Myoepithelial Tumors Research Articles

Abstract P4-01-18: A discrete population of p63+/K5/14+ cells implicated in the pathogenesis of salivary gland-like tumors of the breast

Abstract Background: Salivary gland-like tumors are currently subdivided into those with and those without myoepithelial differentiation. Furthermore, they show a wide range of differentiation patterns including squamous differentiation. Many authors believe that the myoepithelial cell plays a major role in this context. However, currently little is known about the evolution and cellular differentiation of these tumors. Material and Methods: For that reason, we performed an in situ Triple Immunofluorescence Lineage/Differentiation Tracing (isTILT) and qRT-PCR study of basal (K5/K14), glandular (K7/K8/18), and epidermal-specific squamous (K10) keratins, p63, and smooth muscle actin (SMA; myoepithelial marker) with the aim to trace different cell lineages and define their cellular hierarchy in tumors. We investigated 50 cases of salivary gland-like tumors of the breast (11 Adenoid-cystic carcinomas, 9 (adeno-)myoepithelial tumors, 8 adeno-squamous carcinomas including 12 syringomas of the nipple, 10 squamous cell carcinomas), and their corresponding counterparts. In 4 cases, the corresponding cell cultures were also analysed. Results: All tumor types contained p63+/K5/14+ progenitor cells in varying frequencies from a few percent up to 15%. These tumor cells were found to differentiate to glandular (K8/18-positive) or to myoepithelial (SMA-positive) lineage specific cells; they were also shown to generate various heterologeous cell differentiations such as squamous and mesenchymal progenies. p63 was partly retained in the myoepithelial and squamous cells lineages but not in the glandular cells lineage. These data were corroborated by RNA-expression results. The corresponding counterpart tumors of the salivary/lacrimal glands were found to have identical cellular compositions. Conclusions: Our findings clearly demonstrate that p63+/K5/14+ tumor cells in salivary gland-like tumors of the breast and in their counterparts are key players in tumor development and differentiation. They undergo a transition from their original p63+/K5/14+ precursor state to new p63+/K5/14+/SMA+ myoepithelial and/or p63+/K10+ squamous lineages, and/or to a K7+/K8/18+ glandular state, which can be pictured by isTILT-experiments and RNA-expression studies. Given the phenotypic similarity of p63+/K5/14+ tumor cells to physiological counterparts in the normal breast and salivary duct epithelium and considering the fact that these cells may give rise to a number of different progenies with specific differentiation lineages, we suggest that this cell and its physiological differentiation potential provides an important ontogenetic key to a better understanding of these tumors. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P4-01-18.

Clinicopathological and Molecular Spectrum of Ewing Sarcomas/PNETs, Including Validation of EWSR1 Rearrangement by Conventional and Array FISH Technique in Certain Cases

