Breast adenomyoepithelioma and adenomyoepithelioma with carcinoma (malignant adenomyoepithelioma) with associated breast malignancies: A case series emphasizing histologic,radiologic, and clinical correlation

The 2012 World Health Organization (WHO) classification of breast tumors distinguishes adenomyoepitheliomas (AMEs) as benign tumors composed of a biphasic proliferation of phenotypically variable myoepithelial cells around small epithelial lined spaces. Many AMEs have demonstrated benign behavior and are often cured with excision with negative margins, but some have exhibited malignant transformation of the myoepithelial cells, ductal epithelial cells, or both. When one of the components is histologically malignant, it is termed AME with carcinoma. Due to the rarity, the literature correlating imaging, histology, and clinical outcome is limited. A retrospective review was undertaken. A review of an institutional pathology database identified 14 cases with AME or malignant AME. Most AMEs had nonspecific imaging findings and were categorized as Bi-Rads 4. Histologic features of AME did not correlate with prior or concurrent breast malignancies or any radiographic features. Clinical follow up could be obtained for all but one case (mean follow up time = 75 months). 5 cases had no known treatment post-biopsy and 5 patients received mastectomy. No recurrences were noted. 3/13 cases of benign AME had associated breast malignancies including invasive ductal adenocarcinoma and ductal carcinoma in-situ. 1 case of malignant AME had a synchronous separate malignant phyllodes tumor. Given the unclear and unpredictable propensity for malignant transformation, conservative excision with negative margins currently seems appropriate.     

Myoepithelial Carcinoma of the Breast with Focal Rhabdoid Features

Myoepithelial carcinoma of the breast is extremely rare and only 33 cases have been reported in the English literature. Herein, we report a case of myoepithelial carcinoma of the breast with focal rhabdoid features. The patient was a 67‐year‐old woman, who presented with a lump of the left breast that rapidly grew to 3 cm in diameter within 3 months. Lumpectomy revealed a solid and whitish colored tumor, which was composed mainly of elongated spindle‐shaped cells with mild atypia, focal necrosis, and infiltrative margin. In a small area of the lesion, ovoid tumor cells exhibited eccentric nuclei with centrally located nucleoli and plump cytoplasm including round eosinophilic inclusions, resembling a rhabdoid tumor. Immunohistochemically, both types of tumor cells exhibited a myoepithelial phenotype. MIB‐1 index was 30%. The cytoplasmic inclusion of the ovoid cells exhibited immunopositivity for both vimentin and cytokeratin. From these findings, this tumor was diagnosed as a myoepithelial carcinoma with focal rhabdoid features. Although rhabdoid features have been reported in some types of malignant and benign tumors, this is the first report of such features in myoepithelial carcinoma of the breast.     

Myoepithelial cell cocktail (p63+SMA) for the evaluation of sclerosing breast lesions

Sclerosing breast lesions may sometimes mimic the appearance of infiltrating carcinoma due to the entrapment of ductular structures in a fibrotic core. The immunohistochemical detection of the outer myoepithelial cell layer that is indicative of a non-infiltrating lesion is a valuable clue for the diagnosis of such ambiguous cases. The myoepithelial cell markers smooth muscle actin (SMA) and p63 are most commonly used since their specificity and sensitivity are well established. However, recent studies have indicated that some morphologically distinct myoepithelial cells fail to stain for SMA and that p63 positivity can be rarely expressed by a subset of malignant epithelial cells. Moreover, SMA can also be positive in stromal myofibroblastic cells and normal vessels that can be found close to the entrapped ductules and might be erroneously interpreted as myoepithelial cells. In this study, we used a double-immunolabeling technique combining both SMA and p63 antibodies (myoepithelial cell cocktail), in order to investigate whether this technique is advantageous over either marker used alone, in diagnosing sclerosing breast lesions. Our results indicate that p63 alone is not a useful myoepithelial cell marker if applied in large sclerosing breast lesions, however, in smaller lesions it is still of high value. On the contrary, SMA proved significantly useful in the evaluation of myoepithelial cells in larger but not in smaller complex sclerosing lesions. The myoepithelial cell cocktail has a staining sensitivity identical to that of SMA. Nevertheless, in a certain number of cases the cocktail might be useful in differentiating myoepithelial cells from stromal myofibroblasts or vascular smooth muscle cells due to the false impression of a higher staining intensity of the cocktail resulting from the expression of both nuclear and cytoplasmic/membranous antibodies that occupy a wider area of the cell under control.     

