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Q & A Column, 2/13

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Submit your pathology-related question for reply by appropriate medical consultants. CAP TODAY will make every effort to answer all relevant questions. However, those questions that are not of general interest may not receive a reply. For your question to be considered, you must include your name and address; this information will be omitted if your question is published in CAP TODAY.

Submit a Question [hr] [pulledquote]Q. What are the limitations of using myoepithelial markers in diagnostic breast pathology?[/pulledquote]

A. Immunohistochemical studies using antibodies to highlight myoepithelial cells (MEC) can be useful adjuncts to traditional morphologic diagnosis in the practice of breast pathology.

Antibodies commonly used to detect MEC include smooth muscle actin, calponin, smooth muscle myosin heavy chain, p63, CD10, cytokeratin 5/6, and p75, and each shows varying sensitivity and specificity.1–4 The presence of MEC may indicate a noninvasive process, but there are several settings in which caution should be exercised when interpreting immunohistochemical results. For example, sclerotic lesions, such as radial scars and sclerosed papillomas, may show decreased numbers of MEC or decreased intensity of expression of MEC markers.4,5 Moreover, if the lesion has been previously biopsied, MEC may not be well preserved due to disruption and reaction to the procedure. Myoepithelial markers may also be absent in the setting of ductal carcinoma in situ (DCIS), especially high-grade DCIS.5 The question of microinvasion associated with high-grade DCIS is a common diagnostic dilemma. One can be confident of a noninvasive process if at least some MEC are present surrounding the suspicious area. However, the absence of MEC in this setting does not guarantee an invasive process. It is recommended that a panel of MEC markers be used, rather than relying on a single antibody.

In general, the presence of MEC supports a noninvasive process, but there are instances when invasive carcinoma may show myoepithelial differentiation. For instance, adenoid cystic carcinoma expresses p63. Metaplastic carcinomas, as well as triple-negative carcinomas with basaloid features, express myoepithelial markers.6 In general, the irregular infiltrative pattern on H&E is characteristic of invasive carcinoma, but being aware of myoepithelial differentiation in these settings will prevent confusion in interpretation.

In summary, the presence of MEC supports a noninvasive process, but the results of immunohistochemical studies for MEC expression should be interpreted within the morphologic context.

References

1.    Moritani S, Kushima R, Sugihara H, et al. Availability of CD10 immunohistochemistry as a marker of breast myoepithelial cells on paraffin sections. Mod Pathol. 2002;15:397–405.
2.    Collins LC, Schnitt SJ. Papillary lesions of the breast: selected diagnostic and management issues. Histopathology. 2008;52:20–29.
3.    Werling RW, Hwang H, Yaziji H, et al. Immunohistochemical distinction of invasive from noninvasive breast lesions: a comparative study of p63 versus calponin and smooth muscle myosin heavy chain. Am J Surg Pathol. 2003;27:82–90.
4.    Hilson JB, Schnitt SJ, Collins LC. Phenotypic alterations in myoepithelial cells associated with benign sclerosing lesions of the breast. Am J Surg Pathol. 2010;34:896–900.
5.    Hilson JB, Schnitt SJ, Collins LC. Phenotypic alterations in ductal carcinoma in situ-associated myoepithelial cells: biologic and diagnostic implications. Am J Surg Pathol. 2009;33:227–232.
6.    Rakha EA, Putti TC, Abd El-Rehim DM, et al. Morphological and immunophenotypic analysis of breast carcinomas with basal and myoepithelial differentiation. J Pathol. 2006;208:495–506.

Jean F. Simpson, MD
Vanderbilt University, Nashville
Member, CAP Immunohistochemistry Committee

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