Benign proliferative nipple duct lesions frequently contain CAM 5.2 and anti-cytokeratin 7 immunoreactive cells in the overlying epidermis

Benign proliferative nipple duct lesions (PNDLs) pose a diagnostic problem for clinicians and pathologists. Clinically, they may be associated with sk in changes typically present in Paget's disease of the nipple. The identifi cation of numerous scattered cells in the epidermis that are immunoreactive for low-molecular-weight cytokeratin may lead to further confusion with Pa get's disease. We studied the nipple epidermis in nine cases of PNDL and co mpared them with 26 histologically normal nipples from mastectomy specimens . CAM 5.2 and anticytokeratin 7 (CK7) immunoreactive cells were identified in the epidermis of seven of nine nipples associated with PNDL. The cytoker atin-positive cells appeared cytologically benign and were dispersed singly (scattered in seven of seven cases and frequent in four of seven cases) or formed small aggregates with occasional tubular structures (three of seven cases) in the basal and middle layers of the epidermis. In two of seven ca ses, these epidermal immunoreactive cells showed continuity with the underl ying PNDL, suggesting the spread or continuation of lesional cells to the e pidermis. Dispersed single immunoreactive cells were identified in small nu mbers (scattered) in the basal layer of the epidermis in 12 of 26 normal ni pples and more frequently in 1 of 12 cases. In all cases, the intraepiderma l cells were negative for carcinoembryonic antigen (CEA) and Her-2/neu. We conclude that intraepidermal CAM 5.2 aid anti-CK7 immunoreactive cells, whi ch are normally present in the nipple epidermis, may proliferate and form a ggregates when there is an underlying PNDL. The presence of these cells doe s not imply Paget's disease when the intraepidermal cells have a bland cyto logic appearance, fail to overexpress Her-2/neu, and there is no carcinoma within the PNDL or elsewhere in the breast.