CD10|p63及calponin在乳腺良恶性病变鉴别诊断中的意义

目的探讨乳腺肌上皮细胞标志物CD10,p63及calponin在乳腺良、恶性上皮性病变鉴别诊断中的意义。方法应用免疫组织化学染色法检测CD10,p63及calponin在乳腺普通型增生(UDH),非典型导管上皮增生(ADH),导管原位癌(DCIS)和浸润性导管癌(IDC)中的表达,分析其在乳腺良、恶性上皮病变诊断中的意义。结果 3种标志物在UDH,ADH和DCIS组中均有不同程度的表达,且主要表达于导管周围的肌上皮。该3组间calponin的表达量无明显差异(P>0.05);p63的表达量依次为UDH组>ADH组>DCIS组(均P<0.05);CD10的表达量在UDH组与ADH组间无明显差异,但两组均明显高于DCIS组(均P<0.05)。IDC组几乎无CD10和p63的表达,肿瘤间质有少量calponin的表达,与前3组比较,差异均有统计学意义(均P<0.0 5)。结论联合应用CD1 0,p6 3及calponin标志物的检测可鉴别诊断乳腺良恶性病变,CD1 0和p6 3特异性较好,而calponin的敏感性较好,但特异性较差。     

Adenomyoepithelioma: clinical, histologic, and immunohistologic evaluation of a series of related lesions

Adenomyoepithelioma, strictly defined, is a proliferation of both epithelial and myoepithelial elements. The broad range of lesions that may fall under this umbrella, however, may be quite diverse. The diagnostic confusion surrounding this entity and its prognostic implications have led to a diagnosis by default as malignant and to overtreatment of some patients. We evaluated available material from a series of 35 women whose slides were seen in consultation and who were diagnosed with adenomyoepithelioma or a closely related lesion. This comprehensive review of the varied histology of adenomyoepithelioma and similar lesions and their immunohistochemical properties will assist general pathologists in evaluating these sometimes difficult lesions. Follow-up and treatment information demonstrates their benignity. Architecture and histologic features should be combined with immunohistochemistry when determining categorization.     

Immunohistochemical analysis of benign and malignant papillary lesions of the breast

The histocytological diagnostic criteria and recently developed immunohistochemical procedures selective for either the epithelial or the myoepithelial mammary cells have been tested in a series of 60 cases of papillary lesions of the breast. These included 15 benign solitary intraductal papillomas, 41 papillary carcinomas (29 pure and 12 associated with other types of in situ or invasive ductal carcinoma), and four cases of "suspected" papillary carcinomas. Markers for epithelial cells (EMA) and for apocrine metaplasia (GCDFP-15) did not permit a distinction between benign and malignant papillary lesions; however, immunocytochemical staining for CEA using monoclonal antibodies, and for actin (a marker of the myoepithelial cells) was discriminative in this respect. Benign papillomas have a basal layer of actin-rich myoepithelial cells; the cytoplasm of the epithelial cells is CEA negative. Papillary carcinomas lack the myoepithelial layer, except in areas where multiple papillomas are present, associated with ductal or papillary cancer. CEA was detected in 85% of carcinomas. Two of the cases of "suspected carcinoma" lacked myoepithelial cells and were interpreted as carcinomas. It is concluded that the immunocytochemical methods for cell markers can offer valuable data in the study and diagnosis of papillary lesions of the breast; it is difficult, however, to be categorical in borderline cases since in our experience, the behavior of the malignant papillary lesions of the breast is usually favorable. Residual foci of multiple intraductal papillomas were found in seven cases of papillary carcinoma, supporting the pre-neoplastic potential of this condition.     

