Metaplastic carcinoma of the breast with dominant squamous and sebaceous differentiation in the primary tumor and osteochondroid metaplasia in a distant metastasis: report of a case with review of sebaceous differentiation in breast tumors

Metaplastic breast carcinoma is an uncommon tumor that develops from conventional ductal mammary carcinoma, usually consisting of squamous and/or spindle cell components and/or mesenchymal elements. Although several morphological subtypes of metaplastic breast carcinoma are known, sebaceous metaplasia has not yet been described in this context. The authors report a case of an 84-year-old woman with a huge, ulcerated primary tumor in her left breast that had already been present for 10 years. Pulmonary and bone metastases and a tumor nodule in the contralateral breast were also detected at the time of admission. Left simple mastectomy was performed. Histological examination of the tumor revealed metaplastic carcinoma consisting of ductal carcinoma, which immunohistochemically exhibited a triple-negative immunoprofile, along with dominant areas of squamous and sebaceous differentiation. Adjuvant chemotherapy was subsequently given with partial regression of the systemic metastases. Seven months after surgery and diagnosis, a new, rapidly growing, large soft tissue metastatic tumor appeared in the intramuscular compartment of the patient's right thigh, which was removed and histologically examined. Morphologically this metastatic tumor showed ductal adenocarcinoma along with areas of sebaceous differentiation and, in addition, osteochondroid metaplasia. Immunohistochemically, unlike the primary, this tumor expressed HER-2. The case is presented because of its rarity, and sebaceous differentiation is also proposed as a novel type of metaplasia in this context, expanding the spectrum of the histological patterns of metaplastic breast carcinoma. The literature concerning breast sebaceous lesions is reviewed, and the hypothetical biological mechanisms responsible for the tumor pathogenesis in this case are discussed.     

Metaplastic breast carcinoma: a retrospective study of 26 cases

Metaplastic breast carcinoma is a rare invasive breast cancer. Metaplastic breast carcinoma is mainly characterized by an epithelial or mesenchymal cell population mixed with adenocarcinoma. We collected 26 cases of metaplastic breast carcinoma in the First Affiliated Hospital of Bengbu Medical College from 2008 to 2014. Tumor size, tumor grade, vascular invasion, ER/PR status, histologic classification, and HER2/neu status were assessed for all cases and the literature was reviewed. Clinicopathologic characteristics of patients diagnosed with metaplastic breast carcinomas and its key points of differential diagnosis were discussed. All patients were female, with the median age of 50 years. The mean tumor size was 3.2 cm. 4 subtypes of metaplastic breast carcinomas were documented. Fibromatosis-like metaplastic carcinomas are typically characterized by wavy, intertwined, gentle spindle cells. When the tumor components are almost squamous cell carcinoma components and the primary squamous cell carcinoma of other organs and tissues are excluded, we can diagnose breast squamous cell carcinoma. In spindle cell carcinoma, atypical spindle cells are arranged in many ways and are usually accompanied by inflammatory cell infiltrate. Cancer with interstitial differentiation has mixed malignant epithelial and mesenchymal differentiation, and the mesenchymal components are diverse. Most tumors are triple negative. At present, surgical resection combined with chemotherapy or radiation therapy is the most effective and acceptable method for treating metaplastic breast carcinoma.     

Metaplastic breast carcinoma with melanocytic differentiation

Metaplastic carcinoma of the breast is a rare heterogeneous malignancy, accounting for <1% of all invasive breast carcinomas, in which adenocarcinoma is found to coexist with an admixture of spindle, squamous, chondroid or bone-forming neoplastic cells. Metaplastic breast carcinoma composed of both epithelial and melanocytic elements is rare, and only seven cases have been reported so far. Reported herein is the case of a 38-year-old woman with a nodular mass in her left breast suspicious of malignancy, discovered during routine ultrasound examination. After histological and immunohistochemical examination of the resected tumor mass, initial diagnosis was collision tumor: ductal invasive carcinoma and metastatic melanoma. The patient underwent quadrantectomy, chemotherapy and radiotherapy. At 6 years follow up the patient was alive and healthy, without local recurrence or metastases. After revising slides and the literature, in addition to patient follow up, it was concluded that this case represents metaplastic carcinoma with melanocytic differentiation.     

