4 Ioannis Kioumis,4 Ilias Karapantzos,6 Chrysanthi Karapantzou,6 Nikos Sachpekidis,5 Paul Zarogoulidis,4 Nikolaos Barbetakis1 1Thoracic Surgery Department, 2Department of Pathology, Theagenio Cancer Hospital, Thessaloniki, 3Nuclear Medicine Department, University General Hospital of Alexandroupolis, Democritus University of Thrace, Alexandroupolis, 4Pulmonary Department – Oncology Unit, “G. Papanikolaou” General Hospital, Aristotle University of Thessaloniki, 5Cardiothoracic Surgery Department, 6Ear, Nose and Throat Department, “Saint Luke” Private Hospital, Panorama, Thessaloniki, Greece Abstract: Metastases from melanoma have a very poor prognosis for the patient. Single metastatic lesions in the sternum due to melanoma are extremely rare. A rare case of a presternal mass in a 56-year-old patient who had undergone excision for malignant melanoma is presented. Review of the patient’s history and surgical resection of a single metastatic soft tissue lesion offer the best chance of long-term survival. Keywords: melanoma, metastasis, chest wall, sternum

  2. Malignant melanoma in the penguin: characterization of the clinical, histologic, and immunohistochemical features of malignant melanoma in 10 individuals from three species of penguin.

    Science.gov (United States)

    Duncan, Ann E; Smedley, Rebecca; Anthony, Simon; Garner, Michael M

    2014-09-01

    Malignant melanomas are aggressive neoplasms that are relatively common in penguins compared to other avian species. In this study, the clinical and pathologic characteristics of melanocytic neoplasms in five macaroni (Eudyptes chrysolophus), three rock hopper (Eudyptes chrysocome), and two Humboldt (Spheniscus humboldti) penguins are described. Tumors most commonly occurred in the skin of the foot or hock, and were seen in the subcutaneous muscle, especially near the beak/oral cavity. Gross lesions were usually heavily pigmented, becoming raised and ulcerated over time. Humboldt penguins had a unique presentation, forming variably pigmented, cornified lesions in the inguinal area. Original case materials were obtained from all but two cases, and were assessed to define the characteristics of malignancy, evaluate four immunohistochemical markers for melanoma, and look for factors useful to informing prognosis and clinical decisions. Diagnosis was made histologically, based on morphologic features and pigmentation. Though not necessary for diagnosis, PNL-2 was found to be a useful immunohistochemical marker. HMB-45 showed unreliable positive labelling and S-100, Melan-A and Ki67 were not useful. Several factors were associated with prognosis, including gross surface dimension, mitotic index, depth of neoplastic cell invasion, and degree of surface ulceration. Metastatic spread occurred to the liver, lung, adrenal gland, brain, and bone; all lesions showed positive labelling to PNL-2. The average survival after diagnosis was 7 mo, though complete surgical excision of tumors less than 2.0 cm was curative in two cases and radiation therapy prolonged survival in one penguin. The underlying pathogenesis associated with the high prevalence of melanocytic neoplasms in captive penguins could not be identified. Three different molecular methods were performed to look for viral particles and results were negative. Advanced age is the most probable associated risk factor

  3. The sentinel-lymphonodectomy in malignant melanoma; Die Sentinel-Lymphonodektomie beim malignen Melanom

    Energy Technology Data Exchange (ETDEWEB)

    Bachter, D.; Starz, H.; Volkmar, C.; Balda, B.R. [Zentralklinikum Augsburg (Germany). Klinik fuer Dermatologie und Allergologie; Vogt, H. [Zentralklinikum Augsburg (Germany). Klinik fuer Nuklearmedizin; Buechels, H. [Zentralklinikum Augsburg (Germany). II. Chirurgische Klinik

    1999-10-01

    The concept of the removal of the sentinel lymph node (SLN) opens a new era in the primary therapy of malignant melanoma. This procedure allows an exact staging of the regional lymph nodes and selects only those patients with metastases for an early regional lymphadenectomy. Lymphoscintigraphy by Technetium-labeled human albumin and the intraoperative localization of the SLN guided by a gammaprobe combined with blue dye injections for the persecution of the lymph ways delivers optimal results. The histological proof of the often tiny micrometastases succeeds best in doing serial sectioning with confirmatory immunohistochemistry. We recommend the sentinel lymphonodectomy (SLNE) in all new diagnosed melanomas in clinical stages Ib to IIIa (DDG-classification). When finding metastases in the SLN, a radical lymphadenectomy should follow. Although a survival benefit has not yet shown, the SLNE allows to select patients for further therapies in very early stage of the disease. (orig.) [German] Das Konzept zur operativen Entfernung des Sentinel-Lymphknotens (SLN) leitet eine neue Aera in der Primaertherapie des malignen Melanoms ein. Dieses Verfahren erlaubt ein exaktes Staging der regionaeren Lymphknoten und selektioniert somit nur diese Patienten fuer eine fruehe regionaere Lymphknotendissektion, bei denen Tumorbefall nachgewiesen werden konnte. Die Darstellung des SLN gelingt am besten mit Hilfe von Technetium-markiertem Humanalbumin zur intraoperativen Lokalisation mittels einer Szintillationsmesssonde in Kombination mit einer Patentblaumarkierung des Lymphabflusses. Die histologische Aufarbeitung der Lymphknoten in Schnittserien mit entsprechenden immunhistochemischen Faerbungen erleichtert den mikroskopischen Nachweis der oft sehr kleinen Mikrometastasen. Wir halten die Sentinel-Lymphonodektomie (SLNE) bei neu diagnostizierten Melanomen in den klinischen Stadien Ib-IIIa fuer dringend indiziert. Bei Nachweis von Melanommetastasen im SLN ist derzeit allerdings noch

  4. Childhood Body Size and the Risk of Malignant Melanoma in Adulthood

    DEFF Research Database (Denmark)

    Meyle, Kathrine D; Gamborg, Michael; Sørensen, Thorkild I A

    2017-01-01

    Malignant melanoma (MM) is the most aggressive form of skin cancer. Adult anthropometry influences MM development; however, associations between childhood body size and future melanomagenesis are largely unknown. We investigated whether height, body mass index (BMI; weight (kg)/height (m)2......), and body surface area (BSA) at ages 7-13 years and birth weight are associated with adult MM. Data from the Copenhagen School Health Records Register, containing annual height and weight measurements of 372,636 Danish children born in 1930-1989, were linked with the Danish Cancer Registry. Cox regression......, without any comparable influence of BMI or BSA. Melanoma transformation is unlikely to be due to height per se; however, height-regulating processes in childhood present new areas for mechanistic explorations of this disease....

  5. High expression of cytoplasmic phosphorylated CSE1L in malignant melanoma but not in benign nevi: phosphorylated CSE1L for the discrimination between melanoma and benign nevi.

    Science.gov (United States)

    Chin, Szu-Ying; Wu, Pei-Ru; Shih, Yi-Hsien; Yeh, Chung-Min; Lee, Woan-Ruoh; Shen, Shing-Chuan; Yeh, Kun-Tu; Jiang, Ming-Chung; Tseng, Jonathan Te-Peng

    2015-01-01

    Melanoma is difficult to treat when it has metastasized. Discrimination between melanoma and benign nevi in melanocytic lesions is crucial for identifying melanomas and consequently improving melanoma treatment and prognosis. The chromosome segregation 1-like (CSE1L) protein has been implicated in cancer progression and is regulated by phosphorylation by extracellular signal-regulated kinase 1/2 (ERK1/2) signaling, a critical pathway in melanoma progression. We studied phosphorylated CSE1L expression in human melanoma and benign nevi specimens. Immunohistochemistry with tissue microarray using antibody against phosphorylated CSE1L showed that melanomas exhibited considerable staining for phosphorylated CSE1L (100%, 34/34), whereas the benign nevi showed only faint staining (0%, 0/34). Melanomas mainly exhibited cytoplasmic phospho-CSE1L distribution, whereas the benign nevi mainly exhibited nuclear phospho-CSE1L distribution. Moreover, immunohistochemistry with anti-CSE1L antibody revealed that CSE1L mainly exhibited cytoplasmic/nuclear distribution and nuclear distribution was the dominant. Immunofluorescence with B16F10 melanoma cells showed cytoplasmic distribution of phospho-CSE1L and nuclear distribution of CSE1L. Our results indicated that nuclear CSE1L is mainly non-phosphorylated CSE1L and is involved in gene regulation and cytoplasmic CSE1L is mainly phosphorylated CSE1L and is involved in cytoplasmic signaling regulation in melanocytic tumorigenesis. Furthermore, immunohistochemical analysis of cytoplasmic phospho-CSE1L may aid in the diagnosis of melanoma.

  6. Budget impact analysis of a novel gene expression assay for the diagnosis of malignant melanoma.

    Science.gov (United States)

    Cassarino, David S; Lewine, Nicolas; Cole, Doria; Wade, Brandon; Gustavsen, Gary

    2014-11-01

    Traditional pathology techniques alone can be insufficient to reliably distinguish between malignant melanoma, dysplastic nevi, and benign nevi in biopsies of suspicious pigmented lesions. Numerous studies have shown high rates of ambiguity when assessing such samples. A novel gene expression assay has been developed to objectively differentiate malignant melanoma from benign nevi. The purpose of this study was to quantify the economic impact of the gene expression assay on a US commercial health plan. The clinical paradigm of care was modeled for a hypothetical cohort of patients with suspicious pigmented lesions that are difficult-to-diagnose. Costs were assigned to each unit of care provided based on 2013 Medicare fee-for-service rates. Patients were followed for 10 years and were modeled to progress according to the natural history of their disease. The total cost of care was calculated for two scenarios: a Reference Scenario, representing current clinical practice, and a Test Scenario, in which each lesion was tested with the gene expression assay and diagnosed. Total cost of care was compared between the two scenarios to determine overall budget impact. Sensitivity analyses were performed to test the robustness of the model. The gene expression assay reduces costs by $1268 per patient tested over 10 years, a decrease of 8.3%, after accounting for the cost of the assay. For a health plan with 10 million members, this would translate to over $8 million in savings. The largest portion of this saving comes from reducing the number of missed melanomas, which would otherwise progress to advanced disease. In sensitivity analyses, no single model input changed within a reasonable range of values caused the model to show that the assay was not cost-saving. In addition to improving the diagnosis of melanoma, this gene expression assay would likely reduce costs for health plans that choose to cover it.

  7. Case of malignant melanoma of rectum. Complete regression of local recurrence by small source radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Moriya, Yoshihiro; Koyama, Yasuo; Yanagawa, Shigeo; Kakehi, Masae; Ushio, Kyosuke (National Cancer Center, Tokyo (Japan))

    1982-11-01

    Malignant melanoma of anorectum is a rare and highly-malignant lesion. Its 5-year survival rate is approximately 20 per cent. A 69 year-old woman was admitted to the hospital because of severe constipation and rectal bleeding. A radical abdomino-perineal excision and bilateral groin dissection were performed. Six months later, she developed intestinal obstruction and received emergency laparotomy. A local recurrence, 7 x 6 cm in size, was found in the right side of the presacral region. Three silicon-made tubes were inserted intratumorusly. After operation, the patient received three times of small sourse radiotherapy through the tubes using 1 Ci /sup 60/Co and external pelvic irradiation of 2160 rad. After that, systemic chemotherapy using ACNU and DTIC was added. Unfortunately, the patient died of massive intestinal hemorrhage one year after initial operation. By autopsy, no tumor was found not only in the presacral region, but in the organs or tissues of the whole body. To improve the survival rate of the malignant melanoma of anorectum, a wide anatomical lymphadenectomy and an effective adjuvant radio-chemotherapy should be performed.

  8. Comparing disciplines: outcomes of non melanoma cutaneous malignant lesions in oral and maxillofacial surgery and dermatology.

    Science.gov (United States)

    Thavarajah, M; Szamocki, S; Komath, D; Cascarini, L; Heliotis, M

    2015-01-01

    300 cases of non-melanoma cutaneous lesion procedures carried out by the Oral and Maxillofacial Surgery and Dermatology departments in a North West London hospital over a 6 month period between September 2011 and February 2012 were included in a retrospective case control study. The results from each speciality were compared. The mean age of the OMFS group was 75.8 years compared to 69.9 years in the dermatology group. There was no statistically significant difference in gender between the 2 groups. The OMFS group treated a higher proportion of atypical (17%) and malignant (64.9%) cases compared to the dermatology group (11.3% and 50.5% respectively). This could also account for the fact that the OMFS group carried out a higher number of full excisions compared to dermatology. Both groups had a similar number of false positives (a benign lesion initially diagnosed as malignant) and a similar proportion of false negatives (a malignant lesion initially diagnosed as benign). Overall, the results show that both specialities had similar outcomes when managing non-melanoma cutaneous lesions. Both groups adhere to the guidelines set out by the British Association of Dermatologists and the National Institute of Clinical Excellence when managing such lesions. Crown Copyright © 2014. Published by Elsevier Ltd. All rights reserved.

  9. Transcription analysis in the MeLiM swine model identifies RACK1 as a potential marker of malignancy for human melanocytic proliferation

    Directory of Open Access Journals (Sweden)

    Vincent-Naulleau Silvia

    2008-04-01

    Full Text Available Abstract Background Metastatic melanoma is a severe disease. Few experimental animal models of metastatic melanoma exist. MeLiM minipigs exhibit spontaneous melanoma. Cutaneous and metastatic lesions are histologically similar to human's. However, most of them eventually spontaneously regress. Our purpose was to investigate whether the MeLiM model could reveal markers of malignancy in human melanocytic proliferations. Results We compared the serial analysis of gene expression (SAGE between normal pig skin melanocytes and melanoma cells from an early pulmonary metastasis of MeLiM minipigs. Tag identification revealed 55 regulated genes, including GNB2L1 which was found upregulated in the melanoma library. In situ hybridisation confirmed GNB2L1 overexpression in MeLiM melanocytic lesions. GNB2L1 encodes the adaptor protein RACK1, recently shown to influence melanoma cell lines tumorigenicity. We studied the expression of RACK1 by immunofluorescence and confocal microscopy in tissues specimens of normal skin, in cutaneous and metastatic melanoma developped in MeLiM minipigs and in human patients. In pig and human samples, the results were similar. RACK1 protein was not detected in normal epidermal melanocytes. By contrast, RACK1 signal was highly increased in the cytoplasm of all melanocytic cells of superficial spreading melanoma, recurrent dermal lesions and metastatic melanoma. RACK1 partially colocalised with activated PKCαβ. In pig metastases, additional nuclear RACK1 did not associate to BDNF expression. In human nevi, the RACK1 signal was low. Conclusion RACK1 overexpression detected in situ in human melanoma specimens characterized cutaneous and metastatic melanoma raising the possibility that RACK1 can be a potential marker of malignancy in human melanoma. The MeLiM strain provides a relevant model for exploring mechanisms of melanocytic malignant transformation in humans. This study may contribute to a better understanding of melanoma

  10. Ophiobolin A Induces Autophagy and Activates the Mitochondrial Pathway of Apoptosis in Human Melanoma Cells.

    Directory of Open Access Journals (Sweden)

    Carlo Rodolfo

    Full Text Available Ophiobolin A, a fungal toxin from Bipolaris species known to affect different cellular processes in plants, has recently been shown to have anti-cancer activity in mammalian cells. In the present study, we investigated the anti-proliferative effect of Ophiobolin A on human melanoma A375 and CHL-1 cell lines. This cellular model was chosen because of the incidence of melanoma malignant tumor on human population and its resistance to chemical treatments. Ophyobolin A strongly reduced cell viability of melanoma cells by affecting mitochondrial functionality. The toxin induced depolarization of mitochondrial membrane potential, reactive oxygen species production and mitochondrial network fragmentation, leading to autophagy induction and ultimately resulting in cell death by activation of the mitochondrial pathway of apoptosis. Finally, a comparative proteomic investigation on A375 cells allowed to identify several Ophiobolin A down-regulated proteins, which are involved in fundamental processes for cell homeostasis and viability.

  11. Linear accelerator-based stereotactic radiosurgery in 140 brain metastases from malignant melanoma.

    Science.gov (United States)

    Hauswald, Henrik; Stenke, Alina; Debus, Jürgen; Combs, Stephanie E

    2015-07-23

    To retrospectively access outcome and prognostic parameters of linear accelerator-based stereotactic radiosurgery in brain metastases from malignant melanoma. Between 1990 and 2011 140 brain metastases in 84 patients with malignant melanoma (median age 56 years) were treated with stereotactic radiosurgery. At initial stereotactic radiosurgery 48 % of patients showed extracerebral control. The median count of brain metastases in a single patient was 1, the median diameter was 12 mm. The median dose applied was 20 Gy/80 % isodose enclosing. The median follow-up was 7 months and the median overall survival 9 months. The 6-, 12- and 24 month overall survival rates were 71 %, 39 % and 25 % respectively. Cerebral follow-up imaging showed complete remission in 20 brain metastases, partial remission in 39 brain metastases, stable disease in 54 brain metastases, progressive disease in 24 brain metastases and pseudo-progression in 3 brain metastases. Median intracerebral control was 5.3 months and the 6- and 12-month intracerebral progression-free survival rates 48 % and 38 %, respectively. Upon univariate analysis, extracerebral control (log-rank, p stereotactic radiosurgery (log-rank, p stereotactic radiosurgery high dose region. Stereotactic radiosurgery is a well-tolerated and effective treatment option for brain metastases in malignant melanoma and was able to achieve local remissions in several cases. Furthermore, especially patients with controlled extracerebral disease and a low count of brain metastases seem to benefit from this treatment modality. Prospective trials analysing the effects of combined stereotactic radiosurgery and new systemic agents are warranted.

  12. Incidence, Survival, and Mortality of Malignant Cutaneous Melanoma in Wisconsin, 1995-2011.

    Science.gov (United States)

    Peterson, Molly; Albertini, Mark R; Remington, Patrick

    2015-10-01

    To assess trends in malignant melanoma incidence, survival, and mortality in Wisconsin. Incidence data for Wisconsin were obtained from the Wisconsin Cancer Reporting System Bureau of Health Information using Wisconsin Interactive Statistics on Health, while incidence data for the United States were obtained from the Surveillance, Epidemiology, and End Results system (SEER). The mortality to incidence ratio [1 - (mortality/incidence)] was used as a proxy to estimate relative 5-year survival in Wisconsin, while observed 5-year survival rates for the United States were obtained from SEER. Mortality data for both Wisconsin and the United States were extracted using the Centers for Disease Control and Prevention Wide-ranging Online Data for Epidemiologic Research. During the past decade, malignant melanoma incidence rates increased 57% in Wisconsin (from 12.1 to 19.0 cases per 100,000) versus a 33% increase (from 20.9 to 27.7 cases per 100,000) in the United States during the same time period. The greatest Wisconsin increase in incidence was among women ages 45-64 years and among men ages 65 years and older. Overall relative percent difference in 5-year survival in Wisconsin rose 10% (from 77% to 85%) and was unchanged (82%) for the United States. Wisconsin overall mortality rates were unchanged at 2.8 deaths per 100,000, compared to a 10% increase in the United States (from 3.1 to 3.4 deaths per 100,000). Wisconsin mortality rates improved for women ages 45-64 and for men ages 25-44. Despite improvements in malignant melanoma survival rates, increases in incidence represent a major public health challenge for physicians and policymakers.

  13. Malignant melanoma brain metastases. Review of Roswell Park Memorial Institute experience.

    Science.gov (United States)

    Madajewicz, S; Karakousis, C; West, C R; Caracandas, J; Avellanosa, A M

    1984-06-01

    One-hundred twenty five of 700 patients with malignant melanoma treated at Roswell Park Memorial Institute from 1972 to 1978 were found to have brain metastases. Seventy-three percent of the patients had multiple brain metastases. Male to female ratio was 1.9:1. The median survival of the untreated group of patients was 3 weeks as compared with that of 6 weeks for the patients maintained on steroids only, 9 weeks for those who received radiotherapy, 11 weeks for the patients treated with intraarterial chemotherapy, and 26 weeks for the patients who underwent successful surgical excision of a solitary lesion.

  14. A case of collision tumor or transdifferentiation between malignant melanoma and leiomyosarcoma

    OpenAIRE

    Jamshaid Ul-Mulk; Helle Rasmussen; Line Breiting; Elsebeth Siim

    2012-01-01

    A 73-year-old woman was referred to the hospital due to a pigmented, asymptomatic nevus on her right arm that had changed in size and color. The histopathological examination showed a superficial spreading malignant melanoma, Clark level III, 2.26 mm in thickness. Two years later, the patient presented a 10 cm rapidly growing mass in her right axilla. The mass in the axilla measured 12.5 ΄ 9 ΄ cm. It revealed a lymph node metastases with a tumor growth composed of two different contiguous mor...

  15. In-situ hybridization based quantification of hTR: a possible biomarker in malignant melanoma

    DEFF Research Database (Denmark)

    Vagner, Josephine; Steiniche, Torben; Stougaard, Magnus

    2015-01-01

    Aims Telomerase is reactivated in most cancers and there is accumulating evidence for it being a driver event in malignant melanoma (MM). Thus, our aim was to evaluate if in situ hybridisation (ISH)-based quantification of the telomerase RNA (hTR) could be used to distinguish MM from nevi...... thickness suggesting that hTR might be a valuable biomarker in MM. Furthermore, as ISH-based detection requires presence of both hTR and the reverse transcriptase (hTERT) it might be an indicator of active telomerase and thus have future relevance as a predictive biomarker for anti-telomerase treatment....

  16. Photothermal therapy combined with dinitrophenyl hapten for the treatment of late stage malignant melanoma

    Science.gov (United States)

    Li, Xiaosong; Du, Nan; Li, Haijun; Long, Shan; Chen, Dianjun; Zhou, Feifan; Xu, Yuanyuan; Wang, Fuli; Chen, Wei R.

    2017-02-01

    To evaluate the efficacy and safety of photothermal with dinitrophenyl hapten (DNP) for patients with malignant melanoma (MM), Patients with pathology confirmed stage III or IV MM were enrolled. Seventy-two patients were randomized into two groups, DNP alone group (n=36) and DNP plus photothermal therapy group (n=36). The results showed that the patients in the combination treatment group had longer median progression-free survival time (19.0m vs. 12.0m, p=0.007). No severe adverse events were observed in both groups. Thus, the combination of photothermal therapy and DNP maybe a new therapeutic strategy for patients with advanced MM.

  17. The first attempt in local excision of anorectal malignant melanoma using transanal endoscopic microsurgery

    Science.gov (United States)

    Kong, Xiangyi; Liu, Qi; Lin, Guole; Zhao, Dachun; Qiu, Huizhong; Cui, Quancai

    2015-01-01

    Anorectal malignant melanoma (AMM) is an uncommon malignancy that is thought to arise from melanocytes in the mucosa around the anorectal junction. AMM is commonly misdiagnosed, and definitive preoperative diagnosis is often difficult. The prognosis of AMM is relatively poor. Although radical resection is required for AMM, there is still no consensus at this moment on which surgical approach is preferred. We herein report a rare case of AMM which was treated by transanal endoscopic microsurgery (TEM) in combination with radiotherapy, which resulted in complete excision of the lesion without complications. The successful treatment for this AMM using TEM emphasizes the need to broaden its application in the treatment of various rectal lesions while preserving organ function and decreasing recurrence. PMID:26617919

  18. A mathematical analysis of the ABCD criteria for diagnosing malignant melanoma

    Science.gov (United States)

    Lee, Hyunju; Kwon, Kiwoon

    2017-03-01

    The medical community currently employs the ABCD (asymmetry, border irregularity, color variegation, and diameter of the lesion) criteria in the early diagnosis of a malignant melanoma. Although many image segmentation and classification methods are used to analyze the ABCD criteria, it is rare to see a study containing mathematical justification of the parameters that are used to quantify the ABCD criteria. In this paper, we suggest new parameters to assess asymmetry, border irregularity, and color variegation, and explain the mathematical meaning of the parameters. The suggested parameters are then tested with 24 skin samples. The parameters suggested for the 24 skin samples are displayed in three-dimensional coordinates and are compared to those presented in other studies (Ercal et al 1994 IEEE Trans. Biomed. Eng. 41 837-45, Cheerla and Frazier 2014 Int. J. Innovative Res. Sci., Eng. Technol. 3 9164-83) in terms of Pearson correlation coefficient and classification accuracy in determining the malignancy of the lesions.

  19. Detection of melanomas by digital imaging of spectrally resolved UV light-induced autofluorescence of human skin

    Science.gov (United States)

    Chwirot, B. W.; Chwirot, S.; Jedrzejczyk, W.; Redzinski, J.; Raczynska, A. M.; Telega, K.

    2001-07-01

    We studied spectral and spatial distributions of the intensity of the ultraviolet light-excited fluorescence of human skin. Our studied performed in situ in 162 patients with malignant and non-malignant skin lesions resulted in a new method of detecting melanomas in situ using digital imaging of the spectrally resolved fluorescence. With our diagnostic algorithm we could successfully detect 88.5% of the cases of melanoma in the group of patients subject to examinations with the fluorescence method. A patent application for the method has been submitted to the Patent Office in Warsaw.