A Case of Adenomyoepithelioma of the Breast Showing Strong Uptake of 18F‐Fluorodeoxyglucose on a Positron Emission Tomography

An adenomyoepithelioma of the breast is a rare tumor characterized by biphasic proliferation of both epithelial and myoepithelial cells. This tumor is generally considered as a benign neoplasm, and there are few reports describing the imaging features of this tumor through ¹⁸F‐fluorodeoxyglucose positron emission tomography (FDG‐PET). Here, we report a case of an adenomyoepithelioma that showed strong uptake of FDG on PET similar to that observed with a malignant tumor. A 73‐year‐old woman presented to our hospital with a 3.5‐cm, mobile, and elastic hard tumor in the upper area of the left breast. Although the findings of mammography, ultrasonography, and contrast‐enhanced magnetic resonance imaging suggested that the tumor was malignant, it was diagnosed as an adenomyoepithelioma by core needle biopsy. An invasive ductal carcinoma, 0.5‐cm in size, was detected in the medial upper area of the ipsilateral breast during an examination. Although FDG‐PET demonstrated no lymph node or distant metastases from the invasive ductal carcinoma, strong uptake of FDG was detected in the adenomyoepithelioma. Breast conserving surgery and sentinel lymph node biopsy for the invasive ductal carcinoma together with resection of the adenomyoepithelioma was performed. A diagnosis of adenomyoepithelioma was confirmed through histologic examination of the resected specimen. This case indicates that some adenomyoepitheliomas may show a strong uptake of FDG on PET, which resembles a malignant tumor.     

Is it ductal carcinoma in situ with microinvasion or “Ductogenesis”? The role of myoepithelial cell markers

Mammary myoepithelial cells have been under‐recognized for many years since they were considered less important in breast cancer tumorigenesis compared to luminal epithelial cells. However, in recent years with advances in genomics, cell biology, and research in breast cancer microenvironment, more emphasis has been placed on better understanding of the role that myoepithelial cells play in breast cancer progression. As the result, it has been recognized that the presence or absence of myoepithelial cells play a critical role in the assessment of tumor invasion in diagnostic breast pathology. In addition, advances in screening mammography and breast imaging has resulted in increased detection of ductal carcinoma in situ and consequently more diagnosis of ductal carcinoma in situ with microinvasion. In the present review, we discuss the characteristics of myoepithelial cells, their genomic markers and their role in the accurate diagnosis of ductal carcinoma in situ with microinvasion. We also share our experience with reporting of various morphologic features of ductal carcinoma in situ that may mimic microinvasion and introduce the term of ductogenesis.     

Adenomyoepithelioma of the breast diagnosed by a mammotome biopsy: Report of a case

Adenomyoepithelioma is an uncommon primary breast tumor. It is conspicuous for two elements of the tumor, namely, ductal and myoepithelial components. Recently, a Mammotome biopsy, or stereotactic vacuum-assisted biopsy has become popular and various benign or borderline lesions are obtained. We report an adenomyoepithelioma of the breast in a 56-year-old woman. She was pointed out to have a cluster of some microcalcifications on mammography and a 9-mm hypoechoic mass lesion was detected by ultrasound. A Mammotome biopsy revealed a well-defined lesion. Histologically, the tumor demonstrated a thick and bi-cellular growth pattern consisting of ducts and myoepithelium. Immunohistochemically, epithelial cells were positive for cytokeratin AE1/AE3 and cytokeratin, epithelial membrane antigen (EMA), and carcinoembryonic antigen (CEA), negative for alpha-smooth muscle actin (alpha-SMA). In addition, myoepithelial cells were positive for alpha-SMA and CEA, which were scatterly positive for cytokeratin AE1/AE3, and negative for EMA. In examinations of non-palpable lesions found on mammography and ultrasound, a Mammotome biopsy is useful for making diagnosis, however, and adenomyoepithelioma is rarely found. In diagnosing such a rare disease from the limited information obtained from a needle biopsy, an immunohistochemical study was thus found to be useful for making a differential diagnosis.     