Over the years, a wide clinicopathological spectrum has been identified within Ewing family of tumors (EFTs). As these tumors are chemosensitive, their correct and timely identification is necessary. The aims of this study were (1) to present the diverse clinicopathological and molecular profile of EFTs in our settings, (2) to identify a pragmatic approach for diagnosing EFTs, especially for application of ancillary techniques, namely RT-PCR for specific transcripts (EWS-FLI1, EWS-ERG) and FISH for EWSR1 gene rearrangement, in certain cases and (3) to show the utility of tissue microarray in establishing a new FISH test. Fifty-eight EFTs were identified in 38 males and 20 females within an age-range of 1-65 years (median, 16), mostly in lower extremities (14) (24.1 %). Therapeutically, most patients underwent neoadjuvant chemotherapy with subsequent surgery. Histopathologically, diagnosis of EFTs was initially offered in 41/58 (70.6 %) tumors. On review, 59 % tumors showed diffuse pattern, while 41 % displayed rosettes. Immunohistochemically, tumor cells were mostly diffusely positive for CD99 (48/52) (92.3 %); FLI-1 (17/18) (94.4 %); variably for BCL2 (16/18) (88.8 %), synaptophysin (6/20) (35 %), S100-P (2/7) (28.5 %), CD56 (2/5) (40 %), NSE (2/5) (40 %), calponin (3/4) (75 %), EMA (5/24) (20.8 %) and CK (3/24) (12.5 %), the latter two mostly focally. Fifty five tumors were EWS-FLI1 positive, while a single tumor was EWS-ERG positive. Sensitivity for PCR was 61 %. EWSR1 rearrangement was detected by FISH in 12/13 Ewing sarcomas/PNETs. Sensitivity for EWSR1 test was 92.3 % and specificity was 100 %. Thirty-eight tumors, including 14 molecular confirmed EFTs and 21 other tumors were tested for EWSR1 rearrangement. Among 21 unrelated tumors, EWSR1 rearrangement was detected in few myoepithelial tumors, occasional desmoplastic small round cell tumor and an extraskeletal myxoid chondrosarcoma. Further, a tissue microarray with a separate set of 8 EFTs, confirmed at another laboratory was analysed for validation of EWSR1 rearrangement test. 23/28 (82.1 %) tissue cores of the tissue microarray, stained by FISH were interpretable, including EWSR1 rearrangement, detected in 20/28 tissue cores; not detected in 3 liver cores and uninterpretable in 5 (17.8 %) cores. Classical EFTs can be diagnosed with diffuse, membranous CD99 positivity, intranuclear FLI1 positivity and LCA negativity in malignant round cells. In unconventional cases, it is indispensable to reveal the concomitant fusion m-RNA by RT-PCR. In case of negative molecular results, it is necessary to prove EWSR1 rearrangement by FISH. These tests should be interpreted with clinicopathological correlation. Tissue microarrays for FISH are useful during validation of a new test, especially when sarcomas like EFTs show less genetic heterogeneity within tumor cells.

The diversity of soft tissue tumours with EWSR1 gene rearrangements: a review

Many soft tissue sarcomas have chromosomal translocations with resultant formation of new fusion genes. Among the genes that can be rearranged, the EWSR1 gene has been identified as a partner in a wide variety of clinically and pathologically diverse sarcomas as well as some non-mesenchymal tumours. The former include Ewing sarcoma and similar (Ewing-like) small round cell sarcomas, desmoplastic small round cell tumour, myxoid liposarcoma, extraskeletal myxoid chondrosarcoma, angiomatoid fibrous histiocytoma, clear cell sarcoma of soft tissue and clear cell sarcoma-like tumours of the gastrointestinal tract, primary pulmonary myxoid sarcoma, extrasalivary myoepithelial tumours and sporadic examples of low-grade fibromyxoid sarcoma, sclerosing epithelioid fibrosarcoma and mesothelioma. EWSR1 is a 'promiscuous' gene that can fuse with many different partner genes, but sometimes this results in phenotypically identical tumours. EWSR1 can, conversely, partner with the same genes in morphologically and behaviourally different neoplasms. This paper reviews the diversity of the several soft tissue tumour types that are associated with rearrangement of the EWSR1 gene.

Immunohistochemical validation of INI1/SMARCB1 in a spectrum of musculoskeletal tumors: An experience at a Tertiary Cancer Referral Centre

The purpose of this study was to evaluate and validate immunohistochemical (IHC) expression of INI1/SMARCB1 in various musculoskeletal tumors in the light of the established literature.Twenty-seven cases of epithelioid sarcoma (ES); 4 of extrarenal rhabdoid tumor (ERRT) of soft tissue and 97 other tumors, including 16 cases of synovial sarcoma (SS), were evaluated for IHC expression of INI1 on formalin-fixed, paraffin-embedded tissue sections of various biopsies.Out of 128 tumors, INI1/SMARCB1 staining was completely lacking in cases of ES (23/27) (85.1%), ERRTs (4/4) (100%), myoepithelial tumors (4/14) (28.5%) and in (1/16) (6.2%) cases of SS. Fourteen out of 15 SSs displayed a reduced staining pattern. Other 67 studied tumors were INI1-positive. Sensitivity for complete INI1 negativity in ES was 85.1%, and specificity with respect to its differentials, excluding ERRTs, was 94.8%.Complete lack of INI1 immunostaining in most ESs indicates its value as a diagnostic marker for ESs, including those occurring at rare sites; in ERRTs and in some myoepithelial tumors, within an appropriate clinicopathological context, in all kinds of biopsies. ES, at least in some cases, is immunohistochemically the most closely related tumor to an ERRT. A unique pattern of reduced INI1 expression in a SS is useful during triage of some cases for molecular testing. Its expression should be interpreted in the tumor cells, rather than intermixed stromal cells and or inflammatory cells that retain INI1 expression.

