Metaplastic Breast Carcinoma: Update on Histopathology and Molecular Alterations.

CONTEXT—: Metaplastic carcinoma is a rare, triple-negative carcinoma of the breast that exhibits transformation of part or all of its glandular carcinomatous component into a nonglandular, or metaplastic, component. The World Health Organization currently recognizes 5 variants of metaplastic carcinoma based on their histologic appearance. OBJECTIVE—: To review the histologic classifications, differential diagnosis, prognosis, and recent laboratory studies of metaplastic breast carcinoma. DATA SOURCES.—: We reviewed recently published studies that collectively examine metaplastic carcinomas, including results from our own research. CONCLUSIONS.—: Metaplastic breast carcinoma has a broad spectrum of histologic patterns, often leading to a broad differential diagnosis. Diagnosis can typically be rendered by a combination of morphology and immunohistochemical staining for high-molecular-weight cytokeratins and p63. Recent studies elucidate new genes and pathways involved in the pathogenesis of metaplastic carcinoma, including the downregulation of CCN6 and WNT pathway gene mutations, and provide a novel MMTV-Cre;Ccn6fl/fl knockout disease-relevant mouse model to test new therapies.