Fine-needle aspiration biopsy of metaplastic carcinoma of the breast: Report of a case with abundant myxoid ground substance

Metaplastic carcinoma (MC) is an uncommon neoplasm of the breast. There are several variants of MC depending on the dominant histologic pattern. The components include overt infiltrating ductal carcinoma, extensive squamous differentiation and spindle cell proliferation with or without chondroid or osseous heterologous elements. In FNA smears, only 57% of cases show both ductal carcinoma and metaplastic component. Thus, in almost one half of the cases, the diagnosis is not possible by FNA. Often it is difficult to define the epithelial or sarcomatous character of malignant cells. We describe a case of metaplastic carcinoma of the breast studied by fine-needle aspiration cytology in which myxoid ground substance was the dominant feature in the cytology smears. The rest of the material was composed of scanty isolated atypical cells with large and irregular nuclei. It is important to bear in mind the diagnosis of MC and make a careful search for atypical cells when the cytological smears are mainly composed of myxoid ground substance. Diagn Cytopathol 1996;14:325–327. © 1996 Wiley-Liss, Inc.     

Mixed metaplastic carcinoma of the breast associated with pregnancy: Diagnostic dilemmas in fine‐needle aspiration cytology

Metaplastic carcinoma of the breast represents a rare entity characterized by the simultaneous presence of ductal, squamous, and/or mesenchymal components in several proportions. There are limitations in fine‐needle aspiration diagnosis due to its pathological heterogeneity. When it develops under pregnancy and lactation influence, the cytologic evaluation appears to be more difficult and accurate diagnosis often proves challenging. We describe a case of mixed metaplastic carcinoma with dominant areas of squamous metaplasia, sarcomatoid stroma with spindle cells, and a minor component of cartilaginous metaplasia. We notify our experience in diagnostic approach of this entity focusing on differential diagnosis. Diagn. Cytopathol. 2009. © 2009 Wiley‐Liss, Inc.     

Fine-needle aspiration of a metaplastic breast carcinoma with extensive melanocytic differentiation: a case report

Metaplastic carcinomas of the breast are uncommon breast tumors with aberrant cellular differentiation, most commonly showing ductal, squamous, and mesenchymal components. A breast carcinoma composed of both epithelial and melanocytic differentiation is rare, with only four previously reported cases in the literature. We present the fifth reported case, where the diagnosis was suggested by fine-needle aspiration (FNA) and later confirmed after the surgical specimen was excised. Histologically, this neoplasm revealed multidirectional differentiation, consisting primarily of squamous and melanocytic cell types, with focal glandular and osseous metaplasia. Based on the morphologic, immunohistochemical, and ultrastructural findings, we conclude that such tumors fall within the spectrum of metaplastic carcinomas of the breast. We believe that this case will further contribute to the understanding of this enigmatic tumor.     

Metaplastic carcinoma of the breast (carcinosarcoma variant): a case report

A case of a female patient aged 60 yrs, with metaplastic carcinoma of the breast which is a rare neoplasm is presented. Although it is a tumor of the ductal type, the predominant component of the neoplasm has an appearance other than glandular pattern and more in keeping with other cell types. Metaplastic carcinoma runs a very aggressive course and bears an unfavourable prognosis.     

Report of a metaplastic carcinoma of the breast with multi-directional differentiation: an adenoid cystic carcinoma,a spindle cell carcinoma and melanoma

Metaplastic carcinoma of the breast is a heterogeneous neoplasia, generally composed of both epithelial and mesenchymal components. We report an unusual case of mammary metaplastic carcinoma in a 51-year-old female patient. Needle core biopsy from the tumour mass showed malignant epithelial and sarcomatous features. The resection specimen revealed a multi-directional tumour differentiation consisting predominantly of: firstly, a poorly differentiated basaloid epithelial cell type, consistent with an adenoid cystic carcinoma; secondly, areas of a spindle cell carcinoma; and, thirdly, areas with a melanocytic differentiation. This is the first report on a metaplastic carcinoma of the breast presenting as an admixture of an adenoid cystic carcinoma and melanoma.     

Metaplastic carcinoma of the breast

Metaplastic carcinomas of the breast are a rare but morphologically heterogeneous group of tumours with a distinct immunoprofile. We describe a case of metaplastic carcinoma with mesenchymal differentiation in a patient who presented with a left breast lump. These tumours are typically composed of metaplastic cartilaginous, osseous or rhabdomyoid elements, usually with a malignant epithelial component. Here we outline the current WHO classification of metaplastic carcinomas of the breast, key clinical features and some diagnostic challenges.     

