Abstract

Abstract: Squamous intraepithelial lesions of the vulva, known as vulvar intraepithelial neoplasia, or VIN, are considered to be precursors of invasive squamous cell carcinoma. About a third of invasive squamous cell carcinomas are associated with human papillomavirus (HPV), but no link with HPV is detected in the remaining two thirds. Among intraepithelial lesions, the ratio of HPV-associated to non–HPV-associated lesions is reversed. HPV-associated VIN of the warty (condylomatous) and basaloid types is the most common and best-recognized form of VIN. A rare variant, pagetoid VIN, mimics Paget disease because the abnormal cells grow in a nested pattern and have pale cytoplasm. In this report, we present a case that illustrates the features of an important but often-unrecognized type of VIN, the differentiated or simplex type. It is frequently observed adjacent to non–HPV-associated squamous cell carcinomas, but it also occurs independent of invasive cancer. It differs from the more familiar HPV-associated Bowenoid types of VIN in that the most atypical cells are confined to the basal portion of the epithelium, and the more superficial epithelium consists of differentiated squamous cells. The pattern of differentiation is abnormal, as keratinization is often premature and exaggerated, keratin pearls are present in the deep epidermis or rete ridges, intercellular bridges are more prominent than usual, suprabasal cells have atypical nuclei, and there are suprabasal mitotic figures. Differentiated VIN is a precursor of keratinizing squamous cell carcinoma, and it is important to recognize it and differentiate it from nonneoplastic vulvar disorders such as squamous hyperplasia and lichen sclerosus.

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