The WHO 2022 classification of penile and scrotal cancers: updates and evolution

Abstract

Squamous cell carcinoma (SCC) is the most common malignant tumor of the penis. The 2022 WHO classification reinforces the 2016 classification and subclassifies precursor lesions and tumors into HPV-associated and HPV-independent types. HPV-associated Penile intraepithelial neoplasia (PeIN) is a precursor lesion of invasive HPV- associated SCC, whereas differentiated PeIN is a precursor lesion of HPV independent SCC. Block-type positivity of p16 immunohistochemistry is the most practical daily utilizedmethod to separate HPV associated from HPV independent penile SCC. If this is not feasible, the term SCC, NOS is appropriate. Certain histologies which were previously classified as"subtypes" are now grouped, and coalesced as "patterns", under the rubric of usual type SCC and verrucous carcinoma (e.g., usual-type SCC includes pseudohyperplastic and acantholytic/ pseudoglandular carcinoma, and carcinoma cuniculatum is included as a pattern of verrucous carcinoma). If there is an additional component of the usual type of invasive SCC (formerly termed as hybrid histology), the tumour would be a mixed carcinoma (e.g., carcinoma cuniculatum or verrucous carcinoma with usual invasive SCC); in such cases, reporting of the relative percentages in mixed tumours may be useful. The consistent use of uniform nomenclature and reporting of percentages will inform the refinement of future reporting classification schemes and guidelines/recommendations. The classification of scrotal tumors is provided for the first time in the fifth edition of the WHO Blue book, and it follows the schema of penile cancer classification for both precursor lesions and the common SCC of scrotum. Basal cell carcinoma of scrotum, may have a variable clinical course and finds a separate mention.

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Journal Histopathology
Pages Epub ahead of print
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