Study of the histopathological types of cutaneous melanoma in Palmas-TO from 2001 to 2011.

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Costa, Nilo Fernandes da; Fernandes, Nurimar Conceição; Borges, Myrlena Regina Machado Mescouto

2015-01-01

Cutaneous melanoma (CM) is considered serious for causing frequent metastasis, presenting high mortality, resistance to available therapies and incidences in laboring activity. To study the histopathological types of cutaneous melanoma in Palmas-TO from 2001 to 2011, according to risk factors, location of lesions, Clark levels and Breslow thickness. A descriptive, retrospective and quantitative research in reports of the Serviços de Anatomia Patológica in Palmas (SAPP) and Registro de Câncer de Base Populacional de Palmas (RCBPP). The years of highest incidences were: 2004 (8 cases/17.8%), 2008 and 2011 (7 cases each/15.6%) and 2010 (6 cases/13.3%). Among the 45 cases studied, there were predominance in patients between 41 and 60 years old, women, caucasians, farmers, located in trunk, in situ type, superficial extensive and metastatic cutaneous, Clark levels I (20%) and IV (17.7%), Breslow thickness ≤1 mm (35.5%) and 2.01 to 4 mm (24.4%). The most common histopathological types were: cutaneous melanoma in situ, superficial extensive and metastatic, followed by nodular cutaneous melanoma, and finally, by other forms. In this study, Clark levels and Breslow thickness pointed to greater importance of thin melanomas and sun exposure without appropriate protection in farmers.

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

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

1985-01-01

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

Monoclonal anti-melanoma antibodies and their possible clinical use

International Nuclear Information System (INIS)

Hellstroem, K.E.; Hellstroem, Ingegerd; Washington Univ., Seattle; Washington Univ., Seattle

1985-01-01

Cell surface antigens of human melanoma, as defined by monoclonal antibodies, are discussed and in particular the three antigens p97, a GD3 ganglioside and a proteoglycan. The potential diagnostic uses of antibodies to melanoma antigens are reviewed including in vitro diagnosis by immuno-histology, in vitro diagnosis by serum assays and in vivo diagnosis by tumour imaging using radioactively labelled antibodies. The potential therapeutic uses of monoclonal antibodies to melanoma antigens are also reviewed including targets for antibody therapy, the use of antibodies alone, radiolabelled antibodies, antibody-toxin conjugates, antibody-drug conjugates, anti-idiotypic antibodies and vaccines. (UK)

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

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

2010-06-01

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

POLE mutations in families predisposed to cutaneous melanoma

DEFF Research Database (Denmark)

Aoude, Lauren G; Heitzer, Ellen; Johansson, Peter

2015-01-01

Germline mutations in the exonuclease domain of POLE have been shown to predispose to colorectal cancers and adenomas. POLE is an enzyme involved in DNA repair and chromosomal DNA replication. In order to assess whether such mutations might also predispose to cutaneous melanoma, we interrogated...... variants in the exonuclease domain of POLE. Although this frequency is not significantly higher than that in unselected Caucasian controls, we observed multiple cancer types in the melanoma families, suggesting that some germline POLE mutations may predispose to a broad spectrum of cancers, including...

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

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

2016-05-24

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

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

Science.gov (United States)

Cohen, Philip R

2017-09-18

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

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

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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.

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...

[Cutaneous melanoma - "black death" of modern times? Traces in contemporary literature].

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Bahmer, F A; Bahmer, J A

2013-11-01

Cutaneous melanoma, sometimes labeled as "black skin cancer", is increasing in frequency and becoming a more common literary motive. In US literature, Sylvia Plath and Charles Bukowski depicted melanoma more than 50 years ago, later Stephen King and Thomas C. Boyle. In German literature, Charlotte Roche shortly mentioned this tumor. Jörg Pönnighaus, both poet and dermatologist, intensively deals in his poems with the effects melanoma has on patients and doctors alike. Melanoma definitely is not the "Black Death" of modern times. However, the perception of this tumor as extremely malignant and as life-threatening makes melanoma a metaphor of the deadly danger of cancer.

Occupational Exposure to Pesticides With Occupational Sun Exposure Increases the Risk for Cutaneous Melanoma.

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Fortes, Cristina; Mastroeni, Simona; Segatto M, Marjorie; Hohmann, Clarissa; Miligi, Lucia; Bakos, Lucio; Bonamigo, Renan

2016-04-01

The objective of the study was to examine the association between occupational exposure to pesticides and cutaneous melanoma, controlling for all possible confounders. A pooled analysis of two case-control studies was conducted in two different geographic areas (Italy and Brazil). Detailed pesticides exposure histories were obtained. Ever use of any pesticide was associated with a high risk of cutaneous melanoma (odds ratio 2.58; 95% confidence interval 1.18-5.65) in particular exposure to herbicides (glyphosate) and fungicides (mancozeb, maneb), after controlling for confounding factors. When subjects were exposed to both pesticides and occupational sun exposure, the risk increased even more (odds ratio 4.68; 95% confidence interval 1.29-17.0). The study suggests an augmented risk of cutaneous melanoma among subjects with exposure to pesticides, in particular among those exposed to occupational sun exposure.

SOLAR RADIATION AS A RISK FACTOR FOR CUTANEOUS MELANOMA: REVIEW

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Marianna Pesce

2013-04-01

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

BAP1 has a survival role in cutaneous melanoma.

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

2015-04-01

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

Selenium for the Prevention of Cutaneous Melanoma

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Cassidy, Pamela B.; Fain, Heidi D.; Cassidy, James P.; Tran, Sally M.; Moos, Philip J.; Boucher, Kenneth M.; Gerads, Russell; Florell, Scott R.; Grossman, Douglas; Leachman, Sancy A.

2013-01-01

The role of selenium (Se) supplementation in cancer prevention is controversial; effects often depend on the nutritional status of the subject and on the chemical form in which Se is provided. We used a combination of in vitro and in vivo models to study two unique therapeutic windows for intervention in the process of cutaneous melanomagenisis, and to examine the utility of two different chemical forms of Se for prevention and treatment of melanoma. We studied the effects of Se in vitro on UV-induced oxidative stress in melanocytes, and on apoptosis and cell cycle progression in melanoma cells. In vivo, we used the HGF transgenic mouse model of UV-induced melanoma to demonstrate that topical treatment with l-selenomethionine results in a significant delay in the time required for UV-induced melanoma development, but also increases the rate of growth of those tumors once they appear. In a second mouse model, we found that oral administration of high dose methylseleninic acid significantly decreases the size of human melanoma xenografts. Our findings suggest that modestly elevation of selenium levels in the skin might risk acceleration of growth of incipient tumors. Additionally, certain Se compounds administered at very high doses could have utility for the treatment of fully-malignant tumors or prevention of recurrence. PMID:23470450

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....

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...

Some interesting prognostic factors related to cutaneous malignant melanoma

International Nuclear Information System (INIS)

Figueroa, Alejandro Yuri Joan; Diaz Anaya, Amnia; Montero Leon, Jorge Felipe; Jimenez Mendes, Lourdes

2009-01-01

The aim of present research was to determine the independent prognostic value and the 3 and 5 years survival of more significant clinicopathological prognostic factors and in each stage, according to pathological staging system of tumor-nodule-metastasis (TNM) in patients with cutaneous malignant melanoma (CMM)

Selenium for the Prevention of Cutaneous Melanoma

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Douglas Grossman

2013-03-01

Full Text Available The role of selenium (Se supplementation in cancer prevention is controversial; effects often depend on the nutritional status of the subject and on the chemical form in which Se is provided. We used a combination of in vitro and in vivo models to study two unique therapeutic windows for intervention in the process of cutaneous melanomagenisis, and to examine the utility of two different chemical forms of Se for prevention and treatment of melanoma. We studied the effects of Se in vitro on UV-induced oxidative stress in melanocytes, and on apoptosis and cell cycle progression in melanoma cells. In vivo, we used the HGF transgenic mouse model of UV-induced melanoma to demonstrate that topical treatment with l-selenomethionine results in a significant delay in the time required for UV-induced melanoma development, but also increases the rate of growth of those tumors once they appear. In a second mouse model, we found that oral administration of high dose methylseleninic acid significantly decreases the size of human melanoma xenografts. Our findings suggest that modestly elevation of selenium levels in the skin might risk acceleration of growth of incipient tumors. Additionally, certain Se compounds administered at very high doses could have utility for the treatment of fully-malignant tumors or prevention of recurrence.

[Cutaneous malignant melanomas in New Caledonia. Study of the Cancer Registry (1977-1987)].

Science.gov (United States)

Di Schino, M; Merouze, F; Huerre, M; Grimaldi, F; Lorthioir, J M; Breda, Y; Merrien, Y

1989-01-01

Investigation of cancer registration files in New Caledonia over a period of 11 years (1977-1987) draws the following conclusions: --The uncorrected incidence rate of cutaneous malignant melanoma is 3.63/100,000 inhabitants/year, for all ethnic groups together. --The incidence rate in the "non-European" population is 0.6/100,000 inhabitants/year. This low incidence and the anatomo-clinical manifestations observed (lentiginous melanoma of extremities) are common in coloured people. --The incidence rate in the "European" population is 8.75/100,000 inhabitants/year is noticeably higher than the incidence in the metropolitan population. Such conclusions are in accordance with the admitted data regarding epidemiology of cutaneous melanoma in high insolation countries. Cumulated incidence rate and topography of lesions are similar in this series whatever the sex.

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

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Ismail Yilmaz

2015-01-01

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

Germline BAP1 inactivation is preferentially associated with metastatic ocular melanoma and cutaneous-ocular melanoma families.

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Ching-Ni Jenny Njauw

Full Text Available BAP1 has been shown to be a target of both somatic alteration in high-risk ocular melanomas (OM and germline inactivation in a few individuals from cancer-prone families. These findings suggest that constitutional BAP1 changes may predispose individuals to metastatic OM and that familial permeation of deleterious alleles could delineate a new cancer syndrome.To characterize BAP1's contribution to melanoma risk, we sequenced BAP1 in a set of 100 patients with OM, including 50 metastatic OM cases and 50 matched non-metastatic OM controls, and 200 individuals with cutaneous melanoma (CM including 7 CM patients from CM-OM families and 193 CM patients from CM-non-OM kindreds.Germline BAP1 mutations were detected in 4/50 patients with metastatic OM and 0/50 cases of non-metastatic OM (8% vs. 0%, p = 0.059. Since 2/4 of the BAP1 carriers reported a family history of CM, we analyzed 200 additional hereditary CM patients and found mutations in 2/7 CM probands from CM-OM families and 1/193 probands from CM-non-OM kindreds (29% vs. 0.52%, p = .003. Germline mutations co-segregated with both CM and OM phenotypes and were associated with the presence of unique nevoid melanomas and highly atypical nevoid melanoma-like melanocytic proliferations (NEMMPs. Interestingly, 7/14 germline variants identified to date reside in C-terminus suggesting that the BRCA1 binding domain is important in cancer predisposition.Germline BAP1 mutations are associated with a more aggressive OM phenotype and a recurrent phenotypic complex of cutaneous/ocular melanoma, atypical melanocytic proliferations and other internal neoplasms (ie. COMMON syndrome, which could be a useful clinical marker for constitutive BAP1 inactivation.

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

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Mahtab Rahbar

2015-01-01

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

Treatment of cutaneous melanoma: current approaches and future prospects

International Nuclear Information System (INIS)

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

2010-01-01

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

Imaging of melanoma with 131I-labeled monoclonal antibodies

International Nuclear Information System (INIS)

Larson, S.M.; Brown, J.P.; Wright, P.W.; Carrasquillo, J.A.; Hellstroem, I.; Hellstroem, K.E.

1983-01-01

Mouse monoclonal antibodies and Fab fragments specific for p97, a melanoma-associated antigen, were used to image metastatic human melanoma. Preclinical studies in athymic mice showed antigen-specific uptake in melanoma xenografts, and toxicity tests in rabbits gave no evidence for tissue damage after injection of up to 100 times the amount of antibody used in humans. Six patients received 1 mg labeled antibody, and one patient received 1 mg of labeled Fab. No. toxic side effects were observed. All of the six patients had positive scans, visualizing 22 of 25 (88%) of lesions larger than 1.5 cm. In tumors from two patients, greater uptake of p97-specific, versus control IgG and Fab, respectively, was documented by biopsy. Antibodies to mouse immunoglobulin appeared in three patients receiving 1 mg or more of radiolabeled mouse antibody

Germline RAD51B truncating mutation in a family with cutaneous melanoma

DEFF Research Database (Denmark)

Wadt, Karin A W; Aoude, Lauren G; Golmard, Lisa

2015-01-01

Known melanoma predisposition genes only account for around 40% of high-density melanoma families. Other rare mutations are likely to play a role in melanoma predisposition. RAD51B plays an important role in DNA repair through homologous recombination, and inactivation of RAD51B has been implicated...... in tumorigenesis. Thus RAD51B is a good candidate melanoma susceptibility gene, and previously, a germline splicing mutation in RAD51B has been identified in a family with early-onset breast cancer. In order to find genetic variants associated with melanoma predisposition, whole-exome sequencing was carried out...... on blood samples from a three-case cutaneous melanoma family. We identified a novel germline RAD51B nonsense mutation, and we demonstrate reduced expression of RAD51B in melanoma cells indicating inactivation of RAD51B. This is only the second report of a germline truncating RAD51B mutation. While...

Radioimmunodetection of human melanoma tumor xenografts with human monoclonal antibodies

International Nuclear Information System (INIS)

Gomibuchi, Makoto; Saxton, R.E.; Lake, R.R.; Katano, Mitsuo; Irie, R.F.

1986-01-01

A human IgM monoclonal antibody has been established that defines a tumor-associated membrane antigen expressed on human melanoma cells. The antigen has been identified as the ganglioside GD2. In this paper, the authors describe the potential usefulness of the human monoclonal antibody for radioimaging. Nude mice bearing tumors derived from a human melanoma cell line were used as a model. Antibody activity was degradated significantly after labeling with 131 I by the use of a modified chloramine-T method. After testing various concentrations, labeled antibody of a specific activity of 2.8μCi/μg produced the best results. Balb/c nude mice bearing a GD2-positive M14 melanoma cell line were injected with 10-30μg of labeled antibody, and its radiolocalization in different organs and in the whole body were evaluated. The best tumor image was obtained on Day 6. The labeled antibody uptake ratio between tumor and muscle was 9.2:1; the ratio between tumor and liver was 1.4:1. These studies represent the first report of experimental tumor imaging with human monoclonal antibody. Human monoclonals will probably prove to be superior reagents for tumor imaging in melanoma patients if the problem of anti-body radiolysis is resolved. (author)

Patients highly value routine follow-up of skin cancer and cutaneous melanoma

DEFF Research Database (Denmark)

Themstrup, Lotte; Jemec, Gregor E; Lock-Andersen, Jørgen

2013-01-01

INTRODUCTION: Skin cancer follow-up is a substantial burden to outpatient clinics. Few studies have investigated patients' views on skin cancer follow-up and cutaneous melanoma. The objective was to investigate patients' perceived benefits and the impact of follow-up. MATERIAL AND METHODS...

Ethnicity and cutaneous melanoma in the city of Sao Paulo, Brazil: a case-control study.

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Olinda C Luiz

Full Text Available BACKGROUND: Over the last century the incidence of cutaneous melanoma has increased worldwide, a trend that has also been observed in Brazil. The identified risk factors for melanoma include the pattern of sun exposure, family history, and certain phenotypic features. In addition, the incidence of melanoma might be influenced by ethnicity. Like many countries, Brazil has high immigration rates and consequently a heterogeneous population. However, Brazil is unique among such countries in that the ethnic heterogeneity of its population is primarily attributable to admixture. This study aimed to evaluate the contribution of European ethnicity to the risk of cutaneous melanoma in Brazil. METHODOLOGY/PRINCIPAL FINDINGS: We carried out a hospital-based case-control study in the metropolitan area of Sao Paulo, Brazil. We evaluated 424 hospitalized patients (202 melanoma patients and 222 control patients regarding phenotypic features, sun exposure, and number of grandparents born in Europe. Through multivariate logistic regression analysis, we found the following variables to be independently associated with melanoma: grandparents born in Europe-Spain (OR = 3.01, 95% CI: 1.03-8.77, Italy (OR = 3.47, 95% CI: 1.41-8.57, a Germanic/Slavic country (OR = 3.06, 95% CI: 1.05-8.93, or ≥ 2 European countries (OR = 2.82, 95% CI: 1.06-7.47; eye color-light brown (OR = 1.99, 95% CI: 1.14-3.84 and green/blue (OR = 4.62; 95% CI 2.22-9.58; pigmented lesion removal (OR = 3.78; 95% CI: 2.21-6.49; no lifetime sunscreen use (OR = 3.08; 95% CI: 1.03-9.22; and lifetime severe sunburn (OR = 1.81; 95% CI: 1.03-3.19. CONCLUSIONS: Our results indicate that European ancestry is a risk factor for cutaneous melanoma. Such risk appears to be related not only to skin type, eye color, and tanning capacity but also to others specific characteristics of European populations introduced in the New World by European immigrants.

Ethnicity and Cutaneous Melanoma in the City of Sao Paulo, Brazil: A Case-Control Study

Science.gov (United States)

Luiz, Olinda C.; Gianini, Reinaldo José; Gonçalves, Fernanda T.; Francisco, Guilherme; Festa-Neto, Cyro; Sanches, José Antonio; Gattas, Gilka J. F.; Chammas, Roger; Eluf-Neto, José

2012-01-01

Background Over the last century the incidence of cutaneous melanoma has increased worldwide, a trend that has also been observed in Brazil. The identified risk factors for melanoma include the pattern of sun exposure, family history, and certain phenotypic features. In addition, the incidence of melanoma might be influenced by ethnicity. Like many countries, Brazil has high immigration rates and consequently a heterogenous population. However, Brazil is unique among such countries in that the ethnic heterogeneity of its population is primarily attributable to admixture. This study aimed to evaluate the contribution of European ethnicity to the risk of cutaneous melanoma in Brazil. Methodology/Principal Findings We carried out a hospital-based case-control study in the metropolitan area of Sao Paulo, Brazil. We evaluated 424 hospitalized patients (202 melanoma patients and 222 control patients) regarding phenotypic features, sun exposure, and number of grandparents born in Europe. Through multivariate logistic regression analysis, we found the following variables to be independently associated with melanoma: grandparents born in Europe—Spain (OR = 3.01, 95% CI: 1.03–8.77), Italy (OR = 3.47, 95% CI: 1.41–8.57), a Germanic/Slavic country (OR = 3.06, 95% CI: 1.05–8.93), or ≥2 European countries (OR = 2.82, 95% CI: 1.06–7.47); eye color—light brown (OR = 1.99, 95% CI: 1.14–3.84) and green/blue (OR = 4.62; 95% CI 2.22–9.58); pigmented lesion removal (OR = 3.78; 95% CI: 2.21–6.49); no lifetime sunscreen use (OR = 3.08; 95% CI: 1.03–9.22); and lifetime severe sunburn (OR = 1.81; 95% CI: 1.03–3.19). Conclusions Our results indicate that European ancestry is a risk factor for cutaneous melanoma. Such risk appears to be related not only to skin type, eye color, and tanning capacity but also to others specific characteristics of European populations introduced in the New World by European immigrants. PMID:22558444

Dual-energy computed tomography in patients with cutaneous malignant melanoma: Comparison of noise-optimized and traditional virtual monoenergetic imaging.

Science.gov (United States)

Martin, Simon S; Wichmann, Julian L; Weyer, Hendrik; Albrecht, Moritz H; D'Angelo, Tommaso; Leithner, Doris; Lenga, Lukas; Booz, Christian; Scholtz, Jan-Erik; Bodelle, Boris; Vogl, Thomas J; Hammerstingl, Renate

2017-10-01

The aim of this study was to investigate the impact of noise-optimized virtual monoenergetic imaging (VMI+) reconstructions on quantitative and qualitative image parameters in patients with cutaneous malignant melanoma at thoracoabdominal dual-energy computed tomography (DECT). Seventy-six patients (48 men; 66.6±13.8years) with metastatic cutaneous malignant melanoma underwent DECT of the thorax and abdomen. Images were post-processed with standard linear blending (M_0.6), traditional virtual monoenergetic (VMI), and VMI+ technique. VMI and VMI+ images were reconstructed in 10-keV intervals from 40 to 100keV. Attenuation measurements were performed in cutaneous melanoma lesions, as well as in regional lymph node, subcutaneous and in-transit metastases to calculate objective signal-to-noise (SNR) and contrast-to-noise (CNR) ratios. Five-point scales were used to evaluate overall image quality and lesion delineation by three radiologists with different levels of experience. Objective indices SNR and CNR were highest at 40-keV VMI+ series (5.6±2.6 and 12.4±3.4), significantly superior to all other reconstructions (all Ptraditional VMI in patients with cutaneous malignant melanoma at thoracoabdominal DECT. Copyright © 2017 Elsevier B.V. All rights reserved.

Technetium-99m labeled monoclonal antibodies in the detection of metastatic melanoma

International Nuclear Information System (INIS)

Serafini, A.N.; Kotler, J.; Feun, L.; Dewanjee, M.; Robinson, D.; Salk, D.; Sfakianakis, G.; Abrams, P.; Savaraj, N.; Goodwin, D.

1989-01-01

Twenty-six stage II/III malignant melanoma patients with 321 measurable metastatic lesions were imaged using Fab fragments of an IgG murine monoclonal antibody labeled specifically with 10-30 mCi Tc-99m with a bi-functional chelating method (NeoRx, Seattle, WA). There were no side effects or adverse reactions. Immunoscintigraphy demonstrated 66.6% of lesions larger than 1 cm and 92.5% of lesions larger than 3 cm. Most frequently detected metastases were in lymph nodes, subcutaneous areas, and bone. Of lesions less than 1 cm, 23.6% were detected if superficial cutaneous lesions were excluded. The smallest detectable lesion was 4 mm. Twenty-one additional clinically unsuspected sites were visualized in 12 of the 26 patients studied. Of these, 56% were confirmed as metastasis by other tests. There were apparent nonspecific localizations owing to other causes, including fracture, varicosities, skin abscess and pneumonitis. Increased experience in image analysis facilitates correct interpretation of these localizations. This study demonstrates that imaging with Tc-99m labeled antibody fragments detects melanoma lesions in organs routinely surveyed and in other areas not routinely assessed by other imaging techniques. The procedure is readily performed and safe. The principal advantage of the test is its ability to survey the entire body and all organs with a single test. Its principal limitation, in common with other diagnostic imaging procedures, is its poor sensitivity for detecting lesions less than 1 cm

Breast metastasis from cutaneous malignant melanoma mimicking a breast cancer.

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

2015-06-25

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

Expression profiles analysis of long non-coding RNAs identified novel lncRNA biomarkers with predictive value in outcome of cutaneous melanoma.

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Ma, Xu; He, Zhijuan; Li, Ling; Yang, Daping; Liu, Guofeng

2017-09-29

Recent advancements in cancer biology have identified a large number of lncRNAs that are dysregulated expression in the development and tumorigenesis of cancers, highlighting the importance of lncRNAs as a key player for human cancers. However, the prognostic value of lncRNAs still remains unclear and needs to be further investigated. In the present study, we aim to assess the prognostic value of lncRNAs in cutaneous melanoma by integrated lncRNA expression profiles from TCGA database and matched clinical information from a large cohort of patients with cutaneous melanoma. We finally identified a set of six lncRNAs that are significantly associated with survival of patients with cutaneous melanoma. A linear combination of six lncRNAs ( LINC01260, HCP5, PIGBOS1, RP11-247L20.4, CTA-292E10.6 and CTB-113P19.5 ) was constructed as a six-lncRNA signature which classified patients of training cohort into the high-risk group and low-risk group with significantly different survival time. The prognostic value of the six-lncRNA signature was validated in both the validation cohort and entire TCGA cohort. Moreover, the six-lncRNA signature is independent of known clinic-pathological factors by multivariate Cox regression analysis and demonstrated good performance for predicting three- and five-year overall survival by time-dependent receiver operating characteristic (ROC) analysis. Our study provides novel insights into the molecular heterogeneity of cutaneous melanoma and also shows potentially important implications of lncRNAs for prognosis and therapy for cutaneous melanoma.

The occurrence of non-melanoma malignant skin lesions and non-cutaneous squamous-cell carcinoma among metastatic melanoma patients: an observational cohort study in Denmark.

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Li, Haojie; Pedersen, Lars; Nørgaard, Mette; Ulrichsen, Sinna P; Thygesen, Sandra K; Nelson, Jeanenne J

2016-05-03

Inhibitors of mutant BRAF are emerging as standard of care in patients with metastatic melanoma who carry relevant oncogenic mutations. However, BRAF inhibitors are found to induce cutaneous squamous cell carcinoma (cuSCC). Population-based background rates of cuSCC and non-cutaneous squamous cell carcinoma (non-cuSCC) in the metastatic melanoma population may contextualize safety signals from randomized clinical trials or the clinics. However, these background rates are lacking. We conducted a historical cohort study to evaluate the background rates of new-onset non-melanoma skin lesions and non-cuSCC among 2,814 metastatic malignant melanoma patients diagnosed in 1997-2010, identified through the Danish Cancer Registry and the National Pathology Registry. Patients were excluded if they had a history of cancer before the metastatic melanoma diagnosis, other than skin cancers. We determined the incidence of non-melanoma malignant skin lesions and non-cuSCC that occurred post metastatic melanoma diagnosis, censoring patients at death, emigration, or December 31, 2011 (end of study period), whichever came first. The median age at metastatic melanoma diagnosis was 64 years. Over 40% of patients died within one year of metastatic diagnosis and ~70% died within 5 years. The percentages of patients with prior history or prevalent disease at metastatic melanoma diagnosis included: 8.6% with cuSCC or basal cell carcinoma (BCC), 3.9% with actinic keratosis (AK), and 0.7% with Bowen's disease. No patients had past or current non-cuSCC per study exclusion criterion. The incidence of non-melanoma skin lesions during the 6 months post-metastatic melanoma diagnosis was as follows: BCC, 1.8% (42.5 per 1000 person-years [PY]); AK, 0.8% (18.6 per 1000 PY); cuSCC, 0.1% (1.7 per 1000 PY); Bowen's disease, 0.04% (0.8 per 1000 PY); and keratoacanthoma (KA), 0%. Non-cuSCC was observed in 3 patients (0.1%; 2.5 per 1000 PY) at 3 sites: bronchi, heart and lung. CuSCC and non-cuSCC were

The occurrence of non-melanoma malignant skin lesions and non-cutaneous squamous-cell carcinoma among metastatic melanoma patients: an observational cohort study in Denmark

International Nuclear Information System (INIS)

Li, Haojie; Pedersen, Lars; Nørgaard, Mette; Ulrichsen, Sinna P.; Thygesen, Sandra K.; Nelson, Jeanenne J.

2016-01-01

Inhibitors of mutant BRAF are emerging as standard of care in patients with metastatic melanoma who carry relevant oncogenic mutations. However, BRAF inhibitors are found to induce cutaneous squamous cell carcinoma (cuSCC). Population-based background rates of cuSCC and non-cutaneous squamous cell carcinoma (non-cuSCC) in the metastatic melanoma population may contextualize safety signals from randomized clinical trials or the clinics. However, these background rates are lacking. We conducted a historical cohort study to evaluate the background rates of new-onset non-melanoma skin lesions and non-cuSCC among 2,814 metastatic malignant melanoma patients diagnosed in 1997–2010, identified through the Danish Cancer Registry and the National Pathology Registry. Patients were excluded if they had a history of cancer before the metastatic melanoma diagnosis, other than skin cancers. We determined the incidence of non-melanoma malignant skin lesions and non-cuSCC that occurred post metastatic melanoma diagnosis, censoring patients at death, emigration, or December 31, 2011 (end of study period), whichever came first. The median age at metastatic melanoma diagnosis was 64 years. Over 40 % of patients died within one year of metastatic diagnosis and ~70 % died within 5 years. The percentages of patients with prior history or prevalent disease at metastatic melanoma diagnosis included: 8.6 % with cuSCC or basal cell carcinoma (BCC), 3.9 % with actinic keratosis (AK), and 0.7 % with Bowen’s disease. No patients had past or current non-cuSCC per study exclusion criterion. The incidence of non-melanoma skin lesions during the 6 months post-metastatic melanoma diagnosis was as follows: BCC, 1.8 % (42.5 per 1000 person-years [PY]); AK, 0.8 % (18.6 per 1000 PY); cuSCC, 0.1 % (1.7 per 1000 PY); Bowen’s disease, 0.04 % (0.8 per 1000 PY); and keratoacanthoma (KA), 0 %. Non-cuSCC was observed in 3 patients (0.1 %; 2.5 per 1000 PY) at 3 sites: bronchi, heart and lung. CuSCC and

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

Directory of Open Access Journals (Sweden)

Amy E Gilbert

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

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

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

2011-01-01

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

ASIP and TYR pigmentation variants associate with cutaneous melanoma and basal cell carcinoma.

NARCIS (Netherlands)

Gudbjartsson, D.F.; Sulem, P.; Stacey, S.N.; Goldstein, A.M.; Rafnar, T.; Sigurgeirsson, B.; Benediktsdottir, K.R.; Thorisdottir, K.; Ragnarsson, R.; Sveinsdottir, S.G.; Magnusson, V.; Lindblom, A.; Kostulas, K.; Botella-Estrada, R.; Soriano, V.; Juberias, P.; Grasa, M.; Saez, B.; Andres, R.; Scherer, D.; Rudnai, P.; Gurzau, E; Koppova, K.; Kiemeney, L.A.L.M.; Jakobsdottir, M.; Steinberg, S.; Helgason, A.; Gretarsdottir, S.; Tucker, M.A.; Mayordomo, J.I.; Nagore, E.; Kumar, R.; Hansson, J.; Olafsson, J.H.; Gulcher, J.R.; Kong, A.; Thorsteinsdottir, U.; Stefansson, K.

2008-01-01

Fair color increases risk of cutaneous melanoma (CM) and basal cell carcinoma (BCC). Recent genome-wide association studies have identified variants affecting hair, eye and skin pigmentation in Europeans. Here, we assess the effect of these variants on risk of CM and BCC in European populations

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

NARCIS (Netherlands)

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

2008-01-01

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

Inverse association between dietary vitamin D and risk of cutaneous melanoma in a northern Italy population

Science.gov (United States)

Vinceti, Marco; Malagoli, Carlotta; Fiorentini, Chiara; Longo, Caterina; Crespi, Catherine M.; Albertini, Giuseppe; Ricci, Cinzia; Lanzoni, Anna; Reggiani, Maurizio; Virgili, Annarosa; Osti, Federica; Lombardi, Mara; Santini, Marcello; Fanti, Pier Alessandro; Dika, Emi; Sieri, Sabina; Krogh, Vittorio; Seidenari, Stefania; Pellacani, Giovanni

2010-01-01

The possibility of an inverse association between vitamin D and risk of cancer and, in particular, of cutaneous malignant melanoma has been suggested, but results of epidemiologic studies are still conflicting. We examined the relation between dietary vitamin D intake and melanoma risk through a population-based case-control study (380 cases, 719 controls) in a northern region of Italy, a country with average vitamin D intake lower than in northern Europe or the US. We assessed average daily intake of vitamin D from foodstuffs using the European Prospective Investigation into Cancer and Nutrition (EPIC) semiquantitative food frequency questionnaire. In this population, levels of vitamin D intake were considerably lower than those observed in recent US studies. We found an inverse relation between dietary vitamin D and melanoma risk in the sample as a whole, in both crude and adjusted analyses. In sex and age-specific analyses, this association appeared to be stronger among males and among older subjects. These findings suggest that, at the relatively low levels of intake observed in this sample, an inverse relation between dietary vitamin D and risk of cutaneous malignant melanoma may exist. PMID:21541899

RARE METASTASES OF MALIGNANT MELANOMA

Directory of Open Access Journals (Sweden)

Marija Trenkić-Božinović

2014-09-01

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

Radioimmunoimaging in malignant melanoma with 111In-labeled monoclonal antibody 96.5

International Nuclear Information System (INIS)

Murray, J.L.; Rosenblum, M.G.; Sobol, R.E.

1985-01-01

A radiolabeled monoclonal antibody (96.5) reactive with an Mr 97,000 antigen found on over 80% of melanoma cell lines and tissue extracts was examined for its ability to detect malignant melanoma metastases in vivo. For imaging purposes, it was conjugated with diethyltriaminepentaacetic acid and subsequently labeled with 111 In by chelation. Thirty-one patients with metastatic melanoma received single injections of monoclonal antibody 96.5 at concentrations ranging from 0.5 to 20 mg and at specific activities of 111 In ranging from 0.125 to 4 mCi/mg. Total-body scans were performed at various time intervals following administration. No serious side effects were observed. Of a total of 100 previously documented metastatic sites, 50 imaged for a specificity of 50%. The number of sites imaged increased significantly as the amount of antibody administered increased relative to the average radiation dose. Considerable background uptake of isotope was observed in blood pool and other organs with gradual acquisition of label in tumor sites by 48 to 72 h. Hence, tumor imaging of melanoma using 111 In-labeled monoclonal antibody 96.5 appeared feasible, especially at antibody doses above 2 mg

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.

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

Science.gov (United States)

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

2017-05-01

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

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

Science.gov (United States)

MacKie, R. M.; Aitchison, T.

1982-01-01

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

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

Science.gov (United States)

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

2017-04-01

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

2-cm versus 4-cm surgical excision margins for primary cutaneous melanoma thicker than 2 mm: a randomised, multicentre trial

DEFF Research Database (Denmark)

Gillgren, Peter; Drzewiecki, Krzysztof T; Niin, Marianne

2011-01-01

Optimum surgical resection margins for patients with clinical stage IIA-C cutaneous melanoma thicker than 2 mm are controversial. The aim of the study was to test whether survival was different for a wide local excision margin of 2 cm compared with a 4-cm excision margin.......Optimum surgical resection margins for patients with clinical stage IIA-C cutaneous melanoma thicker than 2 mm are controversial. The aim of the study was to test whether survival was different for a wide local excision margin of 2 cm compared with a 4-cm excision margin....

Characteristic features of cutaneous melanoma in a dermatology referral centre in Tehran, Iran.

Science.gov (United States)

Kamyab, Kambiz; Kazemi, Sheyda; Azimi, Pourya; Azizpour, Arghavan; Ghandi, Narges; Pirooz, Elham; Noormohammadpour, Pedram; Mirshams-Shahshahani, Mostafa; Daneshpazhooh, Maryam

2017-11-01

The characteristics of cutaneous melanoma in the Middle-Eastern countries is poorly described. Therefore we conducted this study to determine the characteristics of melanoma in Iran. A retrospective, cross sectional study of melanoma patients seen at a tertiary referral centre, Iran, from May 2004 to October 2014. Clinical data included age and gender of the patients at the time of diagnosis, tumour location and tumour size. Histological characteristics included Breslow thickness, Clark level and subtype of tumour. A total of 450 cases of melanoma with a male/female ratio of 1.1:1 were reviewed. The mean age of patients was 57.5 years. The most frequent histological subtypes were acral lentiginous melanoma (30%) and lentigo maligna melanoma (29%). In 215 cases (49%) the tumour was located on the extremities. The second most common site was the face. Tumour invasion was mainly at Clark level III and IV. The mean Breslow thickness was 2.8 mm; 143 (38%) melanomas had a Breslow thickness less than 1 mm (T1) and 86 (23%) were more than 4 mm (T4). This study indicates that clinical and histological features of melanoma in Iranians (who are mainly of skin phototypes 3-4) are different from those observed in Western countries. Further cohort studies are required to evaluate the role of ethnic and environmental risk factors for melanoma in different populations. © 2017 The Australasian College of Dermatologists.

Lock-in thermal imaging for the early-stage detection of cutaneous melanoma: a feasibility study.

Science.gov (United States)

Bonmarin, Mathias; Le Gal, Frédérique-Anne

2014-04-01

This paper theoretically evaluates lock-in thermal imaging for the early-stage detection of cutaneous melanoma. Lock-in thermal imaging is based on the periodic thermal excitation of the specimen under test. Resulting surface temperature oscillations are recorded with an infrared camera and allow the detection of variations of the sample's thermophysical properties under the surface. In this paper, the steady-state and transient skin surface temperatures are numerically derived for a different stage of development of the melanoma lesion using a two-dimensional axisymmetric multilayer heat-transfer model. The transient skin surface temperature signals are demodulated according to the digital lock-in principle to compute both a phase and an amplitude image of the lesions. The phase image can be advantageously used to accurately detect cutaneous melanoma at an early stage of development while the maximal phase shift can give precious information about the lesion invasion depth. The ability of lock-in thermal imaging to suppress disturbing subcutaneous thermal signals is demonstrated. The method is compared with the previously proposed pulse-based approaches, and the influence of the modulation frequency is further discussed. Copyright © 2014 Elsevier Ltd. All rights reserved.

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

Science.gov (United States)

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

2016-08-01

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

Estrogen Receptor ? in Melanoma: From Molecular Insights to Potential Clinical Utility

OpenAIRE

Marzagalli, Monica; Montagnani Marelli, Marina; Casati, Lavinia; Fontana, Fabrizio; Moretti, Roberta Manuela; Limonta, Patrizia

2016-01-01

Cutaneous melanoma is an aggressive tumor with its incidence increasing faster than any other cancer in the past decades. Melanoma is a heterogeneous tumor, with most patients harboring mutations in the BRAF or NRAS oncogenes, leading to the overactivation of the MAPK/ERK and PI3K/Akt pathways. The current therapeutic approaches are based on therapies targeting mutated BRAF and the downstream pathway, and on monoclonal antibodies against the immune checkpoint blockade. However, treatment res...

Epidemiología del melanoma cutáneo Epidemiology of cutaneous melanoma

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R M C Leitner

2006-06-01

Full Text Available Durante las últimas décadas hubo un aumento de la incidencia del melanoma cutáneo en la población caucásica del mundo, aunque este tumor puede afectar a cualquier grupo étnico. En la actualidad se considera a la exposición solar intermitente como un factor de riesgo cierto, en el desarrollo del melanoma cutáneo. La incidencia del melanoma cutáneo en Auckland, Nueva Zelanda, es la mayor del mundo. En Europa, la incidencia y la mortalidad fue creciente hasta que en la década de los 80 se estabilizó. En EEUU también se observó una estabilización de la incidencia. Con respecto a la edad, según la bibliografía consultada la incidencia aumenta a partir de los 20 años; en algunos pacientes con más de 200 nevos y sin pautas de protección solar antes de los 5 años de vida. También se observa aumento de la incidencia en los adultos mayores de 60 años de edad. Con respecto al sexo, en los EEUU y la Argentina es más frecuente en los hombres y en Europa en el sexo femenino.During the last decades there was an increase of incidence of cutaneous melanoma in Caucasian population worldwide, but this tumor can affect any ethnic group. Nowadays, the intermittent solar exposition is a well known predisposing factor. The incidence in Auckland, New Zealand, is the highest in the world. In Europe and in the USA, the incidence and mortality rates decreased until the 80's when it stabilized. Regarding the age of appearance, the incidence increases starting at 20 years of age in patients with more than 200 nevi and without history of sun protection in childhood. There was also an increase in the incidence in adults (>60 y-o. The distribution by sex in USA and Argentina is more frequent in males and in Europe in females.

Cutaneous malignant melanoma show geographic and socioeconomic disparities in stage at diagnosis and excess mortality

DEFF Research Database (Denmark)

Strömberg, Ulf; Peterson, Stefan; Holmberg, Erik

2016-01-01

Background Preventive measures are needed to counteract the increasing burden of cutaneous malignant melanoma (CMM). As a basis for rational melanoma prevention, we investigated geographic differences and impact from socioeconomic factors related to incidence, clinical stage at diagnosis...... and the national Melanoma Quality Register. Geographic and socioeconomic differences in incidence per stage at diagnosis were mapped and correlated to excess mortality. Results Disease mapping based on 9743 cases in 99 municipalities and 20 metropolitan districts showed marked, regional disparities in stage.......37-2.40). Conclusion Residential region and educational level influenced CMM stage and, thereby, excess mortality. These observations suggest that geographic as well as socioeconomic data should be considered in prevention of CMM....

Interferon alpha for the adjuvant treatment of cutaneous melanoma.

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Mocellin, Simone; Lens, Marko B; Pasquali, Sandro; Pilati, Pierluigi; Chiarion Sileni, Vanna

2013-06-18

Interferon alpha is the only agent approved for the postoperative adjuvant treatment of high-risk cutaneous melanoma. However, the survival advantage associated with this treatment is unclear, especially in terms of overall survival. Thus, adjuvant interferon is not universally considered a gold standard treatment by all oncologists. To assess the disease-free survival and overall survival effects of interferon alpha as adjuvant treatment for people with high-risk cutaneous melanoma. We searched the following databases up to August 2012: the Cochrane Skin Group Specialised Register, CENTRAL in The Cochrane Library (2012, issue 8), MEDLINE (from 2005), EMBASE (from 2010), AMED (from 1985), and LILACS (from 1982). We also searched trials databases in 2011, and proceedings of the ASCO annual meeting from 2000 to 2011. We checked the reference lists of selected articles for further references to relevant trials. We included only randomised controlled trials (RCTs) comparing interferon alpha to observation (or any other treatment) for the postoperative (adjuvant) treatment of patients with high-risk skin melanoma, that is, people with regional lymph node metastasis (American Joint Committee on Cancer (AJCC) TNM (tumour, lymph node, metastasis) stage III) undergoing radical lymph node dissection, or people without nodal disease but with primary tumour thickness greater than 1 mm (AJCC TNM stage II). Two authors extracted data, and a third author independently verified the extracted data. The main outcome measure was the hazard ratio (HR), which is the ratio of the risk of the event occurring in the treatment arm (adjuvant interferon) compared to the control arm (no adjuvant interferon). The survival data were either entered directly into Review Manager (RevMan) or extrapolated from Kaplan-Meier plots and then entered into RevMan. Based on the presence of between-study heterogeneity, we applied a fixed-effect or random-effects model for calculating the pooled estimates

Cutaneous melanoma in women

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Mi Ryung Roh, MD

2015-02-01

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

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

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

2017-12-29

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

The prognostic value of serum S100B in patients with cutaneous melanoma: a meta-analysis.

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Mocellin, Simone; Zavagno, Giorgio; Nitti, Donato

2008-11-15

S100B protein detected in the serum of patients with cutaneous melanoma has been long reported as a prognostic biomarker. However, no consensus exists on its implementation in the routine clinical setting. This study aimed to comprehensively and quantitatively summarize the evidence on the suitability of serum S100B to predict patients' survival. Twenty-two series enrolling 3393 patients with TNM stage I to IV cutaneous melanoma were reviewed. Standard meta-analysis methods were applied to evaluate the overall relationship between S100B serum levels and patients' survival (meta-risk). Serum S100B positivity was associated with significantly poorer survival (hazard ratio [HR] = 2.23, 95% CI: 1.92-2.58, p < 0.0001). Between-study heterogeneity was significant, which appeared to be related mainly to dissemination bias and the inclusion of patients with stage IV disease. Considering stage I to III melanoma (n = 1594), the meta-risk remained highly significant (HR = 2.28, 95% CI: 1.8-2.89; p < 0.0001) and studies' estimates were homogeneous. Subgroup analysis of series reporting multivariate survival analysis supported S100B as a prognostic factor independent of the TNM staging system. Our findings suggest that serum S100B detection has a clinically valuable independent prognostic value in patients with melanoma, with particular regard to stage I-III disease. Further investigation focusing on this subset of patients is justified and warranted before S100B can be implemented in the routine clinical management of melanoma. (c) 2008 Wiley-Liss, Inc.

Primary Anorectal Melanoma: An Update

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

2012-01-01

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

Geographic region: Does it matter in cutaneous melanoma of the head and neck?

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Kılıç, Suat; Unsal, Aykut A; Chung, Sei Y; Samarrai, Ruwaa; Kılıç, Sarah S; Baredes, Soly; Eloy, Jean Anderson

2017-12-01

The head and neck are two of the most common locations for cutaneous melanoma. We present the first population-based analysis of geographic differences in anatomic subsite, clinicopathologic and demographical traits, histopathologic subtype, treatment modality, and disease-specific survival (DSS) of cutaneous head and neck melanoma (CHNM). Retrospective database analysis. The Surveillance, Epidemiology, and End Results database was queried for cases of CHNM reported between 2000 and 2013. Patients were grouped into East, Midwest, South, and West regions of the United States. Overall incidence, demographic traits, primary tumor site, clinicopathologic traits, histopathologic subtype, treatment modality, and DSS were compared among regions. There were 49,365 patients with CHNM identified. The West (4.60) and the South (4.42) had significantly higher incidence (per 100,000) than the East (3.84) and Midwest (3.65) (P regions (P region may play a significant role in CHNM. Incidence is higher in the South and the West. Incidence, histologic subtype, treatment modality, and DSS vary among regions. DSS is lower in the South than the West, even after accounting for other major prognostic factors. 4. Laryngoscope, 127:2763-2769, 2017. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.

Effect of vaccination with N-glycolyl GM3/VSSP vaccine by subcutaneous injection in patients with advanced cutaneous melanoma

International Nuclear Information System (INIS)

Osorio, Marta; Gracia, Elias; Reigosa, Edmundo; Hernandez, Julio; Torre, Ana de la; Saurez, Giselle; Perez, Kirenia; Viada, Carmen; Cepeda, Meylán; Carr, Adriana; Ávila, Yisel; Rodríguez, Migdalia; Fernandez, Luis E

2012-01-01

NeuGc-containing gangliosides have been described in melanoma cells and are an attractive target for cancer immunotherapy because they are minimally or not expressed in normal human tissues. Melanoma patients treated with a vaccine based on N-glycolyl gangliosides have shown benefit in progression free survival and overall survival. We conducted a multicenter Phase I/II clinical trial in patients with metastatic cutaneous melanoma treated with the N-gycolyl GM3/very-small-size proteoliposomes vaccine by the subcutaneous route. Selecting the optimal biological dose of the vaccine was the principal objective based on immunogenicity, efficacy, and safety results. Six dose levels were studied and the treatment schedule consisted of five doses administered every 2 weeks and then monthly until 15 doses had been given. Dose levels evaluated were 150, 300, 600, 900, 1200, and 1500 μg with five patients included in each dose level except the 900 μg dose (n = 10). Immunogenicity was determined by antibody titers generated in patients after vaccination. Antitumor effect was measured by response criteria of evaluation in solid tumors and safety was evaluated by common toxicity criteria of adverse events. The vaccine was safe and immunogenic at all doses levels. The most frequent adverse events related to vaccination were mild to moderate injection site reactions and flu-like symptoms. Vaccination induced specific anti-NeuGcGM3 immunoglobulin M and immunoglobulin G antibody responses in all patients. Disease control (objective response or stable disease) was obtained in 38.46% of patients. Global median overall survival was 20.20 months. Two patients achieved overall survival duration of about 4 and 5 years, respectively. The 900 μg dose resulted in overall survival duration of 19.40 months and was selected as the biological optimal dose

Identification of an Immunogenic Subset of Metastatic Uveal Melanoma.

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

2016-05-01

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

A cryptic BAP1 splice mutation in a family with uveal and cutaneous melanoma, and paraganglioma

DEFF Research Database (Denmark)

Wadt, K.; Choi, J.; Chung, J.Y.

