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. 2022 Aug 1;46(8):1071-1077.
doi: 10.1097/PAS.0000000000001885. Epub 2022 Mar 17.

HPV-negative Penile Intraepithelial Neoplasia (PeIN) With Basaloid Features

José Guerrero  1 , Isabel Trias  1 , Luis Veloza  2 , Marta Del Pino  3 , Adriana Garcia  1 , Lorena Marimon  4 , Sherley Diaz-Mercedes  1 , Maria T Rodrigo-Calvo  1 , Silvia Alós  1 , Tarek Ajami  5 , Rafael Parra-Medina  6 , Antonio Martinez  1   7 , Oscar Reig  8   7 , Maria J Ribal  5 , Juan M Corral-Molina  5 , Jaume Ordi  1   4 , Inmaculada Ribera-Cortada  1 , Natalia Rakislova  1   4
Affiliations

HPV-negative Penile Intraepithelial Neoplasia (PeIN) With Basaloid Features

José Guerrero et al. Am J Surg Pathol. .

Abstract

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.

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Conflict of interest statement

Conflicts of Interest and Source of Funding: Project “PI17/00772; “Valor de la detección del ARNm de los biomarcadores CDKN2A, MKi67, TOP2A en la prevención secundaria del cáncer de cuello de útero, funded by Instituto de Salud Carlos III and co-funded by the European Union (ERDF) “A way to make Europe”. ISGlobal receives support from the Spanish Ministry of Science and Innovation through the “Centro de Excelencia Severo Ochoa 2019-2023” Program (CEX2018-000806-S), and support from the Generalitat de Catalunya through the CERCA Program. The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article.

Figures

FIGURE 1
FIGURE 1
Study algorithm.
FIGURE 2
FIGURE 2
Two cases (cases 1 and 3) with penile HPV-independent PeIN simulating HPV-associated PeIN (HSIL). Case 1 (A, A′), The epidermis is markedly disorganized, showing the “wind-blown” appearance, abundant mitotic features and atypical, slightly enlarged keratinocytes. Only minimal maturation is observed in the superficial layer. p16 staining is negative. Case 3 (B, B′), The epidermis is thickened and entirely replaced by small, undifferentiated, basaloid-like keratinocytes disposed in a disorganized manner. Mitotic figures are evident throughout the epithelium. p16 is negative in the lesion.
FIGURE 3
FIGURE 3
Histologic and IHC features of HPV-independent lesions mimicking HSIL. Case 1. A, The epidermis shows marked architectural and cellular atypia. A′, p53 stain showing suprabasal overexpression. A″, Negative p16 stain. Case 2. B, Acanthotic epidermis filled with small, basaloid-like cells. B′, p53 stain showing absence of expression (null pattern), with conserved staining in the inflammatory cells. B″, Negative p16 stain. H/E indicates hematoxylin and eosin.
See this image and copyright information in PMC

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