Myoepithelial Tumors Research Articles

Primary Pulmonary Epithelial- Myoepithelial Tumour - Report of an Aggressive Clinical Case

Primary Pulmonary Epithelial- Myoepithelial Tumour - Report of an Aggressive Clinical Case

Investigation of the PLAG1 Rearrangement in Minor Salivary Gland Neoplasms with A Myoepithelial Component and Ectomesenchymal Chondromyxoid Tumor of the Tongue. A pilot study

Investigation of the PLAG1 Rearrangement in Minor Salivary Gland Neoplasms with A Myoepithelial Component and Ectomesenchymal Chondromyxoid Tumor of the Tongue. A pilot study

Sox10--a marker for not only schwannian and melanocytic neoplasms but also myoepithelial cell tumors of soft tissue: a systematic analysis of 5134 tumors.

Sox10 transcription factor is expressed in schwannian and melanocytic lineages and is important in their development and can be used as a marker for corresponding tumors. In addition, it has been reported in subsets of myoepithelial/basal cell epithelial neoplasms, but its expression remains incompletely characterized. In this study, we examined Sox10 expression in 5134 human neoplasms spanning a wide spectrum of neuroectodermal, mesenchymal, lymphoid, and epithelial tumors. A new rabbit monoclonal antibody (clone EP268) and Leica Bond Max automation were used on multitumor block libraries containing 30 to 70 cases per slide. Sox10 was consistently expressed in benign Schwann cell tumors of soft tissue and the gastrointestinal tract and in metastatic melanoma and was variably present in malignant peripheral nerve sheath tumors. In contrast, Sox10 was absent in many potential mimics of nerve sheath tumors such as cellular neurothekeoma, meningioma, gastrointestinal stromal tumors, perivascular epithelioid cell tumor and a variety of fibroblastic-myofibroblastic tumors. Sox10 was virtually absent in mesenchymal tumors but occasionally seen in alveolar rhabdomyosarcoma. In epithelial tumors of soft tissue, Sox10 was expressed only in myoepitheliomas, although often absent in malignant variants. Carcinomas, other than basal cell-type breast cancers, were only rarely positive but included 6% of squamous carcinomas of head and neck and 7% of pulmonary small cell carcinomas. Furthermore, Sox10 was often focally expressed in embryonal carcinoma reflecting a primitive Sox10-positive phenotype or neuroectodermal differentiation. Expression of Sox10 in entrapped non-neoplastic Schwann cells or melanocytes in various neoplasms has to be considered in diagnosing Sox10-positive tumors. The Sox10 antibody belongs in a modern immunohistochemical panel for the diagnosis of soft tissue and epithelial tumors.

Low grade myoepithelial carcinoma: a mini case series analysis including a case with sacral disease and a case with forearm disease

Myoepithelial (ME) tumours of soft tissue are rare tumours that were first described in 1995. A wide spectrum of architectural and histological patterns make diagnosis difficult; as is differentiating benign or low grade from malignant or high grade tumours to guide treatment and predict patient outcome. We report two cases of low grade ME tumours of soft tissue treated at our institution in 2013. The first one was in a 24 year old previously healthy male who presented with three separate deposits of tumour. The two largest were a sacral mass measuring 8 x 12 x 21cm and left inguinal mass measuring 8.6 x 10 x 8cm. He was successfully treated with neoadjuvant chemotherapy and wide local excision with flap reconstruction. The second case was in a 35 year old female who presented with a slowly growing right forearm mass. Due to positive margins she underwent three excisions and post operative brachytherapy for recurrence prevention. Both patients are disease free at 6 month follow up. A review of the current literature surrounding presentation, epidemiology, histopathological findings and management of ME tumours of soft tissue is correlated with findings from this mini case series analysis.

Angiomatoid fibrous histiocytoma: comparison of fluorescence in situ hybridization and reverse transcription polymerase chain reaction as adjunct diagnostic modalities.