2012-01-01

Inactivating germ line BRCA1-associated protein-1 (BAP1) mutations have recently been reported in families with uveal or cutaneous malignant melanoma (UMM, CMM), mesothelioma, and meningioma. Although apparently predisposing to a wide range of tumors, the exact tumor spectrum associated with germ...

Title: hypofractionated postoperative irradiation for cutaneous melanoma of the head and neck

International Nuclear Information System (INIS)

Omizo, Russ T.; Marquez, Carol M.; Vetto, John T.

1996-01-01

Purpose/Objective: To evaluate the efficacy and tolerance of hypofractionated postoperative irradiation in patients with head and neck cutaneous melanoma at high risk for local-regional recurrence. Methods and Materials: Between May 1990 to February 1995, 26 patients with cutaneous melanoma of the head and neck were evaluated in the Department of Radiation Oncology at the Oregon Health Sciences University for elective postoperative hypofractionated irradiation. Twelve patients were excluded from analysis because of simultaneous distant metastatic disease. The remaining 14 patients were at high risk for local-regional recurrence because of either nodal disease, T3 or greater disease, recurrent disease following previous treatment or a combination of the above. TNM stage distribution for patients treated at initial presentation was: T4aN1-2, T4aN0-3, T3bN0-1, T3aN0-1, T2N1-1 and TxN1-1. The initial TNM stage for patients presenting with recurrent disease was: T4aN2-a, T4aN1-1, T1N0-1, T2N0-1 and TxN1-1. All patients received adjuvant irradiation to at least 2 echelons of draining lymph nodes +/- the primary site. The median elapsed time between surgery and irradiation was 4 weeks. Hypofractionated irradiation consisted of 600 cGy fractions given twice weekly for 5 fractions. Twelve patients were treated with electrons of appropriate energy, 1 with photons and 1 with photons and electrons. Median duration of treatment was 15 days. Results: With a median follow-up of 41 months, 2 patients have failed local-regionally and at distant sites and one patient has failed with distant disease only. The actuarial 5 year local-regional control rate is 86% with a standard error of 9%. The actuarial 5 year survival is 60% with a standard error of 16%. Acute side effects were self limiting and were most commonly erythema and mucositis. Chronic side effects were mild and included fibrosis, telangiectasias and xerostomia. Conclusions: Adjuvant hypofractionated irradiation provides

Strong antitumor activities of IgG3 antibodies to a human melanoma-associated ganglioside

International Nuclear Information System (INIS)

Hellstroem, I.; Brankovan, V.; Hellstroem, K.E.

1985-01-01

Three mouse monoclonal IgG3 antibodies, 2B2, IF4, and MG-21, recognize a G/sub D3/ ganglioside antigen that is expressed at the cell surface of most human melanomas. All three antibodies mediate antibody-dependent cellular cytotoxicity (ADCC) in vitro when tested with human lymphocytes or effector cells in a 2-hr or 4-hr 51 Cr-release test, and one antibody, MG-21, also gives strong complement-dependent cytotoxicity with human serum. Antibody 2B2, which gives ADDC also in the presence of mouse lymphocytes, inhibited the outgrowth of a human melanoma in nude mice, but antibody IF4, which showed no ADCC with mouse lymphocyte effectors, did not

Survival of cutaneous malignant melanoma patients at University of Iowa Hospitals: 1950--1974.

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Griffel, M

1981-01-01

Survival of 387 patients treated for cutaneous malignant melanoma at University of Iowa Hospitals during the period 1950--1974 was analyzed. For the entire period, the observed five-year survivals were 57% for women and 33% for men; the corresponding ten-year survivals were 43 and 23%. For both men and women, there was an impressive improvement in outcome between the earliest and the latest periods, so that for 1970--1974, the five-year observed survival was 68% for women and 49% for men. Data are presented on mean age at diagnosis, distribution by stage, site, and sex, and survival by site and sex. The question is raised whether the biologic nature of malignant melanoma is variable, so that increased incidence is associated with better prognosis.

Cutaneous Papillomaviruses and Non-melanoma Skin Cancer: Causal Agents or Innocent Bystanders?

Science.gov (United States)

Hasche, Daniel; Vinzón, Sabrina E; Rösl, Frank

2018-01-01

There is still controversy in the scientific field about whether certain types of cutaneous human papillomaviruses (HPVs) are causally involved in the development of non-melanoma skin cancer (NMSC). Deciphering the etiological role of cutaneous HPVs requires - besides tissue culture systems - appropriate preclinical models to match the obtained results with clinical data from affected patients. Clear scientific evidence about the etiology and underlying mechanisms involved in NMSC development is fundamental to provide reasonable arguments for public health institutions to classify at least certain cutaneous HPVs as group 1 carcinogens. This in turn would have implications on fundraising institutions and health care decision makers to force - similarly as for anogenital cancer - the implementation of a broad vaccination program against "high-risk" cutaneous HPVs to prevent NMSC as the most frequent cancer worldwide. Precise knowledge of the multi-step progression from normal cells to cancer is a prerequisite to understand the functional and clinical impact of cofactors that affect the individual outcome and the personalized treatment of a disease. This overview summarizes not only recent arguments that favor the acceptance of a viral etiology in NMSC development but also reflects aspects of causality in medicine, the use of empirically meaningful model systems and strategies for prevention.

Cutaneous Papillomaviruses and Non-melanoma Skin Cancer: Causal Agents or Innocent Bystanders?

Directory of Open Access Journals (Sweden)

Daniel Hasche

2018-05-01

Full Text Available There is still controversy in the scientific field about whether certain types of cutaneous human papillomaviruses (HPVs are causally involved in the development of non-melanoma skin cancer (NMSC. Deciphering the etiological role of cutaneous HPVs requires – besides tissue culture systems – appropriate preclinical models to match the obtained results with clinical data from affected patients. Clear scientific evidence about the etiology and underlying mechanisms involved in NMSC development is fundamental to provide reasonable arguments for public health institutions to classify at least certain cutaneous HPVs as group 1 carcinogens. This in turn would have implications on fundraising institutions and health care decision makers to force – similarly as for anogenital cancer – the implementation of a broad vaccination program against “high-risk” cutaneous HPVs to prevent NMSC as the most frequent cancer worldwide. Precise knowledge of the multi-step progression from normal cells to cancer is a prerequisite to understand the functional and clinical impact of cofactors that affect the individual outcome and the personalized treatment of a disease. This overview summarizes not only recent arguments that favor the acceptance of a viral etiology in NMSC development but also reflects aspects of causality in medicine, the use of empirically meaningful model systems and strategies for prevention.

Worldwide Increasing Incidences of Cutaneous Malignant Melanoma

International Nuclear Information System (INIS)

Godar, D. E.

2011-01-01

The incidence of cutaneous malignant melanoma (CMM) has been increasing at a steady rate in fair-skinned populations around the world for decades. Scientists are not certain why CMM has been steadily increasing, but strong, intermittent UVB (290-320 nm) exposures, especially sunburn episodes, probably initiate, CMM, while UVA (321-400 nm) passing through glass windows in offices and cars probably promotes it. The CMM incidence may be increasing at an exponential rate around the world, but it definitely decreases with increasing latitude up to∼ 50 degree N where it reverses and increases with the increasing latitude. The inversion in the incidence of CMM may occur because there is more UVA relative to UVB for most of the year at higher latitudes. If windows, allowing UVA to enter our indoor-working environment and cars, are at least partly responsible for the increasing incidence of CMM, then UV filters can be applied to reduce the rate of increase worldwide.

Worldwide Increasing Incidences of Cutaneous Malignant Melanoma

Directory of Open Access Journals (Sweden)

Dianne E. Godar

2011-01-01

Full Text Available The incidence of cutaneous malignant melanoma (CMM has been increasing at a steady rate in fair-skinned populations around the world for decades. Scientists are not certain why CMM has been steadily increasing, but strong, intermittent UVB (290–320 nm exposures, especially sunburn episodes, probably initiate, CMM, while UVA (321–400 nm passing through glass windows in offices and cars probably promotes it. The CMM incidence may be increasing at an exponential rate around the world, but it definitely decreases with increasing latitude up to ~50°N where it reverses and increases with the increasing latitude. The inversion in the incidence of CMM may occur because there is more UVA relative to UVB for most of the year at higher latitudes. If windows, allowing UVA to enter our indoor-working environment and cars, are at least partly responsible for the increasing incidence of CMM, then UV filters can be applied to reduce the rate of increase worldwide.

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

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Parvin Rajabi

2012-01-01

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

Disparities of Immunotherapy Utilization in Patients with Stage III Cutaneous Melanoma: A National Perspective.

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Al-Qurayshi, Zaid; Crowther, Jason E; Hamner, John B; Ducoin, Christopher; Killackey, Mary T; Kandil, Emad

2018-05-01

Immunotherapy combined with surgery is associated with better survival than surgery alone in patients with advanced melanoma. This study examined the utilization of immunotherapy in relation to population characteristics and the associated survival benefit. This was a retrospective cohort study utilizing the US National Cancer Database. The study population included 6,165 adult patients (≥18 years) with stage III cutaneous melanoma (median follow-up=32 months). A total of 1,854 patients underwent immunotherapy in addition to surgery, which was associated with a survival benefit over surgery alone (hazard ratio(HR)=0.66, 95% confidence interval(CI)=0.56-0.77, pimmunotherapy utilization (all pimmunotherapy usage was found (p=0.07). Compared to other demographic factors, insurance status was associated with the greatest disparities in immunotherapy utilization and mortality for patients who underwent surgery for advanced melanoma. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Burden of Melanoma

NARCIS (Netherlands)

C. Holterhues (Cynthia)

2011-01-01

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

Antibody Therapy Targeting CD47 and CD271 Effectively Suppresses Melanoma Metastasis in Patient-Derived Xenografts

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Michael Ngo

2016-08-01

Full Text Available The high rate of metastasis and recurrence among melanoma patients indicates the existence of cells within melanoma that have the ability to both initiate metastatic programs and bypass immune recognition. Here, we identify CD47 as a regulator of melanoma tumor metastasis and immune evasion. Protein and gene expression analysis of clinical melanoma samples reveals that CD47, an anti-phagocytic signal, correlates with melanoma metastasis. Antibody-mediated blockade of CD47 coupled with targeting of CD271+ melanoma cells strongly inhibits tumor metastasis in patient-derived xenografts. This therapeutic effect is mediated by drastic changes in the tumor and metastatic site immune microenvironments, both of whichwhich exhibit greatly increased density of differentiated macrophages and significantly fewer inflammatory monocytes, pro-metastatic macrophages (CCR2+/VEGFR1+, and neutrophils, all of which are associated with disease progression. Thus, antibody therapy that activates the innate immune response in combination with selective targeting of CD271+ melanoma cells represents a powerful therapeutic approach against metastatic melanoma.

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

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Mara Giavina-Bianchi

2015-01-01

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

ACUTE EXUDATIVE PARANEOPLASTIC POLYMORPHOUS VITELLIFORM MACULOPATHY DURING VEMURAFENIB AND PEMBROLIZUMAB TREATMENT FOR METASTATIC MELANOMA.

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Sandhu, Harpal S; Kolomeyer, Anton M; Lau, Marisa K; Shields, Carol L; Schuchter, Lynn M; Nichols, Charles W; Aleman, Tomas S

2017-06-13

To describe a patient with BRAF mutation-positive cutaneous melanoma who developed acute exudative polymorphous vitelliform maculopathy during vemurafenib and pembrolizumab treatment for metastatic melanoma. Retrospective case report documented with wide-field fundus imaging, spectral domain optical coherence tomography, and fundus autofluorescence imaging. A 55-year-old woman with bilateral ductal breast carcinoma and BRAF mutation-positive metastatic cutaneous melanoma complained of bilateral blurred vision within 5 days of starting vemurafenib (BRAF inhibitor). She had been on pembrolizumab (program death receptor antibody) and intermittently on dabrafenib (BRAF inhibitor) and trametinib (MEK inhibitor), and had a normal ophthalmologic examination. On presentation three weeks after the introduction of vemurafenib, her visual acuity had declined to 20/40 in both eyes. Her examination showed diffuse elevation of the fovea with multifocal yellow-white, crescent-shaped subretinal deposits within the macula of both eyes and bilateral neurosensory retinal detachments by spectral domain optical coherence tomography. Discontinuation of vemurafenib and introduction of difluprednate and dorzolamide led to a gradual resolution (over four months) of the neurosensory detachments with recovery of vision. This case report suggests that acute exudative polymorphous vitelliform maculopathy may be directly associated with the use of BRAF inhibitors as treatment for metastatic cutaneous melanoma, or indirectly by triggering autoimmune-paraneoplastic processes. Future identification of similar associations is required to unequivocally link vemurafenib and/or pembrolizumab to acute exudative polymorphous vitelliform maculopathy in metastatic melanoma.

Epidermotropic metastatic melanoma with perilesional depigmentation in an Indian male

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Bhavana Doshi

2013-01-01

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

Majority of the most-cited articles on cutaneous malignant melanoma are published in non-dermatology/melanoma specialized journals.

Science.gov (United States)

Tas, Faruk

2016-01-01

The most-cited articles. (MCAs) are likely those that impressed other researchers and had profound influence on clinical practice or future developments in the related scientific field. This study was conducted to explore a bibliometric approach to assess in where the cutaneous malignant melanoma. (CMM) related MCAs have been published. We identified journals for publications with the word "melanoma" in the title by using the ISI Web of Knowledge Database between 2000 and 2010. The term MCAs arbitrarily defined as equal or more than 100 citations. A total of 425 MCAs were published in 93 journals, led by the Cancer Research. (n = 58) and Journal of Clinical Oncology. (n = 53). Journal categories with the MCAs were the Oncology with 232 articles, followed by the Medicine with 138. articles. The median number of citations was 147. The total numbers of citations were most prominent for the journal Nature and the New England Journal of Medicine. (NEJM) (median 385 and 354, respectively). Total number of citations was the highest for the Science.categorized journals. (median 211). Articles categorized as Dermatology and Melanoma was the least (median 132.5). The median number of citations per year was 14.91. The most valuable cited articles of per year were also published in the journal Nature. (median 59.67) and the NEJM. (median 48.67). The number of citation was the highest for the Science-categorized journals. (median 25.92). Majority of the MCAs on CMM were published in non-dermatology/melanoma specialized journals.

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

Directory of Open Access Journals (Sweden)

Guo Yajun

2006-01-01

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

Immunohistochemical detection of XIAP in melanoma.

Science.gov (United States)

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

2008-03-01

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

Asymptomatic brain metastases in patients with cutaneous metastatic malignant melanoma

DEFF Research Database (Denmark)

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

2013-01-01

-enhanced CT scan of the brain before the start of interleukin-2 (IL-2)-based immunotherapy. Among the 697 patients, 80 had asymptomatic brain metastases (12%). Patients' characteristics did not differ significantly between groups with and without brain metastases. Patients received systemic treatment (IL-2......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......-based or cytotoxic chemotherapy), local treatment (stereotactic radiotherapy, whole-brain radiotherapy or surgery), or best supportive care only. The survival was significantly shorter for patients with asymptomatic brain metastases compared with patients without brain metastases (P...

Meta-analysis of the performance of 18F-FDG PET in cutaneous melanoma

International Nuclear Information System (INIS)

Jimenez-Requena, Felisa; Perez-Vazquez, Jose M.; Delgado-Bolton, Roberto C.; Carreras-Delgado, Jose L.; Fernandez-Perez, Cristina; Gambhir, Sanjiv S.; Schwimmer, Judy

2010-01-01

The aim of this study was to perform a systematic review of the literature to evaluate the accuracy of FDG-PET in staging and restaging of cutaneous melanoma. Systematic methods were used to identify, select, and evaluate the methodologic quality of the studies as well as to summarize the overall findings of sensitivity and specificity. The search strategy consisted of identifying studies published between 2000 and 2006. Inclusion criteria were studies that evaluated the diagnostic performance of FDG-PET in staging/restaging of cutaneous melanoma. The results were compared and pooled with a meta-analysis published previously that included studies published until 1999. The meta-analysis included 95% confidence intervals (CI) of sensitivity, specificity, likelihood-ratio (LR), and diagnostic-odds-ratio (DOR). The quantitative meta-analysis included 24 studies that were analysed in two groups: eight studies were included only in the regional staging analysis (group I), 13 studies were included only in the detection of distant metastases analysis (group II), and three studies were included in both analyses. Compliance with the methodologic-quality criteria was acceptable. We analysed the results of data presented in patients, lesions, basins, lymph-nodes, areas, and scans. Regarding the performance of FDG-PET in the detection of metastases, the pooled studies presented homogeneity for the negative-LR (0.15; 95% CI, 0.10-0.22) when analyzing lesions. When analyzing scans, there was global homogeneity for specificity (0.86; 95% CI, 0.77-0.92), positive-LR (5.86; 95% CI, 3.64-9.43), and DOR (37.89; 95% CI, 15.80-90.86). The pooled studies presented heterogeneity for the other items analysed. Regarding the detection of regional metastases, when analyzing lymph-nodes there was global homogeneity for specificity (0.99; 95% CI, 0.97-0.99; P = 0.101). The meta-regression evidenced that the variable that most influenced the DOR of the different studies and that can explain the

Laser radiation therapy of skin melanoma

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

1981-10-01

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

Akt Inhibitor MK2206 and Hydroxychloroquine in Treating Patients With Advanced Solid Tumors, Melanoma, Prostate or Kidney Cancer

Science.gov (United States)

2018-05-15

Adult Solid Neoplasm; Hormone-Resistant Prostate Carcinoma; Recurrent Melanoma; Recurrent Prostate Carcinoma; Recurrent Renal Cell Carcinoma; Stage IIIA Cutaneous Melanoma AJCC v7; Stage IIIB Cutaneous Melanoma AJCC v7; Stage IIIC Cutaneous Melanoma AJCC v7; Stage IV Cutaneous Melanoma AJCC v6 and v7; Stage IV Prostate Cancer AJCC v7; Stage IV Renal Cell Cancer AJCC v7

Preliminary studies of monoclonal antibody lymphoscintigraphy in malignant melanoma

International Nuclear Information System (INIS)

Nelp, W.B.; Eary, J.F.; Jones, R.F.; Hellstrom, K.E.; Hellstrom, I.; Beaumier, P.L.; Krohn, K.A.

1987-01-01

Lymphoscintigraphy was performed at 3 and 20 hr following subcutaneous injection of 131 I anti-melanoma antibody (Fab) in 11 patients who had surgical resection of lymph nodes (neck, axilla, groin) at 24 hr for suspected metastatic melanoma. Comparable amounts of 125 I nonspecific control antibody (Fab) were co-administered. Six patients had nodal metastases and three showed positive images at both time periods. Five patients had no metastases though one was image positive. Four other nondiseased inguinal node groups were image negative. A total of 28 tumored nodes and 110 normal nodes were removed, counted and histologically examined. All metastatic tumors expressed antigen against which the specific Fab was directed. The concentrations of both specific and nonspecific Fab were similar in tumored nodes and both were significantly greater than in normal nodes showed essentially identical intranodal spatial distribution of the specific and control Fab in areas containing tumor. These preliminary results suggest the increased concentration of murine immunoglobulin (Fab) retained in diseased nodes was a nonspecific phenomenon

Localization of integrin alpha(v)beta3 and vascular endothelial growth factor receptor-2 (KDR/Flk-1) in cutaneous and oral melanomas of dog.

Science.gov (United States)

Rawlings, N G; Simko, E; Bebchuk, T; Caldwell, S J; Singh, B

2003-07-01

Melanomas are common neoplasms of dogs and arise from pigment-producing cells called melanocytes or melanoblasts. Melanomas of skin are often easily cured by surgical excision, but those of oral mucosa are aggressive, metastasize to the regional lymph nodes and lungs, and respond poorly to conventional therapy. Tumor growth is sustained by proliferation of microvessels via a process called angiogenesis. Integrin alpha(v)beta3 is expressed in proliferating but not in quiescent microvessels suggesting a role in angiogenesis. Vascular endothelial growth factor (VEGF) manifests its mitogenic and angiogenic effects mainly via VEGF receptor-2 (VEGFR-2/Flk-1). We conducted this immunocytochemical study to investigate the expression of integrin alpha(v)beta3 and VEGFR-2 in archival and fresh samples from cases of canine melanomas. Results show that integrin alpha(v)beta3 was expressed in 72% and 88% of cutaneous and oral melanomas, respectively, and the expression was restricted to and immediately around the melanocytes and endothelial cells. VEGFR-2 staining of selected cases of melanoma revealed that its expression overlapped with the alpha(v)beta3 integrin. Dual immuno-gold electron microscopy confirmed co-localization of integrin alpha(v)beta3 and VEGFR-2 in melanocytes and endothelial cells. These data demonstrate expression and co-localization of integrin alpha(v)beta3 and VEGFR-2 in cutaneous and oral melanomas of dogs.

Analysis of the B-RAFV600E mutation in cutaneous melanoma patients with occupational sun exposure

Science.gov (United States)

CANDIDO, SAVERIO; RAPISARDA, VENERANDO; MARCONI, ANDREA; MALAPONTE, GRAZIA; BEVELACQUA, VALENTINA; GANGEMI, PIETRO; SCALISI, AURORA; McCUBREY, JAMES A.; MAESTRO, ROBERTA; SPANDIDOS, DEMETRIOS A.; FENGA, CONCETTINA; LIBRA, MASSIMO

2014-01-01

Sun-exposure is one of the risk factors associated with the development of a cutaneous neoplasm. In melanoma, the Ras-Raf-MEK-ERK (MAPK) signaling pathway is constitutively activated through multiple mechanisms, including B-RAF mutation. It has been hypothesized that B-RAF mutations in melanocytic lesions arise from DNA damage induced by ultraviolet (UV) radiation. However, it is still discussed if B-RAF mutations are associated with melanoma patients exposed to the sun. Therefore, in the present study, the known B-RAFV600E mutation was analysed in melanoma samples from 30 indoor and 38 outdoor workers. B-RAFV600E mutation was detected in 52 and 73% of outdoor workers and indoor workers, respectively. Of note, this mutation was identified in 12 of 14 (85%) melanoma of the trunk diagnosed in indoor workers and in 9 of 19 (47%) samples from outdoor workers (p=0.03). By analyzing melanomas of other body sites, no statistical difference in the frequency of B-RAFV600E mutation was identified between the groups of workers. It appears that the mutation detected among indoor workers may be associated with a recreational or intermittent exposure to the sun, as usually the trunk is a sun-protected body site. Overall, these data indicate that the B-RAFV600E mutation detected in melanoma is not associated with a chronic exposure to the sun. Mutations detected in other genes may also contribute to melanoma development in the subset of patients exposed to UV radiation. PMID:24424406

Cutaneous melanoma in situ: translational evidence from a large population-based study.

Science.gov (United States)

Mocellin, Simone; Nitti, Donato

2011-01-01

Cutaneous melanoma in situ (CMIS) is a nosologic entity surrounded by health concerns and unsolved debates. We aimed to shed some light on CMIS by means of a large population-based study. Patients with histologic diagnosis of CMIS were identified from the Surveillance Epidemiology End Results (SEER) database. The records of 93,863 cases of CMIS were available for analysis. CMIS incidence has been steadily increasing over the past 3 decades at a rate higher than any other in situ or invasive tumor, including invasive skin melanoma (annual percentage change [APC]: 9.5% versus 3.6%, respectively). Despite its noninvasive nature, CMIS is treated with excision margins wider than 1 cm in more than one third of cases. CMIS is associated with an increased risk of invasive melanoma (standardized incidence ratio [SIR]: 8.08; 95% confidence interval [CI]: 7.66-8.57), with an estimated 3:5 invasive/in situ ratio; surprisingly, it is also associated with a reduced risk of gastrointestinal (SIR: 0.78, CI: 0.72-0.84) and lung (SIR: 0.65, CI: 0.59-0.71) cancers. Relative survival analysis shows that persons with CMIS have a life expectancy equal to that of the general population. CMIS is increasingly diagnosed and is often overtreated, although it does not affect the life expectancy of its carriers. Patients with CMIS have an increased risk of developing invasive melanoma (which warrants their enrollment in screening programs) but also a reduced risk of some epithelial cancers, which raises the intriguing hypothesis that genetic/environmental risk factors for some tumors may oppose the pathogenesis of others.

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.

Intravenous cidofovir for resistant cutaneous warts in a patient with psoriasis treated with monoclonal antibodies.

LENUS (Irish Health Repository)

McAleer, M A

2012-02-01

Human papilloma virus is a common and often distressing cutaneous disease. It can be therapeutically challenging, especially in immunocompromised patients. We report a case of recalcitrant cutaneous warts that resolved with intravenous cidofovir treatment. The patient was immunocompromised secondary to monoclonal antibody therapy for psoriasis.

2-cm versus 4-cm surgical excision margins for primary cutaneous melanoma thicker than 2 mm: a randomised, multicentre trial

DEFF Research Database (Denmark)

Gillgren, Peter; Drzewiecki, Krzysztof T; Niin, Marianne

2011-01-01

Optimum surgical resection margins for patients with clinical stage IIA-C cutaneous melanoma thicker than 2 mm are controversial. The aim of the study was to test whether survival was different for a wide local excision margin of 2 cm compared with a 4-cm excision margin....

DNA repair gene polymorphisms and risk of cutaneous melanoma: a systematic review and meta-analysis.

Science.gov (United States)

Mocellin, Simone; Verdi, Daunia; Nitti, Donato

2009-10-01

Polymorphisms of DNA repair-related genes might modulate cancer predisposition. We performed a systematic review and meta-analysis of the available evidence regarding the relationship between these polymorphisms and the risk of developing cutaneous melanoma. Relevant studies were searched using PubMed, Medline, Embase, Cancerlit, Cochrane and ISI Web of Knowledge databases. Data were gathered according to the Meta-analysis Of Observational Studies in Epidemiology (MOOSE) guidelines. The model-free approach was adopted to perform the meta-analysis of the retrieved data. We identified 20 original reports that describe the relationship between melanoma risk and the single-nucleotide polymorphisms (SNPs) of 16 genes (cases = 4195). For seven SNPs considered in at least two studies, the findings were heterogeneous. Data were suitable for meta-analysis only in the case of the XPD/ERCC2 SNP rs13181 (cases = 2308, controls = 3698) and demonstrated that the variant C allele is associated with increased melanoma risk (odds ratio = 1.12, 95% confidence interval = 1.03-1.21, P = 0.01; population attributable risk = 9.6%). This is the first meta-analysis suggesting that XPD/ERCC2 might represent a low-penetrance melanoma susceptibility gene. Much work is still to be done before definitive conclusions can be drawn on the role of DNA repair alterations in melanomagenesis since for the other genes involved in this highly complex process, the available information is scarce or null.

Melanoma genetics

DEFF Research Database (Denmark)

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

2015-01-01

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

Immunohistochemical Expression of MCAM/CD146 in Canine Melanoma.

Science.gov (United States)

Abou Asa, S

2017-07-01

MCAM/CD146 (melanoma cell adhesion molecule/CD146) is a transmembrane immunoglobulin superfamily cell adhesion molecule involved in transendothelial migration and signal transduction. It is expressed in melanoma, squamous cell carcinoma, prostatic, ovarian, cervical and endometrial cancers and promotes tumour growth, angiogenesis and metastasis. Melanoma is the most common malignant oral tumour of dogs and also arises in the skin, nail bed and footpad. The aim of this study was to investigate the immunohistochemical expression of MCAM/CD146 in 51 canine melanomas, including oral, cutaneous and ocular tumours. Seventeen of the 51 (33.3%) cases were negative, eight (15.7%) were weakly positive, seven (13.7%) were moderately positive and 19 (37.3%) were strongly positive. MCAM/CD146 was expressed by both oral and cutaneous melanomas; however, the intensity and the extent of the immunoreactivity was higher in oral (P = 0.009) than in cutaneous tumours (P = 0.058). Most ocular melanomas did not express MCAM/CD146 (P = 0.256). Expression of MCAM/CD146 by canine melanomas may suggest the molecule as a target for treatment, especially in oral melanomas. Copyright © 2017 Elsevier Ltd. All rights reserved.

Vemurafenib for the treatment of melanoma.

LENUS (Irish Health Repository)

Jordan, Emmet John

2012-12-01

Metastatic melanoma is an aggressive disease resistant to chemotherapy. Recent clinical trials have reported improved survival for two novel agents; ipilimumab, a humanized, IgG1 monoclonal antibody that blocks cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and vemurafenib , a BRAF (v-raf murine sarcoma viral oncogene homolog B1) inhibitor targeting an activating mutation in the serine-threonine-protein kinase BRAF gene. AREAS COVERED: The authors reviewed preclinical and clinical data examining the safety of vemurafenib in melanoma. MEDLINE and EMBASE were searched using the medical subject heading \\'vemurafenib\\' and the following text terms: melanoma, BRAF inhibition, vemurafenib. This review provides the reader with an overview of current data examining the efficacy and safety of vemurafenib in metastatic melanoma. EXPERT OPINION: Vemurafenib is an oral agent licensed for patients with BRAF V600E mutation-positive inoperable and metastatic melanoma. The most common adverse effects observed in Phase III clinical trials were dermatological events, arthralgia and fatigue. Specific dermatological toxicities included development of cutaneous squamous cell cancers and keratoacanthomas. Prolongation of the QT interval was also reported. Regular dermatological assessments and electrocardiograms are recommended. Ongoing trials are examining vemurafenib in both the adjuvant setting and metastatic setting in combination with ipilimumab and MEK inhibitors (mitogen-activated protein kinase\\/extracellular signal-regulated kinase). Understanding and overcoming mechanisms of resistance to BRAF inhibitors is the focus of ongoing research.

Epidemiological trends and clinicopathological features of cutaneous melanoma in sporadic and xeroderma pigmentosum Tunisian patients.

Science.gov (United States)

Naouali, Chokri; Jones, Meriem; Nabouli, Imen; Jerbi, Manel; Tounsi, Haifa; Ben Rekaya, Mariem; Ben Ahmed, Melika; Bouhaouala, Balkiss; Messaoud, Olfa; Khaled, Aida; Zghal, Mohamed; Abdelhak, Sonia; Boubaker, Samir; Yacoub-Youssef, Houda

2017-01-01

Epidemiological features and trends of cutaneous melanoma (CM) in North-African populations remain unclear. Those populations are of particular interest as they belong to a mosaic of various other origins (sub-Saharan, European Ancestry, and North-African Berbers). The aim of this study is to draw epidemiological profile and clinicopathological features of CM in the Tunisian population. Incidence analyses were based on data from regional cancer registries. Clinical data were collected from dermatological departments and xeroderma pigmentosum (XP) referral centers and provided CM clinicopathological characteristics and progression. Statistical analyses were achieved using R packages and SPSS 20.0. The incidence of CM in Tunisia is relatively low (0.5-0.7 per 100,000 inhabitants per year). Gender differences were observed regarding anatomical distribution (P = 0.004). Acral lentiginous melanoma (ALM) was the most frequent histological subtype (32.3%); however, nodular melanoma (NM) was the most aggressive and responsible for 54.8% of deaths. CM in XP patients develops at a median age that is 42 years earlier than sporadic cases, with preferential localization on the head and neck (P Xeroderma pigmentosum stands as the major predisposing host factor. © 2016 The International Society of Dermatology.

Anti-cytotoxic T lymphocyte antigen-4 antibodies in melanoma

Directory of Open Access Journals (Sweden)

Tosti G

2013-10-01

Full Text Available Giulio Tosti, Emilia Cocorocchio, Elisabetta PennacchioliDivisione Melanomi e Sarcomi, Istituto Europeo di Oncologia, Milano, ItalyAbstract: Approaches aimed at enhancement of the tumor specific response have provided proof for the rationale of immunotherapy in cancer, both in animal models and in humans. Ipilimumab, an anti-cytotoxic T lymphocyte antigen-4 (CTLA-4 antibody, is a new generation immunotherapeutic agent that has shown activity in terms of disease free and overall survival in metastatic melanoma patients. Its use was approved by the US Food and Drug Administration in March 2011 to treat patients with late stage melanoma that has spread or that cannot be removed by surgery. The mechanism of action of CTLA-4 antibodies in the activation of an antitumor immune response and selected clinical studies of ipilimumab in advanced melanoma patients are discussed. Ipilimumab treatment has been associated with immune related adverse events due to T-cell activation and proliferation. Most of these serious adverse effects are associated with the gastrointestinal tract and include severe diarrhea and colitis. The relationship between immune related adverse events and antitumor activity associated with ipilimumab was explored in clinical studies. Potential biomarkers predictive for clinical response and survival in patients treated with anti-CTLA-4 therapy are presently under investigation. Besides the conventional patterns of response and stable disease as defined by standard Response Evaluation Criteria in Solid Tumors criteria, in subsets of patients, ipilimumab has shown patterns of delayed clinical activity which were associated with an improved overall survival. For this reason a new set of response criteria for tumor immunotherapy has been proposed, which was termed immune related response criteria. These new criteria are presently used to better analyze clinical activity of immunotherapeutic regimens. Ipilimumab is currently under

Dermatoscopic Findings of Seborrheic Keratosis in Melanoma.

Science.gov (United States)

Brandão, Maria Luiza; Oliveira Lima, Cíntia Maria; Moura, Heloísa Helena; Ishida, Cleide; Campos-do-Carmo, Gabriella; Cuzzi, Tullia; Ramos-E-Silva, Marcia

2016-06-01

Cutaneous melanoma may in some instances be confused with seborrheic keratosis, which is a very common neoplasia, more often mistaken for actinic keratosis and verruca vulgaris. Melanoma may clinically resemble seborrheic keratosis and should be considered as its possible clinical simulator. We report a case of melanoma with dermatoscopic characteristics of seborrheic keratosis and emphasize the importance of the dermatoscopy algorithm in differentiating between a melanocytic and a non-melanocytic lesion, of the excisional biopsy for the establishment of the diagnosis of cutaneous tumors, and of the histopathologic examination in all surgically removed samples.

Validation of anti-FXR1 antibodies in the canine species and application to an immunohistochemical study of canine oral melanomas

Directory of Open Access Journals (Sweden)

Laura Nordio

2017-05-01

Full Text Available FXR1 (Fragile X mental retardation-related protein 1 is a cytoplasmic RNA binding protein, which genetic expression has been related to metastatic potential in human melanoma. The aims of the present study were: the validation of two commercially available clones of polyclonal anti-human FXR1 antibody in dogs; their application to investigate FXR1 expression in a group of canine oral melanomas. Anti-FXR1 antibody was not previously validated in the canine species. Two different commercially available polyclonal anti-FXR1 antibodies (respectively made in goat and in rabbit were used. FXR1 protein in canine serum was identified by western blot after SDS-PAGE, using human serum as control. FXR1 immunohistochemical expression was tested in a series of normal tissues, that are expected to express FXR1, and in 31 cases of oral melanomas. The final immunohistochemical protocol used heat-induced unmasking and overnight incubation. FXR1 protein bands in canine serum were detected by tested antibodies, in a more specific way by the rabbit antibody. FXR1 immunohistochemical staining was positive in all tested organs, with different levels of expression. FXR1 was also expressed in 31/31 tested melanomas, with variable intensity and percentage of positive cells (Figure 1. Equal results were achieved with the two antibodies in 8 cases of melanoma, whereas there were variable differences in 22, and one case stained only with goat antibody. The rabbit antibody gave less background staining. This study validated anti-FXR1 antibodies for use in the canine species. This protein was expressed in various normal tissues, as well as in the tested neoplasms. Significance of different level of expression is undergoing evaluation with further studies.

Routine X-ray of the chest is not justified in staging of cutaneous melanoma patients

DEFF Research Database (Denmark)

Gjorup, Caroline Asirvatham; Hendel, Helle Westergren; Pilegaard, Rita Kaae

2016-01-01

-up was 34 months (range: 13-75 months). Of the 603 patients, 25 (4%) had a positive CXR and 578 (96%) had a negative CXR. Four (0.7%) patients had lung metastases of whom two had a true positive and two a false negative CXR, respectively. The sensitivity was 50%, specificity was 96%, the positive predictive...... received funding from the Department of Plastic Surgery, the Research Council at Herlev Gentofte Hospital and the Danish Cancer Society. TRIAL REGISTRATION: The Danish Regional Committee on Biomedical Research Ethics (r. no.: H-4-2014-127), the Danish Data Protection Agency (2012-58-0004, local record no......INTRODUCTION: The incidence of cutaneous melanoma is increasing in Denmark and worldwide. However, the prevalence of distant metastases at the time of diagnosis has decreased to 1%. We therefore questioned the value of routine preoperative chest X-ray (CXR) for staging asymptomatic melanoma...

Ultraviolet Radiation-Induced Cytogenetic Damage in White, Hispanic and Black Skin Melanocytes: A Risk for Cutaneous Melanoma

Energy Technology Data Exchange (ETDEWEB)

Dasgupta, Amrita [Hampton University Skin of Color Research Institute, Hampton, VA 23668 (United States); Katdare, Meena, E-mail: mkatdare@gmail.com [Hampton University Skin of Color Research Institute, Hampton, VA 23668 (United States); Department of Dermatology, Eastern Virginia Medical School, Norfolk, VA 23507 (United States)

2015-08-14

Cutaneous Melanoma (CM) is a leading cause of cancer deaths, with reports indicating a rising trend in the incidence rate of melanoma among Hispanics in certain U.S. states. The level of melanin pigmentation in the skin is suggested to render photoprotection from the DNA-damaging effects of Ultraviolet Radiation (UVR). UVR-induced DNA damage leads to cytogenetic defects visualized as the formation of micronuclei, multinuclei and polymorphic nuclei in cells, and a hallmark of cancer risk. The causative relationship between Sun exposure and CM is controversial, especially in Hispanics and needs further evaluation. This study was initiated with melanocytes from White, Hispanic and Black neonatal foreskins which were exposed to UVR to assess their susceptibility to UVR-induced modulation of cellular growth, cytogenetic damage, intracellular and released melanin. Our results show that White and Hispanic skin melanocytes with similar levels of constitutive melanin are susceptible to UVR-induced cytogenetic damage, whereas Black skin melanocytes are not. Our data suggest that the risk of developing UVR-induced CM in a skin type is correlated with the level of cutaneous pigmentation and its ethnic background. This study provides a benchmark for further investigation on the damaging effects of UVR as risk for CM in Hispanics.

Ultraviolet Radiation-Induced Cytogenetic Damage in White, Hispanic and Black Skin Melanocytes: A Risk for Cutaneous Melanoma

International Nuclear Information System (INIS)

Dasgupta, Amrita; Katdare, Meena

2015-01-01

Cutaneous Melanoma (CM) is a leading cause of cancer deaths, with reports indicating a rising trend in the incidence rate of melanoma among Hispanics in certain U.S. states. The level of melanin pigmentation in the skin is suggested to render photoprotection from the DNA-damaging effects of Ultraviolet Radiation (UVR). UVR-induced DNA damage leads to cytogenetic defects visualized as the formation of micronuclei, multinuclei and polymorphic nuclei in cells, and a hallmark of cancer risk. The causative relationship between Sun exposure and CM is controversial, especially in Hispanics and needs further evaluation. This study was initiated with melanocytes from White, Hispanic and Black neonatal foreskins which were exposed to UVR to assess their susceptibility to UVR-induced modulation of cellular growth, cytogenetic damage, intracellular and released melanin. Our results show that White and Hispanic skin melanocytes with similar levels of constitutive melanin are susceptible to UVR-induced cytogenetic damage, whereas Black skin melanocytes are not. Our data suggest that the risk of developing UVR-induced CM in a skin type is correlated with the level of cutaneous pigmentation and its ethnic background. This study provides a benchmark for further investigation on the damaging effects of UVR as risk for CM in Hispanics

Safety and Efficacy of 188-Rhenium-Labeled Antibody to Melanin in Patients with Metastatic Melanoma

Directory of Open Access Journals (Sweden)

M. Klein

2013-01-01

Full Text Available There is a need for effective “broad spectrum” therapies for metastatic melanoma which would be suitable for all patients. The objectives of Phase Ia/Ib studies were to evaluate the safety, pharmacokinetics, dosimetry, and antitumor activity of 188Re-6D2, a 188-Rhenium-labeled antibody to melanin. Stage IIIC/IV metastatic melanoma (MM patients who failed standard therapies were enrolled in both studies. In Phase Ia, 10 mCi 188Re-6D2 were given while unlabeled antibody preload was escalated. In Phase Ib, the dose of 188Re-6D2 was escalated to 54 mCi. SPECT/CT revealed 188Re-6D2 uptake in melanoma metastases. The mean effective half-life of 188Re-6D2 was 12.4 h. Transient HAMA was observed in 9 patients. Six patients met the RECIST criteria for stable disease at 6 weeks. Two patients had durable disease stabilization for 14 weeks and one for 22 weeks. Median overall survival was 13 months with no dose-limiting toxicities. The data demonstrate that 188Re-6D2 was well tolerated, localized in melanoma metastases, and had antitumor activity, thus warranting its further investigation in patients with metastatic melanoma.

Cutaneous melanoma in Latin America: the need for more data El melanoma cutáneo en América Latina: la necesidad de más datos

Directory of Open Access Journals (Sweden)

Rafael A Schmerling

2011-11-01

Full Text Available OBJECTIVE: To identify the scientific literature on cutaneous melanoma in Latin America and compile all available epidemiologic data to demonstrate the need for reliable regional and country-specific data on incidence and mortality estimates. METHODS: Literature searches were conducted in PubMed, Embase, LILACS, and Google Scholar databases for epidemiologic studies from 1 January 2000 to 31 October 2010 related to melanoma in Argentina, Brazil, Colombia, Mexico, Puerto Rico, and Venezuela. A final search on melanoma cases was carried out using country-specific population-based cancer registries. No statistical analyses were conducted. RESULTS: For all six countries, most epidemiological research on cutaneous melanoma consists of hospital-based or case-control studies. Very few studies report incidence and mortality rates. Attempts to estimate disease rates have relied on national incidence and mortality data and information extracted from cancer registries. While predominance of European ancestry is a known risk factor for developing melanoma, the association of melanoma and ethnicity is not well-documented in some of the populations reviewed. Latin Americans are frequently exposed to ultraviolet (UV radiation due to the tropical weather, high altitude, and thinning ozone layer in some regions. Tanned skin is viewed as healthy and beautiful. While melanoma public health campaigns have been under way in Latin America for decades, increasing melanoma awareness remains imperative. CONCLUSIONS: There is an urgent need to collect accurate epidemiologic melanoma data in Latin America. Future research in the region should include more comprehensive, countryspecific, population-based studies to allow for comparative evaluation of incidence and mortality ratesOBJETIVO: Identificar la literatura científica sobre el melanoma cutáneo en América Latina y recopilar todos los datos epidemiológicos disponibles, con objeto de demostrar la necesidad de

Melanin-targeting antibody as a potential agent for radioimmunotherapy of melanoma

International Nuclear Information System (INIS)

Dadachova, E.; Nosanchuk, J.D.; Shi, L.; Casadevall, A.

2002-01-01

Aim: Melanoma is a cancer of increasing incidence for which new methods of treatment and imaging are urgently needed. Currently there is no effective therapy for metastatic melanoma as this tumor is resistant to radiation and chemotherapy. The majority of human melanomas are pigmented with melanin. Here we investigated the possibility of using a melanin-binding antibody (mAb 6D2) which was originally developed against fungal melanin as a delivery vehicle for RIT of pigmented melanoma. Materials and Methods: MAb 6D2 (IgM type) was generated from hybridomas obtained from mice immunized with melanin isolated from Cryptococcus neoformans. The mAb was radiolabeled with 213 Bi or 111 In via bifunctional chelator CHXA'' and with 188 Re - via 'direct labeling'. The immunoreactivity of radiolabeled 6D2 mAb towards fungal melanin was tested by immunofluorescence. Cell binding of 213 Bi-6D2, 188 Re-6D2 and irrelevant IgM 12A1 was evaluated by incubating 2 μg/mL mAb with 0.23-2 x 10 6 human slightly pigmented melanoma cells SK-28-MEL (whole or lysed) which were grown with or without 110 μM L-tyrosine to promote melanin formation. In vivo binding of 111 In-6D2 was studied by scintigraphic imaging in nude mice injected IP with 2.8 x 10 6 SK-28-MEL cells 24 h before 111 In-6D2; biodistribution of 188 Re-6D2 was performed in nude mice bearing SK-28-MEL xenografted tumors. Results: The immunoreactivity of radiolabeled 6D2 mAb to melanin was demonstrated by immunofluorescence. Cell binding of 213 Bi-6D2 and 188 Re-6D2 was higher for the melanoma cells grown with 110 μM L-tyrosine suggesting melanin-specific binding. There was no significant difference (P>0.05) in binding to the whole or lysed cells which may be due to reactivity with melanin or precursors found on the cell surface. In mice injected IP with SK-28-MEL cells there was more retention of 111 In-6D2 in intraperitoneal cavity compared to irrelevant 111 In-IgM and control animals with no tumor cells. The biodistribution

The measurement of constitutive and facultative skin pigmentation and estimation of sun exposure in Caucasians with basal cell carcinoma and cutaneous malignant melanoma

DEFF Research Database (Denmark)

Lock-Andersen, J; Drzewiecki, K T; Wulf, H C

1998-01-01

In two identical and simultaneously performed case-control studies of basal cell carcinoma (BCC) and cutaneous malignant melanoma (CMM) with age-matched, sex-matched and residence-matched controls, skin pigmentation was measured objectively by skin reflectance spectroscopy in 145 BCC patients...

Scintigraphic detection of metastatic melanoma using indium 111/DTPA conjugated anti-gp240 antibody (ZME-018)

International Nuclear Information System (INIS)

Kirkwood, J.M.; Neumann, R.D.; Zoghbi, S.S.; Ernstoff, M.S.; Cornelius, E.A.; Shaw, C.; Ziyadeh, T.; Fine, J.A.; Unger, M.W.

1987-01-01

We evaluated the toxicity, pharmacokinetics, and localization of a monoclonal IgG2 alpha murine anti-human melanoma (gp240) antibody (ZME-018) that recognizes a tumor-associated cell surface glycoprotein of 240,000 molecular weight present in most melanomas. The antibody was conjugated with DTPA (diethylenetriamine pentaacetic acid) and labeled by chelation of 111 In. One mg of antibody labeled with 5 mCi of 111 In was infused, together with 0 to 40 mg of cold carrier ZME-018. The blood clearance, urinary excretion, and in vivo localization were determined in 26 patients. Scintigraphic images were obtained at 24 hours and 72 hours in all patients. Mild toxicity occurred in one patient. The half-time clearance of labeled monoclonal murine antibody (MoAb) from the blood increased from 16.1 hours at an antibody dose of 1 mg to 35.9 hours at 40 mg. Males showed faster clearance from the blood than did females or a single castrated male, perhaps due to selective concentration of antibody in the testes. Nonspecific uptake in liver, spleen, bone marrow, and intestine was seen in all patients. The percentage of known metastatic foci detected increased with the total dosage of antibody, from 23% at doses less than or equal to 5 mg, to 65%, 87% and 78% for 10, 20, and 40 mg, respectively. We conclude that at doses of greater than or equal to 10 mg, ZME-018 is a safe and potentially useful agent for the scintigraphic detection of metastatic malignant melanoma

Basal cell carcinoma, squamous cell carcinoma and melanoma of the head and face.

