Pleomorphic lobular carcinoma of the breast: a morphologically and clinically distinct variant of lobular carcinoma.

Pleomorphic lobular carcinoma is an uncommon variant of lobular carcinoma, characterized by significant cytologic atypia that contrasts with the low pleomorphism of classical lobular carcinoma. It accounts for approximately 1% of all epithelial breast malignancies. In addition to its pleomorphism, it is characterized by aggressive behavior and shortened patient survival. Although the morphologic features of pleomorphic lobular carcinoma are well described, it often eludes accurate pathologic characterization. Some controversy surrounds the pathogenesis of pleomorphic lobular carcinoma; however, it is now considered a well-defined variant of invasive lobular carcinoma. Pleomorphic lobular carcinoma shares molecular alterations with classical lobular carcinoma, such as alterations in the gene CDH1 on chromosome band 16q22 that results in changes in E-cadherin protein function. The aggressive biology of pleomorphic lobular carcinoma relates to the acquisition of genetic alterations typical of high-grade ductal carcinoma, such as overexpression of HER2/neu and c-myc.