-
The American Journal of Surgical... Oct 2019Cutaneous syncytial myoepithelioma (CSM) is a rare but distinctive benign variant in the family of myoepithelial neoplasms of skin and soft tissue. CSM has unique...
Cutaneous syncytial myoepithelioma (CSM) is a rare but distinctive benign variant in the family of myoepithelial neoplasms of skin and soft tissue. CSM has unique morphologic and immunohistochemical features, characterized by intradermal syncytial growth of spindled, ovoid, and histiocytoid cells and consistent staining for S-100 protein and EMA, and differs from other myoepithelial tumors by showing only infrequent keratin staining. Rearrangement of the EWSR1 gene is now known to occur in up to half of all skin and soft tissue myoepithelial tumors, with a wide family of documented fusion partners. In 2013, we reported frequent (80%) EWSR1 rearrangements in CSM, but were unable to identify the fusion partner using available studies at that time. After recent identification of an index case of CSM harboring an EWSR1-PBX3 fusion, we used a combination of targeted RNA sequencing and fluorescence in situ hybridization (FISH) studies to investigate the genetic features of a cohort of CSM. An EWSR1-PBX3 fusion was identified in all 13 cases successfully tested. RNA sequencing was successful in 8/13 cases, all of which were found to have identical breakpoints fusing exon 8 of EWSR1 to exon 5 of PBX3. FISH confirmed both EWSR1 and PBX3 rearrangements in 9/9 cases tested, which included 4 confirmed to have EWSR1-PBX3 fusion by RNA-Seq, 3 cases that failed RNA-Seq, and 2 cases examined by FISH alone. Two cases failed RNA sequencing but had no additional tissue remaining for FISH studies. Our findings demonstrate that EWSR1-PBX3 fusions occur in most (and possibly all) cases of CSM.
Topics: Adolescent; Adult; Aged; Biomarkers, Tumor; Female; Gene Fusion; Gene Rearrangement; Genetic Predisposition to Disease; Homeodomain Proteins; Humans; In Situ Hybridization, Fluorescence; Male; Middle Aged; Myoepithelioma; Proto-Oncogene Proteins; RNA-Binding Protein EWS; Sequence Analysis, RNA; Skin Neoplasms; Young Adult
PubMed: 31135487
DOI: 10.1097/PAS.0000000000001286 -
The Journal of Cell Biology Oct 2018The mammary epithelium is composed of an inner luminal and surrounding myoepithelial cell layer. The presence of cancer cells beyond the myoepithelium defines invasive...
The mammary epithelium is composed of an inner luminal and surrounding myoepithelial cell layer. The presence of cancer cells beyond the myoepithelium defines invasive breast cancer, yet the role of the myoepithelium during invasion remains unclear. We developed a 3D organotypic culture assay to model this process through lineage-specific expression of the prometastatic transcription factor We sought to distinguish the functional role of the myoepithelium in regulating invasion and local dissemination. Myoepithelial-specific expression induced cell-autonomous myoepithelial cell escape. Remarkably, luminal-specific expression was rarely sufficient for escape. Time-lapse microscopy revealed that myoepithelial cells collectively restrain and reinternalize invading Twist1 luminal cells. Barrier function correlated with myoepithelial abundance and required the expression of α-smooth muscle actin and P-cadherin. We next demonstrated that myoepithelial cells can restrain and recapture invasive cancer cells. Our data establish the concept of the myoepithelium as a dynamic barrier to luminal dissemination and implicate both smooth muscle contractility and intercellular adhesion in barrier function.
Topics: Animals; Cadherins; Female; Mammary Glands, Animal; Mammary Neoplasms, Animal; Mice; Mice, Transgenic; Myoepithelioma; Neoplasm Invasiveness; Neoplasm Proteins; Nuclear Proteins; Twist-Related Protein 1
PubMed: 30061105
DOI: 10.1083/jcb.201802144 -
Genes, Chromosomes & Cancer Jan 2023The RREB1::MRTFB (former RREB1::MKL2) fusion characterizes ectomesenchymal chondromyxoid tumors (EMCMT) of the tongue. Only five molecularly confirmed extra-glossal...