Science.gov (United States)

Feller, L; Khammissa, R A G; Kramer, B; Altini, M; Lemmer, J

2016-02-05

Ultraviolet light (UV) is an important risk factor for cutaneous basal cell carcinoma, cutaneous squamous cell carcinoma and cutaneous melanoma of the skin. These cancers most commonly affect persons with fair skin and blue eyes who sunburn rather than suntan. However, each of these cancers appears to be associated with a different pattern of UV exposure and to be mediated by different intracellular molecular pathways.Some melanocortin 1 receptor (MC1R) gene variants play a direct role in the pathogenesis of cutaneous basal cell carcinoma, cutaneous squamous cell carcinoma and cutaneous melanoma apart from their role in determining a cancer-prone pigmentory phenotype (fair skin, red hair, blue eyes) through their interactions with other genes regulating immuno-inflammatory responses, DNA repair or apoptosis.In this short review we focus on the aetiological role of UV in cutaneous basal cell carcinoma, cutaneous squamous cell carcinoma and cutaneous melanoma of the skin, and on some associated biopathological events.

Real-world healthcare costs of ipilimumab in patients with advanced cutaneous melanoma in The Netherlands.

Science.gov (United States)

Franken, Margreet G; Leeneman, Brenda; Jochems, Anouk; Schouwenburg, Maartje G; Aarts, Maureen J B; van Akkooi, Alexander C J; van den Berkmortel, Franchette W P J; van den Eertwegh, Alfonsus J M; de Groot, Jan Willem B; van der Hoeven, Koos J M; Hospers, Geke A P; Kapiteijn, Ellen; Koornstra, Rutger; Kruit, Wim H J; Louwman, Marieke W J; Piersma, Djura; van Rijn, Rozemarijn S; Suijkerbuijk, Karijn P M; Ten Tije, Albert J; Vreugdenhil, Gerard; Wouters, Michel W J M; van Zeijl, Michiel; Haanen, John B A G; Uyl-de Groot, Carin A

2018-07-01

There is limited evidence on the costs associated with ipilimumab. We investigated healthcare costs of all Dutch patients with advanced cutaneous melanoma who were treated with ipilimumab. Data were retrieved from the nation-wide Dutch Melanoma Treatment Registry. Costs were determined by applying unit costs to individual patient resource use. A total of 807 patients who were diagnosed between July 2012 and July 2015 received ipilimumab in Dutch practice. The mean (median) episode duration was 6.27 (4.61) months (computed from the start of ipilimumab until the start of a next treatment, death, or the last date of follow-up). The average total healthcare costs amounted to &OV0556;81 484, but varied widely (range: &OV0556;18 131-&OV0556;160 002). Ipilimumab was by far the most important cost driver (&OV0556;73 739). Other costs were related to hospital admissions (&OV0556;3323), hospital visits (&OV0556;1791), diagnostics and imaging (&OV0556;1505), radiotherapy (&OV0556;828), and surgery (&OV0556;297). Monthly costs for resource use other than ipilimumab were &OV0556;1997 (SD: &OV0556;2629). Treatment-naive patients (n=344) had higher total costs compared with previously-treated patients (n=463; &OV0556;85 081 vs. &OV0556;78 811). Although patients with colitis (n=106) had higher costs for resource use other than ipilimumab (&OV0556;11 426) compared with patients with other types of immune-related adverse events (n=90; &OV0556;9850) and patients with no immune-related adverse event (n=611; &OV0556;6796), they had lower total costs (&OV0556;76 075 vs. &OV0556;87 882 and &OV0556;81 480, respectively). In conclusion, this nation-wide study provides valuable insights into the healthcare costs of advanced cutaneous melanoma patients who were treated with ipilimumab in clinical practice. Most of the costs were attributable to ipilimumab, but the costs and its distribution varied considerably across subgroups.

PRIMARY MALIGNANT MELANOMA OF ARYEPIGLOTTIC FOLD

African Journals Online (AJOL)

2015-12-01

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

Evaluation of a direct immunofluorescent antibody (difma test using Leishmania genus - specific monoclonal antibody in the routine diagnosis of cutaneous leishmaniasis

Directory of Open Access Journals (Sweden)

Martha E. Chico

1995-06-01

Full Text Available A direct immunofluorescent antibody (DIFMA test using a Leishmania genus- specific monoclonal antibody was evaluated in the routine diagnosis of cutaneous leishmaniasis (CL in Ecuador. This test was compared with the standard diagnostic techniques of scrapings, culture and histology. Diagnostic samples were taken from a total of 90 active dermal ulcers from patients from areas of Ecuador known to be endemic for cutaneous leishmaniasis. DIFMA was positive in all lesions. It was shown to be significantly superior to standard diagnostic methods either alone or in combination. The sensitivity of DIFMA did not diminish with chronicity of lesions. This test proved to be extremely useful in the routine diagnosis of CL because it is highly sensitive, is easy to use and produces rapid results.

Limited value of 18F-FDG PET/CT and S-100B tumour marker in the detection of liver metastases from uveal melanoma compared to liver metastases from cutaneous melanoma

International Nuclear Information System (INIS)

Strobel, K.; Veit-Haibach, P.; Fischer, D.R.; Steinert, Hans C.; Schulthess, G.K. von; Bode, B.; Dummer, R.; Imhof, L.; Goldinger, S.

2009-01-01

The objective of this study was to evaluate the value of 18 F-FDG PET/CT and S-100B tumour marker for the detection of liver metastases from uveal melanoma in comparison to liver metastases from cutaneous melanoma. A retrospective evaluation was conducted of 27 liver metastases in 13 patients with uveal melanoma (UM) (mean age: 56.8, range: 30-77) and 43 liver metastases in 14 patients (mean age: 57.9, range: 40-82) with cutaneous melanoma (CM) regarding size and FDG uptake by measuring the maximum standardized uptake value (SUV max ). S-100B serum tumour markers were available in 20 patients. Cytology, histology, additional morphological imaging and follow-up served as reference standard. In nine patients liver metastases were further evaluated histologically regarding GLUT-1 and S-100 receptor expression and regarding epithelial or spindle cell growth pattern. Of 27 liver metastases in 6 of 13 patients (46%) with UM, 16 (59%) were FDG negative, whereas all liver metastases from CM were positive. Liver metastases from UM showed significantly (p max (mean: 3.5, range: 1.5-13.4) compared with liver metastases from CM (mean: 6.6, range: 2.3-15.3). In four of six (66.7%) patients with UM and liver metastases S-100B was normal and in two (33.3%) increased. All PET-negative liver metastases were detectable by morphological imaging (CT or MRI). S-100B was abnormal in 13 of 14 patients with liver metastases from CM. S-100B values were significantly higher (p = 0.007) in the CM patient group (mean S-100B: 10.9 μg/l, range: 0.1-115 μg/l) compared with the UM patients (mean: 0.2 μg/l, range: 0.0-0.5 μg/l). Histological work-up of the liver metastases showed no obvious difference in GLUT-1 or S-100 expression between UM and CM liver metastases. The minority (36%) of patients with UM had extrahepatic metastases and the majority (86%) of patients with CM had extrahepatic metastases, respectively. There was a close to significant trend to better survival of UM patients

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

Directory of Open Access Journals (Sweden)

Andrea Fernandes de Oliveira

2010-10-01

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

Melanoma stem cells in experimental melanoma are killed by radioimmunotherapy

International Nuclear Information System (INIS)

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

2013-01-01

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

Distribution quantification on dermoscopy images for computer-assisted diagnosis of cutaneous melanomas.

Science.gov (United States)

Liu, Zhao; Sun, Jiuai; Smith, Lyndon; Smith, Melvyn; Warr, Robert

2012-05-01

Computerised analysis on skin lesion images has been reported to be helpful in achieving objective and reproducible diagnosis of melanoma. In particular, asymmetry in shape, colour and structure reflects the irregular growth of melanin under the skin and is of great importance for diagnosing the malignancy of skin lesions. This paper proposes a novel asymmetry analysis based on a newly developed pigmentation elevation model and the global point signatures (GPSs). Specifically, the pigmentation elevation model was first constructed by computer-based analysis of dermoscopy images, for the identification of melanin and haemoglobin. Asymmetry of skin lesions was then assessed through quantifying distributions of the pigmentation elevation model using the GPSs, derived from a Laplace-Beltrami operator. This new approach allows quantifying the shape and pigmentation distributions of cutaneous lesions simultaneously. Algorithm performance was tested on 351 dermoscopy images, including 88 malignant melanomas and 263 benign naevi, employing a support vector machine (SVM) with tenfold cross-validation strategy. Competitive diagnostic results were achieved using the proposed asymmetry descriptor only, presenting 86.36 % sensitivity, 82.13 % specificity and overall 83.43 % accuracy, respectively. In addition, the proposed GPS-based asymmetry analysis enables working on dermoscopy images from different databases and is approved to be inherently robust to the external imaging variations. These advantages suggested that the proposed method has good potential for follow-up treatment.

Eradication of Human Hepatic and Pulmonary Melanoma Metastases in SCID Mice by Antibody--Interleukin 2 Fusion Proteins

Science.gov (United States)

Becker, Jurgen C.; Pancook, James D.; Gillies, Stephen D.; Mendelsohn, John; Reisfeld, Ralph A.

1996-04-01

Antibody--cytokine fusion proteins combine the unique targeting ability of antibodies with the multifunctional activity of cytokines. Here, we demonstrate the therapeutic efficacy of such constructs for the treatment of hepatic and pulmonary metastases of different melanoma cell lines. Two antibody--interleukin 2 (IL-2) fusion proteins, ch225-IL2 and ch14.18-IL2, constructed by fusion of a synthetic sequence coding for human IL-2 to the carboxyl end of the Cγ 1 gene of the corresponding antibodies, were tested for their therapeutic efficacy against xenografted human melanoma in vivo. Tumorspecific fusion proteins completely inhibited the growth of hepatic and pulmonary metastases in C.B-17 scid/scid mice previously reconstituted with human lymphokine-activated killer cells, whereas treatment with combinations of the corresponding antibodies plus recombinant IL-2 only reduced the tumor load. Even when treatment with fusion proteins was delayed up to 8 days after inoculation of tumor cells, it still resulted in complete eradication of micrometastases that were established at that time point. Selection of tumor cell lines expressing or lacking the targeted antigen of the administered fusion protein proved the specificity of the observed antitumor effect. Biodistribution analysis demonstrated that the tumorspecific fusion protein accumulated not only in subcutaneous tumors but also in lungs and livers affected with micrometastases. Survival times of animals treated with the fusion protein were more than doubled as compared to those treated with the combination of the corresponding antibody plus IL-2. Our data demonstrate that an immunotherapeutic approach using cytokines targeted by antibodies to tumor sites has potent effects against disseminated human melanoma.

Superior outcome of women with stage I/II cutaneous melanoma: Pooled analysis of four European organisation for research and treatment of cancer phase III trials

NARCIS (Netherlands)

A. Joosse (Arjen); S. Collette (Sandra); S. Suciu (Stefan); T.E.C. Nijsten (Tamar); F.J. Lejeune (Ferdy); U.R. Kleeberg (Ulrich); J.W.W. Coebergh (Jan Willem); A.M.M. Eggermont (Alexander); E.G.E. de Vries (Elisabeth)

2012-01-01

textabstractPurpose: Several studies observed a female advantage in the prognosis of cutaneous melanoma, for which behavioral factors or an underlying biologic mechanism might be responsible. Using complete and reliable follow-up data from four phase III trials of the European Organisation for

Evaluation of 18F-FDG PET/CT Parameters for Detection of Lymph Node Metastasis in Cutaneous Melanoma.

Science.gov (United States)

Cha, Jongtae; Kim, Soyoung; Wang, Jiyoung; Yun, Mijin; Cho, Arthur

2018-02-01

The purpose of this study was to investigate the value of 18 F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) parameters in the detection of regional lymph node (LN) metastasis in patients with cutaneous melanoma. We evaluated patients with cutaneous melanoma who underwent FDG PET/CT for initial staging or recurrence evaluation. A total of 103 patients were enrolled, and 165 LNs were evaluated. LNs that were confirmed pathologically or by follow-up imaging were included in this study. PET parameters, including maximum standardized uptake value (SUVmax), total lesion glycolysis and tumour-to-liver ratio, were used to determine the presence of metastases, and the results were compared with CT-determined LN metastasis. Receiver operating characteristic (ROC) curve analysis was used to determine the optimal cut-off values of the FDG PET parameters. A total of 93 LNs were malignant, and 84 LNs were smaller than 10 mm. In all 165 LNs, an SUVmax of >2.51 showed a sensitivity of 73.1%, a specificity of 88.9%, and an accuracy of 80.0% in detecting metastatic LNs. CT showed a higher specificity (87.3%) and lower accuracy (65.5%). For non-enlarged regional LNs (2.4 showed a high sensitivity (91%) and accuracy (89%) in detecting metastasis in LNs ≥1 cm, and LNs <1 cm with an SUVmax <1.4 were likely to be benign.

/sup 99m/Tc radiolabelling and quality control tests of anti-melanoma monoclonal antibodies and F(ab')/sub 2/ fragments for immunoscintigraphy

International Nuclear Information System (INIS)

Callegaro, L.; Deleide, G.; Dovis, M.; Cecconato, E.; Scassellati, G.A.

1986-01-01

Tumour radioimmunodetection was first developed by using radiolabelled polyclonal antibodies, raised in goats against tumour associated antigens (TAA). The availability of monoclonal antibodies to TAA has definitely contributed to more extensive in vivo use of radiolabelled antibodies. However, many factors are involved in tumour radioimmunolocalization, related either to the antibody and radioisotope features or to the natural history of the tumour itself. The experimental protocol developed by the authors allows a full evaluation of the properties of a particular MoAb.This paper illustrates the work done with on a particular set of monoclonal antibodies, raised against human melanoma associated antigens, with the aim of visualizing primary and metastatic lesions in melanoma patients

Eye and hair colour, skin type and constitutive skin pigmentation as risk factors for basal cell carcinoma and cutaneous malignant melanoma. A Danish case-control study

DEFF Research Database (Denmark)

Lock-Andersen, J; Drzewiecki, K T; Wulf, H C

1999-01-01

To assess the importance of hair and eye colour, skin type and constitutive skin pigmentation as risk factors for basal cell carcinoma and cutaneous malignant melanoma in fair-skinned Caucasians, we conducted two identical case-control studies in Denmark. We studied 145 cases with basal cell...... the present hair colour and eye colour, and the constitutive skin pigmentation was measured objectively by skin reflectance of UV unexposed buttock skin. There were no differences between basal cell carcinoma cases and controls in hair colour or eye colour or constitutive skin pigmentation, but more cases...... were of skin type II than skin type IV; skin type 11 was a risk factor for basal cell carcinoma with an odds ratio (OR) of 2.3. For cutaneous malignant melanoma, more cases than controls were red-haired or blond and of skin type II, but there was no difference in constitutive skin pigmentation. Hair...

Molecular Prognostic Markers in Uveal Melanoma: Expression Profiling and Genomic Studies

NARCIS (Netherlands)

W. Gils (Walter)

2008-01-01

textabstractUveal Melanomas (UMs) arise from melanocytes. This cell type originates from neural crest cells and thereby uveal melanomas share their origin with pheochromocytomas, neuroblastomas, paragangliomas and cutaneous melanomas, other tumors that develop from neural crest originating cells.

Association between risk factors and detection of cutaneous melanoma in the setting of a population-based skin cancer screening.

Science.gov (United States)

Hübner, Joachim; Waldmann, Annika; Eisemann, Nora; Noftz, Maria; Geller, Alan C; Weinstock, Martin A; Volkmer, Beate; Greinert, Rüdiger; Breitbart, Eckhard W; Katalinic, Alexander

2017-07-07

Early detection is considered to improve the prognosis of cutaneous melanoma. The value of population-based screening for melanoma, however, is still controversial. The aim of this study was to evaluate the predictive power of established risk factors in the setting of a population-based screening and to provide empirical evidence for potential risk stratifications. We reanalyzed data (including age, sex, risk factors, and screening results) of 354 635 participants in the Skin Cancer Research to provide Evidence for Effectiveness of Screening in Northern Germany project conducted in the German state of Schleswig-Holstein (2003-2004). In multivariable analysis, atypical nevi [odds ratio (OR): 17.4; 95% confidence interval (CI): 14.4-20.1], personal history of melanoma (OR: 5.3; 95% CI: 3.6-7.6), and multiple (≥40) common nevi (OR: 1.3; 95% CI: 1.1-1.6) were associated with an increased risk of melanoma detection. Family history and congenital nevi were not significantly associated with melanoma detection in the Skin Cancer Research to provide Evidence for Effectiveness of Screening in Northern Germany population. The effects of several risk-adapted screening strategies were evaluated. Hypothesizing a screening of individuals aged more than or equal to 35 years, irrespective of risk factors (age approach), the number needed to screen is 559 (95% CI: 514-612), whereas a screening of adults (aged ≥20) with at least one risk factor (risk approach) leads to an number needed to screen of 178 (95% CI: 163-196). Converted into one screen-detected melanoma, the number of missed melanomas is 0.15 (95% CI: 0.12-0.18) with the age approach and 0.22 (95% CI: 0.19-0.26) with the risk approach. The results indicate that focusing on individuals at high risk for melanoma may improve the cost-effectiveness and the benefit-to-harm balance of melanoma screening programs.

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...... 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...... suggest that patients with CMM do not maintain a cautious sun behavior in connection with an increase in UVR exposure, especially on days with body exposure, when abroad, and on holidays....

Inverse association between atopy and melanoma: A case-control study

NARCIS (Netherlands)

Marasigan, V. (Vivien); M.-A. Morren (Marie-Anne); J. Lambert; Medaer, K. (Karen); Fieuws, S. (Steffen); T.E.C. Nijsten (Tamar); Garmyn, M. (Marjan)

2017-01-01

textabstractHeightened cutaneous immune surveillance in atopic patients may inhibit development of melanoma. The aim of this study was to analyse the association between atopy and melanoma (development and outcome). A total of 188 cases of melanoma and 596 healthy controls were interviewed by

Melanoma of unknown origin: a case series.

LENUS (Irish Health Repository)

Kelly, J

2010-12-01

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

Is UV-A radiation a cause of malignant melanoma?

International Nuclear Information System (INIS)

Moan, J.

1994-01-01

The first action spectrum for cutaneous malignant melanoma was published recently. This spectrum was obtained using the fish Xiphophorus. If the same action spectrum applies to humans, the following statements are true: Sunbathing products (agents to protect against the sun) that absorb UV-B radiation provide almost no protection against cutaneous malignant melanoma. UV-A-solaria are more dangerous than expected so far. If people are determined to use artificial sources of radiation for tanning, they should choose UV-B solaria rather than UV-A-solaria. Fluorescent tubes and halogen lamps may have weak melanomagenic effects. Ozone depletion has almost no effect on the incidence rates of CMM, since ozone absorbs very little UV-A radiation. Sunbathing products which contain UV-A-absorbing compounds or neutral filter (like titanium oxide) provide real protection against cutaneous malignant melanoma, at least if they are photochemically inert. 34 refs., 2 figs

Electrochemotherapy in the treatment of metastatic malignant melanoma

DEFF Research Database (Denmark)

Kunte, C; Letulé, V; Gehl, J

2017-01-01

BACKGROUND: (ECT) is an effective local treatment for cutaneous metastasis. Treatment involves the administration of chemotherapeutic drugs followed by delivery of electrical pulses to the tumour. OBJECTIVES: To investigate the effectiveness of ECT in cutaneous metastases of melanoma and to ident...

[Melanoma in organ transplant patients].

Science.gov (United States)

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

2000-02-01

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

A challenging case of ocular melanoma.

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

2015-01-01

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

Eye and hair colour, skin type and constitutive skin pigmentation as risk factors for basal cell carcinoma and cutaneous malignant melanoma. A Danish case-control study

DEFF Research Database (Denmark)

Lock-Andersen, J; Drzewiecki, K T; Wulf, H C

1999-01-01

To assess the importance of hair and eye colour, skin type and constitutive skin pigmentation as risk factors for basal cell carcinoma and cutaneous malignant melanoma in fair-skinned Caucasians, we conducted two identical case-control studies in Denmark. We studied 145 cases with basal cell...

Peptides in melanoma therapy.

Science.gov (United States)

Mocellin, Simone

2012-01-01

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

Immunotherapy of metastatic melanoma by reversal of immune suppression

Energy Technology Data Exchange (ETDEWEB)

Biggs, M.W.; Eiselein, J.E.

1997-01-01

Beginning with the observation that the human enteorvirus, Poliovirus Sabin 1, will lyse human melanoma cells in culture, clinical trials involving two patients with advance melanoma were performed. Parenteral injection of the viable Poliovirus into cutaneous melanoma metastases followed in 24 hours by oral administration of cyclophosphamide. The results of these two trials are described.

Efficacy and Safety of Nivolumab Alone or in Combination With Ipilimumab in Patients With Mucosal Melanoma: A Pooled Analysis

DEFF Research Database (Denmark)

D'Angelo, Sandra P; Larkin, James; Sosman, Jeffrey A

2017-01-01

Purpose Mucosal melanoma is an aggressive malignancy with a poor response to conventional therapies. The efficacy and safety of nivolumab (a programmed death-1 checkpoint inhibitor), alone or combined with ipilimumab (a cytotoxic T-lymphocyte antigen-4 checkpoint inhibitor), have not been reported...... in this rare melanoma subtype. Patients and Methods Data were pooled from 889 patients who received nivolumab monotherapy in clinical studies, including phase III trials; 86 (10%) had mucosal melanoma and 665 (75%) had cutaneous melanoma. Data were also pooled for patients who received nivolumab combined...... with ipilimumab (n = 35, mucosal melanoma; n = 326, cutaneous melanoma). Results Among patients who received nivolumab monotherapy, median progression-free survival was 3.0 months (95% CI, 2.2 to 5.4 months) and 6.2 months (95% CI, 5.1 to 7.5 months) for mucosal and cutaneous melanoma, with objective response...

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.

Validation of the prognostic value of lymph node ratio in patients with cutaneous melanoma: a population-based study of 8,177 cases.

Science.gov (United States)

Mocellin, Simone; Pasquali, Sandro; Rossi, Carlo Riccardo; Nitti, Donato

2011-07-01

The proportion of positive among examined lymph nodes (lymph node ratio [LNR]) has been recently proposed as an useful and easy-to-calculate prognostic factor for patients with cutaneous melanoma. However, its independence from the standard prognostic system TNM has not been formally proven in a large series of patients. Patients with histologically proven cutaneous melanoma were identified from the Surveillance Epidemiology End Results database. Disease-specific survival was the clinical outcome of interest. The prognostic ability of conventional factors and LNR was assessed by multivariable survival analysis using the Cox regression model. Eligible patients (n = 8,177) were diagnosed with melanoma between 1998 and 2006. Among lymph node-positive cases (n = 3,872), most LNR values ranged from 1% to 10% (n = 2,187). In the whole series (≥5 lymph nodes examined) LNR significantly contributed to the Cox model independently of the TNM effect on survival (hazard ratio, 1.28; 95% confidence interval, 1.23-1.32; P < .0001). On subgroup analysis, the significant and independent prognostic value of LNR was confirmed both in patients with ≥10 lymph nodes examined (n = 4,381) and in those with TNM stage III disease (n = 3,658). In all cases, LNR increased the prognostic accuracy of the survival model. In this large series of patients, the LNR independently predicted disease-specific survival, improving the prognostic accuracy of the TNM system. Accordingly, the LNR should be taken into account for the stratification of patients' risk, both in clinical and research settings. Copyright © 2011 Mosby, Inc. All rights reserved.

Primary cutaneous malignancies in the Northern Cape Province of ...

African Journals Online (AJOL)

Results. A total of 4 270 biopsies (13 cutaneous malignancies) were identified. The commonest was squamous cell carcinoma (SCC), followed by basal cell carcinoma, Kaposi's sarcoma (KS), cutaneous malignant melanoma (CMM) and basosquamous carcinoma, in descending order. The odds of a white male developing ...

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

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Martyna Śniegocka

2018-04-01

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

166Ho and 90Y labeled 6D2 monoclonal antibody for targeted radiotherapy of melanoma: Comparison with 188Re radiolabel

International Nuclear Information System (INIS)

Thompson, S.; Ballard, B.; Jiang, Z.; Revskaya, E.; Sisay, N.; Miller, W.H.; Cutler, C.S.; Dadachova, E.; Francesconi, L.C.

2014-01-01

Introduction: An approach to radioimmunotherapy (RIT) of metastatic melanoma is the targeting of melanin pigment with monoclonal antibodies (mAbs) to melanin radiolabeled with therapeutic radionuclides. The proof of principle experiments were performed using a melanin-binding antibody 6D2 of IgM isotype radiolabeled with a β emitter 188 Re and demonstrated the inhibition of tumor growth. In this study we investigated the efficacy of 6D2 antibody radiolabeled with two other longer lived β emitters 90 Y and 166 Ho in treatment of experimental melanoma, with the objective to find a possible correlation between the efficacy and half-life of the radioisotopes which possess high energy β (E max > 1.5 MeV) emission properties. Methods: 6D2 was radiolabeled with longer lived β emitters 90 Y and 166 Ho in treatment of experimental melanoma in A2058 melanoma tumor-bearing nude mice. The immunoreactivity of the radiolabeled 6D2 mAb, its in vitro binding to the MNT1 human melanoma cells, the biodistribution and therapy in A2058 human melanoma bearing nude mice as well as dosimetry calculations were performed. Results: When labeled with the longer lived 90 Y radionuclide, the 6D2 mAb did not produce any therapeutic effect in tumor bearing mice while the reduction of the tumor growth by 166 Ho-6D2 was very similar to the previously reported therapy results for 188 Re-6D2. In addition, 166 Ho-labeled mAb produced the therapeutic effect on the tumor without any toxic effects while the administration of the 90 Y-labeled radioconjugate was toxic to mice with no appreciable anti-tumor effect. Conclusions: 166 Ho-labeled mAb to melanin produced some therapeutic effect on the tumor without any toxic effects while the administration of the 90 Y-labeled radioconjugate was toxic to mice with no appreciable anti-tumor effect. We concluded that the serum half-life of the 6D2 carrier antibody matched well the physical half-life of 166 Ho to deliver the tumoricidal absorbed dose to the

DMBT1 expression distinguishes anorectal from cutaneous melanoma

DEFF Research Database (Denmark)

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

2009-01-01

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

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

Science.gov (United States)

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

2014-01-01

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

IgG4 subclass antibodies impair antitumor immunity in melanoma

Science.gov (United States)

Karagiannis, Panagiotis; Gilbert, Amy E.; Josephs, Debra H.; Ali, Niwa; Dodev, Tihomir; Saul, Louise; Correa, Isabel; Roberts, Luke; Beddowes, Emma; Koers, Alexander; Hobbs, Carl; Ferreira, Silvia; Geh, Jenny L.C.; Healy, Ciaran; Harries, Mark; Acland, Katharine M.; Blower, Philip J.; Mitchell, Tracey; Fear, David J.; Spicer, James F.; Lacy, Katie E.; Nestle, Frank O.; Karagiannis, Sophia N.

2013-01-01

Host-induced antibodies and their contributions to cancer inflammation are largely unexplored. IgG4 subclass antibodies are present in IL-10–driven Th2 immune responses in some inflammatory conditions. Since Th2-biased inflammation is a hallmark of tumor microenvironments, we investigated the presence and functional implications of IgG4 in malignant melanoma. Consistent with Th2 inflammation, CD22+ B cells and IgG4+-infiltrating cells accumulated in tumors, and IL-10, IL-4, and tumor-reactive IgG4 were expressed in situ. When compared with B cells from patient lymph nodes and blood, tumor-associated B cells were polarized to produce IgG4. Secreted B cells increased VEGF and IgG4, and tumor cells enhanced IL-10 secretion in cocultures. Unlike IgG1, an engineered tumor antigen-specific IgG4 was ineffective in triggering effector cell–mediated tumor killing in vitro. Antigen-specific and nonspecific IgG4 inhibited IgG1-mediated tumoricidal functions. IgG4 blockade was mediated through reduction of FcγRI activation. Additionally, IgG4 significantly impaired the potency of tumoricidal IgG1 in a human melanoma xenograft mouse model. Furthermore, serum IgG4 was inversely correlated with patient survival. These findings suggest that IgG4 promoted by tumor-induced Th2-biased inflammation may restrict effector cell functions against tumors, providing a previously unexplored aspect of tumor-induced immune escape and a basis for biomarker development and patient-specific therapeutic approaches. PMID:23454746

[Acute dyspnea in malignant melanoma].

Science.gov (United States)

Franzen, A M; Günzel, T

2011-09-01

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

The use of a cocktail of single chain Fv antibody fragments to improve the in vitro and in vivo targeting of melanoma

International Nuclear Information System (INIS)

Pacifico, M.D.; Pearl, R.A.; Kupsch, J.M.

2006-01-01

Radio scintigraphy using single chain antibody fragments (scFvs) offers a potenti al means of early detection of melanoma metastases. However, previous studies have shown suboptimal levels of tumour localization and nonspecific background accumulation which may be due to antigen heterogeneity. We aimed to improve tumour localization by using a cocktail of different scFvs targeting different epitopes on melanoma cells. We have previously developed three scFvs against distinct and highly tumour-specific melanoma cell-surface antigens by chain shuffling and antibody phage selection on melanoma cells. Three scFvs, RAFT3, B3 and B4 were labeled with 1 25I odine and tested both individually and as a cocktail in a nude mouse xenograft model far human melanoma. Results demonstrated improved tumour localization in vivo when compared to the individual scFvs. Tumour uptake of the cocktail at l hour was 24.220% ID/g (injected dose/gram) compared with 2.854%, 2.263% and 1.355% far B4, RAFT3 and B3, respectively, when injected individually. In addition, the cocktail exhibited significantly superior tumour to normal tissue ratios far muscle and spleen (p<0.05). A combination or cocktail of scFv clones may have an advantage aver individual scFvs far melanoma targeting in patients because of heterogeneity in the expression of different epitopes of antigens on melanoma cells

Sequential use of indium-111 labeled monoclonal antibodies 96.5 and ZME-018 does not increase detection sensitivity for metastatic melanoma

International Nuclear Information System (INIS)

Frontiera, M.; Murray, J.L.; Lamki, L.

1989-01-01

Two indium-111 labeled anti-melanoma murine monoclonal antibodies (MAb), 96.5 and ZME-018, each recognizing separate antigens on melanoma cells, were administered intravenously to 17 patients with melanoma in a sequential fashion to determine whether: (1) additional tumor sites could be imaged with the combination compared to a single Mab; (2) the first MAb influenced the biodistribution and tumor localization of the second; and (3) significantly toxicity occurred with the combination. Patients were randomized to receive either 96.5, followed by ZME-018, ZME-018 followed by 96.5, or each MAb followed by itself (controls). Infusions of the second MAb occurred 10 days after the first infusion. Gamma camera images were obtained 72 hours after each antibody infusion. There were 139 known metastatic sites of which 72 lesions were localized by either MAb for an overall sensitivity of 52%. The detection rate was higher when lesions only greater than 1.5 cm were considered. Imaging results were independent of MAb administration sequence. When ZME-018 was given as the first infusion, when ZME-018 was given as a second infusion (p = NS). However, mean sensitivities using 96.5 as the first or second infusion were 48% and 66% respectively (p = NS). There was not a significant number of sites detected by MAb 2 that were missed by MAb 1. Human anti-murine antibody (HAMA) response occurred in seven of eight patients studied; two patients who experienced toxicity had levels of HAMA greater than 2000 ng/ml. We conclude that the use of these two murine anti-melanoma monoclonal antibodies given in sequential fashion did not significantly change the imaging sensitivity from that seen with each individual antibody

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

Science.gov (United States)

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

2010-07-01

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

RAC1 P29S regulates PD-L1 expression in melanoma

Science.gov (United States)

Vu, Ha Linh; Rosenbaum, Sheera; Purwin, Timothy J.; Davies, Michael A.; Aplin, Andrew E.

2015-01-01

Summary Whole exome sequencing of cutaneous melanoma has led to the detection of P29 mutations in RAC1 in 5–9% of samples, but the role of RAC1 P29 mutations in melanoma biology remains unclear. Using reverse phase protein array analysis to examine the changes in protein/phospho-protein expression, we identified cyclin B1, PD-L1, Ets-1, and Syk as being selectively upregulated with RAC1 P29S expression and downregulated with RAC1 P29S depletion. Using the melanoma patient samples in TCGA, we found PD-L1 expression to be significantly increased in RAC1 P29S patients compared to RAC1 WT as well as other RAC1 mutants. The finding that PD-L1 is upregulated suggests that oncogenic RAC1 P29S may promote suppression of the antitumor immune response. This is a new insight into the biological function of RAC1 P29S mutations with potential clinical implications as PD-L1 is a candidate biomarker for increased benefit from treatment with anti-PD1 or anti-PD-L1 antibodies. PMID:26176707

Current Research and Development of Chemotherapeutic Agents for Melanoma

Directory of Open Access Journals (Sweden)

Kyaw Minn Hsan

2010-04-01

Full Text Available Cutaneous malignant melanoma is the most lethal form of skin cancer and an increasingly common disease worldwide. It remains one of the most treatment-refractory malignancies. The current treatment options for patients with metastatic melanoma are limited and in most cases non-curative. This review focuses on conventional chemotherapeutic drugs for melanoma treatment, by a single or combinational agent approach, but also summarizes some potential novel phytoagents discovered from dietary vegetables or traditional herbal medicines as alternative options or future medicine for melanoma prevention. We explore the mode of actions of these natural phytoagents against metastatic melanoma.

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

Science.gov (United States)

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

2014-01-01

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

Surgery of Primary Melanomas

Energy Technology Data Exchange (ETDEWEB)

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

2010-05-11

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

Surgery of Primary Melanomas

International Nuclear Information System (INIS)

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

2010-01-01

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

Surgery of Primary Melanomas

Directory of Open Access Journals (Sweden)

Piotr Rutkowski

2010-05-01

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

Real-world use, safety, and survival of ipilimumab in metastatic cutaneous melanoma in The Netherlands.

Science.gov (United States)

Jochems, Anouk; Leeneman, Brenda; Franken, Margreet G; Schouwenburg, Maartje G; Aarts, Maureen J B; van Akkooi, Alexander C J; van den Berkmortel, Franchette W P J; van den Eertwegh, Alfonsus J M; Groenewegen, Gerard; de Groot, Jan Willem B; Haanen, John B A G; Hospers, Geke A P; Kapiteijn, Ellen; Koornstra, Rutger H; Kruit, Wim H J; Louwman, Marieke W J; Piersma, Djura; van Rijn, Rozemarijn S; Ten Tije, Albert J; Vreugdenhil, Gerard; Wouters, Michel W J M; Uyl-de Groot, Carin A; van der Hoeven, Koos J M

2018-07-01

Phase III trials with ipilimumab showed an improved survival in patients with metastatic melanoma. We evaluated the use and safety of ipilimumab, and the survival of all patients with metastatic cutaneous melanoma (N=807) receiving ipilimumab in real-world clinical practice in The Netherlands using data from the Dutch Melanoma Treatment Registry. Patients who were registered between July 2012 and July 2015 were included and analyzed according to their treatment status: treatment-naive (N=344) versus previously-treated (N=463). Overall, 70% of treatment-naive patients and 62% of previously-treated patients received all four planned doses of ipilimumab. Grade 3 and 4 immune-related adverse events occurred in 29% of treatment-naive patients and 21% of previously-treated patients. No treatment-related deaths occurred. Median time to first event was 5.4 months [95% confidence interval (CI): 4.7-6.5 months] in treatment-naive patients and 4.4 months (95% CI: 4.0-4.7 months) in previously-treated patients. Median overall survival was 14.3 months (95% CI: 11.6-16.7 months) in treatment-naive patients and 8.7 months (95% CI: 7.6-9.6 months) in previously-treated patients. In both patient groups, an elevated lactate dehydrogenase level (hazard ratio: 2.25 and 1.70 in treatment-naive and previously-treated patients, respectively) and American Joint Committee on Cancer M1c-stage disease (hazard ratio: 1.81 and 1.83, respectively) were negatively associated with overall survival. These real-world outcomes of ipilimumab slightly differed from outcomes in phase III trials. Although phase III trials are crucial for establishing efficacy, real-world data are of great added value enhancing the generalizability of outcomes of ipilimumab in clinical practice.

Prolonged Survival in Stage III Melanoma with Ipilimumab Adjuvant Therapy

DEFF Research Database (Denmark)

Eggermont, Alexander M M; Chiarion-Sileni, Vanna; Grob, Jean-Jacques

2016-01-01

undergone complete resection of stage III melanoma. Methods After patients had undergone complete resection of stage III cutaneous melanoma, we randomly assigned them to receive ipilimumab at a dose of 10 mg per kilogram (475 patients) or placebo (476) every 3 weeks for four doses, then every 3 months...

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

Science.gov (United States)

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

1991-08-01

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

[Ultrasound in the management of non-melanoma skin cancer].

Science.gov (United States)

Hernández Ibáñez, C; Aguilar Bernier, M; de Troya Martín, M

2015-11-01

Cutaneous ultrasound plays an important role in the study and management of non-melanoma skin cancer. Among other factors, this technique contributes to the diagnosis and differential diagnosis of these tumours, the establishment of their size and relation to neighbouring structures, the delimitation of surgical margins, and the detection of subclinical and recurrent lesions. The present article analyses the role of cutaneous ultrasound in the field of non-melanoma skin cancer (basal and squamous cell carcinomas, lymphomas and dermatofibrosarcoma) through a literature review. Copyright © 2015 Academia Española de Dermatología y Venereología. Published by Elsevier España, S.L.U. All rights reserved.

IQGAP1 is an oncogenic target in canine melanoma.

Directory of Open Access Journals (Sweden)

Becky H Lee

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

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

Science.gov (United States)

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

2016-02-01

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

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.

Preliminary experiences of intralesional immunotherapy in cutaneous metastatic melanoma.

Science.gov (United States)

Ridolfi, Laura; Ridolfi, Ruggero

2002-01-01

Antigen presenting cells are inactive within tumor tissue because of local immunosuppression. Tumor infiltrating lymphocyte signal activation transducing mechanisms are also seriously impaired. Administration of granulocyte macrophage-colony stimulating factor may lead to antigen-presenting cell recovery and interleukin-2 may restore local tumor infiltrating lymphocyte activation. Moreover, interleukin-2 increases the systemic lymphocyte population, an event which seems to correlate with a better prognosis. The present phase I-II study was carried out to examine whether intralesional injection of granulocyte macrophage-colony stimulating factor followed by subcutaneous interleukin-2 would induce a clinical response in advanced, pretreated and elderly melanoma patients. Fourteen patients over 60 years of age received intralesional granulocyte macrophage-colony stimulating factor (150 micrograms per lesion on day 1), generally divided between the two largest cutaneous lesions, followed by perilesional subcutaneous interleukin-2 (3.000.000/IU) for 5 days (3 to 7) every 3 weeks. All patients received 6 courses of treatment unless progression occurred. Clinical evaluation of the treated cutaneous lesions was assessed at the baseline and before every cycle. Distant lesions were checked every two cycles. Four clinical responses (2 partial responses and 2 minimal responses) (28.5%), which also involved lesions that had not been directly treated, and seven cases of stable disease were observed. The response duration for partial response and minimal response was 9, 4, 4 and 2.5+ months, respectively. Stable disease (50%) recorded in the 7 patients was short term, 3-6 months. Three patients rapidly progressed after 2, 2, and 1 therapy cycles, respectively. The patient who reached the best partial response had a fairly high absolute lymphocyte count (1600 to 2400/mm3). The second one, who reached a complete remission after subsequent locoregional chemotherapy and hyperthermia

Adoptive Cell Therapy with Tumor-Infiltrating Lymphocytes in Advanced Melanoma Patients

Directory of Open Access Journals (Sweden)

Mélanie Saint-Jean

2018-01-01

Full Text Available Immunotherapy for melanoma includes adoptive cell therapy with autologous tumor-infiltrating lymphocytes (TILs. This monocenter retrospective study was undertaken to evaluate the efficacy and safety of this treatment of patients with advanced melanoma. All advanced melanoma patients treated with TILs using the same TIL expansion methodology and same treatment interleukin-2 (IL-2 regimen between 2009 and 2012 were included. After sterile intralesional excision of a cutaneous or subcutaneous metastasis, TILs were produced according to a previously described method and then infused into the patient who also received a complementary subcutaneous IL-2 regimen. Nine women and 1 man were treated for unresectable stage IIIC (n=4 or IV (n=6 melanoma. All but 1 patient with unresectable stage III melanoma (1st line had received at least 2 previous treatments, including anti-CTLA-4 antibody for 4. The number of TILs infused ranged from 0.23 × 109 to 22.9 × 109. Regarding safety, no serious adverse effect was reported. Therapeutic responses included a complete remission, a partial remission, 2 stabilizations, and 6 progressions. Among these 4 patients with clinical benefit, 1 is still alive with 9 years of follow-up and 1 died from another cause after 8 years of follow-up. Notably, patients treated with high percentages of CD4 + CD25 + CD127lowFoxp3+ T cells among their TILs had significantly shorter OS. The therapeutic effect of combining TILs with new immunotherapies needs further investigation.

Some interesting prognostic factors related to cutaneous malignant melanoma

International Nuclear Information System (INIS)

Joan Figueroa, AlejandroYuri; Diaz Anaya, Amnia; Montero Leon, Jorge Felipe; Jimenez Mendes, Lourdes

2010-01-01

INTRODUCTION: The aim of present research was to determine the independent prognostic value and the 3 and 5 years survival of more significant clinicopathological prognostic factors and in each stage, according to pathological staging system of tumor-nodule-metastasis (TNM) in patients with cutaneous malignant melanoma (CMM). METHODS: A longitudinal, descriptive and retrospective study was conducted applying the Cox proportional risk form and the Kaplan-Meier method, aimed to search of different risk variables in patients with CMM. We studied 157 patients with CMM, seen during 8 years (1993 to 2001), diagnosed and treated in National Institute of Oncology and Radiobiology of La Habana. RESULTS: The more powerful prognostic variables related to localized disease (stage I and II) were the Breslow density (P: 0,000), the mitosis rate (P: 0,004), and the Clark level (P: 0,04); among the variables related to the regional disease (stage III) the number of lymphatic ganglia involved was the more weighthy (P:0,000) and the more important in Stage IV was the distant visceral metastasis (P:0,003). Survival was decreasing according to the advance of the pathological stage of disease. CONCLUSIONS: The more involved independent prognostic factors were the Breslow rate, the number of involved regional lymphatic nodules and the distant visceral metastasis, which is endorsed by a world consensus. However, variables as age, sex, lesion site, ulceration, host-tumor inflammatory response, histological subtype, satellitosis and transient metastasis, considered as independent prognostic indicators in big casuistries, had not statistical significance in present paper. (author)

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

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Dennis J. Baumgardner

2014-01-01

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

Boronated monoclonal antibody 225.28S for potential use in neutron capture therapy of malignant melanoma

International Nuclear Information System (INIS)

Tamat, S.R.; Moore, D.E.; Patwardhan, A.; Hersey, P.

1989-01-01

The concept of conjugating boron cluster compounds to monoclonal antibodies has been examined by several groups of research workers in boron neutron capture therapy (BNCT). The procedures reported to date for boronation of monoclonal antibodies resulted in either an inadequate level of boron incorporation, the precipitation of the conjugates, or a loss of immunological activity. The present report describes the conjugation of dicesium-mercapto-undecahydrododecaborate (Cs2B12H11SH) to 225.28S monoclonal antibody directed against high molecular weight melanoma-associated antigens (HMW-MAA), using poly-L-ornithine as a bridge to increase the carrying capacity of the antibody and to minimize change in the conformational structure of antibody. The method produces a boron content of 1,300 to 1,700 B atoms per molecule 225.28S while retaining the immunoreactivity. Characterization in terms of the homogeneity of the conjugation of the boron-monoclonal antibody conjugates has been studied by gel electrophoresis and ion-exchange HPLC

Immunoscintigraphy in ocular melanoma

International Nuclear Information System (INIS)

Scheidhauer, K.; Scober, O.; Scheidler, J.; Leinsinger, G.; Scheiffarth, O.; Riedel, K.; Schumacher, U.

1990-01-01

Immunoscintigraphy (IS) of malignant tumors has become an encouraging tool in nuclear medicine. Early diagnosis of small lesions is mandatory for successful cancer therapy generally. The scintigraphic detectability of small lesions ( 2 fragments of the anti-melanoma monoclonal antibody 225.28S; this antibody recognizes the high-molecular-weight melanoma-associated antigen. No adverse effects were observed. In terms of true positive results, Single Photon Emission CT proved to be superior compared to planar scans (81 versus 46 percent true positive results). (author). 30 refs

Estrogen Receptor β in Melanoma: From Molecular Insights to Potential Clinical Utility

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Monica Marzagalli

2016-10-01

Full Text Available Cutaneous melanoma is an aggressive tumor with its incidence increasing faster than any other cancer in the past decades. Melanoma is a heterogeneous tumor, with most patients harboring mutations in the BRAF or NRAS oncogenes, leading to the overactivation of the MAPK/ERK and PI3K/Akt pathways. The current therapeutic approaches are based on therapies targeting mutated BRAF and the downstream pathway, and on monoclonal antibodies against the immune checkpoint blockade. However, treatment resistance and side effects are common events of these therapeutic strategies.Increasing evidence supports that melanoma is a hormone-related cancer. Melanoma incidence is higher in males than in females and females have a significant survival advantage over men. Estrogens exert their effects through estrogen receptors (ER and ERβ that exert opposite effects on cancer growth: ER is associated with a proliferative action and ERβ with an anticancer effect. ERβ is the predominant estrogen receptor in melanoma and its expression decreases in melanoma progression, supporting its role as a tumor suppressor. Thus, ERβ is now considered as an effective molecular target for melanoma treatment. 17β-estradiol was reported to inhibit melanoma cells proliferation. However, clinical trials did not provide the expected survival benefits. In vitro studies demonstrate that ERβ ligands inhibit the proliferation of melanoma cells harboring the NRAS (but not the BRAF mutation, suggesting that ERβ activation might impair melanoma development through the inhibition of the PI3K/Akt pathway. These data suggest that ERβ agonists might be considered as an effective treatment strategy, in combination with MAPK inhibitors, for NRAS mutant melanomas. In an era of personalized medicine, pretreatment evaluation of the expression of ER isoforms together with the concurrent oncogenic mutations should be considered before selecting the most appropriate therapeutic intervention

Estrogen Receptor β in Melanoma: From Molecular Insights to Potential Clinical Utility

Science.gov (United States)

Marzagalli, Monica; Montagnani Marelli, Marina; Casati, Lavinia; Fontana, Fabrizio; Moretti, Roberta Manuela; Limonta, Patrizia

2016-01-01

Cutaneous melanoma is an aggressive tumor; its incidence has been reported to increase fast in the past decades. Melanoma is a heterogeneous tumor, with most patients harboring mutations in the BRAF or NRAS oncogenes, leading to the overactivation of the MAPK/ERK and PI3K/Akt pathways. The current therapeutic approaches are based on therapies targeting mutated BRAF and the downstream pathway, and on monoclonal antibodies against the immune checkpoint blockade. However, treatment resistance and side effects are common events of these therapeutic strategies. Increasing evidence supports that melanoma is a hormone-related cancer. Melanoma incidence is higher in males than in females, and females have a significant survival advantage over men. Estrogens exert their effects through estrogen receptors (ERα and ERβ) that affect cancer growth in an opposite way: ERα is associated with a proliferative action and ERβ with an anticancer effect. ERβ is the predominant ER in melanoma, and its expression decreases in melanoma progression, supporting its role as a tumor suppressor. Thus, ERβ is now considered as an effective molecular target for melanoma treatment. 17β-estradiol was reported to inhibit melanoma cells proliferation; however, clinical trials did not provide the expected survival benefits. In vitro studies demonstrate that ERβ ligands inhibit the proliferation of melanoma cells harboring the NRAS (but not the BRAF) mutation, suggesting that ERβ activation might impair melanoma development through the inhibition of the PI3K/Akt pathway. These data suggest that ERβ agonists might be considered as an effective treatment strategy, in combination with MAPK inhibitors, for NRAS mutant melanomas. In an era of personalized medicine, pretreatment evaluation of the expression of ER isoforms together with the concurrent oncogenic mutations should be considered before selecting the most appropriate therapeutic intervention. Natural compounds that specifically bind to

Adoptive Cell Therapy with Tumor-Infiltrating Lymphocytes in Advanced Melanoma Patients

OpenAIRE

Mélanie Saint-Jean; Anne-Chantal Knol; Christelle Volteau; Gaëlle Quéreux; Lucie Peuvrel; Anabelle Brocard; Marie-Christine Pandolfino; Soraya Saiagh; Jean-Michel Nguyen; Christophe Bedane; Nicole Basset-Seguin; Amir Khammari; Brigitte Dréno

2018-01-01

Immunotherapy for melanoma includes adoptive cell therapy with autologous tumor-infiltrating lymphocytes (TILs). This monocenter retrospective study was undertaken to evaluate the efficacy and safety of this treatment of patients with advanced melanoma. All advanced melanoma patients treated with TILs using the same TIL expansion methodology and same treatment interleukin-2 (IL-2) regimen between 2009 and 2012 were included. After sterile intralesional excision of a cutaneous or subcutaneous ...

