Vulvar Melanoma: Molecular Characteristics, Diagnosis, Surgical Management, and Medical Treatment

Abstract

Ten percent of all women have pigmented vulvar lesions. Fortunately, most of these are benign but 1% of all melanomas in women affect the vulva. While the mortality rate of cutaneous melanoma has dropped by 7% annually during the last 5 years, the prognosis of vulvar melanoma remains dismal: the 5-year overall survival rate is 47% compared with 92% for cutaneous melanoma. The current evidence suggests that this likely results from a combination of delayed diagnosis and different tumor biology, treatment strategies, and treatment response. Although many landmark trials on checkpoint inhibitors included mucosal and vulvar melanomas, the results were often not reported separately. Post-hoc analyses indicate overall response rates between 19 and 37% for checkpoint inhibitors. A recently published retrospective study on vulvar melanomas suggests an objective response in 33.3% with a similar safety profile to cutaneous melanoma. Tyrosine kinase inhibitors may be considered in recurrent disease if a c-KIT mutation is present.

Fig. 1

A–C Summary of the frequencies of c-KIT, NRAS, and BRAF mutations from previously published studies that reported details on vulvar melanomas. The affected exons are highlighted in blue, red, and green and the corresponding mutations are shown in different gradations of blue, red, and green. A In c-KIT, 66.7% of the mutations were located on exon 11, 19.0% on exon 13, 11.9% on exon 17, and 2.4% on exon 9. B In NRAS, 64.3% of the mutations were located on exon 2 and 35.7% on exon 3. C In BRAF, 88.9% were located on exon 15 and 11.1% on exon 14

Fig. 2

Disease-specific survival (DSS) [A] and overall survival (OS) [B] of primary malignant melanoma of the vulva by American Joint Committee on Cancer (AJCC) stages derived from the Surveillance, Epidemiology and End Results-18 population between 2000 and 2017 (November 2019 submission) of the National Cancer Institute [135]. In the lower part of the figure, the DSS and OS rates by year are shown for AJCC stages I–IV and all stages combined

Fig. 3

Characteristic dermoscopy features of malignant melanomas of the vulva

Fig. 4

A–F Key steps in the surgical management of vulvar melanoma. The sentinel technique is now considered standard of care in the management of vulvar cancer and melanoma in women with clinically negative lymph nodes. Radiocolloid tracers, methylene blue dye, indocyanine green, or a combination of these can be used to locate the sentinel node in vulvar melanoma (A). Radiocolloid tracers facilitate the localization of the sentinel node using a gamma probe and a small incision is made at the region of the located sentinel node (B). The anatomical landmarks of the femoral triangle are the inguinal ligament, the adductor longus muscle, and the sartorius muscle. The sentinel node can be visualized if methylene blue or indocyanine green have been used and confirmed with a gamma probe if radiocolloid tracers have been injected (C). If possible, a local wide excision is usually preferred over more radical procedures. The suggested surgical margin depends on the depth of invasion, i.e. Breslow’s thickness of the primary tumor (D). The specimen should be marked for further pathologic work-up in the anatomically correct orientation in case a re-resection due to R1 status is necessary (E). The wound should be closed in layers to reduce the risk of hematoma formation. The top layer is often closed using single mattress sutures to reduce the risk of wound breakdown (F).