RREB1::MRTFB fusion-positive extra-glossal mesenchymal neoplasms: A series of five cases expanding their anatomic distribution and highlighting significant morphological and phenotypic diversity.
The RREB1::MRTFB (former RREB1::MKL2) fusion characterizes ectomesenchymal chondromyxoid tumors (EMCMT) of the tongue. Only five molecularly confirmed extra-glossal EMCMT cases have been reported recently; all occurring at head and neck or mediastinal sites. We herein describe five new cases including the first two extracranial/extrathoracic cases. The tumors occurred in three male and two female patients with an age ranging from 18 to 61 years (median, 28). Three tumors were located in the head and neck (jaw, parapharyngeal space, and nasopharyngeal wall) and two in the soft tissue (inguinal and presacral). The tumor size ranged from 3.3 to 20 cm (median, 7). Treatment was surgical without adjuvant treatment in all cases. Two cases were disease-free at 5 and 17 months; other cases were lost to follow-up. Histologically, the soft tissue cases shared a predominant fibromyxoid appearance, but with variable cytoarchitectural pattern (cellular perineurioma-like whorls and storiform pattern in one case and large polygonal granular cells embedded within a chondromyxoid stroma in the other). Two tumors (inguinal and parapharyngeal) showed spindled to ovoid and round cells with a moderately to highly cellular nondescript pattern. One sinonasal tumor closely mimicked nasal chondromesenchymal hamartoma (NCMH). Mitotic activity was low (0-5 mitoses/10 hpfs). Immunohistochemical findings were heterogeneous with variable expression of S100 (2/5), EMA (2/3), CD34 (1/4), desmin (1/4), and GFAP (1/3). Targeted RNA sequencing revealed the same RREB1::MRTFB fusion in all cases, with exon 8 of RREB1 being fused to exon 11 of MRTFB. This study expands the topographic spectrum of RREB1::MRTFB fusion-positive mesenchymal neoplasms, highlighting a significant morphological and phenotypic diversity. Overall, RREB1::MRTFB-rearranged neoplasms seem to fall into two subcategories: tumors with lobulated, chondroid, or myxochondroid epithelioid morphology (Cases 2 and 3) and those with more undifferentiated hypercellular spindle cell phenotype (Cases 1, 4, and 5). Involvement of extracranial/extrathoracic sites and the NCMH-like pattern are novel. The biology of these likely indolent or benign tumors remains to be verified in the future.
Topics: Male; Female; Humans; Biomarkers, Tumor; Tongue Neoplasms; Gene Fusion; Myoepithelioma; Phenotype; Soft Tissue Neoplasms; DNA-Binding Proteins; Transcription Factors
PubMed: 35763541
DOI: 10.1002/gcc.23082 -
BMJ Case Reports Oct 2019Myoepithelioma is rare benign neoplasm, usually involves salivary glands and very less often seen in minor salivary glands of nose. Clinically it resembles like other...
Myoepithelioma is rare benign neoplasm, usually involves salivary glands and very less often seen in minor salivary glands of nose. Clinically it resembles like other tumour masses and thus posed challenge to clinician and pathologist. It becomes very difficult to diagnose due to its varied presentation and propensity for malignant transformation. We reported a case of a male patient with pink fleshy mass in the left nose with epistaxis and nasal obstruction. Preliminary biopsy and contrast-enhanced CT were done to delineate tumour size and type and then patient underwent endoscopic en-bloc resection. Histopathology and immunohistochemistry were found to be consistent for myoepithelioma. No recurrence was seen during a 6-month follow-up period. Its rarity should be a part of differential diagnosis among nasal tumours. Many of the tumour recurrences are associated with incomplete surgical resection so wide local excision with regular follow-up is essential for this rare entity.
