Metaplastic breast carcinomas: are they of myoepithelial differentiation?: immunohistochemical profile of the sarcomatoid subtype using novel myoepithelial markers

Department of Pathology, Medical University of Graz, Graz, Austria.
American Journal of Surgical Pathology (Impact Factor: 5.15). 04/2005; 29(3):347-53.
Source: PubMed


We investigated 20 spindle cell (sarcomatoid) metaplastic carcinomas (MCs) without squamous differentiation. In addition, five high-grade phyllodes tumors were assessed for comparison. Our immunohistochemical antibody panel included pan-cytokeratin (CK), low molecular weight CK (CK8/18), four basal cell type CKs (34betaE12, CK5/6, CK14, and CK17), vimentin antibodies, as well as antibodies to established (SMA, CD10, p63, S-100, maspin, calponin, GFAP, SM-myosin), and novel (CD29, 14-3-3sigma) myoepithelial markers. Sixteen of the 20 tumors (80%) expressed at least two markers of the combination CD10/p63/SMA. S-100 detected 1 case negative for CD10/p63/SMA and 3 cases that only expressed one marker of this combination. While 18 MCs (90%) were positive for CD29, 14-3-3sigma (11 cases) and maspin (9 cases) were observed in 55% and 45%, respectively. Antibodies to pan-CK and the basal cell type CKs were strongly reactive in 12 tumors (60%), but in 6 cases (30%) positivity for these markers was weak and only focal; 2 MCs showed no positivity for CK. The stromal component of all phyllodes tumors was positive for vimentin, whereas all other investigated markers were absent except for focal p63 and CD10 expression in 1 case each. Our findings convincingly show a myoepithelial immunophenotype in sarcomatoid MCs, which is demonstrated by the presence of basal cell type CKs and the combination of the established myoepithelial markers CD10, p63, SMA, and S-100. We conclude that tumors with weak or even absent CK expression should only be diagnosed as primary sarcomas of the breast after exclusion of a myoepithelial immunophenotype. CD29 and 14-3-3sigma represent valuable novel myoepithelial markers in these diagnostically difficult cases.

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    • "The histogenesis of spindle cell carcinoma remains controversial. However, recent immunohistochemical and genomic profiling studies indicate that these tumors are part of the spectrum of basal-like carcinomas and display a myoepithelial or epithelial to mesenchymal transition-like molecular make-up [9] [10] [11]. "
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    ABSTRACT: Compared to epithelial lesions, spindle-cell lesions of the breast are relatively uncommon and, because of that, may cause diagnostic difficulty. The majority of these spindle cell lesions, such as fibromatosis, nodular fasciitis, spindle-cell carcinoma, inflammatory myofibroblatic tumor and angiosarcoma, resemble their more common non-mammary counterparts. A few others, such as pseudoangiomatous stromal hyperplasia for example, specifically arise in breast. This review discusses these mammary spindle cell lesions with a focus on their salient histological features.
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    • "The 14-3-3 r protein has been described as a valuable myoepithelial marker in human mammary tissue (Simpson et al., 2004; Leibl et al., 2005). In our study, double immunostaining of tissues for 14-3-3 r and the MEC specific marker p63, confirmed that 14- 3-3 r is a highly sensitive marker of MECs since all p63 positive cells were also positive for 14-3-3 r. "
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    • "An immunohistochemical panel for keratins was essential to the diagnostic workup of the latter case. Currently, no specific myoepithelial marker is available, so a battery of myogenic markers including basal cell type cytokeratins, p63, and S-100 was performed on subsequent biopsy specimens to establish a myoepithelial differentiation [10]. The cytology in the third case demonstrated large, sarcomatous cells and some multinucleated cells, thereby allowing for the detection of the neoplasm's mesenchymal derivation. "
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    ABSTRACT: Because metaplastic carcinoma of the breast encompasses a great variety of histopathology, diagnostic challenges abound, especially within the realm of cytology. The authors compiled and studied an eight-case series comprised of metaplastic breast carcinomas and lesions initially suspicious cytologically for metaplastic carcinoma in order to assess the degree of cytologic-histologic correlation and to identify recurring problematic themes surrounding the cytology-based diagnosis of this neoplasm. The cytologic and histologic slides from eight cases suspicious for metaplastic breast carcinoma diagnosed by fine needle aspiration (FNA) were collected and analyzed through a seven-year retrospective search of case files at our institution. Based on cytologic characteristics, the cases were separated into three groups. Group 1 consisted of three cases presenting with poorly differentiated adenocarcinoma and squamoid components on FNA. Group 2 was composed of two cases that featured a monophasic, malignant ductal cell population on cytology, while the cytologic specimens for the third group of cases presented with a mesenchymal component with or without a malignant glandular constituent. Cytologic-histologic correlation was present in two of three cases demonstrating a mesenchymal component, and there was 100% sensitivity in the cytologic detection of those mesenchymal elements. However, in only one of three cases was there an accurate cytologic diagnosis of metaplastic carcinoma when squamoid changes were present on FNA. Both cases demonstrating only malignant glandular elements on cytologic specimens revealed an additional component of malignant squamous differentiation upon the examination of mastectomy-derived tissue. These results indicate that squamous-like changes identified on FNA should be interpreted with caution and that sampling error remains a problematic recurrence in cytology. Regardless, there appears to be promise concerning the accurate cytologic diagnosis of metaplastic carcinoma when the lesion is characterized by a mesenchymal component. A study implementing a larger case number is essential in determining the significance of these findings.
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