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HPV-independent Precursors Mimicking High-grade Squamous intraepithelial Lesions (HSIL) of the Vulva

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Two etiopathogenic types of vulvar squamous cell carcinoma (VSCC) have been described: human papillomavirus (HPV)-associated and HPV-independent. Precursor lesions, frequently identified in the adjacent skin, are also distinct in the 2 types of VSCC: high-grade squamous intraepithelial lesions (HSILs) in HPV-associated VSCC and differentiated vulvar intraepithelial neoplasia (dVIN) or vulvar acanthosis with altered differentiation in HPV-independent VSCC. Although HPV-independent precursors mimicking HSIL have been described in the vulva, their frequency and morphologic spectrum have not been completely characterized. We explored, in a large series of HPV-independent VSSC, the frequency and the histologic features of precursors mimicking HSIL. We included 779 DNA HPV-negative/p16-negative VSCC with at least 1\xE2\x80\x89cm of adjacent skin. We evaluated the histologic and immunohistochemical (p16 and p53) characteristics of the intraepithelial lesions, focusing on precursors mimicking HPV-associated vulvar HSIL. A total of 254 tumors (33%) had adjacent premalignant lesions. Of them, 186 (73%) had dVIN, 22 (9%) had vulvar acanthosis with altered differentiation, and 46 (18%) had lesions that mimicked HSIL. The mean age of the patients with these HSIL-like lesions was 72\xC2\xB115 years. Twenty-six of these HSIL-like lesions had basaloid morphology, 13 warty, and 7 mixed basaloid/warty features. All the HSIL-like precursors were DNA HPV-negative/p16-negative; 74% of them showed p53 abnormal staining and 35% of them had areas of conventional dVIN. In conclusion, about one fifth of the HPV-independent precursors mimic HSIL, showing either basaloid or warty features. Older age and the presence of areas of typical HPV-independent intraepithelial lesions, together with p16 negativity, should raise suspicion of an HPV-independent etiology.

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RAKISLOVA, Natalia, ALEMANY I VILCHES, Laia, CLAVERO, Omar, PINO, Marta del, SACO, Adela, MARIMON, Lorena, QUIRÓS, Beatriz, LLOVERAS RUBIO, Betlem, RIBERA CORTADA, Inmaculada, ALEJO, Maria, PAWLITA, Michael, QUINT, Wim, SANJOSÉ LLONGUERAS, Silvia de, ORDI I MAJÀ, Jaume, VVAP Study Group. HPV-independent Precursors Mimicking High-grade Squamous intraepithelial Lesions (HSIL) of the Vulva. _American Journal of Surgical Pathology_. 2020. Vol.  vol 44, núm. num 11, pàgs. 1506-1514. [consulta: 21 de gener de 2026]. ISSN: 0147-5185. [Disponible a: https://hdl.handle.net/2445/183066]

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