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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. The objective of this study was to evaluate the author's recent, preliminary experience with the sentinel lymph node procedure in patient with vulvar melanoma and to compare this experience with treatment and follow-up of patients with vulvar melanomas who were treated previously at their institution. METHODS. From 1997, sentinel lymph node procedure with the combined technique ((99m)Technetium-labeled nanocolloid and Patente Blue-V was performed as a standard staging procedure for patients with vulvar melanoma with a thickness > 1 mm and no clinically suspicious inguinofemoral lymph nodes. For the current study, clinicopathologic data from all 33 patients with vulvar melanoma who were treated between 1978 and 2000 at the University Hospital Groningen were reviewed and analyzed. RESULTS. From January 1997 until December 2000, identification of sentinel lymph nodes was successful in all nine patients who were referred for treatment of vulvar melanoma. Three patients underwent subsequent complete inguinofemoral oral lymphadenectomy because of metastatic sentinel lymph nodes. In follow-up, groin recurrences (in-transit metastases) occurred in two of nine patients, both 12 months after primary treatment. Both patients had melanomas with a thickness > 4 mm and previously had negative sentinel lymph nodes. There was a trend toward more frequent groin recurrences in patients after undergoing the sentinel lymph node procedure (2 of 9 patients) compared with 24 historic control patients (0 of 24 patients; P = 0.06). Five of 33 patients developed local recurrences: Two patients had groin recurrences, and 11 patients developed distant metastases. Twelve patients died of vulvar melanoma. Seventeen patients with a median follow-up of 66 months (range, 9-123 months) are currently alive (overall survival rate, 52%). CONCLUSIONS. Although the numbers were small, this study showed that the sentinel lymph node procedure is capable of identifying patients who have occult lymph node metastases and who may benefit from lymphadenectomy for locoregional control and prevention of distant metastases. However, the data also suggest that the sentinel lymph node procedure may increase the risk of locoregional recurrences (in-transit metastases), especially in patients with thick melanomas. The potential role of the sentinel lymph node procedure as an alternative method of lymph node staging in patients with vulvar melanoma needs further investigation only within the protection of clinical trials and probably should be restricted to patients with melanomas with intermediate thickness (1-4 min). (C) 2002 American Cancer Society.

Background In an epidemiologic study of 219 Swedish females with vulvar melanoma, the authors previously established the incidence of this disease as 0.19 per 100,000 women, with a 3% annual decrease from 1960 to 1984 and a 5-year relative survival rate of 47%. After reviewing the medical histories of all of the 219 patients, the authors documented their precise clinical and histopathologic features, which, along with treatment, are assessed herein as predictors of survival. Methods Of 219 consecutive cases of vulvar melanoma collected from the Swedish National Cancer Registry, 21 were excluded because of inadequate data. Clinical and histopathologic materials from the remaining 198 cases were then reexamined. With a clinical three-stage system, lesion types and treatment modalities were assessed as survival factors in univariate and multivariate analyses. Results In univariate analysis, significant predictors of survival for patients at Stage I were tumor thickness, ulceration, number of mitoses, macroscopic amelanosis, preexisting nevi, extent of tumor invasion (lateral labia majora), and patient age. The mode of treatment was not significant. In multivariate analysis, staging (Stage I vs. II and III) and tumor thickness were independent predictors of survival. For Stage I only, tumor thickness, ulceration, and clinical amelanosis independently predicted survival time. Conclusions To the authors' knowledge, this is the largest series of patients with vulvar melanoma ever reviewed, and an ethnically homogeneous and nationwide female population is represented. In this series, clinical stage, macroscopic amelanosis, and tumor characteristics such as tumor thickness and ulceration, rather than treatment mode, were the best factors for predicting the outcome of these patients.