Glomus tumor of the mediastinum

Glomus tumors are rare benign myoepithelial neoplasms that can present with intractable pain. We report the case of a 59-year-old gentleman who presented with upper abdominal and chest pain caused by a posterior mediastinal glomus tumor arising from the spinal column, which required surgical resection. As glomus tumors usually develop in the limbs, this case highlights the complexity of diagnosis and treatment of glomus tumors when they present in rare locations.

Mucinous Myoepithelioma, a Recently Described New Myoepithelioma Variant

Myoepithelial neoplasms are tumors composed almost exclusively of cells with myoepithelial differentiation. They frequently contain spindle, plasmacytoid or epithelioid shaped cells and may have oncocytic or clear cytoplasmic features. They are uncommon, accounting for 1.5 % of all salivary gland tumors and for 2.2-5.7 % of major and minor salivary gland tumors, respectively. Recently this author, together with several colleagues, have described three unusual myoepithelial tumors, two benign and one malignant that contained abundant intracellular mucin material, which they termed the mucinous variant of myoepithelioma. This represents a unique, previously undescribed subtype that does not fit in the current classification system. A literature review revealed several similar cases reported as "signet ring-cell" adenocarcinomas of salivary gland, which stained for myoepithelial markers, in addition to containing intracellular mucin material, that are more accurately classified as mucinous myoepithelioma. To date, there are 17 reported mucinous myoepitheliomas; four were classified as benign and 13 as malignant. Thirteen arose in minor salivary glands and four in the parotid gland. One patient presented with a lymph node metastasis. With minimal follow-up currently available, this appears to be a benign to low-grade malignancy.

Cutaneous Syncytial Myoepithelioma

Cutaneous myoepithelial tumors demonstrate heterogenous morphologic and immunophenotypic features. We previously described, in brief, 7 cases of cutaneous myoepithelioma showing solid syncytial growth of ovoid, spindled, or histiocytoid cells. We now present the clinicopathologic features in a series of 38 cases of this distinctive syncytial variant, which were diagnosed between 1997 and 2012 (mostly seen in consultation). There were 27 men and 11 women, with a median age of 39 years (range, 2 mo to 74 y). Primary anatomic sites were the upper extremity (11, including 2 on the hand), upper limb girdle (3), lower extremity (14; 3 on the foot), back (6), face (2), chest (1), and buttock (1); the typical presentation was as either a polypoid or papular lesion. Tumors were well circumscribed and centered in the dermis and ranged in size from 0.3 to 2.7 cm (median 0.8 cm). Microscopically all tumors showed a solid sheet-like growth of uniformly sized ovoid to spindled or histiocytoid cells with palely eosinophilic syncytial cytoplasm. Nuclei were vesicular with fine chromatin and small or inconspicuous nucleoli and exhibited minimal to no atypia. Mitoses ranged from 0 to 4 per 10 HPF; 28 tumors showed no mitoses. Necrosis and lymphovascular invasion were consistently absent. Adipocytic metaplasia, appearing as superficial fat entrapped within the tumor, was seen in 12 cases. Chondro-osseous differentiation was seen in 1 tumor. All tumors examined were diffusely positive for EMA, and the majority showed diffuse staining for S-100 protein (5 showing focal staining). Keratin staining was focal in 1 of 33 tumors and seen in rare cells in 3 other cases. There was also positivity for GFAP (14/33), SMA (9/13), and p63 (6/11). Most lesions were treated by local excision. The majority of tumors tested (14/17; 82%) were positive by fluorescence in situ hybridization for EWSR1 gene rearrangement; testing for potential fusion partners (PBX1, ZNF444, POU5F1, DUX4, ATF1, CREB1, NR4A3, DDIT3, and NFATc2) was negative in all EWSR1-rearranged tumors. No FUS gene rearrangement was detected in 2 tumors lacking EWSR1 rearrangement. Follow-up information is available for 21 patients (mean follow-up 15 mo). One patient with a positive deep margin developed a local recurrence 51 months after initial biopsy. All other patients with available follow-up information, including 11 who had positive deep margins, are alive with no evidence of disease and no reported metastases. In summary, cutaneous syncytial myoepithelioma is a morphologically distinct variant that more frequently affects men, occurs over a wide age range, and usually presents on the extremities. Tumors are positive for S-100 protein and EMA, and, unlike most myoepithelial neoplasms, keratin staining is infrequent. EWSR1 gene rearrangement is present in nearly all tumors tested and likely involves a novel fusion partner. Prior reports describe some risk of recurrence and metastasis for cutaneous myoepithelial tumors; however, the syncytial variant appears to behave in a benign manner and only rarely recurs locally.

