Nonneoplastic alterations of the mammary epithelium can mimic atypia

The pathologist evaluating breast biopsy specimens sometimes encounters nonneoplastic alterations of the mammary epithelium that raise the differential diagnosis of atypia. Because the identification of atypical ductal hyperplasia of the breast has significant clinical implications, it is important to correctly recognize its nonneoplastic morphologic mimics.

To highlight a spectrum of physiologic and treatment-related changes that can occur in the mammary epithelium and to discuss the differential diagnosis with true atypia.

A comprehensive review of the published English literature on physiologic and treatment-related changes of the breast epithelium was performed.

Among physiologic alterations of the ductal epithelium, luteal-phase changes and secretory changes can sometimes be overinterpreted as atypical. Treatment-related changes, secondary to chemotherapy and radiation, can pose a major diagnostic challenge and their misinterpretation as neoplastic carries major clinical consequences. Familiarity with the morphology of both physiologic and treatment-related alterations of the mammary epithelium is essential to avoid misdiagnosis.