CK17 Immunohistochemistry Is a Useful Adjunct in the Diagnosis of HPV-independent, TP53-wild-type Verruciform/Acanthotic Vulvar Intraepithelial Neoplasia (vaVIN)

Verruciform/acanthotic vulvar intraepithelial neoplasia (vaVIN) is a rare, recently defined HPV-independent, TP53-wild type lesion of the vulva that predisposes to vulvar squamous cell carcinoma (VSCC). VaVIN encompasses a variety of histomorphologic subtypes, including verruciform lichen simplex chronicus (vLSC), differentiated exophytic vulvar intraepithelial lesion (DEVIL), and vulvar acanthosis with altered differentiation (VAAD). Given the rarity of the lesion, subtle histopathologic features, and overlap with other preneoplastic entities and benign dermatoses, vaVIN is a diagnostic challenge. Therefore, immunohistochemistry (IHC) may be a helpful diagnostic adjunct in differentiating vaVIN from mimickers. Cytokeratin 17 (CK17) immunohistochemistry has been previously described as a useful diagnostic tool in diagnosing differentiated vulvar intraepithelial neoplasia (dVIN) and VSCC and has only recently been applied to vaVIN. In this study, we identified a total of ten cases of vaVIN, including four classified as vLSC, five classified as DEVIL, and one classified as VAAD. CK17 was expressed by all vaVIN lesions, with superficial to suprabasal expression in the vLSC subtype and uniform suprabasal expression in the DEVIL and VAAD subtypes. The pattern of CK17 expression may be helpful in differentiating vaVIN subtypes, notably demonstrating only superficial expression in some cases of the least aggressive phenotype, vLSC. Suprabasal expression corresponds to the more aggressive phenotypes of DEVIL and VAAD. However, additional confirmatory studies in a larger cohort are needed to validate these findings.