  20. Use of fluorine-18 fluorodeoxyglucose positron emission tomography in the detection of silent metastases from malignant melanoma

    DEFF Research Database (Denmark)

    Jakobsen, Annika Loft; Andersson, A P; Dahlstrøm, K

    2000-01-01

    Correct staging is crucial for the management and prognosis of patients with malignant melanoma. The aim of this prospective study was to compare staging by whole-body positron emission tomography using fluorine-18 fluorodeoxyglucose (18F-FDG) with staging by conventional methods. Thirty-eight pa......Correct staging is crucial for the management and prognosis of patients with malignant melanoma. The aim of this prospective study was to compare staging by whole-body positron emission tomography using fluorine-18 fluorodeoxyglucose (18F-FDG) with staging by conventional methods. Thirty......-eight patients with malignant melanoma of clinical stage II (local recurrence, in-transit and regional lymph node metastases) or III (metastases to other sites than in stage II) were included in the study. The results of the PET scans were compared with those obtained by clinical examination, computed tomography...... method superior to conventional methods for detecting widespread metastases from malignant melanoma. Mutilating surgery of no benefit can thereby be avoided. 18F-FDG PET is useful as a supplement to clinical examination in melanoma staging....

  1. Loco-Regional Control With Complete Resection and Tongue Reconstruction on the Malignant Melanoma in the Tongue.

    Science.gov (United States)

    Alkaff, Tuqa; Jeong, Woo Shik; Nam, Soon Yuhl; Choi, Jong Woo

    2017-07-01

    Primary malignant melanoma in the tongue is very uncommon disease that is considered low in comparison to cutaneous melanoma. In this report, the authors described a case of the hemitongue reconstruction with fasciocutaneous free flap on the patient who suffered from the malignant melanoma primarily originating from the base of the tongue that was treated with surgery and radiotherapy but developed a lung metastasis. A 76-year-old man was referred to the otorhinolaryngology clinic after complaining of a painful mass present for 3 months on the right side of the tongue. A punch biopsy was revealed atypical cells with pigmentation that is consistent with malignant melanoma. After wide excision and bilateral neck dissection performed, hemipartial tongue reconstruction was done using a radial forearm free flap. The patient had an uneventful recovery and received a course of radiotherapy along with follow-up examinations for 3 years. The authors report this rare patient for providing the other surgeons with the useful information regarding the management of the malignant melanoma on the tongue with free flap reconstruction which turned out to be successful in loco-regional control.

  2. Substantial expression of luteinizing hormone-releasing hormone (LHRH) receptor type I in human uveal melanoma

    Science.gov (United States)

    Schally, Andrew V.; Block, Norman L; Dezso, Balazs; Olah, Gabor; Rozsa, Bernadett; Fodor, Klara; Buglyo, Armin; Gardi, Janos; Berta, Andras; Halmos, Gabor

    2013-01-01

    Uveal melanoma is the most common primary intraocular malignancy in adults, with a very high mortality rate due to frequent liver metastases. Consequently, the therapy of uveal melanoma remains a major clinical challenge and new treatment approaches are needed. For improving diagnosis and designing a rational and effective therapy, it is essential to elucidate molecular characteristics of this malignancy. The aim of this study therefore was to evaluate as a potential therapeutic target the expression of luteinizing hormone-releasing hormone (LHRH) receptor in human uveal melanoma. The expression of LHRH ligand and LHRH receptor transcript forms was studied in 39 human uveal melanoma specimens by RT-PCR using gene specific primers. The binding charachteristics of receptors for LHRH on 10 samples were determined by ligand competition assays. The presence of LHRH receptor protein was further evaluated by immunohistochemistry. The expression of mRNA for type I LHRH receptor was detected in 18 of 39 (46%) of tissue specimens. mRNA for LHRH-I ligand could be detected in 27 of 39 (69%) of the samples. Seven of 10 samples investigated showed high affinity LHRH-I receptors. The specific presence of full length LHRH receptor protein was further confirmed by immunohistochemistry. A high percentage of uveal melanomas express mRNA and protein for type-I LHRH receptors. Our results support the merit of further investigation of LHRH receptors in human ophthalmological tumors. Since diverse analogs of LHRH are in clinical trials or are already used for the treatment of various cancers, these analogs could be considered for the LHRH receptor-based treatment of uveal melanoma. PMID:24077773

  3. Improved malignant melanoma prognosis at a consultant-delivered multidisciplinary pigmented lesion clinic in Cork.

    LENUS (Irish Health Repository)

    Field, S

    2010-02-01

    Early detection and excision is the only effective treatment for malignant melanoma. To assess the effect of a consultant-delivered, rapid-access pigmented lesion clinic (PLC) established at the South Infirmary-Victoria University Hospital (SIVUH), we analyzed melanoma tumour-stage prior to (1998-2002) and after (2003-2007) the advent of the PLC. Patients attending SIVUH had a greater proportion of early-stage tumours (65.3%) compared to the rest of Cork (51.2%), County Cork as a whole (56.7%) and all of Ireland (57.4%). The proportion of SIVUH males with early-stage tumours was statistically significantly higher than the rest of County Cork (chi2 = 11.23, P < 0.05). The proportion of patients > 50y with early-stage tumours was also statistically significantly higher than the rest of County Cork (chi2 = 18.88, P < 0.05), the whole of County Cork (chi2 = 7.84, P < 0.05) and all of Ireland (chi2 = 9.67, P < 0.05). We believe that the early detection and improved prognosis of Cork melanoma patients is at least partly due to the PLC.

  4. Improved malignant melanoma prognosis at a consultant-delivered multidisciplinary pigmented lesion clinic in Cork.

    LENUS (Irish Health Repository)

    Field, S

    2012-02-01

    Early detection and excision is the only effective treatment for malignant melanoma. To assess the effect of a consultant-delivered, rapid-access pigmented lesion clinic (PLC) established at the South Infirmary-Victoria University Hospital (SIVUH), we analyzed melanoma tumour-stage prior to (1998-2002) and after (2003-2007) the advent of the PLC. Patients attending SIVUH had a greater proportion of early-stage tumours (65.3%) compared to the rest of Cork (51.2%), County Cork as a whole (56.7%) and all of Ireland (57.4%). The proportion of SIVUH males with early-stage tumours was statistically significantly higher than the rest of County Cork (chi2 = 11.23, P < 0.05). The proportion of patients > 50y with early-stage tumours was also statistically significantly higher than the rest of County Cork (chi2 = 18.88, P < 0.05), the whole of County Cork (chi2 = 7.84, P < 0.05) and all of Ireland (chi2 = 9.67, P < 0.05). We believe that the early detection and improved prognosis of Cork melanoma patients is at least partly due to the PLC.

  5. Use of fluorine-18 fluorodeoxyglucose positron emission tomography in the detection of silent metastases from malignant melanoma

    DEFF Research Database (Denmark)

    Eigtved, A; Andersson, A P; Dahlstrøm, K

    2000-01-01

    Correct staging is crucial for the management and prognosis of patients with malignant melanoma. The aim of this prospective study was to compare staging by whole-body positron emission tomography using fluorine-18 fluorodeoxyglucose (18F-FDG) with staging by conventional methods. Thirty-eight pa......Correct staging is crucial for the management and prognosis of patients with malignant melanoma. The aim of this prospective study was to compare staging by whole-body positron emission tomography using fluorine-18 fluorodeoxyglucose (18F-FDG) with staging by conventional methods. Thirty...

  6. Atypical melanocytic nevi of genital type: a distinctive pigmented lesion of the genital tract often confused with malignant melanoma.

    Science.gov (United States)

    Quddus, M Ruhul; Rashid, Lanita B; Sung, C James; Robinson-Bostom, Leslie; Lawrence, W Dwayne

    2010-02-15

    A 30-year-old female presented with a 0.3 cm slightly raised tan-brown papule with somewhat irregular borders on her right labia minora. The papule was detected by her gynecologist during an annual gynecologic visit. Excision of the lesion revealed an atypical melanocytic nevus of genital type (AMNGT). This nevus is often confused with other pigmented lesions especially dysplastic nevus or even malignant melanoma. This distinctive melanocytic nevus often causes significant concern to pathologists and dermatologists. The diagnostic criteria and differentiating features from dysplastic nevi and malignant melanoma are discussed.

  7. DNA level, tumor thickness, and stereological estimates of nuclear volume in stage I cutaneous malignant melanomas. A comparative study with analysis of prognostic impact

    DEFF Research Database (Denmark)

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

    1991-01-01

    The mutual relation and prognostic value of three quantitative variables were investigated in a retrospective series of 56 stage I cutaneous malignant melanomas. Unbiased stereological estimates of nuclear volume, nuclear nu v were obtained along with measurements of melanoma thickness. The DNA......, nuclear nu v was the only independent, prognostically significant variable. Physical, three-dimensional nuclear volume is not solely a reflection of nuclear DNA content, and may represent a valuable, quantitative prognostic indicator in cutaneous malignant melanomas....

  8. [Effect of dermoscopy on diagnostic accuracy of pigmented skin lesions emphasizing malignant melanoma].

    Science.gov (United States)

    Schein, Ophir; Westreich, Moshe; Shalom, Avshalom

    2009-12-01

    Skin tumors are the most common malignancies in the Western population, with surgical excision being the definitive treatment. The authors' objectives were to compare the precision of clinical diagnosis of malignant melanomas (MM) by a plastic surgeon in a community clinic with and without the use of dermoscopy. The control group comprised of all patients operated on solely by one plastic surgeon between 2001 and 2003, at which time dermoscopy was not used. The study group included all patients operated on by the same surgeon between the years 2007 and 2008. Clinical, dermoscopic and histological data for both groups were reviewed. The sensitivity and positive predictive value (PPV) were measured and compared using the Fisher's exact test and chi square test. Overall, 1806 skin lesions were excised in the control group compared to 1039 lesions in the study group. A total of 680 melanocytic lesions, 167 dysplastic melanocytic lesions and 20 MM were excised in the control group. The sensitivity for the diagnosis of melanoma was 80% and the PPV was 53%. In the study group 415 melanocytic lesions where excised, of which 63 were dysplastic lesions and 14 MM. The sensitivity for MM diagnosis was 77% and the PPV was 83%. The authors found a statistically significant improvement in the positive predictive value (Plesions was also observed (Plesions diagnosis thus reducing unnecessary benign excisions.

  9. The role of surgical methods in the treatment of anorectal malignant melanoma (AMM).

    Science.gov (United States)

    Keskin, S; Tas, F; Karabulut, S; Yildiz, I; Kiliç, L; Ciftci, R; Vatansever, S

    2013-01-01

    Anorectal malignant melanoma (AMM) is a rare tumor with a poor prognosis. The aim of this study was to investigate the clinicopathological characteristics and treatment outcomes in patients with AMM. The study included 21 patients diagnosed with AMM between 2000 and 2010 that were evaluated with regard to age, sex, disease stage, treatment modality, and survival. Stage I, II, and III were defined as localized primary malignant melanoma, regional lymph node metastasis, and distant metastasis, respectively. In all, 12 (57%) patients were female and 9 (43%) were male ; median age was 61 years (range : 30-84 years). Among the 21 patients, 7 (47%) underwent abdominoperineal resection and 8 (53%) were treated using wide local excision. Four (19%) patients were classified as stage I, 10 (48%) as stage II, and 7 (33%) patients as stage III. In total, 10 patients received adjuvant therapy. Median overall and progression-free survival was 12 and 9 months, respectively. The 1-year and 5-year overall survival estimates were 59% and 42%, and progression free survival were 49% and 7%, respectively. Patients aged > 60 years (P = 0.145), female patients (P = 0.076), patients with localized disease (P = 0.045), patients that underwent wide local excision (P = 0.619), and patients that received adjuvant therapy (P = 0.962) had longer survival. The prognosis of AMM remains very poor and disease stage is the only predictor of survival. Abdominoperineal resection does not confer an advantage, in terms of survival, in patients with AMM.

  10. Malignant melanoma of the oral cavity. Review of the literature and experience in a Peruvian Population.

    Science.gov (United States)

    Guevara-Canales, J-O; Gutiérrez-Morales, M-M; Sacsaquispe-Contreras, S-J; Sánchez-Lihón, J; Morales-Vadillo, R

    2012-03-01

    To determine the epidemiological profile of malignant melanoma cases treated at the National Institute for Neoplastic Diseases "Dr. Eduardo Caceres Graziani" (INEN) over the period 1952 to 2008. All clinical records with complete data of patients presenting a histopathological diagnosis of malignant melanoma of the oral cavity were reviewed. Data such as age, gender, location, tumor size, disease length, presence of metastasis, treatment received and year of admission were recorded. During the study period 97 cases were found. The average age of patients was 52.85±1.6 years old mostly between 50 and 59 years old; the predominant gender was the female. The most common location was the palate and there was 58.8% of cases with a tumor size bigger than or equal to 4 cm. The length of the disease in 38.1% of the cases was longer than a year and in great part of the cases (69.1%) there was no metastasis. The treatment of choice was the surgery plus radiotherapy in 38.1% of the cases. According to the admission date it was also noted that the number of cases is increasing. The results of this study demonstrate a late diagnosis and an increasing frequency of this neoplasia in the oral cavity.

  11. Oral Malignant Melanoma Initially Misdiagnosed as a Racial Pigmentation: A Case Report

    Directory of Open Access Journals (Sweden)

    Carla Patrícia Martinelli-Kläy

    2016-02-01

    Full Text Available Oral malignant melanoma (OMM is rare, representing less than 0.5% of all oral malignancies. The most affected sites are the palate and the maxillary gingiva. Histological examination is important to establish the diagnosis of any suspicious pigmented lesion in the oral cavity, mainly if a precise clinical diagnosis is not possible. We present one case of OMM that was initially diagnosed as a racial pigmentation elsewhere 2 years earlier. Clinical examination showed multiple macules and nodules located on the hard and soft palate, gingiva and superior alveolar mucosa. These lesions were painless and presented a color variation going from dark blue to black. Histological analysis showed sheets and nests of atypical melanocytes displaying a range of shapes such as plasmacytoid, epithelioid, and round cells, located in the superficial corium extending to the deep tissues. A few tumor cells contained variable amounts of melanin. There was no invasion of blood vessels or nerve fibers. Immunohistochemical analysis revealed that the neoplastic cells were positive for HMB-45, melan-A, S-100 and negative for AE1/AE3, confirming the diagnosis of melanoma. The Ki-67 labeling index was around 25%. The patient refused any treatment and died 11 months later.

  12. Collision Tumour of Squamous Cell Carcinoma and Malignant Melanoma in the Oral Cavity of a Dog.

    Science.gov (United States)

    Rodríguez, F; Castro, P; Ramírez, G A

    2016-05-01

    A 7-year-old, male cocker spaniel was presented with a gingival proliferative lesion in the rostral maxilla and enlargement of the regional lymph node. Morphological and immunohistochemical analysis revealed a collision tumour composed of two malignant populations, epithelial and melanocytic, with metastasis of the neoplastic melanocytes to the regional lymph node. The epithelial component consisted of trabeculae and islands of well-differentiated squamous epithelium immunoreactive to cytokeratins. The melanocytic component had a varying degree of pigmentation of polygonal and spindle-shaped cells, growing in nests or densely packed aggregates and immunolabelled with S100, melanoma-associated antigen (melan A), neuron-specific enolase and vimentin antibodies. Protein markers involved in tumorigenesis or cell proliferation (i.e. COX-2, p53, c-kit and Ki67), were overexpressed by the neoplastic cells. To the authors' knowledge, this is the first description of an oral collision tumour involving malignant melanoma and squamous cell carcinoma in the dog. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. A newly developed mouse monoclonal SOX10 antibody is a highly sensitive and specific marker for malignant melanoma, including spindle cell and desmoplastic melanomas.

    Science.gov (United States)

    Tacha, David; Qi, Weimin; Ra, Seong; Bremer, Ryan; Yu, Charlie; Chu, Joseph; Hoang, Laura; Robbins, Bruce

    2015-04-01

    Recent immunohistochemical studies have demonstrated Sry-related HMG-Box gene 10 (SOX10) expression in malignant melanomas, malignant peripheral nerve sheath tumors, a subset of breast carcinomas, and gliomas. SOX10 has shown important clinical utility in its ability to detect desmoplastic and spindle cell melanomas. To date, most publications have employed a research use-only goat polyclonal SOX10 antibody for immunohistochemical staining. To describe the development of a new mouse monoclonal SOX10 antibody (BC34) and evaluate its immunohistochemical staining profile in a wide range of normal and neoplastic tissues, with an emphasis on melanoma. SOX10 antibody was optimized for staining using a polymer detection system and visualization with diaminobenzidine. In normal tissues, SOX10 was expressed in skin melanocytes and eccrine cells, breast myoepithelial and lobular epithelial cells, salivary gland myoepithelial cells, peripheral nerve Schwann cells, and central nervous system glial cells. SOX10 was expressed in 238 of 257 melanomas (92.6%), including 50 of 51 of both spindle cell and desmoplastic melanomas (98%). SOX10 was expressed in 100% of nevi (20 of 20) and schwannomas (28 of 28). In other neoplasms, SOX10 was expressed in 18 of 109 invasive ductal breast carcinomas (16.5%). All other carcinomas were negative for SOX10. SOX10 was identified in 25 of 52 central nervous system neoplasms, primarily in astrocytomas (22 of 41; 53.7%), and in 4 of 99 various sarcomas examined (4.0%). The newly developed mouse monoclonal SOX10 antibody BC34 is highly sensitive and specific for malignant melanoma, including desmoplastic and spindle cell variants, and appears highly suitable for clinical use.

  14. Unusual subcutaneous metastatic spreading pattern of malignant melanoma; Ungewoehnliches subkutanes Metastasierungsmuster eines malignen Melanoms

    Energy Technology Data Exchange (ETDEWEB)

    Dorenbeck, U.; Feuerbach, S. [Inst. fuer Roentgendiagnostik, Universitaetsklinik Regensburg (Germany); Abels, C. [Klinik und Poliklinik fuer Dermatologie, Universitaetsklink Regensburg (Germany)

    1999-11-01

    The contribution is a case report on massive, subcutaneous metastatic spreading of a malignant melanoma. Ten months after excision of a malignant melanoma, the truncus of the 51 year-old male patient showed multiple hematomas sized from 1-3 cm{sup 2}, located above cutaneous/subcutaneous lumps of which some were painful and non-displaceable. The examinations for detection of meatastes as well had shon an unusual picture in that there was no spreading to the lungs. CT scans revealed subcutaneous filiae to an extent unseen before. This final diagnosis is all the more of high interest as an initial diagnosis falsely interpreted this metastatic spreading pattern to be a hemorrhagic diathesis. Together with the unusual non-spreading to the lungs, this case of subcutaneous formation of metastases indicates that in staging examinations of melanoma patients, such rare patterns of metastatic spreading should be taken into account. (orig./CB) [Deutsch] Es wird ueber den Fall einer massiven subkutanen Metastasierung eines malignen Melanoms berichtet. Zehn Monate nach der Exzision eines malignen Melanoms zeigten sich bei dem 51jaehrigen maennlichen Patienten am Stamm multiple 1-3 cm{sup 2} grosse flaechige Haematome ueber kutanen/subkutanen, teils schmerzhaften und nicht verschieblichen Knoten. Auffallend war, dass auch im Verlauf keine intrapulmonalen Absiedlungen gefunden wurden. Interessant ist die Darstellung der subkutanen Filiae im Computertomogramm, die wir so massiv noch nicht gesehen haben. Da die Metastasierung zuerst als haemorrhagische Diathese fehldiagnostiziert wurde, scheint die Diagnose einer subkutanen Aussaat eines malignen Melanoms um so interessanter. Der zusaetzlich zur subkutanen Metastasierung fehlende Lungenbefall zeigt, dass bei Staginguntersuchungen von Melanompatienten ein Metastasierungstyp vorliegen kann, welcher erheblich von gaengigen Metastasierungsmodellen abweichen kann. (orig.)

  15. 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.

  16. Risk of subsequent cutaneous malignancy in patients with prior melanoma: a systematic review and meta-analysis.

    Science.gov (United States)

    van der Leest, R J T; Flohil, S C; Arends, L R; de Vries, E; Nijsten, T

    2015-06-01

    Melanoma patients are known to be at risk of developing multiple cutaneous (pre-) malignancies, however, the exact dimensions of these risks are unknown. In this meta-analysis, risks of developing a melanoma, basal cell carcinoma (BCC) or squamous cell carcinoma (SCC) after a melanoma were investigated. An extensive systematic literature search was conducted (last performed on 18 January 2012). Studies reporting risks, i.e. proportions, standardized incidence ratios (SIR) and cumulative risks (CRs) were included. Fifty, of 233 fully read articles, met selection criteria. Two independent reviewers extracted data on study characteristics and risks measurements. Random-effects meta-analyses were used to pool the risk estimates for the three tumour combinations. In melanoma patients, pooled proportions for a subsequent melanoma, BCC or SCC were respectively 3.8% (n = 47), 2.8% (n = 5) and 1.0% (n = 6). The pooled SIRs for a subsequent melanoma, BCC or SCC in melanoma patients were respectively 10.4 (n = 12), 4.6 (n = 2) and 2.8 (n = 2). Mean 20-year CRs of a subsequent melanoma, BCC or SCC in melanoma patients were respectively 5.4% (n = 3), 14.0% (n = 1) and 4.0% (n = 1). Subgroup analyses showed substantial differences in reported risks between continents and study design. In conclusion, a history of a prior melanoma is a strong predictor for development of a subsequent melanoma (approximately 10-fold increased risk) and to a lesser extent BCC or SCC. This information could serve as information for health care systems. Further, secondary prevention seems pivotal in this patient group. © 2014 European Academy of Dermatology and Venereology.

  17. Birth outcome in women with breast cancer, cutaneous malignant melanoma, or Hodgkin's disease: a review

    Directory of Open Access Journals (Sweden)

    Vivian Langagergaard

    2010-12-01

    Full Text Available Vivian LangagergaardDepartment of Clinical Epidemiology, Aarhus University Hospital, Aarhus, DenmarkBackground: Data on birth outcome in women diagnosed with cancer before, during, or shortly after pregnancy are very sparse. The purpose of this review was to summarize the existing epidemiologic evidence of the adverse effect of breast cancer, cutaneous malignant melanoma, and Hodgkin's disease on birth outcome.Methods: The MEDLINE database was used to review the literature systematically. Studies that examined the following outcomes were included: preterm birth, low birth weight, low birth weight at term, stillbirths, congenital abnormalities, male proportion of newborns, and mean birth weight. Studies were grouped according to whether the woman had been diagnosed with the specific cancer before, during, or shortly after pregnancy.Results: Few data exist on birth outcome in women with breast cancer, melanoma, or Hodgkin's disease. The overall results from the limited number of studies, which included a comparison group for birth outcome, were reassuring. However, for women diagnosed with breast cancer before pregnancy, the only 2 studies that included comparison groups for birth outcome had conflicting results regarding the risk of preterm birth and congenital abnormalities. Furthermore, a recent cohort study of birth outcome in women who were diagnosed with Hodgkin's disease before pregnancy indicated a slightly increased risk of congenital abnormalities among the newborns.Conclusion: Overall, the existing studies offer reassuring results concerning the risks of adverse birth outcome for women diagnosed with breast cancer, melanoma, or Hodgkin's disease before, during or shortly after pregnancy. A limitation of most studies was the imprecise risk estimates caused by the small number of adverse birth outcomes and the lack of results stratified by treatment. Therefore, international collaboration is necessary in the future, to obtain more precise

  18. IMP-3 EXPRESSION IN BENIGN MELANOCYTIC NEVI, DYSPLASTIC NEVI AND MALIGNANT MELANOMA: PRELIMINARY FINDINGS IN BULGARIAN PATIENTS.

    Science.gov (United States)

    Chokoeva, A A; Ananiev, J; Wollina, U; Tana, C; Lotti, T; Cardoso, J C; Tchernev, G

    2015-01-01

    IMP-3 is generally considered as an oncofetal protein, which plays a critical role in regulation of cell proliferation via an IGF-II-dependent pathway in K562 leukemia cells. IMP-3 expression has been detected in malignancies with various origins, while its appearance in adult tissue is generally considered abnormal, with some exceptions. IMP3 is also considered a prognostic biomarker in patients with renal cell carcinoma and clear-cell type ovarian carcinoma, hepatocellular carcinoma, pancreatic ductal adenocarcinoma and in patients with poorly differentiated thyroid carcinoma and uterine cervical carcinomas, testicular cancer and malignant melanoma. To our knowledge, no more than 4 PubMed-indexed studies have investigated the expression of IMP-3 in melanocytic lesions, namely its role in the differentiation between benign and malignant neoplasms. We investigated the expression of IMP-3 in a small series of benign melanocytic lesions, dysplastic nevi and melanomas, aiming to establish its significance as a marker for their distinction, comparing the results with those from the literature. IMP- 3 immunostaining was performed in 30 melanocytic lesions: 10 malignant melanomas, 10 dysplastic nevi and 10 benign melanocytic nevi. Our results revealed expression in 20% of dysplastic lesions and 40% of melanoma cases, while none of the benign nevi showed positive expression. These data contradict some of the results from other studies and raise some questions regarding the correlation between IMP- 3 and the degree of dysplasia of melanocytic nevi, as well as its potential relationship with prognostic parameters in melanoma, including tumor thickness and mitotic rate. Our results suggest that IMP-3 expression could be only an auxiliary marker for differentiation between dysplastic nevi and benign nevi, since although it is not expressed in all dysplastic lesions, staining correlates with the degree of dysplasia/atypia. It seems that IMP-3 expression is not a useful

  19. [Malignant nasosinusal melanomas. Review of the literature apropos of 12 cases].

