Most human papillomavirus (HPV)-independent penile squamous cell carcinomas (PSCCs) originate from an intraepithelial precursor called differentiated penile intraepithelial neoplasia, characterized by atypia limited to the basal layer with marked superficial maturation. Previous studies in vulvar cancer, which has a similar dual etiopathogenesis, have shown that about one fifth of HPV-independent precursors are morphologically indistinguishable from high-grade squamous intraepithelial lesions (HSILs), the precursor of HPV-asssociated carcinomas. However, such lesions have not been described in PSCC. From 2000 to 2021, 55 surgical specimens of PSCC were identified. In all cases, thorough morphologic evaluation, HPV DNA detection, and p16, p53, and Ki-67 immunohistochemical (IHC) staining was performed. HPV-independent status was assigned based on both negative results for p16 IHC and HPV DNA. Thirty-six of the 55 PSCC (65%) were HPV-independent. An intraepithelial precursor was identified in 26/36 cases (72%). Five of them (19%) had basaloid features, morphologically indistinguishable from HPV-associated HSIL. The median age of the 5 patients was 74 years (range: 67 to 83 y). All 5 cases were p16 and DNA HPV-negative. Immunohistochemically, 3 cases showed an abnormal p53 pattern, and 2 showed wild-type p53 staining. The associated invasive carcinoma was basaloid in 4 cases and the usual (keratinizing) type in 1. In conclusion, a small proportion of HPV-independent PSCC may arise on adjacent intraepithelial lesions morphologically identical to HPV-associated HSIL. This unusual histologic pattern has not been previously characterized in detail in PSCC. p16 IHC is a valuable tool to identify these lesions and differentiate them from HPV-associated HSIL.
The American journal of surgical pathology. 2022 Mar 17 [Epub ahead of print]
José Guerrero, Isabel Trias, Luis Veloza, Marta Del Pino, Adriana Garcia, Lorena Marimon, Sherley Diaz-Mercedes, Maria T Rodrigo-Calvo, Silvia Alós, Tarek Ajami, Rafael Parra-Medina, Antonio Martinez, Oscar Reig, Maria J Ribal, Juan M Corral-Molina, Jaume Ordi, Inmaculada Ribera-Cortada, Natalia Rakislova
Department of Pathology Uro-Oncology Unit Institute of Hematologic and Oncologic Diseases, Hospital Clinic of Barcelona, University of Barcelona Institute of Gynecology, Obstetrics, and Neonatology, Hospital Clinic-the August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Faculty of Medicine-University of Barcelona Barcelona Institute for Global Health (ISGlobal), Hospital Clínic-Universitat de Barcelona The August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, Spain Institute of Pathology, Lausanne University Hospital, Lausanne University, Lausanne, Switzerland Department of Pathology, Research Institute, Health Sciences University Foundation, Bogotá, Colombia.