Fig. 5: Differential diagnosis of HPV-independent, p53-wild-type verruciform acanthotic Vulvar Intraepithelial Neoplasia.

High grade squamous intraepithelial lesion / usual vulvar intraepithelial neoplasia can feature verruciform growth, often due to superimposed lichen simplex chronicus. Maturation in this setting is abrupt, and the lower epithelial layers still show an immature, basaloid and highly atypical appearance (A, B, higher magnification in insets). Vulvar condyloma, caused by low-risk HPV types, is characteristically verrucoid with bulbous papillary projections (C, D). Acanthosis and parakeratosis are usually not prominent, the granular cell layer is retained and there is absence of cytoplasmic pallor. In addition, viral koilocytic change can be appreciated (C, D insets).