Soft tissue myoepithelial carcinoma-a case report with molecular and electron microscopic analysis.

Myoepithelial tumors are rare neoplasms that primarily occur in the salivary gland but over the last decade have also been described in other locations, including soft tissue. Myoepithelial carcinoma of soft tissue has shown to have a recurrence rate of 39-42% and distant metastases in 32-53% of patients. The only known predictor of malignancy in soft tissue myoepithelial tumors described is cytologic atypia. There are no other validated criteria for differentiating benign and malignant tumors, neither for grading nor for standard of care for these tumor types. Herein, we present a case of myoepithelial carcinoma of inguinal soft tissue in a 37-year male. We also describe the molecular and previously sparingly described detailed electron microscopic features of this case.

Histomorphological and immunophenotypical spectrum of cutaneous myoepitheliomas: A series of 35 cases.

Myoepithelial tumors comprise a group of mesenchymal lesions that show heterogeneous histomorphological features, including dual epithelial, neural, and myoid differentiation. Cutaneous myoepithelioma is a rare neoplasm that is composed primarily of myoepithelial cells and represents one end of a histopathological spectrum of cutaneous myoepithelial neoplasms including chondroid syringoma and myoepithelial carcinoma. These tumors display a wide histopathological spectrum and immunophenotypical profile often showing epithelial and myoepithelial differentiation. In this series, we studied 35 cases of cutaneous myoepitheliomas. Our cases highlighted the broad histopathological range where most cases showed a non-infiltrative and non-encapsulated tumor exclusively located in the dermis and with no subcutaneous involvement. The majority of our cases had a solid growth pattern (syncytial pattern) and the remainder of cases had a multinodular growth pattern. The tumor cells were epithelioid in 23 cases, spindled in eight cases and there was a mixture of epithelioid and spindled cells in four cases. Mitotic figures ranged from 0 to 5 per 10 HPF. By immunohistochemistry epithelial membrane antigen (EMA) was expressed in 59% of cases S100 was positive in 88% of cases, CAM 5.2 was positive in 16% of cases, AE1/AE3 was positive in 44% of cases, p63 was positive in 17% of cases, smooth muscle actin was positive in 38% of cases, desmin was positive in 6% of cases, calponin was positive in 22% of cases, and glial fibrillary acidic protein was positive in 36% of cases. In addition, there were five cases without EMA, keratin, or p63 expression that only showed S100 expression. We describe a large series of cutaneous myoepitheliomas delineating their histomorphological spectrum and immunophenotypical profile. Awareness of some of the unusual histopathological features and the heterogeneous immunohistochemical may pose difficulties for the diagnosis.

Myoepithelioma of bone: ultrastructural, immunohistochemical and molecular study of three cases.

Primary intraosseous myoepithelial tumors are rare neoplasms with only a handful of cases described in the medical literature. To date, intraosseous variant of benign myoepithelioma, due to its rarity, has not been studied ultrastructurally, and only one case of a malignant intraosseous myoepithelioma has been described. Three cases were retrieved from the files at the Massachusetts General Hospital (MGH). A diagnosis of benign myoepithelioma was made in case 1 and malignant epithelioma in cases 2 and 3. Ultrastructurally, intermediate filaments (without dense bodies) were found in each case with an abundance in case 1 and lesser amounts in cases 2 and 3. Surprisingly, cell junctions were not identified in case 1. However, they were found occasionally as intermediate junctions in case 2 and were easily identified as desmosome like junctions in case 3. The nucleus was irregular in the neoplastic cells of benign myoepithelioma which contrasted with cases 2 and 3 where the nuclei were oval yet had visible nucleoli. Herein, we add three new cases, including two new cases of malignant myoepithelioma. We also provide the first ultrastructural description of benign myoepithelioma of bone.

Primary cutaneous biphasic sarcomatoid basal cell carcinoma with myoepithelial carcinoma differentiation: A new variant.

Isolated cases of basal cell carcinoma (BCC) with partial myoepithelial component have been described. However, myoepithelial differentiation has not been described in sarcomatoid basal cell carcinomas, which usually show features resembling osteosarcoma, chondrosarcoma, or leiomyosarcoma. We report a case of an 87-year-old man with a forehead lesion that histologically showed a minor component of conventional nodular BCC in transition with a major biphasic sarcomatoid growth composed of invasive spindle-cell and epithelial-like components, the latter with a reticular pattern and scattered ductal structures. Both components showed cytological atypia and high mitotic rate (26/10HPF), with atypical mitotic figures. BER-EP4 immunostaining was exclusively found in the nodular BCC component whereas the sarcomatoid component revealed immunostaining for α-smooth muscle actin (SMA), muscle-specific actin (MSA), calponin, and p63 in both epithelial-like and spindle-cell populations. Focal immunoreactivity was observed in the epithelial component for S100 and glial fibrillary acidic protein (GFAP). Furthermore, EWSR1-PBX1 gene fusion was also detected. This is to our knowledge, the first fully documented case of biphasic sarcomatoid BCC with myoepithelial carcinoma differentiation.

