Immunoreactivity for c-kit and p63 as an adjunct in the diagnosis of adenoid cystic carcinoma of the breast

Abstract

Adenoid cystic carcinoma of the breast represents a unique clinicopathologic entity with a variable histological appearance and a relatively indolent clinical course in most of the cases. Adenoid cystic carcinoma may be difficult to differentiate from infiltrating duct carcinomas, and in particular from tubular and cribriform carcinomas, especially in core or vacuum-assisted biopsies. We evaluated the prevalence of c-kit, p63, and e-cadherin immunoreactivity in a series of 20 adenoid cystic carcinomas, comparing the results with those obtained in a series of infiltrating tubular carcinomas and infiltrating cribriform carcinomas. The hormone receptor status, proliferation labeling index, and HER/2 immunoreactivity had been previously investigated in all the cases. Three (15%) adenoid cystic carcinomas and all infiltrating tubular and cribriform carcinomas showed estrogen receptor and/or progesterone receptor immunoreactivity (Po0.00001 for estrogen and P ¼ 0.00002 for progesterone receptors). Adenoid cystic carcinomas consistently lacked any immunoreactivity for HER/2, whereas three (15%) infiltrating and cribriform carcinomas showed weak and incomplete membrane staining (P ¼ 0.23077). Membranous immunoreactivity for c-kit was found in all except one (predominantly basaloid) adenoid cystic carcinomas (95%), and in none of the infiltrating tubular and cribriform carcinomas (Po0.00001). Nuclear immunoreactivity for p63 was found in all except three (predominantly basaloid) adenoid cystic carcinomas (85%) and in none of the infiltrating tubular and cribriform carcinomas (Po0.00001). All infiltrating tubular and cribriform carcinomas and 18/20 (90%) adenoid cystic carcinomas showed immunoreactivity for e-cadherin (P ¼ 0.48718). In summary, adenoid cystic carcinomas showed the following phenotype: estrogen receptorþ (two cases, 10%), and estrogen receptor þ /progesterone receptor À /c-kit þ /p63 þ (one case). By contrast, all the infiltrating tubular and cribriform carcinomas showed the estrogen receptor þ /progesterone receptor þ /c-kit À /p63 À phenotype. Our data provide evidence that immunoreactivity for c-kit and/or p63 may be useful in differentiating adenoid cystic carcinomas from other types of breast cancer.

Immunophenotypic overlap between adenoid cystic carcinoma and collagenous spherulosis of the breast: potential diagnostic pitfalls using myoepithelial markers

“…This constellation of findings is relevant because cribriform lesions in the breast may be challenging to diagnose by routine morphology, especially in core needle biopsies, and recent studies recommend an immunohistochemical approach to complement morphologic impressions. 1,3 The overlap in immunophenotype that we report here and its diagnostic implications are not emphasized in the literature.…”

“…Recently, two immunohistochemical features of adenoid cystic carcinoma have been documented: expression of p63, a marker of stem cell or myoepithelial differentiation, and expression of c-kit, a transmembrane tyrosine kinase receptor protein; expression of these markers is similar in adenoid cystic carcinoma arising in the breast and in the head and neck. [1][2][3][23][24][25] The myoepithelial-like tumor cells express p63 in a nuclear pattern, whereas the ductular epithelial cells do not express p63. The converse is seen for c-kit expression: there is cytoplasmic and membrane staining of ductular epithelium but no staining of the myoepithelial-like cells.…”

“…Morphologic and immunohistochemical features helpful in this differential diagnosis have been addressed by others. 1 If the pseudoglandular spaces of adenoid cystic carcinoma are prominent, owing to abundant cylindromatous basement membrane deposits, then the lesion could be mistaken for collagenous spherulosis. In collagenous spherulosis, a well-defined eosinophilic cuticle, representing myoepithelial cell cytoplasm, typically forms a ring-like structure encompassing eosinophilic basement membrane material, or less commonly basophilic mucinous material.…”

“…3 Several studies show that immunoexpression of p63 by the myoepithelial-like tumor cells and of c-kit by the ductular epithelial tumor cells of adenoid cystic carcinoma reliably distinguishes it from both cribriform carcinoma and ductal carcinoma in situ. [1][2][3]7,8 These studies propose that in the evaluation of cribriform breast lesions, p63, and c-kit can be used adjunctively to confirm a diagnosis of adenoid cystic carcinoma. This proposal is potentially problematic because collagenous spherulosis remains in the differential diagnosis and is known to express p63, as well as other myoepithelial markers expressed by adenoid cystic carcinoma, including smooth muscle actin and s100.…”

“…The second, a less numerous population, consists of ductal epithelial cells that form narrow lumens embedded throughout the lesion. [1][2][3][4][5][6] Despite the fact that adenoid cystic carcinoma generally does not express estrogen or progesterone receptors and does not show HER2 gene amplification, it typically behaves favorably and should be distinguished from invasive cribriform carcinoma. 3 Several studies show that immunoexpression of p63 by the myoepithelial-like tumor cells and of c-kit by the ductular epithelial tumor cells of adenoid cystic carcinoma reliably distinguishes it from both cribriform carcinoma and ductal carcinoma in situ.…”