Topics: Adult; Diagnosis, Differential; Endoscopy; Epistaxis; Humans; Male; Myoepithelioma; Nasal Obstruction; Nasal Septum; Nose Neoplasms; Salivary Gland Neoplasms; Salivary Glands, Minor
PubMed: 31653626
DOI: 10.1136/bcr-2019-230926 -
Cureus Mar 2017A 58-year-old female had a mass in the right breast palpable beneath the areola. A mammogram revealed a 1.5-centimeter soft tissue density that was confirmed with a...
A 58-year-old female had a mass in the right breast palpable beneath the areola. A mammogram revealed a 1.5-centimeter soft tissue density that was confirmed with a subsequent ultrasound. The patient underwent a core needle biopsy which was initially reported as a moderately differentiated invasive ductal carcinoma. Immunohistochemical analysis revealed negative staining for estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor (HER2), mammaglobin, and gross cystic disease fluid protein 15 (GCDFP-15). A wide local excision of the mass was performed. The pathology report stated the tumor had an infiltrative growth pattern with a desmoplastic stromal response with enhanced epithelial atypia consistent with malignant transformation of a nodular clear cell hidradenoma. Clear cell hidradenoma is a very rare tumor originating from the sweat gland and has a propensity for the face and extremities. The malignant variant of this tumor is extremely rare and has been reported to originate from the breast in few cases. This case represents the difficulty in diagnosing this tumor along with the radiographic and histologic features that can distinguish this malignancy from other entities.
PubMed: 28409065
DOI: 10.7759/cureus.1064 -
International Journal of Surgery Case... Jul 2024Tumours of salivary glands are rare and have various histo-pathological subtypes. Myoepitheliomas were first classified by Sheldon et al. and the criterion to classify...
INTRODUCTION
Tumours of salivary glands are rare and have various histo-pathological subtypes. Myoepitheliomas were first classified by Sheldon et al. and the criterion to classify or diagnose it was first defined by Barnes et al. and Sciubba and Brannon. Myoepithelioma accounts for less than 1 % of all salivary gland tumours, 40 % of these tumours occur in the parotid gland while 21 % occur in the minor salivary glands. A case of myoepithelioma of a minor salivary gland of the cheek is described, emphasizing the problems of the differential diagnosis.
PRESENTATION OF THE CASE
A 40-year-old female reported to the department with a complaint of a cheek bite on her right side for a few months. The physical examination showed a presence of lobulated whitish mucosa on the right buccal mucosa at the level of the occlusal plane, on palpation it revealed a non-painful mass approximately 1.5 cm in radius, mobile to bimanual palpation. An excisional biopsy was performed under local anaesthesia. Microscopic and immunohistochemistry confirmed the tumour to be a myoepithelioma of a minor salivary gland with the absence of definitive features of malignancy.
DISCUSSION
Due to their infrequency and multiplicity of histopathology, myoepitheliomas present difficulties in diagnosis. Cellular varieties can be misdiagnosed as malignancies. A key to determining diagnostic criteria for myoepitheliomas is to study cellular morphology, cytoplasmic filament expression, and ultrastructural features of the tumour and apply this information to defining myoepitheliomas.
CONCLUSION
Myoepitheliomas are rare tumours, utilization of immunohistochemical staining and electron microscopy are useful tools for the diagnosis of myoepitheliomas to ensure proper treatment and follow-up.