Preclinical and phase I studies of monoclonal antibodies in melanoma: Application to boron neutron capture therapy of melanoma

International Nuclear Information System (INIS)

Hersey, P.

1989-01-01

Monoclonal antibodies (MAbs) provide an attractive method of selectively localizing sufficient boron atoms around tumour cells to capture neutrons. Assuming that 10(8)-10(10) 10B atoms are needed for one capture event and that 10(3)-10(4) atoms can be coupled to each antibody molecule, then 10(5)-10(6) antibody molecules gathered on an individual cell will destroy that cell. Binding to normal tissues, on the other hand, would need to be at least 20-fold less than that to tumour tissues to avoid toxic effects of neutrons on surrounding tissues. Preclinical studies in animals show that several MAbs may bind to melanoma cells in sufficient quantities in vitro to localize the required amount of boron per cell. Whether this will occur in vivo, however, may depend not only on antigen density but a variety of other properties of the tumour cells and MAbs. These include the Ig class and affinity of the antibody and whether the antibody is internalized into the tumour cell. The ratio of uptake between tumour and normal tissue is governed by such factors as the percentage of tumour cells within a tumour expressing the antigen and whether the MAb react with normal tissues. Use of Fab or F(ab)2 preparations of the MAb may increase the uptake ratio by preventing uptake of MAb by cells with Fc receptors. In contrast to preclinical animal studies, tumour/normal tissue uptake ratios in phase I studies in humans have been disappointingly low.80 references

Monoclonal antibody OKM5 inhibits the in vitro binding of Plasmodium falciparum-infected erythrocytes to monocytes, endothelial, and C32 melanoma cells

International Nuclear Information System (INIS)

Barnwell, J.W.; Ockenhouse, C.F.; Knowles, D.M. II

1985-01-01

Plasmodium falciparum-infected erythrocytes bind in vitro to human endothelial cells, monocytes, and a certain melanoma cell line. Evidence suggests that this interaction is mediated by similar mechanisms which lead to the sequestration of parasitized erythrocytes in vivo through their attachment to endothelial cells of small blood vessels. They show here the monoclonal antibody OKM5, previously shown to react with the membranes of endothelial cells, monocyte,s and platelets, also reacts with the C32 melanoma cell line which also binds P. falciparum-infected erythrocytes. At relatively low concentrations, OKM5 inhibits and reverses the in vitro adherence of infected erythrocytes to target cells. As with monocytes, OKM5 antibody recognizes an 125 I-labeled protein of approximately 88 Kd on the surface of C32 melanoma cells. It seems likely, therefore, that the 88 Kd polypeptide plays a role in cytoadherence, possibly as the receptor or part of a receptor for a ligand on the surface of infected erythrocytes

Primary malignant melanoma

Directory of Open Access Journals (Sweden)

A. Ferhat Mısır

2016-04-01

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

Abnormal responses to the carcinogen 4-nitroquinoline 1-oxide of cultured fibroblasts from patients with dysplastic nevus syndrome and hereditary cutaneous malignant melanoma

International Nuclear Information System (INIS)

Smith, P.J.; Greene, M.H.; Adams, D.; Paterson, M.C.

1983-01-01

The dysplastic nevus syndrome (DNS) is a preneoplastic melanocyte abnormality which occurs in families affected by hereditary cutaneous malignant melanoma (HCMM). A putative role of host-environmental interactions in the etiology of hereditary melanoma has been strengthened by the recent finding that fibroblasts derived from HCMM/DNS patients demonstrated enhanced sensitivity to u.v.-irradiation in vitro. An extension of these studies is reported in which we have examined the invitro responses to a model environmental carcinogen, 4-nitroquinoline 1-oxide (4NQO), of six non-tumor skin fibroblast strains from HCMM/DNS patients representing five families. Three of the six HCMM/DNS strains showed enhanced cell killing with sensitivities greater than that of a xeroderma pigmentosum (XP) variant strain but less than those of ataxia telangiectasia and XP Group D cell strains. The inhibition and recovery of de novo DNA synthesis, together with the expression of repair synthesis, following 4NQO exposure appeared to be normal in HCMM/DNS strains, irrespective of their subsequent clonogenic potential. The data point to a metabolic anomaly which may contribute to the carcinogenic risk of the melanoma prone preneoplastic state presented by some DNS patients

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

Science.gov (United States)

Mocellin, Simone; Pasquali, Sandro; Nitti, Donato

2011-02-01

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

New-onset mediastinal and central nervous system sarcoidosis in a patient with metastatic melanoma undergoing CTLA4 monoclonal antibody treatment.

LENUS (Irish Health Repository)

Murphy, Kevin P

2014-01-01

Ipilimumab, a cytotoxic monoclonal antibody that inhibits cytotoxic T lymphocyte-associated antigen-4 (CTLA-4), has been established as an effective therapy in the management of advanced melanoma. Immune-mediated adverse events are a common side effect.

Cutaneous melanoma: hints from occupational risks by anatomic site in Swedish men

Science.gov (United States)

Perez-Gomez, B; Pollan, M; Gustavsson, P; Plato, N; Aragones, N; Lopez-Abente, G

2004-01-01

Aims: To improve knowledge of the epidemiology of melanoma by comparing occupational risks of cutaneous melanoma (CM) by anatomic site in Swedish workers. Methods: Male workers employed in 1970 and living in the country in 1960 were followed up from 1971 to 1989 using the Swedish Registers of Death and Cancer. A more specifically exposed subcohort included men reporting the same occupation in 1960 and 1970. For each location, occupational risk ratios (RRs) were extracted from Poisson regression models adjusted by age, period, town size, and geographical area. To diminish the influence of socioeconomic factors, intrasector analyses, comparing only jobs belonging to the same occupational sector, were performed. Risk patterns for different locations were compared. Results: High RRs for different sites were found among workers exposed to UV sources (dentists, physiotherapists, and lithographers), and sun exposed workers (harbour masters, and lighthouse/related work). Risk excesses were seen in fur tailors, tanners/fur dressers, patternmakers/cutters, electrical fitters/wiremen, telephone/telegraph installers/repairmen, and some glass/pottery/tile workers. Results for lower and upper limbs were significantly correlated but somewhat independent of those found in thorax, the most frequent location. Correlation between head/neck and thorax was moderate. Specific risk excesses were found for rolling mill workers in head/neck, for chimney sweeps in upper limbs, and for aircraft pilots/navigators/flight engineers in lower limbs. Conclusions: High RRs in the trunk among occupations with UV exposure from artificial sources suggest an effect not restricted to exposed sites. An unusual distribution of cases and RRs in chimney sweeps, rolling-mill, or glass/pottery/tile workers suggests local effects of exposures. The not previously reported risk excess in this job and in fur related processes, and the RR in electrical fitters and telephone/telegraph installers deserve further

Is UV-A radiation a cause of malignant melanoma. Er UV-A aarsak til malignt melanom

Energy Technology Data Exchange (ETDEWEB)

Moan, J. (Det Norske Radiumhospital, Oslo (Norway))

1994-03-01

The first action spectrum for cutaneous malignant melanoma was published recently. This spectrum was obtained using the fish Xiphophorus. If the same action spectrum applies to humans, the following statements are true: Sunbathing products (agents to protect against the sun) that absorb UV-B radiation provide almost no protection against cutaneous malignant melanoma. UV-A-solaria are more dangerous than expected so far. If people are determined to use artificial sources of radiation for tanning, they should choose UV-B solaria rather than UV-A-solaria. Fluorescent tubes and halogen lamps may have weak melanomagenic effects. Ozone depletion has almost no effect on the incidence rates of CMM, since ozone absorbs very little UV-A radiation. Sunbathing products which contain UV-A-absorbing compounds or neutral filter (like titanium oxide) provide real protection against cutaneous malignant melanoma, at least if they are photochemically inert. 34 refs., 2 figs.

Immunizing Patients With Metastatic Melanoma Using Recombinant Adenoviruses Encoding MART-1 or gp100 Melanoma Antigens

Science.gov (United States)

Rosenberg, Steven A.; Zhai, Yifan; Yang, James C.; Schwartzentruber, Douglas J.; Hwu, Patrick; Marincola, Francesco M.; Topalian, Suzanne L.; Restifo, Nicholas P.; Seipp, Claudia A.; Einhorn, Jan H.; Roberts, Bruce; White, Donald E.

2008-01-01

Background: The characterization of the genes encoding melanoma-associated antigens MART-1 or gp100, recognized by T cells, has opened new possibilities for the development of immunization strategies for patients with metastatic melanoma. With the use of recombinant adenoviruses expressing either MART-1 or gp100 to immunize patients with metastatic melanoma, we evaluated the safety, immunologic, and potential therapeutic aspects of these immunizations. Methods: In phase I studies, 54 patients received escalating doses (between 107 and 1011 plaque-forming units) of recombinant adenovirus encoding either MART-1 or gp100 melanoma antigen administered either alone or followed by the administration of interleukin 2 (IL-2). The immunologic impact of these immunizations on the development of cellular and antibody reactivity was assayed. Results: Recombinant adenoviruses expressing MART-1 or gp100 were safely administered. One of 16 patients with metastatic melanoma receiving the recombinant adenovirus MART-1 alone experienced a complete response. Other patients achieved objective responses, but they had received IL-2 along with an adenovirus, and their responses could be attributed to the cytokine. Immunologic assays showed no consistent immunization to the MART-1 or gp100 transgenes expressed by the recombinant adenoviruses. High levels of neutralizing antibody were found in the pretreatment sera of the patients. Conclusions: High doses of recombinant adenoviruses could be safely administered to cancer patients. High levels of neutralizing antibody present in patients' sera prior to treatment may have impaired the ability of these viruses to immunize patients against melanoma antigens. PMID:9862627

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

Science.gov (United States)

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

2017-10-16

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

Analysis of the Antitumor Activity of Clotrimazole on A375 Human Melanoma Cells

DEFF Research Database (Denmark)

Adinolfi, Barbara; Carpi, Sara; Romanini, Antonella

2015-01-01

AIM: The current study was designed to characterize the anticancer effects of clotrimazole on human cutaneous melanoma cells. MATERIALS AND METHODS: The v-raf murine sarcoma viral oncogene homolog B1 V600E mutant melanoma cell line A375 was used as an in vitro model. Characterization tools includ...

Orbital amelanotic melanoma in xeroderma pigmentosum: A rare association

Science.gov (United States)

Amitava, Abadan K; Mehdi, Ghazala; Sharma, Rajeev; Alam, Mohammad S

2008-01-01

Xeroderma pigmentosum (XP) is an autosomal recessive genetic disorder of DNA repair in which the body′s normal ability to repair damage caused by ultraviolet light is deficient. This leads to a 1000-fold increased risk of cutaneous and ocular neoplasms. Ocular neoplasms occurring in XP in order of frequency are squamous cell carcinoma, basal cell carcinoma and melanoma. Malignant melanomas occur at an early age in patients with XP. We report a case of XP with massive orbital melanoma in an eight-year-old boy which is unique due to its amelanotic presentation confirmed histopathologically. PMID:18711275

Estimation of Direct Melanoma-related Costs by Disease Stage and by Phase of Diagnosis and Treatment According to Clinical Guidelines

Directory of Open Access Journals (Sweden)

Alessandra Buja

2017-11-01

Full Text Available Cutaneous melanoma is a major concern in terms of healthcare systems and economics. The aim of this study was to estimate the direct costs of melanoma by disease stage, phase of diagnosis, and treatment according to the pre-set clinical guidelines drafted by the AIOM (Italian Medical Oncological Association. Based on the AIOM guidelines for malignant cutaneous melanoma, a highly detailed decision-making model was developed describing the patient’s pathway from diagnosis through the subsequent phases of disease staging, surgical and medical treatment, and follow-up. The model associates each phase potentially involving medical procedures with a likelihood measure and a cost, thus enabling an estimation of the expected costs by disease stage and clinical phase of melanoma diagnosis and treatment according to the clinical guidelines. The mean per-patient cost of the whole melanoma pathway (including one year of follow-up ranged from €149 for stage 0 disease to €66,950 for stage IV disease. The costs relating to each phase of the disease’s diagnosis and treatment depended on disease stage. It is essential to calculate the direct costs of managing malignant cutaneous melanoma according to clinical guidelines in order to estimate the economic burden of this disease and to enable policy-makers to allocate appropriate resources.

Rare variants analysis of cutaneous malignant melanoma genes in Parkinson's disease.

Science.gov (United States)

Lubbe, S J; Escott-Price, V; Brice, A; Gasser, T; Pittman, A M; Bras, J; Hardy, J; Heutink, P; Wood, N M; Singleton, A B; Grosset, D G; Carroll, C B; Law, M H; Demenais, F; Iles, M M; Bishop, D T; Newton-Bishop, J; Williams, N M; Morris, H R

2016-12-01

A shared genetic susceptibility between cutaneous malignant melanoma (CMM) and Parkinson's disease (PD) has been suggested. We investigated this by assessing the contribution of rare variants in genes involved in CMM to PD risk. We studied rare variation across 29 CMM risk genes using high-quality genotype data in 6875 PD cases and 6065 controls and sought to replicate findings using whole-exome sequencing data from a second independent cohort totaling 1255 PD cases and 473 controls. No statistically significant enrichment of rare variants across all genes, per gene, or for any individual variant was detected in either cohort. There were nonsignificant trends toward different carrier frequencies between PD cases and controls, under different inheritance models, in the following CMM risk genes: BAP1, DCC, ERBB4, KIT, MAPK2, MITF, PTEN, and TP53. The very rare TYR p.V275F variant, which is a pathogenic allele for recessive albinism, was more common in PD cases than controls in 3 independent cohorts. Tyrosinase, encoded by TYR, is the rate-limiting enzyme for the production of neuromelanin, and has a role in the production of dopamine. These results suggest a possible role for another gene in the dopamine-biosynthetic pathway in susceptibility to neurodegenerative Parkinsonism, but further studies in larger PD cohorts are needed to accurately determine the role of these genes/variants in disease pathogenesis. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

Acetylcholine receptor binding antibody-associated myasthenia gravis and rhabdomyolysis induced by nivolumab in a patient with melanoma.

Science.gov (United States)

Shirai, Takushi; Sano, Tasuku; Kamijo, Fuminao; Saito, Nana; Miyake, Tomomi; Kodaira, Minori; Katoh, Nagaaki; Nishie, Kenichi; Okuyama, Ryuhei; Uhara, Hisashi

2016-01-01

We reported an 81-year-old woman with metastatic melanoma, in whom myasthenia gravis and rhabdomyolysis developed after nivolumab monotherapy. The first symptom of myasthenia gravis was dyspnea. Ultrasonography detected hypokinesis of the bilateral diaphragm suggesting myasthenia gravis, although there was no abnormal finding of the lungs in computed tomography images. Acetylcholine receptor binding antibodies were low-titer positive in the preserved serum before administration of nivolumab, strongly suggesting that the myasthenia gravis was a nivolumab-related immune adverse event. Despite the remarkable clinical benefits of immune checkpoint inhibitors for patients with advanced melanoma, it is important to recognize unexpected immune-related adverse events. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Cytokines and Growth Factors Expressed by Human Cutaneous Melanoma

Energy Technology Data Exchange (ETDEWEB)

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

2010-05-07

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

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

Directory of Open Access Journals (Sweden)

Niti Singhal

2011-01-01

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

[In-transit metastasis in melanoma: Efficacy of topical imiquimod combined with carbon dioxide laser or with electrocautery].

Science.gov (United States)

Elfatoiki, F-Z; Longvert, C; Clerici, T; Bourgault-Villada, I; Roudier-Pujol, C; Vasseur, E; Saiag, P

2014-02-01

In-transit metastases in cutaneous melanoma are common and difficult to manage. Therapy is mainly palliative. Use of topical imiquimod has been assessed for surface metastases. We report on four patients with cutaneous melanoma metastases treated with topical imiquimod associated with carbon dioxide laser in the first two patients and with electrocoagulation in the two others. For two patients, we noted complete regression of the lesions after 15 and 18 months. For the two others, treatment was stopped after 9 to 10 months because of progression of subcutaneous metastasis and distant metastasis. Topical imiquimod is an alternative treatment used in superficial in-transit metastasis of melanoma. Its use as a monotherapy is sometimes ineffective. We elected to use combined pre-treatment with carbon dioxide laser or electrocoagulation in order to potentiate the action of imiquimod. This simple and inexpensive therapeutic strategy constitutes a palliative treatment that can allow prolonged local control of cutaneous metastasis. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Contemporary Management of Early-Stage Melanoma: A Systematic Review.

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Rosko, Andrew J; Vankoevering, Kyle K; McLean, Scott A; Johnson, Timothy M; Moyer, Jeffrey S

2017-05-01

The incidence of melanoma is increasing, with 76 380 new cases of invasive melanoma and 68 480 new cases of melanoma in situ expected in 2016. To review the contemporary management of early-stage melanoma. We searched PubMed, MEDLINE, and the Cochrane Database of Systematic Reviews databases from January 1, 2011, to May 1, 2016, yielding 966 articles. We focused our search on early-stage (melanoma in situ, stage I, and stage II) cutaneous melanoma. After excluding articles, 41 articles were manually reviewed. A review of the bibliographies of selected articles generated additional references. While the majority of recent advances have been in the treatment of advanced melanoma, surgical excision with margins based on the presence and depth of invasion continues to be the cornerstone of management. Sentinel lymph node biopsy plays a central role in the staging and treatment of melanoma. Accurate diagnosis and adequate surgical excision are critical in reducing local recurrences and improving outcomes. Sentinel lymph node biopsy is useful in staging the regional nodal basin and guiding treatment in appropriately selected patients.

Exploiting cannabinoid-induced cytotoxic autophagy to drive melanoma cell death.

Science.gov (United States)

Armstrong, Jane L; Hill, David S; McKee, Christopher S; Hernandez-Tiedra, Sonia; Lorente, Mar; Lopez-Valero, Israel; Eleni Anagnostou, Maria; Babatunde, Fiyinfoluwa; Corazzari, Marco; Redfern, Christopher P F; Velasco, Guillermo; Lovat, Penny E

2015-06-01

Although the global incidence of cutaneous melanoma is increasing, survival rates for patients with metastatic disease remain viability, and activation of apoptosis, whereas cotreatment with chloroquine or knockdown of Atg7, but not Beclin-1 or Ambra1, prevented THC-induced autophagy and cell death in vitro. Administration of Sativex-like (a laboratory preparation comprising equal amounts of THC and cannabidiol (CBD)) to mice bearing BRAF wild-type melanoma xenografts substantially inhibited melanoma viability, proliferation, and tumor growth paralleled by an increase in autophagy and apoptosis compared with standard single-agent temozolomide. Collectively, our findings suggest that THC activates noncanonical autophagy-mediated apoptosis of melanoma cells, suggesting that cytotoxic autophagy induction with Sativex warrants clinical evaluation for metastatic disease.

Cytokines and Growth Factors Expressed by Human Cutaneous Melanoma

Directory of Open Access Journals (Sweden)

Elias G. Elias

2010-05-01

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

Adjuvant radiotherapy for cutaneous melanoma: Comparing hypofractionation to conventional fractionation

International Nuclear Information System (INIS)

Chang, Daniel T.; Amdur, Robert J.; Morris, Christopher G. M.S.; Mendenhall, William M.

2006-01-01

Purpose: To examine locoregional control after adjuvant radiotherapy (RT) for cutaneous melanoma and compare outcomes between conventional fractionation and hypofractionation. Methods and Materials: Between January 1980 and June 2004, 56 patients with high-risk disease were treated with adjuvant RT. Indications for RT included: recurrent disease, cervical lymph node involvement, lymph nodes >3 cm, more than three lymph nodes involved, extracapsular extension, gross residual disease, close or positive margins, or satellitosis. Hypofractionation was used in 41 patients (73%) and conventional fractionation was used in 15 patients (27%). Results: The median age was 61 years (21->90). The median follow-up among living patients was 4.4 years (range, 0.6-14.4 years). The primary site was located in the head and neck in 49 patients (87%) and below the clavicles in 7 patients (13%). There were 7 in-field locoregional failures (12%), 3 out-of-field regional failures (5%), and 24 (43%) distant failures. The 5-year in-field locoregional control (ifLRC) and freedom from distant metastases (FFDM) rates were 87% and 43%, respectively. The 5-year cause-specific (CSS) and overall survival (OS) was 57% and 46%, respectively. The only factor associated with ifLRC was satellitosis (p = 0.0002). Nodal involvement was the only factor associated with FFDM (p = 0.0007), CSS (p = 0.0065), and OS (p = 0.016). Two patients (4%) who experienced severe late complications, osteoradionecrosis of the temporal bone and radiation plexopathy, and both received hypofractionation (5%). Conclusions: Although surgery and adjuvant RT provides excellent locoregional control, distant metastases remain the major cause of mortality. Hypofractionation and conventional fractionation are equally efficacious

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

Directory of Open Access Journals (Sweden)

Faghihi Gita

2005-01-01

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

Conjunctival malignant melanoma in Denmark: epidemiology, treatment and prognosis with special emphasis on tumorigenesis and genetic profile

DEFF Research Database (Denmark)

Larsen, Ann-Cathrine

2016-01-01

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 ...... melanoma patients may benefit from therapies that are effective for cutaneous and mucosal melanoma. Additionally, the identification of several up-regulated microRNAs may prove to be useful as prognostic or therapeutic targets in conjunctival melanoma...

Large-Scale Purification of r28M: A Bispecific scFv Antibody Targeting Human Melanoma Produced in Transgenic Cattle.

Directory of Open Access Journals (Sweden)

Katrin Spiesberger

Full Text Available 30 years ago, the potential of bispecific antibodies to engage cytotoxic T cells for the lysis of cancer cells was discovered. Today a variety of bispecific antibodies against diverse cell surface structures have been developed, the majority of them produced in mammalian cell culture systems. Beside the r28M, described here, no such bispecific antibody is known to be expressed by transgenic livestock, although various biologicals for medical needs are already harvested-mostly from the milk-of these transgenics. In this study we investigated the large-scale purification and biological activity of the bispecific antibody r28M, expressed in the blood of transgenic cattle. This tandem single-chain variable fragment antibody is designed to target human CD28 and the melanoma/glioblastoma-associated cell surface chondroitin sulfate proteoglycan 4 (CSPG4.With the described optimized purification protocol an average yield of 30 mg enriched r28M fraction out of 2 liters bovine plasma could be obtained. Separation of this enriched fraction by size exclusion chromatography into monomers, dimers and aggregates and further testing regarding the biological activity revealed the monomer fraction as being the most appropriate one to continue working with. The detailed characterization of the antibody's activity confirmed its high specificity to induce the killing of CSPG4 positive cells. In addition, first insights into tumor cell death pathways mediated by r28M-activated peripheral blood mononuclear cells were gained. In consideration of possible applications in vivo we also tested the effect of the addition of different excipients to r28M.Summing up, we managed to purify monomeric r28M from bovine plasma in a large-scale preparation and could prove that its biological activity is unaffected and still highly specific and thus, might be applicable for the treatment of melanoma.

Thick melanoma in Tuscany.

Science.gov (United States)

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

2017-03-14

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

Targeting of indium 111-labeled bivalent hapten to human melanoma mediated by bispecific monoclonal antibody conjugates: Imaging of tumors hosted in nude mice

International Nuclear Information System (INIS)

Le Doussal, J.M.; Gruaz-Guyon, A.; Martin, M.; Gautherot, E.; Delaage, M.; Barbet, J.

1990-01-01

Antibody conjugates were prepared by coupling F(ab')2 or Fab' fragments of an antibody specific for the human high molecular weight-melanoma associated antigen to Fab' fragments of an antibody specific for indium-diethylenetriaminepentaacetate complexes. Monovalent and bivalent haptens were synthesized by reacting the dipeptide tyrosyl-lysine with diethylenetriaminepentaacetic cyclic anhydride. In vitro, the antibody conjugate mediated binding of the 111In-labeled haptens to melanoma cells. In vivo, it allowed specific localization of the haptens in A375 tumors. The bivalent hapten exhibited much higher efficiency at targeting 111In onto cells, both in vitro and in vivo. Antibody conjugate and hapten doses (2 micrograms and 1 pmol, respectively) and the delay between antibody conjugate and tracer injections (24 h) were adjusted to maximize tumor uptake (4% injected dose/g) and tumor to normal tissue contrast (greater than 3) obtained 3 h after injection of the 111In-labeled bivalent hapten. This two-step technique, when compared to direct targeting of 111In-labeled F(ab')2 fragments, provided lower localization of injected activity into the tumor (x 0.25), but higher tumor/tissue ratios, especially with respect to liver (x 7), spleen (x 8), and kidneys (x 10). In addition, high contrast images were obtained within 3 hours, instead of days. Thus, antibody conjugate-mediated targeting of small bivalent haptens, labeled with short half-life isotopes, is proposed as a general method for improving tumor radioimmunolocalization

Malignant melanoma in 63 dogs (2001-2011): the effect of carboplatin chemotherapy on survival.

Science.gov (United States)

Brockley, L K; Cooper, M A; Bennett, P F

2013-01-01

The aim of the study was to compare the effect of carboplatin chemotherapy on the survival of canine patients diagnosed with malignant melanoma after loco-regional control or as a sole therapy. A retrospective study of 63 dogs with oral, digital or cutaneous malignant melanoma treated with surgery and/or chemotherapy was undertaken. Dogs were grouped based on the anatomical site of melanoma development. For oral melanoma, dogs were subclassified into two groups: loco-regional control and gross disease. All patients in the digital and cutaneous groups had achieved loco-regional control with surgery. Comparisons between survival data for each group at each anatomical site were then made. Within the loco-regional control groups survival time was compared between those treated with and without chemotherapy post surgery. For the oral melanoma patients with gross disease survival was compared between those treated with chemotherapy and palliative therapy. The toxicity of carboplatin chemotherapy was evaluated overall. The overall median survival times for patients with oral, digital and cutaneous melanoma were 389, 1,350 days and not reached (with a median follow-up of 776 days) respectively. Median survival time was defined as "not reached" when less than 50% of the subjects died of the disease at the end of the follow-up period, or at the time they were lost to follow-up. The addition of chemotherapy to surgery did not confer a survival benefit in the loco-regional control setting when assessing survival for each anatomical site. For oral melanoma patients with gross disease there was no difference between survival of patients treated with chemotherapy and palliative intent therapy. There was however an improvement in survival in the three dogs that responded to chemotherapy (978 days; p=0.039) compared to the eight non-responders (147 days). On univariate and multivariate analysis, anatomic location was the only variable that was significantly related to survival (p=0

Antiangiogenic Metargidin Peptide (AMEP) Gene Therapy in Disseminated Melanoma

DEFF Research Database (Denmark)

Spanggaard, Iben; Gehl, Julie

2015-01-01

Gene delivery by electroporation is an efficient method for transfecting genes into various tissues including tumors. Here we present the treatment protocol used in a phase 1 study on gene electrotransfer of plasmid DNA encoding an antiangiogenic peptide into cutaneous melanoma....

Germline mutations in candidate predisposition genes in individuals with cutaneous melanoma and at least two independent additional primary cancers.

Science.gov (United States)

Pritchard, Antonia L; Johansson, Peter A; Nathan, Vaishnavi; Howlie, Madeleine; Symmons, Judith; Palmer, Jane M; Hayward, Nicholas K

2018-01-01

While a number of autosomal dominant and autosomal recessive cancer syndromes have an associated spectrum of cancers, the prevalence and variety of cancer predisposition mutations in patients with multiple primary cancers have not been extensively investigated. An understanding of the variants predisposing to more than one cancer type could improve patient care, including screening and genetic counselling, as well as advancing the understanding of tumour development. A cohort of 57 patients ascertained due to their cutaneous melanoma (CM) diagnosis and with a history of two or more additional non-cutaneous independent primary cancer types were recruited for this study. Patient blood samples were assessed by whole exome or whole genome sequencing. We focussed on variants in 525 pre-selected genes, including 65 autosomal dominant and 31 autosomal recessive cancer predisposition genes, 116 genes involved in the DNA repair pathway, and 313 commonly somatically mutated in cancer. The same genes were analysed in exome sequence data from 1358 control individuals collected as part of non-cancer studies (UK10K). The identified variants were classified for pathogenicity using online databases, literature and in silico prediction tools. No known pathogenic autosomal dominant or previously described compound heterozygous mutations in autosomal recessive genes were observed in the multiple cancer cohort. Variants typically found somatically in haematological malignancies (in JAK1, JAK2, SF3B1, SRSF2, TET2 and TYK2) were present in lymphocyte DNA of patients with multiple primary cancers, all of whom had a history of haematological malignancy and cutaneous melanoma, as well as colorectal cancer and/or prostate cancer. Other potentially pathogenic variants were discovered in BUB1B, POLE2, ROS1 and DNMT3A. Compared to controls, multiple cancer cases had significantly more likely damaging mutations (nonsense, frameshift ins/del) in tumour suppressor and tyrosine kinase genes and

Targeting surface nucleolin with a multivalent pseudopeptide delays development of spontaneous melanoma in RET transgenic mice

International Nuclear Information System (INIS)

El Khoury, Diala; Courty, José; Hovanessian, Ara G; Prévost-Blondel, Armelle; Destouches, Damien; Lengagne, Renée; Krust, Bernard; Hamma-Kourbali, Yamina; Garcette, Marylène; Niro, Sandra; Kato, Masashi; Briand, Jean-Paul

2010-01-01

The importance of cell-surface nucleolin in cancer biology was recently highlighted by studies showing that ligands of nucleolin play critical role in tumorigenesis and angiogenesis. By using a specific antagonist that binds the C-terminal tail of nucleolin, the HB-19 pseudopeptide, we recently reported that HB-19 treatment markedly suppressed the progression of established human breast tumor cell xenografts in the athymic nude mice without apparent toxicity. The in vivo antitumoral action of HB-19 treatment was assessed on the spontaneous development of melanoma in the RET transgenic mouse model. Ten days old RET mice were treated with HB-19 in a prophylactic setting that extended 300 days. In parallel, the molecular basis for the action of HB-19 was investigated on a melanoma cell line (called TIII) derived from a cutaneous nodule of a RET mouse. HB-19 treatment of RET mice caused a significant delay in the onset of cutaneous tumors, several-months delay in the incidence of large tumors, a lower frequency of cutaneous nodules, and a reduction of visceral metastatic nodules while displaying no toxicity to normal tissue. Moreover, microvessel density was significantly reduced in tumors recovered from HB-19 treated mice compared to corresponding controls. Studies on the melanoma-derived tumor cells demonstrated that HB-19 treatment of TIII cells could restore contact inhibition, impair anchorage-independent growth, and reduce their tumorigenic potential in mice. Moreover, HB-19 treatment caused selective down regulation of transcripts coding matrix metalloproteinase 2 and 9, and tumor necrosis factor-α in the TIII cells and in melanoma tumors of RET mice. Although HB-19 treatment failed to prevent the development of spontaneous melanoma in the RET mice, it delayed for several months the onset and frequency of cutaneous tumors, and exerted a significant inhibitory effect on visceral metastasis. Consequently, HB-19 could provide a novel therapeutic agent by itself or

Perineural extension of facial melanoma

Energy Technology Data Exchange (ETDEWEB)

Kalina, Peter [Mayo Clinic, Department of Radiology, Rochester, Minnesota (United States); Bevilacqua, Paula

2005-05-01

A 64-year-old man presented with a pigmented cutaneous lesion on the right side of his face along with right facial numbness. Histological examination revealed malignant melanoma. Magnetic resonance imaging (MRI) revealed perineural extension along the entire course of the maxillary division of the right trigeminal nerve. This is a rare but important manifestation of the spread of head and neck malignancy. (orig.)

A canine chimeric monoclonal antibody targeting PD-L1 and its clinical efficacy in canine oral malignant melanoma or undifferentiated sarcoma.

Science.gov (United States)

Maekawa, Naoya; Konnai, Satoru; Takagi, Satoshi; Kagawa, Yumiko; Okagawa, Tomohiro; Nishimori, Asami; Ikebuchi, Ryoyo; Izumi, Yusuke; Deguchi, Tatsuya; Nakajima, Chie; Kato, Yukinari; Yamamoto, Keiichi; Uemura, Hidetoshi; Suzuki, Yasuhiko; Murata, Shiro; Ohashi, Kazuhiko

2017-08-21

Immunotherapy targeting immune checkpoint molecules, programmed cell death 1 (PD-1) and PD-ligand 1 (PD-L1), using therapeutic antibodies has been widely used for some human malignancies in the last 5 years. A costimulatory receptor, PD-1, is expressed on T cells and suppresses effector functions when it binds to its ligand, PD-L1. Aberrant PD-L1 expression is reported in various human cancers and is considered an immune escape mechanism. Antibodies blocking the PD-1/PD-L1 axis induce antitumour responses in patients with malignant melanoma and other cancers. In dogs, no such clinical studies have been performed to date because of the lack of therapeutic antibodies that can be used in dogs. In this study, the immunomodulatory effects of c4G12, a canine-chimerised anti-PD-L1 monoclonal antibody, were evaluated in vitro, demonstrating significantly enhanced cytokine production and proliferation of dog peripheral blood mononuclear cells. A pilot clinical study was performed on seven dogs with oral malignant melanoma (OMM) and two with undifferentiated sarcoma. Objective antitumour responses were observed in one dog with OMM (14.3%, 1/7) and one with undifferentiated sarcoma (50.0%, 1/2) when c4G12 was given at 2 or 5 mg/kg, every 2 weeks. c4G12 could be a safe and effective treatment option for canine cancers.

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

Science.gov (United States)

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

2018-04-03

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

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

Directory of Open Access Journals (Sweden)

Leonardo Vinícius Monteiro de Assis

2018-04-01

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

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

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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.

Ultraviolet-induced formation of micronuclei and sister chromatid exchange in cultured fibroblasts of patients with cutaneous malignant melanoma

International Nuclear Information System (INIS)

Roser, M.; Boehm, A.O.; Oldigs, M.; Weichenthal, M.; Reimers, U.; Schmidt-Preuss, U.; Breitbart, E.W.; Ruediger, H.W.

1989-01-01

Genetically enhanced sensitivity to ultraviolet (UV) radiation may play an important role in the development of cutaneous malignant melanoma (CMM). This was studied in cultured fibroblasts of 26 CMM patients and controls by micronucleus (MN) test and sister chromatid exchange (SCE) after UV irradiation (375 J/m2). Sister chromatid exchange and MN formation were used as parameters to detect the UV-induced genotoxic damage in the individual cell strains. We found that the UV-induced level of MN was significantly increased in CMM patients (p = 0.0005), being most pronounced in the familial cases (p = 0.0001). Ultraviolet-induced SCE was also elevated in CMM patients (p = 0.001), but there was no difference between familial and nonfamilial cases. The present findings indicate that genetic predisposition contributes to the development of CMM in a subset of CMM patients and may be due to an enhanced susceptibility to UV light

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

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Ana Maria Carreño

2013-04-01

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

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

Science.gov (United States)

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

2008-01-01

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

Podoplanin Expression in Canine Melanoma.

Science.gov (United States)

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

2016-12-01

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

Expression of leptin and iNOS in oral melanomas in dogs.

Science.gov (United States)

Greene, V R; Wilson, H; Pfent, C; Roethele, J; Carwile, J; Qin, Y; Grimm, E; Ellerhorst, J A

2013-01-01

Oral melanoma (OM) in dogs is an aggressive malignancy, with clinical behavior resembling cutaneous melanomas in humans. Melanoma in humans is promoted by an inflammatory environment that is contributed to by leptin and inducible nitric oxide synthase (iNOS). To determine if the patterns of leptin and iNOS expression are similar in OM in dogs and cutaneous melanomas in humans. Twenty client-owned dogs. Retrospective case study. Immunostaining of the OM tumors from each dog was scored for percentage and intensity of leptin and iNOS expression. Mitotic index was used as an indicator of tumor aggression. Leptin was detected in ≥75% of the tumor cells in specimens from 11 dogs. One tumor expressed leptin in ≤25% of the cells. The intensity of leptin expression was variable with 6, 9, and 5 cases exhibiting low-, moderate-, and high-intensity staining, respectively. OM with the lowest percentage of iNOS positive cells displayed the highest mitotic indices (P = .006, ANOVA). The expression of leptin is a common finding in melanomas in dogs. These data suggest that the possibility of future clinical applications, such as measuring the concentrations of plasma leptin as a screening tool or leptin as a target for therapy. The relevance of iNOS is not as clear in dogs with OM, for which other directed therapeutics might be more appropriate. Copyright © 2013 by the American College of Veterinary Internal Medicine.

Sarcoidosis in Melanoma Patients: Case Report and Literature Review

Energy Technology Data Exchange (ETDEWEB)

Beutler, Bryce D., E-mail: brycebeutler@hotmail.com [School of Allied Health Sciences, University of Nevada, Las Vegas, 1060 Wiegand Road, Encinitas, CA 92024 (United States); Cohen, Philip R., E-mail: brycebeutler@hotmail.com [Department of Dermatology, University of California San Diego, 10991 Twinleaf Court, San Diego, CA 92131 (United States)

2015-06-15

Sarcoidosis is a systemic inflammatory disease characterized by the development of noncaseating granulomas in multiple organ systems. Many hematologic malignancies and solid tumors, including melanoma, have been associated with sarcoidosis. We describe the clinical and pathologic findings of a 54-year-old man with melanoma-associated sarcoidosis. In addition, we not only review the literature describing characteristics of other melanoma patients with sarcoidosis, but also the features of melanoma patients with antineoplastic therapy-associated sarcoidosis. Sarcoidosis has been described in 80 melanoma patients; sufficient information for analysis was provided in 39 of these individuals. In 43.6% of individuals (17 out of 39), sarcoidosis was directly associated with melanoma; in 56.4% of oncologic patients (22 out of 39), sarcoidosis was induced by antineoplastic therapy that had been administered for the treatment of their metastatic melanoma. The discovery of melanoma preceded the development of sarcoidosis in 12 of the 17 (70.5%) individuals who did not receive systemic treatment. Pulmonary and/or cutaneous manifestations of sarcoidosis were common among both groups of patients. Most patients did not require treatment for sarcoidosis. Melanoma patients—either following antineoplastic therapy or without systemic treatment—may be at an increased risk to develop sarcoidosis. In antineoplastic therapy naive melanoma patients, a common etiologic factor—such as exposure to ultraviolet light—may play a role in their developing melanoma and sarcoidosis.

Sentinel nodes outside lymph node basins in patients with melanoma

NARCIS (Netherlands)

Roozendaal, GK; de Vries, JDH; van Poll, D; Jansen, L; Nieweg, OE; Kroon, BBR; Schraffordt Koops, H.

Background: Lymphoscintigraphy occasionally reveals hot spots outside lymph node basins in patients with melanoma. The aim of this study was to evaluate such abnormally located hot spots. Methods: Sentinel node biopsy was studied prospectively in 379 patients with clinically localized cutaneous

Cutaneous metastasis to the face from lung adenocarcinoma ...

African Journals Online (AJOL)

Cutaneous metastases in the facial region occur in less than 0.5% of patients with metastatic cancer, and they usually originate from malignant melanoma. In this report, we describe an unusual case of lung adenocarcinoma metastasizing to his face at the time of initial diagnosis. The patient was 64-year-old man, a heavy ...

Lysosomal-associated membrane protein-2 plays an important role in the pathogenesis of primary cutaneous vasculitis.

Science.gov (United States)

Takeuchi, Sora; Kimura, Satoko; Soma, Yoshinao; Waki, Masashi; Yamaguchi, Madoka; Nakazawa, Daigo; Tomaru, Utano; Ishizu, Akihiro; Kawakami, Tamihiro

2013-09-01

Recent research suggests that lysosomal-associated membrane protein-2 (LAMP-2) could be one of the target antigens in the pathogenesis of vasculitides. We established a transgenic rat model, env-pX rats, with various vasculitides including cutaneous vasculitis. Human primary cutaneous vasculitis includes cutaneous polyarteritis nodosa (CPN) and Henoch-Schönlein purpura (HSP). We measured serum anti-LAMP-2 antibody levels in morbid env-pX rats and injected anti-LAMP-2 antibody into premorbid env-pX rats. We further measured serum anti-LAMP-2 antibody levels in patients with CPN and HSP. Cutaneous vasculitis was observed in ∼30% of 6-month-old morbid env-pX rats. In contrast, these findings were rare in premorbid env-pX rats under 3 months old. We also examined 85 patients with CPN and 36 adult patients with HSP. Serum anti-LAMP-2 antibody levels were determined using ELISA. Premorbid env-pX rats under 3 months old were given an i.v. injection of anti-LAMP-2 antibody at day 0 and day 7. At day 14, these rats underwent histopathological and direct immunofluorescence examination. Cell surface LAMP-2 expression of rat neutrophils was examined by flow cytometry. Serum anti-LAMP-2 antibody levels were significantly higher in morbid env-pX rats than in wild-type normal rats. In addition, the levels in the cutaneous vasculitis group of morbid env-pX rats were significantly higher than the no cutaneous vasculitis group. Intravenous anti-LAMP-2 antibody injection into premorbid env-pX rats under 3 months old induced infiltration of neutrophils into cutaneous small vessels. Anti-LAMP-2 antibody-binding neutrophils were detected there. LAMP-2 expression on the cell surface of neutrophils in premorbid env-pX rats under PMA stimulation was higher compared with controls. Serum anti-LAMP-2 antibody levels in CPN and HSP were significantly higher than those of healthy controls. These data support a positive relationship between anti-LAMP-2 antibody and cutaneous vasculitis.

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

Science.gov (United States)

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

2018-01-19

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

Multiple cutaneous malignancies in xeroderma pigmentosum

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Mohanty Prasenjeet

2001-01-01

Full Text Available A case of xeroderma pigmentosum with multiple cutaneous malignancies is being reported. The case presented with freckles, letigens, and keratosis, a non-tender ulcerated nodular lesion on the nose, a nodular ulcerated lesion on the right outer canthus of the conjunctiva, and a nodular growth which developed on the right cheek which on histopathology was found to be squamous cell cercinoma, basal cell carcinoma and malignant melanoma respectively.

Etiology, risk factors, epidemiology, and public health issues in melanoma and other cutaneous neoplasms

International Nuclear Information System (INIS)

Lee, J.A.

1992-01-01

The cytogenetic features of melanoma, including the contribution of specific genes, are beginning to be unraveled. Reproductive factors have been shown to have little relationship to melanoma. The puzzles over apparent systemic effects of exposure have persisted, however. Evidence was published that the history of reaction to sun exposure altered when a diagnosis of melanoma was made. An interesting suggestion was made that the classic melanoma risk factors are associated with promotion rather than initiation of the disease. There is further evidence that exposure decreases melanoma risk in people who tan well but increases it in those who do not. Also reviewed is the evidence that the ozone layer of the stratosphere began to decrease in thickness under the influence of the chlorofluorocarbon gases

Cutaneous side-effects during therapy of melanoma by vemurafenib

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Anna Ankudowicz

2015-06-01

Full Text Available Introduction. Vemurafenib is a selective inhibitor of serine-threonine kinase BRAF used in the treatment of advanced melanoma with BRAF mutation. Effectiveness of this drug was confirmed in a large clinical trial, which led to the increase of its usage. During treatment with vemurafenib, particular attention should be paid to the numerous side effects, including those concerning the skin. Vemurafenib is highly toxic to the skin. Skin lesions occurring during the treatment of melanoma with this medicament can be divided into: early (observed 3 to 6 weeks after beginning treatment, late (observed 6 weeks after beginning treatment and hypersensitivity reactions to vemurafenib. Objective. Presentation of vemurafenib toxic effects on the skin and side effects that can be caused by this drug. Case report. We present a 58-year-old woman with metastatic melanoma who was treated with vemurafenib. During the course of therapy, numerous adverse reactions, including inflammatory tumors, emergence of a number of melanocytic naevi, skin horns, alopecia, hyperkeratosis of the palms and soles, and palmar erythrodysesthesia were observed. She was treated with anti-inflammatory drugs, an antibiotic, circulation-improving preparations and local moisturizing and keratolytic treatment. The patient remains under the care of oncologists and dermatologists. Conclusions. The new generation anti-cancer drugs bring hope for a cure or prolongation of life, but can also significantly reduce the quality of life by inducing both general and local adverse side effects. Oncological patients should also be taken care of by dermatologists.

Increased levels of circulating platelet-derived microparticles are associated with metastatic cutaneous melanoma.

Science.gov (United States)

Moreau, Joséphine; Pelletier, Fabien; Biichle, Sabeha; Mourey, Guillaume; Puyraveau, Marc; Badet, Nicolas; Caubet, Matthieu; Laresche, Claire; Garnache-Ottou, Francine; Saas, Philippe; Seilles, Estelle; Aubin, François

2017-10-01

We investigated the plasma levels of PMPs in patients with 45 stage III and 45 stage IV melanoma. PMPs were characterised by flow cytometry and their thrombogenic activity. We also investigated the link between PMPs circulating levels and tumor burden. The circulating levels of PMPs were significantly higher in stage IV (8500 μL -1 ) than in patients with stage III (2041 μL -1 ) melanoma (P=.0001). We calculated a highly specific (93.3%) and predictive (91.7%) cut-off value (5311 μL -1 ) allowing the distinction between high-risk stage III and metastatic stage IV melanoma. The thrombogenic activity of PMPs was significantly higher in patients with stage IV melanoma (clotting time: 40.7 second vs 65 second, P=.0001). There was no significant association between the radiological tumoral syndrome and the plasma level of PMPs. Our data suggest the role of PMPs in metastatic progression of melanoma. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Prevalence of left-sided melanomas in an Irish population.