Frequent PLAG1 gene rearrangements in skin and soft tissue myoepithelioma with ductal differentiation

A subset of cutaneous and superficial soft tissue myoepithelial (ME) tumors displays a distinct ductal component and closely resembles mixed tumors/pleomorphic adenomas of salivary gland. As PLAG1 and HMGA2 rearrangements are the most common genetic events in pleomorphic adenomas, we sought to investigate if these abnormalities are also present in the skin/soft tissue ME lesions. In contrast, half of the deep-seated soft tissue ME tumors lacking ductal differentiation are known to be genetically unrelated, showing EWSR1 rearrangements. FISH analysis to detect PLAG1 and HMGA2 abnormalities was performed in 35 ME tumors, nine skin and 26 soft tissue, lacking EWSR1 and FUS rearrangements. For the PLAG1-rearranged tumors, FISH and RACE were performed to identify potential fusion partners, including CTNNB1 (beta-catenin) on 3p21 and LIFR (leukemia inhibitory factor receptor) on 5p13. Recurrent PLAG1 rearrangement by FISH was detected in 13 (37%) lesions, including three (33%) in the skin and 10 (38%) in the soft tissue. All were classified as benign and all except one showed abundant tubulo-ductal differentiation (comprising 12/24 [50%] of all tumors with ductal structures). A LIFR-PLAG1 fusion was detected by RACE and then confirmed by FISH in one soft tissue ME tumor with tubular formation. No CTNNB1 or LIFR abnormalities were detected in any of the remaining PLAG1-rearranged tumors. No structural HMGA2 abnormalities were detected in any of the 22 ME lesions tested. A subset of cutaneous and soft tissue ME tumors appears genetically linked to their salivary gland counterparts, displaying frequent PLAG1 gene rearrangements and occasionally LIFR-PLAG1 fusion.

Unusual myoid, perivascular, and postradiation lesions, with emphasis on atypical vascular lesion, postradiation cutaneous angiosarcoma, myoepithelial tumors, myopericytoma, and perivascular epithelioid cell tumor

In recent years, a number of new soft tissue tumor entities have been described that occur in the skin only, or that also occur in other sites but form clinically and pathologically distinct subsets when arising in the skin and subcutaneous tissue. These include a variety of mesenchymal lineages and have variable malignant potential, although superficial malignant soft tissue tumors generally have a more favorable outcome than their more deeply located counterparts. This article reviews the clinical and pathologic features and differential diagnoses of atypical vascular lesion, postradiation cutaneous angiosarcoma, myoepithelioma, myopericytoma, and perivascular epithelioid cell tumor.

Intraoral myoepithelial tumors: A review and case reports

Myoepithelial cells that express both epithelial and smooth muscle phenotype have a potential to differentiate into various cytomorphologic forms such as spindle, plasmacytoid, epitheloid and clear cells. Salivary gland tumors composed entirely or almost exclusively of myoepithelial cells are referred to as myoepitheliomas. They may be benign or malignant in nature and about 90% of them are benign and only 10% are malignant. The palate is the most common intraoral site of occurrence for both the variants. In this paper, we report one case of myoepithelioma occurring on the palate and two cases of myoepithelial carcinomas, one seen on the palate and the other rare case seen on the alveolar mucosa, along with an elaborate review on benign and malignant myoepitheliomas of salivary glands along with their ultra-structural, cytological and immunohistochemical profiles.