PubMed: 38875824
DOI: 10.1016/j.ijscr.2024.109849 -
The American Journal of Surgical... Jul 2021Epithelial-myoepithelial carcinoma (EMC) is a rare salivary gland cancer characterized by biphasic tubular structures composed of inner ductal and outer clear... (Comparative Study)
Comparative Study
Epithelial-myoepithelial carcinoma (EMC) is a rare salivary gland cancer characterized by biphasic tubular structures composed of inner ductal and outer clear myoepithelial cells. Because of its histologic variety and overlap of histologic features with other salivary gland tumors, there are broad differential diagnoses. The HRAS Q61R mutation has been reported to be frequent in and specific to EMC. We evaluated the usefulness of RAS Q61R mutant-specific immunohistochemical (IHC) staining for detecting this genetic alteration in EMC. We investigated 83 EMC cases and 66 cases of salivary gland tumors with an EMC-like component, including pleomorphic adenoma, adenoid cystic carcinoma, basal cell adenoma/adenocarcinoma, and myoepithelial carcinoma. Sanger sequencing was performed for HRAS, KRAS, and NRAS. The diffuse and membranous/cytoplasmic RAS Q61R IHC expression was observed in 65% of EMC cases, in which all cases harbored the HRAS Q61R mutation. IHC-positive cases were present only in de novo EMCs (54/76 cases, 71%) but not in EMCs ex pleomorphic adenoma. The immunoreactivity was almost always restricted to the myoepithelial cells. Conversely, all EMC cases lacking the HRAS Q61R mutation were negative on IHC. In addition, only 3% of EMC-like tumors showed the abovementioned immunopositivity. None of the cases examined carried KRAS or NRAS mutations. IHC for RAS Q61R is highly sensitive and specific for detecting the HRAS Q61R mutation in EMC. Since significant immunopositivity was almost exclusively identified in nearly two thirds of EMCs but seldom in the histologic mimics, the IHC of RAS Q61R is a useful tool for diagnosing EMC in general pathology laboratories.
Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; DNA Mutational Analysis; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Japan; Male; Middle Aged; Mutation; Myoepithelioma; Neoplasms, Glandular and Epithelial; Predictive Value of Tests; Proto-Oncogene Proteins p21(ras); Reproducibility of Results; Retrospective Studies; Salivary Gland Neoplasms
PubMed: 33481388
DOI: 10.1097/PAS.0000000000001673 -
Head and Neck Pathology Jun 2023Secretory myoepithelial carcinomas (SMCA) are rare, mucinous, signet ring predominant tumors with primitive myoepithelial features. While many mucinous salivary gland...
BACKGROUND
Secretory myoepithelial carcinomas (SMCA) are rare, mucinous, signet ring predominant tumors with primitive myoepithelial features. While many mucinous salivary gland tumors have now been molecularly characterized, key drivers in SMCA have yet to be elucidated. Recently, NKX3.1, a homeodomain transcription factor implicated in salivary mucous acinar development was also shown in a subset of salivary mucinous neoplasms, salivary intraductal papillary mucinous neoplasms (SG-IPMN). To date, NKX3.1 expression has not been characterized in other mucinous salivary lesions. Here, we report molecular and extended immunophenotypic findings in SMCA and NKX3.1 expression in the context of other head and neck lesions.
METHODS
We retrieved 4 previously reported SMCA, performed additional immunohistochemical and targeted next-generation sequencing (NGS). We also investigated the use of NKX3.1 as a marker for SMCA in the context of its prevalence and extent (using H-score) in a mixed cohort of retrospectively and prospectively tested head and neck lesions (n = 223) and non-neoplastic tissues (n = 66).
RESULTS
NKX3.1 positivity was confirmed in normal mucous acini as well as in mucous acinar class of lesions (5/6, mean H-score: 136.7), including mucinous adenocarcinomas (3/4), SG-IPMN (1/1), and microsecretory adenocarcinoma (MSA) (1/1). All SMCA were positive. Fluorescence in situ hybridization for SS18 rearrangements were negative in all successfully tested cases (0/3). NGS was successful in two cases (cases 3 and 4). Case 3 demonstrated a PTEN c.655C>T p.Q219* mutation and a SEC16A::NOTCH1 fusion while case 4 (clinically aggressive) showed a PTEN c.1026+1G>A p.K342 splice site variant, aTP53 c.524G>A p.R175H mutation and a higher tumor mutation burden (29 per Mb). PTEN immunohistochemical loss was confirmed in both cases and a subset of tumor cells showed strong (extreme) staining for P53 in Case 4.