Malignant Adenomyoepithelioma of the Breast with Lung Metastases: Report of a Case

Adenomyoepithelioma of the breast is a rare lesion, and has a bicellular pattern of epithelial and myoepithelial cells which are regularly distributed in the tubular structures based on the histologic and ultrastructural features. It is thought to be a benign or a low-grade malignant disease. We herein describe a case of malignant adenomyoepithelioma of the breast with lung metastases in an 86-year-old woman. A primary massive tumor in the left breast grew rapidly within a short period of time. A simple mastectomy with sampling of the axillary lymph nodes was performed. The obtained lymph nodes did not include any metastatic lesions. Malignancy was evidenced by the presence of a high mitotic rate and severe nuclear atypia. Three months after the operation, radiology showed multiple lung metastases, and the patient died 2 weeks thereafter. Reviewing the literature, nine similar cases were reported, and the prognosis of malignant adenomyoepithelioma of the breast with distant metastases was very poor with the time of recurrence varying after initial treatments. Malignant adenomyoepithelioma should be followed up with careful screening for distant metastases. Received: November 16, 2000 / Accepted: May 15, 2001     

Myoepithelial lesions of the breast. Myoepitheliosis, adenomyoepithelioma, and myoepithelial carcinoma.

The clinical and pathologic features of 31 breast lesions composed of a prominent proliferation of myoepithelial cells either admixed with epithelial cells or in pure form were studied. The lesions were divided into three categories: myoepitheliosis, adenomyoepithelioma, and malignant myoepithelioma (myoepithelial carcinoma); the latter is the only lesion composed purely of myoepithelial cells. Three multifocal, microscopic lesions located in the peripheral duct system were designated as myoepitheliosis. Twenty-seven solitary, grossly palpable, predominantly centrally located lesions qualified as adenomyoepithelioma. These were further subdivided into spindle-cell, tubular, and lobulated variants. Two lesions in the latter group had a carcinoma arising within them. Only one case, which was characterized by a solitary mass composed of an infiltrative spindle cell proliferation, qualified as malignant myoepithelioma (myoepithelial carcinoma). Two patients with adenomyoepithelioma developed recurrences; one tumor was of the tubular type, the other of the lobulated type. Both of these tumors had irregular margins. One of these patients had two recurrences and is currently well 8.5 years after the initial excision. The second patient developed a recurrence 8 months after initial excision; the recurrence presented as multiple nodules. One of the patients with myoepithelial carcinoma arising in an adenomyoepithelioma also developed a recurrence within 2.3 years. Her initial tumor was located in the axillary tail of the breast, and she had axillary node metastasis at the time of presentation. All remaining patients with follow-up are well without evidence of recurrence up to 17.3 years after the initial diagnosis (average follow-up, 6.1 years); one patient died of unrelated causes.     

Myoepithelial Carcinoma: A Rare Neoplasm of the Breast

BACKGROUND: Malignant myoepitheliomas of the breast are extremely rare. There has been a limited number of published reports of myoepithelial carcinomas originating from the breast. CASE REPORT: We describe a malignant myoepithelioma of the breast in a 56-year-old woman. Histological examination showed polygonal epithelioid cells and spindle cells with moderate to marked nuclear atypia. Immunohistochemistry showed reactivity in the spindle cells for smooth muscle actin, cytokeratin (AE1/AE3), and p63, indicating a myoepithelial cell lineage of tumor cells. The patient underwent radical surgical excision of the lesion and axillary lymph node dissection. She demonstrated no evidence of recurrence over an 11-month follow-up. CONCLUSIONS: We suggest myoepithelial carcinomas of the breast be managed with appropriate surgical clearance. A multidisciplinary approach is usually required.     

