Metaplastic Breast Carcinoma: Update on Histopathology and Molecular Alterations

Abstract

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.