    Science.gov (United States)

    Poissonnet, G; Castillo, L; Dassonville, O; Ettore, F; Birtwisle-Peyrottes, I; Santini, J; Demard, F

    1997-01-01

    Malignant melanoma with primary onset in the nasal cavity and paranasal sinuses remains a scarcely encountered malignancy and we report 12 cases of our own experience from 1991. These mucosal melanomas occur mainly in the elderly and present most commonly as a one sided airway obstructive syndrome with often bleeding in the nasal cavity. No sex or race ratio is found. Histological examination of the surgical specimen has been made easier since the use of immunohistochemical studies. The original site of onset is commonly located at the inferior part of the nasal cavity but in many cases, it is noted several sites of tumor localization. Despite well conducted treatment the prognosis remains quite deceiving and significantly poor. In our study, the 4-year actuarial survival was 26%. The 5-year survival rate ranges in the literature from 10% to 40%. Short and long term follow-up show an important rate of recurrence (local and lymph node metastases as well as distant metastases). The insidious evolution of the malignancy usually happens during the first year. Computed tomography and MRI are essential in the evaluation of tumor extension. The treatment is based on the combination of surgery and radiotherapy: Surgery is practised first and must ensure sufficient excision of the tumor without minimal functional or aesthetic damage in this complex region. This surgery is based on surgical approaches to the midface known as Lateral rhinotomy and midfacial degloving. When there is cervical lymph node involvement at the time of diagnosis it is suitable to treat it, even in case of recurrence. Complementary high dose radiation is required to treat tumors which could not undergo surgery and also as adjuvant therapy after removal of the mass.

  20. Malignant melanoma slide review project: Patients from non-Kaiser hospitals in the San Francisco Bay Area. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Reynolds, P. [California Dept. of Health Services, Berkeley, CA (United States)

    1993-01-05

    This project was initiated, in response to concerns that the observed excess of malignant melanoma among employees of Lawrence Livermore National Laboratory (LLNL) might reflect the incidence of disease diagnostically different than that observed in the general population. LLNL sponsored a slide review project, inviting leading dermatopathology experts to independently evaluate pathology slides from LLNL employees diagnosed with melanoma and those from a matched sample of Bay Area melanoma patients who did not work at the LLNL. The study objectives were to: Identify all 1969--1984 newly diagnosed cases of malignant melanoma among LLNL employees resident in the San Francisco-Oakland Metropolitan Statistical Area, and diagnosed at facilities other than Kaiser Permanente; identify a comparison series of melanoma cases also diagnosed between 1969--1984 in non-Kaiser facilities, and matched as closely as possible to the LLNL case series by gender, race, age at diagnosis, year of diagnosis, and hospital of diagnosis; obtain pathology slides for the identified (LLNL) case and (non-LLNL) comparison patients for review by the LLNL-invited panel of dermatopathology experts; and to compare the pathologic characteristics of the case and comparison melanoma patients, as recorded by the dermatopathology panel.

  1. Linkage of cutaneous malignant melanoma/dysplastic Nevi to chromosome 9p, and evidence for genetic heterogeneity

    Energy Technology Data Exchange (ETDEWEB)

    Goldstein, A.M.; Fraser, M.C.; Tucker, M.A.; Dracopoli, N.C.; Engelstein, M. (Massachusetts Institute of Technology, Cambridge, MA (United States)); Clark, W.H. Jr. (Univ. of Pennyslvania School of Medicine, Philadelphia, PA (United States))

    1994-03-01

    The authors examined the relationship between cutaneous malignant melanoma/dysplastic nevi (CMM/DN) and chromosome 9p in 13 pedigrees with two or more living cases of invasive melanoma. They used two highly informative (CA)[sub n] repeats, D9S126 and IFNA, previously implicated in familial malignant melanoma (MLM), to conduct linkage analysis. Three analyses were performed: (1) CMM alone - all individuals without either confirmed melanoma or borderline lesions were considered unaffected (model A); (2) CMM/DN with both variable age at onset and sporadics (model B); and (3) CMM affecteds only - all individuals either without confirmed melanoma or with borderline lesions were designated unknown' (model C). There was significant evidence for linkage to IFNA in all three models. For CMM along, the maximum lod score (Z[sub max]) was 4.36 at 0 = .10 for model A and 3.39 at 0 = .10 for model C. For CMM/DN (model B), Z[sub max] = 3.05 at 0 = .20. There was no significant evidence for heterogeneity when a homogeneity test allowing for linkage to chromosome 9p or chromosome 1p or neither region was used. These results suggest that there is an MLM susceptibility locus on chromosome 9p but that familial melanoma is heterogeneous and not all families with CMM/DN are linked to a locus in this region. 30 refs., 1 fig., 5 tabs.

  2. [Role of high-definition and high frequency ultrasonography in determining tumor thickness in cutaneous malignant melanoma].

    Science.gov (United States)

    Solivetti, F M; Thorel, M F; Di Luca Sidozzi, A; Bucher, S; Donati, P; Panichelli, V

    1998-12-01

    We investigated the predictive capabilities of high frequency, high resolution ultrasound (US) in the preoperative assessment of tumor thickness in cutaneous malignant melanomas. This evaluation is a valuable help for correct surgical planning. December 1997 to August 1998, we studied with US over 120 pigmented skin lesions and collected the data, including the final histologic diagnosis, of 78 of them, which make our series. Sixty-six of 78 lesions were histologically defined as cutaneous malignant melanomas with superficial spread and the other 12 as melanocytic nevi. All examinations were carried out with an Esaotebiomedica AU 5 Harmonic scanner equipped with a 20-MHz annular array probe and a linear 13-MHz probe; B-mode, color and power Doppler images were always acquired. The statistical analysis of the comparative US and histologic measurements of tumor thickness showed very good agreement, with a high Pearson's coefficient (R: .93). However, US frequently underestimated the actual thickness relative to histology, which is in contradiction with previous literature reports. We could study with US the melanoma in situ, which has never been described before. Last but not least, low-thickness melanomas had very few color and power Doppler signals. US is the correct tool for the preoperative assessment of the thickness of cutaneous malignant melanomas because it provides high agreement with histologic data even in lesions thinner than 1 mm.

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

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    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.

  4. First experiences of photoacoustic imaging for detection of melanoma metastases in resected human lymph nodes.

    Science.gov (United States)

    Grootendorst, D J; Jose, J; Wouters, M W; van Boven, H; Van der Hage, J; Van Leeuwen, T G; Steenbergen, W; Manohar, S; Ruers, T J M

    2012-09-01

    Excision and histological assessment of the first draining node (sentinel lymph node) is a frequently used method to assess metastatic lymph node involvement related to cutaneous melanoma. Due to the time required for accurate histological assessment, nodal status is not immediately available to the surgeon. Hence, in case histological examination shows metastases, the patient has to be recalled to perform additional lymphadenectomy. To overcome these drawbacks we studied the applicability of photoacoustic tomographic imaging as an intra-operative modality for examining the status of resected lymph nodes. In melanoma patients undergoing lymphadectomy for metastatic disease, six suspect lymph nodes were photoacoustically (PA) imaged using multiple wavelengths. Histopathologal examination showed three nodes without tumor cells (benign nodes) and three nodes with melanoma cells (malignant nodes). PA images were compared with histology and anatomical features were analyzed. In addition, PA spectral analysis was performed on areas of increased signal intensity. After correlation with histopathology, multiple areas containing melanoma cells could be identified in the PA images due to their increased response. Malignant nodes showed a higher PA response and responded differently to an increase in excitation wavelength than benign nodes. In addition, differences in anatomical features between the two groups were detected. Photoacoustic detection of melanoma metastases based on their melanin content proves to be possible in resected human lymph nodes. The amount of PA signal and several specific anatomical features seem to provide additional characteristics for nodal analysis. However, it is as yet preliminary to designate a highly accurate parameter to distinguish between malignant and benign nodes. We expect to improve the specificity of the technique with a future implementation of an adjusted illumination scheme and depth correction for photon fluence. Copyright © 2012

  5. Evaluation of primary cutaneous malignant melanoma according to Breslow and Clarke pathological indices

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    Z. Safaii Naraghi

    2006-07-01

    Full Text Available Background: Malignant melanoma is one of the fatal cutaneous neoplasms which are curable by early diagnosis. This neoplasm is diagnosed by the biopsy of the suspected lesion. It is essential to classify the tumor based on its histology, thickness, phase of growth, level of invasion, mitotic rate, presence of regression, inflammatory infiltration and ulceration. These descriptions yield some knowledge about the progression of disease and suggest an estimate of the status of the screening system for early diagnosis. Methods: This is a cross-sectional retrospective descriptive study. Pathological slides with diagnosis of malignant melanoma from 1377 to 1379 that present in the pathology department were assessed according to mentioned pathological indices and the 10-year survival calculated in this regard. Results: We assessed 47 cases with mean age of 57.38 (SD=5.85 and the gender distribution was 51.1% male and 42.2% female. More than 42% of cases were in Clarke level I, 2.1% Clarke level II, 6.4% Clarke level III, 40.4% Clarke level IV and 8.5% Clarke level V. Fifty three percent of patients were breslow thickness equal to or less than 0.75 millimeter(mm , 8.5% between 0.76 to 1.69 mm , 27.7% between 1.7 to 3.6 mm and 10.6% greater than 3.61 mm. Mean breslow thickness show no significant difference between males and females but there is a significant relation between thickness and age of the patients. Mean 10-year survivals of patients were 75% and were greater in females than males. We found a linear relation between patient age and breslow thickness that is calculated by the following equation: Log Breslow thickness (mm = - 0.625 + 0.016×age (year Conclusion: Complete recording of clinical and pathological data of patients with malignant melanoma make a proper stream to reach a surveillance system.

  6. Clinical validation of a gene expression signature that differentiates benign nevi from malignant melanoma.

    Science.gov (United States)

    Clarke, Loren E; Warf, M B; Flake, Darl D; Hartman, Anne-Renee; Tahan, Steven; Shea, Christopher R; Gerami, Pedram; Messina, Jane; Florell, Scott R; Wenstrup, Richard J; Rushton, Kristen; Roundy, Kirstin M; Rock, Colleen; Roa, Benjamin; Kolquist, Kathryn A; Gutin, Alexander; Billings, Steven; Leachman, Sancy

    2015-04-01

    Histopathologic examination is sometimes inadequate for accurate and reproducible diagnosis of certain melanocytic neoplasms. As a result, more sophisticated and objective methods have been sought. The goal of this study was to identify a gene expression signature that reliably differentiated benign and malignant melanocytic lesions and evaluate its potential clinical applicability. Herein, we describe the development of a gene expression signature and its clinical validation using multiple independent cohorts of melanocytic lesions representing a broad spectrum of histopathologic subtypes. Using quantitative reverse-transcription polymerase chain reaction (PCR) on a selected set of 23 differentially expressed genes, and by applying a threshold value and weighting algorithm, we developed a gene expression signature that produced a score that differentiated benign nevi from malignant melanomas. The gene expression signature classified melanocytic lesions as benign or malignant with a sensitivity of 89% and a specificity of 93% in a training cohort of 464 samples. The signature was validated in an independent clinical cohort of 437 samples, with a sensitivity of 90% and specificity of 91%. The performance, objectivity, reliability and minimal tissue requirements of this test suggest that it could have clinical application as an adjunct to histopathology in the diagnosis of melanocytic neoplasms. © 2015 The Authors. Journal of Cutaneous Pathology published by John Wiley & Sons Ltd.

  7. Immunohistochemical Analysis of PD-L1 Expression in Canine Malignant Cancers and PD-1 Expression on Lymphocytes in Canine Oral Melanoma.

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    Naoya Maekawa

    Full Text Available Spontaneous cancers are common diseases in dogs. Among these, some malignant cancers such as oral melanoma, osteosarcoma, hemangiosarcoma, and mast cell tumor are often recognized as clinical problems because, despite their high frequencies, current treatments for these cancers may not always achieve satisfying outcomes. The absence of effective systemic therapies against these cancers leads researchers to investigate novel therapeutic modalities, including immunotherapy. Programmed death 1 (PD-1 is a costimulatory receptor with immunosuppressive function. When it binds its ligands, PD-ligand 1 (PD-L1 or PD-L2, PD-1 on T cells negatively regulates activating signals from the T cell receptor, resulting in the inhibition of the effector function of cytotoxic T lymphocytes. Aberrant PD-L1 expression has been reported in many human cancers and is considered an immune escape mechanism for cancers. In clinical trials, anti-PD-1 or anti-PD-L1 antibodies induced tumor regression for several malignancies, including advanced melanoma, non-small cell lung carcinoma, and renal cell carcinoma. In this study, to assess the potential of the PD-1/PD-L1 axis as a novel therapeutic target for canine cancer immunotherapy, immunohistochemical analysis of PD-L1 expression in various malignant cancers of dogs was performed. Here, we show that dog oral melanoma, osteosarcoma, hemangiosarcoma, mast cell tumor, mammary adenocarcinoma, and prostate adenocarcinoma expressed PD-L1, whereas some other types of cancer did not. In addition, PD-1 was highly expressed on tumor-infiltrating lymphocytes obtained from oral melanoma, showing that lymphocytes in this cancer type might have been functionally exhausted. These results strongly encourage the clinical application of PD-1/PD-L1 inhibitors as novel therapeutic agents against these cancers in dogs.

  8. In vivo skin fluorescence imaging in young Caucasian adults with early malignant melanomas

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    Piérard GE

    2014-08-01

    Full Text Available Gérald E Piérard,1 Trinh Hermanns-Lê,2 Sébastien L Piérard,3 Lucas Dewalque,4 Corinne Charlier,4 Claudine Piérard-Franchimont,2 Philippe Delvenne2 1Laboratory of Skin Bioengineering and Imaging (LABIC, Department of Clinical Sciences, Liège University, 2Department of Dermatopathology, Unilab Lg, University Hospital of Liège, 3INTELSIG Laboratory, Montefiore Institute, University of Liège, 4Department of Clinical, Forensic and Environmental Toxicology, University Hospital of Liège, Liège, Belgium Background: Human cutaneous malignant melanoma (CMM is an aggressive cancer showing a dramatic worldwide increase in incidence over the past few decades. The most prominent relative epidemiological increase has been disclosed in young women. The aim of the study was to assess the effects of chronic sun exposures in order to rate the extend of melanocytic stimulations in the vicinity of CMM. Methods: The study was designed to evaluate the melanin distribution and density using ultraviolet light illumination. The present study was performed on surgical excision specimens of thin CMM lesion removed from the upper limbs of 55 Caucasian adults (37 women and 18 men. Two control groups comprised 23 men and 21 women of similar ages who had medium-size congenital melanocytic nevi, also present on the upper limbs. The peritumoral skin was scrutinized using a Visioscan® VC98 device, revealing the faint mosaic melanoderma (FMM pattern that grossly indicates early signs of chronic photodamage in epidermal melanin units. Results: The median extent of relative FMM was significantly higher in the CMM male group. By contrast, the CMM female group showed a reverse bimodal distribution in FMM size. Only 12/37 (32.5% of the CMM female group had an increased FMM size, whereas 25/37 (67.5% of females with CMM had a global FMM extent in the normal range, relative to the controls. Conclusion: Thin CMM supervening in young women appear unrelated to repeat

  9. MicroRNA-365 inhibits growth, invasion and metastasis of malignant melanoma by targeting NRP1 expression.

    Science.gov (United States)

    Bai, Juanjuan; Zhang, Zhongling; Li, Xing; Liu, Huifan

    2015-01-01

    The role of miR-365 in cancer cells seemed controversial in previous studies. We thereby in this article aimed to define the role of miR-365 in malignant melanoma (MM) pathogenesis. We detected miR-365 expression in malignant melanoma cell lines and then investigated the effects of miR-365 on the metastasis and malignancy of melanoma cells. The correlation between miR-365 level and NRP1 (neuropilin1) was further investigated in clinical malignant melanoma specimens. MiR-365 was strongly down-regulated in malignant melanoma (MM) tissues and cell lines, and its expression levels were associated with lymph node metastasis and clinical stage, as well as overall survival and replase-free survival of MM. We also found that ectopic expression of miR-365 inhibited MM cell proliferation and MM metastasis in vitro and in vivo. We further identified a novel mechanism of miR-365 to suppress MM growth and metastasis. NRP1 was proved to be a direct target of miR-365, using luciferase assay and western blot. NRP1 over-expression in miR-365 expressing cells could rescue invasion and growth defects of miR-365. In addition, miR-365 expression inversely correlated with NRP1 protein levels in MM. Our data suggest that miR-365 functions as a tumor suppressor in MM development and progression, and holds promise as a prognostic biomarker and potential therapeutic target for MM.

  10. Head and neck mucosal malignant melanoma: clinicopathologic correlation with contemporary review of prognostic indicators.

    Science.gov (United States)

    Kerr, Elizabeth H; Hameed, Omar; Lewis, James S; Bartolucci, Alfred A; Wang, Dezhi; Said-Al-Naief, Nasser

    2012-02-01

    Unlike their cutaneous counterparts, head and neck mucosal malignant melanomas (HNMM) behave much more aggressively and their prognostic markers have not been fully elucidated. Therefore, the aim of this study was to review the clinicopathologic features of a contemporary series of primary HNMM, retrieved from archival material of 2 large medical centers, and to explore the association, if any, between these variables, the clinical features, and outcomes. The clinicopathologic, radiographic, and follow-up information as well as the dominant histologic pattern, mitotic rate, presence/absence of pigmentation, necrosis, ulceration, vascular invasion, and host-associated lymphocytic response were retrieved and recorded. Twenty cases were identified including 1 melanoma in situ. Eight-five percent of tumors arose in the sinonasal tract and 3 (15%) in the oral cavity. After a median follow-up of 25 months, all patients with invasive melanoma developed recurrence and/or metastasis. Local recurrences occurred in 82% of the patients after a median of 12 months, and distant metastasis occurred in 71% of the patients after a median of 13 months. Of those with adequate follow-up, 82% died with disease, and the remaining 3 had recurrent or metastatic disease. Fourth-seven percent of tumors were pigmented, 89% showed at least focal necrosis, and 93% demonstrated ulceration. Sixth-eight percent showed vascular invasion and 63% had a brisk host lymphocytic response. Mitotic rates ranged from 2 to 60/10 high-power fields. The absence of an invasive component might be associated with a better prognosis but other clinical and pathological features that predict outcome, and/or could influence therapy, remain to be determined in HNMM.

  11. Molecular pathogenesis of malignant melanoma: a different perspective from the studies of melanocytic nevus and acral melanoma.

    Science.gov (United States)

    Takata, Minoru; Murata, Hiroshi; Saida, Toshiaki

    2010-02-01

    The Clark model for melanoma progression emphasizes a series of histopathological changes beginning from benign melanocytic nevus to melanoma via dysplastic nevus. Several models of the genetic basis of melanoma development and progression are based on this Clark's multi-step model, and predict that the acquisition of a BRAF mutation can be a founder event in melanocytic neoplasia. However, our recent investigations have challenged this view, showing the polyclonality of BRAF mutations in melanocytic nevi. Furthermore, it is suggested that many melanomas, including acral and mucosal melanomas, arise de novo, not from melanocytic nevus. While mutations of the BRAF gene are frequent in melanomas on non-chronic sun damaged skin which are prevalent in Caucasians, acral and mucosal melanomas harbor mutations of the KIT gene as well as the amplifications of cyclin D1 or cyclin-dependent kinase 4 gene. Amplifications of the cyclin D1 gene are detected in normal-looking 'field melanocytes', which represent a latent progression phase of acral melanoma that precedes the stage of atypical melanocyte proliferation in the epidermis. Based on these observations, we propose an alternative genetic progression model for melanoma.

  12. Clinical presentation, histology, and prognoses of malignant melanoma in ethnic Chinese: A study of 522 consecutive cases

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    Han Mei

    2011-02-01

    Full Text Available Abstract Background Malignant melanoma is a rare disease in Asia, and knowledge on its characteristics and clinical outcome in Asian patients is limited. The purpose of this observational study was to determine the clinical presentation and outcome of patients with melanoma in China. Methods A database was prospectively established for the purpose of this analysis. The elements of the database included basic demographic data of patients and prognosticators previously reported in literature, as well as follow-up data including clinical outcome after treatment. Medical record of all patients with pathologically diagnosed malignant melanoma consulted in our center since 2006 were retrieved and reviewed. No patient was excluded in this study. Statistical analyses including survival and multivariate analyses of factors associated with survival were respectively performed by Kaplan-Meier method and Cox proportional hazard model. Results A total of 522 consecutive and nonselected cases were evaluated. There were 218 cases (41.8% of acral lentiginous melanoma (ALM, 118 (22.6% of mucosal melanoma (MCM, 103 (19.7% of nodular melanoma (NM, 33 (6.3% of superficial spreading melanoma (SSM, and others were Lentigo maligna melanoma or unclassifiable disease. The proportion of patients with clinical stage I, II, III, and IV diseases were 6.1%, 55.9%, 25.1%, and 12.8%, respectively. Among the 357 cases of cutaneous melanoma, 234 patients (65.5% had ulceration. The 5-year overall survival rate of all 522 patients was 41.6%, and the median survival time was 3.92 years (95% CI, 3.282 to 4.558. Five-year survival rates of patients with stage I, II, III, and IV diseases were 94.1%, 44.0%, 38.4% and 4.6% respectively (P Conclusions Prognoses of patients with malignant melanoma diagnosed in China were suboptimal, and most patients were diagnosed with locally advanced disease (i.e., stage II or above. ALM and MCM are the two most commonly diagnosed pathological subtypes

  13. Coexisting Malignant Melanoma and Blue Nevus of the Uterine Cervix: An Unusual Combination

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    David Parada

    2012-01-01

    Full Text Available Malignant melanoma (MM and blue nevi of the uterine cervix are an extremely rare neoplasm, probably derived from embryologic migration of melanocytes from the neural crest. MM displays aggressive behavior with a poor prognosis. We report the case of a 76-year-old postmenopausal woman abnormal vaginal bleeding. She underwent a hysterectomy and bilateral salpingo-oophorectomy with paraaortic-iliac lymphadenectomy. Histopathological and immunohistochemical studies were consistent with the diagnosis of MM and blue nevi in the uterine cervix. Although it is extremely rare, this case suggests that MM of the uterine cervix should be considered in the differential diagnosis of undifferentiated neoplasm. Early diagnosis is essential in order to warrant a better prognosis, although there are no cases of cure described.

  14. The burden of occupationally-related cutaneous malignant melanoma in Britain due to solar radiation.

    Science.gov (United States)

    Rushton, Lesley; J Hutchings, Sally

    2017-02-14

    Increasing evidence highlights the association of occupational exposure and cutaneous malignant melanoma (CMM). We estimated the burden of CMM and total skin cancer burden in Britain due to occupational solar radiation exposure. Attributable fractions (AF) and numbers were estimated for CMM mortality and incidence using risk estimates from the published literature and national data sources for proportions exposed. We extended existing methods to account for the exposed population age structure. The estimated total AF for CMM is 2.0% (95% CI: 1.4-2.7%), giving 48 (95% CI: 33-64) deaths in (2012) and 241 (95% CI: 168-325) registrations (in 2011) attributable to occupational exposure to solar radiation. Higher exposure and larger numbers exposed led to much higher numbers for men than women. Industries of concern are construction, agriculture, public administration and defence, and land transport. These results emphasise the urgent need to develop appropriate strategies to reduce this burden.

  15. Molecular pathology of malignant melanoma: changing the clinical practice paradigm toward a personalized approach.

    Science.gov (United States)

    Bradish, Joshua R; Cheng, Liang

    2014-07-01

    Melanocytic proliferations are notoriously difficult lesions to evaluate histologically, even among experts, as there is a lack of objective, highly reproducible criteria, which can be broadly applied to the wide range of melanocytic lesions encountered in daily practice. These difficult diagnoses are undeniably further compounded by the substantial medicolegal risks of an "erroneous" diagnosis. Molecular information and classification of melanocytic lesions is already vast and constantly expanding. The application of molecular techniques for the diagnosis of benignity or malignancy is, at times, confusing and limits its utility if not used properly. In addition, current and future therapies will necessitate molecular classification of melanoma into one of several distinct subtypes for appropriate patient-specific therapy. An understanding of what different molecular markers can and cannot predict is of the utmost importance. We discuss both mutational analysis and chromosomal gains/losses to help clarify this continually developing and confusing facet of pathology. Copyright © 2014 Elsevier Inc. All rights reserved.

  16. A 3-Year Follow-up of Sun Behavior in Patients With Cutaneous Malignant Melanoma

    DEFF Research Database (Denmark)

    Idorn, Luise Winkel; Datta, Pameli; Heydenreich, Jakob

    2014-01-01

    IMPORTANCE UV radiation (UVR) exposure is the primary environmental risk factor for developing cutaneous malignant melanoma (CMM). OBJECTIVE To measure changes in sun behavior from the first until the third summer after the diagnosis of CMM using matched controls as a reference. DESIGN, SETTING...... skin type participated in the study. Exposure to UVR was assessed the first and second summers (n = 20) and the first and third summers (n = 22) after diagnosis. Data from 40 participants were analyzed. MAIN OUTCOMES AND MEASURES Exposure to UVR was assessed by personal electronic UVR dosimeters...... that measured time-related UVR in standard erythema dose (SED) and corresponding sun diaries (mean, 74 days per participant each participation year). RESULTS Patients' daily UVR dose and UVR dose in connection with various behaviors increased during follow-up (quantified as an increase in daily UVR dose each...