Myoepithelial Cells: Autocrine and Paracrine Suppressors of Breast Cancer Progression

Host cellular paracrine regulation of tumor progression is an important determinant of tumor biology but one cell that has been ignored in this regulation is the myoepithelial cell. Myoepithelial cells surround normal ducts and precancerous lesions, especially of the breast and form a natural border separating proliferating epithelial cells from proliferating endothelial cells (angiogenesis). Myoepithelial cells may thus negatively regulate tumor invasion and metastasis. Whereas epithelial cells are susceptible targets for transforming events, myoepithelial cells are resistant. Therefore, it can be said that myoepithelial cells function as both autocrine as well as paracrine tumor suppressors. Our laboratory has found that myoepithelial cells secrete a number of suppressor molecules including high amounts of diverse proteinase inhibitors and angiogenic inhibitors but low amounts of proteinases and angiogenic factors compared to common malignant cell lines. This observation has been made in vitro, in mice, and in humans and suggests that myoepithelial cells exert pleiotropic suppressive effects on tumor progression. The gene expression profile of myoepithelial cells may explain the pronounced anti-invasive and anti-angiogenic effects of myoepithelial cells on carcinoma cells and may also account for the reduced malignancy of myoepithelial tumors, which are devoid of appreciable angiogenesis and invasive behavior.     

Benign mixed tumors (pleomorphic adenomas) of the breast.

Six cases of benign mixed tumors of the female breast are described. The tumors were found in three settings: (a) as a de-novo lesion arising from breast parenchyma, (b) as single or multiple nodules arising in a background of benign proliferative epithelial elements, and (c) in association with breast carcinoma. The tumors ranged from 1 to 4 cm in diameter, and were histologically characterized by the admixture in various proportions of benign glandular epithelial and myoepithelial elements and cartilaginous or myxoid components. Immunohistochemical staining supported this interpretation. One of the cases was remarkable for the presence of abundant tyrosine-like crystals, a feature described in benign mixed tumors of salivary glands. None of the tumors has recurred during a follow-up period of 1-7 years. Mixed tumors of the breast are considered to be similar to their dermal and salivary gland counterparts.     

Complex Collagenous Spherulosis of the Breast Presenting as a Palpable Mass: A Case Report with Immunohistochemical and Ultrastructural Studies

Abstract: Collagenous spherulosis is a rare, benign breast lesion occuring in less than 1% of benign breast biopsies. All previously reported cases have been discovered as incidental microscopic findings in association with a range of benign to malignant processes. The authors report the first case of collagenous spherulosis presenting as a palpable mass. Immunohistochemistry and electron microscopy performed on this lesion demonstrated the presence of two cell types: epithelial cells and myoepithelial cells with associated basement membranelike material. Collagenous spherulosis may mimic adenoid cystic carcinoma since the epithelial proliferation and spherule formation in collagenous spherulosis closely resembles the changes in adenoid cystic carcinoma. However, adenoid cystic carcinoma is an invasive lesion that is almost always palpable, while collagenous spherulosis is almost always an incidental microscopic finding. Our case illustrates that collagenous spherulosis can also result in a palpable mass, thus palpability of the lesion cannot be used to differentiate these conditions.     

Myoepithelial Cells: Their Origin and Function in Breast Morphogenesis and Neoplasia

The human breast epithelium is a branching ductal system composed of an inner layer of polarized luminal epithelial cells and an outer layer of myoepithelial cells that terminate in distally located terminal duct lobular units (TDLUs). While the luminal epithelial cell has received the most attention as the functionally active milk-producing cell and as the most likely target cell for carcinogenesis, attention on myoepithelial cells has begun to evolve with the recognition that these cells play an active part in branching morphogenesis and tumor suppression. A major question that has been the subject of investigation pertains to how the luminal epithelial and myoepithelial lineages are related and precisely how they arise from a common putative stem cell population within the breast. Equally important is the question of how heterotypic signaling occurs between luminal epithelial and surrounding myoepithelial cells in normal breast morphogenesis and neoplasia. In this review we discuss data from our laboratories and from others regarding the cellular origin of human myoepithelial cells, their function in maintaining tissue polarity in the normal breast, and their role during neoplasia.     

