Metaplastic Breast Carcinoma

Metaplastic breast carcinomas are a heterogeneous group that can display adenocarcinoma, squamous, spindle cell, and/or heterologous mesenchymal growth patterns, often in various combinations. These combinations have suggested monikers such as matrix-producing carcinoma , carcinosarcoma , spindle cell carcinoma , and carcinoma with pseudosarcomatous metaplasia . The carcinomatous component may be minimal, be hard to find, or present only as carcinoma in situ.

Metaplastic carcinomas as defined here account for less than 1% of all invasive mammary carcinomas, but up to 5% of mammary carcinomas may undergo some metaplastic change into a nonglandular growth pattern. The extent of metaplasia varies from a few microscopic foci in an otherwise typical mammary carcinoma to complete replacement of glandular growth by the metaplastic tumor pattern. Breast carcinomas with metaplasia are usually derived from poorly differentiated duct carcinomas, but metaplasia can occur in well-differentiated tumors and, less commonly, in breast carcinomas of special type.

Metaplastic breast carcinomas showing mesenchymal differentiation with or without heterologous elements originate from carcinomas that undergo sarcomatous neometaplasia as a result of further genetic instability or mutations. Indeed, Zhuang and colleagues have provided convincing proof of this assertion by demonstrating identical clonality of the carcinomatous and spindle cell components, even identical to a focus of ductal carcinoma in situ (DCIS) presented in one case. The authors concluded that the two components of carcinosarcoma and its precursor were clonal and that the sarcomatous and spindle cell components arose from mutation of the carcinoma. Likewise, after an investigation of p53 mutations in a series of metaplastic breast carcinomas, Lien and coworkers found convincing evidence for the monoclonal histogenesis of the various components of metaplastic breast carcinoma.

Abundant ultrastructural and immunohistochemical (IHC) studies have indicated that the spindle cell components show variable myoepithelial differentiation, akin to that in mixed tumors (pleomorphic adenomas) of the salivary glands. Some believe the IHC findings in metaplastic (sarcomatoid) breast carcinoma are so convincingly of a myoepithelial immunophenotype (i.e., the frequent presence of basal cell–type cytokeratins [CKs] 5/14/17 and the combination of the established myoepithelial markers CD10, p63, smooth muscle actin [SMA], and S100) that all sarcomatoid breast tumors, even those with weak or absent CK expression, should be diagnosed as primary sarcomas of the breast only after exclusion of a myoepithelial immunophenotype. Some authors have suggested the moniker myoepithelial carcinoma for breast carcinomas with myoepithelial differentiation, but it appears that the traditional or classic types of metaplastic sarcomatoid or spindle cell breast carcinomas are expected to show myoepithelial differentiation. Hence, this distinction seems arbitrary and of little known clinicopathological significance. What is important is that pathologists use a tumor moniker that allows clinicians to link the patient care literature with the clinicopathological features of the tumor in their patient, and the vast bulk of the literature is published under the rubric of metaplastic spindle cell or sarcomatoid breast carcinoma . Creating unnecessary new names for well-described lesions can lead to confusion and potentially cause patient harm.

It is fascinating that some myoepithelial-like differentiation has been found in basal-like breast carcinoma. Thus, it is interesting that Sarrió and associates studied metaplastic breast carcinomas and found that the epithelial-mesenchymal transition (EMT), as defined by the loss of epithelial characteristics and the acquisition of a mesenchymal phenotype, can be associated with increased aggressiveness and invasive and metastatic potential. They found that upregulation of EMT markers (vimentin, SMA, N-Cadherin, and cadherin-11) and overexpression of proteins involved in extracellular matrix remodeling and invasion (SPARC, laminin, and fascin), together with a reduction of characteristic epithelial markers (E-Cadherin [ECAD], claudins and CKs), preferentially occur in breast tumors with the basal-like phenotype. Also, they observed that most breast carcinosarcomas had a basal-like phenotype (also triple-negative and claudin-low) and showed expression of mesenchymal markers in their sarcomatous and epithelial components. They found that basal-like cells had intrinsic phenotypic plasticity for mesenchymal transition, suggesting that EMT likely occurs within a specific genetic context, the basal phenotype, and that this proclivity to mesenchymal transition may be related to the high aggressiveness and the characteristic metastatic spread of these tumors, at least the higher-grade examples.