Angiomatoid fibrous histiocytoma (AFH) is a rare soft tissue neoplasm of intermediate biologic potential and uncertain differentiation, most often arising in the extremities of children and young adults. Although it has characteristic histologic features of a lymphoid cuff surrounding nodules of ovoid cells with blood-filled cystic cavities, diagnosis is often difficult due to its morphologic heterogeneity and lack of specific immunoprofile. Angiomatoid fibrous histiocytoma is associated with recurrent chromosomal translocations, leading to characteristic EWSR1-CREB1, EWSR1-ATF1, and, rarely, FUS-ATF1 gene fusions; fluorescence in situ hybridization (FISH), detecting EWSR1 or FUS rearrangements, and reverse transcription-polymerase chain reaction (RT-PCR) for EWSR1-CREB1 and EWSR1-ATF1 fusion transcripts have become routine ancillary tools. We present a large comparative series of FISH and RT-PCR for AFH. Seventeen neoplasms (from 16 patients) histologically diagnosed as AFH were assessed for EWSR1 rearrangements or EWSR1-CREB1 and EWSR1-ATF1 fusion transcripts. All 17 were positive for either FISH or RT-PCR or both. Of 16, 14 (87.5%) had detectable EWSR1-CREB1 or EWSR1-ATF1 fusion transcripts by RT-PCR, whereas 13 (76.5%) of 17 had positive EWSR1 rearrangement with FISH. All 13 of 13 non-AFH control neoplasms failed to show EWSR1-CREB1 or EWSR1-ATF1 fusion transcripts, whereas EWSR1 rearrangement was present in 2 of these 13 cases (which were histopathologically myoepithelial neoplasms). This study shows that EWSR1-CREB1 or EWSR1-ATF1 fusions predominate in AFH (supporting previous reports that FUS rearrangement is rare in AFH) and that RT-PCR has a comparable detection rate to FISH for AFH. Importantly, cases of AFH can be missed if RT-PCR is not performed in conjunction with FISH, and RT-PCR has the added advantage of specificity, which is crucial, as EWSR1 rearrangements are present in a variety of neoplasms in the histologic differential diagnosis of AFH, that differ in behavior and treatment.

Myoepithelial neoplasms of soft tissue: an updated review of the clinicopathologic, immunophenotypic, and genetic features.

Myoepithelial tumors in skin and soft tissue are uncommon but have been increasingly characterized over the past decade. Men and women are equally affected across all age groups and lesions arise most frequently on the extremities and limb girdles. Approximately 20 % of cases occur in pediatric patients, in whom they are frequently malignant. Similar to their salivary gland counterparts, myoepithelial tumors of soft tissue demonstrate heterogeneous morphologic and immunophenotypic features. Tumors are classified as mixed tumor/chondroid syringoma, myoepithelioma, and myoepithelial carcinoma; in soft tissue, tumors having at least moderate cytologic atypia are classified as malignant. Mixed tumor and myoepithelioma show a benign clinical course, with recurrence in up to 20 % (typically secondary to incomplete excision), and do not metastasize. In contrast, myoepithelial carcinoma shows more aggressive behavior with recurrence and metastasis in up to 40-50 % of cases. The majority of myoepithelial neoplasms typically coexpress epithelial antigens (cytokeratin and/or EMA) and S-100 protein; GFAP and p63 are frequently positive and a subset of malignant neoplasms lose INI1 expression. Up to 45 % of myoepitheliomas and myoepithelial carcinomas harbor EWSR1 gene rearrangements, unlike mixed tumor/chondroid syringoma which is characterized by PLAG1 gene rearrangement. While mixed tumor/chondroid syringoma are likely related to primary salivary myoepithelial tumors, soft tissue myoepithelioma and myoepithelial carcinoma appear to be pathologically distinct neoplasms.

Novel FUS-KLF17 and EWSR1-KLF17 fusions in myoepithelial tumors.

