Precancerous Lesions of the Vulva: Classification, Histology and Molecular Pathology - an Update

Vulvar carcinoma is a rare malignant tumor with an incidence 3-5 % of all malignancies the female genital tract. It can also be preceded by precancerous lesions, termed vulvar intraepithelial neoplasias (VIN). The most recent WHO classification for these neoplasms favors the traditional 3-grade system of VIN 1-3, similar to the CIN concept for the cervix uteri. However, on the basis of clinical, histopathological and molecular data, the International Society for the Study of Vulvovaginal Disease (ISSVD) has proposed only a single classification. Thus, the ISSVD system would eliminate VIN 1 and combine VIN 2 and 3 into a single grade (VIN), on the grounds that VIN 1 has not been shown to be a reproducible diagnosis and VIN 2 and 3 cannot be reliably separated. Two types of VIN have been defined, based on the morphology and pathogenesis of the lesion: the common type is characterized by a strong association to high risk HPV infection, occurrence at a younger age, and multifocality, and is mostly associated with non-keratinizing squamous cell carcinoma. The differentiated (or simplex) type is rare and is associated with an older age and p53-alterations; it is typically diagnosed coincidentally with keratinizing squamous cell carcinoma. Vulvar Paget's disease is an uncommon, minimally invasive lesion that accounts for 2.5 % of all vulvar malignancies, affecting older patients. It has been hypothesized that Paget's cells derive from undifferentiated basal cells of the stratum germinativum showing apocrine and/or eccrine differentiation. Only a minority of lesions of vulvar Paget's disease (2-15 %) are associated with adenocarcinomas of the urogenital tract or the skin appendages, representing an intraepidermal spread of these malignancies.