Proliferative epidermal lesions associated with anogenital Paget's disease

A series of 35 cases of Paget's disease (PD) of the vulva and perianal area were studied to characterize the spectrum of proliferative epidermal lesions that occur in this rare disease but generally have been overlooked. The study group consisted of 8 men and 27 women with a median age of 66 years. Nineteen patients (54%) had one or more benign proliferative epidermal lesions, including 7 of 22 patients (32%) with vulvar PD and 12 of 13 patients (92%) with perianal PD. Two patients also had malignant squamous cell neoplasms. Three categories of epidermal hyperplasia were identified: (1) squamous hyperplasia NOS (34%), (2) fibroepithelioma-like hyperplasia (32%), and (3) papillomatous hyperplasia (29%). Small nests of hyperplastic squamous cells protruding into the dermis simulated microinvasive squamous carcinoma in three of these cases. None of the nine papillomatous hyperplasias tested for HPV by in-situ hybridization were positive. The squamous hyperplasia NOS and the papillomatous hyperplasia did not show a predilection for an anatomic site. In contrast, fibroepithelioma-like hyperplasia occurred in 69% of perianal PD compared with only 9% of vulvar cases. There was no association between the type of epidermal hyperplasia and the presence of a regional internal cancer. Two patients with vulvar PD had malignant squamous lesions, including one with squamous cell carcinoma in-situ (CIS) of classic type and one patient with invasive squamous cell carcinoma (InvSCC); the latter also had invasive PD. The malignant squamous component in both patients was positive for HPV 16/18, whereas the associated Paget's cells were HPV-negative. The finding of fibroepithelioma-like hyperplasia in the anogenital skin should prompt a thorough search for Paget' s cells. Papillomatous hyperplasia may be misinterpreted as condyloma acuminatum when Paget's cells are few in number and have koilocytotic-like vacuolar change or for warty (condylomatous) carcinoma when pseudoinvasive foci are present. When Paget's cells are florid and diffusely infiltrate an acanthotic epidermis, classic CIS may be misdiagnosed. Cytokeratin 7 immunostain is an excellent marker for intraepithelial and invasive Paget's cells that aids in their distinction from hyperplastic and malignant squamous cells.