BACKGROUND Because the clinical and histopathologic features of vulvar melanoma had not been characterized completely in a large, homogeneous population, the authors retrospectively analyzed all such patients recorded in Sweden during a 25-year period. METHODS The Swedish National Cancer Registry opened its records to the authors for review of all 219 females with primary vulvar melanoma reported from 1960 to 1984. Histopathologic specimens and clinical histories of the 198 patients who qualified for this study were reanalyzed and the tumors rigorously subtyped. RESULTS Macroscopically amelanotic tumors were observed in 27% of patients, predominantly in glabrous skin; the clitoral area and labia majora were the most common primary sites. Of all melanomas, 46% emerged in glabrous skin, 12% emerged in hairy skin, and 35% extended to both areas. On average, approximately 2.5 times more melanomas appeared in the vulva than on the whole body surface. Overall, 57% were of the mucosal lentiginous (MLM) type, 22% were nodular melanomas (NMs), 12% were unclassified, and only 4% were superficial spreading melanomas (SSMs); this was the reverse of the order observed for cutaneous melanoma. Almost all vulvar melanomas underwent a vertical growth phase; other common features were marked thickness and ulceration, particularly in the glabrous skin. Preexisting nevi occurred in 11 cases, all in hairy skin, and 71% in conjunction with SSM but only 4% with MLM. CONCLUSIONS Several clinical and histopathologic features indicated that the natural history of vulvar melanomas is at variance with that of cutaneous melanomas. Because preexisting nevi, which are often considered a precursor to melanoma, were significantly linked to SSM and only in the vulvar hairy skin, melanomas in the glabrous skin apparently emerged de novo. Cancer 1999;86:1273–84. © 1999 American Cancer Society.

BACKGROUND Rates of melanoma have increased worldwide over the last few decades. Currently, this rate of increase is greater for melanoma than for any other cancer in the U.S. Approximately 3% of all melanomas diagnosed in women are located within the genital tract, predominantly affecting the vulva. Overall, melanomas of the vulva account for 2–10% of all malignancies of the female external genitalia. Due to the rarity of this disease, treatment recommendations do not exist. METHODS This retrospective study was designed to evaluate the significance of clinical and pathologic features for survival among 89 patients examined for malignant melanoma at 5 hospitals in Germany from 1978 to 1991. A complete workup based on age, initial symptoms, tumor localization, presence of ulceration, postoperative stage, surgical procedure, and survival, was performed. RESULTS The overall 5-year survival rate of 36.7% confirms the poor prognosis of this disease. Definitive treatment concepts require a standardized treatment of patients with malignant melanoma of the vulva; however, because of the rarity of vulvar melanomas, prospective studies are difficult to perform. CONCLUSIONS Parameters such as age, Breslow's thickness of invasion, Clark's level of invasion, lymph node involvement, anatomic site, and postoperative stage are prognostic factors for survival. Surgery should be performed in accordance with the accepted standards for cutaneous melanoma. Cancer 1996;78:2353-8.

Background. To the authors' knowledge, the potential prognostic value of DNA ploidy in vulvar melanoma has not been evaluated in previous series. Methods. Clinical data and follow-up information were retrieved from the hospital records of 75 patients treated from 1956 to 1987. Histopathologic specimens were reviewed for histologic type, depth of invasion, vessel invasion, and ulceration. Flow cytometric DNA measurements were performed on paraffin embedded samples. Results. Forty-three patients had International Federation of Gynecology and Obstetrics Stage I disease, 14 Stage II, 8 Stage III and 10 Stage IV. Sixty-five patients were treated by surgery, six by radiotherapy, and four patients with advanced disease received no therapy. The surgical procedure was local excision in 17 patients, vulvectomy in 22, and radical vulvectomy with inguinal lymph node dissection in 26. Five- and 10-year corrected survival rates were 46% and 37%, respectively. Recurrences were seen in 43 (66%) of the patients treated by surgery. Independent prognostic factors for corrected survival in the entire group of 75 patients were inguinal lymph node metastases (P = 0.016), angioinvasion (P = 0.027), tumor localization to clitoris, and multifocal tumors (P = 0.043). For the 65 patients treated by surgery, independent prognostic factors for disease free survival were angioinvasion (P < 0.001), age at diagnosis (P = 0.003), DNA ploidy (P = 0.004), and ulceration (P = 0.027). The independent prognostic factors for long term survival were tumor localization to clitoris (P = 0.018), DNA ploidy (P = 0.045), and inguinal lymph node involvement (P = 0.053). Radical surgery did not improve disease free or long term survival. Conclusions. DNA ploidy is an independent factor that predicts prognosis in patients with vulvar melanoma, and should be considered together with previously known factors. Radical surgery does not improve prognosis and is not recommended when the inguinal lymph nodes are clinically negative.

