Low‐risk <scp>HPV</scp> ‐associated invasive carcinoma with squamous and glandular features arising in a Buschke–Löwenstein tumour

AIMS: Low-risk human papillomavirus (LR-HPV) types 6 and 11 are classically associated with benign anogenital condylomas and are only rarely implicated in malignant transformation. Reported carcinomas associated with LR-HPV have exclusively demonstrated purely squamous morphology. We describe an unusual LR-HPV-associated invasive anal carcinoma with mixed squamous and glandular differentiation arising in a Buschke-Löwenstein tumour (BLT). METHODS AND RESULTS: A 70-year-old woman underwent abdominoperineal resection for an anal mass associated with a perirectal abscess and rectovaginal fistula. Histological examination demonstrated a circumferential papillary-verrucous lesion consistent with condyloma acuminatum/BLT with areas transitioning to invasive carcinoma. The invasive tumour extended through the anal wall and showed intimately admixed squamous and mucinous glandular components, including pure glandular and pure squamous areas. The glandular component was CK7 positive and negative for CDX2 and CK20, supporting a non-colorectal phenotype. High-risk HPV in situ hybridization was negative, and p16 showed only patchy, non-block-type staining. In situ hybridization for LR-HPV (types 6/11) demonstrated positive signals in both the condylomatous and invasive glandular and squamous components. CONCLUSIONS: This case expands the morphological spectrum of LR-HPV-associated anal neoplasia by documenting invasive carcinoma with true glandular and squamous differentiation arising in a BLT in the absence of detectable high-risk HPV. The findings support the capacity of LR-HPV-associated lesions, although exceptionally rarely, to undergo malignant transformation with divergent glandular differentiation.