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BACKGROUND Optimal treatments for vulvar and vaginal melanomas (VVMs) have not been identified. Herein, the authors compare molecular profiles between VVM and nongynecologic melanoma (NGM) subtypes with the objective of identifying novel, targetable biomarkers. METHODS In total, 2304 samples of malignant melanoma that were submitted to Caris Life Sciences between 2009 and 2015 were reviewed. In situ hybridization and immunohistochemistry were used to assess copy numbers and protein expression of selected genes. Sequenced variants were analyzed using a proprietary cancer panel. RESULTS In total, 51 VVMs (14 vaginal and 37 vulvar melanomas) were compared with 2253 malignant NGMs, including 2127 cutaneous, 105 mucosal, and 21 acral melanomas. In VVMs, B-Raf proto-oncogene serine/threonine kinase (BRAF) was the most frequently mutated gene (26%) compared with 8.3% of mucosal NGMs (P = .008). In BRAF-mutated tumors, fewer VVMs (50%), compared with NGMs (82.1%), had a variant within the valine codon 600 (V600) domain. The KIT mutation rate was highest in VVMs (22%) compared with 3% in cutaneous (P

BACKGROUND. This study reviews the case-mix characteristics, management, and outcomes of melanoma cases occuring in the U. S. within the last decade. METHODS. Analyses of the National Cancer Data Base (NCDB) were performed on cases diagnosed between 1985 through 1994. A total of 84,836 cases comprised of cutaneous and noncutaneous melanomas were evaluated. RESULTS. The percentages of melanomas that were cutaneous, ocular, mucosal, and unknown primaries were 91.2%, 5.2%, 1.3%, and 2.2%, respectively. For cutaneous melanomas, the proportion of patients presenting with American Joint Committee on Cancer Stages 0, I, II, III, and IV were 14.9%, 47.7%, 23.1%, 8.9%, and 5.3%, respectively. Factors associated with decreased survival included more advanced stage at diagnosis, nodular or acral lentiginous histology, increased age, male gender, nonwhite race, and lower income. Multivariate analysis identified stage, histology, gender, age, and income as independent prognostic factors. For ocular melanomas, 85.0% were uveal, 4.8% were conjunctival, and 10.2% occurred at other sites. During the study period, there was a large increase in the proportion of ocular melanoma patients treated with radiation therapy alone. For mucosal melanomas, the distribution of head and neck, female genital tract, anal/rectal, and urinary tract sites was 55.4%, 18.0%, 23.8%, and 2.8%, respectively. Patients with lymph node involvement had a poor prognosis. For unknown primary melanomas, the distribution of metastases as localized to a region or multiple sites at presentation was 43.0% and 57.0%, respectively. Surgical treatment of patients with unknown primary site of the melanoma resulted in better survival compared with no treatment. CONCLUSIONS. Treatment of early stage cutaneous melanoma resulted in excellent patient outcomes. In addition to conventional prognostic factors, socioeconomic factors were found to be associated with survival. Cancer 1998;83:1664 ‐78. © 1998 American Cancer Society.

Background. Malignant melanomas of the vulva and vagina are rare tumors located in areas of the body not exposed to ultraviolet radiation. Investigations comprising large consecutive population-based series of patients with these diseases have not been published previously, to the knowledge of the authors. Methods. Trends in incidence, age distribution, and prognosis were investigated among 219 consecutive cases of malignant melanoma of the vulva and 26 cases in the vagina, reported to the Swedish National Cancer Registry and representing virtually all primary tumors of that kind in Sweden during a 25-year period, 1960–1984. Results. On average, 75% of the patients with vulvar melanoma and 73% with vaginal melanoma were older than 60 years of age. The mean age increased slightly but not significantly during the period. The age-standardized incidence of vulvar melanoma decreased from 0.27 to 0.14 per 100,000 Swedish women, or by 3% per year. The observed 5-year survival rate of patients with vulvar melanoma was 35%, and the relative survival rate was 47%. The observed and relative survival rates at 10 years were 23% and 44%, respectively. Observed and relative survival rates among patients with vaginal melanoma after 5 years were 13% and 18%, respectively. Conclusions. Accordingly, there was a decreasing incidence of vulvar and vaginal melanoma over the observed 25 years. This is in contrast to the trends in incidence for cutaneous melanomas in Sweden, which, during the same time period, increased almost 6% per year.

Between 1964 and 1987 ten patients with vaginal melanoma were treated at The University of Michigan Hospital. Five of the six patients who underwent radical surgery had adequate information concerning the first site of relapse, and in four of these five, pelvic sites or locoregional lymph nodes were the first sites of recurrent disease. One of these patients developed a 17-cm pelvic recurrence, which responded with a 75% reduction in size 3 months after completion of radiotherapy given in high individual fractions (400 cGy X 11). Three patients were managed with local resection, and all developed recurrent locoregional disease. One patient presented with metastatic disease. We conclude that locoregional control of vaginal melanoma is difficult to achieve with surgery alone. We hypothesize that preoperative radiotherapy to the pelvis (500 cGy X 6 given 3 days a week to the whole pelvis with subsequent consideration for a vaginal boost field) may improve the poor rate of locoregional control of vaginal melanoma that is seen when surgery alone is used.