Synchronous Cervical and Vulvar High-Grade Squamous Intraepithelial Lesions with Unusual p16/p53 Immunophenotype: A Case Report

Background and Objectives: Synchronous cervical and vulvar squamous intraepithelial lesions are rarely reported. In most cases, these lesions are associated with high-risk human papillomavirus (HPV) infection and follow the conventional HPV-related pathway. Rarely, vulvar lesions may show an unusual immunohistochemical profile, with block-type p16 expression accompanied by aberrant p53 staining, creating diagnostic and etiopathogenetic challenges. Case Presentation: We report the case of an 83-year-old woman who presented with metrorrhagia and a symptomatic vulvar lesion. Histopathological evaluation revealed synchronous high-grade squamous intraepithelial lesion of the cervix and vulvar high-grade squamous intraepithelial lesion (VIN 3). Immunohistochemically, the cervical lesion showed block-type p16 positivity and a wild-type p53 pattern, supporting a conventional HPV-associated profile. In contrast, the vulvar lesion also demonstrated block-type p16 positivity, but with aberrant p53 overexpression, representing an unusual double-positive immunophenotype. Conclusions: This case highlights a rare presentation of synchronous lower genital tract squamous intraepithelial lesions with divergent immunophenotypic features. Accurate interpretation requires integration of morphology and immunohistochemistry, while the absence of direct HPV testing and TP53 molecular analysis limits definitive etiopathogenetic classification. Reporting such cases may broaden awareness of unusual vulvar precursor lesions and potential diagnostic pitfalls in routine practice.