Metastatic metaplastic carcinoma of the breast: diagnosis by bronchial brush cytology

Metaplastic carcinoma of the female breast is an uncommon lesion that may metastasize to body sites. To our knowledge, this is the first reported case of pulmonary metastasis diagnosed on bronchial brush cytology. The patient presented with pulmonary symptomatology 1 yr and 3 mo after a left modified radical mastectomy for breast carcinoma. Bronchoscopic examination revealed an endobronchial lesion partially obstructing the bronchus intermedius. Bronchial brush cytology showed the presence of nonkeratinizing squamous tumor cells admixed with a few scattered clusters of tumor cells with glandular features. Histologic review of the original breast lesion showed a metaplastic carcinoma of the breast with a predominant squamous-cell component. Accurate knowledge of a patient's clinical history is necessary to differentiate a second primary lesion from a metastatic one, particularly when the original lesion is so uncommon.     

Metaplastic carcinomas of the breast: diagnostic challenges and new translational insights

Comprising less than 1% of invasive carcinomas of the breast, metaplastic carcinomas are a heterogeneous group of malignant tumors in which part or all of the carcinomatous epithelium is transformed into a nonglandular (metaplastic) growth process. Metaplastic carcinomas with a low-grade spindle cell component resembling fibromatosis, as in our present case, are worthy of particular note because they are infrequent, difficult to recognize, and have a high risk of local recurrence. The differential diagnosis of metaplastic carcinomas depends on the degree of atypia observed in the tumor and includes exuberant scars, fibromatosis, nodular fasciitis, myofibroblastomas, pseudoangiomatous stromal hyperplasia, acute and chronic abscess with fat necrosis, malignant phyllodes tumor, and primary or metastatic sarcoma. Limited studies done on the molecular pathology of metaplastic carcinomas show that activation of the Wnt signaling pathway is common in these tumors and that approximately 70% of metaplastic carcinomas show EGFR gene amplification and overexpression. This may have treatment implications because they may lead to targeted treatment for patients with metaplastic carcinomas.     

Metastatic metaplastic breast carcinoma mimicking pulmonary squamous cell carcinoma on fine‐needle aspiration

Metaplastic squamous cell carcinoma (SCC) of the breast is a rare type of breast cancer. Metastases to the lung, which can be a major site of second primary tumor development among breast cancer patients, are difficult to distinguish from primary SCC of the lung and present a unique challenge for pathologists. There are few available discriminating immunohistochemical markers as squamous differentiation typically leads to loss of expression of characteristic primary epithelial cell markers of both breast and lung origin. GATA protein binding 3 (GATA‐3) is a useful marker of breast origin in metastatic ductal and lobular carcinomas including poorly differentiated triple‐negative carcinomas and some metaplastic carcinomas. Here, we present a case of metastatic SCC presenting as a solitary lung mass with regional lymph node metastases and a single satellite lesion in a patient with a history of metaplastic SCC of the breast. In addition to the routine markers of squamous differentiation, the metastases were also positive for estrogen receptor (ER) and GATA‐3 on cytologic material obtained by transbronchial FNA. This suggests that immunoreactivity for ER and GATA‐3 may support a diagnosis of metastatic SCC in the context of a prior metaplastic SCC of the breast. Diagn. Cytopathol. 2015;43:844–849. © 2015 Wiley Periodicals, Inc.     

Metaplastic carcinoma with extensive chondroid differentiation in the breast (chondroid carcinoma)

Metaplastic breast carcinoma is very rare, and metaplastic carcinoma with chondroid differentiation is even rarer. Here, we report a case of metaplastic carcinoma with extensive chondroid differentiation mimicking chondrosarcoma that was challenging to diagnose. The tumor was characterized by an abundant chondromyxoid matrix. The definitive area of classic invasive ductal carcinoma was minimal. The peripheral portion of the tumor showed increased cellularity with pleomorphism and definitive invasive growth. Tumor cells in the chondrosarcomatous areas were diffusely immunoreactive for S-100 protein, patchy positive for cytokeratin, but negative for epithelial membrane antigen (EMA). Tumor cells in carcinomatous areas were diffusely positive for cytokeratin, S-100 protein, and patchy positive for EMA. In both areas, tumor cells were negative for smooth muscle actin (SMA) and CD34, while oncoprotein p53 was overexpressed. When pathologists encounter breast tumors with chondroid differentiation, careful sampling and immunohistochemistry for cytokeratin and SMA are most helpful to differentiate metaplastic carcinoma from malignant phyllodes tumor and malignant adenomyoepithelioma.     

