Abstract

Penile intraepithelial neoplasia (PeIN) is a histopathologic diagnosis describing a precancerous lesion with potential to progress into invasive penile squamous cell carcinoma (PSCC). PSCC arises from two pathways: human papilloma virus (HPV)-associated and HPV-independent. HPV-associated PeIN can be further differentiated into warty PeIN with parakeratosis, papillary appearance, and pleomorphic koilocytosis; and basaloid PeIN with small, uniform basaloid cells involving the full epithelial thickness. Most HPV-independent PSCCs originate from differentiated PeIN (dPeIN), which is histologically characterized by acanthosis, eosinophilic cytoplasm, and atypia limited to the basal layer with marked superficial maturation. We report a case of a 73-year-old man with an HPV-independent dPeIN with a verrucous histologic appearance, a pattern not previously described. A shave biopsy was performed on the glans penis showing marked epidermal acanthosis and a verruciform appearance. Hyperkeratosis was present on the surface and there was dysplasia centered in the basal layer of the mucosa. The Ki67 showed a markedly increased proliferation index, particularly at the mucosal base. Immunohistochemical testing did not reveal aberrant p53 expression. Treponema pallidum immunostain, Grocott methenamine silver (GMS) stain, and RNA scope in-situ hybridization for low-risk and high-risk HPV were negative. A diagnosis of dPeIN was favored. Recognizing HPV-independent malignant precursors is important as it is possible that HPV status may have prognostic implications. A small subset of HPV-independent PeIN with basaloid histology has been previously described, and we now describe a case with verrucous features. HPV-independent dPeIN may have a broader morphologic spectrum than originally thought.