Myoepithelial (ME) tumors of soft tissue and bone display a heterogeneous histologic spectrum and in about half of the cases harbor EWSR1 gene rearrangements. Despite rare case reports, the prevalence of fused in sarcoma (FUS) gene abnormalities and its related fusion partners remains undetermined among ME tumors. Therefore, we screened 66 EWSR1-negative ME tumors for FUS abnormalities by fluorescence in situ hybridization (FISH). In an index FUS-rearranged case, 3'-rapid amplification of cDNA ends (RACE) was applied to identify the fusion partner. Results were further confirmed by reverse transcription-PCR, followed by FISH screening the entire cohort of FUS-rearranged and EWSR1-positive ME lesions lacking a known fusion partner. The correlation between genotype and clinicopathological features was also investigated. As a result, six (9%) FUS-rearranged cases were identified, spanning divergent age groups, tumor locations, and morphologic features. A novel FUS-KLF17 fusion was identified by 3'-RACE in an 11-year-old girl with a foot lesion associated with locoregional metastases. Three additional cases with FUS-KLF17 fusions were identified and one KLF17 rearrangement (6.3%) was found among the 16 EWSR1-positive cases tested. The KLF17-related ME tumors affected younger patients and often exhibited trabecular growth in a myxohyaline stroma, but this genotype did not correlate with a malignant phenotype. In conclusion, a small subset of ME tumors harbor FUS rearrangements, two thirds of them being associated with KLF17 fusion. FUS FISH analysis is recommended in EWSR1-negative lesions in which a ME diagnosis is suspected. KLF17 is also a rare gene fusion partner to EWSR1-rearranged ME tumors.

Cutaneous syncytial myoepithelioma: A case report with emphasis on the differential diagnosis of problematic dermal tumors.

Cutaneous myoepithelioma is a peculiar and recently recognized neoplasm exhibiting purely myoepithelial differentiation. These lesions affect different areas of the body, and are characterized by heterogenous morphological and immunophenotypical features. The majority of cutaneous myoepitheliomas behave in a benign fashion, however, the risk for local recurrence is higher with incomplete resection. A relatively newly described variant of myoepithelioma exhibits syncytial cytological features. The current study reports a case of cutaneous syncytial myoepithelioma presenting as a painless and papular skin lesion. The presence of the Ewing sarcoma RNA-binding protein 1 gene rearrangement in the present case supported the diagnosis of a myoepithelial tumor. The patient subsequently underwent local excision of the tumor and was followed up twice in the year after surgery. At the time of writing, the patient was alive and no recurrences had been identified. Furthermore, the current study discusses how this myoepithelial neoplasm may be distinguished from other problematic spindle or epithelioid cell tumors, particularly superficial dermal lesions.

New insights in soft tissue tumours

This lecture will focus on three broad areas which have brought new insights or broadened our understanding of soft tissue neoplasia – specifically, selected newly recognised tumour types, conceptual advances and shifts in classification schemes. New entities will include angiofibroma of soft tissue, epithelioid inflammatory myofibroblastic sarcoma, epithelioid rhabdomyosarcoma and round cell sarcomas with CIC-DUX4 gene fusion. Evolving concepts include so-called cutaneous ‘leiomyosarcoma’, diagnostic criteria for dedifferentiated liposarcoma and increasing characterisation of myoepithelial tumours arising in soft tissue. Some issues of classification revolve around the impact of novel genetic data and uncertainties as to their significance.

English

INTRODUCTION: A benign tumour of Schwann cells of the peripheral nerve sheath is called Schwannoma, also called as neurilemoma or neurinoma. Most breast cancers and other breast tumors have an epithelial cell origin, with stromal and myoepithelial cell tumors being less common. A nerve sheath tumor arising from neural crest-derived Schwann cells within the breast is rarer still. For unknown reasons, these cells can sometimes grow in a neoplastic fashion which results in a benign tumor termed as schwannoma. Neurilemoma, neurinoma, peripheral nerve sheath tumor and schwannoma are considered to be synonymous though the term schwannoma appears to be more precise than the others as this tumour is believed to arise from schwan cells. Schwannoma are commonly slow growing solitary lesions which rarely show malignant transformation. The clinical significance of this benign tumor is that it may clinically and radiographically simulate malignant

ERG and SALL4 expressions in SMARCB1/INI1-deficient tumors: a useful tool for distinguishing epithelioid sarcoma from malignant rhabdoid tumor.