  17. Primary malignant melanoma of the uterine cervix treated with ultraradical surgery: a case report.

    Science.gov (United States)

    Calderón-Salazar, Luz; Cantú de Leon, David; Perez Montiel, Delia; Almogabar-Villagrán, Erika; Villavicencio, Verónica; Cetina, Lucely

    2011-01-01

    Primary melanomas of the uterine cervix are rare tumors with no more than 60 cases reported in the world literature. Poor prognosis is considered for the neoplasia itself as well as for diagnostic tardiness. There is no standard treatment; however, radical surgery is the treatment cornerstone. Our aim was to present the case of a 34-year-old woman with a primary malignant melanoma in the uterine cervix with affectation of the posterior face of the vagina without metastasis. Total infraelevator pelvic exenteration and adjuvant radiotherapy was performed. The patient was under surveillance for 8 years of followup without evidence of local or distant disease. The majority of case reports found suggests radical hysterectomy as the treatment indicated for these patients. Notwithstanding this, survival is very short when patients are treated in this manner. Based on our results and on those reported in the literature, we propose initial treatment with total pelvic exenteration as optimal management for this neoplasia in its initial form.

  18. Clinical genetic aspects of cutaneous malignant melanoma: I. Prevalence, familial study, genetic heterogeneity

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    Gar`kavtseva, R.F.; Sitnikova, T.S.; Kazubskaya, T.P. [Institute of Clinical Oncology, Moscow (Russian Federation)] [and others

    1995-11-01

    Epidemiological and clinical genetic data on cutaneous malignant melanoma (CMM) are presented. CMM morbidity in Moscow from 1983 to 1987 was analyzed. Cumulative incidence (cumulative risk) of CMM was calculated for various life periods on the basis of estimates for various age groups, which were used as population frequencies. By the age of 85, these frequencies were 0.35% for males and 0.38% for females. Among relatives of patients, the incidence of CMM was 1.420{plus_minus}0.498% for males and 1. 110{plus_minus} 0.348% for females; i.e., it exceeded the population frequency by a factor of 3 or 4. As a whole, the familial frequency of cancer was equal to 13.3% for male probands and 14.2% for female probands, i.e., more than three times higher than the population frequency. The data obtained formed the basis for the development of CMM classification. Hereditary and nonhereditary variants of cutaneous melanoma were identified. Familial cases and CMM that occurred against the background of inherited diseases or syndromes were classified as hereditary variants of CMM; taken together, they accounted for 38.8%. The data provided grounds for identification of families at increased risk for the development of CMM. 10 refs., 2 tabs.

  19. Synchronously diagnosed lymph nodal collision tumor of malignant melanoma and chonic lymphocytic leukemia/small lymphocytic lymphoma: case report

    Directory of Open Access Journals (Sweden)

    Sur Monalisa

    2007-08-01

    Full Text Available Abstract Synchronous composite tumors have been described but are uncommon. Moreover, simultaneous occurrence of synchronous tumors in the same tissue or organ is even less common. We report a case of chronic lymphocytic leukemia (CLL/small lymphocytic lymphoma and malignant melanoma (MM occurring synchronously in the same lymph node. Several cases of an association between cutaneous malignancies and lymphoproliferative disorders have been reported. Some of which included CLL and MM, occurring in the same patient often CLL after MM. The risk of having CLL after MM has been reported to be increased. Various genetic and environmental etiologies have been postulated, but have as yet not been proven. To our knowledge this is the first time that synchronous occurrence of these two malignant processes in the same tissue is described. In this case it is important that the melanoma was recognized in the excised lymph node, as this finding had much more critical treatment and long term survival consequences.

  20. Merlin is a negative regulator of human melanoma growth.

    Science.gov (United States)

    Murray, Lucas B; Lau, Ying-Ka Ingar; Yu, Qin

    2012-01-01

    Merlin is encoded by the neurofibromatosis type 2 (NF2) gene and is a member of the Band 4.1 protein family. This protein acts as a linker that connects cell surface proteins to the actin cytoskeleton. Defects caused by mutations of the NF2 gene give rise to NF2 disease, which is generally characterized by the formation of bilateral vestibular schwannomas and, to a lesser extent, meningiomas and ependymomas. In addition to these tumor types, NF2 is mutated and/or merlin expression is reduced or lost in numerous non-NF2 associated tumors, including melanoma. However, the role of merlin in human melanoma growth and the mechanism underlying its effect are currently unknown. In the present study, we show that merlin knockdown enhances melanoma cell proliferation, migration, and invasion in vitro and that decreased merlin expression promotes subcutaneous melanoma growth in immunocompromised mice. Concordantly, we find that increased expression of merlin in a metastatic melanoma cell line reduced their in vitro migration and proliferation, and diminished their ability to grow in an anchorage independent manner. Increased merlin expression also inhibits in vivo growth of these melanoma cells. Lastly, we demonstrate that higher merlin levels in human melanoma cells promote the H(2)O(2)-induced activation of MST1/2 Ser/Thr kinases, which are known tumor suppressors in the Hippo signaling pathway. Taken together, these results provide for the first time evidence that merlin negatively regulates human melanoma growth, and that loss of merlin, or impaired merlin function, results in an opposite effect. In addition, we show that increased merlin expression leads to enhanced activation of the MTS1/2 kinases, implying the potential roles of MST1/2 in mediating the anti-melanoma effects of merlin.

  1. Melanin content of hamster tissues, human tissues, and various melanomas

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    Watts, K.P.; Fairchild, R.G.; Slatkin, D.N.; Greenberg, D.; Packer, S.; Atkins, H.L.; Hannon, S.J.

    1981-02-01

    Melanin content (percentage by weight) was determined in both pigmented and nonpigmented tissues of Syrian golden hamsters bearing Greene melanoma. Melanin content was also measured in various other melanoma models (B-16 in C57 mice, Harding-Passey in BALB/c mice, and KHDD in C3H mice) and in nine human melanomas, as well as in selected normal tissues. The purpose was to evaluate the possible efficacy of chlorpromazine, which is known to bind to melanin, as a vehicle for boron transport in neutron capture therapy. Successful therapy would depend upon selective uptake and absolute concentration of borated compounds in tumors; these parameters will in turn depend upon melanin concentration in melanomas and nonpigmented ''background'' tissues. Hamster whole eyes, hamster melanomas, and other well-pigmented animal melanomas were found to contain 0.3 to 0.8% melanin by weight, whereas human melanomas varied from 0.1 to 0.9% (average, 0.35%). Other tissues, with the exception of skin, were lower in content by a factor of greater than or equal to30. Melanin pigment was extracted from tissues, and the melanin content was determined spectrophotometrically. Measurements were found to be sensitive to the presence of other proteins. Previous procedures for isolating and quantifying melanin often neglected the importance of removing proteins and other interfering nonmelanic substances.

  2. Theranostic Properties of a Survivin-Directed Molecular Beacon in Human Melanoma Cells

    Science.gov (United States)

    Carpi, Sara; Fogli, Stefano; Giannetti, Ambra; Adinolfi, Barbara; Tombelli, Sara; Da Pozzo, Eleonora; Vanni, Alessia; Martinotti, Enrica; Martini, Claudia; Breschi, Maria Cristina; Pellegrino, Mario

    2014-01-01

    Survivin is an inhibitor of apoptosis overexpressed in different types of tumors and undetectable in most terminally differentiated normal tissues. In the current study, we sought to evaluate the in vitro theranostic properties of a molecular beacon-oligodeoxynucleotide (MB) that targets survivin mRNA. We used laser scanning confocal microscopy to study MB delivery in living cells and real-time PCR and western blot to assess selective survivin-targeting in human malignant melanoma cells. We further assess the pro-apoptotic effect of MB by measuring internucleosomal DNA fragmentation, dissipation of mitochondrial membrane potential (MMP) and changes in nuclear morphology. Transfection of MB into A375 and 501 Mel cells generated high signal intensity from the cytoplasm, while no signal was detected in the extracellular environment and in survivin-negative cells (i.e., human melanocytes and monocytes). MB time dependently decreased survivin mRNA and protein expression in melanoma cells with the maximum effect reached at 72 h. Treatment of melanoma cells with MB induced apoptosis by significant changes in MMP, accumulation of histone-complexed DNA fragments in the cytoplasm and nuclear condensation. MB also enhanced the pro-apoptotic effect of standard chemotherapeutic drugs tested at clinically relevant concentrations. The MB tested in the current study conjugates the ability of imaging with the pharmacological silencing activity against survivin mRNA in human melanoma cells and may represent an innovative approach for cancer diagnosis and treatment. PMID:25501971

  3. Theranostic properties of a survivin-directed molecular beacon in human melanoma cells.

    Directory of Open Access Journals (Sweden)

    Sara Carpi

    Full Text Available Survivin is an inhibitor of apoptosis overexpressed in different types of tumors and undetectable in most terminally differentiated normal tissues. In the current study, we sought to evaluate the in vitro theranostic properties of a molecular beacon-oligodeoxynucleotide (MB that targets survivin mRNA. We used laser scanning confocal microscopy to study MB delivery in living cells and real-time PCR and western blot to assess selective survivin-targeting in human malignant melanoma cells. We further assess the pro-apoptotic effect of MB by measuring internucleosomal DNA fragmentation, dissipation of mitochondrial membrane potential (MMP and changes in nuclear morphology. Transfection of MB into A375 and 501 Mel cells generated high signal intensity from the cytoplasm, while no signal was detected in the extracellular environment and in survivin-negative cells (i.e., human melanocytes and monocytes. MB time dependently decreased survivin mRNA and protein expression in melanoma cells with the maximum effect reached at 72 h. Treatment of melanoma cells with MB induced apoptosis by significant changes in MMP, accumulation of histone-complexed DNA fragments in the cytoplasm and nuclear condensation. MB also enhanced the pro-apoptotic effect of standard chemotherapeutic drugs tested at clinically relevant concentrations. The MB tested in the current study conjugates the ability of imaging with the pharmacological silencing activity against survivin mRNA in human melanoma cells and may represent an innovative approach for cancer diagnosis and treatment.

  4. Incidence of different histologic types of malignant melanoma during the 1996-2006 period in the zenica area

    Directory of Open Access Journals (Sweden)

    I. Drljević

    2007-08-01

    Full Text Available The number of skin malign neoplasms is constantly increasing. Malignant melanoma has shown the greatest increase in its incidence. A retrospective and prospective, descriptive, targeted, controlled and open study covered the period from 1996-2006 and included all the patients with malignant melanoma verified and histologically confirmed by the Department for Pathological Anatomy and Histology of the Cantonal Hospital in Zenica. During the 1996-2006 period 99 melanoma have been detected. MM was found with equal frequency in males and females (p< 0,05. The most frequent clinical and histological type of melanoma was a nodular one found in 71,72% cases. The most frequent anatomic site of MM appearance was trunk in both sexes. The number of diagnosed MM increased with age and reached its peak in the 40-49 age group. The highest incidence was noted in Zenica which was 0.093 in 1998 to 0.201 in 2005 per 1,000 inhabitants. The results indicate the need for active prevention and educational programs in this population.

  5. Use of fluorine-18 fluorodeoxyglucose positron emission tomography in the detection of silent metastases from malignant melanoma

    DEFF Research Database (Denmark)

    Jakobsen, Annika Loft; Andersson, A P; Dahlstrøm, K

    2000-01-01

    Correct staging is crucial for the management and prognosis of patients with malignant melanoma. The aim of this prospective study was to compare staging by whole-body positron emission tomography using fluorine-18 fluorodeoxyglucose (18F-FDG) with staging by conventional methods. Thirty-eight pa...... method superior to conventional methods for detecting widespread metastases from malignant melanoma. Mutilating surgery of no benefit can thereby be avoided. 18F-FDG PET is useful as a supplement to clinical examination in melanoma staging.......-eight patients with malignant melanoma of clinical stage II (local recurrence, in-transit and regional lymph node metastases) or III (metastases to other sites than in stage II) were included in the study. The results of the PET scans were compared with those obtained by clinical examination, computed tomography......, ultrasound, radiography, and liver function tests and histology or clinical follow-up. With 18F-FDG PET we found for all foci a sensitivity of 97% and a specificity of 56%, compared with 62% and 22%, respectively, when using routine methods. For intra-abdominal foci, the sensitivity and specificity were 100...

  6. Collagen XVII is expressed in malignant but not in benign melanocytic tumors and it can mediate antibody induced melanoma apoptosis.

    Science.gov (United States)

    Krenacs, T; Kiszner, G; Stelkovics, E; Balla, P; Teleki, I; Nemeth, I; Varga, E; Korom, I; Barbai, T; Plotar, V; Timar, J; Raso, E

    2012-10-01

    The 180 kDa transmembrane collagen XVII is known to anchor undifferentiated keratinocytes to the basement membrane in hemidesmosomes while constitutively shedding a 120 kDa ectodomain. Inherited mutations or auto-antibodies targeting collagen XVII cause blistering skin disease. Collagen XVII is down-regulated in mature keratinocytes but re-expressed in skin cancer. By recently detecting collagen XVII in melanocyte hyperplasia, here we tested its expression in benign and malignant melanocytic tumors using endodomain and ectodomain selective antibodies. We found the full-length collagen XVII protein in proliferating tissue melanocytes, basal keratinocytes and squamous cell carcinoma whereas resting melanocytes were negative. Furthermore, the cell-residual 60 kDa endodomain was exclusively detected in 62/79 primary and 15/18 metastatic melanomas, 8/9 melanoma cell lines, HT199 metastatic melanoma xenografts and atypical nests in 8/63 dysplastic nevi. The rest of 19 nevi including common, blue and Spitz subtypes were also negative. In line with the defective ectodomain, sequencing of COL17A1 gene revealed aberrations in the ectodomain coding region including point mutations. Collagen XVII immunoreaction-stained spindle cell melanomas, showed partly overlapping profiles with those of S100B, Melan A and HMB45. It was concentrated at vertical melanoma fronts and statistically associated with invasive phenotype. Antibody targeting the extracellular aa507-529 terminus of collagen XVII endodomain promoted apoptosis and cell adhesion, while inhibiting proliferation in HT199 cells. These results suggest that the accumulation of collagen XVII endodomain in melanocytic tumors is associated with malignant transformation to be a potential marker of malignancy and a target for antibody-induced melanoma apoptosis.

  7. Checkpoint inhibitors for malignant melanoma: a systematic review and meta-analysis

    Directory of Open Access Journals (Sweden)

    Karlsson AK

    2017-08-01

    Full Text Available Adam K Karlsson,1 Sohag N Saleh2 1Faculty of Medicine, Imperial College London, 2Faculty of Medicine, Hammersmith Hospital, Imperial College London, London, UK Background and objectives: Rates of malignant melanoma are continuing to increase, and until recently effective treatments were lacking. However, since 2011 three immunotherapeutic agents, known as checkpoint inhibitors, have been approved. This review aims to establish whether these three drugs – ipilimumab, nivolumab, and pembrolizumab – offer greater efficacy and tolerability compared to control interventions (placebo, immunotherapy, or chemotherapy in patients with stage III or IV unresectable cutaneous melanoma. Materials and methods: A search on four major medical and scientific databases yielded 7,553 records, of which seven met the inclusion criteria, with a total study population of 3,628. Only prospective Phase II or III randomized controlled trials on checkpoint inhibitors for patients with unresectable cutaneous melanoma that reported data on survival (overall or progression-free, tumor response, or adverse events were included. Three meta-analyses were carried out. Results: The hazard ratio for progression or death was 0.54 (95% confidence interval [CI]: 0.44–0.67, and the odds ratio for best overall response rate was 4.48 (95% CI: 2.77–7.24, both in favor of checkpoint inhibitors. However, control treatments were associated with an insignificantly lower rate of discontinuation of treatment due to adverse effects or treatment-related adverse events (odds ratio =1.63 [95% CI: 0.55–4.88]. Conclusion: This study finds that checkpoint inhibitors are more effective than control interventions, both in terms of survival and tumor response, and yet no less tolerable. PD1 therapies (nivolumab and pembrolizumab appear to offer greater efficacy than CTLA4 therapy (ipilimumab. The combination of nivolumab and ipilimumab was, however, the most effective, but significantly less

  8. IgG1-iS18 impedes the adhesive and invasive potential of early and late stage malignant melanoma cells.

    Science.gov (United States)

    Munien, Carmelle; Rebelo, Thalia M; Ferreira, Eloise; Weiss, Stefan F T

    2017-02-15

    The 37kDa/67kDa laminin receptor (LRP/LR) is a non-integrin laminin receptor which is overexpressed in tumorigenic cells and supports progression of cancer via promoting metastasis, angiogenesis and telomerase activity and impediment of apoptosis. The present study investigates the role of LRP/LR on the metastatic potential of early (A375) and late (A375SM) stage malignant melanoma cells. Flow cytometry revealed that both early and late stage malignant melanoma cells display high levels of LRP/LR on their cell surface. Flow cytometry and western blot analysis showed that late stage malignant melanoma cells display significantly higher total and cell surface LRP/LR levels in comparison to early stage malignant melanoma cells and the poorly invasive breast cancer (MCF-7) control cell line. Targeting LRP/LR using the LRP/LR specific antibody IgG1-iS18 resulted in a significant reduction of the adhesive potential to laminin-1 and the invasive potential through the 'ECM-simulating' Matrigel™ of both early and late stage malignant melanoma cells. Furthermore, Pearson's correlation coefficient confirmed that increased LRP levels correlate with the increased invasive and adhesive potential in early and late stage melanoma cells. Thus, blocking LRP/LR using the IgG1-iS18 antibody may therefore be a promising therapeutic strategy for early and late stage malignant melanoma treatment. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Resilience in patients and spouses faced with malignant melanoma. A qualitative longitudinal study.

    Science.gov (United States)

    Engeli, L; Moergeli, H; Binder, M; Drabe, N; Meier, C; Buechi, S; Dummer, R; Jenewein, J

    2016-01-01

    Life-threatening diseases like malignant tumours are associated with considerable existential distress. Little is known about the factors that promote resilience within these individuals. This longitudinal qualitative partner study aimed to analyse resilience as per Antonovsky's sense of coherence. Eight patients with malignant melanoma and their partners were interviewed. They were asked about their coping strategies, attitudes towards the meaning of life and their cancer, and comprehension of what is happening to them. The questions were asked shortly after their diagnosis was made and 6 months later. All interviews were audio-taped and later transcribed and analysed according to the method of qualitative content analysis described by P. Mayring. At baseline, the majority of statements made (261; patients = 141/spouses = 120) related to coping/manageability of disease, with only 26 statements (patients = 15/spouses = 11) related to meaning and 127 (patients = 64/spouses = 63) to comprehension. There were no significant differences between the responses of patients and their partners and no significant changes in the number of statements during the 6-month interview. The most significant theme that emerged was manageability of disease, with distraction the most commonly utilised coping skill. The comprehension and meaning themes were far less prevalent. Hence, support should focus on disease and situational manageability. © 2014 John Wiley & Sons Ltd.

  10. Dermoscopic clues in the diagnosis of amelanotic and hypomelanotic malignant melanoma Pistas dermatoscópicas no diagnóstico de melanoma maligno amelanótico e hipomelanótico

    Directory of Open Access Journals (Sweden)

    Raquel Bissacotti Steglich

    2012-12-01

    Full Text Available The clinical identification of amelanotic malignant melanoma (AMM and hypomelanotic malignant melanoma (HMM becomes difficult due to the lack of pigmentation and to the diverse clinical presentations. Dermoscopy is very useful in these cases, increasing the level of suspicion of malignancy. We report 4 cases of amelanotic malignant melanoma and hypomelanotic malignant melanoma with characteristic dermoscopic findings. Dermoscopy under polarized light demonstrates vascular polymorphism, globules and milky-red areas, in addition to chrysalis and multiple blue-gray dots.A identificação clínica de melanoma maligno amelanótico e hipomelanótico torna-se difícil devido à falta de pigmentação e às diversas apresentações desse tipo de tumor. A dermatoscopia é muito útil nestes casos, aumentando o grau de suspeição de malignidade. Relatamos 4 casos de melanoma maligno amelanótico e melanoma maligno hipomelanótico com achados dermatoscópicos característicos. A dermatoscopia com luz polarizada demonstra polimorfismo vascular, glóbulos e áreas vermelholeitosas, assim como crisálides e múltiplos pontos azul-acinzentados.

  11. The Inhibitory Activity of Luzonicosides from the Starfish Echinaster luzonicus against Human Melanoma Cells

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    Olesya S. Malyarenko

    2017-07-01

    Full Text Available Malignant melanoma is the most dangerous form of skin cancer, with a rapidly increasing incidence rate. Despite recent advances in melanoma research following the approval of several novel targeted and immuno-therapies, the majority of oncological patients will ultimately perish from the disease. Thus, new effective drugs are still required. Starfish steroid glycosides possess different biological activities, including antitumor activity. The current study focused on the determination of the in vitro inhibitory activity and the mechanism of action of cyclic steroid glycosides isolated from the starfish Echinaster luzonicus—luzonicoside A (LuzA and luzonicoside D (LuzD—in human melanoma RPMI-7951 and SK-Mel-28 cell lines. LuzA inhibited proliferation, the formation of colonies, and the migration of SK-Mel-28 cells significantly more than LuzD. Anti-cancer activity has been ascribed to cell cycle regulation and apoptosis induction. The molecular mechanism of action appears to be related to the regulation of the activity of cleaved caspase-3 and poly(ADP-ribose polymerase (PARP, along with Survivin, Bcl-2, p21 and cyclin D1 level. Overall, our findings support a potential anti-cancer efficacy of luzonicosides A and D on human melanoma cells.

  12. Diagnostic Distinction of Malignant Melanoma and Benign Nevi by a Gene Expression Signature and Correlation to Clinical Outcomes.

    Science.gov (United States)

    Ko, Jennifer S; Matharoo-Ball, Balwir; Billings, Steven D; Thomson, Brian J; Tang, Jean Y; Sarin, Kavita Y; Cai, Emily; Kim, Jinah; Rock, Colleen; Kimbrell, Hillary Z; Flake, Darl D; Warf, M Bryan; Nelson, Jonathan; Davis, Thaylon; Miller, Catherine; Rushton, Kristen; Hartman, Anne-Renee; Wenstrup, Richard J; Clarke, Loren E

    2017-07-01

    Background: Histopathologic examination alone can be inadequate for diagnosis of certain melanocytic neoplasms. Recently, a 23-gene expression signature was clinically validated as an ancillary diagnostic test to differentiate benign nevi from melanoma. The current study assessed the performance of this test in an independent cohort of melanocytic lesions against clinically proven outcomes.Methods: Archival tissue from primary cutaneous melanomas and melanocytic nevi was obtained from four independent institutions and tested with the gene signature. Cases were selected according to pre-defined clinical outcome measures. Malignant lesions were defined as stage I-III primary cutaneous melanomas that produced distant metastases (metastatic to sites other than proximal sentinel lymph node(s)) following diagnosis of the primary lesion. Melanomas that were metastatic at the time of diagnosis, all re-excisions, and lesions with Benign lesions were defined as cutaneous melanocytic lesions with no adverse long-term events reported.Results: Of 239 submitted samples, 182 met inclusion criteria and produced a valid gene expression result. This included 99 primary cutaneous melanomas with proven distant metastases and 83 melanocytic nevi. Median time to melanoma metastasis was 18 months. Median follow-up time for nevi was 74.9 months. The gene expression score differentiated melanoma from nevi with a sensitivity of 93.8% and a specificity of 96.2%.Conclusions: The results of gene expression testing closely correlate with long-term clinical outcomes of patients with melanocytic neoplasms.Impact: Collectively, this provides strong evidence that the gene signature adds valuable adjunctive information to aid in the accurate diagnosis of melanoma. Cancer Epidemiol Biomarkers Prev; 26(7); 1107-13. ©2017 AACR. ©2017 American Association for Cancer Research.

  13. Vanillin Suppresses Cell Motility by Inhibiting STAT3-Mediated HIF-1α mRNA Expression in Malignant Melanoma Cells

    Directory of Open Access Journals (Sweden)

    Eun-Ji Park

    2017-03-01

    Full Text Available Recent studies have shown that vanillin has anti-cancer, anti-mutagenic, and anti-metastatic activity; however, the precise molecular mechanism whereby vanillin inhibits metastasis and cancer progression is not fully elucidated. In this study, we examined whether vanillin has anti-cancer and anti-metastatic activities via inhibition of hypoxia-inducible factor-1α (HIF-1α in A2058 and A375 human malignant melanoma cells. Immunoblotting and quantitative real time (RT-PCR analysis revealed that vanillin down-regulates HIF-1α protein accumulation and the transcripts of HIF-1α target genes related to cancer metastasis including fibronectin 1 (FN1, lysyl oxidase-like 2 (LOXL2, and urokinase plasminogen activator receptor (uPAR. It was also found that vanillin significantly suppresses HIF-1α mRNA expression and de novo HIF-1α protein synthesis. To understand the suppressive mechanism of vanillin on HIF-1α expression, chromatin immunoprecipitation was performed. Consequently, it was found that vanillin causes inhibition of promoter occupancy by signal transducer and activator of transcription 3 (STAT3, but not nuclear factor-κB (NF-κB, on HIF1A. Furthermore, an in vitro migration assay revealed that the motility of melanoma cells stimulated by hypoxia was attenuated by vanillin treatment. In conclusion, we demonstrate that vanillin might be a potential anti-metastatic agent that suppresses metastatic gene expression and migration activity under hypoxia via the STAT3-HIF-1α signaling pathway.