Background Beginning in 1983, the Gynecologic Oncology Group (GOG) conducted a prospective clinicopathologic study of primary malignant melanoma of the vulva. The objectives of this study were to determine the relationship of histopathologic parameters and microstaging to the International Federation of Gynaecology and Obstetrics (FIGO) staging and prognosis. Methods All patients with primary untreated malignant melanoma of the vulva and no history of previous or subsequent other primary invasive malignancy were eligible for study entry. All patients were required to have modified radical hemivulvectomy as minimal therapy. Groin dissection was optional. Histopathologic specimens were reviewed for capillary space involvement, Clark's level, Breslow's depth of invasion, cell type, and melanin distribution. Patient characteristics were analyzed in their relationship to groin node status and recurrence-free interval. Results Between 1983 and 1990, 81 patients were entered in the study. Of these, 71 were evaluable. Thirty-four patients underwent radical hemivulvectomy, and 37 patients underwent radical vulvectomy. In addition, 56 patients underwent groin node dissection. The factors that were independently correlated with groin node status were: capillary lymphatic space involvement (p = 0.0001) and central primary tumor location (i.e., bilateral/clitoral/T3) (P = 0.003). The other factors that were significant--clinical tumor size, vulvar staging (FIGO), GOG performance status, and Breslow's depth of invasion--were not independent predictors of positive nodes. The factor with the highest significant correlation with recurrence-free interval was the 1992 staging system of the American Joint Committee on Cancer (AJCC) for malignant melanoma of the skin. Using multiple regression, AJCC stage was the only independent prognostic factor. In the absence of AJCC stage, Breslow's depth of invasion was the most prognostic. Conclusion The biologic behavior of vulvar melanoma is similar to other nongenital cutaneous malignant melanoma.

Background. Melanoma of the vulva has traditionally been treated with radical vulvectomy and bilateral inguinofemoral lymphadenectomy. Cutaneous nonvulvar melanoma has been successfully treated with local excision with selective therapeutic regional node dissection. Methods. A retrospective analysis of 16 patients with primary malignant melanoma of the vulva who underwent surgery from 1973 to 1988 at Indiana University Hospital was conducted. The purpose of this analysis was to determine if less radical surgery, such as that performed for cutaneous nonvulvar melanoma, might be adopted for patients with vulvar melanoma without compromising 5-year survival results. Results. Surgical therapy included radical vulvectomy with bilateral inguinofemoral lymphadenectomy (n = 11), radical vulvectomy alone (n = 1), and wide local excision (n = 4). Treated International Federation of Gynecology and Obstetrics (1971) stages included I (n = 12), II (n = 3), and III (n = 1). The median age of the patients was 59 years (range, 29–79 years). The median depth of invasion according to the Breslow method was 3 mm (range, 0.1–8 mm). Patients were observed for a median of 24 months (range, 3–143 months). The Kaplan-Meier 5-year survival estimate was 30%. There were nine recurrences: five distant, one central, one nodal, and two mixed. A median depth of 0.9 mm (range, 0.1–1.75 mm) was noted in those who remained disease-free versus 4.6 mm (range, 3–8 mm) in those who experienced a recurrence (P < 0.01). None of the patients with lesion depths of 1.75 mm or smaller experienced a recurrence, whereas all of those with lesion depths larger than 1.75 mm suffered a recurrence (P = 0.0004). Conclusions. Patients with lesion depths of 1.75 mm or smaller may be treated with wide local excision. Patients with greater lesion depths are at high risk for the development of distant metastases. The patients with well-lateralized lesions may be equally well served with a less morbid procedure deferring therapeutic node dissection until there is a regional recurrence. Cancer 1993; 72:143–6.

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.

A spindle cell melanoma of the clitoris was associated with a large area of lentiginous melanocytic dysplasia in the vulva of a 51-year-old woman. There was extensive neoplastic infiltration of the dermis, a desmoplastic reaction, and replacement of perineurial and Schwann cells by tumor cells (neurotropism). The superficial dysplastic components were pigmented, but melanosomes were not identified in a lymph node metastasis. Here the internuclear areas strongly resembled neuropil. Vulvar melanoma is rare, and this is the first report of neurotropic melanoma in this site.