Vulvar dysplasia

Vulvar squamous cell carcinomas and their precursor lesions are subclassified based on association with HPV infection, as HPV-associated or HPV-independent. Subclassification is determined by the presence or absence of strong block-like expression of p16. HPV-associated precursors are further subclassified as low-grade squamous intraepithelial lesion (LSIL/VIN1) or high-grade squamous intraepithelial lesion (HSIL/VIN2/3). High-risk HPV is associated with HSIL, whereas many LSIL harbour low-risk HPV. LSIL are flat and resemble cervical LSIL; HSIL resemble cervical HSIL and are graded as 2 or 3 based on extent of involvement of the epithelium. HPV-independent precursor lesions are further subclassified based on whether there is a pathogenic TP53 mutation with associated strong overexpression of p53 on immunohistochemistry (mutant pattern). Precursors with a pathogenic TP53 mutation and an associated strong overexpression of p53 on immunohistochemistry (mutant pattern) are designated as HPV-independent VIN, p53 aberrant (p53 mutant), while less common precursors without a TP53 pathogenic mutation and normal p16 expression are designated as HPV-independent VIN, p53 wild type. HPV-independent VIN, p53 aberrant (p53 mutant) precursors exhibit significant basal cell atypia and altered maturation of the keratinocytes, while HPV-independent VIN, p53 wild type precursors exhibit minimal cytologic atypia and a verruciform, acanthotic architecture with altered maturation.