  14. DNA level, tumor thickness, and stereological estimates of nuclear volume in stage I cutaneous malignant melanomas. A comparative study with analysis of prognostic impact

    DEFF Research Database (Denmark)

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

    1991-01-01

    The mutual relation and prognostic value of three quantitative variables were investigated in a retrospective series of 56 stage I cutaneous malignant melanomas. Unbiased stereological estimates of nuclear volume, nuclear nu v were obtained along with measurements of melanoma thickness. The DNA i...

  15. [Initial evaluation, diagnosis, staging, treatment, and follow-up of patients with primary cutaneous malignant melanoma. Consensus statement of the Network of Catalan and Balearic Melanoma Centers].

    Science.gov (United States)

    Mangas, C; Paradelo, C; Puig, S; Gallardo, F; Marcoval, J; Azon, A; Bartralot, R; Bel, S; Bigatà, X; Curcó, N; Dalmau, J; del Pozo, L J; Ferrándiz, C; Formigón, M; González, A; Just, M; Llambrich, A; Llistosella, E; Malvehy, J; Martí, R M; Nogués, M E; Pedragosa, R; Rocamora, V; Sàbat, M; Salleras, M

    2010-03-01

    The consensus statement on the management of primary cutaneous melanoma that we present here was based on selection, discussion, review, and comparison of recent literature (including national and international guidelines). The protocols for the diagnosis, treatment, and follow-up used in the hospital centers throughout Catalonia and the Balearic Isles belonging to the Network of Catalan and Balearic Melanoma Centers were also considered. The main objective of this statement was to present the overall management of melanoma patients typically used in our region at the present time. As such, the statement was not designed to be an obligatory protocol for health professionals caring for this group of patients, and neither can it nor should it be used for this purpose. Professionals reading the statement should not therefore consider it binding on their practice, and in no case can this text be used to guarantee or seek responsibility for a given medical opinion. The group of dermatologists who have signed this statement was created 3 years ago with the aim of making our authorities aware of the importance of this complex tumor, which, in comparison with other types of cancer, we believe does not receive sufficient attention in Spain. In addition, the regular meetings of the group have produced interesting proposals for collaboration in various epidemiological, clinical, and basic applied research projects on the subject of malignant melanoma in our society.

  16. Early diagnosis of malignant melanoma: Proposal of a working formulation for the management of cutaneous pigmented lesions from the Melanoma Cooperative Group.

    Science.gov (United States)

    Ascierto, Paolo A; Palmieri, Giuseppe; Botti, Gerardo; Satriano, Rocco A; Stanganelli, Ignazio; Bono, Riccardo; Testori, Alessandro; Bosco, Leonardo; Daponte, Antonio; Caracò, Corrado; Chiofalo, Maria Grazia; Melucci, Maria Teresa; Calignano, Rosario; Tatangelo, Fabiana; Cochran, Alistair J; Castello, Giuseppe

    2003-06-01

    Epiluminescence microscopy (ELM) strongly improves the separation of different types of cutaneous pigmented lesions (CPL) and facilitates the early diagnosis of cutaneous melanoma (CM). ELM alone is not 100% accurate in routine diagnosis, and should not be considered the only criterion in the diagnosis of high-risk skin lesions. We have however, demonstrated close agreement between ELM classification criteria and histology in 2,731 cutaneous lesions. In the past five years, our Melanoma Cooperative Group has evaluated 61,000 skin lesions from 30,000 individuals and identified 478 cutaneous melanomas. Most newly diagnosed patients had very early stage melanoma [299 (62%) were Stage I (203 Stage IA and 96 Stage IB), by the American Joint Committee on Cancer (AJCC) criteria]. We have compared data from the patient histories and clinical evaluations with ELM-based morphological patterns to better characterize skin lesions and minimize interpretative problems. From these comparisons, we propose new guidelines for the management of CPL to provide a standard diagnostic and therapeutic approaches and to foster the early identification of lesions at risk for malignant transformation.

  17. Thymosin beta-10 expression in melanoma cell lines and melanocytic lesions: a new progression marker for human cutaneous melanoma

    NARCIS (Netherlands)

    Weterman, M. A.; van Muijen, G. N.; Ruiter, D. J.; Bloemers, H. P.

    1993-01-01

    When screening a subtraction library for sequences that were specifically expressed in highly metastatic human melanoma cell lines, a cDNA clone was isolated encoding thymosin beta-10. We found that expression of thymosin beta-10 mRNA was associated with metastatic behavior of various human melanoma

  18. A novel function of Junctional Adhesion Molecule-C in mediating melanoma cell metastasis

    Science.gov (United States)

    Langer, Harald F.; Orlova, Valeria V.; Xie, Changping; Kaul, Sunil; Schneider, Darius; Lonsdorf, Anke S.; Fahrleitner, Manuela; Choi, Eun Young; Dutoit, Vanessa; Pellegrini, Manuela; Grossklaus, Sylvia; Nawroth, Peter P.; Baretton, Gustavo; Santoso, Sentot; Hwang, Sam T.; Arnold, Bernd; Chavakis, Triantafyllos

    2011-01-01

    Hematogenous dissemination of melanoma is a life-threatening complication of this malignant tumor. Here, we identified Junctional Adhesion Molecule-C (JAM-C) as a novel player in melanoma metastasis to the lung. JAM-C expression was identified in human and murine melanoma cell lines, in human malignant melanoma, as well as in metastatic melanoma including melanoma lung metastasis. JAM-C expressed on both murine B16 melanoma cells as well as on endothelial cells, promoted the transendothelial migration of the melanoma cells. We generated mice with inactivation of JAM-C. JAM-C−/− mice as well as endothelial-specific JAM-C-deficient mice displayed significantly decreased B16 melanoma cell metastasis to the lung, whereas treatment of mice with soluble JAM-C prevented melanoma lung metastasis. Together, JAM-C represents a novel therapeutic target for melanoma metastasis. PMID:21593193

  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. 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.

  1. Melanose neurocutânea. Relato de caso com melanoma maligno do sistema nervoso central Neurocutaneous melanosis. Case report of a malignant melanoma of the central nervous system

    Directory of Open Access Journals (Sweden)

    J.M. Juang

    1998-03-01

    Full Text Available A melanose neurocutânea é uma síndrome rara caracterizada por nevos melanocíticos congênitos gigantes e excessiva melanose da leptomeninge. A síndrome parece representar um erro na morfogênese do neuroectoderma embrionário. Os autores apresentam o caso e necropsia de um paciente masculino de 19 anos que desenvolveu melanoma maligno do sistema nervoso central.The neurocutaneous melanosis is a rare syndrome in which the congenital melanocytic nevi and excessive melanosis are the main features. The syndrome seems to be a morphogenesis error of the embryonic neuroectoderm. A clinical case with necroscopy in a 19 year-old man who had developed malign melanoma in his central nervous system is reported.

  2. Characterization of melanoma associated spongiform scleropathy

    DEFF Research Database (Denmark)

    Alyahya, Ghassan Ayish Jabur; Heegaard, Steffen; Prause, J.U.

    2002-01-01

    ophthalmology, melanoma associated spongiform scleropathy (MASS), MASS, malignant uveal melanoma, sclera, ciliary body, choroid, histopathology......ophthalmology, melanoma associated spongiform scleropathy (MASS), MASS, malignant uveal melanoma, sclera, ciliary body, choroid, histopathology...

  3. A case-control study of malignant melanoma among Lawrence Livermore National Laboratory employees: A critical evaluation

    Energy Technology Data Exchange (ETDEWEB)

    Kupper, L.L.; Setzer, R.W.; Schwartzbaum, J.; Janis, J.

    1987-07-01

    This document reports on a reevaluation of data obtained in a previous report on occupational factors associated with the development of malignant melanomas at Lawrence Livermore National Laboratory. The current report reduces the number of these factors from five to three based on a rigorous statistical analysis of the original data. Recommendations include restructuring the original questionnaire and trying to contact more individuals that worked with volatile photographic chemicals. 17 refs., 7 figs., 22 tabs. (TEM)

  4. [Construction of recombinant lentiviral vector of Tie2-RNAi and its influence on malignant melanoma cells in vitro].

    Science.gov (United States)

    Shan, Xiu-ying; Liu, Zhao-liang; Wang, Biao; Guo, Guo-xiang; Wang, Mei-shui; Zhuang, Fu-lian; Cai, Chuan-shu; Zhang, Ming-feng; Zhang, Yan-ding

    2011-07-01

    To construct lentivector carrying Tie2-Small interfering RNA (SiRNA), so as to study its influence on malignant melanoma cells. Recombinant plasmid pSilencer 1.0-U6-Tie2-siRNA and plasmid pNL-EGFP were digested with XbaI, ligated a target lentiviral transfer plasmid of pNL-EGFP-U6-Tie2-I or pNL-EGFP-U6-Tie2-II, and then the electrophoresis clones was sequenced. Plasmids of pNL-EGFP-U6-Tie2-I and pNL-EGFP-U6-Tie2-II were constructed and combined with pVSVG and pHelper, respectively, to constitute lentiviral vector system of three plasmids. The Lentiviral vector system was transfected into 293T cell to produce pNL-EGFP-U6-Tie2- I and pNL-EGFP-U6-Tie2-II lentivirus. Then the supernatant was collected to determine the titer. Malignant melanoma cells were infected by both lentiviruses and identified by Realtime RT-PCR to assess inhibitory efficiency. The recombinant lentiviral vectors of Tie2-RNAi were constructed successfully which were analyzed with restriction enzyme digestion and identified by sequencing. And the titer of lentiviral vector was 8.8 x 10(3)/ml, which was determined by 293T cell. The results of Realtime RT-PCR demonstrated that the lentiviral vectors of Tie2-RNAi could infect malignant melanoma cells and inhibit the expression of Tie2 genes in malignant melanoma cells (P0.05) between the two lentiviral vectors of Tie2-RNAi. Lentivector carrying Tie2-SiRNA can be constructed successfully and inhibit the expression of Tie2 gene in vitro significantly. The study will supply the theory basis for the further research on the inhibition of tumor growth in vivo.

  5. Oxidative stress inhibits distant metastasis by human melanoma cells.

    Science.gov (United States)

    Piskounova, Elena; Agathocleous, Michalis; Murphy, Malea M; Hu, Zeping; Huddlestun, Sara E; Zhao, Zhiyu; Leitch, A Marilyn; Johnson, Timothy M; DeBerardinis, Ralph J; Morrison, Sean J

    2015-11-12

    Solid cancer cells commonly enter the blood and disseminate systemically, but are highly inefficient at forming distant metastases for poorly understood reasons. Here we studied human melanomas that differed in their metastasis histories in patients and in their capacity to metastasize in NOD-SCID-Il2rg(-/-) (NSG) mice. We show that melanomas had high frequencies of cells that formed subcutaneous tumours, but much lower percentages of cells that formed tumours after intravenous or intrasplenic transplantation, particularly among inefficiently metastasizing melanomas. Melanoma cells in the blood and visceral organs experienced oxidative stress not observed in established subcutaneous tumours. Successfully metastasizing melanomas underwent reversible metabolic changes during metastasis that increased their capacity to withstand oxidative stress, including increased dependence on NADPH-generating enzymes in the folate pathway. Antioxidants promoted distant metastasis in NSG mice. Folate pathway inhibition using low-dose methotrexate, ALDH1L2 knockdown, or MTHFD1 knockdown inhibited distant metastasis without significantly affecting the growth of subcutaneous tumours in the same mice. Oxidative stress thus limits distant metastasis by melanoma cells in vivo.

  6. Human Melanoma-Derived Extracellular Vesicles Regulate Dendritic Cell Maturation.

    Science.gov (United States)

    Maus, Rachel L G; Jakub, James W; Nevala, Wendy K; Christensen, Trace A; Noble-Orcutt, Klara; Sachs, Zohar; Hieken, Tina J; Markovic, Svetomir N

    2017-01-01

    Evolution of melanoma from a primary tumor to widespread metastasis is crucially dependent on lymphatic spread. The mechanisms regulating the initial step in metastatic dissemination via regional lymph nodes remain largely unknown; however, evidence supporting the establishment of a pre-metastatic niche is evolving. We have previously described a dysfunctional immune profile including reduced expression of dendritic cell (DC) maturation markers in the first node draining from the primary tumor, the sentinel lymph node (SLN). Importantly, this phenotype is present prior to evidence of nodal metastasis. Herein, we evaluate melanoma-derived extracellular vesicles (EVs) as potential mediators of the premetastatic niche through cargo-specific polarization of DCs. DCs matured in vitro in the presence of melanoma EVs demonstrated significantly impaired expression of CD83 and CD86 as well as decreased expression of Th1 polarizing chemokines Flt3L and IL15 and migration chemokines MIP-1α and MIP-1β compared to liposome-treated DCs. Profiling of melanoma EV cargo identified shared proteomic and RNA signatures including S100A8 and S100A9 protein cargo, which in vitro compromised DC maturation similar to melanoma EVs. Early evidence demonstrates that similar EVs can be isolated from human afferent lymphatic fluid ex vivo. Taken together, here, we propose melanoma EV cargo as a mechanism by which DC maturation is compromised warranting further study to consider this as a potential mechanism enabled by the primary tumor to establish the premetastatic niche in tumor-draining SLNs of patients.

  7. Malignant melanoma in pigmented skin: does the current interventional model fit a different clinical, histologic, and molecular entity?

    Science.gov (United States)

    Alexandrescu, Doru T; Maslin, Benjamin; Kauffman, Catherine Lisa; Ichim, Thomas E; Dasanu, Constantin A

    2013-09-01

    Although the incidence of malignant melanoma in African Americans is considerably lower than in Caucasians, African Americans have a less-favorable prognosis related to later presentation and more deeply invasive lesions at diagnosis. To review the current literature addressing the specific clinical, histopathologic, and molecular features of melanoma in darkly pigmented individuals. We reviewed the most up-to-date literature pertaining to melanoma in this patient population, including data from clinical studies, epidemiologic analyses, and molecular and genetic studies. Several studies have suggested differences between lightly and darkly pigmented populations with regard to clinicopathologic character and the underlying genetic processes affecting its pathogenesis. Further investigation is warranted to better elucidate the clinical and underlying biological differences in melanoma between Caucasians and African Americans. Such research may help to ameliorate the disparities in melanoma outcomes through improved screening, public health measures aimed at prevention, and potentially novel targeted therapeutic approaches. © 2013 by the American Society for Dermatologic Surgery, Inc. Published by Wiley Periodicals, Inc.

  8. Development of a practical guide for the early recognition for malignant melanoma of the foot and nail unit

    Directory of Open Access Journals (Sweden)

    de Berker David AR

    2010-09-01

    Full Text Available Abstract Background Malignant melanoma is a rare but potentially lethal form of cancer which may arise on the foot. Evidence suggests that due to misdiagnosis and later recognition, foot melanoma has a poorer prognosis than cutaneous melanoma elsewhere. Methods A panel of experts representing podiatry and dermatologists with a special interest in skin oncology was assembled to review the literature and clinical evidence to develop a clinical guide for the early recognition of plantar and nail unit melanoma. Results A systematic review of the literature revealed little high quality data to inform the guide. However a significant number of case reports and series were available for analysis. From these, the salient features were collated and summarised into the guide. Based on these features a new acronym "CUBED" for foot melanoma was drafted and incorporated in the guide. Conclusions The use of this guide may help clinicians in their assessment of suspicious lesions on the foot (including the nail unit. Earlier detection of suspicious pedal lesions may facilitate earlier referral for expert assessment and definitive diagnosis. The guide is currently being field tested amongst practitioners.

  9. A Case of Malignant Melanoma with In-Transit Metastasis That Responded to Intravenous Infusion of Interferon-β

    Directory of Open Access Journals (Sweden)

    Masaru Arima

    2014-03-01

    Full Text Available A 77-year-old man with a history of surgical resection of malignant melanoma involving the fifth toe of his left foot 14 years ago presented at the Kariya Toyota General Hospital with a 3-month history of skin ulcer at the same site and red nodules on the lower left leg. Malignant melanoma was suspected, and the patient was referred to our department. On examination, a skin ulcer measuring 25 × 20 mm was observed at the amputation site on the left foot. In addition, multiple red nodules were observed on the lower left leg. Skin biopsies of the ulcer and nodules revealed recurrent malignant melanoma with in-transit metastasis. Two weeks later, he developed acute myocardial infarction and was hospitalized at the Kariya Toyota General Hospital. One month later, the myocardial infarction ameliorated, and he was transferred to our department. As the myocardial infarction had decreased the patient's tolerance to surgery, interferon-β was administered by intravenous infusion. The skin ulcer and red nodules on the lower left leg disappeared 26 weeks after infusion had been initiated. The patient's progress has been satisfactory, with no evidence of recurrence or metastasis at 1 year and 9 months after the initiation of intravenous infusion.

  10. Animal-type malignant melanoma associated with nevus of Ota in the orbit of a Japanese woman: a case report

    Science.gov (United States)

    Kashima, Tomoyuki; Mayuzumi, Hideyasu; Akiyama, Hideo; Miyanaga, Tomomi; Hirato, Junko; Kishi, Shoji

    2014-01-01

    We present a patient with an animal-type malignant melanoma associated with the nevus of Ota in the orbit who showed a good prognosis after a combination of orbital extirpation, chemotherapy, stereotactic radiotherapy, and gamma knife. A 42-year-old Japanese woman presented with two tumors, one pathologically diagnosed as right-sided intraconal animal-type malignant melanoma and the other intracranially, presumed to be of the same pathogenesis and both were considered to have arisen from the nevus of Ota. She underwent an extirpation of the orbit, chemotherapy (DAV therapy, which is a combination of dacarbazine, nimustine, and vincristine), stereotactic radiotherapy (54 Gy in 27 fractions), and gamma knife (marginal dose was 17 Gy, target volume was 0.2 ml). She has been alive for 33 months since the extirpation, with no sign of local recurrence, new metastasis, nor enlargement of the intracranial tumor. Not just combination therapy but also the low malignancy of animal-type melanoma may have contributed toward the good prognosis. PMID:24686419

  11. Phosphorylation of ectopically expressed L-plastin enhances invasiveness of human melanoma cells.

    Science.gov (United States)

    Klemke, Martin; Rafael, Maria T; Wabnitz, Guido H; Weschenfelder, Tatjana; Konstandin, Mathias H; Garbi, Natalio; Autschbach, Frank; Hartschuh, Wolfgang; Samstag, Yvonne

    2007-06-15

    The leukocyte specific actin-binding protein L-plastin is aberrantly expressed in several nonhematopoetic malignant tumors. However, little is known about the functional consequences of L-plastin expression. Here, we investigated the function of L-plastin in human malignant melanoma cells. Knock-down of endogenous L-plastin by siRNA treatment reduced migration of the melanoma cell line IF6. However, in melanoma patients, no correlation existed between L-plastin expression and tumor stages. This implied that additional factors such as phosphorylation of L-plastin may influence its function in tumor cells. To investigate this further, EGFP-tagged wild-type L-plastin (wt-LPL-EGFP) and a mutated, nonphosphorylatable L-plastin protein (5A7A-LPL-EGFP), were expressed in the L-plastin negative melanoma cell line MV3. Biochemical analysis revealed that wt-LPL-EGFP is phosphorylated in MV3 cells while 5A7A-LPL-EGFP is not. Although both wt-LPL-EGFP and 5A7A-LPL-EGFP were targeted to, and promote the formation of, vinculin-containing adhesion sites, static adhesion to either Matrigel or isolated extracellular matrix molecules was neither influenced by expression of wt-LPL-EGFP nor by expression of 5A7A-LPL-EGFP when compared with EGFP expressing control cells. In contrast, haptotactic, but not chemotactic, migration of melanoma cells towards either Matrigel or isolated extracellular matrix molecules was similarly enhanced, if either 5A7A-LPL-EGFP or wt-LPL-EGFP were expressed in MV3 cells. Interestingly, only cells expressing the phosphorylatable wt-LPL-EGFP protein showed enhanced invasion into Matrigel. In line with these findings the in vivo metastatic capacity of mouse B16 melanoma cells correlates with expression and phosphorylation of L-plastin. These data show that an increase in melanoma cell invasiveness requires not only expression but also phosphorylation of L-plastin.

  12. High expression of cytoplasmic phosphorylated CSE1L in malignant melanoma but not in benign nevi: phosphorylated CSE1L for the discrimination between melanoma and benign nevi

    National Research Council Canada - National Science Library

    Chin, Szu-Ying; Wu, Pei-Ru; Shih, Yi-Hsien; Yeh, Chung-Min; Lee, Woan-Ruoh; Shen, Shing-Chuan; Yeh, Kun-Tu; Jiang, Ming-Chung; Tseng, Jonathan Te-Peng

    2015-01-01

    Melanoma is difficult to treat when it has metastasized. Discrimination between melanoma and benign nevi in melanocytic lesions is crucial for identifying melanomas and consequently improving melanoma treatment and prognosis...

  13. RASSF10 promoter hypermethylation is frequent in malignant melanoma of the skin but uncommon in nevus cell nevi.

    Science.gov (United States)

    Helmbold, Peter; Richter, Antje M; Walesch, Sara; Skorokhod, Alexander; Marsch, Wolfgang Ch; Enk, Alexander; Dammann, Reinhard H

    2012-03-01

    The Ras association domain family (RASSF) consists of several tumor suppressor genes, which are frequently silenced in human cancers. We analyzed the epigenetic inactivation of RASSF2 and RASSF10 in malignant melanoma (MM) of the skin, including 5 MM cell lines, 28 primary MM, 33 metastases of MM, 47 nevus cell nevi (NCN), and 22 control tissues. The RASSF2 promoter was epigenetically downregulated in two MM cell lines only, but not in any of the investigated tumor samples. In contrast, hypermethylation of the RASSF10 promoter was found in all investigated cell lines, 19/28 (68%) of the primary MM and 30/33 (91%) of the MM metastases, 2/18 (11%) of the dysplastic NCN, and 0/29 (0%) of the non-dysplastic NCN (difference between MM and all nevi, Ptreatment with a DNA methylation inhibitor reactivated RASSF10 transcription. Furthermore, immunohistological RASSF10 expression corresponds negatively to its promoter methylation state. In summary, RASSF10 proved to be a characteristically epigenetically silenced tumor suppressor in melanomagenesis, and analysis of RASSF10 methylation status represents a new candidate tool to assist in discrimination between MM and NCN.

  14. C-fos protein expression in Spitz nevi, common melanocytic nevi, and malignant melanomas.

    Science.gov (United States)

    Bergman, R; Kerner, H; Manov, L; Friedman-Birnbaum, R

    1998-06-01

    The expression of c-fos protein was studied in formalin-fixed, paraffin-embedded sections of 11 compound Spitz nevi (SNs), 16 ordinary compound melanocytic nevi (MNs), and 17 malignant melanomas (MMs) using monoclonal antibody MAB1283 and an immunoperoxidase technique. Eleven (100%) SNs, 15 (94%) MNs, and 16 (94%) MMs showed positive reactions in some of the tumor cells (p = nonsignificant). In the majority of the tumors the staining was located in nuclei and graded as moderate to strong in intensity. The percentages of positively stained cells did not differentiate the three types of tumor, although they were higher in the melanocytic nevi. Most of the lesions with a significant dermal component did not show stratification of staining with progressive descent into the dermis. Positive staining for c-fos was also frequently found in the normal skin constituents within and adjacent to the melanocytic tumors. In conclusion, the pattern of expression of c-fos in routinely processed specimens does not differentiate between SNs, MNs, and MMs.

  15. Automated detection of malignant features in confocal microscopy on superficial spreading melanoma versus nevi

    Science.gov (United States)

    Gareau, Dan; Hennessy, Ricky; Wan, Eric; Pellacani, Giovanni; Jacques, Steven L.

    2010-11-01

    In-vivo reflectance confocal microscopy (RCM) shows promise for the early detection of superficial spreading melanoma (SSM). RCM of SSM shows pagetoid melanocytes (PMs) in the epidermis and disarray at the dermal-epidermal junction (DEJ), which are automatically quantified with a computer algorithm that locates depth of the most superficial pigmented surface [DSPS(x,y)] containing PMs in the epidermis and pigmented basal cells near the DEJ. The algorithm uses 200 noninvasive confocal optical sections that image the superficial 200 μm of ten skin sites: five unequivocal SSMs and five nevi. The pattern recognition algorithm automatically identifies PMs in all five SSMs and finds none in the nevi. A large mean gradient ψ (roughness) between laterally adjacent points on DSPS(x,y) identifies DEJ disruption in SSM ψ = 11.7 +/- 3.7 [-] for n = 5 SSMs versus a small ψ = 5.5 +/- 1.0 [-] for n = 5 nevi (significance, p = 0.0035). Quantitative endpoint metrics for malignant characteristics make digital RCM data an attractive diagnostic asset for pathologists, augmenting studies thus far, which have relied largely on visual assessment.