ERG is immunoexpressed in vascular endothelial tumors, blastic extramedullary myeloid tumors, and tumors with ERG-involved translocation, such as prostate carcinoma or Ewing sarcoma. Recently, ERG immunoexpression was reported in an epithelioid sarcoma, which is a SMARCB1/INI1-deficient tumor, although epithelioid sarcoma is not associated with chromosomal translocations involving ERG and is categorized as a tumor with uncertain differentiation. SALL4 is essential for a proliferation and stabilization of embryonic stem cells. It was reported that SALL4 expression may aid in distinguishing epithelioid sarcoma from malignant rhabdoid tumor. We analyzed the frequency of ERG and SALL4 expressions in 80 SMARCB1/INI1-deficient tumors, including 45 epithelioid sarcomas (conventional-type, 24; proximal-type, 20), 17 malignant rhabdoid tumors, 5 atypical teratoid/rhabdoid tumors, 6 undifferentiated/unclassified sarcomas, 5 myoepithelial tumors, and 4 extraskeletal myxoid chondrosarcomas. We found that ERG expression was present in 18 of the epithelioid sarcomas (41%), including 13 conventional-type (54%) and 5 proximal-type (25%), whereas all 17 of the malignant rhabdoid tumors exhibited negative immunoreactivity. One atypical teratoid/rhabdoid tumor (20%), 1 myoepithelial carcinoma (20%), 1 undifferentiated/unclassified sarcoma (17%), and no extraskeletal myxoid chondrosarcomas (0%) also showed ERG expression. SALL4 expression was recognized in 5 epithelioid sarcomas (11%), 12 malignant rhabdoid tumors (71%), 2 atypical teradoid/rhabdoid tumors (40%), 4 undifferentiated/unclassified sarcomas (67%), 1 myoepithelial tumor (20%), and none of the extraskeletal myxoid chondrosarcomas (0%). Therefore, the evaluation of ERG and SALL4 immunoexpressions may be a useful diagnostic tool to distinguish epithelioid sarcoma, especially proximal type, from malignant rhabdoid tumor.

Myoepithelial tumor of soft tissue: histology and genetics of an evolving entity.

Myoepithelial neoplasms represent a heterogeneous group of tumors of which classification is incomplete and evolving. Those of the soft tissues often form genetically distinct subgroups that differ from those arising within salivary glands. Soft-tissue myoepithelial tumors (including mixed tumors that show true glandular or ductal differentiation) exhibit a spectrum of different morphologic patterns, making them difficult to distinguish from a variety of other neoplasms. They have been increasingly shown to harbor genetic fusions involving EWSR1 and partner genes that are not seen in the well-characterized tumor classes involving EWSR1 translocations. We review the spectrum of soft-tissue myoepithelial tumors, discussing recent immunohistochemical and genetic findings and the differential diagnosis.

EWSR1‐PBX3: A novel gene fusion in myoepithelial tumors

The genetics of myoepithelial tumors (ME) of soft tissue and bone have recently been investigated, with EWSR1-related gene fusions being seen in approximately half of the tumors. The fusion partners of EWSR1 so far described include POU5F1, PBX1, ZNF444 and, in a rare case, ATF1. We investigated by RNA sequencing an index case of EWSR1-rearranged ME of the tibia, lacking a known fusion partner, and identified a novel EWSR1-PBX3 fusion. The fusion was further validated by reverse transcriptase polymerase chain reaction and fluorescence in situ hybridization (FISH). To evaluate if this is a recurrent event, an additional cohort of 22 EWSR1-rearranged ME cases lacking a fusion partner were screened by FISH for abnormalities in PBX3 gene. Thus, two additional cases were identified showing an EWSR1-PBX3 gene fusion. One of them was also intraosseous involving the ankle, while the other occurred in the soft tissue of the index finger. The morphology of the EWSR1-PBX3 fusion positive cases showed similar findings, with nests or sheets of epithelioid to spindle cells in a partially myxoid to collagenous matrix. All three cases showed expression of S100 and EMA by immunohistochemistry. In summary, we report a novel EWSR1-PBX3 gene fusion in a small subset of ME, thereby expanding the spectrum of EWSR1-related gene fusions seen in these tumors. This gene fusion seems to occur preferentially in skeletal ME, with two of the three study cases occurring in intraosseous locations.

