Mammary Paget Disease : Pathogenesis

Paget disease (PD) of the nipple and areola is a rare form of intraepidermal adenocarcinoma that is almost always associated with in-situ or invasive breast cancer. It appears as an eczematous, scaling, pruritic eruption of the skin that clinically mimics inflammatory dermatoses. PD arises by intraepidermal migration of ductal carcinoma cells through the lactiferous ducts to the surface epithelium of the nipple and areola. The rare cases not associated with breast carcinoma are thought to arise from the epidermal Toker cells. Paget cells infiltrate the entire thickness of epidermis singly or in nests. They have voluminous clear or pale eosinophilic cytoplasm, vesicular nuclei, prominent nucleoli, and increased mitotic activity. Glandular and acinar structures and signet ring cells with intracytoplasmic mucin may be present. Immunohistochemistry: Positive for LMWCK (CAM5.2, CK7), AE1/AE3, EMA, HER2, GATA3; variably positive for CEA and GCDFP-15; negative for CK20, p63, ER, PR, and melanocytic markers (Melan-A, SOX10, HMB-45; S-100 is +ve in 20% of cases). Differential diagnosis : pagetoid Bowen disease, superficial spreading melanoma, pagetoid dyskeratosis, clear cell papulosis, and inflammatory dermatoses. References:Dabbs, David J. (2017). Breast Pathology - 2nd Edition. Elsevier. Calonje, E et al (2020). McKee's Pathology of the Skin with Clinical Correlations - 5th Ed. Elsevier.