A diagnostically challenging case of CK7-negative mammary Paget's disease

Summary: A 39-year-old patient without significant past medical history presented with left nipple crusting for 18 months. On physical exam, the left nipple and areola were red and mildly thickened, with no suspicious masses palpated. Imaging studies, including magnetic resonance, showed slight asymmetric thickening and enhancement of the left nipple areolar complex compared to the right, without lesions in bilateral breasts or axillae. The initial clinical differential included eczema, contact dermatitis, Bowen's disease, melanoma, and mammary Paget's disease. A shave biopsy showed occasional large cells with abundant pale cytoplasm and large nuclei with prominent nucleoli predominantly in the basal epidermis and dispersed singly among maturing keratinocytes. These cells were positive for AE1/AE3, CAM5.2, GATA-3, ER, and PR, while CK7, Mucicarmin, and HER2 were negative. These cells were also negative for CK5/6, p63, SOX10, and Melan A. The rarity of lesional cells, coupled with CK7 and HER2-negative status and negative breast imaging, made the diagnosis of Paget's disease difficult. The patient went on to have a left mastectomy that identified ductal carcinoma in situ (DCIS) involving nipple epidermis (Paget's disease) and underlying breast parenchyma. The non-conventional immunostaining of Paget's cells in a patient with radiologically occult breast cancer represents a diagnostic challenge.