Oral amelanotic malignant melanoma: a rare entity with diagnostic challenge

Primary malignant melanomas of the mucosal areas of the head and neck are very rare tumors and they account for less than 1% of all melanomas. A 61-year-old male was referred to our clinic for the management of a palatal lesion that had been diagnosed from the referral center, as a malignant myoepithelial tumor. Intraoral examination revealed a large variegated, lobulated palatal swelling, which covered the hard and soft palate. A re-biopsy at our center revealed sheets, bundles, and occasional fascicles of atypical elongated epithelioid and spindle shaped cells, exhibiting vesicular and enlarged nuclei with prominent nucleoli. The nucleoli appeared to be ‘cherry red’ in color. Melanin pigment was however not identified in any of the cells, hence the suspicion of an amelanotic melanoma. Immunohistochemical staining was strongly positive for HMB45, S100 and vimentin. Hence we report a case of intra-oral amelanotic elanoma, which based on the English literature and to the best of our knowledge, is the first case report from West Africa.

Non-rhabdoid pediatric SMARCB1-deficient tumors: overlap between chordomas and malignant rhabdoid tumors?

Somatic alterations in the tumor suppressor gene SMARCB1 were first described in the malignant rhabdoid tumor (MRT) of infancy. Since then, SMARCB1 alterations have been found in other tumors, forming a varied group of SMARCB1-deficient tumors, which sometimes shares overlapping immunohistochemical and histological findings. Thus, the diagnosis is challenging. We report two cases of pediatric SMARCB1-deficient tumors from the clivus that illustrate the diagnostic difficulties. Both cases were strongly positive for epithelial markers associated with loss of BAF47 (INI1) expression, and were negative for S100 and CD34. Molecular analyses of the SMARCB1 gene found a deletion of all nine exons in both cases. In the first case, a 5-year-old girl presented with a thoracic metastasis of a clival tumor, which was diagnosed as MRT and treated accordingly. The morphological findings and the expression of brachyury would favor the diagnosis of a poorly differentiated chordoma. The second case was a quickly fatal clival tumor in a 2-year-old boy: This tumor was morphologically undifferentiated and raises the problem of differential diagnosis between an MRT, a malignant myoepithelial tumor, or an undifferentiated chordoma due to the location and the expression of brachyury. Studies of biological signatures, such as transcriptome profiling, could help to understand the apparent overlap between these tumors.

Secretory Myoepithelial Carcinoma: A Histologic and Molecular Survey and a Proposed Nomenclature for Mucin Producing Signet Ring Tumors

Signet ring cell (mucin producing) adenocarcinoma is a rare low grade salivary gland malignancy. While currently designated as an adenocarcinoma, myoepithelial differentiation has been implied in previously reported cases. We herein perform a survey of our cases of signet ring cell adenocarcinoma and review the literature in order to refine categorization of this rare tumor. Five cases were retrieved. One was reclassified as a mammary analogue secretory carcinoma, leaving four that fulfilled the criteria for signet ring cell adenocarcinoma: the presence of prominent signet ring or vacuolated cells arranged in islands, interconnecting strands, cords or sheets in a myxoid or hyaline stroma, or pools of mucin. An extensive panel of histochemical and immunohistochemical stains and fluorescence in situ hybridization (FISH) (modeled after common phenotypes and molecular alterations seen in signet ring and myoepithelial tumors at other sites) was performed. The male-to-female ratio was 3:1. The mean age was 56years (range 18-81). Sites involved included buccal mucosa (2), soft palate (1) and deep parotid (1). Perineural and angiolymphatic invasion were present in three and two cases respectively. One patient was lost to follow up and the remainder were alive and without disease at time of last follow up (mean 38months). All cases showed mucicarmine positive vacuolated/signet ring cells embedded in a myxoid stroma. Three cases showed at least focal p63 staining and two cases showed positivity for calponin. Membranous E-cadherin was retained in all cases. FISH was negative for ETV6, EWSR1, and ALK1 rearrangements in all four cases. Based on the current series and the previously reported cases, it is evident that signet ring adenocarcinomas have a dual secretory and myoepithelial phenotype and thus as a whole more appropriately designated as 'secretory myoepithelial carcinoma.' They behave in a fairly indolent fashion and do not share the major molecular alterations seen in other signet ring and myoepithelial tumor types.

