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.

KIT mutations and CD 117 overexpression are markers of better progression‐free survival in vulvar melanomas

“…Nevertheless, CD117 overexpression (which was significantly associated with KIT mutation) retained its significance as a marker for improved PFS in multivariate analysis. Whereas KIT expression has been proposed as a marker of poor disease‐free survival in one series, another study found no association between KIT expression or mutational status with OS . Variabilities of antibodies and staining methods might account for these differences.…”

Nonoverlapping Clinical and Mutational Patterns in Melanomas from the Female Genital Tract and Atypical Genital Nevi

“…Studies targeting BRAF , NRAS and KIT have shown that vulvovaginal melanomas, in contrast to conventional cutaneous melanomas, typically harbor wild-type BRAF , while KIT and NRAS mutations are present in approximately 20% of cases (Heinzelmann-Schwarz et al , 2014, Tseng et al , 2014, van Engen-van Grunsven et al , 2014). Conversely, separate studies analyzing the same genes in AGN have shown frequent BRAF mutations, particularly V600E (Nguyen et al , 2010).…”

Cancer of the vulva

“…In line with trends toward more conservative surgery for cutaneous melanomas, there is a trend toward more conservative resection of vulvar melanomas [57–59]. Primary lesions should be treated by radical local excision, with margins around the lesion of at least 1 cm.…”