Anatomic Pathology: Gynecologic Pathology

• Melanoma of the vulva is the second most common vulvar malignancy. However, it represents less than 1% of all melanomas. In women, melanoma of the vulva accounts for 1% to 2.3% of all melanomas. The overall prognosis is poor with 5-year survival ranging from 35% to 50%.

• Melanoma of the vulva tends to be a disease of elderly women, with diagnosis most common in the seventh and eighth decades. The lesions tend to be diagnosed at an advanced stage, contributing to the documented poor prognosis of the lesion.

• Lymph node status is the strongest predictor of survival for melanoma of the vulva and of vulvar cancer in general. Lymph node metastasis is a predictor of shortened survival. Sentinel lymph node biopsy is being used in some centers to assess lymph node involvement. In patients with positive sentinel lymph nodes, lymphadenectomy is performed in an attempt to improve survival.

• Melanomas may be completely amelanotic or contain little melanin pigment. This diagnostic dilemma can be solved in most cases with an immunohistochemical panel that includes S-100, MelanA, HMB-45, keratin, and CD45. Most melanomas stain positively for S-100, MelanA, and HMB-45 and stain negatively for CD45 and keratin. Desmoplastic melanomas are often negative for HMB-45, so the three markers should be used together for an optimal diagnostic result. Melanocytic lesions also stain positively for tyrosinase.

• Differential diagnoses for melanoma include dysplastic nevi and Spitz nevi, which also can occur on the vulva. These lesions can be immensely difficult to distinguish from melanoma in many cases. Histologic features that aid in the diagnosis of melanoma versus nevi include lesion asymmetry (best appreciated on a resection specimen); mitotic activity, especially atypical mitoses; lack of maturation of the lesional cells; and cytologic atypia.