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The clinicopathologic features of 32 metaplastic carcinomas with heterologous osteocartilaginous elements are reported. Each neoplasm consisted of invasive adenocarcinoma accompanied by a cartilaginous or osseous component. In 10 neoplasms, this consisted of cartilage and in 2 the heterologous element was osteoid or bone exclusively. The remaining 20 neoplasms contained a mixture of cartilaginous and osseous components. All patients were women; mean age was 56 years. Twenty-four patients were treated using mastectomy and eight by local excision. Twenty-six patients underwent axillary lymph node dissection. Lymph node metastases were detected in 6 of the 26 (23%) patients who underwent axillary dissection. Clinical follow-up was available for 29 of 32 patients (91%). Local recurrence or distant metastases developed in 6 patients (21%) within 2 years of initial treatment, and 4 of these patients died of metastatic carcinoma. The overall 5-year survival rate was 60%. When compared with control patients with infiltrating duct carcinoma, the group with metaplastic carcinoma tended to have a more favorable prognosis after adjustment for nodal status and tumor size. The prognosis of patients with metaplastic mammary carcinoma with heterologous osteocartilaginous elements is dependent on tumor stage at diagnosis. Immunohistochemical studies for 34BE12, p53, retinoblastoma protein, HER/2neu (polyclonal), epidermal growth factor receptor, and cyclin D1 were performed in 18 cases. Positive immunohistochemical staining was found as follows: 34BE12: n = 13 (72%); p53: n = 11 (61%); retinoblastoma protein: n = 12 (66%); HER2/neu: n = 2 (11%); epidermal growth factor receptor: n = 7 (38%); and cyclin Dm: n = 5 (28%). Positive staining for 34BE12 was observed in the carcinomatous component in 5 (38%) of the neoplasms, in the metaplastic component in 2 (15%), and in both elements in 6 (64%). A p53 staining was observed in the carcinomatous component exclusively in 4 (36%) of 11 p53-positive tumors. No disparity in p53 staining was noted between the epithelial and metaplastic elements in the other p53-positive tumors. Expression of these markers did not correlate with clinicopathologic features such as patient age, tumor size, tumor type, relative proportion of metaplastic elements, and axillary nodal status and was not predictive of disease-free survival.
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PMID:Metaplastic carcinoma of the breast with osteocartilaginous heterologous elements. 950 Feb 19

Metaplastic breast carcinomas are rare neoplasms showing both carcinomatous and sarcomatous elements. In this report we describe eleven cases of metaplastic breast carcinoma focusing on pathological features and the clinical behaviour of six patients with breast carcinoma with chondroid metaplasia (MCC). We collected eleven cases from 1996 to 2001: immunohistochemical tests were performed in order to obtain data on estrogen and progesterone receptors and the production of p53 gene and HER/2 neu. Neoangiogenesis was studied counting vessels immunohistochemically-stained with CD31 antibody. Six cases showed chondroid metaplasia, three cases were spindle cell carcinoma and two were metaplastic squamous carcinoma. The majority of patients (64%) had pT2 tumors without axillary node metastases: only two cases with spindle or squamous metaplasia showed nodal involvement. Fifty percent of MCC were pT1b-c tumors: no axillary metastases were observed. Vascular invasion was observed in all squamous and spindle cell types and in 66% of MCC: estrogen and progesterone receptors were absent in 90% of the tumors. Immunohistochemical staining for HER2/neu was detected in 72% of spindle cell and squamous carcinomas and in 33% of MCC. Three cases staining highly for p53 were chondroid carcinomas: the staining was uniform both in carcinomatous and in sarcomatous tissue. The majority of metaplastic carcinomas had high angionesis. One patient with a chondroid metaplastic carcinoma was found to be a carrier of a BRCA1 mutation similar to the one responsible for sickle cell disease, possibly altering the spatial structure of the gene product. Only six patients had follow-up periods longer than 36 months: five women were alive and disease-free: one patient with pT2N1 squamous metaplastic carcinoma died of disease 14 months after diagnosis. The six women with MCC were alive and disease-free. Surgical and adjuvant treatment should follow the guidelines for the other most common breast cancers even if the need for chemotherapy is unknown due to the absence of large series randomized or observational data.
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PMID:Metaplastic breast carcinoma: pathology and clinical outcome. 1268 Jan 65