Myoepithelioma of the lateral abdominal wall: A case report.

RATIONALE: Soft-tissue myoepithelioma is a rare neoplasm. It usually occurs in the distal or proximal extremities, but seldomly arises in the abdominal wall. PRESENTING CONCERNS OF THE PATIENT: The patient is a 40-year-old woman who presented with a painless mass at the lateral abdominal wall for 6 months. Computed tomography scan revealed a lobulated and well-defined iso-density mass showing heterogeneously moderate enhancement. The mass exhibited intermediate T1 signal and obvious high T2 signal on magnetic resonance imaging. INTERVENTIONS: The tumor was excised. Hematoxylin-eosin stain and immunohistochemical stain showed that the tumor was myoepithelioma. OUTCOMES: The patient did not undergo chemotherapy and radiotherapy. No recurrence or metastasis was noted during the 1 year follow-up. LESSONS: Radiologists should consider myoepithelioma in the differential diagnosis when finding a tumor in the abdominal wall.

Establishment and characterization of METON myoepithelioma cell line derived from human palatal myoepithelioma: apical reference to the diverse differentiation potential.

Myoepithelioma is an extremely rare condition that accounts for 1-1.5 % of salivary gland tumors. It was formerly regarded as a subtype of pleomorphic adenoma, in which myoepithelial structural components predominated, but was listed as a separate disease entity in the 1991 World Health Organization classification (Seifert in Histological typing of salivary gland tumours. Springer, Berlin, 1991). Its histology is highly varied and recurrence is frequent (El-Naggar et al. in J Larygol Otol 103:1192-1197, 1989), with cases of malignant transformation having been reported (Seifert in Histological typing of salivary gland tumours. Springer, Berlin, 1991; Barnes et al. in Pathology and Genetics of head and neck tumours. IARC Press, Lyon, 2005), making this a difficult tumor to control in many cases. This is thought to be due to the multiple differentiation potential of myoepithelial cells, but the details are unknown. There have been a number of reports of the establishment of cell lines (Shirasuna et al. Cancer. 45:297-305, 1980; Jaeger et al. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 84:663-667, 1997), but numerous points remain unclear. We established a myoepithelial cell line designated METON, and investigated its characteristics. METON consists of cells with two different morphologies: spindle-shaped cells and epithelial-like cells. Then. we also used single-cell cloning method to establish various subclones (epithelial-like, spindle-like, and mixed epithelial-like/spindle-like cell lines). Among these, pluripotency markers were expressed by the mixed epithelial-like/spindle-like cell lines. The newly established cell line expressing these pluripotency markers will be extremely useful for elucidating the diverse histologies of salivary gland tumors.

Adenomioepitelioma de la mama: reporte de un caso / Adenomyoepithelioma of the breast: a case report

El adenomioepitelioma es un infrecuente tumor de la mama, conformado por una proliferación bifásica de células epiteliales y mioepiteliales. Presentamos las características clínicas y morfológicas de un caso de adenomioepitelioma benigno diagnosticado en una paciente de 34 años en la Unidad de Anatomía Patológica del Hospital Hernán Henríquez Aravena de Temuco.

Breast adenomyoepithelioma is a rare tumor, characterized bythe biphasic proliferation of epithelial and myoepithelial cells. We present clinical and morphological features of a case of benign adenomyoepithelioma diagnosed in a 34 year old patient in the Hernán Henríquez Aravena Hospital in Temuco.

Clear-cell myoepithelial carcinoma of the salivary glands: a clinicopathologic, immunohistochemical, and ultrastructural study of two cases involving the submandibular gland with review of the literature.