LENUS (Irish Health Repository)

de Blacam, C

2012-02-01

BACKGROUND: A predominance of melanomas on the left side of the body has recently been described. No associations between tumour laterality and gender, age or anatomical site have been identified. AIM: The aim of this study was to investigate the prevalence of left-sided melanomas in an Irish population and to examine potential associations with various patient and tumour characteristics. METHODS: A retrospective chart review of patients with cutaneous melanoma who were treated over a 10-year period was carried out. Lateral distribution of melanoma on either side of the body was compared using chi(2) analysis and evaluated by gender, age group, anatomic location, histologic subtype and Breslow depth. RESULTS: More melanomas occurred on the left side (57%, P = 0.015), and this finding was particularly significant in females. For both genders combined, there were no statistically significant differences in laterality by age group, anatomic location, type of melanoma and Breslow depth. There were significantly more superficial spreading melanomas on the left side in both men and women. CONCLUSIONS: This study demonstrates a predominance of left-sided melanomas in Irish patients. While a number of demographic and molecular associations have been proposed, further research is required to fully explain this phenomenon.

Prevalence of left-sided melanomas in an Irish population.

LENUS (Irish Health Repository)

de Blacam, C

2011-04-17

BACKGROUND: A predominance of melanomas on the left side of the body has recently been described. No associations between tumour laterality and gender, age or anatomical site have been identified. AIM: The aim of this study was to investigate the prevalence of left-sided melanomas in an Irish population and to examine potential associations with various patient and tumour characteristics. METHODS: A retrospective chart review of patients with cutaneous melanoma who were treated over a 10-year period was carried out. Lateral distribution of melanoma on either side of the body was compared using χ(2) analysis and evaluated by gender, age group, anatomic location, histologic subtype and Breslow depth. RESULTS: More melanomas occurred on the left side (57%, P = 0.015), and this finding was particularly significant in females. For both genders combined, there were no statistically significant differences in laterality by age group, anatomic location, type of melanoma and Breslow depth. There were significantly more superficial spreading melanomas on the left side in both men and women. CONCLUSIONS: This study demonstrates a predominance of left-sided melanomas in Irish patients. While a number of demographic and molecular associations have been proposed, further research is required to fully explain this phenomenon.

LFA-1 and ICAM-1 expression induced during melanoma-endothelial cell co-culture favors the transendothelial migration of melanoma cell lines in vitro

International Nuclear Information System (INIS)

Ghislin, Stephanie; Obino, Dorian; Middendorp, Sandrine; Boggetto, Nicole; Alcaide-Loridan, Catherine; Deshayes, Frederique

2012-01-01

Patients with metastatic melanoma have a poor median rate of survival. It is therefore necessary to increase our knowledge about melanoma cell dissemination which includes extravasation, where cancer cells cross the endothelial barrier. Extravasation is well understood during travelling of white blood cells, and involves integrins such as LFA-1 (composed of two chains, CD11a and CD18) expressed by T cells, while ICAM-1 is induced during inflammation by endothelial cells. Although melanoma cell lines cross endothelial cell barriers, they do not express LFA-1. We therefore hypothesized that melanoma-endothelial cell co-culture might induce the LFA-1/ICAM ligand/receptor couple during melanoma transmigration. A transwell approach has been used as well as blocking antibodies against CD11a, CD18 and ICAM-1. Data were analyzed with an epifluorescence microscope. Fluorescence intensity was quantified with the ImageJ software. We show here that HUVEC-conditioned medium induce cell-surface expression of LFA-1 on melanoma cell lines. Similarly melanoma-conditioned medium activates ICAM-1 expression in endothelial cells. Accordingly blocking antibodies of ICAM-1, CD11a or CD18 strongly decrease melanoma transmigration. We therefore demonstrate that melanoma cells can cross endothelial monolayers in vitro due to the induction of ICAM-1 and LFA-1 occurring during the co-culture of melanoma and endothelial cells. Our data further suggest a role of LFA-1 and ICAM-1 in the formation of melanoma cell clumps enhancing tumor cell transmigration. Melanoma-endothelial cell co-culture induces LFA-1 and ICAM-1 expression, thereby favoring in vitro melanoma trans-migration

LFA-1 and ICAM-1 expression induced during melanoma-endothelial cell co-culture favors the transendothelial migration of melanoma cell lines in vitro

Directory of Open Access Journals (Sweden)

Ghislin Stephanie

2012-10-01

Full Text Available Abstract Background Patients with metastatic melanoma have a poor median rate of survival. It is therefore necessary to increase our knowledge about melanoma cell dissemination which includes extravasation, where cancer cells cross the endothelial barrier. Extravasation is well understood during travelling of white blood cells, and involves integrins such as LFA-1 (composed of two chains, CD11a and CD18 expressed by T cells, while ICAM-1 is induced during inflammation by endothelial cells. Although melanoma cell lines cross endothelial cell barriers, they do not express LFA-1. We therefore hypothesized that melanoma-endothelial cell co-culture might induce the LFA-1/ICAM ligand/receptor couple during melanoma transmigration. Methods A transwell approach has been used as well as blocking antibodies against CD11a, CD18 and ICAM-1. Data were analyzed with an epifluorescence microscope. Fluorescence intensity was quantified with the ImageJ software. Results We show here that HUVEC-conditioned medium induce cell-surface expression of LFA-1 on melanoma cell lines. Similarly melanoma-conditioned medium activates ICAM-1 expression in endothelial cells. Accordingly blocking antibodies of ICAM-1, CD11a or CD18 strongly decrease melanoma transmigration. We therefore demonstrate that melanoma cells can cross endothelial monolayers in vitro due to the induction of ICAM-1 and LFA-1 occurring during the co-culture of melanoma and endothelial cells. Our data further suggest a role of LFA-1 and ICAM-1 in the formation of melanoma cell clumps enhancing tumor cell transmigration. Conclusion Melanoma-endothelial cell co-culture induces LFA-1 and ICAM-1 expression, thereby favoring in vitro melanoma trans-migration.

Surgery and radiotherapy in the treatment of cutaneous melanoma

DEFF Research Database (Denmark)

Testori, A; Rutkowski, P; Marsden, J

2009-01-01

on individual circumstances. Radiotherapy is indicated as a treatment option in select patients with lentigo maligna melanoma and as an adjuvant in select patients with regional metastatic disease. Radiotherapy is also indicated for palliation, especially in bone and brain metastases....

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; thi...

Activation of the MAPK pathway is a common event in uveal melanomas although it rarely occurs through mutation of BRAF or RAS.

Science.gov (United States)

Zuidervaart, W; van Nieuwpoort, F; Stark, M; Dijkman, R; Packer, L; Borgstein, A-M; Pavey, S; van der Velden, P; Out, C; Jager, M J; Hayward, N K; Gruis, N A

2005-06-06

In contrast to cutaneous melanoma, there is no evidence that BRAF mutations are involved in the activation of the mitogen-activated protein kinase (MAPK) pathway in uveal melanoma, although there is increasing evidence that this pathway is activated frequently in the latter tumours. In this study, we performed mutation analysis of the RAS and BRAF genes in a panel of 11 uveal melanoma cell lines and 19 primary uveal melanoma tumours. In addition, Western blot and immunohistochemical analyses were performed on downstream members of the MAPK pathway in order to assess the contribution of each of these components. No mutations were found in any of the three RAS gene family members and only one cell line carried a BRAF mutation (V599E). Despite this, mitogen-activated protein kinase/extracellular signal-regulated kinase kinase (MEK), ERK and ELK were constitutively activated in all samples. These data suggest that activation of the MAPK pathway is commonly involved in the development of uveal melanoma, but occurs through a mechanism different to that of cutaneous melanoma.

Podoplanin Expression in Canine Melanoma

OpenAIRE

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

2016-01-01

A type I transmembrane protein, podoplanin (PDPN), is expressed in several normal cells such as lymphatic endothelial cells or pulmonary type I alveolar cells. We recently demonstrated that anticanine PDPN monoclonal antibody (mAb), PMab-38, recognizes canine PDPN of squamous cell carcinomas, but does not react with lymphatic endothelial cells. Herein, we investigated whether PMab-38 reacts with canine melanoma. PMab-38 reacted with 90% of melanoma cells (9/10 cases) using immunohistochemistr...

Cost-effectiveness of preoperative SPECT/CT combined with lymphoscintigraphy vs. lymphoscintigraphy for sentinel lymph node excision in patients with cutaneous malignant melanoma

Energy Technology Data Exchange (ETDEWEB)

Stoffels, Ingo; Leyh, Julia; Schadendorf, Dirk; Klode, Joachim [University of Duisburg-Essen, Department of Dermatology, Venerology and Allergology, University-Hospital Essen, Essen (Germany); Mueller, Markus [University of Duisburg-Essen, Department of Medical controlling, University-Hospital Essen, Essen (Germany); Geisel, Marie Henrike [University of Duisburg-Essen, Institute for Medical Informatics, Biometry and Epidemiology, University-Hospital Essen, Essen (Germany); Poeppel, Thorsten [University of Duisburg-Essen, Department of Nuclear Medicine, University-Hospital Essen, Essen (Germany)

2014-09-15

Malignant melanoma has become a major growing interdisciplinary problem in public health worldwide. Sentinel lymph node excision (SLNE) in conjunction with preoperative SPECT/CT is considered the most sensitive and specific staging test for the detection of micrometastatic melanoma in regional lymph nodes. Among patients with clinically lymph node-negative melanoma, the use of SPECT/CT-aided SLNE compared with SLNE alone has been found to be associated with a higher frequency of metastatic involvement and a higher rate of disease-free survival. The aim of this study was to analyse the cost-effectiveness of SLNE with preoperative SPECT/CT for detecting sentinel lymph nodes versus that of standard SLNE with preoperative lymphoscintigraphy from a single-institution database. Cost-effectiveness analysis of two surgical approaches for SLNE for malignant melanoma at the University Hospital Essen, Skin Cancer Center in Essen, Germany. Between March 2003 and April 2011 464 patients eligible for SLNE were identified. Of these patients, 403 with clinically negative lymph nodes who underwent SLNE with or without preoperative SPECT/CT qualified for subsequent analysis. Between March 2003 and October 2008, 254 patients were operated upon with the standard technique. From November 2008, 149 patients underwent the SPECT/CT technique. Cost analysis showed a mean cost saving of EUR 710.50 when SPECT/CT was added to preoperative imaging. This was achieved by a reduction in operative time (median, Q1;Q3, 40 min, 40;50 min, vs. 45 min, 35;60 min; p = 0.002), hospital stay duration (5 days, 3;8 days, vs. 8 days, 4.5;14.5 days; p < 0.001) and more frequent use of local anaesthesia (90.6 % vs. 70.5 %; p < 0.001). The median cost of SLNE using SPECT/CT was EUR 1,619.7 (Q1;Q3 EUR 1,317.0;2,603.4) and of SLNE without SPECT/CT was EUR 2,330.2 (EUR 1,468.3;4,058.1; p < 0.001), a cost saving of 30.5 %. In patients with cutaneous melanoma, the use of preoperative SPECT/CT-aided SLNE compared

Integrative Genome Comparison of Primary and Metastatic Melanomas

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

2010-01-01

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

Dermatologia comparativa: dermatoscopia em melanoma cutâneo Comparative dermatology: dermatoscopy of cutaneous melanoma

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Otávio Sérgio Lopes

2008-10-01

Full Text Available Os autores apresentam imagens de dermatoscopia em uma fruta (manga-rosa, contaminada pela antracnose, mostrando sua semelhança com o melanoma extensivo superficial.The authors present images from a dermatoscopy performed in a fruit (mango that was contaminated by anthracnosis, showing its similarity to superficial spreading melanona.

Pharmacokinetics of 111In-labeled anti-p97 monoclonal antibody in patients with metastatic malignant melanoma

International Nuclear Information System (INIS)

Rosenblum, M.G.; Murray, J.L.; Haynie, T.P.; Glenn, H.J.; Jahns, M.F.; Benjamin, R.S.; Frincke, J.M.; Carlo, D.J.; Hersh, E.M.

1985-01-01

Twenty-eight patients with metastatic malignant melanoma received anti-p97 murine monoclonal antibody (96.5) infused over 2 h at doses between 1 and 20 mg coupled to either 2.5 or 5.0 mCi of 111 In by the bifunctional chelating agent diethyltriaminepentaacetic acid. Clearance of 111 In from plasma closely fit an open, one-compartment mathematical model (r2 greater than 0.90). The overall half-life of 111 In plasma was approximately 31 h and did not appear to be dependent on the total dose of antibody administered. The apparent volume of distribution of the 111 In label approximated the total blood volume (7.8 +/- 0.7 liters) at the 1-mg dose and decreased to 3.0 +/- 0.14 liters at the 20-mg dose, suggesting saturation of antigenic or other extravascular binding sites at higher antibody doses. The clearance of the murine monoclonal antibody itself from plasma was measured by an enzyme-linked immunosorbent assay. The pharmacokinetics for the murine antibody in plasma also fit an open, one-compartment mathematical model. All pharmacokinetic parameters for unlabeled antibody closely paralleled those found for 111 In-labeled antibody pharmacokinetics. This suggests that the 111 In radiolabel remains complexed to the monoclonal antibody after in vivo administration. The cumulative urinary excretion of the 111 In label over 48 h was between 12 and 23% of the total administered dose and is assumed to represent 111 In-labeled chelate complex unattached to antibody. Analysis of the 111 In label in spleen, liver, heart, and kidney showed that the concentration of label in liver tissue was reduced with increasing antibody doses and coincided with changes in the apparent volume of distribution

Study Suggests Smaller Melanoma Excision Margins May Be Option for Some Patients

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A randomized controlled trial of patients with stage IIA–C cutaneous melanoma thicker than 2-mm found that a 2-cm surgical resection margin is sufficient and is as safe for patients as a 4-cm margin.

Intussusception of the small intestine caused by a primary melanoma?

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

2012-01-01

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

Intussusception of the Small Intestine Caused by a Primary Melanoma

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M. Schoneveld

2012-01-01

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

Spontaneous regression of metastases from malignant melanoma: a case report

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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...

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

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

1991-01-01

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

Melanoma and tattoos: a case report and review of the literature.

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Ricci, Francesco; Paradisi, Andrea; Maier, Stephanie Alissa; Kovacs, Maximilian; Podda, Maurizio; Peris, Ketty; Abeni, Damiano

2018-02-01

Malignant melanoma cases arising in tattoos have been increasingly described, however, there is no clear relationship between this practice and the development of cutaneous malignancies. We report a new case of melanoma in a dark-blue tattoo and we review all cases of melanoma reported in the medical literature from 1938 to date. Pubmed and Google Scholar were searched using the terms "melanoma tattoo", "tattoo skin tumour" and "ink melanoma". In most cases, the melanoma occurred on dark blue (10/30), black (8/30), or blue ink (3/30). The Breslow thickness at diagnosis was ≤1 mm in 13/30, 1-2 mm in 3/30, 2-4 mm in 2/30, >4 mm in 5/30, and Clark II in 2/30 (not available in 5/30). Both the incidence of melanoma and the number of tattoos have been increasing in recent years, but a possible carcinogenic effect of tattoos remains unproven. The spread of this decorative custom will make observation of melanoma in tattoos more frequent in dermatological practice, therefore these cases should be reported in national skin cancer registries.

Neuro tropic Melanoma: The Management of Localised Disease

International Nuclear Information System (INIS)

Croker, J.; Burmeister, B.; Foote, M.

2012-01-01

Neuro tropic melanoma is a rare subtype of cutaneous malignant melanoma. Compared with conventional melanoma, it is more locally aggressive with an increased tendency for local recurrence but less likely for nodal or distant metastases. These tumours can be a diagnostic dilemma with a variety of morphological, histopathological, and immunophenotypical expressions. The often amelanotic, benign appearance may lead to treatment issues such as late presentation, diagnostic delay, misdiagnosis, insufficient surgical margins, and recurrence with resulting poor outcome. The neuro tropic nature of the disease and prevalence in the head and neck region can result in peri neural and neural invasion along named large nerves into the brain with resulting neuropathies. Wide local excision with adjuvant radiotherapy where indicated remains the current practice for treatment with chemotherapy predominately being reserved as a salvage treatment for patients with disseminated disease.

Real-world treatment patterns and outcomes among metastatic cutaneous melanoma patients treated with ipilimumab.

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Mohr, P; Ascierto, P; Arance, A; McArthur, G; Hernaez, A; Kaskel, P; Shinde, R; Stevinson, K

2018-06-01

There is a scarcity of real-world data on treatment patterns and outcomes among advanced melanoma patients treated with immunotherapies including ipilimumab, an anti-CTLA-4 antibody approved since 2011. To evaluate ipilimumab and postipilimumab treatment patterns and outcomes among patients with advanced melanoma in Australia, Germany, Italy and Spain, following regulatory approval. Retrospective multicentre, multinational, observational chart review study. Data were extracted from the start of ipilimumab therapy until the end of at least 40 weeks of follow-up, or death. Data from 371 patients (Australia, 103; Germany, 152; Italy, 76; Spain, 40) were analysed. Mean age was 65 years; 62% were male. Eastern Cooperative Oncology Group performance status (ECOG PS) was 0 or 1 for 94%. In 67%, ipilimumab was initially received as second-line or later therapy. Patients received on average 3.4 ipilimumab doses. The ipilimumab-refractory cohort comprised of 226 patients. Of these, 17% in Australia, 47% in Germany, 29% in Italy and 14% in Spain received another antimelanoma treatment after ipilimumab including chemotherapy in 26% and BRAF/other kinase inhibitors in 11%. Ipilimumab-refractory patients who received postipilimumab treatment showed a 40% reduced hazard of dying than those not receiving treatment after ipilimumab (HR 0.60; 95% CI 0.43-0.83), after adjustment for potential confounders. During the time observed, ipilimumab was mainly used as second-line or later therapy. A significant proportion of patients received postipilimumab therapy, most of which was chemotherapy. Nevertheless, overall survival following progression on ipilimumab treatment remained poor, highlighting the need for research to develop more effective end-of-life treatment options. © 2017 European Academy of Dermatology and Venereology.

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.

Critérios histopatológicos para diagnóstico de melanoma maligno cutâneo: análise comparativa de sua freqüência em lesões benignas e melanomas de pequena espessura (< 2 mm Histopathological criteria for cutaneous malignant melanoma: comparative analysis between benign and thin malignant lesions (< 2 mm

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Luiz Alberto Veronese

2007-10-01

Full Text Available INTRODUÇÃO: A histopatologia convencional continua sendo o padrão-ouro no diagnóstico dos melanomas cutâneos, apesar do progresso da imuno-histoquímica e da biologia molecular. Os critérios microscópicos existentes para esse diagnóstico são numerosos, porém nenhum deles é específico para se afirmar que uma determinada lesão é maligna quando ele está presente, ou é benigna na sua ausência. Alguns critérios têm uma relevância maior para o diagnóstico em relação a outros. OBJETIVO: Este estudo propõe uma análise daqueles critérios considerados mais importantes, comparando sua presença em lesões melanocíticas benignas e melanomas. MATERIAL E MÉTODOS: Foram estudadas 33 lesões melanocíticas benignas (nevo de Spitz: 13; nevo de Reed: 6; nevo displásico: 6; nevo congênito: 3; nevo adquirido: 3; nevo combinado: 1; nevo recorrente: 1, bem como 101 casos de melanomas extensivo/superficiais: 25 intra-epidérmicos e 76 invasivos de pequena espessura (INTRODUCTION: Conventional histopathology has been considered as the gold standard in the diagnosis of cutaneous malignant melanoma, despite the progress of molecular biology and immunohistochemistry. There are many microscopic criteria for diagnosis of melanoma, however there is not a single one that can be useful to define malignancy. AIM: Our purpose is to analyse the criteria considered more important to the diagnosis of melanoma, comparing their presence in benign melanocytic lesions and melanomas. MATERIAL AND METHODS: We studied 33 benign melanocytic lesions (Spitz nevi, 13; Reed nevi, 6; dysplastic nevi, 6; congenital nevi, 3; acquired nevi, 3; combined nevus, 1; recurrent nevus, 1 and 101 extensive/superficial melanomas (25 in situ and 76 invasive up to 2 mm thickness. RESULTS: Some criteria showed high frequency in benign lesions, showing low-specificity, while others had low-positivity in the benign and high-frequency in malignant lesions, consequently high

Racial and ethnic variations in incidence and survival of cutaneous melanoma in the United States, 1999-2006.

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Wu, Xiao-Cheng; Eide, Melody J; King, Jessica; Saraiya, Mona; Huang, Youjie; Wiggins, Charles; Barnholtz-Sloan, Jill S; Martin, Nicolle; Cokkinides, Vilma; Miller, Jacqueline; Patel, Pragna; Ekwueme, Donatus U; Kim, Julian

2011-11-01

Most melanoma studies use data from the National Cancer Institute Surveillance, Epidemiology, and End Results Program or individual cancer registries. Small numbers of melanoma cases have limited in-depth analyses for all racial and ethnic groups. We sought to describe racial and ethnic variations in melanoma incidence and survival. Incidence for invasive melanoma and 5-year melanoma-specific survival were calculated for whites, blacks, American Indians/Alaskan Natives, Asians/Pacific Islanders (API), and Hispanics using data from 38 population-based cancer registries. Incidence rates of melanoma were significantly higher for females than males among whites and Hispanics under 50 years of age and APIs under 40 years of age. White and black patients were older (median age: 59-63 years) compared with Hispanics, American Indians/Alaskan Natives, and API (median age: 52-56 years). The most common histologic type was acral lentiginous melanoma among blacks and superficial spreading melanoma among all other racial and ethnic groups. Hispanics had the highest incidence rate of acral lentiginous melanoma, significantly higher than whites and API. Nonwhites were more likely to have advanced and thicker melanomas at diagnosis and lower melanoma-specific survival compared with whites. Over 50% of melanoma cases did not have specified histology. The numbers of nonwhite patients were still relatively small despite broad population coverage (67% of United States). Racial and ethnic differences in age at melanoma diagnosis, anatomic sites, and histologic types suggest variations in etiologic pathways. The high percentages of advanced and thicker melanomas among nonwhites highlight the need to improve melanoma awareness for all race and ethnicity in the United States. Copyright © 2011 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

The role of spectrophotometry in the diagnosis of melanoma

Science.gov (United States)

2010-01-01

Background Spectrophotometry (SPT) could represent a promising technique for the diagnosis of cutaneous melanoma (CM) at earlier stages of the disease. Starting from our experience, we further assessed the role of SPT in CM early detection. Methods During a health campaign for malignant melanoma at National Cancer Institute of Naples, we identified a subset of 54 lesions to be addressed to surgical excision and histological examination. Before surgery, all patients were investigated by clinical and epiluminescence microscopy (ELM) screenings; selected lesions underwent spectrophotometer analysis. For SPT, we used a video spectrophotometer imaging system (Spectroshade® MHT S.p.A., Verona, Italy). Results Among the 54 patients harbouring cutaneous pigmented lesions, we performed comparison between results from the SPT screening and the histological diagnoses as well as evaluation of both sensitivity and specificity in detecting CM using either SPT or conventional approaches. For all pigmented lesions, agreement between histology and SPT classification was 57.4%. The sensitivity and specificity of SPT in detecting melanoma were 66.6% and 76.2%, respectively. Conclusions Although SPT is still considered as a valuable diagnostic tool for CM, its low accuracy, sensitivity, and specificity represent the main hamper for the introduction of such a methodology in clinical practice. Dermoscopy remains the best diagnostic tool for the preoperative diagnosis of pigmented skin lesions. PMID:20707921

Efficient adenovector CD40 ligand immunotherapy of canine malignant melanoma.

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von Euler, Henrik; Sadeghi, Arian; Carlsson, Björn; Rivera, Patricio; Loskog, Angelica; Segall, Thomas; Korsgren, Olle; Tötterman, Thomas H

2008-05-01

Cutaneous canine melanomas are usually benign in contrast to human malignant melanoma. However, the canine oropharyngeal, uveal, and mucocutaneous neoplasms are aggressive and have metastatic potential. Surgery and to a lesser extent radiotherapy and chemotherapy are widely adopted treatments but are seldom curative in advanced stages. The similarities between human and canine melanoma make spontaneous canine melanoma an excellent disease model for exploring novel therapies. Herein, we report the first 2 adenovector CD40L immunogene (AdCD40L) treatments of aggressive canine malignant melanoma. Case no. 1 was an advanced stage III oral melanoma that was cured from malignant melanoma with 2 intratumor AdCD40L injections before cytoreductive surgery. After treatment, the tumor tissue was infiltrated with T lymphocytes and B lymphocytes suggesting immune activation. This dog survived 401 days after the first round of gene therapy and was free of melanoma at autopsy. Case no. 2 had a conjunctival malignant melanoma with a rapid progression. This case was treated with 6 AdCD40L injections over 60 days. One hundred and twenty days after start of gene therapy and 60 days after the last injection, the tumor had regressed dramatically, and the dog had a minimal tumor mass and no signs of progression or metastasis. Our results indicate that AdCD40L immunogene therapy is beneficial in canine malignant melanoma and could be considered for human malignant melanoma as well.

Gene electrotransfer of plasmid antiangiogenic metargidin peptide (AMEP) in disseminated melanoma

DEFF Research Database (Denmark)

Spanggaard, Iben; Snoj, Marko; Cavalcanti, Andrea

2013-01-01

). In each patient, two cutaneous lesions were identified (one treated and one control). At day 1 and day 8, plasmid AMEP was injected intratumorally followed by electrotransfer. Patients were monitored weekly until day 29, and at day 64. Local efficacy was assessed at day 29 by direct measurement...... lesions increased more than 20%. No response occurred in distant lesions. This first-in-man study on electrotransfer of plasmid AMEP into cutaneous melanoma shows that the procedure and drug are safe and that local transfection was obtained....

HMB-45 and Melan-A are useful in the differential diagnosis between granular cell tumor and malignant melanoma.

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Gleason, Briana C; Nascimento, Alessandra F

2007-02-01

Granular cell tumors (GCTs), especially if atypical or malignant, may share cytomorphologic and architectural features with malignant melanoma, when the latter shows granular cell change. In many cases, these neoplasms can be differentiated from each other on histologic grounds, but distinction may sometimes be challenging. By immunohistochemistry, both tumors are strongly positive for S-100 protein and frequently express other nonspecific markers such as CD68, NSE, and NKIC3. In the current study, we reviewed 60 cases of conventional cutaneous, mucosal, and visceral GCT and studied the use of immunoperoxidase staining for the differential diagnosis between malignant melanoma and GCT. Immunohistochemical stains for S-100 protein, A, HMB-45, and microphthalmia transcription factor (MITF) were performed in all cases. All of the tumors were positive for S-100 protein. MITF immunostaining was diffusely positive in 53 (88%) cases, focally positive in three (5%) cases, and negative in four (7%). Fifty-seven (95%) tumors were negative for Melan-A, one case was focally positive, and two cases showed rare positive tumor cells. None of the tumors expressed HMB-45. In conclusion, GCT and malignant melanoma can be reliably differentiated on the basis of immunohistochemical stains in the majority of cases. Although not always positive in malignant melanoma, in this context, HMB-45 expression seems to be 100% specific for the diagnosis of melanoma. Melan-A is slightly less specific, with rare cases of GCT showing focal positivity. MITF is not useful in this differential-93% of the GCTs in our series showed nuclear reactivity for this marker. The latter finding highlights the limited specificity of this antibody in the diagnosis of melanocytic tumors.

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

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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

Lack of GNAQ and GNA11 germ-line mutations in familial melanoma pedigrees with uveal melanoma or blue nevi

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Jason Ezra Hawkes

2013-06-01

Full Text Available Approximately 10% of melanoma cases are familial, but only 25-40% of familial melanoma cases can be attributed to germ-line mutations in the CDKN2A - the most significant high-risk melanoma susceptibility locus identified to date. The pathogenic mutation(s in most of the remaining familial melanoma pedigrees have not yet been identified. The most common mutations in nevi and sporadic melanoma are found in BRAF and NRAS, both of which result in constitutive activation of the MAPK pathway. However, these mutations are not found in uveal melanomas or the intradermal melanocytic proliferations known as blue nevi. Rather, multiple studies report a strong association between these lesions and somatic mutations in Guanine nucleotide-binding protein G(q subunit alpha (GNAQ, Guanine nucleotide-binding protein G(q subunit alpha-11 (GNA11 and BRCA1 associated protein-1 (BAP1. Recently, germ-line mutations in BAP1, the gene encoding a tumor suppressing deubiquitinating enzyme, have been associated with predisposition to a variety of cancers including uveal melanoma, but no studies have examined the association of germ-line mutations in GNAQ and GNA11 with uveal melanoma and blue nevi. We have now done so by sequencing exon 5 of both of these genes in 13 unique familial melanoma pedigrees, members of which have had either uveal or cutaneous melanoma and/or blue nevi. Germ-line DNA from a total of 22 individuals was used for sequencing; however no deleterious mutations were detected. Nevertheless, such candidate gene studies and the discovery of novel germ-line mutations associated with an increased MM susceptibility can lead to a better understanding of the pathways involved in melanocyte transformation, formulation of risk assessment, and the development of specific drug therapies.

Reflectance confocal microscopy features of thin versus thick melanomas.

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Kardynal, Agnieszka; Olszewska, Małgorzata; de Carvalho, Nathalie; Walecka, Irena; Pellacani, Giovanni; Rudnicka, Lidia

2018-01-24

In vivo reflectance confocal microscopy (RCM) plays an increasingly important role in differential diagnosis of melanoma. The aim of the study was to assess typical confocal features of thin (≤1mm according to Breslow index) versus thick (>1mm) melanomas. 30 patients with histopathologically confirmed cutaneous melanoma were included in the study. Reflectance confocal microscopy was performed with Vivascope equipment prior to excision. Fifteen melanomas were thin (Breslow thickness ≤ 1mm) and 15 were thick melanomas (Breslow thickness >1mm). In the RCM examination, the following features were more frequently observed in thin compared to thick melanomas: edged papillae (26.7% vs 0%, p=0.032) and areas with honeycomb or cobblestone pattern (33.3% vs 6.7%, p=0.068). Both features are present in benign melanocytic lesions, so in melanoma are good prognostic factors. The group of thick melanomas compared to the group of thin melanomas in the RCM images presented with greater frequency of roundish cells (100% vs 40%, p=0.001), non-edged papillae (100% vs 60%, p=0.006), numerous pagetoid cells (73.3% vs 33.3%, p=0.028), numerous atypical cells at dermal-epidermal junction (53.3% vs 20%, p=0.058) and epidermal disarray (93.3% vs 66.7%, p=0.068). Non-invasive imaging methods helps in deepening of knowledge about the evolution and biology of melanoma. The most characteristic features for thin melanomas in confocal examination are: fragments of cobblestone or honeycomb pattern and edged papillae (as good prognostic factors). The features of thick melanomas in RCM examination are: roundish cells, non-edged papillae, numerous pagetoid cells at dermal-epidermal junction and epidermal disarray.

Balloon cell melanoma of the anal canal: A wolf in sheep′s clothing?

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Munita Meenu Bal

2013-01-01

Full Text Available Balloon cell melanoma (BCM is a rare histologic variant of cutaneous malignant melanoma with exceptional reports of occurrences at non-cutaneous sites. Herein we present a case of primary amelanotic BCM of anal canal, a heretofore undescribed location. Histologically, the tumor was characterized by sheets of pale cells that bore striking resemblance to foamy macrophages. Presence of rare atypical mitoses confirmed the malignant nature of the cells. Neoplastic cells were immunoreactive for S100, Melan-A, and focally for HMB-45 while were negative for myogenic, gastrointestinal stromal tumor, epithelial and neuroendocrine markers. Resemblance to foamy macrophages, bland cytology and absence of pigment imparts this tumor a deceptively benign histological appearance making it prone to diagnostic pitfalls. Awareness of this rare entity and judicious employment of immunohistochemistry is imperative in segregating it from its diverse mimics.

Protective immunization with B16 melanoma induces antibody response and not cytotoxic T cell response

International Nuclear Information System (INIS)

Sarzotti, M.; Sriyuktasuth, P.; Klimpel, G.R.; Cerny, J.

1986-01-01

C57BL/6 mice immunized with three intraperitoneal injections of syngeneic, irradiated B16 melanoma cells, became resistant to B16 tumor challenge. Immunized mice had high levels of serum antibody against a membrane antigen of B16 cells. The B16 antigen recognized by the anti-B16 sera formed a major band of 90 KD in gel electrophoresis. The anti-B16 antibody was partially protective when mixed with B16 cells and injected into normal recipient mice. Surprisingly, B16 resistance mice were incapable of generating cytotoxic T cells (CTL) specific for the B16 tumor. Both spleen and lymph node cell populations from immunized mice did not generate B16-specific CTL. Allogeneic mice (DBA/2 or C3H) were also unable to generate B16-specific CTL: however, alloreactive CTL produced in these strains of mice by immunization with C57BL/6 lymphocytes, did kill B16 target cells. Interestingly, spleen cells from syngeneic mice immunized with B16 tumor produced 6-fold more interleukin-2 (IL-2) than normal spleen cells, in vitro. These data suggest that immunization with B16 tumor activates a helper subset of T cells (for antibody and IL-2 production) but not the effector CTL response

Combined endovascular and surgical treatment of melanoma of the nasal cavity: a case report; Melanoma de fosas nasales. Tratamiento combinado endovascular y quirurgico. A proposito de un caso

Energy Technology Data Exchange (ETDEWEB)

Romero, A.; Delgado, F.; Ramos, M.; Bravo, F. [Hospital Universitario Reina Sofia. Cordoba (Spain)

2000-07-01

Melanoma of the nasal cavity is a rare tumor with a worse prognosis than cutaneous melanoma. It usually presents as nasal obstruction and/or epistaxis. The observation of a pigmented mass in the nasal cavity is highly suggestive of this lesion. Computed tomography shows a mass with nonspecific features. In magnetic resonance studies, it has a characteristics signal consisting of hyperintensity of T1-weighted images and hypointensity on T2-weighted images, depending on the amount of melanin. The treatment of choice is surgical resection. We present a case of melanoma of the nasal cavity in which endovascular embolization of the tumor was performed prior to surgical treatment. (Author) 11 refs.

Xeroderma Pigmentosum with Melanoma of Face and Its Prosthetic Management

International Nuclear Information System (INIS)

Sadaf, A.; Yazdanie, N.

2013-01-01

Xeroderma pigmentosum is a rare genetic disorder, characterized by cutaneous, ocular and neurological symptoms. Squamous cell carcinoma and melanoma are also its secondary characters. This case report is about maxillofacial prosthetic management of a 10 years old child presented with xeroderma pigmentosum. The nose of the patient was excised surgically due to melanoma. This case report elaborates the role of prosthodontist and the whole procedure of constructing the nasal prosthesis via conventional technique by using the patient's sibling nasal form as template. Regular follow up revealed marked improvement in esthetics, function and ultimately patient's quality of life. (author)

Xeroderma pigmentosum with melanoma of face and its prosthetic management.

Science.gov (United States)

Sadaf, Ayesha; Yazdanie, Nazia

2013-10-01

Xeroderma pigmentosum is a rare genetic disorder, characterized by cutaneous, ocular and neurological symptoms. Squamous cell carcinoma and melanoma are also its secondary characters. This case report is about maxillofacial prosthetic management of a 10 years old child presented with xeroderma pigmentosum. The nose of the patient was excised surgically due to melanoma. This case report elaborates the role of prosthodontist and the whole procedure of constructing the nasal prosthesis via conventional technique by using the patient's sibling nasal form as template. Regular follow up revealed marked improvement in esthetics, function and ultimately patient's quality of life.

Mast cells in cutaneous tumors: innocent bystander or maestro conductor?

Science.gov (United States)

Biswas, Asok; Richards, Joanna E; Massaro, Joseph; Mahalingam, Meera

2014-07-01

Evidence favoring a critical role for mast cells (MC) in cutaneous malignancies is conflicting. Using the immunohistochemical stain tryptase, MC counts were performed in the following tumor categories: epithelial (basal cell carcinoma [BCC]: nodular [N], n = 10, infiltrative [I], n = 10; squamous cell carcinoma [SCC]: well differentiated [W], n = 9, moderate/poorly differentiated [MP], n = 15); melanocytic (intradermal nevus, n = 10, malignant melanoma in situ [MMIS], n = 8, invasive melanoma, n = 15); vascular (hemangioma [HEM], n = 11, Kaposi's sarcoma [KS], n = 14, angiosarcoma [AS] n = 8); and fibrohistiocytic (dermatofibroma [DF], n = 7, atypical fibroxanthoma [AFX], n = 5, dermatofibrosarcoma protuberans [DFSP], n = 5). MC (intra- and peritumoral) were expressed as cells per 10 high-power fields. Mean MC counts were: BCCN 166.30; BCCI 130; SCCW 167.22; SCCMP 133.80; nevus 156.40; MMIS 93; MM radial growth phase 73.86; MM vertical growth phase 82.13; HEM 165.18; KS 120.57; AS 168.13; DF 247.86; AFX 280.20; and DFSP 83.60. Using a one-way analysis of variance, statistically significant differences were observed in the following pairs: AFX and DF vs. DFSP, nevus vs. melanoma, AS and HEM vs. Our findings appear to point towards a dichotomous role for mast cells in fibrohistiocytic and vascular neoplasms and argue against their preferential recruitment in epithelial malignancies and malignant melanoma. The value of mast cell counts as a prognostic index appears to be limited in most cutaneous malignancies. © 2013 The International Society of Dermatology.

[Cutaneous and mucosal manifestations associated with cocaine use].

Science.gov (United States)

Imbernón-Moya, Adrián; Chico, Ricardo; Aguilar-Martínez, Antonio

2016-06-17

Complications due to cocaine are a public health problem. The typical cutaneous disease is leukocytoclastic vasculitis and/or thrombotic vasculopathy affecting mainly the ears. No intense systemic involvement is usually present, but there may be several cutaneous, mucosal and systemic manifestations. Other findings associated as arthralgia, neutropaenia or agranulocytosis, low titer positive antinuclear antibodies, antiphospholipid antibody positivity and neutrophil cytoplasmic antibodies against multiple antigens help the diagnosis. This disease requires a clinical suspicion with a clinical history, a complete physical examination and a broad differential diagnosis for an early and correct diagnosis. The course is usually self-limited. In most cases the only treatment is to discontinue the use of cocaine associated with symptomatic treatment, no proven benefit of systemic corticosteroids. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

Diagnosis and treatment of melanoma. European consensus-based interdisciplinary guideline - Update 2016

DEFF Research Database (Denmark)

Garbe, Claus; Peris, Ketty; Hauschild, Axel

2016-01-01

Cutaneous melanoma (CM) is potentially the most dangerous form of skin tumour and causes 90% of skin cancer mortality. A unique collaboration of multi-disciplinary experts from the European Dermatology Forum, the European Association of Dermato-Oncology and the European Organisation of Research a...

Effect of DETOX as an adjuvant for melanoma vaccine.

Science.gov (United States)

Schultz, N; Oratz, R; Chen, D; Zeleniuch-Jacquotte, A; Abeles, G; Bystryn, J C

1995-04-01

The identification of effective adjuvants is critical for tumor vaccine development. Towards this end, we examined whether the immunogenicity of a melanoma vaccine could be potentiated by DETOX, an adjuvant consisting of monophosphoryl lipid A (MPL) and purified mycobacterial cell-wall skeleton (CWS). Nineteen patients with resected stage III melanoma were immunized with a polyvalent melanoma antigen vaccine (40 micrograms) admixed with DETOX, q3 wks x 4. Seven patients received vaccine + low-dose DETOX (10 micrograms MPL + 100 micrograms CWS) and 12 received vaccine + high-dose DETOX (20 micrograms MPL + 200 micrograms CWS). A non-randomized control group of 35 patients was treated similarly with 40 micrograms vaccine + alum. One week after the fourth vaccine immunization, melanoma antibodies were increased over baseline in 7/7 (100%) patients treated with vaccine + low-dose DETOX, 8/12 (67%) patients treated with vaccine + high-dose DETOX, and in 4/19 (21%) of vaccine + alum patients. For the entire DETOX group, the antibody response rate was 15/19 (79%) compared 4/19 (21%) in the alum group (p or = 15 mm increase in DTH response over baseline) was induced in 50% of the entire DETOX group versus in 47% of the alum group. Median disease-free (DF) survival for the entire DETOX group was 17.8 months compared with 32.1 months in the alum group (p DETOX markedly potentiated antibody but had little effect on DTH responses to melanoma vaccine immunization. It did not appear to improve disease-free survival in comparison to alum in this non-randomized study.

Multiple cutaneous malignancies in a patient of xeroderma pigmentosum.

Science.gov (United States)

Grampurohit, Vandana U; Dinesh, U S; Rao, Ravikala

2011-01-01

Xeroderma pigmentosum is a genodermatosis characterized by photosensitivity and the development of cutaneous and internal malignancies at an early age. The basic defect underlying the clinical manifestations is a nucleotide excision repair defect, leading to defective repair of DNA damaged by ultraviolet radiation. These patients exhibit enhanced sensitivity to ionizing radiation. Patients with xeroderma pigmentosum who are younger than 20 years of age have a greater than 1000-fold increased risk of developing skin cancer. Early detection of these malignancies is necessary because they are fast growing, metastasize early and lead to death. Although, early detection and treatment of cutaneous malignancies will reduce the morbidity and mortality, genetic counseling remains the most important measure for preventing xeroderma pigmentosum. We report a case of xeroderma pigmentosum in an 18-year-old male presenting with multiple cutaneous malignancies: squamous cell carcinoma, malignant melanoma and pigmented basal cell carcinoma.

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

Science.gov (United States)

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

2018-03-01

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

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

Science.gov (United States)

Tchernev, Georgi

2018-02-15

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

Towards a Better Understanding of the Molecular Mechanisms Involved in Sunlight-Induced Melanoma

Directory of Open Access Journals (Sweden)

Williams Mandy

2005-01-01

Full Text Available Although much less prevalent than its nonmelanoma skin cancer counterparts, cutaneous malignant melanoma (CMM is the most lethal human skin cancer. Epidemiological and biological studies have established a strong link between lifetime exposure to ultraviolet (UV light, particularly sunburn in childhood, and the development of melanoma. However, the specific molecular targets of this environmental carcinogen are not known. Data obtained from genetic and molecular studies over the last few years have identified the INK4a/ARF locus as the “gatekeeper” melanoma suppressor, encoding two tumour suppressor proteins in human, p16 INK4a and p14 ARF . Recent developments in molecular biotechnology and research using laboratory animals have made a significant gene breakthrough identifying the components of the p16 INK4a /Rb pathway as the principal and rate-limiting targets of UV radiation actions in melanoma formation. This review summarizes the current knowledge of the molecular mechanisms involved in melanoma development and its relationship to sunlight UV radiation.

Comparative study of angio genesis radiopharmaceuticals for melanoma detection; Estudo comparativo de radiofarmacos para angiogenese na deteccao de melanoma

Energy Technology Data Exchange (ETDEWEB)

Oliveira, Erica Aparecida de

2011-07-01

Early diagnosis and treatment of melanoma, a cutaneous tumor with a serious prognosis, is extremely important for optimal clinical outcome. Phage display peptide libraries are a useful screening resource for identifying bioactive peptides that interact with cancer targets. The aim of this study was the evaluation of two technetium-99m tracers for angio genesis detection in melanoma model, using cyclic peguilated pentapeptide with RGD and NGR motifs conjugated with bifunctional chelator MAG3. The conjugated peptides (10 {mu}L of a {mu}g/{mu}L solution) were labeled with technetium-99m using a sodium tartrate buffer. Radiochemical evaluation was done by ITLC and confirmed by HPLC. Partition coefficient was determined and internalization assays were performed in two melanoma cells (B16F10 and SKMEL28). Biodistribution evaluation of the tracers was done in healthy animals at different times and also in mice bearing the tumor cells at 120 min post injection. Blocking studies were also conducted by co-injection of cold peptides. The conjugated showed the same profile in many evaluations. They were radiolabeled with high radiochemical purity (>97%). Both were hydrophilic, with preferential renal excretion. Tumor uptake was higher for human melanoma cells than for murinic melanoma cells, specially for {sup 99m}Tc-MAG3-PEG{sub 8}-c(RGDyK) (7.85{+-}{+-}2.34 %ID/g) at 120 min post injection. The performance of {sup 99m}Tc-MAG{sub 3}-PEG{sub 8}-c(RGDyk) was much better than NGR tracer concerning human melanoma uptake and might be considered in future investigations focusing radiotracers for melanoma diagnosis. (author)

Melanomas: radiobiology and role of radiation therapy

International Nuclear Information System (INIS)

Peschel, Richard E.

1995-01-01

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

CHOROIDAL MELANOMA IN PHAKOMATOSIS PIGMENTOVASCULARIS WITH KLIPPEL-TRENAUNAY SYNDROME.

Science.gov (United States)

Shields, Carol L; Di Nicola, Maura; Pellegrini, Marco; Shields, Jerry A

2017-09-20

To describe the relationship of choroidal melanoma with phakomatosis pigmentovascularis in patients with Klippel-Trenaunay syndrome. Retrospective review of 5 patients. In all 5 cases, the patient was white and the cutaneous port-wine stain was congenital. The port-wine stain involved the chin (n = 1), jawline (n = 2), lower cheek (n = 1), thorax (n = 5), abdomen (n = 4), upper (n = 4), and lower (n = 3) limb(s). The ocular melanocytosis involved the sclera (n = 5), iris (n = 2) and choroid (n = 4). At diagnosis of choroidal melanoma, mean patient age was 57 years (median 61, range 17-83 years). The melanoma demonstrated mean basal diameter of 11.6 mm (median 12, range 5-16 mm) and mean thickness of 5.7 mm (median 6.1, range 2-9), revealing intrinsic tumor pigment and subretinal fluid in all cases. Melanoma management included plaque radiotherapy (n = 3), thermotherapy (n = 1), or enucleation (n = 1). At mean follow-up of 4 years, one patient demonstrated melanoma-related metastasis with death. Phakomatosis pigmentovascularis represents coexistence of Klippel-Trenaunay syndrome (or Sturge-Weber syndrome) and oculo(dermal) melanocytosis, promoting risk for life-threatening uveal melanoma. The authors suggest that all patients with Klippel-Trenaunay syndrome be evaluated for phakomatosis pigmentovascularis and affected patients have dilated fundus examination once or twice a year.

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

International Nuclear Information System (INIS)

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

2013-01-01

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

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.

Combined endovascular and surgical treatment of melanoma of the nasal cavity: a case report

International Nuclear Information System (INIS)

Romero, A.; Delgado, F.; Ramos, M.; Bravo, F.

2000-01-01

Melanoma of the nasal cavity is a rare tumor with a worse prognosis than cutaneous melanoma. It usually presents as nasal obstruction and/or epistaxis. The observation of a pigmented mass in the nasal cavity is highly suggestive of this lesion. Computed tomography shows a mass with nonspecific features. In magnetic resonance studies, it has a characteristics signal consisting of hyperintensity of T1-weighted images and hypointensity on T2-weighted images, depending on the amount of melanin. The treatment of choice is surgical resection. We present a case of melanoma of the nasal cavity in which endovascular embolization of the tumor was performed prior to surgical treatment. (Author) 11 refs

Clinical radiobiology of malignant melanoma

International Nuclear Information System (INIS)

Bentzen, S.M.; Overgaard, J.; Overgaard, M.; Thames, H.D.; Vejby Hansen, P.; Von der Maase, H.; Meder, J.

