Histologic characteristics and terminology of vulvar squamous intraepithelial lesions

HPV status	Lesion	Histologic characteristics
HPV-associated vulvar intraepithelial lesions	Low-grade squamous intraepithelial lesions (LSIL) of the vulva (vulvar LSIL, flat condyloma, or HPV effect)	Cytologic atypia is most often represented by koilocytosis or basal cell hyperplasia and increased mitotic activity, with squamous maturation occurring in the upper two-thirds of the epithelium.
HPV-associated vulvar intraepithelial lesions	High-grade squamous intraepithelial lesions (HSIL) of the vulva (vulvar HSIL, VIN usual type [uVIN])	Loss of maturation includes the middle (formerly VIN 2) and upper third to full thickness (formerly VIN 3) of the squamous epithelium. Cytologic changes may be significant with bizarre mitotic figures and significant pleomorphism. Stromal invasion is not present.
HPV-independent vulvar intraepithelial lesions	Vulvar intraepithelial neoplasia differentiated type (dVIN)	Differentiated VIN lesions affect the parabasal layer and exhibit keratin formation. The epithelium is generally thickened and parakeratotic with elongated and anastomosing rete ridges. The abnormal cells have prominent eosinophilic cytoplasm and are confined to the parabasal and basal portion of the rete pegs with little or no atypia above.
HPV-independent vulvar intraepithelial lesions	Vulvar acanthosis with altered differentiation (VAAD), differentiated exophytic vulvar intra-epithelial lesion (DEVIL), and verruciform lichen simplex chronicus (vLSC)	These lesions represent a spectrum of HPV and p53-independent preinvasive verruciform lesions of the vulva with significant histopathological and clinical overlap. Common characteristics include exophytic growth, acanthotic or verruciform architecture, and an absence of significant nuclear atypia.

HPV: human papillomavirus; VIN: vulvar intraepithelial neoplasia.

References:

Roy SF, Wong J, Le Page C, et al. DEVIL, VAAD and vLSC constitute a spectrum of HPV-independent, p53-independent intra-epithelial neoplasia of the vulva. Histopathology 2021; 79:975.
WHO Classification of Tumours Editorial Board (Eds). Tumours of the vulva. In: Female Genital Tumours, 5th ed, Vol. 4, International Agency for Research on Cancer 2020.

Adapted from: Bornstein J, Bogliatto F, Haefner HK, et al. The 2015 International Society for the Study of Vulvovaginal Disease (ISSVD) terminology of vulvar squamous intraepithelial lesions. J Low Genit Tract Dis 2016; 20:11.

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Histologic characteristics and terminology of vulvar squamous intraepithelial lesions