Spindle cell carcinoma of the breast,a mimicker of benign lesions: case report and review of the literature

The clinical and pathologic features of a breast tumor with unusual morphology in a 69-year-old woman are presented. Spindle cell carcinoma is considered one of the variants of metaplastic carcinoma and is commonly described in the upper aerodigestive tract, but it is relatively rare in the breast. This case is uniquely different from the usual cases of spindle cell carcinoma because of the lack of squamous differentiation or a recognizable infiltrating ductal component at the light microscopic level. With immunohistochemical stains using keratin and actin, a rather prominent network of infiltrating compressed ductal structures became apparent. These immunohistochemical features are consistent with the current concept of myoepithelial origin for metaplastic carcinomas. Although mention has been made in the literature of cases in which this "bland" carcinoma could be confused with benign nonneoplastic conditions, few illustrated examples exist. The prognosis for this particular subgroup of metaplastic carcinoma may be somewhat better than that for ordinary ductal carcinoma. For prognostic purposes, this entity should be distinguished from other metaplastic carcinomas and sarcomas, but more importantly, it should be differentiated from lesions such as nodular fasciitis, reactive granulation tissue, and fibromatosis, with which it may be confused histologically.     

Fine-needle aspiration biopsy of monophasic variant of spindle epithelial tumor with thymus-like differentiation of the thyroid: report of one case and review of the literature

Spindle epithelial tumor with thymus-like differentiation (SETTLE) is a rare biphasic tumor of the thyroid with approximately 20 well-documented cases reported in the English literature. Although a monophasic variant of SETTLE is conceivable, the majority of the reported cases were truly biphasic tumors. A minimal amount of epithelial component was present in the reported cases of so-called spindle-cell predominant SETTLE. Here, we report an apparently monophasic case of SETTLE in a 16-yr-old girl, in which no epithelial cells were identified in either fine-needle aspiration biopsy (FNAB) or the subsequent hemithyroidectomy specimen. The FNAB smears were moderately cellular and composed of single and loosely grouped spindle cells with homogenous metachromatic material, which could be mistaken as amyloid, erroneously suggesting medullary thyroid carcinoma. The compact nodules of uniform spindle cells in histology sections raised the possibility of monophasic synovial sarcoma. The spindle cells stained positive for both cytokeratin and vimentin, but were negative for thyroglobulin and calcitonin as well as neuroendocrine markers, confirming the diagnosis of SETTLE.     

伴有神经内分泌分化的乳腺梭形细胞癌

目的探讨乳腺伴有神经内分泌分化的梭形细胞癌的病理形态学和免疫表型特点及鉴别诊断。方法复习2500例乳腺癌切片,找出以梭形细胞占主要优势（〉80％）的癌5例,其中2例梭形细胞型导管内癌和3例梭形细胞型浸润癌。采用HE、阿辛蓝（AB）／PAS和网织染色,以及用癌胚抗原（CEA）、上皮膜抗原（EMA）、细胞角蛋白（CK7、3413E12、AE1／AE3）、神经元特异性烯醇化酶（NSE）、突触素、嗜铬蛋白（cg）A、Lue-7、波形蛋白,S-100、平滑肌肌动蛋白（SMA）、calponin、雌激素受体（ER）、孕激素受体（PR）、c—erbB-2、E-钙黏素、Ki-67、p53抗体进行免疫组织化学观察。其中4例有随访信息。结果患者平均年龄在68岁。镜下：5例癌细胞形态主要为长梭形的上皮样细胞,3例有少数胞质内空泡状细胞,4例可见散在AB阳性细胞。免疫组织化学5例均表达AE1／AE3、EMA、CEA、E-钙黏素和突触素,CK7有4例表达,NSE阳性3例,CgA和Lue7阳性2例,ER阳性4例,PR阳性2例,1例表达c-erbB-2,1例有灶状波形蛋白阳性。免疫组织化学结果显示2例梭形细胞型导管内癌和1例梭形细胞型浸润性癌是梭形细胞型的神经内分泌癌,另外2例梭形细胞型浸润性癌是伴有神经内分泌分化的化生性癌。随访3例存活（24～58个月）,1例27个月内死亡。结论上皮样梭形细胞和细胞内黏液的出现是乳腺伴有神经内分泌分化癌的一个形态学特点。梭形细胞神经内分泌型导管内癌需要和普通导管增生及导管内乳头状瘤鉴别。梭形细胞型的神经内分泌癌和伴神经内分泌分化的梭形细胞浸润性癌需要与梭形细胞肌上皮肿瘤、恶性黑色素瘤及某些软组织肿瘤鉴别。     