We present an extensive immunohistochemical analysis of 7 mammary sarcomas that did not fit into any specific soft tissue sarcoma category. Histologically, they were composed of spindle cells with highly pleomorphic nuclei and abundant mitoses. Our immunohistochemical antibody panel included pan-cytokeratin (CK), basal cell type CKs (34betaE12, CK5/6, CK14, CK17) and vimentin antibodies, antibodies to established (SMA, CD10, p63, S-100, maspin, calponin, GFAP, SM-myosin), and novel (CD29, 14-3-3sigma) myoepithelial markers, as well as antibodies to CD34, desmin, h-caldesmon, steroid receptors (estrogen, progesterone, androgen), and EGFR (Her-1). Whereas CKs, CD34, desmin, and h-caldesmon were not expressed, all tumors were positive for CD10 and vimentin. CD29 and SMA were observed in 3 cases each (43%), and p63 and calponin in 2 cases each (29%). Other myoepithelial markers and steroid receptors were absent, except androgen receptors, which were expressed in one sarcoma. Five sarcomas showed positivity for EGFR. The distinction of specific, histogenetically defined sarcoma entities (such as leiomyosarcoma, angiosarcoma, liposarcoma) from NOS-type sarcoma with CD10 expression is usually clear-cut because the former exhibit a characteristic histomorphology and immunoprofile. Phyllodes tumors with stromal overgrowth or recurrent phyllodes tumors lacking epithelial structures as well as periductal stromal sarcomas can be ruled out by their frequent expression of CD34 and negativity for myoepithelial markers. The most important differential diagnosis is sarcomatoid metaplastic carcinoma because its treatment includes axillary lymphadenectomy. Since some NOS-type sarcomas with CD10 expression and most metaplastic carcinomas show positivity for CD29, SMA, and p63, differential diagnosis can be extremely difficult and requires extensive immunohistochemical evaluation for CKs and additional myoepithelial markers such as S-100, 14-3-3sigma, and maspin. The immunophenotype of NOS-type sarcomas with CD10 expression suggests that these neoplasms represent a mammary sarcoma variant with myoepithelial features.
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PMID:Mammary NOS-type sarcoma with CD10 expression: a rare entity with features of myoepithelial differentiation. 1662 90

Carcinosarcoma of the breast, often referred to as metaplastic carcinoma of the breast, is a rare malignancy with two distinct cell lines described as a breast carcinoma of ductal type with a sarcoma-like component. Clinically, carcinosarcoma of the breast is an aggressive breast cancer. The prognosis for carcinosarcoma of the breast is less favorable compared to more common types of breast cancer such as infiltrating ductal or lobular carcinoma. Currently, the evaluation of breast carcinoma includes hormone receptor analysis of the tumor tissue, with those positive for estrogen or progesterone responding better to both hormonal and chemotherapy.Trastuzumab (Herceptin(R)) is available as an adjunct treatment for tumors which over-express the HER2/neu gene. Typically, metaplastic carcinomas of the breast do not express the estrogen or progesterone receptors and do not over-express the HER2/neu oncogene. As a result of this "triple negative" phenotype, such tumors tend to be more aggressive and are unlikely to respond to targeted therapy with Herceptin. The epidermal growth factor receptor HER-1/EGFR protein is expressed in the majority of metaplastic carcinomas and thus may serve as a potential therapeutic target for EGFR inhibitors such as gefitinib and cetuximab. The two cases we describe exemplify the aggressive nature of carcinosarcoma of the breast and support the findings that this tumor type does not express the common receptors found in other breast carcinomas. These case reports also emphasize the need for investigating the role for blockade of the HER-1/EGFR receptor with targeted therapies when found to be over-expressed in the primary tumor.
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PMID:Carcinosarcoma of the breast: two case reports and review of the literature. 1912 25

