Carcinoma of the vulva represents about 3% of all female genital tract cancers, occurring mostly in women older than age 60. Approximately 90% of carcinomas are squamous cell carcinomas; most of the other tumors are adenocarcinomas or basal cell carcinomas.
There appear to be two distinct forms of vulvar squamous cell carcinomas that differ in pathogenesis and course. The less common form is related to high-risk HPV strains (especially HPV type 16) and occurs in middle-aged women, particularly cigarette smokers. This form is often preceded by precancerous changes in the epithelium termed vulvar intraepithelial neoplasia (VIN). VIN progresses in many patients to greater degrees of atypia and eventually to carcinoma in situ; however, progression to invasive carcinoma is not inevitable and may occur only after many years. Environmental factors such as cigarette smoking and immunodeficiency appear to increase the risk of such progression.
A second form of squamous carcinoma occurs in older women, sometimes following a long history of reactive epithelial changes, principally lichen sclerosus. It is preceded by a subtle lesion, differentiated vulvar intraepithelial neoplasia (dVIN), characterized by cytologic atypia confined to the basal layer and abnormal keratinization. If left untreated it may give rise to HPV negative, well-differentiated, keratinizing squamous cell carcinoma.
MORPHOLOGYVINandearlyvulvarcarcinomascommonlymanifestasareasofleukoplakia.Inaboutone-fourthofthecases,thelesionsarepigmentedowingtothepresenceofmelanin.Withtime,theseareasaretransformedintoovertexophyticorulcerativeendophytictumors.HPV-positivetumorsareoftenmultifocalandwartyandtendtobepoorlydifferentiatedsquamouscellcarcinomas,whereasHPV-negativetumorsusuallyareunifocalandtypicallyarewell-differentiatedkeratinizingsquamouscellcarcinomas.
Both forms of vulvar carcinoma tend to remain confined to their site of origin for a few years but ultimately invade and spread, usually first to regional lymph nodes. The risk of metastasis correlates with the depth of invasion. As with most carcinomas, outcome is dependent on tumor stage. The overall 5-year survival is 70% to 93% for patients with negative lymph nodes but decreases to 25% to 41% for patients with lymph node metastases.
Paget disease is an intraepidermal proliferation of epithelial cells that can occur in the skin of the vulva or nipple of the breast (described later). However, unlike in the breast, where Paget disease is virtually always associated with an underlying carcinoma, only a minority of cases of vulvar (extramammary) Paget disease have an underlying tumor. Instead, vulvar Paget cells most commonly appear to arise from epidermal progenitor cells.
Paget disease manifests as a red, scaly, crusted plaque that may mimic the appearance of an inflammatory dermatitis. On histologic examination, large cells with abundant pale, finely granular cytoplasm and occasional cytoplasmic vacuoles infiltrate the epidermis, singly and in groups (
Fig. 19.3 ). The presence of mucin, as detected by periodic acid–Schiff (PAS) staining, is useful in distinguishing Paget disease from vulvar melanoma, which lacks mucin.
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Fig.19.3Pagetdiseaseofthevulva.Largetumorcellswithpale-pinkcyto-plasmareseeninfiltratingtheepidermis.Chronicinflammatorycellsarepresentintheunderlyingdermis.