Myoepithelial carcinoma (MC) is an uncommon neoplasm of the salivary glands, and cases of the clear-cell (CC) variant are extremely rare. Two cases of MC of the CC variant arising in the left submandibular gland are described herein. Both cases, which involved elderly women, almost exclusively consisted of large glycogen-rich CCs. Both cases were immunopositive for several epithelial and myoepithelial markers, and electron microscopy (EM) demonstrated hybrid epithelial and myoid differentiation in both. Case 1 arose in a pre-existing pleomorphic adenoma ("ex mixed tumor MC"), while Case 2 was a "de novo MC". CC-MC is an aggressive tumor with frequent recurrence, lymph node, and systemic metastases. A total of 14 cases of this type of neoplasm have been reported so far in the salivary glands, two arising from the submandibular gland. To date, only four cases have been studied using EM. The cases of CC-MC presented here are the third and fourth ones, respectively, originating from the submandibular glands, and the first two cases arising from this location, in which EM investigation succeeded in demonstrating myoepithelial differentiation. CC-MC needs to be distinguished from diverse primary and secondary CC neoplasms.

Ossifying fibromyxoid tumor: modified myoepithelial cell tumor? Report of three cases with immunohistochemical and electron microscopic studies.

Ossifying fibromyxoid tumors (OFMT) are rare soft tissue tumors of uncertain histogenesis and clinical behavior. Since Enzinger, Weiss, and Liang first described 59 examples in 1989 (Am Surg Pathol. 13:817-827), approximately 150 cases have been reported. Their clinicopathologic features are fairly well characterized and their histogenesis remains unknown. Three examples of soft tissue tumors with typical histopathologic characteristics of OFMT were studied: case 1, a 43-year-old female with a 2.5-cm tumor of the back; case 2, a 56-year-old man with an 8-cm thigh mass; and case 3, an 81-year-old female with a 13.5-cm buttock tumor. For immunohistochemistry, formalin-fixed, paraffin-embedded tissue sections were stained with antibodies against cytokeratin, smooth muscle actin, desmin, vimentin, S-100 protein, EMA, and collagen type IV using standard ABC-peroxidase methods. For electron microscopy, tissue samples fixed in EM-grade buffered formalin were processed according to routine methods. Immunohistochemistry showed that the tumor cells were positive for vimentin and S-100 protein in all 3 cases. Stains for collagen type IV revealed diffusely positive staining in the stroma with a tendency for stronger staining around the cell borders in 2 out of 3 cases. Desmin was positive in one and actin was positive in one other case. By electron microscopy, tumor cells were characterized by centrally located round to oval nuclei with varying amounts of cytoplasm containing scanty cytoplasmic organelles. There were rare profiles of rough-surfaced endoplasmic reticulum (RER) and rare mitochondria with areas of condensed intermediate filaments. No tonofilaments or actin filaments were present. There were multiple short web-like processes, some of which were attached to that of neighboring cells by primitive cell junctions. In all 3 cases, lesional cells showed external lamina (EL), which was abundant in case 1, forming redundant scrolls frequently. In case 2, EL was less prominent and incomplete, and interrupted portions of EL were present only along the periphery of cell columns or nests bordering the stroma. In case 3, which behaved as a malignant tumor, the tumor cells were less differentiated spindle cells with primitive cellular features, and EL was rarely found along the short span of tumor cell borders. In this study, tumor cells in OFMT were polygonal to stellate often with multiple short cytoplasmic processes. The tumor cells were found to form cell clusters attached by primitive intercellular junctions between cytoplasmic processes forming intercellular bridges. The cell borders facing the stroma around cell clusters tended to be flat and had incomplete EL, while no EL was present along the cell borders facing the inner aspect of cell clusters. These ultrastructural findings together with immunophenotypic expression of S-100 protein presented closer resemblance to those of modified myoepithelial cells in pleomorphic adenomas of salivary glands and skin appendages rather than peripheral nerve sheath tumors. The authors conclude that these findings render more support to the hypothesis of myoepithelial histogenesis of OFMT. They also conclude that ultrastructural study not only helps accurate diagnosis, but also may aid in predicting malignant behavior by the degree of deviation from the typical examples of OFMT.

A case of soft tissue myoepithelial tumor arising in masticator space.

Soft tissue myoepithelial tumors of the head and neck region are very rare, and only one case of soft tissue myoepithelial tumor occurring in the masticator space has been reported in the world literature. A case of soft tissue myoepithelial tumor with benign histomorphology, but with an invasive growth pattern, occurred in the masticator space of a 46-year- old male patient. Magnetic resonance imaging of paranasal sinus/nasopharynx revealed a well-defined, lobulated heterogeneous mass with high signal intensity and dense calcification in the masticator space between the left mandible ramus and pterygoid process. Grossly, the tumor was a well- circumscribed ovoid solid mass and consisted of yellowish gray glistening firm tissue. Histologically, the tumor showed a multinodular growth pattern and consisted of epithelioid cells in chondromyxoid stroma and of spindle-shaped to ovoid cells in the hyaline stroma. The tumor cells appeared bland, and no mitosis or necrosis was found within the tumor. The tumor focally invaded to adhered bone tissue. Immunohistochemically, the tumor cells were diffusely positive for epithelial membrane antigen, smooth muscle actin, but negative for other epithelial markers. Ultrastructurally, the cytoplasm of the tumor cells contained sparse microfilaments and subplasmalemmal densities. Attenuated desmosomes were commonly seen between the tumor cells.