AB 55. Epithelial - myoepithelial carcinoma of the trachea

Background Presentation of a case of an epithelial - myoepithelial tumour with an unusual location.

Histopathological, immunohistochemical and molecular spectrum of myoepithelial tumours of soft tissues

Primary soft tissue myoepithelial tumours (METs) are rare. Recent studies have shown EWSR1 rearrangement in certain METs. We present clinicopathological, immunohistochemical and molecular features of 14 primary soft tissue METs. Fourteen tumours, five benign and nine malignant, occurred in 12 men and two women, with an age range of 18-60 years (mean, 39.2); in upper extremities, four (29 %); chest wall, three (21 %); paraspinal region, three (21 %); pelvis, two (14 %) and lower extremities, two (14 %). Tumour size varied from 2 to 21.6 cm (mean, 8.7). Microscopically, most tumours were at least focally circumscribed. Morphological heterogeneity was noted, commonest patterns being cord-like and diffuse arrangement of polygonal cells in a myxoid stroma. By immunohistochemistry, tumours were positive for epithelial membrane antigen (EMA) (10/12, 83 %), cytokeratin (CK)/MNF116 (3/12, 25 %), p63 (7/10, 70 %), CD10 (4/6, 67 %), calponin (6/6, 100 %), S-100P (11/13, 85 %), glial fibrillary acidic protein (GFAP) (6/12, 50 %), smooth muscle actin (SMA) (3/9, 33 %), INI1/SMARCB1 (6/10, 60 %), brachyury (0/11), CD34 (0/5) and vimentin (4/4, 100 %), implying 93 % positivity for at least one epithelial marker. EWSR1 gene rearrangement was detected in 3/6 (50 %) METs (one benign and two malignant) and in an eccrine porocarcinoma which was included for reasons of comparison. Outcome details were available for six patients all surgically treated; three tumours (two malignant and one benign) resected with unknown marginal status recurred; two patients died and a single patient with myoepithelial carcinoma, who underwent a wide excision, is disease-free. This study illustrates the wide morphological spectrum of soft tissue METs, including benign and malignant subtypes. EMA and S-100P are optimal markers that should be supplemented with broad spectrum keratins, such as AE1/AE3, along with p63, GFAP and calponin in case of need but the results must be correlated with morphological features. Brachyury is useful in separating parachordoma/myoepithelioma from chordoma. EWSR1 rearrangement mostly occurs in METs that are deep-seated, irrespective of benign or malignant behaviour. Most malignant METs are INI1 negative.

Myoepithelial carcinoma of the retromolar area with extensive mandibular involvement

Myoepithelial tumors were first described in 1943, and account for less than 1% of all salivary gland neoplasms. Their malignant variant, myoepithelial carcinoma, was first reported by Stromeyer et al. in 1975 and represents a very rare entity, characterized by distinct morphologic heterogeneity and an infiltrative growth pattern into adjacent tissues. However, there have been few reports on myoepithelial carcinoma affecting intra-oral minor salivary glands, and its immunohistochemical features have been poorly illustrated. We herein describe a rare case of myoepithelial carcinoma affecting the retromolar region of a 52-year-old woman that caused extensive mandibular bone destruction. We also reviewed the English literature concerning the involvement of intra-oral minor salivary glands by myoepithelial carcinoma.

Myoepithilial tumours of the breast

Myoepithelial lesions of the breast are defined as lesions arising from or composed of a dominant pure population of myoepithelial cells. They include adenoid cystic carcinoma, pleomorphic adenoma, myoepitheliosis, adenomyoepithelial adenosis, adenomyoepithelioma and myoepithelioma. The last two can be benign or malignant. Myoepithelial tumours of the breast are extremely rare. The benign myoepitheliomas are composed of a solid proliferation of cells with abundant eosinophilic syncytial cytoplasm. Although the biological behaviour of these remains uncertain, the tumours are considered to be myoepitheliomas with benign features due to mild nuclear pleomorphism, sparse mitotic figures and low ki67 index. Malignant myoepitheliomas represent the malignant end of the spectrum of myoepithelial lesions in the breast, usually arising de novo or in a pre-existing benign adenomyoepithelioma. Myoepitheliomas most often have spindle cell morphology and may mimic benign and malignant lesions. We report two cases of myoepithelial tumours and present a review of the current literature. Case presentation: The two patients were females aged 60 and 85 years, respectively. One patient had a palpable breast lump and the other presented as a firm mass without palpable axillary lymph nodes. The diagnosis of the first case was myoepithelioma with uncertain biological behaviour since the mitotic rate was 3-4mf/10High Power Field (HPF), and the second a malignant myoepithelioma due to the high mitotic rate. Conclusion: The patients were treated surgically and remain alive, two years after the initial diagnosis.