CONCLUSION
Despite a partial myoepithelial phenotype, SMCA, along with mucinous adenocarcinomas/SG-IPMN and MSA, provisionally constitute a mucous acinar class of tumors based on morphology and NKX3.1 expression. Like salivary mucinous adenocarcinomas/SG-IPMN, SMCA also show alterations of the PTEN/PI3K/AKT pathway and may show progressive molecular alterations. We document the first extramammary tumor with a SEC16A::NOTCH1 fusion.
Topics: Humans; Adenocarcinoma; Adenocarcinoma, Mucinous; Biomarkers, Tumor; Endoplasmic Reticulum; Golgi Apparatus; In Situ Hybridization, Fluorescence; Myoepithelioma; Pancreatic Intraductal Neoplasms; Phenotype; Phosphatidylinositol 3-Kinases; Retrospective Studies; Salivary Gland Neoplasms; Transcription Factors; Vesicular Transport Proteins
PubMed: 36746884
DOI: 10.1007/s12105-023-01524-2 -
Asian Journal of Neurosurgery 2021Myoepithelial tumors are rare neoplasms that develop from myoepithelial cells in glandular structures and soft tissues. Primary intracranial myoepithelial neoplasms are...
Myoepithelial tumors are rare neoplasms that develop from myoepithelial cells in glandular structures and soft tissues. Primary intracranial myoepithelial neoplasms are even rarer with around ten cases reported. On the other hand, adrenocortical carcinoma (ACC) is also uncommon with an annual incidence of 0.7-2 per million and carries a poor prognosis. It is known to have an association with certain familial cancer syndromes. Even in sporadic cases, a significant portion of them had other malignancies before and after diagnosis of ACC. We reported a 34-year-old gentleman who was diagnosed to have ACC without known familial cancer syndrome. After that, he was also found to have right occipital myoepithelioma that was confirmed by excisional biopsy. There was no known association between these two pathologies. This is the first report of coincidence of ACC and intracranial myoepithelioma.
PubMed: 34660377
DOI: 10.4103/ajns.AJNS_502_20 -
International Journal of Oral Science Feb 2018Prompted by a unique case of an ectomesenchymal chondromyxoid tumor (ECT) of the palate in a 54-year-old female, we reviewed the English and German literature on this... (Review)
Review
Prompted by a unique case of an ectomesenchymal chondromyxoid tumor (ECT) of the palate in a 54-year-old female, we reviewed the English and German literature on this entity until the end of 2016 using PubMed. The search produced 74 lingual cases with a nearly equal sex distribution and a mean age of 39.3 years, and two extra-lingual cases sharing histological and immunohistological features including nodular growth, round, fusiform or spindle-shaped cellular architecture, and chondromyxoid stroma. Immunophenotyping showed the majority of cases to be positive for glial fibrillary acidic protein (GFAP), S-100 protein, glycoprotein CD57, pancytokeratin (AE1/AE3), and smooth muscle actin (SMA); in isolated cases there was molecular-genetic rearrangement or gain of Ewing sarcoma breakpoint region 1 (EWSR1) but no rearrangement of pleomorphic adenoma gene 1 (PLAG1). At present, ectomesenchymal cells that migrate from the neural crest are considered to play a pivotal role in tumor origin. All cases had a benign course, although there were three recurrences. Because of the rarity of this tumor and the need for differential diagnostic differentiation from myoepithelioma and pleomorphic adenoma, both oral surgeons and pathologists should be aware of this entity.
Topics: Biomarkers, Tumor; Chondroma; Diagnosis, Differential; Female; Humans; Immunophenotyping; Mesenchymoma; Middle Aged; Myoepithelioma; Palatal Neoplasms
PubMed: 29491357
DOI: 10.1038/s41368-017-0003-9