Myoepithelial carcinoma of the lung.

Primary lung carcinomas showing features of salivary gland-type neoplasms are rare. Many are mucoepidermoid carcinomas and adenoid cystic carcinomas. Myoepithelial carcinoma of the lung is extremely rare, and in the WHO classification is classified as 'Others' among carcinomas of the salivary gland. The pertinent literature is restricted to a few pathological reports, and hardly any clinical examinations have been performed. Here we report a resected case of myoepithelial carcinoma of the lung, including details of clinical examination, with a review of previously documented cases.

[Myoepithelioma of soft tissue -- case report with clinicopathologic, ultrastructural, and cytogenetic findings]. / Myoepitheliom des Weichgewebes. Fallbericht mit klinisch-pathologischen, ultrastrukturellen und zytogenetischen Befunden.

The case of a soft tissue myoepithelioma is presented including clinicopathologic, ultrastructural, and genetic findings. A 30-year-old male patient suffered from a soft tissue tumor within the deep soft tissues of the right lower leg measuring 13.2 x 8.2 x 9 cm. Histologically, the lesion was diagnosed as a myoepithelioma displaying a lobulated architecture with cords and nests of epithelioid and spindle cells without cytologic atypia lying within a fibromyxoid and partly chondroid matrix; immunohistochemistry was positive for pancytokeratin, S100-protein, calponin and partly for GFAP and EMA. Ultrastructural analysis revealed glycogen deposits and cell-membrane-associated plaque structures, whereas true myofilaments could not be identified (with immunohistochemistry being negative for actin). Using comparative genomic hybridization (CGH), a gain of chromosome Y was detected. A loss on 17p could not be detected unambiguously. However, based on the low resolution of CGH a small loss cannot be excluded. The patient was free of disease 25 months following complete tumor resection. Myoepitheliomas/mixed tumors of deep soft tissue represent rare soft tissue lesions that may reach a considerable size and may mimic other soft tissue tumors or sarcomas. Based on a local relapse rate of approximately 20% according to the literature, a complete resection with thorough follow-up should be recommended.

Malignant myoepithelioma (myoepithelial carcinoma) of soft tissue.

Malignant myoepithelioma of soft tissue is extremely rare. Presented herein is a case arising in a 17-year-old man. The tumor was initially noticed as a painless deep soft-tissue mass in the right forearm when the patient was aged 3 years. Thereafter, it grew without remarkable symptoms, such as pain or tenderness, until his visit to the hospital because of swelling of his forearm when he was 17 years old. An excisional biopsy specimen disclosed an invasive tumor exhibiting a lobular architecture. The tumor cells were arranged in a reticular and/or trabecular fashion with a myxoid background, and nuclear atypia was evident. Mitoses and tumor necrosis were also observed. Immunohistochemically, S-100 protein and epithelial markers were diffusely positive. Faint intercellular junctions and basal laminae were identified by electronmicroscopy. On the basis of these findings, the tumor was diagnosed as a malignant myoepithelioma of soft tissue. Six months later, multiple lung metastases were observed, and an open biopsy revealed a neoplasm displaying the same histological feature as the previously biopsied specimens. The patient died of his disease 18 months after the lung biopsy. Malignant myoepithelioma should be kept in mind in diagnosis of deep soft-tissue tumors with epithelioid features.

Myoepithelial mRNA expression profiling reveals a common tumor-suppressor phenotype.