Apocrine adenomyoepithelioma - a rare but distinctive primary sweat gland neoplasm

Adenomyoepithelioma is a rare, microscopically distinctive tumor of the skin. This article explores an example that presented in the inguinal area in a 29-year-old woman, mimicking adenopathy. Histopathologically, the tumor included two different areas: a cystic area consisting of tubules and glands in hyalinized stroma and a solid area showing marked myoepithelial proliferation. The diagnosis of adenomyoepithelioma was confirmed by the presence of a biphasic immunoprofile, with expression of cytokeratins and epithelial membrane antigen in the glandular epithelium and with expression of vimentin and smooth muscle actin in the myoepithelial cells. An interesting novel finding was the expression of claudin-10 by myoepithelial cells, which to date has not been reported in the literature. The absence of metaplastic changes in the tumor stroma is crucial in the differential diagnosis with apocrine mixed tumor. Given that soft tissue adenomyoepithelioma is a benign tumor believed to originate from conventional sweat glands, its classification as a cutaneous myoepithelial neoplasm seems reasonable.

NR4A3 rearrangement reliably distinguishes between the clinicopathologically overlapping entities myoepithelial carcinoma of soft tissue and cellular extraskeletal myxoid chondrosarcoma

Myoepithelial carcinoma of soft tissue (MEC) and cellular extraskeletal myxoid chondrosarcoma (cEMC) share striking similarities. In this paper, we compare ten MECs with five cEMCs. MEC patients had an equal gender distribution. The age range was 15–76 years (mean, 42 years). Tumours were located on extremities, pelvic girdle, vulva and neck. Follow-up, available for nine patients, ranged from 4 to 85 months (mean, 35 months). Five patients were alive without evidence of disease, two were alive with disease and two died 8 months after the initial diagnosis. cEMCs were from three males and two females with an age range of 37–82 years (mean, 57 years); they presented in extremities, shoulder and paravertebral/cervical. Follow-up, available for four patients, ranged from 6 to 220 months (mean, 61 months). All patients were alive, two with recurrences and/or metastases and two without evidence of disease. Morphologically, the distinction between these two entities was difficult since all cases exhibited features typically seen in myoepithelial tumours. Immunohistochemically, MECs expressed pan-keratin (80 %), epithelial membrane antigen (EMA; 57 %), S100 (50 %), alpha-smooth muscle actin (ASMA; 75 %), calponin (67 %) and p63 (25 %). S100 and EMA were expressed in 40 % of cEMC cases respectively with additional immunoreactivity for p63, ASMA and glial fibrillary acidic protein in one case. Pan-keratin was negative in all neoplasms. NR4A3 rearrangement was present in four of four cEMCs and in none of the MECs. In contrast, three of nine (33 %) MECs and four of five (80 %) cEMCs showed an EWSR1 rearrangement. In summary, MECs and cEMCs share clinical, morphological, immunohistochemical and genetic characteristics. The pathognomic rearrangement of NR4A3 is a useful diagnostic feature in identifying cEMCs.

P-glycoprotein expression in canine mammary gland tumours related with myoepithelial cells

P-glycoprotein is influential in chemotherapy-resistance in numerous cancers and has been widely studied in human breast cancer research, but is less studied in canine mammary gland tumour (MGT). The study was to evaluate P-glycoprotein expression and its localisations related with prognostic factors with monoclonal antibody C219, by immunohistochemistry (IHC) of 68 cases of canine malignant (n=54) and benign (n=14) MGT. Additional immunofluorescence (IF) and reverse transcriptase-polymerase chain reaction (RT-PCR) were also performed. There was a novel finding that P-glycoprotein expression with C219 localised at two different cell types: epithelial and myoepithelial cells. Myoepithelial localised tumours were 5 benign (35.5%) and 21 malignant (63.6%), while epithelial localised tumours were 12 cases, all malignant (36.5%). Unlike conventional belief, semi-quantitative evaluation of IHC intensity scores of C219 expression in malignant MGT was related with favourable histopathological parameters.

