HPV-associated Vulvar Intraepithelial Carcinoma With Sebaceous Differentiation: Report of 2 Cases

Abstract

Sebaceous carcinoma (SC) is a malignant neoplasm demonstrating sebocytic differentiation, commonly in the periocular area. Sebocytic differentiation is recognized by multivesicular cytoplasmic clearing with frequent nuclear scalloping. The vesicles can be highlighted by immunohistochemical stains against the perilipin family proteins including adipophilin. Extraocular SC is uncommon but well reported, often in the setting of Muir-Torre syndrome; however, vulvar SC is exceptionally rare. The literature review yielded only 12 prior cases of vulvar SC, all of which showed invasion. Here we report 2 additional similar cases from 2 different institutions of an intraepithelial carcinoma with sebaceous differentiation. Histologic examination of multiple specimens from both patients showed similar features: a multifocal intraepithelial basaloid nodular neoplasm sparing the basal layer with occasional pagetoid spread. The tumor cells demonstrated a high nuclear to cytoplasmic ratio, mitoses, variably foamy vacuolated cytoplasm, and nuclear indentation. Multiple specimens from both patients showed evidence of sebaceous differentiation (substantiated by adipophilin positivity in a membranous vesicular pattern in case 1 and by androgen receptor and epithelial membrane antigen positivity in case 2), and squamous differentiation (substantiated by p63/p40 and weak CK 5/6 expression), as well as human papillomavirus (HPV) association (substantiated by p16 block positivity and detection of high-risk HPV by in situ hybridization). One case was a true in situ lesion without evidence of invasion, and the other case was predominantly an in situ carcinoma with prominent adnexal extension and focal superficial invasion of <1 mm seen in one of multiple specimens. To our knowledge, these 2 cases are the first to show a vulvar SC/carcinoma with sebaceous differentiation that is predominantly limited to the epidermis, and the first documentation of HPV infection in vulvar sebaceous neoplasms. Vulvar intraepithelial carcinoma with sebaceous differentiation is the umbrella term we chose for this entity. Whether this is a true SC in situ that is HPV positive/driven, or a vulvar intraepithelial neoplasia with sebaceous differentiation, is not entirely clear. We emphasize the importance of looking for this morphology to avoid misclassification. Due to the rarity of cases, optimal treatment at this site has not been established.

Eccrine Porocarcinoma of the Vulva With Sarcomatoid Transformation, a New Human Papillomavirus-associated Malignancy? Case Report and Review of the Literature

“…Two of the published cases of vulvar porocarcinoma in the literature (cases 7 and 9 in Table 1), reported strong p16 staining in the tumor, but neither investigated the presence of HPV beyond this. Interestingly, a recent report from Hamza et al Pathology of the Lower 26 . demonstrated high-risk HPV in 2 lesions of intraepithelial carcinoma with sebaceous differentiation, suggesting another link between HPV and novel carcinomas arising from cutaneous adnexal structures.…”

HPV-associated vulvar carcinoma with sebaceous differentiation

“…In this report, we present a rare case of vulvar carcinoma with sebaceous differentiation in a pregnant patient. Sebaceous differentiation is rare in vulvar carcinomas, with only 17 cases reported, to date ( Hamza et al, 2023 ). Additionally, this patient's case is unique because it is the only reported case in which the disease course overlaps with pregnancy and is the third reported case of vSC with HPV association.…”

“…Among vulvar sebaceous carcinoma, an HPV association is rare, with only three cases including the present case reported to date, confirmed by in-situ hybridization (ISH). Four cases were reported to have a negative HPV association, with three of them confirmed by combinations of immunohistochemistry, Southern blot hybridization, and PCR and one with unspecified HPV testing ( Hamza et al, 2023 ). All other cases did not report on HPV status.…”

“…The other was treated with fluorouracil due to poor surgical candidacy, but subsequent punch biopsy demonstrated persistent tumor pathology identical to initial vulvar lesion. In comparison, outcomes for patients undergoing surgical management for vulvar SC were generally superior ( Hamza et al, 2023 ). While routine SLND is recommended in addition for periocular SC, it is not routinely performed for extraocular SC due to limited data and complications including lymphocyst formation, lymphedema, and cellulitis ( Owen et al, 2019 ).…”

“…Vulvar neoplasms are classified as HPV-associated or HPV-independent by the Fifth edition of the World Health Organization Classification of Tumours of the Female Genital Tract ( Höhn et al, 2020 ). Only recently was HPV demonstrated in association with vulvar sebaceous neoplasia ( Hamza et al, 2023 ). Best management practices for vSC are poorly defined due to the limited case data.…”