Collagenous Spherulosis (CS) and Adenoid-Cystic Carcinoma (AdCC) of the breast consist of cribriform proliferations of epithelial and myoepithelial cells with an immunophenotypic overlap of some myoepithelial markers, such as p63 and smooth muscle actin (SMA). To our knowledge, CD10 and HHF35 actin have not been assessed in the differential diagnosis of these two breast lesions. We performed an immunohistochemical study on 6 cases of CS and 9 cases of AdCC. We found CD10, muscle-specific actin (HHF35), Estrogen and Progesterone receptors (ER and PR) to be strongly expressed in CS, but not in AdCC; C-kit was diffusely positive in AdCC and scanty in CS; SMA, p63 and Cytokeratine 5/6 (CK5/6) were positive in both. Our results also confirm that AdCC could be true basal-like neoplasia, probably arising from a basal stem line tending to divergent differentiation toward CK5/6/C-kit+, ER/PR-, epithelial basal-like cell type, and toward a myoepitelial-like cell type, with an incomplete SMA/p63+, CD10/HHF35- immunophenotype. By contrast, CS is a reactive, benign proliferation of two well-differentiated cell types: epithelial (ER/PR+, C-kit-) and myoepithelial cells with a complete immunophenotype including CD10/HHF35 positivity. Our study highlights the usefulness of CD10 and HHF35 in the differential diagnosis and helps to understand the histogenesis of the two lesions.
[Show abstract][Hide abstract] ABSTRACT: Recent biological studies have classified breast carcinomas into HER2-overexpressing, estrogen receptor-positive/luminal, basal- and normal-like groups. According to this new biological classification, the objectives of our study were to assess the clinical, morphologic and immunophenotypic characteristics of adenoid cystic carcinoma of the breast in order to classify this subtype of breast carcinoma. A total of 18 cases of adenoid cystic carcinoma were identified from the Institut Curie files. Clinical information was available for 16 patients with a median follow-up of 6.5 years. Morphologically, all tumors were graded according to the system defined by Kleer and Oberman (histologic and nuclear grade). Immunophenotype was assessed with anti-ER, PR, HER-2, KIT, basal (CK5/6) and luminal cytokeratins (CK8/18) and p63 antibodies. One out of 18 tumors was nuclear grade 1 (16%), nine were nuclear grade 2 (50%) and eight were nuclear grade 3 (44%). All cases were estrogen receptor, progesterone receptor and HER-2 negative. Epithelial cells were strongly positive around glandular lumina with one or both cytokeratins, identifying the coexistence of CK5/6+ cells, CK5/6 and CK8/18+ cells, CK8/18+ cells and p63+ cells. All cases (100%) were also KIT positive. In all, 15 patients were treated by surgery. Nine of them received adjuvant radiotherapy. Follow-up was available for 16 patients. In all, 14 patients were alive. Two of them, initially treated by surgery only, presented a local recurrence. Two patients died (one of them treated by radiation therapy only died from her disease). Our study shows that adenoid cystic carcinoma of the breast is a special, estrogen receptor, progesterone receptor, HER-2 negative and highly KIT-positive, basal-like breast carcinoma, associated with an excellent prognosis. This highly specific immunophenotype could be useful to differentiate adenoid cystic carcinoma of the breast from other subtypes of breast carcinoma such as cribriform carcinoma.
Modern Pathology 01/2006; 18(12):1623-31. DOI:10.1038/modpathol.3800483 · 6.19 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Gene microarray profiling of human breast carcinomas has recently categorized invasive breast carcinomas into 5 distinct subtypes; luminal A, luminal B, normal breastlike, human epithelial growth factor receptor 2 (HER2) overexpressing, and basal-like. Basal-like breast carcinomas are characterized by high expression of basal cytokeratins; low or absent expression of estrogen receptor, progesterone receptor, and HER2/neu; and expression of epidermal growth factor receptor (EGFR) and/or c-kit, and they are frequently associated with breast cancer 1 (BRCA1) mutations and poor clinical outcome. Recent studies have begun to provide insights into the molecular genetics, biology, morphology, and clinical outcome of this subtype of breast carcinoma. We reviewed the literature related to basal-like breast carcinomas to better understand this clinically significant subtype of breast carcinoma.
Archives of pathology & laboratory medicine 01/2010; 134(1):130-3. DOI:10.1043/1543-2165-134.1.130 · 2.84 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Adenoid cystic carcinoma of the breast is a rare neoplasm whose cribriform architecture may mimic invasive cribriform carcinoma, cribriform ductal carcinoma in situ, and collagenous spherulosis. The diagnosis may be even more challenging in needle core biopsies. Immunohistochemical expression of p63 and c-kit distinguishes adenoid cystic carcinoma from invasive cribriform carcinoma and ductal carcinoma in situ. A formal comparison of the immunophenotype of adenoid cystic carcinoma to collagenous spherulosis has not been reported. Of concern is the overlap in myoepithelial markers between these two entities. Both may express S100, smooth muscle actin, and p63. This overlap may cause diagnostic confusion yet is under-emphasized in the literature. The expression profile of newer myoepithelial markers has not been studied in this setting. We evaluated smooth muscle actin, p63, calponin, smooth muscle myosin heavy chain, as well as c-kit, in nine cases of cribriform pattern adenoid cystic carcinoma of the breast in comparison to 12 cases of collagenous spherulosis. Both entities strongly expressed p63 and smooth muscle actin; in adenoid cystic carcinoma, the basaloid myoepithelial-like tumor cells expressed these markers, but the ductular epithelial cells did not. Neither calponin nor smooth muscle myosin heavy chain was expressed in adenoid cystic carcinoma but both were strongly expressed in collagenous spherulosis. Whereas the ductular epithelial cells of adenoid cystic carcinoma were positive for c-kit in all cases, collagenous spherulosis was negative for c-kit. Positive p63 expression by a cribriform breast lesion is not sufficiently specific to confirm a diagnosis of adenoid cystic carcinoma. A broader panel that includes calponin or smooth muscle myosin heavy chain and c-kit is required to exclude collagenous spherulosis in settings in which the distinctive morphologic features that separate these entities are not conspicuously present. Reliance on p63 or smooth muscle actin alone poses a potential diagnostic pitfall in evaluating cribriform breast lesions.
Modern Pathology 11/2006; 19(10):1351-7. DOI:10.1038/modpathol.3800658 · 6.19 Impact Factor
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