Fig. 6: Vulvar squamous cell carcinoma arising in a background of HPV-independent, p53-wild-type verruciform acanthotic Vulvar Intraepithelial Neoplasia.

Verrucous carcinoma overlaps morphologically with HPVi(p53wt) vaVIN. Its diagnosis requires endophytic “pushing” invasion into the underlying stroma in the form of packed nests of squamous epithelium, each with smooth convex borders and a bland squamous population (A, B). Conventional squamous cell carcinoma can also arise from HPVi(p53wt) vaVIN (C); notice the irregularity of the invasive nests (C, left aspect; higher magnification in inset) which facilitates the diagnosis. On occasion, HPVi(p53wt) vaVIN can have superimposed HPVi(p53mutant) dVIN changes, presumably via acquisition of TP53 alterations (D).