  16. Malignant melanoma in Chile: different site distribution between private and state patients.

    Science.gov (United States)

    Zemelman, Viviana B; Valenzuela, Carlos Y; Sazunic, Ivo; Araya, Irene

    2014-01-01

    The body site location of primary Malignant Melanoma (MM) has been correlated with prognosis and survival. Ethnic, genetics, sun exposure factors are related to the anatomical distribution of MM. Low and high socioeconomic strata in Chile differ in ethnic, genetic and cultural conditions. The purpose of this study was to analyze the anatomical MM distribution in the Chilean population in both strata searching for differences due to their ethno-genetic-cultural differences. Records of 1148 MM, 575 cases from state hospitals (Low Socioeconomic Strata, LSS) and 573 cases from private clinics (High Socioeconomic Strata, HSS) were analyzed by body site. Females from LSS showed a higher number of MM in soles, cheeks, and around the eye area. Females from the HSS showed a higher number of MM in dorsal feet and dorsal hands. Males from LSS showed a higher number of MM in soles, around the eye area, and cheeks. However, males from HSS showed a higher number of MM in the trunk, and in the arms. Acral MM was significantly higher in LSS than in the HSS in both sexes. The Chilean population from the HSS and LSS showed differences in the distribution of MM by site. Furthermore, gender differences in the proportion of MM analyzed by anatomical site are observed in both strata. Results show evidence that differential genetics factors, sun exposure, or other environmental or cultural factors of both strata may account for these differences.

  17. Malignant melanoma in Chile: an unusual distribution of primary sites in men from low socioeconomic strata.

    Science.gov (United States)

    Zemelman, V; Roa, J; Tagle, S Ruiz; Valenzuela, C Y

    2006-05-01

    Mortality from malignant melanoma (MM) has increased in Chile in the past decade. The location of MM lesions on the body has been correlated with prognosis and survival. To review body site and gender relationships with histopathologically confirmed primary MM in Chile. Records of 575 cases presenting to 5 state hospitals from 1992 to 2001 were analysed. There were 360 women and 215 men. Women showed a significantly higher number of MM on the legs, cheeks and arms, and in the genital area, whereas men showed a significantly higher number on the ears, backs of the hands, soles and feet. Men had a predilection for MM with a poor prognosis. The different body site distribution of primary MM in men and women may be explained by a different pattern of sun exposure. Ethnic and genetic factors may also be involved. The predominant location of MM in women in Chile is similar to white populations, whereas the location in men is similar to that observed in black and Asian populations. These observations may be relevant to the high mortality of MM in Chilean men.

  18. A psychoeducational nursing intervention to enhance coping and affective state in newly diagnosed malignant melanoma patients.

    Science.gov (United States)

    Fawzy, N W

    1995-12-01

    The primary purpose of this study was to determine if a psychoeducational nursing intervention including (a) health education, (b) stress management, and (c) the teaching of coping skills could enhance the coping behavior and affective state of newly diagnosed Stage I/II malignant melanoma patients. The secondary purpose was to determine if this intervention could be implemented by a nurse and integrated into the overall patient care program. Sixty-one patients were randomized to a control condition or an experimental condition that received and educational manual plus 3 h of individual nurse teaching. Despite randomization, experimental patients had significantly higher baseline distress. By 3 months there was a complete reversal of the baseline trend in Profile of Mood States (POMS) total mood disturbance (TMD), suggesting that the experimental subjects were experiencing less distress over time. Between-group analysis of change scores found significant decreases in experimental subjects for POMS TMD, fatigue, and Brief Symptom Index (BSI) somatization. Within-group analysis found significant experimental decreases for BSI somatization, anxiety, grand total, General Severity Index, and Positive Symptom Distress Index as well as for POMS anxiety, fatigue, confusion, vigor, and TMD. No significant changes were found for controls. Experimental patients were using significantly fewer ineffective passive resignation coping strategies than controls at 3 months.

  19. Cerebral MR imaging of malignant melanoma; Zerebrale MR-Bildgebung beim malignen Melanom

    Energy Technology Data Exchange (ETDEWEB)

    Breckwoldt, M.; Bendszus, M. [Universitaetsklinikum Heidelberg, Abteilung Neuroradiologie, Neurologische Klinik, Heidelberg (Germany)

    2015-01-16

    Melanoma is the third leading cancer entity to metastasize to the central nervous system (CNS) after lung and breast cancer. This is often an early event in the disease course and limits survival. Metastasis in the CNS is the cause of death in 10-40 % of melanoma patients and the incidence of brain metastasis is even higher (50-75 %). Cerebral metastases are commonly found in the subcortical white matter. The signal characteristics can vary substantially and may change over time due to hemorrhages or the accumulation of melanin and paramagnetic ions. It is not yet clear whether novel targeted therapies (e.g. immunotherapy and kinase inhibitors) alter imaging characteristics. Also immune-related side effects, such as hypophysitis (in approximately 5 % of patients receiving ipilimumab therapy) or granulomatous disease (neurosarcoid) can occur. Melanoma metastases are usually hyperdense in computed tomography (CT). In magnetic resonance imaging (MRI) T2-weighted (T2-w) fluid-attentuated inversion recovery (FLAIR) and T1-w sequences (with and without i.v. contrast) should be obtained. Coronal and axial imaging planes should be scanned to cross-correlate findings. Susceptibility-weighted imaging is a new sensitive method to detect melanoma metastases. Approximately 66 % of melanoma metastases show intratumoral susceptibility signals (ITSS). This sets them apart from other metastases (e.g. lung and breast cancer show less ITSSs, specificity approximately 81-96 %). Diffusion imaging plays no major role in melanoma brain imaging. Susceptibility-weighted imaging increases the sensitivity to detect metastases but lacks specificity. Differentiating metastases, microbleeding or calcification can be impossible. It is controversial how to interpret susceptibility signals without correlative signs on other sequences (differential diagnosis: metastasis, microbleeding and calcification). CNS metastases are common in melanoma. MRI screening starting in stage IIc should be considered

  20. Malignant syphilis with human immunodeficiency virus infection

    Directory of Open Access Journals (Sweden)

    Jiby Rajan

    2011-01-01

    Full Text Available Malignant syphilis or Lues maligna, commonly reported in the pre-antibiotic era, has now seen a resurgence with the advent of human immunodeficiency virus (HIV. Immunosuppression and sexual promiscuity set the stage for this deadly association of HIV and Treponema pallidum that can manifest atypically and can prove to cause diagnostic problems. We report one such case in a 30-year-old female who responded favorably to treatment with penicillin.

  1. Expression of glycoprotein non-metastatic melanoma protein B in cutaneous malignant and benign lesions: a tissue microarray study.

    Science.gov (United States)

    Zhao, Yan; Qiao, Zheng-guo; Shan, Shi-jun; Sun, Qing-miao; Zhang, Jian-zhong

    2012-09-01

    Glycoprotein non-metastatic melanoma protein B (GPNMB) plays an important role in the pathogenesis of inflammatory and malignant diseases. We investigated the expression of GPNMB in benign and malignant skin diseases. Tissue microarray was performed in the skin tissues of 102 cases including malignant melanoma (MM), squamous cell carcinoma (SCC), basal cell carcinoma (BCC), and benign dermatosis. The expression of GPNMB in the tissues was detected by immunohistochemistry. Twenty cases of normal skin and adjacent neoplastic normal skin tissues were selected as controls. GPNMB was positively stained in skin malignancies (38/50, 76%), which was significantly higher than that in the control and the benign skin tissues (P = 0.001 and < 0.001 respectively). GPNMB was positively stained in MM (13/15, 87%) and SCC (16/20, 80%) (P < 0.001). Significant higher expression of GPNMB was observed in patients aged ≥ 65 years than those less than 65 years (n = 11 and n = 9 respectively, P = 0.027). No significant difference of the expression rates was observed between normal control and BCC; however, stronger intensity was detected in the latter. Negative or weak expression was observed in the controls. Over-expression of GPNMB correlated strongly and might play an important role in the pathogenesis of MM and SCC.

  2. Pre-diagnostic digital imaging prediction model to discriminate between malignant melanoma and benign pigmented skin lesion.

    Science.gov (United States)

    Christensen, Jeppe H; Soerensen, Mads B T; Linghui, Zhong; Chen, Sun; Jensen, Morten O

    2010-02-01

    Malignant cutaneous melanoma is the most deadly form of skin cancer with an increasing incidence over the past decades. The final diagnosis provided is typically based on a biopsy of the skin lesion under consideration. To assist the naked-eye examination and decision on whether or not a biopsy is necessary, digital image processing techniques provide promising results. The hypothesis of this study was that a computer-aided assessment tool could assist the evaluation of a pigmented skin lesion. Hence, the overall aim was to discriminate between malignant and benign pigmented skin lesions using digital image processing. Discriminating algorithms utilizing novel well-established morphological operations and methods were constructed. The algorithms were implemented utilizing graphical programming (LabVIEW Vision). Verification was performed with reference to an image database consisting of 97 pigmented skin lesion pictures of various resolutions and light distributions. The outcome of the algorithms was analysed statistically with MATLAB and a prediction model was constructed. The prediction model evaluates pigmented skin lesions with regards to the overall shape, border and colour distribution with a total of nine different discriminating parameters. The prediction model outputs an index score, and by using the optimal threshold value, a diagnostic accuracy of 77% in discriminating between malignant and benign skin lesions was obtained. This is an improvement compared with the naked-eye analysis performed by professionals, rendering the system a significant assistance in detecting malignant cutaneous melanoma.

  3. Adrenal malignant melanoma masquerading as a pheochromocytoma in a patient with a history of a multifocal papillary and medullary thyroid carcinoma.

    Science.gov (United States)

    Barmpari, Maria E; Savvidis, Christos; Dede, Anastasia D; Markogiannakis, Haridimos; Dikoglou, Christina; Xekouki, Paraskevi; Stratakis, Constantine A; Manouras, Andreas; Malaktari-Skarantavou, Sofia

    2016-04-01

    Adrenal masses usually represent benign and nonfunctional adrenal adenomas; however, primary or metastatic malignancy should also be considered. Discovery of an adrenal mass needs further evaluation in order to exclude malignancy and hormonal secretion. We present a rare case of a possibly primary adrenal malignant melanoma with imaging and biochemical features of a pheochromocytoma. A 61-year-old male farmer was referred for evaluation of a mass in the right supraclavicular region and a left adrenal lesion. The patient had a history of a multifocal papillary and medullary thyroid carcinoma. Laboratory tests revealed increased 24hour urinary dopamine and also increased serum calcitonin and neuron specific enolase. A pathology report of the resected right supraclavicular mass and left adrenal showed a malignant melanoma. This is a case of a possibly primary adrenal malignant melanoma with imaging and biochemical features of a pheochromocytoma. Although this case is very rare and there are rigid diagnostic criteria for the diagnosis of primary adrenal melanoma, it underlines the fact that the differential diagnosis of a dopamine secreting adrenal mass should include primary or metastatic malignant melanoma in order to determine the best diagnostic approach for the patient and select the most appropriate surgical management.

  4. Treatment side effects and follow-up of malignant melanoma; Therapienebenwirkungen und Nachsorge bei malignem Melanom

    Energy Technology Data Exchange (ETDEWEB)

    Stahl, T. [Klinikum der Stadt Ludwigshafen gGmbH, Zentralinstitut fuer diagnostische und interventionelle Radiologie, Ludwigshafen (Germany); Loquai, C. [Universitaetsmedizin der Johannes-Gutenberg Universitaet Mainz, Hautklinik und Poliklinik, Mainz (Germany)

    2015-01-30

    Side effects in the therapy of malignant melanoma are primarily of importance for radiologists in advanced tumor stages. The available treatment options and their respective side effect profiles have undergone a profound change in recent years after the introduction of modern oncological therapies (e.g. immunotherapy and targeted therapy) with an increasing focus on individual tumor biology and differ significantly from those of classical chemotherapy. The immunotherapeutic agents, in particular ipilimumab, take on a special position because of their specific immune-mediated mechanisms of action and the associated side effects, so-called immune-related adverse events (irAE). The majority of the treatment effects are manifested on the skin (> 50 %) and are generally not detectable by diagnostic radiology. Only a comparatively small proportion of treatment side effects is detectable with diagnostic imaging (15-20 %) but as in the example of therapy-induced colitis with ipilimumab, may be rapidly fatal. In addition to colitis (10-20 %) further therapy side effects apparent in diagnostic imaging are hypophysitis (1.8-17 %), thyroiditis (0.8 %), myositis (1.7 %), fasciitis and sarcoid-like lymph node alterations (6.8 %). To detect radiologically detectable side effects early on and to delineate them especially from tumor progression and (opportunistic) infections, detailed knowledge of the therapeutic methods for melanoma, the mechanisms of action and in particular the sometimes very specific side effects is imperative for radiologists. (orig.) [German] Nebenwirkungen der Therapie des malignen Melanoms sind fuer den Radiologen primaer in fortgeschrittenen Tumorstadien von Bedeutung. Die zur Verfuegung stehenden Therapieoptionen und ihre jeweiligen Nebenwirkungsprofile haben sich in den letzten Jahren nach Einfuehrung moderner onkologischer Therapieoptionen, die sich zunehmend an der individuellen Tumorbiologie orientieren (zielgerichtete Therapie, Immuntherapie), einem

  5. Noncutaneous malignant melanoma: a prognostic model from a retrospective multicenter study

    Directory of Open Access Journals (Sweden)

    Kim Jung Han

    2010-04-01

    Full Text Available Abstract Background We performed multicenter study to define clinical characteristics of noncutaneous melanomas and to establish prognostic factors patients who received curative resection. Methods Of the 141 patients who were diagnosed of non-cutaneous melanoma at 4 institutions in Korea between June 1992 and May 2005, 129 (91.5% satisfied the selection criteria. Results Of the 129 noncutaneous melanoma patients, 14 patients had ocular melanoma and 115 patients had mucosal melanoma. For mucosal melanoma, anorectum was the most common anatomic site (n = 39, 30.2% which was followed by nasal cavity (n = 30, 23.3%, genitourinary (n = 21, 16.3%, oral cavity (n = 14, 10.9%, upper gastrointestinal tract (n = 6, 4.7% and maxillary sinus (n = 5, 3.9% in the order of frequency. With the median 64.5 (range 4.3-213.0 months follow-up, the median overall survival were 24.4 months (95% CI 13.2-35.5 for all patients, and 34.6 (95% CI 24.5-44.7 months for curatively resected mucosal melanoma patients. Adverse prognostic factors of survival for 87 curatively resected mucosal melanoma patients were complete resection (R1 resection margin, and age > 50 years. For 14 ocular melanoma, Survival outcome was much better than mucosal melanoma with 73.3% of 2 year OS and 51.2 months of median OS (P = .04. Conclusion Prognosis differed according to primary sites of noncutaneous melanoma. Based on our study, noncutaneous melanoma patients should be treated differently to improve survival outcome.

  6. Molecular biology of normal melanocytes and melanoma cells.

    Science.gov (United States)

    Bandarchi, Bizhan; Jabbari, Cyrus Aleksandre; Vedadi, Ali; Navab, Roya

    2013-08-01

    Malignant melanoma is one of the most aggressive malignancies in humans and is responsible for 60-80% of deaths from skin cancers. The 5-year survival of patients with metastatic malignant melanoma is about 14%. Its incidence has been increasing in the white population over the past two decades. The mechanisms leading to malignant transformation of melanocytes and melanocytic lesions are poorly understood. In developing malignant melanoma, there is a complex interaction of environmental and endogenous (genetic) factors, including: dysregulation of cell proliferation, programmed cell death (apoptosis) and cell-to-cell interactions. The understanding of genetic alterations in signalling pathways of primary and metastatic malignant melanoma and their interactions may lead to therapeutics modalities, including targeted therapies, particularly in advanced melanomas that have high mortality rates and are often resistant to chemotherapy and radiotherapy. Our knowledge regarding the molecular biology of malignant melanoma has been expanding. Even though several genes involved in melanocyte development may also be associated with melanoma cell development, it is still unclear how a normal melanocyte becomes a melanoma cell. This article reviews the molecular events and recent findings associated with malignant melanoma.

  7. Conjunctival malignant melanoma in Denmark: epidemiology, treatment and prognosis with special emphasis on tumorigenesis and genetic profile.

    Science.gov (United States)

    Larsen, Ann-Cathrine

    2016-05-01

    Conjunctival malignant melanoma is a rare disease associated with considerable mortality. Most published data have been based on case reports or series of referred patients. In addition, very little is known about the genetic and epigenetic profile of conjunctival melanoma and the resemblance to uveal, cutaneous and mucosal melanoma. The aim was to determine the incidence rate of conjunctival melanoma, and to relate clinicopathological features and treatment to prognosis. A further aim was to determine the prevalence of BRAF mutations in conjunctival melanoma, to determine whether BRAF mutations are early events in pathogenesis, and relate clinicopathological features and prognosis to BRAF-mutation status. Finally, we wanted to identify tumour-specific and prognostic microRNAs in conjunctival melanoma, and to compare these with the microRNA expression of other melanoma subtypes. In order to investigate these rare tumours, we studied all the conjunctival melanomas that had been surgically removed in Denmark over a period of 52 years (1960-2012). Tissue samples, clinical files, pathology reports and follow-up data were collected and re-evaluated. Using droplet digital polymerase chain reaction and immunohistochemistry, we investigated BRAF mutations; and using microRNA expression profiling, we investigated differentially expressed microRNAs. The overall incidence of conjunctival melanoma was 0.5/1 000 000/year, and it increased in Denmark over 52 years. The increase was mainly caused by an increase in older patients (>65 years) and bulbar lesions. Clinicopathological features significantly associated with a poor prognosis were extrabulbar location, involvement of adjacent tissue structures, tumour thickness exceeding 2 mm and local tumour recurrence. Patients undergoing incisional biopsy and/or treatment involving excision without adjuvant therapy fared worse than patients treated with excision and any type of adjuvant treatment. We found that 35% (39/110) of

  8. Biologic and Therapeutic Significance of MYB Expression in Human Melanoma

    Science.gov (United States)

    Hijiya, Nobuko; Zhang, Jin; Ratajczak, Mariusz Z.; Kant, Jeffrey A.; Deriel, Kim; Herlyn, Meenhard; Zon, Gerald; Gewirtz, Alan M.

    1994-05-01

    We investigated the therapeutic potential of employing antisense oligodeoxynucleotides to target the disruption of MYB, a gene which has been postulated to play a pathogenetic role in cutaneous melanoma. We found that MYB was expressed at low levels in several human melanoma cell lines. Also, growth of representative lines in vitro was inhibited in a dose- and sequence-dependent manner by targeting the MYB gene with unmodified or phosphorothioate-modified antisense oligodeoxynucleotides. Inhibition of cell growth correlated with specific decrease of MYB mRNA. In SCID mice bearing human melanoma tumors, infusion of MYB antisense transiently suppressed MYB gene expression but effected long-term growth suppression of transplanted tumor cells. Toxicity of the oligodeoxynucleotides was minimal in mice, even when targeted to the murine Myb gene. These results suggest that the MYB gene may play an important, though undefined, role in the growth of at least some human melanomas. Inhibition of MYB expression might be of use in the treatment of this disease.

  9. Efficacy and toxicity of whole brain radiotherapy in patients with multiple cerebral metastases from malignant melanoma

    Directory of Open Access Journals (Sweden)

    Hauswald Henrik

    2012-08-01

    Full Text Available Abstract Background To retrospectively access outcome and toxicity of whole brain radiotherapy (WBRT in patients with multiple brain metastases (BM from malignant melanoma (MM. Patients and methods Results of 87 patients (median age 58 years; 35 female, 52 male treated by WBRT for BM of MM between 2000 and 2011 were reviewed. Total dose applied was either 30 Gy in 10 fractions (n = 56 or 40 Gy in 20 fractions (n = 31. All but 9 patients suffered from extra-cerebral metastases. Prior surgical resection of BM was performed in 18 patients, salvage stereotactic radiosurgery in 13 patients. Results Mean follow-up was 8 months (range, 0–57 months, the 6- and 12-months overall-(OS survival rates were 29.2% and 16.5%, respectively. The median OS was 3.5 months. In cerebral follow-up imaging 6 (11 patients showed a complete (partial remission, while 11 (17 patients had stable disease (intra-cerebral tumor progression. In comparison of total dose, the group treated with 40 Gy in 20 fractions achieved a significant longer OS (p = 0.003, median 3.1 vs. 5.6 months. Furthermore, DS-GPA score (p  Conclusion Treatment of BM from MM with WBRT is tolerated well and some remissions of BM could be achieved. An advantage for higher treatment total doses was seen. However, outcome is non-satisfying, and further improvements in treatment of BM from MM are warranted.

  10. Higher Caffeinated Coffee Intake Is Associated with Reduced Malignant Melanoma Risk: A Meta-Analysis Study

    Science.gov (United States)

    Liu, Jibin; Shen, Biao; Shi, Minxin; Cai, Jing

    2016-01-01

    Background Several epidemiological studies have determined the associations between coffee intake level and skin cancer risk; however, the results were not yet conclusive. Herein, we conducted a systematic review and meta-analysis of the cohort and case-control studies for the association between coffee intake level and malignant melanoma (MM) risk. Methods Studies were identified through searching the PubMed and MEDLINE databases (to November, 2015). Study-specific risk estimates were pooled under the random-effects model. Results Two case-control studies (846 MM patients and 843 controls) and five cohort studies (including 844,246 participants and 5,737 MM cases) were identified. For caffeinated coffee, the pooled relative risk (RR) of MM was 0.81 [95% confidential interval (95% CI) = 0.68–0.97; P-value for Q-test = 0.003; I2 = 63.5%] for those with highest versus lowest quantity of intake. In the dose-response analysis, the RR of MM was 0.955 (95% CI = 0.912–0.999) for per 1 cup/day increment of caffeinated coffee consumption and linearity dose-response association was found (P-value for nonlinearity = 0.326). Strikingly, no significant association was found between the decaffeinated coffee intake level and MM risk (pooled RR = 0.92, 95% CI = 0.81–1.05; P-value for Q-test = 0.967; I2 = 0%; highest versus lowest quantity of intake). Conclusions This meta-analysis suggested that caffeinated coffee might have chemo-preventive effects against MM but not decaffeinated coffee. However, larger prospective studies and the intervention studies are warranted to confirm these findings. PMID:26816289

  11. Higher Caffeinated Coffee Intake Is Associated with Reduced Malignant Melanoma Risk: A Meta-Analysis Study.

    Directory of Open Access Journals (Sweden)

    Jibin Liu

    Full Text Available Several epidemiological studies have determined the associations between coffee intake level and skin cancer risk; however, the results were not yet conclusive. Herein, we conducted a systematic review and meta-analysis of the cohort and case-control studies for the association between coffee intake level and malignant melanoma (MM risk.Studies were identified through searching the PubMed and MEDLINE databases (to November, 2015. Study-specific risk estimates were pooled under the random-effects model.Two case-control studies (846 MM patients and 843 controls and five cohort studies (including 844,246 participants and 5,737 MM cases were identified. For caffeinated coffee, the pooled relative risk (RR of MM was 0.81 [95% confidential interval (95% CI = 0.68-0.97; P-value for Q-test = 0.003; I2 = 63.5%] for those with highest versus lowest quantity of intake. In the dose-response analysis, the RR of MM was 0.955 (95% CI = 0.912-0.999 for per 1 cup/day increment of caffeinated coffee consumption and linearity dose-response association was found (P-value for nonlinearity = 0.326. Strikingly, no significant association was found between the decaffeinated coffee intake level and MM risk (pooled RR = 0.92, 95% CI = 0.81-1.05; P-value for Q-test = 0.967; I2 = 0%; highest versus lowest quantity of intake.This meta-analysis suggested that caffeinated coffee might have chemo-preventive effects against MM but not decaffeinated coffee. However, larger prospective studies and the intervention studies are warranted to confirm these findings.

  12. The number of benign moles excised for each malignant melanoma: the number needed to treat.

    Science.gov (United States)

    Sidhu, S; Bodger, O; Williams, N; Roberts, D L

    2012-01-01

    The ratio of benign moles excised for each malignant melanoma (MM) diagnosed, i.e. the number needed to treat (NNT), may be a useful indicator of diagnostic accuracy and the efficient use of healthcare resources, and may have personal implications for the patient. To assess the NNT for a group of consultant dermatologists serving a population of 600,000, and to compare this with similar studies from other countries. This was a retrospective analysis of data on pigmented lesions excised over a 5-year period (2005-2009). The lesions were divided into three groups: benign naevi (BN), dysplastic naevi (DN) and MM. The NNT ratio was calculated as (BN + DN + MM)/MM. In total, 4691 lesions were examined. The overall mean NNT was 6.3, with a range of 4.9-11.3 for each of nine consultant dermatologists. The mean NNT was 7.6 for female and 4.8 for male patients. There were more patients with BN (n = 3534; 75%) than with DN (n = 407; 9%) or MM (n = 750; 16%). The gender representation was similar in the DN and MM groups, but had a disproportionately female bias in the BN group (67% female, 33% male patients). Overall, there were more female patients in all three groups [2962 female patients (63%) and 1729 male patients (37%)]. The NNT of 6.3 in this study compares favourably with NNT ratios from studies of dermatologists from other countries. This study may encourage other countries and individual doctors to assess their NNT ratios, as it may be an important indicator of the efficient use of resources and the avoidance of unnecessary surgery for patients. © The Author(s). CED © 2011 British Association of Dermatologists.