1989-01-01

Tumor-control probability (TCP) was analyzed in a series of 121 patients having 239 histologically proven recurrent or metastatic malignant melanomas. These were treated with fractionated radiotherapy with various doses per fraction, total doses, and overall times. Cutaneous lesions (127,53%) were treated with electron beams, and more deeply seated tumors (112,47%) with 60 Co or 4-8 MV X-rays. The fraction size was highly variable, and this permitted determination of the α/β ration in the multifraction linearquadratic model, which was estimated at 0.57 Gy with 95% confidence limits [-1.07,2.5]Gy Threatment time had no demonstrable influenc on TCP. Thus this tumor exhibits the fractionation sensitivity characteristic of a late-responding normal tissue, suggesting that an adequate fractionation schedule for malignant melanomas would be characterized by larger-than-conventional doses per fraction, possibly about 6 Gy per fraction. This is consistent with the conclusions of other authors. Tumor size, evaluated as mean tumor diameter, S, had a major impact on TCP: the number of target cells increased as a power function of S with exponent 0.72 (95% confidence limits) [1.49, 0.94]. In fact, a considerable amount of the heterogeneity in the dose-responce data could be removed by accounting for size. Thus, the weak, or absent dose response became highly significant. When a patient had multiple lesions, the responses of these to radiotherapy tended to be similar, thus implying that results were significantly influenced by a 'hidden parameter' (such as inherent radiosensitivity or immunological status). A test of the predictive value of the TCP-model was performed in a different series of 183 cutaneous and lymph node malignant melanomas. The observed dose-response relationship in this data set was in good agreement with the model prediction. A chi-square test for goodness-of-fit showed that the variation between predicted and observed results could be explained by the

Combined SEP and anti-PD-L1 antibody produces a synergistic antitumor effect in B16-F10 melanoma-bearing mice.

Science.gov (United States)

Hu, Zhengping; Ye, Liang; Xing, Yingying; Hu, Jinhang; Xi, Tao

2018-01-09

The increased PD-L1 induces poorer prognosis in melanoma. The treatment with PD-1/PD-L1 antibodies have a low response rate. The combination immunotherapies are the encouraging drug development strategy to receive maximal therapeutic benefit. In this study, we investigated the enhanced antitumor and immunomodulatory activity of combined SEP and αPD-L1 in B16-F10 melanoma-bearing mice. The results shown that combined SEP and αPD-L1 presented significant synergistic antitumor effects, increased the frequency of CD8 + and CD4 + T cells in spleen and tumor, cytotoxic activity of CTL in spleen, and IL-2 and IFN-γ levels in splenocytes and tumor. The combination treatment also produced synergistic increase in P-ERK1/2 level in spleen. Immunohistochemistry shown that SEP induced the PD-L1 expression in melanoma tissue possibly by promoting IFN-γ excretion, which led to the synergistic anti-tumor effects of aPD-L1 and SEP. Furthermore, in the purified T lymphocyte from the naive mice, the combination of SEP and αPD-L1 had more potent than SEP or αPD-L1 in promoting T lymphocyte proliferation and cytokines secretion including IL-2 and IFN-γ, at least partially by activating MEK/ERK pathway. Our study provides the scientific basis for a clinical trial that would involve combination of anti-PD-L1 mAb and SEP for sustained melanoma control.

A Rare Thyroid Metastasis from Uveal Melanoma and Response to Immunotherapy Agents

Directory of Open Access Journals (Sweden)

Dearbhaile Catherine Collins

2016-01-01

Full Text Available Thyroid metastasis is a rare occurrence with cutaneous melanoma and even more uncommon with uveal melanoma. The management of such metastasis is uncertain due to its infrequency and, in the era of immunotherapy, the effect of these novel drugs on uncommon metastasis, such as to the thyroid, is unknown. We report the rare case of a thyroid metastasis in a patient diagnosed with ocular melanoma initially managed with enucleation. Metastatic disease developed in the lung and thyroid gland. The case patient received the immunotherapy ipilimumab with stable disease in the thyroid and progressive disease elsewhere. The patient was then further treated with a second immunotherapy agent, pembrolizumab, and remains with stable disease one year later. We discuss the current literature on thyroid metastases from all causes and the optimal known management strategies. Furthermore, we provide an original report on the response of this disease to the novel immunomodulators, ipilimumab, and pembrolizumab with stable disease four years after initial diagnosis of ocular melanoma.

Uveal melanoma in relation to ultraviolet light exposure and host factors.

Science.gov (United States)

Holly, E A; Aston, D A; Char, D H; Kristiansen, J J; Ahn, D K

1990-09-15

We conducted a case-control interview study among 1277 subjects (407 patients, 870 controls selected by using random digit dial) in 11 western United States to determine whether uveal melanoma and cutaneous melanoma shared common risk factors. After adjustment for other factors, the risk of uveal melanoma was increased for those with green, gray, or hazel eyes [relative risk (RR) = 2.5, P less than 0.001] or blue eyes (RR = 2.2, P less than 0.001) when compared to brown. A tendency to sunburn after 0.5 h midday summer sun exposure increased risk for uveal melanoma (burn with tanning RR = 1.5, P = 0.02; burn with little tanning RR = 1.8, P less than 0.001; burn with no tanning RR = 1.7, P = 0.002); as did exposure to UV or black lights (RR = 3.7, P = 0.003); and welding burn, sunburn of the eye, or snow blindness (RR = 7.2, P less than 0.001). An association with uveal melanoma was also noted with an increasing number of large nevi (P = 0.04 for trend), although the individual risk estimates were not remarkable. These data suggest that host factors and exposure to UV light are risk factors for uveal melanoma.

In-depth characterization of microRNA transcriptome in melanoma.

Directory of Open Access Journals (Sweden)

James Kozubek

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

The clinical role of immunoscintigraphy for the detection of ocular melanoma

Energy Technology Data Exchange (ETDEWEB)

Schaling, D.F. [Leiden, Univ. Hospital (Netherlands). Dipt. of Ophtalmology. Dpt. of Diagnostic Radiology and Nuclear Medicine; Pauwels, E.K. [Leiden, Univ. Hospital (Netherlands). Dipt. of Diagnostic Radiology and Nuclear Medicine

1996-12-01

The value of immunoscintigraphy in the diagnostic of choroidal melanoma is discussed and compared with other diagnostic procedures with isotopes and diagnostic modalities like fluorescein angiography, standardized ultrasonography and magnetic resonance imaging. Consecutive studies with immunoscintigraphy in choroidal melanoma show a sensitivity of 41 to 49%, witch can be improved by use of single photon emission computerized tomography (SPECT). Another technique which has improved the results of radio-immunoscintigraphy is the use of a three-step labelling procedure with biotinylated anti-tumor antibodies and avidin. The specificity of the 225.288 antibody is discussed with regard to the expression of the chondroitin sulfate proteoglycan (CSPG) - to which the 225.288 antibody is directed - in normal tissue and in other malignant tumours.

Comparative study of angio genesis radiopharmaceuticals for melanoma detection

International Nuclear Information System (INIS)

Oliveira, Erica Aparecida de

2011-01-01

Early diagnosis and treatment of melanoma, a cutaneous tumor with a serious prognosis, is extremely important for optimal clinical outcome. Phage display peptide libraries are a useful screening resource for identifying bioactive peptides that interact with cancer targets. The aim of this study was the evaluation of two technetium-99m tracers for angio genesis detection in melanoma model, using cyclic peguilated pentapeptide with RGD and NGR motifs conjugated with bifunctional chelator MAG3. The conjugated peptides (10 μL of a μg/μL solution) were labeled with technetium-99m using a sodium tartrate buffer. Radiochemical evaluation was done by ITLC and confirmed by HPLC. Partition coefficient was determined and internalization assays were performed in two melanoma cells (B16F10 and SKMEL28). Biodistribution evaluation of the tracers was done in healthy animals at different times and also in mice bearing the tumor cells at 120 min post injection. Blocking studies were also conducted by co-injection of cold peptides. The conjugated showed the same profile in many evaluations. They were radiolabeled with high radiochemical purity (>97%). Both were hydrophilic, with preferential renal excretion. Tumor uptake was higher for human melanoma cells than for murinic melanoma cells, specially for 99m Tc-MAG3-PEG 8 -c(RGDyK) (7.85±±2.34 %ID/g) at 120 min post injection. The performance of 99m Tc-MAG 3 -PEG 8 -c(RGDyk) was much better than NGR tracer concerning human melanoma uptake and might be considered in future investigations focusing radiotracers for melanoma diagnosis. (author)

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

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Georgi Tchernev

2018-02-01

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

Spotlighting the role of photodynamic therapy in cutaneous malignancy: an update and expansion.

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Ross, Kate; Cherpelis, Basil; Lien, Mary; Fenske, Neil

2013-12-01

Topical photodynamic therapy (PDT) is an option for the treatment of cutaneous malignancy. To present an update and expansion on a previous review of the use of PDT in the current literature in the treatment of actinic keratoses (AK), superficial and nodular basal cell carcinoma (sBCC, nBCC), squamous cell carcinoma (SCC), Bowen's disease, cutaneous T cell lymphoma (CTCL), malignant melanoma, and its use in chemoprevention. Extensive PubMed search January 2013. We find sufficient evidence to recommend the use of PDT in certain patients in the treatment of AK, Bowen's disease, sBCC, and nBCC. It is especially useful in those with contraindications to surgery, widespread areas of involvement, and large lesions. Not only can it be considered superior to other therapies as far as recovery time, tolerance, and cosmetic outcomes, but it also should be considered, when indicated, as first-line treatment in the above conditions. Investigations continue for the use of PDT in the treatment of melanoma, SCC, chemoprevention, and CTCL. © 2013 by the American Society for Dermatologic Surgery, Inc. Published by Wiley Periodicals, Inc.

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....

Antiphospholipid antibody syndrome complicated by Grave's disease.

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Takahashi, Ayumi; Tamura, Atsushi; Ishikawa, Osamu

2002-12-01

The report describes a woman with primary antiphospholipid antibody syndrome complicated with Grave's disease. Developing symptoms included a small cutaneous nodule on her finger and subsequently ecchymotic purpura on the cheeks, ears, buttocks and lower legs. Histological examinations showed thrombosed vessels in the dermis without or with hemorrhage, respectively. Laboratory investigation revealed positive lupus anticoagulant and immunogenic hyperthyroidism due to Grave's disease. There is a close relationship between the cutaneous manifestation of antiphospholipid antibody syndrome and the activities of Grave's disease and a possible link of antiphospholipid antibody syndrome with Grave's disease was suggested both by the etiology of the disease as well as the disease activity.

Two unusual cases of brain metastases from lung primary malignant melanoma

International Nuclear Information System (INIS)

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

2004-01-01

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

ADVANCED UVEAL MELANOMA WITH SUBDURAL METASTASIS MIMICKING MENINGEOMA - A CASE REPORT

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Predrag Kovačević

2011-03-01

Full Text Available Uveal melanoma is a rare malignancy. Its clinical course is highly agressive. At thetime of diagnosis, extraocular extension is present in most of the cases.We present a case of 69-year-old white man admitted for sharp orbital pain. Advanced uveal melanoma was diagnosed. We found black-colored tumor rotruding from the left eye and multiple cutaneous metastases on the scalp. CT scan revealed intracranial tumor mimicking meningeoma in the left parietal region. Lymhogenous metastases were not found and other hematogenous metastases were excluded. After biopsy of the eye tumor and excisional biopsy of one skin tumor, the uveal melanoma was diagnosed and the left orbital exenteration and extirpation of intracranial tumor were performed. The reconstruction was performed using galeacutaneous flap harvested from craniotomy flap. Postoperative course was uneventful and the patient was released from pain. He refused the additional oncological treatment. After four months, he died of liver metastatic disease.The uveal melanoma is highly aggressive malignancy and isolated subdural metastasis is quite rare. The reconstruction with transposed galeacutaneous flap is versatile and secure technique after orbital exenteration.

Intensity-Modulated Radiotherapy Triggers Onset of Bullous Pemphigoid in a Patient with Advanced Melanoma Treated with Nivolumab

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Kayo Tanita

2018-02-01

Full Text Available Since the efficacy of ipilimumab on nivolumab-resistant advanced melanoma is extremely low, additional supportive therapy for anti-PD-1 antibody therapy-resistant advanced melanoma is needed. Although several supportive therapies that enhance the antitumor immune response of anti-PD-1 antibodies have already been reported, unexpected immune-related adverse events were detected at the same time. In this report, we describe a patient with advanced melanoma treated with nivolumab followed by intensity-modulated radiotherapy, which might have triggered bullous pemphigoid (BP. Although several cases of BP developing in anti-PD-1 antibody-treated patients have already been reported, in this report, we shed light on the possible pathogenesis of BP developing in a patient treated with nivolumab through M2 macrophages.

Biflorin induces cytotoxicity by DNA interaction in genetically different human melanoma cell lines.

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Ralph, Ana Carolina Lima; Calcagno, Danielle Queiroz; da Silva Souza, Luciana Gregório; de Lemos, Telma Leda Gomes; Montenegro, Raquel Carvalho; de Arruda Cardoso Smith, Marília; de Vasconcellos, Marne Carvalho

2016-08-01

Cancer is a public health problem and the second leading cause of death worldwide. The incidence of cutaneous melanoma has been notably increasing, resulting in high aggressiveness and poor survival rates. Taking into account the antitumor activity of biflorin, a substance isolated from Capraria biflora L. roots that is cytotoxic in vitro and in vivo, this study aimed to demonstrate the action of biflorin against three established human melanoma cell lines that recapitulate the molecular landscape of the disease in terms of genetic alterations and mutations, such as the TP53, NRAS and BRAF genes. The results presented here indicate that biflorin reduces the viability of melanoma cell lines by DNA interactions. Biflorin causes single and double DNA strand breaks, consequently inhibiting cell cycle progression, replication and DNA repair and promoting apoptosis. Our data suggest that biflorin could be considered as a future therapeutic option for managing melanoma. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

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Brandon A. Miller MD, PhD

2013-06-01

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

Sentinel lymph node mapping and biopsy for melanoma in South Brazil

International Nuclear Information System (INIS)

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

2004-01-01

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

Subacute cutaneous lupus erythematosus presenting as poikiloderma.

LENUS (Irish Health Repository)

Hughes, R

2012-02-01

Subacute cutaneous lupus erythematosus (SCLE) is a recognised variant of lupus erythematosus (LE), which accounts for 10-15% of all cases of cutaneous LE, occurring most commonly in young to middle-aged white women. Diagnosis is based on the detection of anti-Ro\\/SS-A antibodies in the skin and serum, characteristic clinical and histological cutaneous involvement, and relatively mild systemic involvement. Several unusual variants of SCLE have been reported including erythrodermic SCLE, SCLE with vitiligo-like lesions, acral SCLE and bullous SCLE. Poikoilodermatous SCLE is a recognised but rare variant of SCLE. There are currently only two case reports, comprising five individual cases, in the literature. We present a case of SCLE in which the main clinical findings were an extensive photodistributed poikilodermatous rash and alopecia.

Exponentially increasing incidences of cutaneous malignant melanoma in Europe correlate with low personal annual UV doses and suggests 2 major risk factors.

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Merrill, Stephen J; Ashrafi, Samira; Subramanian, Madhan; Godar, Dianne E

2015-01-01

For several decades the incidence of cutaneous malignant melanoma (CMM) steadily increased in fair-skinned, indoor-working people around the world. Scientists think poor tanning ability resulting in sunburns initiate CMM, but they do not understand why the incidence continues to increase despite the increased use of sunscreens and formulations offering more protection. This paradox, along with lower incidences of CMM in outdoor workers, although they have significantly higher annual UV doses than indoor workers have, perplexes scientists. We found a temporal exponential increase in the CMM incidence indicating second-order reaction kinetics revealing the existence of 2 major risk factors. From epidemiology studies, we know one major risk factor for getting CMM is poor tanning ability and we now propose the other major risk factor may be the Human Papilloma Virus (HPV) because clinicians find β HPVs in over half the biopsies. Moreover, we uncovered yet another paradox; the increasing CMM incidences significantly correlate with decreasing personal annual UV dose, a proxy for low vitamin D3 levels. We also discovered the incidence of CMM significantly increased with decreasing personal annual UV dose from 1960, when it was almost insignificant, to 2000. UV and other DNA-damaging agents can activate viruses, and UV-induced cytokines can hide HPV from immune surveillance, which may explain why CMM also occurs in anatomical locations where the sun does not shine. Thus, we propose the 2 major risk factors for getting CMM are intermittent UV exposures that result in low cutaneous levels of vitamin D3 and possibly viral infection.

Interferon-β gene transfer induces a strong cytotoxic bystander effect on melanoma cells.

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Rossi, Úrsula A; Gil-Cardeza, María L; Villaverde, Marcela S; Finocchiaro, Liliana M E; Glikin, Gerardo C

2015-05-01

A local gene therapy scheme for the delivery of type I interferons could be an alternative for the treatment of melanoma. We evaluated the cytotoxic effects of interferon-β (IFNβ) gene lipofection on tumor cell lines derived from three human cutaneous and four canine mucosal melanomas. The cytotoxicity of human IFNβ gene lipofection resulted higher or equivalent to that of the corresponding addition of the recombinant protein (rhIFNβ) to human cells. IFNβ gene lipofection was not cytotoxic for only one canine melanoma cell line. When cultured as monolayers, three human and three canine IFNβ-lipofected melanoma cell lines displayed a remarkable bystander effect. As spheroids, the same six cell lines were sensitive to IFNβ gene transfer, two displaying a significant multicell resistance phenotype. The effects of conditioned IFNβ-lipofected canine melanoma cell culture media suggested the release of at least one soluble thermolabile cytotoxic factor that could not be detected in human melanoma cells. By using a secretion signal-free truncated human IFNβ, we showed that its intracellular expression was enough to induce cytotoxicity in two human melanoma cell lines. The lower cytoplasmatic levels of reactive oxygen species detected after intracellular IFNβ expression could be related to the resistance displayed by one human melanoma cell line. As IFNβ gene transfer was effective against most of the assayed melanomas in a way not limited by relatively low lipofection efficiencies, the clinical potential of this approach is strongly supported. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

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

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

2014-03-01

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

Successful Treatment of Nivolumab-Resistant Multiple In-Transit Melanomas with Ipilimumab and Topical Imiquimod

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Taku Fujimura

2018-01-01

Full Text Available Simultaneous or sequential, planned administration of ipilimumab could significantly enhance the antitumor effects of nivolumab in advanced melanoma patients. On the other hand, the efficacy of ipilimumab for nivolumab-resistant advanced melanoma is extremely poor. Therefore, additional supportive therapy for anti-PD-1 antibody therapy-resistant advanced melanoma has been widely investigated. In this report, we describe a case of multiple in-transit melanomas developing in a nivolumab-resistant patient successfully treated with ipilimumab in combination with imiquimod. Our present case suggested a possible therapy for nivolumab-resistant multiple in-transit melanomas using ipilimumab in combination with topical imiquimod.

New targeted treatments for cutaneous T-cell Lymphomas

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Martine Bagot

2017-01-01

Full Text Available Cutaneous T-cell lymphomas (CTCLs represent a group of rare and heterogeneous diseases that are very difficult to treat at advanced stages. The development of monoclonal antibodies is a new hope for the treatment of these diseases. Alemtuzumab (Campath is a humanized IgG1 kappa monoclonal antibody specific for CD52, an antigen expressed by most T and B lymphocytes. Alemtuzumab may frequently induce long-term remissions in patients with Sezary syndrome but high-dose treatments lead to severe cytopenia, immune depletion, and opportunistic infections. This treatment is less efficient in mycosis fungoides (MF. Brentuximab vedotin is a chimeric anti-CD30 monoclonal antibody conjugated to monomethyl auristatin E, a cytotoxic antitubulin agent. Brentuximab vedotin is a very interesting new treatment for advanced tumor MF, Sezary syndrome, and primary cutaneous CD30+ lymphoproliferative disorders. The main limiting adverse event is neurosensitive peripheral neuropathy. Mogamulizumab is a humanized anti-C-C chemokine receptor Type 4 monoclonal antibody with a defucosylated Fc region leading to increased antibody-dependent cellular cytotoxicity. Mogamulizumab is very efficient on aggressive peripheral T-cell lymphomas, particularly adult T-cell leukemia/lymphoma and CTCLs, especially on the blood component of tumor cells. The main limiting events are related to the concomitant depletion of regulatory T-cells. IPH4102 is a humanized monoclonal antibody that targets the immune receptor KIR3DL2/CD158k. Preclinical results with this antibody offer proofs of concept for the clinical development of IPH4102 to treat patients with advanced CTCL.

177Lu-DOTA-Bevacizumab: Radioimmunotherapy Agent for Melanoma.

Science.gov (United States)

Camacho, Ximena; Calzada, Victoria; Fernandez, Marcelo; Alonso, Omar; Chammas, Roger; Riva, Eloisa; Gambini, Juan Pablo; Cabral, Pablo

2017-01-01

Vascular endothelial growth factor (VEGF) is one of the classic factors to tumor-induced angiogenesis in several types, including melanoma. Bevacizumab is a humanized monoclonal antibody directed against VEGF. To radiolabel Bevacizumab with 177-Lutetium as a potential radioimmunotherapy agent for melanoma. Bevacizumab was derivatized with DOTA-NHS-ester at 4 ºC for 18 h. DOTABevacizumab was radiolabeled with 177LuCl3 (15 MBq/mg) at 37 ºC for 1 h. The studies were performed in healthy and B16F1 tumor-bearing C57BL/6J mice at 24 and 48 h (n = 5). Scinthigraphic imaging studies were performed at 24 h to determine the radiochemical stability, targeting specificity and pharmacokinetics of the 177Lutetium-labeled antibody. DOTA-Bevacizumab was efficiently labeled with 177LuCl3 at 37 °C. The in-vitro stability of labeled product was optimal over 72 h. In-vivo biodistribution studies showed a high liver and tumor uptake of 177Lu-DOTA-Bevacizumab, with tumor-to-muscle ratios of 11.58 and 6.37 at 24 and 48 h p.i. Scintigraphic imaging of melanoma tumor-bearing C57BL/6J mice showed liver and a high tumor selective uptake of 177Lu-DOTA-Bevacizumab at 24 h. Our results support the potential role of 177Lu-DOTA-Bevacizumab as a novel radioimmunotherapy agent for melanoma. We hope that these novel molecular imaging agents will open the path to new diagnostic and therapeutic strategies for Melanoma disease. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Interferon-induced changes in pharmacokinetics and tumor uptake of 111In-labeled antimelanoma antibody 96.5 in melanoma patients

International Nuclear Information System (INIS)

Rosenblum, M.G.; Lamki, L.M.; Murray, J.L.; Carlo, D.J.; Gutterman, J.U.

1988-01-01

The type I interferons [both partially purified human leukocyte interferon (HuIFN-alpha) and recombinant alpha interferon] and the type II interferons have been shown to increase the expression of tumor-associated antigens in vitro. To determine whether HuIFN-alpha could increase tumor acquisition of the antimelanoma antibody 96.5 in vivo, five patients with metastatic malignant melanoma were treated with HuIFN-alpha at a dose of 3 X 10(6) units daily by im administration. Twenty-four hours after the first dose of HuIFN-alpha, 1 mg of antibody 96.5 labeled with 5 mCi of 111 In was coadministered with 19 mg of unlabeled 96.5. Five patients matched for metastatic site and lesion size who had not received HuIFN-alpha were also given a dose of 5 mCi of radiolabeled 96.5 at the same total antibody dose (20 mg). In patients treated with HuIFN-alpha, there was a statistically significant increase in the plasma half-life of the 111 In label (39.7 +/- 3.3 hr) compared to the untreated control group (29.8 +/- 3.2 hr). In addition, there was an increase in the apparent volume of distribution of the antibody in the HuIFN-alpha group (5.56 +/- 0.67 L) compared to controls (3.15 +/- 0.5 L) suggesting both an increased immediate extravascular distribution of radiolabeled antibody and a decrease in the subsequent rate of clearance of antibody from plasma. These two phenomena result in a 28% decrease in the area under the concentration curve in the HuIFN-alpha-treated group compared to controls. Computer analysis of whole-body scans from patients showed a threefold increase in radiolabeled antibody distributed to tumor relative to blood pool but no change in organ:blood ratios for liver, spleen, bone, or kidney compared to controls

Antiphospholipid Antibody Induced by Nivolumab

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Ahmed Aburahma

2018-01-01

Full Text Available Nivolumab is a monoclonal antibody against the programmed death protein 1 and is used for patients with advanced melanoma. It is associated with potentially immune-related adverse events, including disorders of the skin, GI tract, and the thyroid; these disorders were successfully treated with prednisone and infliximab. Other immunotherapeutic agents were observed to induce the formation of antiphospholipid antibody (APA including α-interferon and interleukin-2. We present a case of APA development after the third dose of nivolumab in a 71-year-old male with advanced melanoma. The APA was detected after finding a prolonged aPTT; the lupus anticoagulant assay tested positive. The patient was treated with prednisone but, unfortunately, he expired a few days later.

Circulating Tumour DNA for Monitoring Treatment Response to Anti-PD-1 Immunotherapy in Melanoma Patients

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Atsuko Ashida

2017-08-01

Full Text Available Anti-programmed cell death-1 (anti-PD-1 antibody shows high therapeutic efficacy in patients with advanced melanoma. However, assessment of its therapeutic activity can be challenging because of tumour enlargement associated with intratumoural inflammation. Because circulating tumour DNA (ctDNA correlates with tumour burden, we assessed the value of ctDNA levels as an indicator of tumour changes. Quantification of ctDNA (BRAFmutant or NRASmutant levels by droplet digital PCR in 5 patients with BRAF or NRAS mutant melanoma during the treatment course showed dynamic changes corresponding to radiological and clinical alterations. In 3 cases in which the anti-PD-1 antibody was effective, ctDNA levels decreased within 2–4 weeks after treatment initiation. In 2 cases in which the anti-PD-1 antibody was ineffective, ctDNA levels did not decrease after treatment initiation. ctDNA could be a useful biomarker to predict early response to treatment in patients with advanced melanoma treated with anti-PD-1 immunotherapy.

Dysplastic vs. Common Naevus-associated vs. De novo Melanomas: An Observational Retrospective Study of 1,021 Patients

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Alejandro Martin-Gorgojo

2018-03-01

Full Text Available The aim of this case-case study was to determine the differences between dysplastic and common naevus-associated melanomas (NAM and de novo melanomas. A total of 1,021 prospectively collected patients with invasive cutaneous melanoma from an oncology referral centre were included in the study. Of these, 75.51% had de novo melanomas, 12.93% dysplastic NAM, and 11.56% common NAM. Dysplastic NAM, compared with de novo melanomas, were associated with intermittently photo-exposed sites, atypical melanocytic naevi, decreased tumour thickness, and presence of MC1R non-synonymous variants. Common NAM were more frequent on the trunk and of superficial spreading type. Comparison of dysplastic with common NAM showed significant difference only with regard to mitoses. Both subtypes of NAM shared less aggressive traits than de novo melanomas, albeit with no significant differences in survival after multivariate adjustment. In conclusion, NAM present with less aggressive traits, mostly due to a greater awareness among patients of changing moles than due to their intrinsic biological characteristics.

Profile of ipilimumab and its role in the treatment of metastatic melanoma

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Patel SP

2011-12-01

Full Text Available Sapna P Patel, Scott E WoodmanMelanoma Medical Oncology Department, University of Texas, MD Anderson Cancer Center, Houston, TX, USAAbstract: Melanoma is an immunogenic cancer. However, the ability of the immune system to eradicate melanoma tumors is affected by intrinsic negative regulatory mechanisms. Multiple immune-modulatory therapies are currently being developed to optimize the immune response to melanoma tumors. Two recent Phase III studies using the monoclonal antibody ipilimumab, which targets the cytotoxic T-lymphocyte antigen (CTLA-4, a negative regulator of T-cell activation, have demonstrated improvement in overall survival of metastatic melanoma patients. This review highlights the clinical trial data that supports the efficacy of ipilimumab, the immune-related response criteria used to evaluate clinical response, and side-effect profile associated with ipilimumab treatment.Keywords: ipilimumab, melanoma, T-cells, CTLA-4

Molecular characterization of melanoma cases in Denmark suspected of genetic predisposition.

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Karin A W Wadt

Full Text Available Both environmental and host factors influence risk of cutaneous melanoma (CM, and worldwide, the incidence varies depending on constitutional determinants of skin type and pigmentation, latitude, and patterns of sun exposure. We performed genetic analysis of CDKN2A, CDK4, BAP1, MC1R, and MITFp.E318K in Danish high-risk melanoma cases and found CDKN2A germline mutations in 11.3% of CM families with three or more affected individuals, including four previously undescribed mutations. Rare mutations were also seen in CDK4 and BAP1, while MC1R variants were common, occurring at more than twice the frequency compared to Danish controls. The MITF p.E318K variant similarly occurred at an approximately three-fold higher frequency in melanoma cases than controls. To conclude, we propose that mutation screening of CDKN2A and CDK4 in Denmark should predominantly be performed in families with at least 3 cases of CM. In addition, we recommend that testing of BAP1 should not be conducted routinely in CM families but should be reserved for families with CM and uveal melanoma, or mesothelioma.

Boronated monoclonal antibody conjugates for neutron capture therapy

International Nuclear Information System (INIS)

Borg, D.C.; Elmore, J.J. Jr.; Ferrone, S.

1986-01-01

This paper describes the effectiveness of 10 B-labeled monoclonal antibodies against Colo-38 human melanoma in vitro. The authors obtained high boron to antibody ratios while maintaining antibody activity by using dextran intermediate carriers to link 10 B to the antibody. They developed a double cell quasi-competitive binding bioassay to minimize the effects of nonspecific binding of boronated complexes to cells. 1 fig., 2 tabs

Investigation of the relationship between dermoscopic features and histopathological prognostic indicators in patients with cutaneous melanoma

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Özlem Özbağçıvan

2015-09-01

Full Text Available Background and Design: Dermoscopy has an important role in the diagnosis of melanoma nowadays. Dermoscopic findings of melanoma had been associated with Breslow thickness and invasion status in previous studies but the relationship between dermatoscopic findings and other histopathological prognostic indicators has not been investigated until today. In this study, our aim is to investigate the relationship between dermatoscopic findings and histopathologic prognostic indicators such as Breslow thickness, invasion status, mitotic rate, lymphovascular invasion (LVI, ulceration and regression in patients who had been diagnosed with melanoma due to their clinical, dermatoscopic and histopatological findings. Materials and Methods: Dermoscopic and histopathological findings of 47 cases of melanoma who applied to our clinic between the years 2000 and 2014 were evaluated. The relationship between the dermoscopic findings which had been reported to be observed in melanomas in previous research and the histopathologic prognostic indicators such as Breslow thickness, invasion status, mitotic rate, lymphovascular invasion, ulceration and regression were investigated. Results: Irregular dots/globules, atypical pigment network, multifocal hypopigmentation, radial streaks and moth-eaten borders have been associated with good prognostic indicators whereas comedo like openings, regular blotch, exophytic papillary structures, dotted, glomerular, lineer irregular vessels, pink/red and blue/gray colors were associated with poor prognostic indicators. Additionally some dermatoscopic findings which are more observed in benign lesions such as multiple milia-like cysts, comedo like openings, moth-eaten borders, regular blotch, exophytic papillary structures and finger print areas have been observed in melanomas in our study. Conclusion: Many dermoscopic findings have demonstrated statistically significant association with the histopathological prognostic indicators

Immunoscintigraphy of malignant melanomas

International Nuclear Information System (INIS)

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

1990-01-01

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

Role of PET in the initial staging of cutaneous malignant melanoma: systematic review.

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Krug, Bruno; Crott, Ralph; Lonneux, Max; Baurain, Jean-François; Pirson, Anne-Sophie; Vander Borght, Thierry

2008-12-01

To calculate summary estimates of the diagnostic performance of fluorine 18 fluorodeoxyglucose (FDG) positron emission tomographic (PET) imaging in the initial staging of cutaneous malignant melanoma (CMM), following the new American Joint Committee on Cancer (AJCC) staging classification on per-patient and per-lesion bases. MEDLINE, EMBASE, Web of Science, and Cochrane Database of Systematic Reviews databases, and reference lists of reviews and included papers were searched, without any language restrictions, for relevant articles published before March 2007. Two reviewers independently assessed study eligibility and methodologic quality by using the quality assessment of diagnostic accuracy studies checklist. A pooled random effect was estimated and a fixed coefficient regression model was used to explore the existing heterogeneity. Twenty-eight studies involving 2905 patients met the inclusion criteria. The pooled estimates of FDG PET for the detection of metastasis in the initial staging of CMM were sensitivity, 83% (95% confidence interval [CI]: 81%, 84%); specificity, 85% (95% CI: 83%, 87%); positive likelihood ratio (LR), 4.56 (95% CI: 3.12, 6.64); negative LR, 0.27 (95% CI: 0.18, 0.40); and diagnostic odds ratio, 19.8 (95% CI: 10.8, 36.4). Results from eight studies suggested that FDG PET was associated with 33% disease management changes (range, 15%-64%). There is good preliminary evidence that FDG PET is useful for the initial staging of patients with CMM, especially as adjunctive role in AJCC stages III and IV, to help detect deep soft-tissue, lymph node, and visceral metastases. FDG PET-computed tomographic imaging seemed to be more precise than PET alone, as suggested by four eligible studies. Further evaluation by using a well-designed prospective study, with clinical outcome-focused measures and cost effectiveness analysis, is needed to clarify the appropriate role of FDG PET in CMM staging. http://radiology.rsnajnls.org/cgi/content/full/249/3/836/DC

Evidence for the Role of Blue Light in the Development of Uveal Melanoma

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Patrick Logan

2015-01-01

Full Text Available Uveal melanoma is the most common malignancy of the adult eye. Although it is a relatively infrequent tumor, clinical prognosis is often poor owing to a high incidence of aggressive metastatic disease, for which there are limited treatment options. Little is known about the etiology of this condition, although several risk factors have been identified. Unlike cutaneous melanoma, however, ultraviolet radiation does not figure prominently among these risk factors. In this review, we focus on an associated form of visible electromagnetic radiation, high-energy short-wave (blue light, a causative agent in various forms of age-related retina damage, as a previously overlooked risk factor in uveal melanoma development and progression. Finally, we discuss the impact of these data on contemporary ocular therapy, particularly the debate surrounding the filtering capabilities of intraocular lenses used to replace dysfunctional crystalline lenses during cataract surgery.

MicroRNA miR-125b induces senescence in human melanoma cells.

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Glud, Martin; Manfé, Valentina; Biskup, Edyta; Holst, Line; Dirksen, Anne Marie Ahlburg; Hastrup, Nina; Nielsen, Finn C; Drzewiecki, Krzysztof T; Gniadecki, Robert

2011-06-01

MicroRNAs (miRNAs) are small noncoding RNA molecules involved in gene regulation. Aberrant expression of miRNA has been associated with the development or progression of several diseases, including cancer. In a previous study, we found that the expression of miRNA-125b (miR-125b) was two-fold lower in malignant melanoma producing lymph node micrometastases than in nonmetastasizing tumors. To get further insight into the functional role of miR-125b, we assessed whether its overexpression or silencing affects apoptosis, proliferation, or senescence in melanoma cell lines. We showed that overexpression of miR-125b induced typical senescent cell morphology, including increased cytoplasmatic/nucleus ratio and intensive cytoplasmatic β-galactosidase expression. In contrast, inhibition of miR-125b resulted in 30-35% decreased levels of spontaneous apoptosis. We propose that downregulation of miR-125b in an early cutaneous malignant melanoma can contribute to the increased metastatic capability of this tumor.

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.

MicroRNA-193b represses cell proliferation and regulates cyclin D1 in melanoma.

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Chen, Jiamin; Feilotter, Harriet E; Paré, Geneviève C; Zhang, Xiao; Pemberton, Joshua G W; Garady, Cherif; Lai, Dulcie; Yang, Xiaolong; Tron, Victor A

2010-05-01

Cutaneous melanoma is an aggressive form of human skin cancer characterized by high metastatic potential and poor prognosis. To better understand the role of microRNAs (miRNAs) in melanoma, the expression of 470 miRNAs was profiled in tissue samples from benign nevi and metastatic melanomas. We identified 31 miRNAs that were differentially expressed (13 up-regulated and 18 down-regulated) in metastatic melanomas relative to benign nevi. Notably, miR-193b was significantly down-regulated in the melanoma tissues examined. To understand the role of miR-193b in melanoma, functional studies were undertaken. Overexpression of miR-193b in melanoma cell lines repressed cell proliferation. Gene expression profiling identified 314 genes down-regulated by overexpression of miR-193b in Malme-3M cells. Eighteen of these down-regulated genes, including cyclin D1 (CCND1), were also identified as putative miR-193b targets by TargetScan. Overexpression of miR-193b in Malme-3M cells down-regulated CCND1 mRNA and protein by > or = 50%. A luciferase reporter assay confirmed that miR-193b directly regulates CCND1 by binding to the 3'untranslated region of CCND1 mRNA. These studies indicate that miR-193b represses cell proliferation and regulates CCND1 expression and suggest that dysregulation of miR-193b may play an important role in melanoma development.

Recurrence and survival after neck dissections in cutaneous head and neck melanoma

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Andersen, Peter Stemann; Chakera, Annette Hougaard; Thamsborg, Andreas Key Milan

2014-01-01

INTRODUCTION: An important prognostic factor in head and neck melanoma is the status of the regional lymph nodes since the presence of metastatic disease in the nodes greatly aggravates the prognosis. There is no consensus on the surgical treatment algorithm for this group. Our aim was to study i...

The features of leptin and its receptor expression in metastatic cutaneous melanoma

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A. A. Lushnikova

2015-01-01

Full Text Available Leptin is a multifunctional hormone with the activity of cytokines, which regulates critical signaling pathways that can induce cell proliferation, invasion, angiogenesis and tumor growth. Leptin plays an important role in the regulation of metabolism, energy exchange, functions of the neuro-endocrine system, including the pituitary, hypothalamus, adrenals, and immune system functions. Recently, some evidences have been appeared concerning the role of leptin in induction of chronic inflammatory processes, autoimmune pathologies, type 2 diabetes and cancer. An elevated blood level of the hormone is considered as a risk factor for different neoplasm developmentObjective. Analysis of the hormone leptin (Lep, the long and short isoforms of its receptor (LepR1 and LepR2 expression in blood, tumor cells and normal skin fibroblasts in the patients with metastatic cutaneous melanoma (CM with various clinico-pathological characteristics for prognostic assessment.Materials and methods. 15 patients with metastatic CM (10 women and 5 men, aged 22 to 67 years with body mass from normal to obese have been studied. The expression of Lep / LepR in the patient and donor blood sera, tumor and normal skin fibroblasts were determined using enzyme-linked immunosorbent assay (ELISA and RT PCR using total RNAs isolated from pairs of tumor samples and normal tissue.Results. Average level of leptin in the blood of CM patients and in tumor cells exceeds the normal one. Concentration of lepin in female CM patients was higher than in male patients. The expression level of Lep and LepR1 genes (but not LepR2 in tumor cells was relatively higher than in normal skin fibroblasts of these patients, and above the level of GAPDH gene expression. In the female patients with overweight (body mass index = 25,00–29,99 kg/m2 there was a trend to higher concentrations of leptin in the blood in comparison of the patients with normal body mass and leptin level in the sera of male CM

In vivo photoacoustic microscopy of human cutaneous microvasculature and a nevus.

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Favazza, Christopher P; Jassim, Omar; Cornelius, Lynn A; Wang, Lihong V

2011-01-01

In several human volunteers, photoacoustic microscopy (PAM) has been utilized for noninvasive cutaneous imaging of the skin microvasculature and a melanocytic nevus. Microvascular networks in both acral and nonacral skin were imaged, and multiple features within the skin have been identified, including the stratum corneum, epidermal-dermal junction, and subpapillary vascular plexus. Several vascular and structural differences between acral and nonacral skin were also observed in the photoacoustic images. In addition, a nevus was photoacoustically imaged, excised, and histologically analyzed. The photoacoustic images allowed for in vivo measurement of tumor thickness, depth, and microvasculature-values confirmed by histologic examination. The presented images demonstrate the potential of PAM to aid in the study and evaluation of cutaneous microcirculation and analysis of pigmented lesions. Through its ability to three-dimensionally image the structure and function of the microvasculature and pigmented lesions, PAM can have a clinical impact in diagnosis and assessment of systemic diseases that affect the microvasculature such as diabetes and cardiovascular disease, cutaneous malignancies such as melanoma, and potentially other skin disorders.

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

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Debora Faraone

2009-08-01

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

Melanoma brain metastases presenting as delirium: a case report

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Sofia Morais

Full Text Available Abstract Background Metastatic tumours sometimes present with neuropsychiatric symptoms, however psychiatric symptoms as rarely the first clinical manifestation. Cutaneous melanoma is the third most common cause of brain metastasis, with known risk factors increasing the chance of such central nervous system metastization. Objectives We present a clinical report of delirium as the first clinical manifestation of melanoma brain metastases, illustrating the relevance of an adequate and early differential diagnosis. Methods In addition to describing the clinical case, searches were undertaken in PubMed and other databases using keywords such as “brain metastasis”, “melanoma”, “agitation”, “psychiatric” and “delirium”. Results We here report the case of a 52-year-old female patient evaluated by Liaison Psychiatry after sudden onset of delirium while admitted at the Gastroenterology Department to study a hypothesis of pancreatitis. A head CT scan identified brain metastases, and after further examination, including brain biopsy, melanoma brain metastization was confirmed. Discussion Some of the diagnostic challenges of psychiatric symptoms associated with secondary brain tumours are discussed, underlining the importance of an adequate differential diagnosis when working in Psychiatry Liaison.

Expression of Estrogen Receptor Alpha in Malignant Melanoma

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Parvin Rajabi

2017-01-01

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

Prevalence of cutaneous viral infections in incident cutaneous squamous cell carcinoma detected among chronic lymphocytic leukemia and hematopoietic stem cell transplant patients.

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Hampras, Shalaka S; Locke, Frederick L; Chavez, Julio C; Patel, Nishit S; Giuliano, Anna R; Miller, Kyle; Gheit, Tarik; Tommasino, Massimo; Rollison, Dana E

2018-04-01

The role of cutaneous viral infections in the development of non-melanoma skin cancer (NMSC), including cutaneous squamous cell carcinoma (SCC), among chronic lymphocytic leukemia (CLL) and blood and marrow transplant (BMT) patients is not established. CLL (n = 977) and BMT (n = 3587) patients treated at the Moffitt Cancer Center were included in a retrospective cohort study. Human papillomavirus (HPV) and human polyomavirus (HPyV) DNA were examined in a subset of incident SCC tumors. Five-year cumulative incidence of NMSC was 1.42% in both BMT (n = 31 NMSCs) and CLL (n = 18 NMSCs) cohorts. Of the nine SCC tumors examined from each cohort, 22.2% and 33.3% were positive for viral DNA in the transplant (HPV 65, MCV) and CLL (HPV 38, HPV 15, HPyV6) cohort, respectively. Enhanced skin cancer screening of BMT/CLL patients should be conducted to better capture incident NMSCs and examine the role of viral infections in these tumors.

FHOD1 formin is upregulated in melanomas and modifies proliferation and tumor growth

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Peippo, Minna; Gardberg, Maria; Lamminen, Tarja; Kaipio, Katja; Carpén, Olli; Heuser, Vanina D.

2017-01-01

The functional properties of actin-regulating formin proteins are diverse and in many cases cell-type specific. FHOD1, a formin expressed predominantly in cells of mesenchymal lineage, bundles actin filaments and participates in maintenance of cell shape, migration and cellular protrusions. FHOD1 participates in cancer-associated epithelial to mesenchymal transition (EMT) in oral squamous cell carcinoma and breast cancer. The role of FHOD1 in melanomas has not been characterized. Here, we show that FHOD1 expression is typically strong in cutaneous melanomas and cultured melanoma cells while the expression is low or absent in benign nevi. By using shRNA to knockdown FHOD1 in melanoma cells, we discovered that FHOD1 depleted cells are larger, rounder and have smaller focal adhesions and inferior migratory capacity as compared to control cells. Importantly, we found FHOD1 depleted cells to have reduced colony-forming capacity and attenuated tumor growth in vivo, a finding best explained by the reduced proliferation rate caused by cell cycle arrest. Unexpectedly, FHOD1 depletion did not prevent invasive growth at the tumor margins. These results suggest that FHOD1 participates in key cellular processes that are dysregulated in malignancy, but may not be essential for melanoma cell invasion.

Effectiveness of carboplatin and paclitaxel as first- and second-line treatment in 61 patients with metastatic melanoma.

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Annette Pflugfelder

Full Text Available BACKGROUND: Patients with metastatic melanoma have a very unfavorable prognosis with few therapeutic options. Based on previous promising experiences within a clinical trial involving carboplatin and paclitaxel a series of advanced metastatic melanoma patients were treated with this combination. METHODS: Data of all patients with cutaneous metastatic melanoma treated with carboplatin and paclitaxel (CP at our institution between October 2005 and December 2007 were retrospectively evaluated. For all patients a once-every-3-weeks dose-intensified regimen was used. Overall and progression free survival were calculated using the method of Kaplan and Meier. Tumour response was evaluated according to RECIST criteria. RESULTS: 61 patients with cutaneous metastatic melanoma were treated with CP. 20 patients (85% M1c received CP as first-line treatment, 41 patients (90.2% M1c had received at least one prior systemic therapy for metastatic disease. Main toxicities were myelosuppression, fatigue and peripheral neuropathy. Partial responses were noted in 4.9% of patients, stable disease in 23% of patients. No complete response was observed. Median progression free survival was 10 weeks. Median overall survival was 31 weeks. Response, progression-free and overall survival were equivalent in first- and second-line patients. 60 patients of 61 died after a median follow up of 7 months. Median overall survival differed for patients with controlled disease (PR+SD (49 weeks compared to patients with progressive disease (18 weeks. CONCLUSIONS: Among patients with metastatic melanoma a subgroup achieved disease control under CP therapy which may be associated with a survival benefit. This potential advantage has to be weighed against considerable toxicity. Since response rates and survival were not improved in previously untreated patients compared to pretreated patients, CP should thus not be applied as first-line treatment.

Interferon alpha adjuvant therapy in patients with high-risk melanoma: a systematic review and meta-analysis.

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Mocellin, Simone; Pasquali, Sandro; Rossi, Carlo R; Nitti, Donato

2010-04-07

Based on previous meta-analyses of randomized controlled trials (RCTs), the use of interferon alpha (IFN-alpha) in the adjuvant setting improves disease-free survival (DFS) in patients with high-risk cutaneous melanoma. However, RCTs have yielded conflicting data on the effect of IFN-alpha on overall survival (OS). We conducted a systematic review and meta-analysis to examine the effect of IFN-alpha on DFS and OS in patients with high-risk cutaneous melanoma. The systematic review was performed by searching MEDLINE, EMBASE, Cancerlit, Cochrane, ISI Web of Science, and ASCO databases. The meta-analysis was performed using time-to-event data from which hazard ratios (HRs) and 95% confidence intervals (CIs) of DFS and OS were estimated. Subgroup and meta-regression analyses to investigate the effect of dose and treatment duration were also performed. Statistical tests were two-sided. The meta-analysis included 14 RCTs, published between 1990 and 2008, and involved 8122 patients, of which 4362 patients were allocated to the IFN-alpha arm. IFN-alpha alone was compared with observation in 12 of the 14 trials, and 17 comparisons (IFN-alpha vs comparator) were generated in total. IFN-alpha treatment was associated with a statistically significant improvement in DFS in 10 of the 17 comparisons (HR for disease recurrence = 0.82, 95% CI = 0.77 to 0.87; P < .001) and improved OS in four of the 14 comparisons (HR for death = 0.89, 95% CI = 0.83 to 0.96; P = .002). No between-study heterogeneity in either DFS or OS was observed. No optimal IFN-alpha dose and/or treatment duration or a subset of patients more responsive to adjuvant therapy was identified using subgroup analysis and meta-regression. In patients with high-risk cutaneous melanoma, IFN-alpha adjuvant treatment showed statistically significant improvement in both DFS and OS.