Ultrastructural contributions to the study of morphological differentiation in malignant mixed (pleomorphic) tumors of salivary gland

Ultrastructural studies of pleomorphic adenoma have shown a coordinated differentiation of luminal epithelial and modified myoepithelial cells with the latter cells related to processes resulting in the myxochondroid stroma. Five examples of various histologic types of malignant mixed tumor of parotid origin were examined by electron microscopy to see if underlying patterns of tumor cell differentiation and organization matched those of pleomorphic adenoma. Whether they were intracapsular tumors (with or without identifiable pleomorphic adenoma), carcinomas ex pleomorphic adenoma, or a true malignant mixed tumor, all lesions had cell types and organizations either identical to those in pleomorphic adenoma or, as in less-differentiated examples, displayed features suggesting origin from luminal cells, myoepithelial cells, or both. Even the chondroid cells in the true malignant mixed tumor expressed ultrastructural features indicating their epithelial derivation. On the basis of these findings, some alterations to the classification and terminology of the subtypes of malignant mixed tumor are suggested.     

Sclerosing adenosis of the prostate gland. A lesion showing myoepithelial differentiation.

Sclerosing adenosis of the prostate is a rare lesion characterized by the proliferation of variably sized glands in a cellular stroma. We report light microscopic, immunohistochemical, and ultrastructural studies in 22 examples from 15 patients. Two cases were identified in 100 consecutive prostates embedded by a whole organ method, giving a prevalence of 2%. Antibodies directed against the following antigens were used: high-molecular-weight cytokeratin (CKH; 34 beta E12); cytokeratin (CK; AE1/AE3), prostatic acid phosphatase (PAP), prostate-specific antigen (PSA), S-100 protein, muscle-specific actin (HHF35), and vimentin (Vim). Cells within the glandular component demonstrated positive reactivity for CK, CHH, PSA, and PAP, indicating a prostatic epithelial origin. In addition, a distinct population of cells reacting for muscle-specific actin and S-100 protein was identified within this glandular element. Adequate material for ultrastructural study was available in five cases; all showed the presence of flattened cells located between the basement membrane and secretory epithelial cells, which had features typical for myoepithelial differentiation. Although the prostate gland does not normally contain myoepithelial cells, we have documented their consistent presence in this unusual lesion; we believe these cells arise by a metaplastic process from the prostatic basal cells.     

Ectopic breast tissue as a possible cause of false-positive axillary sentinel lymph node biopsies

Epithelial inclusions representing ectopic breast tissue are uncommonly seen in axillary lymph nodes. The extensive histopathologic examination of axillary sentinel lymph nodes of patients with breast carcinoma may increase the chances to encounter tiny foci of ectopic breast tissue, which may be misinterpreted as (micro)metastatic disease and lead to unwarranted completion of axillary dissection and to inaccurate staging and improper adjuvant treatments for the patients. Here we report on seven cases of ectopic breast tissue in axillary sentinel lymph nodes. In three cases there were coexistent micrometastases, and in the remaining cases the ectopic tissue was not associated with metastatic disease. The ectopic breast tissue showed remarkably varied morphologic features, including apocrine metaplasia and proliferative changes indistinguishable from those occurring in sclerosing adenosis and florid epithelial hyperplasia of the breast. A peripheral layer of myoepithelial cells was consistently detected in the ectopic glands and ducts. Besides awareness and purely morphologic criteria, a false-positive identification of these inclusions as metastatic carcinoma may be avoided by the use of immunohistochemical reactions for the localization of specific markers of the myoepithelial cell component, which is associated with the ectopic breast tissue.