  13. Dormancy of growth-stunted malignant melanoma: sustainable and smoldering patterns

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    Claudine Piérard-Franchimont

    2014-09-01

    Full Text Available The presentations of primary and metastatic cutaneous malignant melanoma (CMM are very diverse. Evidence increasingly indicates that single CMM cells spread to distant sites quite early during cancer progression and are soon eliminated before they become clinically detectable. However bulky metastases which appear at a later stage might derive from some of these early neoplastic cells. It seems that local CMM single cell micro-metastases commonly predict sentinel lymph node involvement without overtly reflecting CMM progression to bulky visceral metastases. This study is intended to review the current understanding of the mechanisms underlying two CMM presentations. The first is the long interval, apparently disease-free, with persistent CMM dormancy, which may precede overt metastatic growth. Immunosurveillance may induce dormancy in single CMM cells disseminated in the body by blocking their proliferation cycle. The second is the socalled CMM smoldering phenomenon, which is marked by an alternate progression and regression of CMM locally with metastases that wax and wane for long periods of time over restricted skin areas. These very diverse patterns of CMM progression are likely to be ascribable to a number of biological factors, including the activation of CMM stem cells, and the combined phenotypic heterogeneity and variability in proliferative amplification in CMM cell clusters. Furthermore an adequate stimulation of CMM immune-surveillance and the induction of a specific stromal structure and vascular response are required. In this context, most early CMM tumors are in part controlled by lymphocytemediated responses before they become clinically detectable. However both the role of immune-surveillance and the mechanisms underlying both persistent and smoldering CMM dormancy remain unclear.

  14. Dormancy of growth-stunted malignant melanoma: sustainable and smoldering patterns.

    Science.gov (United States)

    Piérard-Franchimont, Claudine; Hermanns-Lê, Trinh; Delvenne, Philippe; Piérard, Gerald E

    2014-09-23

    The presentations of primary and metastatic cutaneous malignant melanoma (CMM) are very diverse. Evidence increasingly indicates that single CMM cells spread to distant sites quite early during cancer progression and are soon eliminated before they become clinically detectable. However bulky metastases which appear at a later stage might derive from some of these early neoplastic cells. It seems that local CMM single cell micro-metastases commonly predict sentinel lymph node involvement without overtly reflecting CMM progression to bulky visceral metastases. This study is intended to review the current understanding of the mechanisms underlying two CMM presentations. The first is the long interval, apparently disease-free, with persistent CMM dormancy, which may precede overt metastatic growth. Immunosurveillance may induce dormancy in single CMM cells disseminated in the body by blocking their proliferation cycle. The second is the so-called CMM smoldering phenomenon, which is marked by an alternate progression and regression of CMM locally with metastases that wax and wane for long periods of time over restricted skin areas. These very diverse patterns of CMM progression are likely to be ascribable to a number of biological factors, including the activation of CMM stem cells, and the combined phenotypic heterogeneity and variability in proliferative amplification in CMM cell clusters. Furthermore an adequate stimulation of CMM immune-surveillance and the induction of a specific stromal structure and vascular response are required. In this context, most early CMM tumors are in part controlled by lymphocyte-mediated responses before they become clinically detectable. However both the role of immune-surveillance and the mechanisms underlying both persistent and smoldering CMM dormancy remain unclear.

  15. Uveal and conjunctival malignant melanoma in denmark 1943-97: observed and relative survival of patients followed through 2002

    DEFF Research Database (Denmark)

    Isager, Peter; Engholm, G.; Overgaard, Jens

    2006-01-01

    PURPOSE: To evaluate the observed and relative survival of patients diagnosed with a malignant melanoma in the ocular region in Denmark during the period 1943-97. METHODS: The study included 2,504 patients (1,292 men and 1,212 women) diagnosed with a melanoma in the ocular region, of which 2......,434 cases could be topographically subclassified into 2,178 in the choroid/ciliary body, 141 in the iris, and 115 in the conjunctiva. The patients were followed through 2002 and the observed survival proportions and relative survival ratios were estimated. RESULTS: For the total ocular region...... and the choroid/ciliary body, the observed survival did not vary statistically significantly with the year of diagnosis. A statistically insignificant higher observed survival for women than men was found for tumors in the ocular region and the subgroups choroid/ciliary body, iris, and conjunctiva. During the 55...

  16. ZNF23 Suppresses Cutaneous Melanoma Cell Malignancy via Mitochondria-Dependent Pathway

    Directory of Open Access Journals (Sweden)

    Xin Zhang

    2017-08-01

    Full Text Available Background/Aims: Cutaneous melanoma is one of the leading causes of cancer deaths with an increasing incidence worldwide. A KRAB-containing zinc finger protein member, zinc finger 23 (ZNF23, was reduced in some types of tumors and inhibited cell growth by inducing cell cycle arrest. However, the role of ZNF23 expression is still poorly understood in melanoma. Methods: The level of ZNF23 expression was detected in cutaneous melanoma, adjacent normal skin tissues and cutaneous melanoma cell lines using immunohistochemistry and western blotting. The correlations between ZNF23 expression and other clinicopathologic parameters were analyzed in melanoma patients. Ectopic expression of ZNF23 plasmid was transfected into melanoma cells, SK-MEL-1 and SK-MEL-28. MTT, flow cytometry and transwell assay were used to measure cell proliferation, apoptosis, invasion and migration abilities, respectively. Mitochondrial functions and structures were detected by mitochondrial membrane potential assay and Transmission electron microscopy (TEM method in melanoma cells transfected with overexpressing ZNF23 plasmid or empty vector. Western blotting was performed to detect the levels of ZNF23, p53, p27, Bcl-2 and cleaved caspase-3 after overexpressing of ZNF23 in melanoma cells. Results: ZNF23 was elevated in adjacent normal skin tissues compared with melanoma tissues. Patients with low level of ZNF23 expression exhibited higher incidence of lymphoid metastasis, thicker size of tumors and worse outcome. By using Cox’s regression analysis, ZNF23 expression, tumor thickness and lymph node metastasis were the independent prognostic factors for overall survival (p < 0.05. Results from cellular experiments indicated that ectopic expression of ZNF23 induced cell apoptosis by activation of caspase-3, p27, p53 expression and down-regulation of Bcl-2 through mitochondria-dependent pathway. Conclusions: Decreased ZNF23 was contributed to melanoma progression and poor survival

  17. Molecular mechanism implicated in Pemetrexed-induced apoptosis in human melanoma cells

    Directory of Open Access Journals (Sweden)

    Buqué Aitziber

    2012-04-01

    Full Text Available Abstract Background Metastatic melanoma is a lethal skin cancer and its incidence is rising every year. It represents a challenge for oncologist, as the current treatment options are non-curative in the majority of cases; therefore, the effort to find and/or develop novel compounds is mandatory. Pemetrexed (Alimta®, MTA is a multitarget antifolate that inhibits folate-dependent enzymes: thymidylate synthase, dihydrofolate reductase and glycinamide ribonucleotide formyltransferase, required for de novo synthesis of nucleotides for DNA replication. It is currently used in the treatment of mesothelioma and non-small cell lung cancer (NSCLC, and has shown clinical activity in other tumors such as breast, colorectal, bladder, cervical, gastric and pancreatic cancer. However, its effect in human melanoma has not been studied yet. Results In the current work we studied the effect of MTA on four human melanoma cell lines A375, Hs294T, HT144 and MeWo and in two NSCLC cell lines H1299 and Calu-3. We have found that MTA induces DNA damage, S-phase cell cycle arrest, and caspase- dependent and –independent apoptosis. We show that an increment of the intracellular reactive oxygen species (ROS and p53 is required for MTA-induced cytotoxicity by utilizing N-Acetyl-L-Cysteine (NAC to blockage of ROS and p53-defective H1299 NSCLC cell line. Pretreatment of melanoma cells with NAC significantly decreased the DNA damage, p53 up-regulation and cytotoxic effect of MTA. MTA was able to induce p53 expression leading to up-regulation of p53-dependent genes Mcl-1 and PIDD, followed by a postranscriptional regulation of Mcl-1 improving apoptosis. Conclusions We found that MTA induced DNA damage and mitochondrial-mediated apoptosis in human melanoma cells in vitro and that the associated apoptosis was both caspase-dependent and –independent and p53-mediated. Our data suggest that MTA may be of therapeutic relevance for the future treatment of human malignant melanoma.

  18. Dacarbazine DTIC and carboplatin as an outpatient treatment for disseminated malignant melanoma

    NARCIS (Netherlands)

    Nieboer, P; Mulder, NH; Van Der Graaf, WTA; Willemse, PHB; Hospers, GAP

    2001-01-01

    Occasionally long-term survival in disseminated melanoma can be obtained through chemotherapy, We treated 22 patients with disseminated melanoma with an outpatient regimen consisting of dacarbazine (DTIC) and carboplatin. Three patients had a complete response lasting 4+, 9 and 9 months (survival

  19. Malignant melanoma of sun-protected sites: a review of clinical, histological, and molecular features.

    Science.gov (United States)

    Merkel, Emily A; Gerami, Pedram

    2017-06-01

    In most cases of cutaneous melanoma, ultraviolet (UV) radiation is recognized as a prominent risk factor. Less is known regarding the mechanisms of mutagenesis for melanoma arising in sun-protected sites, such as acral and mucosal melanoma. Acral and mucosal melanoma share many common features, including a late age of onset, a broad radial growth phase with prominent lentiginous growth, the presence of field cancerization cells, and, in most cases, lack of a precursor nevus. In addition to early chromosomal instability, many of the same genes are also involved in these two distinct melanoma subtypes. To better understand non-UV-mediated pathogenesis in melanoma, we conducted a joint literature review of clinical, histological, and molecular features in acral and mucosal melanoma. We also reviewed the current literature regarding aberrations in KIT, PDGFRA, TERT, and other commonly involved genes. By comparing common features of these two subtypes, we suggest potential mechanisms underlying acral and/or mucosal melanoma and offer direction for future investigations.

  20. Primary glandular melanoma of male breast with nodal metastasis

    OpenAIRE

    Jayabal Pandiaraja

    2016-01-01

    Malignant melanoma is a malignancy that develops from melanocytes. Breast is an uncommon site for malignant melanoma. Melanoma of the breast occurs in various situations such as primary melanoma of breast skin, metastatic melanoma of breast, in-transit metastasis to the breast, and primary glandular breast melanoma. Most of the melanoma breast either cutaneous melanoma or metastatic melanoma. Primary glandular melanoma of male breast with nodal involvement is rarely reported compared to prima...

  1. Pesquisa de células malignas circulantes em pacientes com melanoma maligno de coróide Detection of circulating malignant cells in patients with uveal melanoma

    Directory of Open Access Journals (Sweden)

    Bruno F. Fernandes

    2007-08-01

    Full Text Available OBJETIVO: Avaliar a possibilidade de identificação de células malignas circulantes nas amostras de sangue periférico de pacientes brasileiros com melanoma maligno de coróide enviadas para análise no exterior. MÉTODOS: Os marcadores melan-A e tirosinase foram usados para detectar a presença de células malignas circulantes, pela transcrição reversa seguida de reação em cadeia da polimerase e análise seqüencial de DNA (RT-nested-PCR, em seis pacientes com melanoma maligno de coróide, diagnosticados no Brasil. RESULTADOS: Cinco pacientes deste grupo (83,33% foram considerados positivos. A reação de RT-nested-PCR foi positiva para melan-A em quatro (66,7% e positiva para tirosinase em quatro (66,7% dos seis pacientes testados. Três (50% pacientes foram positivos para os dois marcadores. Um (16,7% paciente foi negativo para ambos marcadores. CONCLUSÃO: A pesquisa de células malignas circulantes usando RT-nested-PCR, foi positiva na maioria dos pacientes estudados. A qualidade das amostras de sangue periférico dos pacientes brasileiros foi mantida no material preservado mesmo após ter sido enviado ao exterior.PURPOSE: The purpose of our study was to detect circulating malignant cells (CMCs in oversea-shipped blood samples of patients with uveal melanoma diagnosed in Brazil. METHODOS: Melan-A and tyrosinase were the two markers used for the detection of CMCs, using reverse transcriptase nested polymerase chain reaction (RT-nested-PCR in 6 patients with uveal melanoma. The expression of beta-actin and GAPDH were used to assess the quality of the material. RESULTS: Five patients (83.33% tested positive for the presence of CMCs. The RT-nested-PCR was positive for melan-A in 4 patients (66.7% and positive for tyrosinase in 4 (66.7% of the 6 patients. Three (50% patients were positive for both markers. One (16.7% patient was negative for both markers. All negative controls were negative. CONCLUSION: The quality of the blood samples

  2. Anti-Proliferative Effect of Rosmarinus officinalis L. Extract on Human Melanoma A375 Cells.

    Science.gov (United States)

    Cattaneo, Lucia; Cicconi, Rosella; Mignogna, Giuseppina; Giorgi, Alessandra; Mattei, Maurizio; Graziani, Giulia; Ferracane, Rosalia; Grosso, Alessandro; Aducci, Patrizia; Schininà, M Eugenia; Marra, Mauro

    2015-01-01

    Rosemary (Rosmarinus officinalis L.) has been used since ancient times in traditional medicine, while nowadays various rosemary formulations are increasingly exploited by alternative medicine to cure or prevent a wide range of health disorders. Rosemary's bioproperties have prompted scientific investigation, which allowed us to ascertain antioxidant, anti-inflammatory, cytostatic, and cytotoxic activities of crude extracts or of pure components. Although there is a growing body of experimental work, information about rosemary's anticancer properties, such as chemoprotective or anti-proliferative effects on cancer cells, is very poor, especially concerning the mechanism of action. Melanoma is a skin tumor whose diffusion is rapidly increasing in the world and whose malignancy is reinforced by its high resistance to cytotoxic agents; hence the availability of new cytotoxic drugs would be very helpful to improve melanoma prognosis. Here we report on the effect of a rosemary hydroalcoholic extract on the viability of the human melanoma A375 cell line. Main components of rosemary extract were identified by liquid chromatography coupled to tandem mass spectrometry (LC/ESI-MS/MS) and the effect of the crude extract or of pure components on the proliferation of cancer cells was tested by MTT and Trypan blue assays. The effect on cell cycle was investigated by using flow cytometry, and the alteration of the cellular redox state was evaluated by intracellular ROS levels and protein carbonylation analysis. Furthermore, in order to get information about the molecular mechanisms of cytotoxicity, a comparative proteomic investigation was performed.

  3. Metastatic pathway and the microvascular and physicochemical microenvironments of human melanoma xenografts.

    Science.gov (United States)

    Huang, Ruixia; Andersen, Lise Mari K; Rofstad, Einar K

    2017-10-10

    Malignant melanoma of the skin can metastasize through blood vessels and lymphatics. The primary tumor develops a vascular microenvironment characterized by abnormal blood vessels and lymphatics and a physicochemical microenvironment characterized by low oxygen tension, regions with hypoxic tissue, and high interstitial fluid pressure (IFP). This study aimed at identifying relationships between the metastatic route of melanomas and characteristic features of the microvascular and physicochemical microenvironments of the primary tumor. Two patient-derived xenograft (PDX) models (E-13, N-15) and four cell line-derived xenografts (CDX) models (C-10, D-12, R-18, T-22) of human melanoma were included in the study. Tumors were transplanted to an orthotopic site in BALB/c-nu/nu mice, and when the tumors had grown to a volume of 500-600 mm3, the IFP of the primary tumor was measured and the hypoxia marker pimonidazole was administered before the host mouse was euthanized. The primary tumor, lungs, and six pairs of lymph nodes were evaluated by examining hematoxylin/eosin-stained and immunostained histological preparations. The expression of angiogenesis-related genes was assessed by quantitative PCR. C-10, D-12, and E-13 tumors disseminated primarily by the hematogenous route and developed pulmonary metastases. These tumors showed high angiogenic activity and high expression of the F3 gene as well as ANGPT2 and TIE1, genes encoding proteins of the angiopoietin-tie system. N-15, R-18, and T-22 tumors disseminated mainly by the lymphogenous route and developed metastases in draining lymph nodes. These tumors had highly elevated IFP and showed high expression of NRP2, a gene encoding neuropilin-2. The primary metastatic route of orthotopic human melanoma xenografts and the development of lung and lymph node metastases are influenced significantly by the microvascular and physicochemical microenvironments of the primary tumor.

  4. Influence of having a home garden on personal UVR exposure behavior and risk of cutaneous malignant melanoma in Denmark

    DEFF Research Database (Denmark)

    Idorn, Luise Winkel; Thieden, Elisabeth; Philipsen, Peter Alshede

    2013-01-01

    There is a need for more knowledge concerning the association of higher socioeconomic status (SES) with cutaneous malignant melanoma (CMM). Having a home garden is associated with a higher SES. We aimed to study the influence of having a home garden on UVR exposure behavior and risk of CMM....... Register study: We collected information from Danish national registers about gender, age, type of home and CMM among persons aged 16-75 in 2002-2006. A total of 5,118 CMM cases were identified. Risk of CMM of the trunk was increased by 46% (p ... of the extremities by 34% (p personal electronic UVR dosimeters measuring time-stamped UVR doses...

  5. Dysfunctional oxidative phosphorylation makes malignant melanoma cells addicted to glycolysis driven by the V600EBRAF oncogene

    DEFF Research Database (Denmark)

    Hall, Arnaldur; Meyle, Kathrine Damm; Lange, Marina Krarup

    2013-01-01

    basis for this addiction is largely unknown. Here we provide evidence for a metabolic rationale behind the addiction to V600EBRAF in two malignant melanoma cell lines. Both cell lines display a striking addiction to glycolysis due to underlying dysfunction of oxidative phosphorylation (OXPHOS). Notably......, even minor reductions in glycolytic activity lead to increased OXPHOS activity (reversed Warburg effect), however the mitochondria are unable to sustain ATP production. We show that V600EBRAF upholds the activity of glycolysis and therefore the addiction to glycolysis de facto becomes an addiction to V...

  6. Dysfunctional oxidative phosphorylation makes malignant melanoma cells addicted to glycolysis driven by the (V600E)BRAF oncogene

    DEFF Research Database (Denmark)

    Hall, Arnaldur; Meyle, Kathrine Damm; Lange, Marina Krarup

    2013-01-01

    basis for this addiction is largely unknown. Here we provide evidence for a metabolic rationale behind the addiction to (V600E)BRAF in two malignant melanoma cell lines. Both cell lines display a striking addiction to glycolysis due to underlying dysfunction of oxidative phosphorylation (OXPHOS......). Notably, even minor reductions in glycolytic activity lead to increased OXPHOS activity (reversed Warburg effect), however the mitochondria are unable to sustain ATP production. We show that (V600E)BRAF upholds the activity of glycolysis and therefore the addiction to glycolysis de facto becomes...

  7. Three-Dimensional Image Fusion of SPECT and CT Scans for Locating Sentinel Lymph Nodes in Malignant Melanomas

    Directory of Open Access Journals (Sweden)

    Michiko Akiyama

    2011-03-01

    Full Text Available Image fusion software can derive a fusion image from single photon emission computed tomography and computed tomography scans. We applied a three-dimensional fusion image to detect sentinel lymph nodes (SLNs in 3 patients with malignant melanomas of the lumbar, vulvar and head region, respectively. During each operation, we detected SLNs at the expected site, as indicated by the fusion images. The three-dimensional image fusion could thus be confirmed as a simple and helpful method for precisely localizing SLNs in these patients.

  8. 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

  9. Serum CEACAM1 Correlates with Disease Progression and Survival in Malignant Melanoma Patients

    Directory of Open Access Journals (Sweden)

    Sapoznik Sivan

    2012-01-01

    Full Text Available The search for melanoma biomarkers is crucial, as the incidence of melanoma continues to rise. We have previously demonstrated that serum CEACAM1 (sCEACAM1 is secreted from melanoma cells and correlates with disease progression in metastatic melanoma patients. Here, we have used a different cohort of melanoma patients with regional or metastatic disease (N=49, treated with autologous vaccination. By monitoring sCEACAM1 in serum samples obtained prior to and after vaccination, we show that sCEACAM1 correlates with disease state, overall survival, and S100B. The trend of change in sCEACAM1 following vaccination (increase/decrease inversely correlates with overall survival. DTH skin test is used to evaluate patients’ anti-melanoma immune response and to predict response to vaccination. Importantly, sCEACAM1 had a stronger prognostic value than that of DTH, and when sCEACAM1 decreased following treatment, this was the dominant predictor of increased survival. Collectively, our results point out the relevance of sCEACAM1 in monitoring melanoma patients.

  10. The burden of malignant melanoma--lessons to be learned from Austria.

    Science.gov (United States)

    Monshi, Babak; Vujic, Marin; Kivaranovic, Danijel; Sesti, Alma; Oberaigner, Willi; Vujic, Igor; Ortiz-Urda, Susana; Posch, Christian; Feichtinger, Hans; Hackl, Monika; Rappersberger, Klemens

    2016-03-01

    Incidence rates of melanoma, generated by cancer registries (CRs), are susceptible to reporting inconsistencies due to increasing decentralisation of diagnosis. We therefore independently assessed the burden of melanoma in Austria. We collected histopathological reports on melanoma of all patients diagnosed in Austria in 2011. Demographic and clinical characteristics, histopathological tumour stages were assessed. Their regional distributions and incidence rates were analysed and compared with data of national and international CRs. A total of 5246 patients were diagnosed with 1951 in-situ and 3295 invasive melanomas in Austria in 2011 (population 8.4 million). Age, sex and anatomic distribution corresponded to findings in other European countries, however, the incidence of 25/100,000 (world age-standardised rate) for invasive melanomas was two-fold higher than published by the Austrian CR (12/100,000). Varying frequencies in diagnosing thin melanomas (≤1 mm; n = 4415) accounted exclusively for significant regional disparities, while advanced tumours (>1 mm; n = 761) were evenly distributed. Western Austria showed the highest rates (36/100,000). Patients from eastern Austria whose melanomas were diagnosed in laboratories in western Austria (n = 76) showed significantly higher proportions of in-situ lesions (n = 43; 57%) compared to those whose tumours were diagnosed in eastern Austria (n = 4014; in-situ = 1369; 34%) (p Austria, the melanoma burden and its potential socio-economic implications are significantly underestimated. Similarities of incidences indicate this could affect other European countries with well-established CRs and compromise international comparability of data. Austrian regional disparities suggest overdiagnosis of thin melanomas due to the variability of pathologists' thresholds for the diagnosis of early stage tumours. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  11. A phase II study of thalidomide in patients with brain metastases from malignant melanoma

    DEFF Research Database (Denmark)

    Vestermark, Lene; Larsen, Susanne; Lindeløv, Birgit

    2008-01-01

    Introduction. Brain metastases develop in nearly half of the patients with advanced melanoma and in 15 to 20% of these patients CNS is the first site of relapse. Overall median survival is short, ranging from 2 to 4 months. Thalidomide has antiangiogenic and immunomodulatory effects. Results...... obtained in prior trials indicate that Thalidomide acts as a cytostatic agent in metastatic melanoma. We evaluated single agent antitumour activity and toxicity of Thalidomide in a phase II setting in patients with brain metastases associated with metastatic melanoma. Material and methods. Patients...