Invasive breast cancer is divided into luminal A, luminal B, HER2 overexpression, basal-like (BL) and normal-like subtypes, among which the BL subtype has the worst prognosis. The purpose of this study was to determine the clinicopathological and cytological characteristics of BL breast cancer (BLBC). Fine-needle aspiration cytology samples from 17 patients with consecutive BLBC were investigated, and the findings were compared with those of other subtypes (10 cases each) for the following cytomorphological features: necrosis; lymphocyte infiltration; mitotic index; apoptosis; naked nuclei; nuclear/cytoplasmic ratio; nuclear margin, size and pleomorphism; chromatin granularity and density; and nucleolar appearance. Histologically, the BLBCs were heterogeneous, and included medullary carcinoma and metaplastic carcinoma, in addition to invasive ductal carcinoma. Cytologically, high mitotic index, naked nuclei, and irregular nuclear margin were significantly observed when compared with both the luminal A and B subtypes. Large nuclei with nucleoli and lymphocyte infiltration were frequently seen compared with the luminal A and B subtypes, respectively. Squamous nodules were seen in all metaplastic cases, but not in the HER2 overexpression subtype. Lymphocyte infiltration, squamous metaplasia, and nuclear findings such as a high mitotic index, naked or large nuclei, an irregular nuclear margin and the presence of nucleoli, may be clues indicating BLBC.
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PMID:Fine-needle aspiration cytology of triple-negative basal-like breast cancer. 2198 94

This study involved 40 ER-negative female patients with invasive breast cancer, aged between 25 and 88 years, diagnosed at Emergency County Hospital of Craiova, Romania, during a two-year interval (2010-2011). All patients that took part in the study were subjected to a preoperative mammography exam, and later to HP and IHC exams, in order to detect the ER, PR and HER2 status. These exams were followed by CISH in ambiguous HER2 cases. The tumor detection method was palpation in 16 cases, whereas in 24 cases the method used was the screening mammography. Histopathologically, the analyzed tumors were infiltrative ductal carcinoma (35 cases), lobular carcinoma (one case), mucinous (two cases) and metaplastic carcinoma (two cases). Depending on the status of the oncoprotein HER2, the 40 ER-negative female patients included in the study formed two groups: the ER-negative, HER2-positive (11 cases, 27.5%) formed the first group and the ER-negative, HER2-negative (29 cases, 72.5%) formed the second group. Depending on the expression of the receptors for progesterone, 60% of cases were classified as triple negative mammary carcinomas (ER-, PR-, HER2-). The comparative study of the ER-negative, HER2-positive and the ER-negative, HER2-negative mammary carcinomas showed that the tumors of the ER-negative, HER2-positive group were mostly high degree cancers (80% vs. 56%), with negative progesterone receptors (81.81% vs. 48.27%), associated with axillary lymph node metastasis (63.63% vs. 48.27%), and were detected at a higher cancer stage (II/III) (81.81% vs. 62.06%). Regarding the mammographic features, the ER-negative HER2-positive breast cancers are more likely to be irregular masses (62.5% vs. 33.33%), with spiculated margins (45.45% vs. 6.9%), frequently associated with dense or heterogeneously dense breast (82% vs. 69%) and pleomorphic calcifications (62.5% vs. 28.57%) comparative with ER-negative HER2-negative cancers that were more frequently round/oval mass, with indistinct margins and a great variety of morphological types of calcifications. The correlations between imaging and clinical aspects, together with the biomarker expression in breast cancers may sooner suggest the biological characteristics of these tumors, thus hinting at their evolution and helping to identify female patients with invasive breast cancer that will positively respond to an aimed therapy.
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PMID:Negative estrogen-receptor invasive breast carcinoma: mammographic aspects, correlations with HER2/neu oncoprotein status. 2318 36

Metaplastic carcinoma of the breast is a rare and heterogeneous subtype of breast carcinoma with a generally poor outcome, and few therapeutic options once disease recurs or progresses. Metaplastic carcinomas of the breast are usually of a larger size at diagnosis, with less frequent nodal metastasis compared with invasive ductal carcinoma no special type, and lack hormone and HER2 receptor expression. Recent research has revealed some potentially actionable genetic changes in a subset of these rare tumours. However, ongoing efforts to further characterise the genetic basis and the molecular alterations underlying the distinctive morphological and clinical characteristics of these tumours are needed in order to identify new targets for treatment. This review will describe the theories of pathogenesis of metaplastic breast carcinoma, and highlight genetic changes and potential therapeutic targets in this generally poor prognosis malignancy.
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PMID:Molecular alterations in metaplastic breast carcinoma. 2337 78