A series of myoepithelial cell lines and xenografts derived from benign human myoepithelial tumors of diverse sources (salivary gland, breast, and lung) exhibit common mRNA expression profiles indicative of a tumor-suppressor phenotype. Previously established myoepithelial cell lines and xenografts (HMS-#; HMS-#X) were compared to nonmyoepithelial breast carcinoma cells (MDA-MB-231 and MDA-MB-468, and inflammatory breast carcinoma samples, IBCr, and IBCw), a normal mammary epithelial cell line (HMEC) and individual cases of human breast cancer (zcBT#T), and matched normal human breast tissues (zcBT#N) (overall samples = 22). The global gene expression profile (22,000 genes) of these individual samples was examined using Affymetrix Microarray Gene Chips and subsequently analyzed with both Affymetrix and DChip algorithms. The myoepithelial cell lines/xenografts were distinct and very different from the nonmyoepithelial breast carcinoma cells and the normal breast and breast tumor biopsies. Two hundred and seven specifically selected genes represented a subset of genes that distinguished (P < 0.05) all the myoepithelial cell lines/xenografts from all the other samples and which themselves exhibited hierarchical clustering. Further analysis of these genes revealed increased expression in genes belonging to the classes of extracellular matrix proteins, angiogenic inhibitors, and proteinase inhibitors and decreased expression belonging to the classes of angiogenic factors and proteinases. Developmental genes were also differentially expressed (either over or underexpressed). These studies confirm our previous impression that human myoepithelial cells express a distinct tumor-suppressor phenotype.

Oncocytic tumor in myoepithelioma arising from the grossopalatine gland.

Oncocytoma or oncocytic change in salivary glands normally occurs in old patients and mostly in the parotid gland, but those arising from the grossopalatine gland in young patients are extremely rare. The present case shows that oncocytic ductal structures were observed in myoepithelioma, consisting of spindle, plasmacytoid or epithelioid cells. The oncocytic tumor contained large amounts of eosinophilic granular cytoplasm and small nuclei.

Mixed tumors, myoepitheliomas, and oncocytomas of the soft tissues are likely members of the same family: a clinicopathologic and ultrastructural study.

Four diagnostically unusual soft tissue tumors are presented. All lesions were of consistent size and long duration. Histologically, one lesion was analogous to mixed tumors of the usual sites (i.e., salivary glands), one lesion was totally spindled, and the two other lesions both had oncocytic appearances (epithelioid and spindle biphasic pattern in a case, purely epithelioid in the other). Immunohistochemically, the mixed tumor was positive for vimentin, cytokeratins, S-100 protein, and focally for EMA. The purely spindled tumor exhibited immunoreactivity for vimentin, actins, S-100 protein, EMA (focally), and GFAP. The oncocytic biphasic tumor was positive for mitochondrial antigen, vimentin, and actins. The purely epithelioid oncocytic neoplasm was immunoreactive only for mitochondrial antigen and vimentin. Ultrastructurally, in the epithelial-like portion of the first (mixed) tumor, peripheral arrays of contractile filaments were detected along with well-developed desmosomes. In the second (spindled) case, peripheral contractile filaments and attenuated desmosomes were also seen. In the third case, a huge number of mitochondria, some desmosomes, and actin-type microfilaments were found. In the fourth case, desmosomes and punctate subplasmalemmal densities, in addition to numerous mitochondria, were documented. In all cases an external basal lamina were present, which was discontinuous in the first three cases and almost continuous in the fourth. These tumors were respectively designated as mixed tumor, myoepithelioma of the classic type, myoepithelioma of oncocytic type with biphasic cell architecture, and true oncocytoma. So far, all tumors have followed benign clinical courses (median follow up: 12 months). Comparisons with similar tumors of other sites are drawn, and suggestions for considering all of them as members of the same myoepithelial-derived tumor family are given.

Myoepithelial carcinoma of the lung arising from bronchial submucosa.

Myoepithelial neoplasm mainly occurs in the salivary glands and breasts and is extremely rare in the lung. To our knowledge, this report describes the first documented case of a myoepithelial carcinoma present in the lung. The tumor derived from the right main bronchial submucosa and exhibited a dual epithelial and smooth muscular phenotype by immunohistochemical and ultrastructural studies. It invaded the neighboring pulmonary tissue and the hilar lymph nodes. Despite a right pneumonectomy and chemotherapy, metastasis was found in the left lung 7 months later.

[Tyrosine-rich crystalloids in a myoepithelioma of the minor salivary glands in the smooth palate]. / Tyrosinreiche Kristalloide in Einem Myoepitheliom der kleinen Speicheldrüsen des Gaumens.

Tyrosine-rich crystalloids in tumors of the salivary glands are rare and have been reported mainly in specimens from Black African patients. The pathogenesis of these structures is still unclear, but pathological secretion by neoplastic myoepithelial cells is supposed. Millon's staining and ultrastructural examinations are used for confirming the diagnosis. We present the case report of a 59-year-old woman with a myoepithelioma of the minor salivary glands in the smooth palate containing tyrosine-rich crystalloids as an example of this rare phenomenon.