DEVIL, VAAD and vLSC constitute a spectrum of HPV-independent, p53-independent intraepithelial neoplasia of the vulva.

Abstract

AIMS\nWe aimed to characterize a large cohort of non-invasive, HPV and p53-independent verruciform lesions, such as vulvar acanthosis with altered differentiation (VAAD), differentiated exophytic vulvar intraepithelial lesion (DEVIL) and verruciform lichen simplex chronicus (vLSC).\n\n\nMETHODS AND RESULTS\nWe retrospectively identified from January 2008 until December 2020, 36 eligible patients with verruciform non-invasive lesions (n=36) and collected clinical, histological and follow-up parameters. Verruciform non-invasive lesions occurred at a median age of 71 years with a median follow-up of 33.5 months. Clinically, pruritus was only reported in patients with VAAD (n=3, 21%). Lesion color was significantly different across categories (p=0.028). Apart from the histopathological criteria already known to distinguish these entities (hypogranulosis, epithelial pallor and low-magnification architecture), no other significant criteria were discovered, and significant overlap was observed, particularly between VAAD and DEVIL. Patients with vLSC trended towards longer survival without recurrence compared to VAAD and DEVIL (P=0.082) yet showed comparable invasion-free survival interval (p=0.782). Squamous cell carcinomas (SCC) associated with either VAAD, DEVIL or vLSC displayed similar clinical, histopathological and biological parameters. In non-invasive precursor lesions, stromal edema was associated with invasion (p=0.015) and remained so upon Cox regression analysis (p=0.009).\n\n\nCONCLUSION\nOur study of HPV and p53 independent non-invasive verruciform lesions of the vulva highlights significant clinical, histopathologic and biologic overlap between VAAD, DEVIL and vLSC suggesting that these pre-invasive lesions should be viewed as a spectrum. We also show that stromal features such as edema might play an import role in progression to invasion.