Accuracy of routine cytology and immunocytochemistry in preoperative diagnosis of oral amelanotic melanomas in dogs.

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Przeździecki, Rafał; Czopowicz, Michał; Sapierzyński, Rafał

2015-12-01

Amelanotic melanomas are one of the most common oral malignancies. The cytologic and histopathologic differentiation between amelanotic melanoma, sarcoma, and poorly differentiated carcinoma is often difficult or even impossible. The aim of this study was to assess the reliability of routine cytology and immunocytochemistry in preoperative diagnosis of canine oral amelanotic melanoma. Cytologic preparations from undifferentiated canine oral tumors were stained with Giemsa and by immunocytochemistry (ICC) using anti-cytokeratin, anti-vimentin, and anti-Melan A antibodies. The final cytologic diagnosis (including ICC) was compared to the final diagnosis based on histopathology and immunohistochemistry (IHC) results, and sensitivity and specificity of cytologic examination were determined. Final cytologic diagnoses of 38 cases agreed well with the histopathologic/immunohistochemical diagnoses, thus both specificity and sensitivity of combined routine cytology and ICC were 100% (95% confidence interval 90.8-100%). Of 32 oral tumors, diagnosis of amelanotic melanoma, sarcoma, and carcinoma was made using routine cytology and ICC. In 4 of 6 aspirates taken from lymph nodes, a preliminary diagnosis of metastatic amelanotic melanoma corresponded with the final diagnosis. Both sensitivity and specificity of routine cytology in diagnosis of amelanotic melanomas were considered moderate (66.7% and 85.7%, respectively). In conclusion, routine cytology is a reliable diagnostic method for canine oral amelanotic melanoma and metastatic amelanotic melanoma, and ICC, using anti-cytokeratin, anti-vimentin, and anti-Melan A antibodies, is an excellent supporting method for presurgical diagnosis of poorly differentiated oral malignancies in dogs. © 2015 American Society for Veterinary Clinical Pathology.

Diagnostic value of HMB-45 and anti-Melan A staining of sentinel lymph nodes with isolated positive cells.

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Mahmood, Muhammad N; Lee, Min W; Linden, Michael D; Nathanson, S D; Hornyak, Thomas J; Zarbo, Richard J

2002-12-01

Numerous immunohistochemical stains have been employed to detect metastatic melanoma in sentinel lymph node (SLN) biopsies. HMB-45 is considered by some as a specific tool to detect early metastatic melanoma (1). Occasionally, one or two isolated HMB-45-positive cells may cause complications in diagnostic interpretation. The goal of this study was to evaluate the reliability of HMB-45 staining of SLNs with sparse isolated positive cells and to compare its staining with anti-Melan A antibody. HMB-45 and anti-Melan A antibody immunostaining was performed on (Group A) 15 histologically negative SLNs excised from patients with malignant melanoma (MM) and on (Group B) 15 histologically negative SLNs excised from patients with breast carcinoma (BC). None of the patients had clinical evidence of systemic metastasis at the time of SLN biopsy. Five cutaneous biopsies with changes of postinflammatory hyperpigmentation (PIHP) were also stained with both antibodies. HMB-45 staining was repeated in all Group B SLNs after blocking endogenous biotins. Electron-microscopic studies were performed on all cases of PIHP. Isolated HMB-45-stained cells were present in 6 of 15 SLNs removed for MM; 8 of 15 for BC; and 3 of 5 cutaneous biopsies of PIHP. HMB-45 reactivity persisted after blocking endogenous biotins in 6 of 8 positive SLNs from Group B. Anti-Melan A antibody was negative in all SLNs of group A and B and in dermal melanophages of all five cases of PIHP. HMB-45 positivity was demonstrated in histologically negative SLNs and cutaneous biopsies, especially in the milieu of aggregated melanophages. Phagocytosis of premelanosomes by macrophages in the draining lymph nodes may account for isolated cell positivity and can hinder correct diagnostic interpretation. HMB-45 may not be a reliable marker for the detection of micro-metastasis of MM and requires correlation with other immunohistochemical markers, such as anti-Melan A antibody, to enhance specificity.

HLA class Ia and Ib molecules and FOXP3+ TILs in relation to the prognosis of malignant melanoma patients

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Melsted, Wenna Nascimento; Johansen, Lasse Lindholm; Lock-Andersen, Jørgen

2017-01-01

HLA class Ia (HLA-ABC) and HLA class Ib (HLA-E, -F and -G) molecules and FOXP3+ tumor-infiltrating lymphocytes (TILs) are often reported as relevant factors of tumor immune regulation. We investigated their expression as prognostic factors in 200 patients with primary cutaneous melanoma (PCM...

Rituximab in the treatment of primary cutaneous B-cell lymphoma: a review.

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Fernández-Guarino, M; Ortiz-Romero, P L; Fernández-Misa, R; Montalbán, C

2014-06-01

Rituximab is a chimeric mouse-human antibody that targets the CD20 antigen, which is found in both normal and neoplastic B cells. In recent years, it has been increasingly used to treat cutaneous B-cell lymphoma and is now considered an alternative to classic treatment (radiotherapy and surgery) of 2 types of indolent lymphoma, namely, primary cutaneous follicle center lymphoma and primary cutaneous marginal zone B-cell lymphoma. Rituximab is also administered as an alternative to polychemotherapy in the treatment of primary cutaneous large B-cell lymphoma, leg type. Its use as an alternative drug led to it being administered intralesionally, with beneficial effects. In the present article, we review the literature published on the use of rituximab to treat primary cutaneous B-cell lymphoma. Copyright © 2012 Elsevier España, S.L. and AEDV. All rights reserved.

Development of a stable radioiodinating reagent to label monoclonal antibodies for radiotherapy of cancer

International Nuclear Information System (INIS)

Wilbur, D.S.; Hadley, S.W.; Hylarides, M.D.; Abrams, P.G.; Beaumier, P.A.; Morgan, A.C.; Reno, J.M.; Fritzberg, A.R.

1989-01-01

A method of radioiodinating monoclonal antibodies such that the labeled antibodies do not undergo in vivo deiodination has been studied. The method utilizes conjugation of succinimidyl para-iodobenzoate to the antibody. The iodobenzoate was radiolabeled by using an organometallic intermediate to facilitate the reaction. Thus, succinimidyl para-tri-n-butylstannylbenzoate was radiolabeled in 60-90% radiochemical yield and subsequently conjugated to the antibody in 80-90% yield. Animal biodistribution studies were carried out with two separate anti-melanoma antibodies (9.2.27 and NR-M1-05) labeled by this method, and examined in nude mice bearing human melanoma tumor xenografts. Very large differences in the localization of radioactivity were observed in the thyroids and stomachs of mice when the iodobenzoyl-labeled antibodies were compared with the same antibodies labeled using the chloramine-T method of radioiodination. Few other significant differences in the tissue distribution of the radioiodinated antibodies were seen

Radiolabeled antibodies in cancer. Oncology Overview

International Nuclear Information System (INIS)

1984-11-01

Oncology Overviews are a service of the International Cancer Research Data Bank (ICRDB) Program of the National Cancer Institute, intended to facilitate and promote the exchange of information between cancer scientists by keeping them aware of literature related to their research being published by other laboratories through the world. Each Oncology Overview represents a survey of the literature associated with a selected area of cancer research. It contains abstracts of articles which have been selected and organized by researchers associated with the field. Contents: Radiolabeled antibodies--labeling and imaging techniques; Radiolabeled antibodies--carcinoembryonic antigen; Radiolabeled antibodies--alpha-fetoprotein; Radiolabeled antibodies--human chorionic gonadotropin; Radiolabeled antibodies--ferritin; Radiolabeled antibodies--imaging of colorectal tumors; Radiolabeled antibodies--imaging of malignant melanoma; Radiolabeled antibodies--imaging of urogenital tumors; Radiolabeled antibodies--imaging of thyroid tumors; Radiolabeled antibodies--other clinical studies; Radiolabeled antibodies--selected preclinical studies; Radiolabeled antibodies--reviews

Contribution of whole body F-18-FDG-PET and lymphoscintigraphy to the assessment of regional and distant metastases in cutaneous malignant melanoma. A pilot study

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Klein, M.; Freedman, N.; Marciano, R.; Moshe, S.; Chisin, R. [Hadassah Univ. Hospital, Jerusalem (Israel). Dept. of Medical Biophysics and Nuclear Medicine; Lotem, M. [Hadassah Univ. Hospital, Jerusalem (Israel). Dept. of Oncology; Gimon, Z. [Hadassah Univ. Hospital, Jerusalem (Israel). Dept. of Surgery

2000-05-01

Aim: This pilot study describes use of whole body PET (WB PET) for staging of melanoma. WB PET in conjunction with lymphoscintigraphy (LS) for evaluating status of the sentinel lymph node (SLN) in primary melanoma was investigated with comparison to histopathological results. WB PET was also used both for primary and metastatic melanoma for screening for distant metastases, restaging and follow-up. Methods: Group I: 17 patients with primary cutaneous melanoma underwent LS, WB PET and SLN dissection. WB PET findings were compared with biopsy results at the SLN site and were used for screening for distant metastases. Group II: 17 patients with a history of melanoma underwent WB PET for follow-up and/or restaging. Results were confirmed or refuted by other radiological modalities or by biopsy of clinical follow-up. Results: Group I: Out of 20 SLNs identified by LS in the 17 patients, 18 were negative on WB PET and 2 were positive. 19/20 WB PET findings were confirmed either by histopathology or by clinical follow-up (20 mo). Accuracy was 94% for the assessment of the status of the SLN. Group II: WB PET findings altered staging and treatment in 12/17 patients and confirmed the validity of treatment in 3/17 patients. Overall, in 15/17 patients (88%), WB PET had an impact on treatment strategy. (orig.) [German] Ziel: Diese Pilot-Studie beschreibt die Anwendung der Ganzkoerper-PET (WB PET) zum Staging beim Melanom. Bei primaerem Melanom wurde WB PET in Verbindung mit der Lymphszintigraphie (LS) angewandt und mit der Histopathologie verglichen, um den Status des Sentinel Lymph Node (SLN) zu untersuchen. Zusaetzlich wurde WB PET fuer primaere und metastatische Melanome zum Screening auf Fernmetastasen, zum Restaging und zum Follow-up benutzt. Methoden: Gruppe I: 17 Patienten mit primaerem kutanem Melanom erhielten LS, WB PET und eine operative SLN-Entfernung. Die WB PET-Ergebnisse wurden mit den SLN-Biopsien verglichen und zum Screening fuer Fernmetastasen benutzt. Gruppe

Detection of Melanoma Metastases in Resected Human Lymph Nodes by Noninvasive Multispectral Photoacoustic Imaging

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Gerrit Cornelis Langhout

2014-01-01

Full Text Available Objective. Sentinel node biopsy in patients with cutaneous melanoma improves staging, provides prognostic information, and leads to an increased survival in node-positive patients. However, frozen section analysis of the sentinel node is not reliable and definitive histopathology evaluation requires days, preventing intraoperative decision-making and immediate therapy. Photoacoustic imaging can evaluate intact lymph nodes, but specificity can be hampered by other absorbers such as hemoglobin. Near infrared multispectral photoacoustic imaging is a new approach that has the potential to selectively detect melanin. The purpose of the present study is to examine the potential of multispectral photoacoustic imaging to identify melanoma metastasis in human lymph nodes. Methods. Three metastatic and nine benign lymph nodes from eight melanoma patients were scanned ex vivo using a Vevo LAZR© multispectral photoacoustic imager and were spectrally analyzed per pixel. The results were compared to histopathology as gold standard. Results. The nodal volume could be scanned within 20 minutes. An unmixing procedure was proposed to identify melanoma metastases with multispectral photoacoustic imaging. Ultrasound overlay enabled anatomical correlation. The penetration depth of the photoacoustic signal was up to 2 cm. Conclusion. Multispectral three-dimensional photoacoustic imaging allowed for selective identification of melanoma metastases in human lymph nodes.

Brain Metastasis as Initial Manifestation of Melanoma (A Case Report

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Vitorino Modesto Santos

2016-06-01

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

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

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

2005-03-01

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

New diagnostic techniques in staging in the surgical treatment of cutaneous malignant melanoma

NARCIS (Netherlands)

Cobben, DCP; Koopal, S; Tiebosch, ATMG; Jager, PL; Elsinga, PH; Wobbes, T; Hoekstra, HJ

2002-01-01

The emphasis of the research on the surgical treatment of melanoma has been on the resection margins, the role of elective lymph node dissection. in high risk patients and the value of adjuvant regional treatment with hyperthermic isolated lymph perfusion with melphalan. Parallel to this research,

Cutaneous Clear Cell Sarcoma: a clinicopathologic, immunohistochemical and molecular analysis of 12 cases emphasizing its distinction from dermal melanoma

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Hantschke, Markus; Mentzel, Thomas; Rütten, Arno; Palmedo, Gabriele; Calonje, Eduardo; Lazar, Alexander J.; Kutzner, Heinz

2010-01-01

Clear cell sarcoma (CCS) of tendons and aponeuroses / malignant melanoma of soft parts is a rare tumor and in the majority of cases presents a characteristic reciprocal translocation t(12;22)(q13;q12) that results in fusion of the EWS and ATF1 genes. Although the melanocytic differentiation of CCS is indisputable, its precise lineage remains unclear. Typically, the slowly growing tumor affects the extremities of adolescents or young adults, especially around the ankle and foot. CCS is classically regarded as a deep soft tissue tumor associated with tendons or aponeuroses. This traditional view is put into perspective by the description of primary CCS of the gastrointestinal tract, which may have a variant fusion gene EWSR1-CREB1. We describe 12 cases of cutaneous CCS and discuss the differential diagnoses. These 12 cases share an identical immunohistochemical profile with malignant melanoma (MM) and thus can easily be confused with a dermal variant of spindle cell MM or metastasis of MM. The patients' ages ranged from 6 to 74 years (median: 25 y), and there was a female predominance (10 females, 2 males). Most tumors (n = 9) were located on the extremities, 2 tumors arose on the back, and 1 on the abdomen. The mean tumor size was 0,97 cm (range, 0,4 to 1,7 cm). Six cases showed invasion of the subcutis, the other 6 cases were entirely dermal. Tumor necrosis was evident in 2 cases, melanin pigment in 2 cases, and ulceration in 1 tumor. All cases showed uniform nests and fascicles of pale spindled or slightly epitheloid cells with finely granular eosinophilic or clear cytoplasm. There was fair pleomorphism with plump spindled nuclei and significantly prominent nucleoli. Multinucleated wreath-like tumor giant cells were observed in two-thirds of cases, but were usually present only focally. The dense cellular aggregates were encased by delicate fibrous septa. The stroma showed a sclerotic reticulated pattern. Partly, the nests of spindle cells bordered the epidermis

Use of antibodies against the variable regions of the T-cell receptor alpha/beta heterodimer for the study of cutaneous T-cell lymphomas.

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Ralfkiaer, E; Wollf-Sneedorff, A; Vejlsgaard, G L

1991-11-01

Recent studies have suggested that antibodies against the variable (V) regions of the T-cell antigen receptor (TCR) may be used as markers for clonality and malignancy in T-cell infiltrates. We have investigated this by examining biopsy samples from 45 patients with cutaneous T-cell lymphomas (CTCL) for reactivity with seven antibodies against different V-gene families on the TCR alpha/beta heterodimer, i.e. ICI (V beta 5a), W112 (V beta 5b), OT145 (V beta 6a), 16G8 (V beta 8a), S511 (V beta 12a), F1 (V alpha 2a) and LC4 (alpha beta Va). Serial biopsies were available in 13 patients and a total of 62 samples were studied. The neoplastic cells in five cases were positive for either V beta 5 (one case), V beta 6 (one case), V beta 8 (two cases) or V beta 12 (one case). In the remaining 40 cases, no staining was seen of the neoplastic cells. These findings indicate that while antibodies against the TCR V-regions may be used as clonotypic markers for certain T-cell neoplasms, there is as yet not a sufficient number of anti-TCR V-region antibodies available for the routine diagnosis of these conditions.

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

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Agarwal, Poojan; Kaushal, Manju

2017-03-01

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

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

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

2009-01-01

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

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

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

2018-01-01

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

Coffee, tea and melanoma risk: findings from the European Prospective Investigation into Cancer and Nutrition.

Science.gov (United States)

Caini, Saverio; Masala, Giovanna; Saieva, Calogero; Kvaskoff, Marina; Savoye, Isabelle; Sacerdote, Carlotta; Hemmingsson, Oskar; Hammer Bech, Bodil; Overvad, Kim; Tjønneland, Anne; Petersen, Kristina E N; Mancini, Francesca Romana; Boutron-Ruault, Marie-Christine; Cervenka, Iris; Kaaks, Rudolf; Kühn, Tilman; Boeing, Heiner; Floegel, Anna; Trichopoulou, Antonia; Valanou, Elisavet; Kritikou, Maria; Tagliabue, Giovanna; Panico, Salvatore; Tumino, Rosario; Bueno-de-Mesquita, H B As; Peeters, Petra H; Veierød, Marit B; Ghiasvand, Reza; Lukic, Marko; Quirós, José Ramón; Chirlaque, Maria-Dolores; Ardanaz, Eva; Salamanca Fernández, Elena; Larrañaga, Nerea; Zamora-Ros, Raul; Maria Nilsson, Lena; Ljuslinder, Ingrid; Jirström, Karin; Sonestedt, Emily; Key, Timothy J; Wareham, Nick; Khaw, Kay-Tee; Gunter, Marc; Huybrechts, Inge; Murphy, Neil; Tsilidis, Konstantinos K; Weiderpass, Elisabete; Palli, Domenico

2017-05-15

In vitro and animal studies suggest that bioactive constituents of coffee and tea may have anticarcinogenic effects against cutaneous melanoma; however, epidemiological evidence is limited to date. We examined the relationships between coffee (total, caffeinated or decaffeinated) and tea consumption and risk of melanoma in the European Prospective Investigation into Cancer and Nutrition (EPIC). EPIC is a multicentre prospective study that enrolled over 500,000 participants aged 25-70 years from ten European countries in 1992-2000. Information on coffee and tea drinking was collected at baseline using validated country-specific dietary questionnaires. We used adjusted Cox proportional hazards regression models to calculate hazard ratios (HR) and 95% confidence intervals (95% CI) for the associations between coffee and tea consumption and melanoma risk. Overall, 2,712 melanoma cases were identified during a median follow-up of 14.9 years among 476,160 study participants. Consumption of caffeinated coffee was inversely associated with melanoma risk among men (HR for highest quartile of consumption vs. non-consumers 0.31, 95% CI 0.14-0.69) but not among women (HR 0.96, 95% CI 0.62-1.47). There were no statistically significant associations between consumption of decaffeinated coffee or tea and the risk of melanoma among both men and women. The consumption of caffeinated coffee was inversely associated with melanoma risk among men in this large cohort study. Further investigations are warranted to confirm our findings and clarify the possible role of caffeine and other coffee compounds in reducing the risk of melanoma. © 2017 UICC.

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.

Radiation port cutaneous metastases: Reports of two patients whose recurrent visceral cancers presented as skin lesions at the site of previous radiation and literature review

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Brian Spencer Hoyt

2014-01-01

Full Text Available Radiation therapy is associated with a variety of complications, including the development of primary skin cancers in the radiated region. However, it is rare for patients with visceral cancers who are treated with radiation therapy to subsequently develop cutaneous metastasis within the radiation port. We describe two patients with internal malignancies who developed cutaneous metastases within their radiation ports following radiotherapy. In addition, we used PubMed to perform an extensive literature review and identify additional reports of cutaneous metastasis within a radiation port. We excluded patients who developed melanoma or primary skin cancers in the radiation port. We also excluded patients with non-solid organ malignancies. Herein, we summarize the characteristics of 23 additional patients who experienced radiation port cutaneous metastases and explore possible mechanisms for the occurrence of radiation port cutaneous metastases.

Effects of BRAF mutations and BRAF inhibition on immune responses to melanoma

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Ilieva, Kristina M.; Correa, Isabel; Josephs, Debra H.; Karagiannis, Panagiotis; Egbuniwe, Isioma U.; Cafferkey, Michiala J.; Spicer, James F.; Harries, Mark; Nestle, Frank O.; Lacy, Katie E.; Karagiannis, Sophia N.

2014-01-01

Malignant melanoma is associated with poor clinical prognosis; however, novel molecular and immune therapies are now improving patient outcomes. Almost 50% of melanomas harbor targetable activating mutations of BRAF which promote RAS-RAF-MEK-ERK pathway activation and melanoma proliferation. Recent evidence also indicates that melanomas bearing mutant BRAF may also have altered immune responses, suggesting additional avenues for treatment of this patient group. The small molecule inhibitors selective for mutant BRAF induce significant but short-lived clinical responses in a proportion of patients, but also lead to immune stimulatory bystander events, which then subside with the emergence of resistance to inhibition. Simultaneous BRAF and MEK inhibition, and especially combination of BRAF inhibitors with new immunotherapies such as checkpoint blockade antibodies, may further enhance immune activation, or counteract immunosuppressive signals. Pre-clinical evaluation and ongoing clinical trials should provide novel insights into the role of immunity in the therapy of BRAF-mutant melanoma. PMID:25385327

Vitamin D receptor polymorphisms and the risk of cutaneous melanoma: a systematic review and meta-analysis.

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Mocellin, Simone; Nitti, Donato

2008-11-01

It has been hypothesized that polymorphisms in the vitamin D receptor (VDR) gene affect the risk of developing melanoma. However, results often are conflicting, and no meta-analysis has been performed to date on published data. Six studies (cases, 2152; controls, 2410) that investigated the association between 5 VDR polymorphisms (TaqI, FokI, BsmI, EcoRV, and Cdx2) and the risk of melanoma were retrieved and analyzed. The model-free approach was applied to meta-analyze these molecular association studies. Available data suggested a significant association between the BsmI VDR polymorphism and melanoma risk (pooled odds ratio [OR], 1.30; 95% confidence interval [CI], 1.11-1.53; P= .002; heterogeneity Cochran Q test, P> .1), and the population-attributable risk was 9.2%. In contrast, the FokI polymorphism did not appear to be associated with such risk (OR, 1.09; 95% CI, 0.99-1.21; P= .07; heterogeneity Cochran Q test, P> .1). For the TaqI and the EcoRV polymorphisms, significant between-study heterogeneity did not support genotype data pooling. Only 1 study investigated the Cdx2 variant, and the findings were negative. Current evidence is in favor of an association between 1 VDR gene polymorphism (BsmI) and the risk of developing melanoma. The current findings prompt further investigation on this subject and indirectly support the hypothesis that sun exposure may have an antimelanoma effect through activation of the vitamin D system.

Melanoma immunotherapy: historical precedents, recent successes and future prospects.

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Raaijmakers, Marieke I G; Rozati, Sima; Goldinger, Simone M; Widmer, Daniel S; Dummer, Reinhard; Levesque, Mitchell P

2013-02-01

The idea of cancer immunotherapy has been around for more than a century; however, the first immunotherapeutic ipilimumab, an anti-CTLA-4 antibody, has only recently been approved by the US FDA for melanoma. With an increasing understanding of the immune response, it is expected that more therapies will follow. This review aims to provide a general overview of immunotherapy in melanoma. We first explain the development of cancer immunotherapy more than a century ago and the general opinions about it over time. This is followed by a general overview of the immune reaction in order to give insight into the possible targets for therapy. Finally, we will discuss the current therapies for melanoma, their shortcomings and why it is important to develop patient stratification criteria. We conclude with an overview of recent discoveries and possible future therapies.

Melanoma Cells Can Adopt the Phenotype of Stromal Fibroblasts and Macrophages by Spontaneous Cell Fusion in Vitro.

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Kemény, Lajos V; Kurgyis, Zsuzsanna; Buknicz, Tünde; Groma, Gergely; Jakab, Ádám; Zänker, Kurt; Dittmar, Thomas; Kemény, Lajos; Németh, István B

2016-06-02

After the removal of primary cutaneous melanoma some patients develop local recurrences, even after having histologically tumor-free re-excision. A potential explanation behind this phenomenon is that tumor cells switch their phenotype, making their recognition via standard histopathological assessments extremely difficult. Tumor-stromal cell fusion has been proposed as a potential mechanism for tumor cells to acquire mesenchymal traits; therefore, we hypothesized that melanoma cells could acquire fibroblast- and macrophage-like phenotypes via cell fusion. We show that melanoma cells spontaneously fuse with human dermal fibroblasts and human peripheral blood monocytes in vitro. The hybrid cells' nuclei contain chromosomes from both parental cells and are indistinguishable from the parental fibroblasts or macrophages based on their morphology and immunophenotype, as they could lose the melanoma specific MART1 marker, but express the fibroblast marker smooth muscle actin or the macrophage marker CD68. Our results suggest that, by spontaneous cell fusion in vitro, tumor cells can adopt the morphology and immunophenotype of stromal cells while still carrying oncogenic, tumor-derived genetic information. Therefore, melanoma-stromal cell fusion might play a role in missing tumor cells by routine histopathological assessments.

In Vivo Targeting of Cutaneous Melanoma Using an Melanoma Stimulating Hormone-Engineered Human Protein Cage with Fluorophore and Magnetic Resonance Imaging Tracers

Czech Academy of Sciences Publication Activity Database

Vannucci, Luca; Falvo, E.; Failla, C. M.; Carbo, M.; Fornara, M.; Canese, R.; Cecchetti, S.; Rajsiglová, Lenka; Stakheev, Dmitry; Křižan, Jiří; Boffi, A.; Carpinelli, G.; Morea, V.; Ceci, P.

2015-01-01

Roč. 11, č. 1 (2015), s. 81-92 ISSN 1550-7033 Institutional support: RVO:61388971 Keywords : Protein-Based Nanoparticles * Ferritin * In Vivo Melanoma-Targeting Subject RIV: EC - Immunology Impact factor: 3.929, year: 2015

Extensive necrosis of visceral melanoma metastases after immunotherapy

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Poston Graeme J

2008-03-01

Full Text Available Abstract Background The prognosis for metastatic melanoma remains poor even with traditional decarbazine or interferon therapy. 5-year survival is markedly higher amongst patients undergoing metastatectomy. Unfortunately not all are suitable for metastatectomy. Alternative agents for systemic therapy have, to date, offered no greater rates of survival beyond traditional therapy. A toll-like receptor 9 agonist, PF-3512676 (formerly known as CPG 7909 is currently being evaluated for its potential. Case presentation We present the case of a 54-year-old Caucasian male with completely resected metastatic cutaneous melanoma after immunotherapy. The patient initially progressed during adjuvant high-dose interferon, with metastases to the liver, spleen, and pelvic lymph nodes. During an 18-month treatment period with PF-3512676 (formerly known as CPG 7909, a synthetic cytosine-phosphorothioate-guanine rich oligodeoxynucleotide, slow radiologic disease progression was demonstrated at the original disease sites. Subsequent excision of splenic and pelvic nodal metastases was performed, followed by resection of the liver metastases. Histologic examination of both hepatic and splenic melanoma metastases showed extensive necrosis. Subsequent disease-free status was demonstrated by serial positron emission tomography (PET. Conclusion Existing evidence from phase I/II trials suggests systemic treatment with PF-3512676 is capable of provoking a strong tumor-specific immune response and may account for the prolonged tumor control in this instance.

Clinical Remission of Cutaneous Squamous Cell Carcinoma of the Auricle with Cetuximab and Nivolumab

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Alessandra Chen

2018-01-01

Full Text Available Cutaneous squamous cell carcinomas (SCC affecting the regions of the head and neck can be challenging to resect surgically and refractory to chemotherapy or radiation therapy. Consequently; the treatment of squamous cell carcinomas of the skin is a focus of current research. One such advancement is immunotherapy. Herein we describe clinical remission of invasive, poorly differentiated squamous cell carcinoma of the pre-auricular region with external auditory canal involvement using cetuximab, an epidermal growth factor receptor (EGFR antibody; and nivolumab, a programmed death receptor-1 (PD-1 antibody. Such durable and comprehensive disease resolution demonstrates the therapeutic potential of cetuximab and nivolumab in surgically challenging, treatment-resistant cutaneous squamous cell carcinoma.

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

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

2014-12-01

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

Risk of invasive melanoma in patients with rheumatoid arthritis treated with biologics

DEFF Research Database (Denmark)

Mercer, Louise K; Askling, Johan; Raaschou, Pauline

2017-01-01

-specific general population of each register as reference, age, sex and calendar year standardised incidence ratios (SIRs) of invasive histology-confirmed cutaneous melanoma were calculated within each register. Pooled SIR and incidence rate ratios (IRRs) comparing biologic cohorts to biologic-naïve were...... calculated across countries by taking the size of the register into account. RESULTS: Overall 130 315 RA patients with a mean age of 58 years contributing 579 983 person-years were available for the analysis and 287 developed a first melanoma. Pooled SIRs for biologic-naïve, TNFi and rituximab...... with TNF inhibitors (TNFi), other biologic disease modifying drugs and non-biologic therapy. METHODS: Eleven biologic registers from nine European countries participated in this collaborative project. According to predefined exposure definitions, cohorts of patients with RA were selected. Using the country...

Development of a practical guide for the early recognition for malignant melanoma of the foot and nail unit

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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.

Placental restriction of fetal growth reduces cutaneous responses to antigen after sensitization in sheep.

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Wooldridge, Amy L; Bischof, Robert J; Meeusen, Els N; Liu, Hong; Heinemann, Gary K; Hunter, Damien S; Giles, Lynne C; Kind, Karen L; Owens, Julie A; Clifton, Vicki L; Gatford, Kathryn L

2014-04-01

Prenatal and early childhood exposures are implicated as causes of allergy, but the effects of intrauterine growth restriction on immune function and allergy are poorly defined. We therefore evaluated effects of experimental restriction of fetal growth on immune function and allergic sensitization in adolescent sheep. Immune function (circulating total red and white blood cells, neutrophils, lymphocytes, monocytes, eosinophils, and basophils, and the antibody response to Clostridial vaccination) and responses to house dust mite (HDM) allergen and ovalbumin (OVA) antigen sensitization (specific total Ig, IgG1, and IgE antibodies, and cutaneous hypersensitivity) were investigated in adolescent sheep from placentally restricted (PR, n = 23) and control (n = 40) pregnancies. Increases in circulating HDM-specific IgE (P = 0.007) and OVA-specific IgE (P = 0.038) were greater in PR than control progeny. PR did not alter total Ig, IgG1, or IgM responses to either antigen. PR increased OVA-specific but not HDM-specific IgA responses in females only (P = 0.023). Multiple birth increased Ig responses to OVA in a sex-specific manner. PR decreased the proportion of positive cutaneous hypersensitivity responders to OVA at 24 h (P = 0.030) but had no effect on cutaneous responses to HDM. Acute wheal responses to intradermal histamine correlated positively with birth weight in singletons (P = 0.023). Intrauterine growth restriction may suppress inflammatory responses in skin downstream of IgE induction, without impairment in antibody responses to a nonpolysaccharide vaccine. Discord between cutaneous and IgE responses following sensitization suggests new mechanisms for prenatal allergy programming.

Treatment recommendations in patients diagnosed with high-risk cutaneous squamous cell carcinoma

International Nuclear Information System (INIS)

Veness, M.J.

2005-01-01

Non-melanoma cutaneous cancers occur at an epidemic rate in Australia. With an ageing population, more Australians will develop these cancers and at an increasing rate. In the majority of cases local treatment is highly curative. However, a subset of the population will be diagnosed with a high-risk cutaneous squamous cell carcinoma. These can be defined as patients at risk of having subclinical metastases to regional lymph nodes based on unfavourable primary lesion features (including inadequately excised and recurrent lesions), patients with metastatic squamous cell carcinoma to regional lymph nodes, and squamous cell carcinoma in immunosuppressed patients. The mortality and morbidity associated with high-risk cutaneous squamous cell carcinoma is usually as a consequence of uncontrolled metastatic nodal disease and, to a lesser extent, distant metastases. Radiotherapy has an essential role in treating these patients and in many cases the addition of adjuvant radiotherapy may be life saving. It is therefore important that all clinicians treating skin cancers have an understanding and awareness of the optimal approach to these patients. The aim of this article is to present treatment recommendations based on an overview of the current published literature. Copyright (2005) Blackwell Science Pty Ltd

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

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

2015-01-01

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

Superficial Spreading Melanoma „Slumbered“ Behind the Shadow of Onychomycosis

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Trayanova E.

2015-05-01

Full Text Available Malignant melanoma is the most aggressive form of cutaneous cancer. Due to the continuously increasing rate of newly detected cases each year and because of its particular low survival rate, the scientific interest in this type of neoplasia is constantly growing. Sun exposure is identified as the major etiologic factor for malignant transformation of the melanocytes. According to the WHO, malignant melanoma is divided into four main groups, as the superficial spreading form is defined as the most “gentle” among them. The name of this subspecies does not have to “drowse” the attention of dermatologists considering the possible metastasic risk, even at a later stage. Due to lack of subjective complaints, patients do not seek active consultation on this occasion, as this type of lesions often remain missed within the clinical examination. Early diagnosis, however, as well as early surgical removal is the key to increasing the survival rate of the patients. We present a case of a 88 year-old female patient consulted with dermatologist on occasion of severe onychomycosis, as a pigment lesion on the anterior surface of the right leg. Clinically and dermatoscopically suspected superficial spreading melanoma was detected within the examination.

Population exposure to ultraviolet radiation in Finland 1920-1995: Exposure trends and a time-series analysis of exposure and cutaneous melanoma incidence

International Nuclear Information System (INIS)

Kojo, Katja; Jansen, Christer T.; Nybom, Pia; Huurto, Laura; Laihia, Jarmo; Ilus, Taina; Auvinen, Anssi

2006-01-01

Ultraviolet radiation (UVR) is the principal cause of cutaneous malignant melanoma (CMM). However, the relation between CMM and UVR exposure is not clear. We present the trends of population exposure to UVR and conduct a time-series analysis of the relation between UVR exposure and incidence of CMM. Data on CMM incidence were obtained from the Finnish Cancer Registry. Clothing coverage of the body was scored from archival photographs and the proportion of uncovered skin was used as a measure of solar exposure. Information on the number of sunny resort holidays, duration of annual holidays, and sunscreen sales were obtained from various sources. Exposed skin area doubled from 1920 to 1985. The average duration of annual holidays increased 30-fold. The number of sunny resort holidays and the sales of sunscreens increased rapidly from 1980. CMM was most strongly associated with solar exposure of 5-19 years earlier. There is a considerable decrease in clothing coverage during the 20th century. UVR exposure preceding CMM occurrence 4 years or less does not appear relevant, whereas the period 5-19 years prior to CMM occurrence might be the most relevant period. However, findings of ecological studies may not be applicable at the individual level

Nailfold capillaroscopy abnormalities correlate with cutaneous and visceral involvement in systemic sclerosis patients.

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Sato, Lucy T; Kayser, Cristiane; Andrade, Luís E C

2009-01-01

The aim of this study was to correlate quantitative and semiquantitative nailfold capillaroscopy (NFC) parameters with the extent of cutaneous and visceral involvement in systemic sclerosis (SSc) patients. The presence of clinical and serological alterations was evaluated retrospectively and correlated with NFC findings (number of capillary loops/mm, vascular deletion score and number of enlarged and giant capillary loops). For evaluation of disease extension five manifestations were analyzed: finger pad lesions, skin involvement, esophageal involvement, interstitial lung disease, and pulmonary hypertension. There were 105 NFC examinations in 92 patients, 13 of whom were evaluated at two different time points. Patients with diffuse cutaneous SSc had a higher vascular deletion score than patients with limited cutaneous SSc, sine scleroderma SSc, and overlap syndrome (1.67+/-0.91 vs 0.99+/-0.82; p=0.0005). Modified Rodnan's skin score correlated positively with capillary deletion, evaluated by the vascular deletion score and the number of capillary loops/mm (p<0.001 and p=0.012; respectively). Patients with three or more involved tracts presented lower number of capillary loops/mm (8.00+/-1.69 vs 9.23+/-1.31 capillary loops/mm; p=0.025) and a higher vascular deletion score (1.41+/-0.95 vs 0.73+/-0.76; p=0.027) when compared to patients with less than three affected tracts. Vascular deletion score was significantly higher in patients with anti-Scl-70 antibodies that in patients without anti-Scl-70 antibodies (p=0.02). NFC abnormalities correlated positively with the diffuse form of SSc, the degree of cutaneous involvement, the number of affected tracts, and the presence of anti-Scl-70 antibodies.

Sentinel lymph node biopsy versus observation in thick melanoma: A multicenter propensity score matching study.

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Boada, Aram; Tejera-Vaquerizo, Antonio; Ribero, Simone; Puig, Susana; Moreno-Ramírez, David; Descalzo-Gallego, Miguel A; Fierro, María T; Quaglino, Pietro; Carrera, Cristina; Malvehy, Josep; Vidal-Sicart, Sergi; Bennássar, Antoni; Rull, Ramón; Alos, Llucìa; Requena, Celia; Bolumar, Isidro; Traves, Víctor; Pla, Ángel; Fernández-Figueras, María T; Ferrándiz, Carlos; Pascual, Iciar; Manzano, José L; Sánchez-Lucas, Marina; Giménez-Xavier, Pol; Ferrandiz, Lara; Nagore, Eduardo

2018-02-01

The clinical value of sentinel lymph node (SLN) biopsy in thick melanoma patients (Breslow >4 mm) has not been sufficiently studied. The aim of the study is to evaluate whether SLN biopsy increases survival in patients with thick cutaneous melanoma, and, as a secondary objective, to investigate correlations between survival and lymph node status. We included 1,211 consecutive patients with thick melanomas (>4 mm) registered in the participating hospitals' melanoma databases between 1997 and 2015. Median follow-up was 40 months. Of these patients, 752 were matched into pairs by propensity scores based on sex, age, tumor location, histologic features of melanoma, year of diagnosis, hospital and adjuvant interferon therapy. The SLN biopsy vs. observation was associated with better DFS [adjusted hazard ratio (AHR), 0.74; 95% confidence interval (CI) 0.61-0.90); p = 0.002] and OS (AHR, 0.75; 95% CI, 0.60-0.94; p = 0.013) but not MSS (AHR, 0.84; 95% CI, 0.65-1.08; p = 0.165). SLN-negative patients had better 5- and 10-year MSS compared with SLN-positive patients (65.4 vs. 51.9% and 48.3 vs. 38.8%; p = 0.01, respectively). As a conclusion, SLN biopsy was associated with better DFS but not MSS in thick melanoma patients after adjustment for classic prognostic factors. SLN biopsy is useful for stratifying these patients into different prognostic groups. © 2017 UICC.

Melanoma reporting to central cancer registries by US dermatologists: an analysis of the persistent knowledge and practice gap.

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Cartee, Todd V; Kini, Seema P; Chen, Suephy C

2011-11-01

Every state requires diagnosing physicians to report new cases of melanoma to its central cancer registry. Previous regional studies and anecdotal experience suggest that few dermatologists are cognizant of this obligation. This oversight could result in a large number of unreported melanomas annually and, in turn, US melanoma statistics that markedly underestimate the true incidence of the disease. We sought to quantify the percentage of dermatologists who are unaware of melanoma reporting requirements (the knowledge gap) and who are not reporting melanoma diagnoses (the practice gap). We also sought to delineate factors predictive of reporting knowledge and behavior. A survey was administered to attendees of the Cutaneous Oncology Symposium at the 2010 American Academy of Dermatology annual meeting. In all, 104 of 419 eligible attendees completed surveys (response rate 26%). Fifty percent of respondents do not believe they are required to report melanomas and 56% do not actively report their diagnoses to a registry. Practice duration of less than 10 years was significantly associated with both a knowledge gap (P = .047) and practice gap (P = .056). Similarly, dermatologists who diagnosed fewer than 10 melanomas per year were more likely to possess a knowledge gap (P = .096) and a practice gap (P = .087) than those who diagnosed more than 10. Limitations include small sample size and low response rate. A majority of dermatologists are not reporting melanomas they diagnose to a cancer registry, and half of those surveyed were not aware that diagnosing physicians are required to report melanoma. Copyright © 2011 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

Thioredoxin induces Tregs to generate an immunotolerant tumor microenvironment in metastatic melanoma

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Wang, Xiaogang; Dong, Haisheng; Li, Qi; Li, Yingxian; Hong, An

2015-01-01

Metastatic melanoma is a highly aggressive cancer that is very difficult to treat. Additionally, the antitumor immune reaction of melanoma is still unclear. Here we demonstrate an association between the expression and secretion of the antioxidant protein thioredoxin (TRX) and increasing tumor stage and metastasis in melanoma. To elucidate the role of TRX in melanoma, we assessed the correlation of TRX expression with different disease parameters in melanoma. We also examined the in vitro and in vivo effects of modulating TRX levels in melanoma cells using various methods of TRX depletion and augmentation. We further explored the effects of TRX on the cytokine milieu and the ability of TRX to regulate the proportion and specific activities of T-cell populations. We demonstrate that TRX expression correlates with Treg representation in clinical samples and, that modulation of TRX influences the induction of Tregs and the generation of an immunotolerant cytokine profile in mouse serum. Using a murine metastatic melanoma model, we identified a tumor immunoevasion mechanism whereby melanoma cell-secreted TRX enhances Treg infiltration. TRX displays chemotactic effects in recruiting Tregs, stimulates the conversion of conventional T cells to Tregs, and confers survival advantage to Tregs in the tumor microenvironment. In turn, this increase of Tregs generates immunotolerance in tissues and therefore decreases antitumor immune reactions. These results elucidate a mechanism by which TRX promotes metastatic melanoma in part through Treg recruitment to inhibit T-cell antitumor effects and suggest that TRX antibody may be useful in the clinic as a therapy against melanoma. PMID:26405597

Targeted alpha therapy for melanoma : from bench to bedside

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Allen, B.J.; Rizvi, S.M.A.; Li, Y.; Tsui, W.; Douglas, S.; Raja, C.; Graham, P.; Smart, R.; Butler, P.; Kearsley, J.; Thompson, J.

2001-01-01

Full text: The control of metastatic melanoma remains an elusive objective. Targeted alpha therapy (TAT) offers a new approach to the control of micrometastases and regression of tumours. The alpha emitting immunoconjugate (AIC) against malignant melanoma has been prepared by chelating Bi-213 to the anti-melanoma antibody 9.2.27, and injected locally at 2 d post-inoculation of 1.5 million melanoma cells, or intralesionally into skin tumours. Human subjects receive 50μCi intralesional dose, escalating to 1 mCi. The clearances from the tumour, kidneys and bladder are monitored by a NaI detector that detects the 440 keV gamma ray. Blood samples and tumour photographs are taken at O. 2 and 4 weeks; tumours are excised at 4 weeks. Isolated cancer cells and preangiogenic cell clusters in mice can be eliminated with 25 μCi local AIC injection, and intra-lesional injections of 100 μCi are sufficient to completely regress melanomas with volumes up to 300 mm 3 without side-effects. Systemic TAT with a single administration is less effective with 100% growth delay of tumours observed, and ∼20% complete inhibition. The clinical TAT trial for recurrent subcutaneous melanoma has been approved by the NSW Radiation Advisory Committee and the SES Human Ethics Committee. In a world first phase 1 study, the first 5 subjects have been treated by intralesional injection, 3 at 50 μCi, and 2 at 150 μCi. All subjects having unchanged blood profiles at 2 and 4 weeks post-therapy. Tumour volumes appear little changed. However, histology of a 3 cm melanoma shows that almost complete cell kill occurred at 150 μCi, with only a few small cell clusters surviving. Local TAT inhibits tumourogenesis and intralesional TAT completely regresses melanoma in mice. Intralesional TAT for melanoma in human subjects is non-toxic so far and appears to be a promising modality. The ultimate objective is to apply systemic TAT for the control of melanoma micrometastases. Copyright (2001) Australasian

Seven Non-melanoma Features to Rule Out Facial Melanoma

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Philipp Tschandl

2017-08-01

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

Advances in Proteomic Techniques for Cytokine Analysis: Focus on Melanoma Research

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Helena Kupcova Skalnikova

2017-12-01

Full Text Available Melanoma is a skin cancer with permanently increasing incidence and resistance to therapies in advanced stages. Reports of spontaneous regression and tumour infiltration with T-lymphocytes makes melanoma candidate for immunotherapies. Cytokines are key factors regulating immune response and intercellular communication in tumour microenvironment. Cytokines may be used in therapy of melanoma to modulate immune response. Cytokines also possess diagnostic and prognostic potential and cytokine production may reflect effects of immunotherapies. The purpose of this review is to give an overview of recent advances in proteomic techniques for the detection and quantification of cytokines in melanoma research. Approaches covered span from mass spectrometry to immunoassays for single molecule detection (ELISA, western blot, multiplex assays (chemiluminescent, bead-based (Luminex and planar antibody arrays, ultrasensitive techniques (Singulex, Simoa, immuno-PCR, proximity ligation/extension assay, immunomagnetic reduction assay, to analyses of single cells producing cytokines (ELISpot, flow cytometry, mass cytometry and emerging techniques for single cell secretomics. Although this review is focused mainly on cancer and particularly melanoma, the discussed techniques are in general applicable to broad research field of biology and medicine, including stem cells, development, aging, immunology and intercellular communication.

European multicenter study on melanoma immunoscintigraphy by means of 99mTc-labelled monoclonal antibody fragments

International Nuclear Information System (INIS)

Siccardi, A.G.; Viale, G.; Natali, P.G.; Scassellati, G.A.; Ferrone, S.

1990-01-01

A total of 493 melanoma patients were investigated by 20 European nuclear medicine departments by means of the same 99m Tc-labelled immunoradiopharmaceutical and the same immunoscintigraphy (ISG) protocol. (i) No chemical or clinical toxicity was detected during or following the studies. (ii) Positive results were obtained in 287/363 (79%) patients (321 carrying known lesions and 42 carrying previously occult lesions): In 231 (80%) of them, 402/402 lesions were imaged; in the remaining 56 ISG-positive patients, 108/204 lesions were imaged; in 76 patients 0/122 lesions were imaged. (iii) The fraction of melanoma lesions visualized by ISG was 510/728 (70.1%); 605 of these lesions were already documented at the time of the study, and 123 were previously occult. (iv) A total of 218 documented melanoma lesions (30%) were not visualized by ISG in 132 patients: About 70% of the ISG-negative lesions were of small size (less than 2 cm diameter). (v) The melanoma nature of 69/123 previously occult lesions was confirmed by clinical criteria and/or additional investigations in follow-up studies. The results obtained in this study are similar to those obtained in the Italian Multicenter Study which had previously been carried out with 258 melanoma patients. (orig.)