Fibromatosis-like metaplastic carcinoma (FLMCa) of the breast is a rare low-grade spindle cell carcinoma, of which the biological characteristics have not been well studied. This study aims to assess, in FLMCa, immunohistochemical expression of claudins (CLDN) and features connected with the claudin-low subtype, such as the presence of tumor initiating cells (TIC), epithelial-mesenchymal transition (EMT) phenotype, as well as EGFR activating mutations. Three cases of FLMCa were retrieved from our hospital archives. Histological and immunohistochemical characteristics were reviewed. Expression of CLDN-1, CLDN-3, CLDN-4 and CLDN-7, CD44 and CD24 (TIC phenotype), and vimentin and E-cadherin (EMT features) were studied. EGFR mutations on exons 18, 19, 20, and 21 were investigated by real-time PCR. In all cases, the low-grade spindle cell component was predominant, with two cases presenting <5 % of epithelioid and squamous areas. The tumors expressed basal cytokeratins and vimentin and were hormone receptor and ERBB2 negative. CLDN membrane expression was negative in the spindle cell component. The epithelioid areas were CLDN-1 positive. Nuclear/cytoplasmatic expression of CLDN-4 was observed in all components, except in one case in which it was strongly expressed in the non-spindle areas. All three cases were CD44+/CD24-. E-cadherin was focally expressed in epithelioid cells, only in the squamous areas. Activating EGFR mutations were not found. One patient developed local recurrences, metastases and died. FLMCa have the immunohistochemical profile of claudin-low breast tumors, with low expression of adhesion molecules, presence of TIC and EMT phenotype. No EGFR activating mutations were found.
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PMID:Fibromatosis-like metaplastic carcinoma of the breast has a claudin-low immunohistochemical phenotype. 2490 73

To establish a series of objective parameters to predict the risk of relapse from axillary lymph node-negative (ANN) breast cancer, and evaluate the patterns of recurrence according to molecular subtypes, we collected information on 2126 consecutive breast cancer patients operated between 2002 and 2006. In this case-control study, 212 patients experiencing recurrence or breast cancer related death were defined as 'poor group'. Another 212 patients were selected from the remaining cases with stratified sampling method to comprise the 'good group'. Significant differences were found in vascular invasion, grade and molecular subtype between the two groups. Expression of ER and PR in the 'poor group' was lower (P < 0.05). However, positive rates of Ki67, p53 and VEGF in the 'poor group' were higher (P < 0.05). Multivariate analysis revealed that molecular subtype, expression of VEGF, tumor grade, and vascular invasion were closely correlated with bad outcome. Analysis of the 'poor group' demonstrated that 'HER2 positive' and 'triple negative' subtypes more commonly suffered from distant metastases and death. No metastasis was found in patients with pure invasive papillary carcinoma, invasive cribriform carcinoma or adenoid cystic carcinoma, whereas the diagnoses of invasive micropapillary carcinoma, invasive apocrine carcinoma, invasive papillary carcinoma mixed with invasive ductal carcinoma, or metaplastic carcinoma were correlated with distant metastasis and death. In conclusion, molecular subtype and expression of VEGF are useful markers for predicting prognosis of ANN breast cancer patients. 'Luminal A-like' subtype has better outcome than others. Moreover, molecular subtypes have different recurrence patterns.
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PMID:Predictors of recurrence in breast cancer subtypes with negative lymph node in a Chinese population. 2503 41

Apocrine carcinoma, which is strictly defined as over 90% of tumor cells showing apocrine differentiation, is a rare variant of breast cancer. Here we report an uncommon case in which apocrine carcinomas developed concurrently in both breasts; in addition, a sarcomatoid spindle cell lesion was coincident in the right breast. Both apocrine carcinomas were immunohistochemically negative for estrogen receptor (ER) and progesterone receptor (PgR), but diffusely positive for androgen receptor (AR), GCDFP-15, and HER2. The presence of intraductal components in bilateral carcinomas and the absence of lymph node metastasis suggested that they were more likely to be individual primary lesions rather than metastatic disease. The spindle cell lesion showed a relatively well-circumscribed nodule contiguous with the apocrine carcinoma. HER2 oncoprotein overexpression was observed not only in the apocrine carcinoma, but also in the spindle cell lesion. Since the spindle cell component was intimately admixed with apocrine carcinoma and had focal cytokeratin expression, we diagnosed it as metaplastic spindle cell carcinoma, which was originated from the apocrine carcinoma. To our knowledge, this is the first case report of a patient with synchronous bilateral apocrine carcinomas coinciding with metaplastic carcinoma.
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PMID:HER2-Positive Metaplastic Spindle Cell Carcinoma Associated with Synchronous Bilateral Apocrine Carcinoma of the Breast. 2530 67


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