Epithelial–myoepthelial carcinoma of the tracheobronchial tree: The prognostic role of myoepithelial cells

ObjectivesEpithelial myoepithelial carcinoma (EMC) of the lung is a very rare tumor that is characterized by biphasic differentiation of epithelial and myoepithelial cells. Current discussion about this entity focuses on the malignant potential of the tumor and the role of myoepithelial cells in diagnosis and patient prognosis. This study reports five EMC cases in the lung and discusses issues related to EMC prognosis. Materials and methodsThe five EMC cases were diagnosed and collected at the Samsung Medical Center (Seoul, Korea) from 1998 to 2012. Four patients with EMC were received a lobectomy and one patient was given a bronchoscopy to excise the tumor. All cases were evaluated with hematoxylin and eosin and immunohistochemical staining, which included S-100 protein, smooth muscle actin, TTF-1, cytokeratin, vimentin, and p27 analysis. Results and conclusionAll cases revealed biphasic differentiation of epithelial and myoepithelial tumor cells with various stromal patterns. One of the cases contained predominantly myoepithelial and focal epithelial differentiation, and the tumor showed recurrence and metastasized to the chest wall. This was the first case of metastatic pulmonary EMC. Therefore, we suggest that EMC of the lung has a malignant potential, and that myoepithelial tumor cells may be associated with a pulmonary EMC prognosis.

Low grade adenosquamous carcinomas of the breast are epithelial and myoepithelial tumors

Breast adenosquamous carcinomas are rare tumors that are categorized as subtypes of metaplastic carcinoma. They are composed of well-developed gland formation intimately admixed with solid nests of squamous cells immersed in a highly cellular spindle cell stroma. A low grade variant has been described to have a relatively indolent clinical course and an uncommon low grade histological pattern. However, some aspects of this tumor remain unclear, due to its rarity. Here, we report 25 cases of adenosquamous carcinoma of the breast: 14 cases of ’pure’ low grade adenosquamous carcinoma, seven cases of metaplastic carcinoma arising within foci of low grade adenosquamous carcinoma, one case of a composite tumor that associated adenosquamous carcinoma and phyllodes sarcoma with liposarcomatous stroma and three cases corresponding to high grade adenosquamous carcinoma. As results, we found that the glandular formations within foci of low grade and high grade adenosquamous carcinoma were surrounded by a certain amount of myoepithelial cells. Furthermore, spindle cells and heterologous elements of the stroma, in all tumor types, arose from the myoepithelial cells and expressed myoepithelial markers, basal keratins and a variable level of epidermal growth factor receptor expression.

Myoepithelial carcinoma of buccal mucosa: A rare tumor

Myoepithelial carcinoma is a rare neoplasm of salivary glands that account for < 1% of all salivary gland tumors. The most common sites of involvement are major salivary glands mainly parotid gland. Intraorally, it can arise from minor salivary glands; palate is the most common site of occurrence. It also occurs in nasopharynx, paranasal sinuses, nasal cavity and larynx in head and neck region. Myoepithelial tumors were first described in 1943. Their malignant variant, myoepithelial carcinoma, was first reported by Stromeyer et al., in 1975, characterized by distinct morphologic heterogeneity and an infiltrative growth pattern into adjacent tissues. Here, we report a rare case of a 55-year-old female with myoepithelial carcinoma of buccal mucosa. It was also rare because of unusual location of tumor. Our patient was treated with wide local resection and remained free of disease for 15 months.

Recently characterized soft tissue tumors that bring biologic insight

Previously unrecognized but clinicopathologically (and often molecularly) distinct types of soft tissue tumor continue to be characterized, allowing wider recognition, more consistent application of diagnostic criteria, more reliable prediction of tumor behavior and enhancement of existing classification schemes. Examples of such ‘entities' that have become much better understood over the past decade or so include deep ‘benign' fibrous histiocytoma, hemosiderotic fibrolipomatous tumor, PEComa, spindle cell liposarcoma, myoepithelial tumors of soft tissue and spindle cell/sclerosing rhabdomyosarcoma. These tumor types, as well as the insights which they have engendered, are briefly reviewed here.