Incorporating Colour Information for Computer-Aided Diagnosis of Melanoma from Dermoscopy Images: A Retrospective Survey and Critical Analysis

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Ali Madooei

2016-01-01

Full Text Available Cutaneous melanoma is the most life-threatening form of skin cancer. Although advanced melanoma is often considered as incurable, if detected and excised early, the prognosis is promising. Today, clinicians use computer vision in an increasing number of applications to aid early detection of melanoma through dermatological image analysis (dermoscopy images, in particular. Colour assessment is essential for the clinical diagnosis of skin cancers. Due to this diagnostic importance, many studies have either focused on or employed colour features as a constituent part of their skin lesion analysis systems. These studies range from using low-level colour features, such as simple statistical measures of colours occurring in the lesion, to availing themselves of high-level semantic features such as the presence of blue-white veil, globules, or colour variegation in the lesion. This paper provides a retrospective survey and critical analysis of contributions in this research direction.

Clinical value of FDG-PET in cutaneous malignant melanoma: First experience in Estonia

International Nuclear Information System (INIS)

Nazarenko, S.; Niin, M.; Paats, A.; Tonnov, A.

2004-01-01

Full text: In November 2002 first 18F-FDG-PET was performed in Estonia using a mobile truck-mounted scanning technology (Accel, Siemens) provided by the International Healthcare Group (IHG, Amersfoort, Netherlands). The FDG was provided by MAP Medical Technologies, Schering, (Helsinki, Finland). In 2003 this scheme was repeated for further scanning sessions. Evaluation of cutaneous malignant melanoma (CMM) using nuclear technique is of particular interest in Estonia as its incidence is on the rise. F-18 fluorodeoxyglucose positron emission tomography (FDG-PET) in CMM has a well-documented high diagnostic accuracy, especially in staging of the disease. The aim of the current study was to assess the impact of 18F-FDG-PET on detailed staging and clinical management in CMM. 30 patients of CMM, 16 males and 14 females, all non-diabetic, in the age range of 26 to 69 years were studied. Of these 30 patients, 12 were of high risk primary CMM, 7 had regional lymph node metastases and 11 had distant metastases. Patients were asked to consume a low-carbohydrate diet 3 days prior to the FDG-PET scan. 194 to 410 MBq (average 335 MBq) 18F-FDG was administered to the patients who were asked to come fasting for a minimum of 6 hours. Whole body scan was performed 40 to 65 minutes after the administration of FDG on the mobile PET. In 13 of the 30 patients (43%) 18F-FDG-PET changed the staging. In remaining 17 patients (57%) 18F-FDG-PET increased confidence level for the chosen treatment. Lymphadenectomy was planned in 2 patients showing lymph node involvement on FDG-PET. In other 2 patients, one with small pulmonary and other with a liver lesions found on PET but negative on radiological examination 'wait-and-watch' strategy was chosen. An unexpected hypermetabolic lesion seen in 1 case turned out to be a benign focus of connective tissue. One patient shown to have multiple distant metastases was started on chemotherapy. Finally in 8 of the 30 (27%) patients an immediate positive

Acute Truncal Lymphedema Secondary to Axillary Metastatic Melanoma Presenting Like Cellulitis

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Shelley J. E. Hwang

2017-01-01

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

Retrospective study of 338 canine oral melanomas with clinical, histologic, and immunohistochemical review of 129 cases.

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Ramos-Vara, J A; Beissenherz, M E; Miller, M A; Johnson, G C; Pace, L W; Fard, A; Kottler, S J

2000-11-01

Diagnostic records from 338 canine oral melanomas in 338 dogs received at the Veterinary Medical Diagnostic Laboratory (1992-1999) were reviewed. Of these tumors, 122 plus an additional 7 metastatic melanomas of unknown origin were selected for clinical follow-up, histologic review, and immunohistochemistry. Chow Chow, Golden Retriever, and Pekingese/Poodle mix breeds were overrepresented, whereas Boxer and German Shepherd breeds were underrepresented. There was no gender predisposition and the average age at presentation was 11.4 years. Forty-nine dogs were euthanized due to recurrence or metastasis. The average postsurgical survival time was 173 days. The gingiva and the labial mucosa were the most common sites. Most tumors were composed of either polygonal cells (27 cases, 20.9%), spindle cells (44 cases, 34.1%), or a mixture of the two (polygonal and spindle) (54 cases, 41.9%). Clear cell (3 cases, 2.3%) and adenoid/papillary (1 case, 0.8%) patterns were uncommon. The metastases of 6/6 oral melanomas had morphologic and immunohistochemical features similar to those of the primary tumors. Immunohistochemically, Melan A was detected in 113/122 oral (92.6%) and 5/7 (71.9%) metastatic melanomas. Only 4/163 nonmelanocytic tumors were focally and weakly positive for Melan A. Antibodies against vimentin, S100 protein, and neuron-specific enolase stained 129 (100%), 98 (76%), and 115 (89.1%) of 129 melanomas, respectively. Antibodies against other melanocytic-associated antigens (tyrosinase, glycoprotein 100) did not yield adequate staining. We conclude that Melan A is a specific and sensitive marker for canine melanomas.

Patient with giant upper limb melanoma presenting to a UK plastic surgery unit: differentials and experience of management.

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Honeyman, Calum Sinclair; Wilson, Paul

2016-02-02

A 57-year-old woman was referred to our regional sarcoma unit following a 2-year history of a progressively enlarging mass on her right forearm. At 14 × 7 × 12 cm, this mass turned out to be one of the largest upper limb cutaneous malignant melanomas ever described, and, to the best of our knowledge, the first documented in the UK. Remarkably, despite having a T4 malignant tumour with a Breslow thickness of 70 mm, this patient is still alive over 4 years later with no locoregional or distant metastatic spread. We present our experience in the management of this giant malignant melanoma of the upper limb and consider important differentials. 2016 BMJ Publishing Group Ltd.

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

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Tarun Mehra

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

Automated melanoma detection with a novel multispectral imaging system: results of a prospective study

International Nuclear Information System (INIS)

Tomatis, Stefano; Carrara, Mauro; Bono, Aldo; Bartoli, Cesare; Lualdi, Manuela; Tragni, Gabrina; Colombo, Ambrogio; Marchesini, Renato

2005-01-01

The aim of this research was to evaluate the performance of a new spectroscopic system in the diagnosis of melanoma. This study involves a consecutive series of 1278 patients with 1391 cutaneous pigmented lesions including 184 melanomas. In an attempt to approach the 'real world' of lesion population, a further set of 1022 not excised clinically reassuring lesions was also considered for analysis. Each lesion was imaged in vivo by a multispectral imaging system. The system operates at wavelengths between 483 and 950 nm by acquiring 15 images at equally spaced wavelength intervals. From the images, different lesion descriptors were extracted related to the colour distribution and morphology of the lesions. Data reduction techniques were applied before setting up a neural network classifier designed to perform automated diagnosis. The data set was randomly divided into three sets: train (696 lesions, including 90 melanomas) and verify (348 lesions, including 53 melanomas) for the instruction of a proper neural network, and an independent test set (347 lesions, including 41 melanomas). The neural network was able to discriminate between melanomas and non-melanoma lesions with a sensitivity of 80.4% and a specificity of 75.6% in the 1391 histologized cases data set. No major variations were found in classification scores when train, verify and test subsets were separately evaluated. Following receiver operating characteristic (ROC) analysis, the resulting area under the curve was 0.85. No significant differences were found among areas under train, verify and test set curves, supporting the good network ability to generalize for new cases. In addition, specificity and area under ROC curve increased up to 90% and 0.90, respectively, when the additional set of 1022 lesions without histology was added to the test set. Our data show that performance of an automated system is greatly population dependent, suggesting caution in the comparison with results reported in the

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

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

2009-08-01

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

No prognostic value added by vitamin D pathway SNPs to current prognostic system for melanoma survival.

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Li Luo

Full Text Available The prognostic improvement attributed to genetic markers over current prognostic system has not been well studied for melanoma. The goal of this study is to evaluate the added prognostic value of Vitamin D Pathway (VitD SNPs to currently known clinical and demographic factors such as age, sex, Breslow thickness, mitosis and ulceration (CDF. We utilized two large independent well-characterized melanoma studies: the Genes, Environment, and Melanoma (GEM and MD Anderson studies, and performed variable selection of VitD pathway SNPs and CDF using Random Survival Forest (RSF method in addition to Cox proportional hazards models. The Harrell's C-index was used to compare the performance of model predictability. The population-based GEM study enrolled 3,578 incident cases of cutaneous melanoma (CM, and the hospital-based MD Anderson study consisted of 1,804 CM patients. Including both VitD SNPs and CDF yielded C-index of 0.85, which provided slight but not significant improvement by CDF alone (C-index = 0.83 in the GEM study. Similar results were observed in the independent MD Anderson study (C-index = 0.84 and 0.83, respectively. The Cox model identified no significant associations after adjusting for multiplicity. Our results do not support clinically significant prognostic improvements attributable to VitD pathway SNPs over current prognostic system for melanoma survival.

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

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

2015-12-01

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

Cutaneous, gastrointestinal, hepatic, endocrine, and renal side-effects of anti-PD-1 therapy.

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Hofmann, Lars; Forschner, Andrea; Loquai, Carmen; Goldinger, Simone M; Zimmer, Lisa; Ugurel, Selma; Schmidgen, Maria I; Gutzmer, Ralf; Utikal, Jochen S; Göppner, Daniela; Hassel, Jessica C; Meier, Friedegund; Tietze, Julia K; Thomas, Ioannis; Weishaupt, Carsten; Leverkus, Martin; Wahl, Renate; Dietrich, Ursula; Garbe, Claus; Kirchberger, Michael C; Eigentler, Thomas; Berking, Carola; Gesierich, Anja; Krackhardt, Angela M; Schadendorf, Dirk; Schuler, Gerold; Dummer, Reinhard; Heinzerling, Lucie M

2016-06-01

Anti-programmed cell death receptor-1 (PD-1) antibodies represent an effective treatment option for metastatic melanoma as well as for other cancer entities. They act via blockade of the PD-1 receptor, an inhibitor of the T-cell effector mechanisms that limit immune responses against tumours. As reported for ipilimumab, the anti-PD-1 antibodies pembrolizumab and nivolumab can induce immune-related adverse events (irAEs). These side-effects affect skin, gastrointestinal tract, liver, endocrine system and other organ systems. Since life-threatening and fatal irAEs have been reported, adequate diagnosis and management are essential. In total, 496 patients with metastatic melanoma from 15 skin cancer centers were treated with pembrolizumab or nivolumab; 242 side-effects were described in 138 patients. In 116 of the 138 patients, side-effects affected the skin, gastrointestinal tract, liver, endocrine, and renal system. Rare side-effects included diabetes mellitus, lichen planus, and pancreas insufficiency due to pancreatitis. Anti-PD1 antibodies can induce a plethora of irAEs. The knowledge of them will allow prompt diagnosis and improve the management resulting in decreased morbidity. Copyright © 2016 Elsevier Ltd. All rights reserved.

On the role of classical and novel forms of vitamin D in melanoma progression and management.

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Slominski, Andrzej T; Brożyna, Anna A; Skobowiat, Cezary; Zmijewski, Michal A; Kim, Tae-Kang; Janjetovic, Zorica; Oak, Allen S; Jozwicki, Wojciech; Jetten, Anton M; Mason, Rebecca S; Elmets, Craig; Li, We; Hoffman, Robert M; Tuckey, Robert C

2018-03-01

Melanoma represents a significant clinical problem affecting a large segment of the population with a relatively high incidence and mortality rate. Ultraviolet radiation (UVR) is an important etiological factor in malignant transformation of melanocytes and melanoma development. UVB, while being a full carcinogen in melanomagenesis, is also necessary for the cutaneous production of vitamin D3 (D3). Calcitriol (1,25(OH) 2 D3) and novel CYP11A1-derived hydroxyderivatives of D3 show anti-melanoma activities and protective properties against damage induced by UVB. The former activities include inhibitory effects on proliferation, plating efficiency and anchorage-independent growth of cultured human and rodent melanomas in vitro, as well as the in vivo inhibition of tumor growth by 20(OH)D3 after injection of human melanoma cells into immunodeficient mice. The literature indicates that low levels of 25(OH)D3 are associated with more advanced melanomas and reduced patient survivals, while single nucleotide polymorphisms of the vitamin D receptor or the D3 binding protein gene affect development or progression of melanoma, or disease outcome. An inverse correlation of VDR and CYP27B1 expression with melanoma progression has been found, with low or undetectable levels of these proteins being associated with poor disease outcomes. Unexpectedly, increased expression of CYP24A1 was associated with better melanoma prognosis. In addition, decreased expression of retinoic acid orphan receptors α and γ, which can also bind vitamin D3 hydroxyderivatives, showed positive association with melanoma progression and shorter disease-free and overall survival. Thus, inadequate levels of biologically active forms of D3 and disturbances in expression of the target receptors, or D3 activating or inactivating enzymes, can affect melanomagenesis and disease progression. We therefore propose that inclusion of vitamin D into melanoma management should be beneficial for patients, at least as

Radioimmunoscintigraphy of human malignant melanoma. I

International Nuclear Information System (INIS)

Svec, J.; Makaiova, I.; Veselovska, Z.; Keszeghova, V.; Reinerova, M.

1989-01-01

The novel RG-12 monoclonal antibody (MoAb) recognizing a high-molecular-weight antigen of human melanoma cells was radioiodinated and its biodistribution and tumor imaging was determined in immunosuppressed mice bearing xenografted human malignant melanoma HMB-2. Control and tumor-bearing mice were injected with 6 μg of 125 I-labeled RG-12 IgG (8.9 MBq 125 I-IgG/animal). Clearance of the MoAb from plasma had a mean half life of 20.6 hours. At day 2 after injection, radiolabeled RG-12 IgG localized in the tumor was 1.43% of the injected dose bound per gram tissue (ID/g), whereas the localization in the healthy kidney was below 0.5%. Tumor to tissue ratio of MoAb accumulation was low for hepatic tissue (1.25) but high for spleen (3.30) and kidney (3.25). Scanning with a gamma camera localized tumor mass in the right kidney and implanted peritoneal metastases. (author). 3 figs., 1 tab., 9 refs

ADAM15 expression is downregulated in melanoma metastasis compared to primary melanoma

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

2010-01-01

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

ADAM15 expression is downregulated in melanoma metastasis compared to primary melanoma

Energy Technology Data Exchange (ETDEWEB)

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

2010-10-22

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

Ocular Melanoma

Science.gov (United States)

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

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

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

2008-04-01

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

Prevalence of variations in melanoma susceptibility genes among Slovenian melanoma families

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Besic Nikola

2008-09-01

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

Communication about melanoma and risk reduction after melanoma diagnosis.

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

2017-12-01

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

High expression of TRF2, SOX10, and CD10 in circulating tumor microemboli detected in metastatic melanoma patients. A potential impact for the assessment of disease aggressiveness.

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Long, Elodie; Ilie, Marius; Bence, Coraline; Butori, Catherine; Selva, Eric; Lalvée, Salomé; Bonnetaud, Christelle; Poissonnet, Gilles; Lacour, Jean-Philippe; Bahadoran, Philippe; Brest, Patrick; Gilson, Eric; Ballotti, Robert; Hofman, Véronique; Hofman, Paul

2016-06-01

Circulating tumors cells (CTCs) can be detected in the blood of metastatic melanoma patients (MMPs) both as isolated circulating tumor cells (iCTCs) and circulating tumor microemboli (CTMs), but their clinical significance remains unknown. The aim of this work was to evaluate the prognostic impact in metastatic cutaneous melanoma of CTMs and iCTCs identified by a cytomorphological approach using the isolation by size of tumor cell (ISET) method. We characterized the phenotype of CTCs using anti-PS100, anti-SOX10, anti-CD10, and anti-TRF2 antibodies. 128 MMPs and 37 control healthy individuals with benign nevi were included in this study. Results were compared to the follow-up of patients. 109/128 (85%) MMPs showed CTCs, 44/128 (34%) with 2 to 6 CTMs and 65/128 (51%) with 4 to 9 iCTCs. PS100 expression was homogeneous in iCTCs and heterogeneous in CTMs. SOX10, CD10, and TRF2 were mainly expressed in CTMs. None of the control subjects demonstrated circulating malignant tumor cells. Overall survival was significantly decreased in patients with CTMs, independently of the therapeutic strategies. In conclusion, the presence of CTMs is an independent predictor of shorter survival from the time of diagnosis of MMPs. © 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Ipilimumab: A First-in-Class T-Cell Potentiator for Metastatic Melanoma

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Chmielowski, B.

2013-01-01

Ipilimumab, a fully human anti-cytotoxic T-lymphocyte antigen-4 monoclonal antibody that potentiate s antitumor T-cell responses, has demonstrated improved survival in previously treated and treatment-naive patients with unresectable stage III/IV melanoma. Survival benefit has also been shown in diverse patient populations, including those with brain metastases. In 2011, ipilimumab (3 mg/kg every 3 weeks for 4 doses) was approved by the Food and Drug Administration for unresectable or metastatic melanoma. Ipilimumab can induce novel response patterns for which immune-related response criteria have been proposed. irAEs are common but are usually low grade; higher grades can be severe and life-threatening. irAEs are usually manageable using established guidelines emphasizing vigilance and prompt intervention. This agent provides an additional therapeutic option in metastatic melanoma, and guidelines for management of adverse events facilitate clinical implementation of this new agent.

Sentinel lymph node biopsy: is it possible to reduce false negative rates by excluding patients with nodular melanoma?

LENUS (Irish Health Repository)

Corrigan, M A

2012-02-03

OBJECTIVE: The aim of this study was to review the outcome of sentinel lymph node biopsy (SLNB) in patients with melanoma and to delineate whether patients with nodular melanoma are more likely to develop nodal recurrence despite negative SLNB. METHODS: Consecutive patients with cutaneous melanoma undergoing SLNB were identified from a departmental database between 1997 and 2005. Factors including demographic data, site, histological subtype, depth and outcome were examined. RESULTS: Of 131 patients, 103 were node negative and eligible for study. The median age was 53 (16-82) years with 46 patients being male (45%) and 57 female (55%). Primary melanoma sites included lower limb (49; 48%), upper limb (29; 28%), head (12; 11%), trunk (7; 7%) and back (6; 6%). The median Breslow thickness was 2mm. Superficial spreading accounted for 43% of melanoma with nodular accounting for 42%. Median follow-up was 40 (3-90) months. Of 20 relapses, seven recurred in the same nodal basin, three were satellite recurrences, one recurred with both satellite and nodal lesions simultaneously, and nine experienced haematogenous spread. Of the eight patients who developed recurrence in the same nodal basin, four were of nodular histological subtype (p=NS). All of the three patients with satellite lesions had nodular melanoma histologically (p=0.02). When nodal and satellite recurrences were combined, eight of 11 were histologically nodular (p=0.01). CONCLUSIONS: This study indicates that lymphatic recurrence occurs more often in SLNB negative patients with nodular melanoma. Further evaluation of the inclusion criteria for sentinel node biopsy is warranted.

High accuracy of family history of melanoma in Danish melanoma cases

DEFF Research Database (Denmark)

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

2015-01-01

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

Stereotactic Radiofrequency Ablation for Metastatic Melanoma to the Liver

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Bale, Reto, E-mail: reto.bale@i-med.ac.at; Schullian, Peter [Medical University Innsbruck, Department of Radiology, Section of Interventional Oncology - Microinvasive Therapy (SIP) (Austria); Schmuth, Matthias [Medical University Innsbruck, Department of Dermatology (Austria); Widmann, Gerlig; Jaschke, Werner [Medical University Innsbruck, Department of Radiology, Section of Interventional Oncology - Microinvasive Therapy (SIP) (Austria); Weinlich, Georg [Medical University Innsbruck, Department of Dermatology (Austria)

2016-08-15

PurposeTo evaluate the outcome of patients with melanoma liver metastasis treated with stereotactic radiofrequency ablation (SRFA).Material and MethodFollowing IRB approval, a retrospective evaluation of the treatment of 20 patients with 75 melanoma liver metastases was performed.ResultsA median number of 2 lesions (range 1–14) per patient with a median size of 1.7 cm (range 0.5–14.5 cm) were treated. 67 lesions were <3 cm (89.3 %) and 8 lesions were >3 cm (10.7 %). Per patient a median of 1 ablation session was performed (range: 1–4) totaling 34 sessions. There were no procedure-related deaths and all major complications (n = 3) could be easily treated by pleural drainages. The primary and secondary success rates were 89.3 and 93.3 %, respectively. The overall local recurrence rate was 13.3 %. Four of ten local recurrences were re-treated successfully by SRFA. During follow-up, 9/20 patients developed extrahepatic metastatic disease and 10/20 had liver recurrence at any location. The median OS from the date of SRFA was 19.3 months, with an OS of 64, 41, and 17 % at 1, 3, and 5 years, with no significant difference for patients with cutaneous and ocular melanoma. The median DFS after SRFA for all 20 patients was 9.5 months, with 37, 9, and 0 % at 1, 3, and 5 years.ConclusionsDue to the high local curative potential and the promising long-term survival rates associated with minimal morbidity and mortality, radiofrequency ablation seems to be an attractive alternative to resection in patients with melanoma liver metastases.

Influence of ipilimumab on expanded tumour derived T cells from patients with metastatic melanoma

DEFF Research Database (Denmark)

Bjørn, Jon; Lyngaa, Rikke Birgitte; Andersen, Rikke

2017-01-01

Introduction: Tumour infiltrating lymphocyte (TIL) based adoptive cell therapy (ACT) is a promising treatment for patients with advanced melanoma. Retrospective studies suggested an association between previous treatment with anti-CTLA-4 antibodies and long term survival after subsequent ACT. Thus...

Influence of ipilimumab on expanded tumour derived T cells from patients with metastatic melanoma

DEFF Research Database (Denmark)

Bjørn, Jon; Lyngaa, Rikke Birgitte; Andersen, Rikke

2017-01-01

Introduction: Tumour infiltrating lymphocyte (TIL) based adoptive cell therapy (ACT) is a promising treatment for patients with advanced melanoma. Retrospective studies suggested an association between previous treatment with anti-CTLA-4 antibodies and long term survival after subsequent ACT. Thu...

Quantitation of passive cutaneous anaphylaxis (PCA) by using radiolabelled antigen

International Nuclear Information System (INIS)

Ring, J.; Seifert, J.; Brendel, W.

1978-01-01

The major problem of detecting reaginic antibody by passive cutaneous anaphylaxis (PCA) is the quantitation of the dye reaction. Radiolabelled antigen was used in an attempt to quantitate the PCA reaction (Radio-PCA). Antisera containing reaginic antibody against human serum albumin (HSA) were produced in rabbits. These antisera were injected into normal rabbit skin in different dilutions. Twentyfour hours later HSA was injected intravenously either with Evans Blue or as 125-I-HSA. Radioactivity found in antibody-containing skin was significantly higher than in control specimens containing saline or normal rabbit serum, as low as antiserum dilutions of 1:1,000. Compared with Evans Blue technique Radio-PCA was able to distinguish quantitatively between different antiserum dilutions at a higher level of statistical significance. (author)

A melanoma risk score in a Brazilian population Um escore de risco para melanoma em uma população brasileira

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Lucio Bakos

2013-04-01

Full Text Available BACKGROUND: Important risk factors for cutaneous melanoma (CM are recognized, but standardized scores for individual assessment must still be developed. OBJECTIVES: The objective of this study was to develop a risk score of CM for a Brazilian sample. METHODS: To verify the estimates of the main risk factors for melanoma, derived from a meta-analysis (Italian-based study, and externally validate them in a population in southern Brazil by means of a case-control study. A total of 117 individuals were evaluated. Different models were constructed combining the summary coefficients of different risk factors, derived from the meta-analysis, multiplied by the corresponding category of each variable for each participant according to a mathematical expression. RESULTS: the variable that best predicted the risk of CM in the studied population was hair color (AUC: 0.71; 95% CI: 0.62-0.79. Other important factors were freckles, sunburn episodes, and skin and eye color. Consideration of other variables such as common nevi, elastosis, family history, and premalignant lesions did not improve the predictive ability of the models. CONCLUSION: The discriminating capacity of the proposed model proved to be superior or comparable to that of previous risk models proposed for CM. FUNDAMENTOS: importantes fatores de risco para melanoma cutâneo são reconhecidos, mas escores padronizados para avaliação individual ainda precisam ser elaborados. OBJETIVOS: o objetivo deste estudo foi desenvolver um escore de risco de melanoma cutâneo para uma amostra brasileira. MÉTODOS: verificar as estimativas dos principais fatores de risco para melanoma, derivado de uma meta-análise (estudo de base italiano e, externamente, validar em uma população do sul do Brasil por um estudo caso-controle. Um total de 117 indivíduos foram avaliados. RESULTADOS: a variável com maior poder preditivo para o risco de melanoma cutâneo na população estudada foi a cor do cabelo (AUC: 0

Subcellular localization and photodynamic activity of Photodithazine (glucosamine salt of chlorin e6) in murine melanoma B16-F10: an in vitro and in vivo study

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Ono, Bruno Andrade; Pires, Layla; Nogueira, Marcelo Saito; Kurachi, Cristina; Pratavieira, Sebastião.

2018-02-01

Photodynamic therapy (PDT) is already a good option for the clinical treatment of several lesions, including mainly nonmelanoma skin cancers. However, cutaneous melanoma treatment remains a challenge when using PDT. One of the reasons for its reduced efficacy is the high pigmentation of melanoma cells. The object of our study is to evaluate the feasibility of the Photodithazine as a photosensitizer for melanoma. Photodithazine is already used in some malignant tumors with satisfactory results and has significant absorption band around 660 nm where the absorption of melanin is low. In this study, we measured the subcellular localization and photodynamic activity of Photodithazine (PDZ) in murine melanoma B16-F10 cell culture. Additionally, a PDT procedure was applied in an animal melanoma model. This first result demonstrates that Photodithazine is more localized at mitochondria in B16F10 cell culture and the cell viability is reduced to less than 90% using 1 µg/mL (PDZ) and 2 J/cm2. We also noticed a rapid PDZ (less than one hour) accumulation in a murine melanoma model. The treatment of melanoma resulted in 20 % more animal survival after one session of PDT compared with the control group. More studies are required to evaluate the cytotoxic effects of Photodithazine at human melanoma.

Cutaneous cancers in the Mosan region and Ardennes of Belgium.

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Piérard-Franchimont, C; Uhoda, I; Piérard, G E

1999-01-01

The ratios of basal cell carcinomas (BBC) to squamous cell carcinomas (SCC) and to malignant melanomas (MM) have changed over time in the white population throughout the world. To evaluate the incidence of skin cancers in the Mosan region and the Belgian Ardennes over the past 6 years. In contrast with epidemiological data reported by the Belgian National Cancer Registry, cutaneous cancers are the commonest malignancies occurring in humans. At the present time, the ratio BCC:SCC roughly equals 4 to 1. When combined, the incidence of BCC and SCC is about 10 times greater than that of MM. The rate of detection of skin cancers does not always correlate with the rate of notification of a national registry.

Illustrative cases for monitoring by quantitative analysis of BRAF/NRAS ctDNA mutations in liquid biopsies of metastatic melanoma patients who gained clinical benefits from anti-PD1 antibody therapy.

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Seremet, Teofila; Planken, Simon; Schreuer, Max; Jansen, Yanina; Delaunoy, Mélanie; El Housni, Hakim; Lienard, Danielle; Del Marmol, Véronique; Heimann, Pierre; Neyns, Bart

2018-02-01

Anti-programmed death 1 (PD-1) monoclonal antibodies improve the survival of metastatic melanoma patients. Predictive or monitoring biomarkers for response to this therapy could improve the clinical management of these patients. To date, no established biomarkers are available for monitoring the response to immunotherapy. Tumor- specific mutations in circulating tumor DNA (ctDNA) such as BRAF and NRAS mutations for melanoma patients have been proposed for monitoring of immunotherapy response. We present seven illustrative cases for the use of ctDNA BRAF and NRAS mutations' monitoring in plasma. The cases described exemplify four distinct clinical benefit patterns: rapid and durable complete response (CR), early progression, followed by CR, CR followed by early progression after interrupting treatment and long-term disease stabilization. These representative cases suggest that comprehensive BRAF/NRAS ctDNA monitoring during anti-PD1 therapy is informative and can be of added value for the monitoring of melanoma patients gaining clinical benefit on anti-PD1 treatment. An important advantage of our approach is that using the cartridge system on the Idylla platform for mutation analysis, the results become available the same day 2 h after plasma collection. Therefore, in the future, the ctDNA level can be an element in the clinical management of the patients.

A Case of Churg-Strauss Syndrome Associated with Antiphospholipid Antibodies

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Ferenczi, Katalin; Chang, Timothy; Camouse, Melissa; Han, Rujing; Stern, Robert; Willis, Joseph; Cooper, Kevin D.; Gilliam, Anita C.

2008-01-01

BACKGROUND Churg-Strauss syndrome (CSS) is a systemic vasculitis affecting small and medium-sized blood vessels, almost invariably affecting the lung and frequently associated with cutaneous involvement. Microvascular vaso-occlusion leading to digital gangrene is not a feature of CSS. OBSERVATIONS We report an unusual case of a patient with Churg Strauss Syndrome with antiphospholipid antibodies who developed severe digital gangrene in addition to cutaneous vasculitis. CONCLUSION The presence of antiphospholipid antibodies is not a feature usually seen in association with Churg-Strauss syndrome. While the full clinical spectrum of Churg Strauss Syndrome is still being defined, identification of additional features associated with this syndrome might help to better understand the pathogenesis of the disease and to have an impact on management and prognosis. PMID:17175066

New Safety Margins for Melanoma Surgery: Nice Possibility for Drinking of "Just That Cup of Coffee"?

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Tchernev, Georgi; Chokoeva, Anastasiya Atanasova

2017-06-15

The American Joint Committee on Cancer (AJCC's) skin melanoma surgical treatment recommendations from 2011 are characterised by a prima facie "freedom of choice" regarding how extensive should be the excisions for melanomas with tumour thickness up to 2 mm and melanoma in situ. It is unclear why the recommended surgical security margins vary between 0.5 and 1 cm for melanoma in situ, whereas for melanomas with a tumour thickness of up to 1.99 mm, the range of variation is also between 1 and 2 cm, without specifying when the surgical field should be broader and, narrower, accordingly. This "uncertainty or lack of intent" of the guilders often leads to the same surgical approach to melanomas at different stages, or to a different approach in cases of melanomas at the same stage, in contrast. Therefore, this should be defined as wrong, logically. We present 3 patients with cutaneous melanomas, treated with similar fields of surgical security. Current issues, generated within the framework of melanoma's surgery guided by the recommendations of the AJCC are also discussed. A new surgical approach in patients with melanoma is recommended, discussed for the first time in world literature. We hypothesize that the introduction of a certain recommendations for a 2 cm surgical field in all directions during the initial excision, combined with the parallel performance of a sentinel lymph node biopsy, will lead in fact to several important advantages: 1) avoiding of the secondary excision in at least 70% - 90% of the patients (depending on the tumor thickness), 2) minimizing the risk of lymphatic effusion change and misinterpretation of the sentinel lymph node biopsy's results in patients with secondary excision; 3) optimization of the surgical team's work; 4) minimizing the possibility of unprepared/uninformed personnel to take part in decisions for treating a specific disease such as skin melanoma, 4) facilitating the appropriate patients' group selection at the appropriate

Effect of radiation on the induction of cell death in melanoma cells

International Nuclear Information System (INIS)

Notcovich, C; Delgado Gonzalez, D; Salguero, N; Bracalente, C; Molinari, B; Duran H

2012-01-01

Apoptosis is one of the desired effects of radiation during tumor treatment with radiotherapy. However, cutaneous melanoma cells are highly resistant to this kind of treatment. In order to understand the impact of radiation on melanoma cells apoptosis, the aim of this study was to characterize the radiobiological response of human melanoma cells, and to study whether a correlation between intrinsic radiosensitivity and apoptosis exists. The human melanoma cell lines A375, MELJ and SB2 were gamma-irradiated ( 137 Cs) and their radiosensitivity was evaluated through the α parameter and surviving fraction at 2 Gy (SF2) of a clonogenic assay, adjusted to the Linear-Quadratic (LQ) survival model. MELJ resulted the most radioresistant (α= 0,150±0,034 SF2= 0,71), while A375 and SB2 were the most sensitive (α=0,45±0,028 SF2=0,29 and α=0,41±0,004 SF2=0,21 respectively). Apoptotic process was evaluated at 0, 2, 6, 24 and 48 hs post irradiation at 2 and 4 Gy. Nuclear morphology was analyzed by Hoechst staining, and PARP-1 cleavage by western blot. The three cell lines nucleus with apoptotic morphology were found, being A375 and SB2 percentage of apoptotic nucleus higher than MELJ (p<0.01%). Besides, PARP-1 western blot showed for MEL-J a low presence of the cleaved forms (apoptosis indicator) compared to A375 and SB2 cell lines. Our results indicate that MELJ, the most radioresistant cell line in this study, is the less radiation induced apoptotic, demonstrating a correlation between cellular intrinsic radiosensitivity and apoptosis. Understanding melanoma radioresistance mechanism becomes extremely important in the search of new therapeutic targets that allow cell sensitization to radiotherapy (author)

Economic burden of advanced melanoma in France, Germany and the UK: a retrospective observational study (Melanoma Burden-of-Illness Study).

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Grange, Florent; Mohr, Peter; Harries, Mark; Ehness, Rainer; Benjamin, Laure; Siakpere, Obukohwo; Barth, Janina; Stapelkamp, Ceilidh; Pfersch, Sylvie; McLeod, Lori D; Kaye, James A; Wolowacz, Sorrel; Kontoudis, Ilias

2017-12-01

The aim of this study was to estimate the cost-of-illness associated with completely resected stage IIIB/IIIC melanoma with macroscopic lymph node involvement, overall and by disease phase, in France, Germany and the UK. This retrospective observational study included patients aged older than or equal to 18 years first diagnosed with stage IIIB/IIIC cutaneous melanoma between 1 January 2009 and 31 December 2011. Data were obtained from medical records and a patient survey. Direct costs, indirect costs and patient out-of-pocket expenses were estimated in euros (€) (and British pounds, £) by collecting resource use and multiplying by country-specific unit costs. National annual costs were estimated using national disease prevalence from the European cancer registry and other published data. Forty-nine centres provided data on 558 patients (58.2% aged <65 years, 53.6% stage IIIB disease at diagnosis). The mean follow-up duration was 27 months (France), 26 months (Germany) and 22 months (UK). The mean total direct cost per patient during follow-up was €23 582 in France, €32 058 in Germany and €37 970 (£31 123) in the UK. The largest cost drivers were melanoma drugs [mean €14 004, €21 269, €29 750 (£24 385), respectively] and hospitalization/emergency treatment [mean: €6634, €6950, €3449 (£2827), respectively]. The total mean indirect costs per patient were €129 (France), €4,441 (Germany) and €1712 (£1427) (UK). Estimates for annual national direct cost were €13.1 million (France), €30.2 million (Germany) and €27.8 (£22.8) million (UK). The economic burden of stage IIIB/IIIC melanoma with macroscopic lymph node involvement was substantial in all three countries. Total direct costs were the highest during the period with distant metastasis/terminal illness.

Prolonged ultraviolet light-induced erythema and the cutaneous carcinoma phenotype

International Nuclear Information System (INIS)

Tanenbaum, L.; Parrish, J.A.; Haynes, H.A.; Fitzpatrick, T.B.; Pathak, M.A.

1976-01-01

A considerable amount of evidence exists in support of the role of ultraviolet radiation as a major etiologic factor in human skin cancer, both melanoma and carcinoma types. On the basis of epidemiologic studies a phenotype has been described which helps to identify the persons who are more susceptible to skin cancer. In an attempt to further define this population, patients with cutaneous carcinoma and a normal control group were exposed to artificial ultraviolet light (UVL) and the erythema and tanning responses of each group were measured over a 21-day period. UVL-induced erythema was prolonged in a significantly higher percentage of patients with skin cancer than in control patients, lasting two to three weeks after single exposures to 6 and 8 times the patient's minimal erythema dose. The presence of prolonged erythema correlated with this history of previous skin cancer but did not correlate with other established risk factors for cutaneous carcinoma, i.e., fair skin, light hair and light eyes, easy sunburning and poor tanning, and Celtic ancestry. Prolonged erythema following UVL radiation may therefore represent an additional risk factor and help to identify the skin cancer-susceptible population

Fisetin, a dietary flavonoid, augments the anti-invasive and anti-metastatic potential of sorafenib in melanoma.

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Pal, Harish C; Diamond, Ariana C; Strickland, Leah R; Kappes, John C; Katiyar, Santosh K; Elmets, Craig A; Athar, Mohammad; Afaq, Farrukh

2016-01-12

Melanoma is the most aggressive and deadly form of cutaneous neoplasm due to its propensity to metastasize. Oncogenic BRAF drives sustained activation of the BRAF/MEK/ERK (MAPK) pathway and cooperates with PI3K/AKT/mTOR (PI3K) signaling to induce epithelial to mesenchymal transition (EMT), leading to cell invasion and metastasis. Therefore, targeting these pathways is a promising preventive/therapeutic strategy. We have shown that fisetin, a flavonoid, reduces human melanoma cell invasion by inhibiting EMT. In addition, fisetin inhibited melanoma cell proliferation and tumor growth by downregulating the PI3K pathway. In this investigation, we aimed to determine whether fisetin can potentiate the anti-invasive and anti-metastatic effects of sorafenib in BRAF-mutated melanoma. We found that combination treatment (fisetin + sorafenib) more effectively reduced the migration and invasion of BRAF-mutated melanoma cells both in vitro and in raft cultures compared to individual agents. Combination treatment also effectively inhibited EMT as observed by a decrease in N-cadherin, vimentin and fibronectin and an increase in E-cadherin both in vitro and in xenograft tumors. Furthermore, combination therapy effectively inhibited Snail1, Twist1, Slug and ZEB1 protein expression compared to monotherapy. The expression of MMP-2 and MMP-9 in xenograft tumors was further reduced in combination treatment compared to individual agents. Bioluminescent imaging of athymic mice, intravenously injected with stably transfected CMV-luciferase-ires-puromycin.T2A.EGFP-tagged A375 melanoma cells, demonstrated fewer lung metastases following combination treatment versus monotherapy. Our findings demonstrate that fisetin potentiates the anti-invasive and anti-metastatic effects of sorafenib. Our data suggest that fisetin may be a worthy adjuvant chemotherapy for the management of melanoma.

Treatment efficacy and immune stimulation by AdCD40L gene therapy of spontaneous canine malignant melanoma.

Science.gov (United States)

Westberg, Sara; Sadeghi, Arian; Svensson, Emma; Segall, Thomas; Dimopoulou, Maria; Korsgren, Olle; Hemminki, Akseli; Loskog, Angelica S I; Tötterman, Thomas H; von Euler, Henrik

2013-01-01

Malignant melanoma is a serious disease in both humans and dogs, and the high metastatic potential results in poor prognosis for many patients. Its similarities with human melanoma make spontaneous canine melanoma an excellent model for comparative studies of novel therapies and tumor biology. We report a pilot study of local adenovector CD40L (AdCD40L) immunogene treatment in 19 cases of canine melanoma (14 oral, 4 cutaneous, and 1 conjunctival). Three patients were World Health Organization stage I, 2 were stage II, 10 stage III, and 4 stage IV. One to 6 intratumoral injections of AdCD40L were given every 7 days, followed by cytoreductive surgery in 9 cases and only immunotherapy in 10 cases. Tumor tissue was infiltrated with T and B lymphocytes after treatment, suggesting immune stimulation. The best overall response included 5 complete responses, 8 partial responses, and 4 stable and 2 progressive disease statuses according to the World Health Organization response criteria. Median survival was 160 days (range, 20-1141 d), with 3 dogs still alive at submission. Our results suggest that local AdCD40L therapy is safe and could have beneficial effects in dogs, supporting further treatment development. Clinical translation to human patients is in progress.

An Unusual Case of Metastatic Malignant Melanoma Presenting as Pseudomesothelioma with Intense Diffuse Pleural FDG Uptake Demonstrated on FDG PET/CT

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Rosamma Bency

2015-06-01

Full Text Available A 75-year-old male, non-smoker with history of asbestos exposure, and excision of 2 mm Clark IV cutaneous malignant melanoma 15 months earlier, presented with rapidly progressive dyspnea, left pleuritic chest pain, and weight loss. CT Pulmonary Angiography (CTPA demonstrated bilateral pulmonary emboli and findings suspicious of mesothelioma. There was no evidence of infection or malignancy in the hemorrhagic pleural fluid aspirate. FDG PET-CT revealed extensive intense FDG uptake throughout the pleura of left hemi-thorax, bilateral hilar and mediastinal lymph nodes, bilateral adrenals and left gluteal musculature. Subsequent pleural biopsy was consistent with metastatic melanoma. The patient was referred for palliative therapy but died 10 days later

Gene Therapy for Advanced Melanoma: Selective Targeting and Therapeutic Nucleic Acids

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Joana R. Viola

2013-01-01

Full Text Available Despite recent advances, the treatment of malignant melanoma still results in the relapse of the disease, and second line treatment mostly fails due to the occurrence of resistance. A wide range of mutations are known to prevent effective treatment with chemotherapeutic drugs. Hence, approaches with biopharmaceuticals including proteins, like antibodies or cytokines, are applied. As an alternative, regimens with therapeutically active nucleic acids offer the possibility for highly selective cancer treatment whilst avoiding unwanted and toxic side effects. This paper gives a brief introduction into the mechanism of this devastating disease, discusses the shortcoming of current therapy approaches, and pinpoints anchor points which could be harnessed for therapeutic intervention with nucleic acids. We bring the delivery of nucleic acid nanopharmaceutics into perspective as a novel antimelanoma therapeutic approach and discuss the possibilities for melanoma specific targeting. The latest reports on preclinical and already clinical application of nucleic acids in melanoma are discussed.

Comparative transforming potential of different human papillomaviruses associated with non-melanoma skin cancer

International Nuclear Information System (INIS)

Massimi, Paola; Thomas, Miranda; Bouvard, Veronique; Ruberto, Irene; Campo, M. Saveria; Tommasino, Massimo; Banks, Lawrence

2008-01-01

It is well established that high-risk human papillomaviruses (HPVs) that infect mucosal epithelia are the causative agents of cervical cancer. In contrast, the association of cutaneo-tropic HPV types with the development of non-melanoma skin cancer (NMSC) is less well defined. In this study, we have analysed the in vitro transforming potential of various cutaneous HPV types. Using oncogene cooperation assays with activated ras, we have shown that diverse cutaneous types, including 12, 14, 15, 24, 36 and 49, have significant transforming potential. Interestingly, most of this activity appears to be encoded by the E6 gene product. In contrast, the common HPV-10 exhibits no significant transforming potential in these assays. This difference may be a reflection of different patterns of cellular localization, with transforming E6s being nuclear and non-transforming being cytoplasmic. These results provide molecular support for a role of these viruses in the development of certain human malignancies

Taking aim at cancer with monoclonal antibodies

International Nuclear Information System (INIS)

Klausner, A.

1986-01-01

Conjugating radioisotopes to monoclonal antibodies could have certain advantages in cancer therapy. Radioactive compounds have the double-edged ability to kill cells that are up to centimeter or more away. This is a plausible way to overcome tumor heterogeneity, but it also means that normal cells near the tumor could be affected. Hybritech (San Diego, CA) has been supplying antibody linked to the radioisotope yttrium-90 for a number of clinical trials. Work at Johns Hopkins University (Baltimore, MD) has focused on polyclonal antibodies to hepatoma. Monoclonal antibodies will be used there soon, and trials could be expanded eventually to include breast, lung, and prostate cancer as well. Hybritech also expects that the yttrium-antibody conjugates developed with NCI will enter the clinic later this year for treating leukemia and lymphoma systems; treatments for melanomas should follow

Tumor localization of 131I-labeled antibodies by radionuclide imaging

International Nuclear Information System (INIS)

Ghose, T.; Tai, J.; Aquino, J.; Guclu, A.; Norvell, S.; MacDondald, A.

1975-01-01

Intravenous injections of 131 I-labeled anti-EL4 lymphoma antibodies showed progressive localization of radioactivity in EL4 transplants but not in B16 melanoma in mice carrying both tumors. Normal rabbit globulin labeled with 131 I did not localize in either tumor and cleared more slowly from the internal organs. Metastatic localization of intravenous 131 I-labeled anti-tumor antibodies was also observed in two cancer patients. (U.S.)

Value of sentinel lymph node biopsy and adjuvant interferon treatment in thick (>4 mm) cutaneous melanoma: an observational study.

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Morera-Sendra, Natalia; Tejera-Vaquerizo, Antonio; Traves, Víctor; Requena, Celia; Bolumar, Isidro; Pla, Angel; Vázquez, Carlos; Soriano, Virtudes; Nagore, Eduardo

2016-01-01

The role of sentinel lymph node biopsy and the benefit of immunotherapy with interferon in thick (>4 mm) melanomas remain uncertain. Our aim was to assess the value of both sentinel lymph node (SLN) biopsy and immunotherapy in the prognosis of thick melanomas. A retrospective study based on a computerized patient database in which patients have been prospectively collected since 2005 was performed. Age, sex, location, Breslow thickness, tumor ulceration, regression, Clark level, tumor infiltrating lymphocytes, tumor mitotic rate, microscopic satellite and vascular invasion were included in the analysis. Disease-free (DFS), disease-specific (DSS) and overall (OS) survivals were evaluated by the Kaplan-Meier method and Cox regression analysis. A series of 141 patients with melanomas thicker than 4 mm were included. Multivariate regression showed a worse prognosis in SLN-positive patients with respect to SLN biopsy-negative patients (DFS, hazard ratio [HR] 2, p = 0.04; DSS, HR 2.2, p = 0.002; OS, HR 2.4, p = 0.02). The observational group was shown to have a worse prognosis than the SLN-positive group but was very similar to the clinically positive group. Immunotherapy with high-dose interferon showed a protective effect (DFS, HR 0.5, p = 0.02; DSS, HR 0.3, p = 0.001; OS, HR 0.3, p = 0.001). Our data indicate that SLN biopsy and adjuvant interferon should be considered for patients with thick melanomas.

Combinations of Radiation Therapy and Immunotherapy for Melanoma: A Review of Clinical Outcomes

International Nuclear Information System (INIS)

Barker, Christopher A.; Postow, Michael A.

2014-01-01

Radiation therapy has long played a role in the management of melanoma. Recent advances have also demonstrated the efficacy of immunotherapy in the treatment of melanoma. Preclinical data suggest a biologic interaction between radiation therapy and immunotherapy. Several clinical studies corroborate these findings. This review will summarize the outcomes of studies reporting on patients with melanoma treated with a combination of radiation therapy and immunotherapy. Vaccine therapies often use irradiated melanoma cells, and may be enhanced by radiation therapy. The cytokines interferon-α and interleukin-2 have been combined with radiation therapy in several small studies, with some evidence suggesting increased toxicity and/or efficacy. Ipilimumab, a monoclonal antibody which blocks cytotoxic T-lymphocyte antigen-4, has been combined with radiation therapy in several notable case studies and series. Finally, pilot studies of adoptive cell transfer have suggested that radiation therapy may improve the efficacy of treatment. The review will demonstrate that the combination of radiation therapy and immunotherapy has been reported in several notable case studies, series and clinical trials. These clinical results suggest interaction and the need for further study