  12. Brain metastases from malignant melanoma; ZNS-Metastasen beim malignen Melanom

    Energy Technology Data Exchange (ETDEWEB)

    Willner, J. [Wuerzburg Univ. (Germany). Klinik und Poliklinik fuer Strahlentherapie; Bohndorf, W. [Wuerzburg Univ. (Germany). Klinik und Poliklinik fuer Strahlentherapie

    1995-03-01

    Between 1985 and 1993 30 patients underwent radiation therapy for brain metastases from malignant melanoma. In 9 patients they had been surgically resected. All except 1 patient received whole brain irradiation with a total dose of 20 to 46 Gy/2 to 5 weeks using daily fractions of 2,0 to 4,0 Gy. In 5 patients a local boost of 20 to 25 Gy/2 weeks was administered. Survival rates were compared using the Cox-method. Univariate and multivariate analyses were performed to define prognostic subgroups. In 6/30 patients (20%) brain metastases were diagnosed at the time of primary manifestation of melanoma. In 83% of patients brain metastases developed during the first 5 years following primary diagnosis. Late manifestation was observed (18 years). Overall survival rate of the whole group was 39% at 6 months and 23% at 1 year. Univariate analysis revealed that age at diagnosis of brain metastases, time to manifestation, number of intracranial metastases and existence of extracerebral distant metastases had significant influence on survival. Sex was not found to influence survival rate. Multivariate analysis identified the existence of extracerebral distant metastases at the time of diagnosis of brain metastases as the most important prognostic factor for survival, followed by age and surgical resection. The role of fractionation was studied separately in a subgroup of patients receiving whole brain irradiation to a total dose of 39 to 42 Gy. Survival rates deteriorated when overall treatment time exceeded 3 weeks. (orig./MG) [Deutsch] Zwischen 1985 und 1993 wurden 30 Patienten mit ZNS-Metastasen bei malignem Melanom einer strahlentherapeutischen Behandlung unterzogen. Bei neun Patienten war eine operative Metastasenresektion vorausgegangen. Alle bis auf einen Patienten erhielten eine Ganzschaedelbestrahlung mit 20 bis 46 Gy in zwei bis fuenf Wochen bei Einzeldosen von 2,0 bis 4,0 Gy. In fuenf Faellen erfolgte eine lokale Aufsaettigung mit 20 bis 25 Gy/2 Wochen. Die

  13. 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

  14. Melanomas metastáticos intracranianos: análise de 13 casos Malignant melanoma brain metastases: analysis of 13 cases

    Directory of Open Access Journals (Sweden)

    João Flávio Mattos Araújo

    1997-06-01

    Full Text Available Os autores apresentam análise retrospectiva de 13 pacientes com o diagnóstico de melanoma metástico intracerebral. A lesão primária foi detectada em 9 pacientes. A idade dos pacientes variou entre 28 e 84 anos. O tempo transcorrido entre o diagnóstico da lesão primária e a metástase cerebral variou entre 6 e 60 meses. Todos os pacientes foram submetidos a craniotomia, com remoção da lesão. A mortalidade nos primeiros 30 dias foi zero. A sobrevida dos pacientes variou entre 2 e 55 meses. O tempo médio de sobrevida de todo o grupo foi 14 meses. Embora o tratamento cirúrgico não seja curativo, a sobrevida é significativamente prolongada. Os critérios para a indicação da cirurgia, radioterapia e quimioterapia são discutidos.The authors present a retrospective review of 13 patients with the diagnostic of intracranial metastatic malignant melanoma. Their ages ranged from 28 to 84 years. The time interval from diagnosis of primary tumor to development of cerebral metastases ranged from 6 to 60 months. There was preoperative evidence of extracranial disease in 9 patients. All patients underwent craniotomy, and the 30-day mortality was zero. The patients survived 2 to 55 months after surgery. Medium survival time for all patients was 14 months. The excision of metastatic melanoma from the brain, although not curative, may increase survival in patients with this metastatic cancer. The criteria for consideration of surgery, radiotherapy and chemotherapy are discussed.

  15. Combined in vivo reflectance confocal microscopy and digital dermoscopy for follow up of patients at high risk of malignant melanoma: A prospective case series study.

    Science.gov (United States)

    Floristán Muruzábal, Uxúa; Gamo Villegas, Reyes; Pampín Franco, Ana; Pinedo Moraleda, Fernando; Pérez Fernández, Elia; López-Estebaranz, José Luis

    2017-06-01

    Digital dermoscopy (DD) follow up is a useful strategy for monitoring patients at high risk of melanoma. Reflectance confocal microscopy (RCM) is a valuable second-level examination after dermoscopy for the evaluation of difficult to diagnose lesions. The aim of this study was to assess the value of RCM in routine DD monitoring of patients at high risk of melanoma. In this prospective study, performed over 22 months, changing melanocytic lesions were detected by DD and excised. RCM imaging was performed before surgical excision of all the lesions, and histopathology used as the gold standard diagnostic test. Eighty-seven lesions, including 11 thin melanomas, were studied. Dermoscopic evaluation at follow up revealed a significant association between melanoma and asymmetry in two axes (P = 0.035). Enlargement and other changes in structure or color did not significantly differ between nevi and melanomas. Widespread pagetoid cells, non-edged papillae, irregular and dishomogeneous junctional clusters, and sheet-like structures were significantly associated with malignancy (P melanoma in 10 of 11 cases (90.9%). The remaining case was classified as a dysplastic nevus. Forty-six lesions (52.8%) in which RCM revealed no atypia were deemed unnecessarily removed. This study was limited by sample size. In conclusion, combined DD and RCM facilitates the recognition of thin malignant melanomas and reduces unnecessary excisions. © 2017 Japanese Dermatological Association.

  16. Novel Genes Associated with Malignant Melanoma but not Benign Melanocytic Lesions

    National Research Council Canada - National Science Library

    Dmitri Talantov; Abhijit Mazumder; Jack X. Yu; Thomas Briggs; Yuqiu Jiang; John Backus; David Atkins; Yixin Wang

    2005-01-01

    .... Experimental Design: Total RNA isolated from 45 primary melanoma, 18 benign skin nevi, and 7 normal skin tissue specimens were analyzed on an Affymetrix Hu133A microarray containing 22,000 probe sets. Results...

  17. Impact of sentinel lymph node management in malignant melanoma; Zur Bedeutung des Sentinel-Lymphknoten-Managements beim malignen Melanom

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    Maza, S.; Munz, D.L. [Klinik fuer Nuklearmedizin, Charite - Universitaetmedizin Berlin (Germany)

    2006-06-15

    Malignant melanoma initially metastasises to regional lymph nodes and belongs to the ''leading candidates'' for sentinel lymph node (SLN) management. In newly diagnosed melanoma stage Ib to IIIa, today the SLN diagnostics is classified as the staging method of first choice. The technique of the SLN diagnostics is described thoroughly, including multimodal imaging if this is required for selective SLN biopsy. The evaluation of the diagnostic results, documentation and classification encompasses an important part. In approximately 2/3 of the melanoma patients there is no presence of metastases in SLN and non-SLN, one of five patients has metastases in SLN with negative non-SLN, every sixth to tenth patient has positive SLN and non SLN. Every thirtieth patient with tumour free SLN exhibits pathological findings in the non-SLN by using conventional examination methods only, every fifteenth if using molecular-genetic methods in addition. Among the prognostic parameters the SLN status has the most significant impact on disease-free and disease-specific survival. (orig.)

  18. Insight into molecular dynamics simulation of BRAF(V600E) and potent novel inhibitors for malignant melanoma.

    Science.gov (United States)

    Tang, Hsin-Chieh; Chen, Yu-Chian

    2015-01-01

    BRAF inhibitors have changed the standard therapeutic protocol for advanced or metastatic melanoma which harbored notorious BRAF(V600E) single mutation. However, drug resistance to BRAF inhibitors happens just like other cancer treatment. In this study, we constructed the ideal BRAF(V600E)-modeled structure through homology modeling and introduced the method of structure-based docking or virtual screening from the large compound database. Through certain methods of molecular dynamics simulation, we realized that BRAF(V600E) had quite prominent difference of molecular character or structural variation from the wild-type BRAF protein. It might confer the metamorphic character of advanced melanoma for the patients who harbored BRAF(V600E) mutation. By the methods of ligand-based quantitative structure-activity relationship and molecular dynamics simulation, we further recommend that aknadicine and 16beta-hydroxy-19s-vindolinine N-oxide from the traditional Chinese medicine are potent novel inhibitors for the management of malignant melanoma in the future.

  19. [Diagnostics of malignant melanoma of the skin : Recommendations of the current S3 guidelines on histology and molecular pathology].

    Science.gov (United States)

    Rose, C

    2017-02-01

    The updated S3 guidelines on malignant melanoma were established in August 2016. The principles of diagnostics and classification are based on the histopathological results from the primary tumor and if necessary the sentinel lymph nodes. The most important factor for prognosis is the tumor thickness according to Breslow and the detection of sentinel node micrometastases. The surgical safety margin after excision is dependent on the tumor thickness. Furthermore, ulceration of the primary tumor and presence of mitosis in melanomas less than 1 mm in thickness are also considered in the T‑classification. The sentinel lymph nodes should be prepared according to established procedures using HE staining and immunohistochemical methods. The largest tumor diameter of a micrometastasis should be measured in tenths of a millimeter (Rotterdam classification). Molecular pathology testing for mutations in the BRAF and NRAS oncogenes should be carried out in patients with metastatic disease or surgically non-resectable tumors. In addition c-KIT mutations should be tested in acral lentiginous and mucosal melanomas. Treatment with signal transduction inhibitors is possible when mutations have been detected.

  20. Preoperative 15-MHz ultrasound assessment of tumor thickness in malignant melanoma.

    Science.gov (United States)

    Fernández Canedo, I; de Troya Martín, M; Fúnez Liébana, R; Rivas Ruiz, F; Blanco Eguren, G; Blázquez Sánchez, N

    2013-04-01

    Tumor thickness is of great importance in the management of cutaneous malignant melanoma (MM): this variable not only affects prognosis but is also a key factor in planning surgical margins and selecting candidates for sentinel node biopsy. Breslow depth is the standard histologic measure of thickness, but technological advances have provided imaging techniques such as cutaneous ultrasound that can potentially assess tumor thickness and enable prompt initiation of definitive treatment. a) To evaluate the utility of ultrasound assessment of tumor thickness in MM, and b) to analyze histologic variables that affect ultrasound assessments of thickness. Retrospective study of a consecutive series of 79 primary cutaneous MMs in which tumor thickness had been assessed by 15-MHz ultrasound before surgery. We gathered data from histology reports, studying Breslow depth and the presence of ulceration, regression, inflammatory infiltrate, and associated nevi. Correlation coefficients were calculated to evaluate the strength of association between Breslow depth and thickness assessed by ultrasound. We also calculated the sensitivity, specificity, and positive and negative predictive values of ultrasound measurement in the diagnosis of MMs more than 1mm thick. Associations between histologic variables and the overestimation of thickness by ultrasound were also analyzed. The 79 primary MMs studied had a mean (SD) Breslow depth of 0.8 (1.4) mm. There was moderate correlation and agreement between Breslow depth and the ultrasound assessment of thickness (Pearson correlation coefficient, 0.678; intraclass correlation coefficient, 0.78). The tendency of ultrasound to overestimate thickness was nonsignificantly related to the presence of a moderate to intense infiltrate and associated nevi (P>.05). The sensitivity of ultrasound for the diagnosis of MM over 1mm thick was 82%; specificity was 80%, and positive and negative predictive values were 54% and 94%, respectively. Ultrasound

  1. A Case of Amelanotic Malignant Melanoma of the Maxillary Sinus Presented with Intraoral Extension.

    Science.gov (United States)

    Singhvi, Abhishek; Joshi, Ashish

    2015-09-01

    Melanoma of the sinonasal cavity has a high incidence of amelanotic presentation. Its diagnosis is difficult for clinicians and pathologists because of its hidden location and lack of pigmentation at the microscopic level. We reported a case of amelanotic melanoma of the maxillary sinus that showed aggressive extension to the oral cavity after extraction of the maxillary tooth. Histologically, the lesion resembled a plasmacytoid tumour. Diagnosis was made through the positive immunohistochemical staining for S100 and HMB-45.

  2. A Case of Amelanotic Malignant Melanoma of the Maxillary Sinus Presented with Intraoral Extension

    OpenAIRE

    Singhvi, Abhishek; Joshi, Ashish

    2015-01-01

    Melanoma of the sinonasal cavity has a high incidence of amelanotic presentation. Its diagnosis is difficult for clinicians and pathologists because of its hidden location and lack of pigmentation at the microscopic level. We reported a case of amelanotic melanoma of the maxillary sinus that showed aggressive extension to the oral cavity after extraction of the maxillary tooth. Histologically, the lesion resembled a plasmacytoid tumour. Diagnosis was made through the positive immunohistochemi...

  3. Interferon Alpha Signalling and Its Relevance for the Upregulatory Effect of Transporter Proteins Associated with Antigen Processing (TAP in Patients with Malignant Melanoma.

    Directory of Open Access Journals (Sweden)

    Ruth Heise

    Full Text Available Interferon alpha (IFNα is routinely used in the clinical practice for adjuvant systemic melanoma therapy. Understanding the molecular mechanism of IFNα effects and prediction of response in the IFNα therapy regime allows initiation and continuation of IFNα treatment for responder and exclusion of non-responder to avoid therapy inefficacy and side-effects. The transporter protein associated with antigen processing-1 (TAP1 is part of the MHC class I peptide-loading complex, and important for antigen presentation in tumor and antigen presenting cells. In the context of personalized medicine, we address this potential biomarker TAP1 as a target of IFNα signalling.We could show that IFNα upregulates TAP1 expression in peripheral blood mononuclear cells (PBMCs of patients with malignant melanoma receiving adjuvant high-dose immunotherapy. IFNα also induced expression of TAP1 in mouse blood and tumor tissue and suppressed the formation of melanoma metastasis in an in vivo B16 tumor model. Besides its expression, TAP binding affinity and transport activity is induced by IFNα in human monocytic THP1 cells. Furthermore, our data revealed that IFNα clearly activates phosphorylation of STAT1 and STAT3 in THP1 and A375 melanoma cells. Inhibition of Janus kinases abrogates the IFNα-induced TAP1 expression. These results suggest that the JAK/STAT pathway is a crucial mediator for TAP1 expression elicited by IFNα treatment.We suppose that silencing of TAP1 expression provides tumor cells with a mechanism to escape cytotoxic T-lymphocyte recognition. The observed benefit of IFNα treatment could be mediated by the shown dual effect of TAP1 upregulation in antigen presenting cells on the one hand, and of TAP1 upregulation in 'silent' metastatic melanoma cells on the other hand. In conclusion, this work contributes to a better understanding of the mode of action of IFNα which is essential to identify markers to predict, assess and monitor therapeutic

  4. Patterns of failure and predictors of outcome in cutaneous malignant melanoma of the scalp.

    Science.gov (United States)

    Terakedis, Breanne E; Anker, Christopher J; Leachman, Sancy A; Andtbacka, Robert H I; Bowen, Glen M; Sause, William T; Grossmann, Kenneth F; Bowles, Tawnya L; Noyes, R Dirk; Hitchcock, Ying J; Boucher, Kenneth M; Shrieve, Dennis C

    2014-03-01

    Patients with melanoma of the scalp may have higher failure (recurrence) rates than melanoma of other body sites. We sought to characterize survival and patterns of failure for patients with scalp melanoma. Between 1998 and 2010, 250 nonmetastatic patients underwent wide local excision of a primary scalp melanoma. Kaplan-Meier analyses were performed to evaluate overall survival, scalp control, regional neck control, distant metastases-free survival, and disease-free survival. Five-year overall survival was 86%, 57%, and 45% for stages I, II, and III, respectively, and 5-year scalp control rates were 92%, 75%, and 63%, respectively. Five-year distant metastases-free survival for these stages were 92%, 65%, and 45%, respectively. Of the 74 patients who recurred, the site of first recurrence included distant disease in 47%, although 31% recurred in the scalp alone. This is a retrospective review. Distant metastases-free survival and overall survival for stage II and III patients with scalp melanoma are poor, and stage III patients experience relatively high rates of scalp failure suggesting that these patients may benefit from additional adjuvant systemic and local therapy. Further research is needed to characterize the environmental, microenvironmental, and genetic causes of the increased aggressiveness of scalp melanoma and to identify more effective treatment and surveillance methods. Copyright © 2013 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

  5. Malignancy without immortality? Cellular immortalization as a possible late event in melanoma progression.

    Science.gov (United States)

    Soo, Julia K; Mackenzie Ross, Alastair D; Kallenberg, David M; Milagre, Carla; Heung Chong, W; Chow, Jade; Hill, Lucy; Hoare, Stacey; Collinson, Rebecca S; Hossain, Mehnaz; Keith, W Nicol; Marais, Richard; Bennett, Dorothy C

    2011-06-01

    Cell senescence is a permanent growth arrest following extended proliferation. Cultured cancer cells including metastatic melanoma cells often appear immortal (proliferate indefinitely), while uncultured benign nevi (moles) show senescence markers. Here, with new explantation methods, we investigated which classes of primary pigmented lesions are typically immortal. Nevi yielded a few proliferating cells, consistent with most nevus cells being senescent. No nevus culture (0/28) appeared immortal. Some thin and thick melanoma cultures proved immortal under these conditions, but surprisingly few (4/37). All arrested cultures displayed three senescence markers in some cells: β-galactosidase, nuclear p16, and heterochromatic foci/aggregates. However, melanoma cultures also showed features of telomeric crisis (arrest because of ultrashort telomeres). Moreover, crisis markers including anaphase bridges were frequent in uncultured vertical growth-phase (VGP) melanomas. Conversely, all immortal melanoma cultures expressed telomerase reverse transcriptase and telomerase, showing aneuploidy. The findings suggest that primary melanomas are typically precrisis, with immortalization/telomere maintenance as a late event. 2011 John Wiley & Sons A/S.

  6. Development of a human three-dimensional organotypic skin-melanoma spheroid model for in vitro drug testing.

    Science.gov (United States)

    Vörsmann, H; Groeber, F; Walles, H; Busch, S; Beissert, S; Walczak, H; Kulms, D

    2013-07-11

    Despite remarkable efforts, metastatic melanoma (MM) still presents with significant mortality. Recently, mono-chemotherapies are increasingly replenished by more cancer-specific combination therapies involving death ligands and drugs interfering with cell signaling. Still, MM remains a fatal disease because tumors rapidly develop resistance to novel therapies thereby regaining tumorigenic capacity. Although genetically engineered mouse models for MM have been developed, at present no model is available that reliably mimics the human disease and is suitable for studying mechanisms of therapeutic obstacles including cell death resistance. To improve the increasing requests on new therapeutic alternatives, reliable human screening models are demanded that translate the findings from basic cellular research into clinical applications. By developing an organotypic full skin equivalent, harboring melanoma tumor spheroids of defined sizes we have invented a cell-based model that recapitulates both the 3D organization and multicellular complexity of an organ/tumor in vivo but at the same time accommodates systematic experimental intervention. By extending our previous findings on melanoma cell sensitization toward TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) by co-application of sublethal doses of ultraviolet-B radiation (UVB) or cisplatin, we show significant differences in the therapeutical outcome to exist between regular two-dimensional (2D) and complex in vivo-like 3D models. Of note, while both treatment combinations killed the same cancer cell lines in 2D culture, skin equivalent-embedded melanoma spheroids are potently killed by TRAIL+cisplatin treatment but remain almost unaffected by the TRAIL+UVB combination. Consequently, we have established an organotypic human skin-melanoma model that will facilitate efforts to improve therapeutic outcomes for malignant melanoma by providing a platform for the investigation of cytotoxic treatments and

  7. Estudo comparativo da flarefotometria em pacientes com melanoma maligno e nevo de coróide Comparative study of flare photometry in patients with choroidal malignant melanoma and choroidal nevus

    Directory of Open Access Journals (Sweden)

    Priscilla Luppi Ballalai

    2002-01-01

    Full Text Available Introdução: Os tumores malignos intra-oculares estão associados com um aumento do "flare" na câmara anterior, causado por uma quebra na barreira hemato-aquosa, que pode ocorrer por vários mecanismos. Estudos utilizando a flarefotometria confirmam o aumento do "flare" em olhos com tumores intra-oculares malignos e benignos. Objetivo: Avaliar a flarefotometria como auxiliar no diagnóstico diferencial de melanoma maligno e nevo de coróide, comparando-se com olhos contralaterais normais. Métodos: Foram avaliados olhos com melanoma maligno e olhos com nevo de coróide diagnosticados por meio de oftalmoscopia indireta e/ou ultra-sonografia. Os olhos normais contralaterais foram utilizados como controles. A flarefotometria foi realizada em todos os pacientes, sob midríase bilateral, utilizando equipamento Laser Flare Meter (FC 500, Kowa. Foram aplicados os testes de Wilcoxon, Mann-Whitney, e Spearman para análise estatística. Resultados: A média da flarefotometria nos olhos com melanoma maligno de coróide foi 17,1 ph/ms e nos olhos normais contralaterais foi 4,06 ph/ms. Nos olhos com nevo de coróide o valor da flarefotometria foi 6,12 ph/ms e nos olhos contralaterais normais foi 4,47 ph/ms. O valor da flarefotometria foi maior nos olhos com melanoma maligno e nevo quando comparado com os olhos contralaterais normais (pIntroduction: Malignant intraocular tumors are associated with an increase in the aqueous flare, caused by alterations of the blood-ocular barriers through various mechanisms. Several studies have demonstrated an ocular flare increase using flare photometry in eyes with benign and malignant tumors. Purpose: To evaluate flare photometry as an adjunct method in the differential diagnosis of choroidal malignant melanoma and choroidal nevus comparing to normal control eyes. Methods: Eyes with melanoma and nevus were diagnosed by indirect binocular ophthalmoscopy and/or ultrasound were evaluated. The fellow normal eyes were used

  8. Detectability of liver metastases in malignant melanoma: prospective comparison of magnetic resonance imaging and positron emission tomography

    Energy Technology Data Exchange (ETDEWEB)

    Ghanem, Nadir [Departments of Diagnostic Radiology, University Hospital Freiburg, Freiburg 79106 (Germany)]. E-mail: gha@mrs1.ukl.uni-freiburg.de; Altehoefer, Carsten [Departments of Diagnostic Radiology, University Hospital Freiburg, Freiburg 79106 (Germany); Hoegerle, Stefan [Departments of Nuclear Medicine, University Hospital Freiburg, Freiburg (Germany); Nitzsche, Egbert [Departments of Nuclear Medicine, University Hospital Freiburg, Freiburg (Germany); Lohrmann, Christian [Departments of Diagnostic Radiology, University Hospital Freiburg, Freiburg 79106 (Germany); Schaefer, Oliver [Departments of Diagnostic Radiology, University Hospital Freiburg, Freiburg 79106 (Germany); Kotter, Elmar [Departments of Diagnostic Radiology, University Hospital Freiburg, Freiburg 79106 (Germany); Langer, Mathias [Departments of Diagnostic Radiology, University Hospital Freiburg, Freiburg 79106 (Germany)

    2005-05-01

    Purpose: We evaluated the diagnostic accuracy of magnetic resonance imaging (MRI) and positron emission tomography (PET) for detection of liver metastases in malignant melanoma. Material and methods: Thirty-five patients with 39 combined unenhanced MRI and fluorine-18 deoxyglucose (F-18 FDG) PET scans were prospectively studied. In discordant imaging findings final diagnosis was proven by clinical follow-up >6 months and demonstration of progressive liver metastases by at least one imaging method. Sensitivities and specificities were compared and the influence of lesion size and melanin content on diagnostic accuracy was determined. Results: MRI and PET were concordantly negative for presence and number of liver metastases in 28 patients and positive in four patients. PET and MRI were false positive in one patient each. In one patient MRI showed a single metastases not seen by PET and in one patient MRI demonstrated more metastases at the first examination. In follow-up investigations MRI revealed more metastases than PET in both patients. The sensitivities for lesion detection were 47% (16/34) for PET and 100% for MRI. Lesion detectability by PET was related to lesion size (P < 0.0001) but not to melanin content. Conclusion: MRI is more sensitive in the detection of liver metastases in patients with malignant melanoma. Small lesions are easily missed by PET, while melanin content does not influence detectability by PET.

  9. Depression, anxiety and quality of life in long-term survivors of malignant melanoma: a register-based cohort study.

    Directory of Open Access Journals (Sweden)

    Manfred E Beutel

    Full Text Available The purpose of the study was to determine anxiety and depression, quality of life, and their determinants in long-term survivors of malignant melanoma.In a state cancer registry a cohort of survivors of malignant melanoma was contacted via the physician registered. Of 1302 contactable patients, 689 (52.2% completed a questionnaire including the Patient Health Questionnaire with generalized anxiety (GAD-7 and depression (PHQ-9 and the EORTC Quality of Life Questionnaire (EORTC QLQ 30. Based on multiple regression analysis, predictors of quality of life and distress were identified. Comparison data were assessed in two waves of representative face-to-face household surveys of the adult German population.An average of 8.4 (5.7 to 12.2 years after diagnosis, distress was higher in women compared to men and in middle adulthood (vs. older patients. Symptoms were higher in women than in men, and there was a decline of functioning and increase of symptoms across the age range of both genders. Compared to the general population, there were slightly increased depression and anxiety (only women, but no impaired global quality of life. Yet, survivors evidenced functional decline and more physical symptoms. Distress and reduced quality of life were consistently predicted by lack of social support, fear of recurrence, pessimism and self-blame. Distress was increased by a family history of melanoma, and additional mental and somatic diseases.Overall, long-term survivors have adjusted well achieving a global quality of life comparable to the general population. Yet, compromised functional dimensions, physical symptoms and distress indicate the need for integrating psychooncological screening into oncological follow-up, which might be guided by predictors such as family history or social support. Further prospective study is needed to determine the course of adaptation to the disease and corroborate the risk factors identified.

  10. Clinical Characteristics of Malignant Melanoma in Southwest China: A Single-Center Series of 82 Consecutive Cases and a Meta-Analysis of 958 Reported Cases.

    Directory of Open Access Journals (Sweden)

    Jia Yu

    Full Text Available The present study determined the clinical characteristics and prognostic factors in patients with malignant melanoma based on a series of 82 cases from January 2009 to December 2014 in Southwest Hospital and a meta-analysis (including 12 articles involving 958 patients in China.The database elements included basic demographic data and prognosticators which were extracted from medical records. Statistical analyses of survival, and multivariate analyses of factors associated with survival were performed using the Kaplan-Meier method, and the Cox proportional hazard model, respectively. Literatures were identified through systematic searches in PubMed, Embase, the Cochrane Library, China National Knowledge Infrastructure (CNKI and Weipu database (VIP database for the period from inception to December 2015. The