Metaplastic carcinoma of the breast--diagnosis by aspiration biopsy cytology: report of two cases and literature review

The unusual metaplastic carcinomas have a variety of names, each emphasizing the dominant histologic pattern. Components may include features of ductal, spindle, or squamous carcinoma with pseudosarcomatous, cartilaginous, or boney areas. A few reports from individual tumors examined by fine-needle aspiration biopsy have emphasized an array of findings. This study includes two of our cases with a review of 12 others from the literature. The breast neoplasm has a characteristic pattern on aspiration biopsy cytology (ABC). The cell-rich aspirate reveals benign multinucleated giant cells intermingled with malignant spindled or squamous cells on a background of necrotic debris, inflammatory cells, and blood. Additionally, cells from infiltrating ductal carcinoma and mesenchymal fragments are often seen.     

Papillary carcinoma of the breast in a male patient with a treated prostatic carcinoma diagnosed by fine-needle aspiration biopsy: a case report and review of the literature

Papillary carcinoma of the male breast is very rare. In this case report, we describe the cytologic, histologic, immunohistochemical, and radiological findings of a papillary carcinoma of male breast. A 67-yr-old man, who had a previous history of prostatic adenocarcinoma, presented with a retroareolar painless mass. There was no known history of breast cancer in his family. A fine-needle aspiration biopsy (FNAB) was performed. Cytological examination revealed a cellular aspirate with three-dimensional papillary clusters. A diagnosis of papillary lesion favoring papillary carcinoma was rendered. Immunohistochemical staining of the cell-block of the FNAB revealed the presence of mammaglobin, and the absence of prostatic specific antigen. The patient underwent lumpectomy, which showed a moderately differentiated infiltrating papillary carcinoma with adjacent areas of ductal carcinoma in situ. FNAB is a useful technique in identifying male breast carcinoma. In conjunction with ancillary studies, this procedure can effectively differentiate between a primary versus metastatic lesion.     

Breast carcinoma with predominant neuroendocrine differentiation

Neuroendocrine differentiation can be identified in a subset of human breast carcinomas, either as scattered cells or as a predominant neuroendocrine component. We report a case of an invasive breast carcinoma largely composed of neuroendocrine cells. Eight years after a left mammary lumpectomy for a pT2N1MO SBR III invasive ductal carcinoma, a 67-years-old woman presented with a metastastic neuroendocrine sternal mass. To establish a relationship between mammary carcinoma and bone metastasis, histological slides of both the breast tumor and axillary lymph nodes were reviewed, and an immunohistochemical study was performed. They showed that: a) the mammary carcinoma was composed of a majority of small and large neuroendocrine cells synaptophysin +, NCAM+, chromogranin - (80%), associated with 2 other differentiated non endocrine components, one of metaplastic squamous carcinoma (10%) and the other of ductal carcinoma (10%); b) 4 axillary lymph nodes were involved by the ductal component which contained few NCAM + but synaptophysin - cells; c) Estrogen and progesterone receptors and HER2 were negative in the breast tumor and the metastatic nodes. We discuss the histogenesis of composite mammary carcinomas with neuroendocrine differentiation, the outcome of each component and the prognostic relevance of such a diagnosis.     

Spindle cell tumours of the breast: practical approach to diagnosis

Spindle cell tumours of the breast are uncommon and often present diagnostic challenges. The most important is the sarcomatoid/metaplastic carcinoma, which has monophasic and biphasic variants. Each of these groups presents special diagnostic difficulties. In the monophasic variant the mesenchymal component predominates and the epithelial element forms a minor component often detected only after immunohistochemical study. The spindle cell areas may be bland and therefore under-diagnosed as nodular fasciitis or fibromatosis. Alternatively they may be highly malignant with a pattern that is misinterpreted as primary sarcoma of the breast. In the biphasic variant, the difficulty is in distinguishing between sarcomatoid carcinoma, myoepithelial carcinoma or malignant phyllodes tumour. Other spindle cell lesions of the breast include the various myofibroblastic tumours, the spindle cell variant of adenomyoepithelioma, the varied primary breast sarcomas, metastatic tumours with spindle cell morphology and, finally, the very rare follicular dendritic cell tumour. A simple practical approach to the diagnosis of spindle cell lesions is presented to help the general surgical pathologist to compile a differential diagnosis and to arrive at the correct conclusion