Phenotypic Alterations in Myoepithelial Cells of the Breast in Normal and Pathologic Conditions

To the Editor: I read, with interest, the recently published article entitled “Phenotypic Alterations in Myoepithelial Cells Associated with Benign Sclerosing Lesions of the Breast” by Hilson et al.5 The researchers have shown that myoepithelial cells (MC) associated with benign sclerosing lesions (sclerosing adenosis, radial scar, and complex sclerosing lesions) may show immunophenotypic differences (for smooth muscle actin, smooth muscle myosin heavy chain, CD10, cytokeratin 5/6, p63, calponin, and p75) from MC associated with normal breast ducts and lobules and also among these different types of sclerosing lesions. The researchers then compare their results with those of their similar earlier study of ductal carcinoma in situ (DCIS) associated MC.4 Although 84% of DCIS cases examined showed decreased expression or absent staining of ≥1 MC marker compared with normal MC, only 48% of benign sclerosing lesion showed decreased expression or absent staining of ≥1 MC marker compared with normal MC. Unfortunately, this study did not seem to take into account the fact (and potential bias) that MC are also morphologically and immunohistochemically heterogeneous in physiological conditions along the normal mammary terminal duct/lobular unit (TDLU) and excretory ducts, that reflects differences in their functional properties. For example, heavy caldesmon and cytokeratin 14 are present in the MC of large ducts (and also terminal ducts for cytokeratin 14), but are not found in intralobular ductules and acini.1,3,6 In contrast, CD10 is expressed uniformly from the terminal duct to the acini.3 Morphologically, the MC layer is also organized differently in the ducts and in the lobules. In the ducts, elongated MC form a fairly continuous layer and are in direct contact with the basement membrane, and hence with the stroma. In contrast, MC are of stellate shape and form a basket-like structure around the acini, resulting in the exposure of most of the basal surface of the luminal cell to the basement membrane.1 This morphologic heterogeneity may explain to some extent the perceptible reduced expression of some immunohistochemical markers. The morphologic and immunohistochemical heterogeneity of normal MC along ductulolobular units and excretory ducts is an important factor to take into consideration when comparing the immunophenotype of normal MC with MC associated with different pathologic conditions (benign sclerosing lesions and DCIS in this study), which may arise from different anatomic compartments of the breast (or even in the same compartment such as the TDLU that may be heterogeneous). Indeed, intraductal proliferative lesions such as DCIS may be present in the major ducts, terminal ducts, or within the TDLU whereas sclerosing adenosis is a lesion of the TDLU. In contrast, complex sclerosing lesions may arise from large ducts as some researchers consider them to be a late stage of sclerosing papilloma in which the architectural distortion precludes its recognition. The potential different anatomic distribution of the lesions assessed in this study may explain the results obtained to some extent. Furthermore, although DCIS associated MC are “normal” nonproliferative constituents, MC may participate actively in the proliferative process in some of the benign sclerosing lesions. In those circumstances, it is well known that MC may alter from their normal phenotype. For example, in mixed tumor (of the breast) such as pleomorphic adenoma, different MC in the same lesion have heterogeneous phenotype, which also differs from normal MC.2 Marc Pusztaszeri MD Division of Clinical Pathology Geneva University Hospital Geneva, Switzerland

Topic: Breast Lesions and Carcinomas
Subfield: Pathology and Forensic Medicine
Field: Medicine
Domain: Health Sciences