Primary Vulvar HPV-independent Adenosquamous Carcinoma: A Case Series of a Rare Neoplasm With an Apparent Predilection for the Upper Vulva

Adenosquamous carcinoma is a rare malignancy described in a variety of body sites, including the uterine cervix. These tumors exhibit morphologically unequivocal areas of squamous and glandular differentiation and are typically associated with an aggressive clinical course. Primary adenosquamous carcinoma of the vulva, arising outside the Bartholin gland, has only been described in a few case reports, is poorly characterized and is currently not included in the 5th Edition WHO Classification of Female Genital Tumours. We report a series of 3 primary vulvar HPV-independent adenosquamous carcinomas, all arising in the upper vulva close to the junction with the vagina, in close proximity to the urethral meatus. All tumors showed surface ulceration, and there were no features of lichen sclerosus or vulvar intraepithelial neoplasia in the adjacent squamous epithelium. The squamous components ranged from 40% to 70% of the neoplasms. All tumors exhibited mutation-type p53 expression and negative/non–block-type staining for p16. Molecular testing confirmed a TP53 mutation in all tumors and showed an additional AMER1 mutation in one. Two patients presented with lymph node metastasis at the time of diagnosis or shortly thereafter. None of the patients died of their disease, with follow-up ranging from 2 to 81 mo. Our findings suggest that primary vulvar HPV-independent adenosquamous carcinoma is a distinct morphologic entity that warrants inclusion in future classifications of primary vulvar neoplasms.