Morphology of the Myoepithelial Cell: Immunohistochemical Characterization from Resting to Motile Phase

Myoepithelium is present in canine mammary tumors as resting and proliferative suprabasal and spindle and stellate interstitial cells. The aim of this paper was to evaluate a panel of markers for the identification of four different myoepithelial cell morphological types in the normal and neoplastic mammary gland and to investigate immunohistochemical changes from an epithelial to a mesenchymal phenotype. Cytokeratin 19 (CK19), cytokeratin 5/6 (CK5/6), cytokeratin 14 (CK14), estrogen receptor (ER), p63 protein, vimentin (VIM), and α-smooth muscle actin (Alpha-SMA) antibodies were used on 29 neoplasms (3 benign and 3 malignant myoepithelial tumors, 7 carcinomas in benign-mixed tumors and 16 complex carcinomas) and on normal tissue of mammary glands. All these antibodies were also tested on 3 mammary tissues from animals with no mammary pathology. The myoepithelial markers were well expressed in the suprabasal cells and gradually lost in the motile types, with the stellate cells maintaining only VIM expression typical of mesenchyma. ER labeled some resting and motile myoepithelial cells. On the basis of our results, we propose a transition from myoepithelial immotile cells into migratory fibroblast-like cells. This transition and the characterization of an immunohistochemical panel for resting and motile myoepithelial cells shed more light on the biological behavior of myoepithelial cells.

EWSR1-ATF1 chimeric transcript in a myoepithelial tumor of soft tissue: a case report

Soft tissue myoepithelial tumors, a recently defined entity, include benign and malignant lesions showing a considerable morphological and immunohistochemical heterogeneity. EWSR1 rearrangements are well recognized in this tumor type, and some of the partner genes have been identified. Herein we describe a soft tissue myoepithelioma arising in the pelvis with an EWSR1-ATF1 fusion, therefore extending the spectrum of partner genes of EWSR1. In addition, this case indicates that there are overlapping genetic features of myoepithelial tumors, clear cell sarcoma, angiomatoid fibrous histiocytoma, and hyalinizing clear-cell carcinoma of the salivary gland.

PLAG1 expression in mesenchymal tumors: An immunohistochemical study with special emphasis on the pathogenetical distinction between soft tissue myoepithelioma and pleomorphic adenoma of the salivary gland

PLAG1, a proto-oncogene activated in several types of tumors including pleomorphic adenoma of the salivary gland and lipoblastoma, is usually overexpressed because of chromosomal aberrations resulting in fusion genes. Myoepithelial tumors in soft tissue are morphologically similar to pleomorphic adenoma, but the genetic profiles of these tumors have not been fully examined. In the present study, we immunohistochemically evaluated the expression of PLAG1 in a series of 243 mesenchymal tumors. We determined that 14 tumors, including eight of 10 lipoblastomas, two of seven gastrointestinal stromal tumors, one of two angiomyofibroblastomas, one of five synovial sarcomas, one of seven leiomyomas and one of 12 myxofibrosarcomas were positive for PLAG1, whereas all seven soft tissue myoepitheliomas were PLAG1 negative. We examined two soft tissue myoepitheliomas, whose paraffin blocks were available, for fusion gene transcripts involving PLAG1 or HMGA2 specific for pleomorphic adenoma by a reverse transcription-polymerase chain reaction assay, and no fusion transcripts were detected. Our results suggest that soft tissue myoepithelioma may be a pathogenetically distinct tumor entity from pleomorphic adenoma based on the absence of PLAG1 overexpression and characteristic fusion genes. On the other hand, PLAG1 immunohistochemistry is useful for distinguishing lipoblastoma from other lipomatous tumors including liposarcoma.