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Mammary Paget Disease

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Squamous cell carcinoma-in-situ (Bowen Disease) & Actinic Keratosis: The anaplastic variant of Paget disease (PD) closely resembles Bowen disease. Features supporting Bowen disease include dyskeratosis, full thickness cytologic atypia, marked anaplasia, acantholysis, and loss of polarity. There is no intracellular mucin, signet ring cells, or glandular structures. CEA and GCDFP-15 are negative. Tumor cells in Bowen disease/actinic keratosis are positive for high molecular weight cytokeratins (CK5, CK14) and p63 and negative for CAM5.2 and CK7. HER2 is negative in Bowen disease. Melanoma-in-situ (MIS): Some cases of PD produce pigment and may be mistaken for MIS with pagetoid spread. In addition, PD may be associated with increased melanin production in the surrounding keratinocytes or melanocytic hyperplasia. The immunohistochemical profile supporting the diagnosis of MIS is as follows: positive for S-100, Melan-A, and HMB-45; negative for CK7, CAM5.2, CEA, and HER2. Mucin is absent and there are no glandular structures. Note: S-100 may be positive in upto 20% of cases of PD. Other entities in the differential diagnosis include: benign conditions showing pagetoid spread such as inflammatory dermatoses, psoriasis, topical drug reactions, pagetoid dyskeratosis, clear cell papulosis (Toker cell hyperplasia), and infections; malignant conditions such as basal cell carcinoma, mycosis fungoides, Langerhans cell histiocytosis, and sebaceous carcinoma of nipple.

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