A clinicopathological review of 33 patients with vulvar melanoma identifies c-KIT as a prognostic marker

Abstract

Vulvar melanoma is the second most common vulvar cancer. Patients with vulvar melanoma usually present with the disease at a late stage and have a poor prognosis. The prognostic predictors reported in the literature are not unequivocal and the role of lichen sclerosus and c-KIT mutations in the aetiology of vulvar melanoma is unclear. Breslow staging currently seems to be the most adequate predictor of prognosis. We thus performed a clinicopathological and literature review to identify suitable predictors of prognosis and survival and investigated the expression of c-KIT (by immunohistochemistry) in patients with vulvar melanoma (n=33) from the Gynaecological Cancer Centres of the Royal Hospital for Women (Sydney, Australia) and John Hunter Hospital (Newcastle, Australia). Our series of 33 patients fitted the expected clinical profile of older women: delayed presentation, high stage, limited response to treatment and poor prognosis. We identified 3 patients (9.1%) with lichen sclerosus associated with melanoma in situ, although no lichen sclerosus was found in the areas of invasive melanoma. No patient had vulvar nevi. We identified a) Breslow's depth, b) an absence of any of the pathological risk factors, such as satellitosis, in-transit metastasis, lymphovascular space invasion (LVSI) and dermal mitosis, c) removal of inguino-femoral lymph nodes, d) lateral margin of >1 cm, and e) c-KIT expression as valuable prognostic predictors for disease-free survival. We conclude that c-KIT expression is, apart from Breslow's depth, another valuable predictor of prognosis and survival. Lichen sclerosus may be associated with vulvar melanoma.

Figure 1

(A) Spindle cell melanoma (arrow) with fibrosis adjacent to the melanoma. (B) Next to the invasive melanoma, there is melanoma in situ (arrow) associated with fibrosis. (C) Further away from the melanoma, there is melanoma in situ (arrow) and lichen sclerosus with characteristic dermal hyalinisation of lichen sclerosus.

Figure 2

Scattered large atypical melanocytes without melanocytic proliferation observed at the periphery of a vulvar melanoma.

Figure 3

Strong c-KIT expression in invasive melanoma of the vulva.

Figure 4

Kaplan-Meier survival curves for relapse-free survival over a specific time frame (months) for patients (A) who had lymphadenectomy performed (x) versus the ones who had not (o); and (B) for patients whose tumours expressed strong c-KIT expression (o) versus those whose tumours did not (x).

Figure 5

Kaplan-Meier survival curves for disease-free survival over a specific time frame (months) for patients (A) with epithelioid or mixed epithelioid tumours (o) or other histotypes (x); and (B) which expressed at least one of the following suspicious pathological features: satellitosis, in-transit metastases, lymphovascular space invasion (LVSI) or dermal mitosis (x) versus the patients which did not (o).