-
The genetic landscape of SMARCB1 alterations in SMARCB1-deficient spectrum of mesenchymal neoplasms.Modern Pathology : An Official Journal... Dec 2022SMARCB1 biallelic inactivation resulting in SMARCB1/INI1 deficiency drives a wide range of malignancies, including many mesenchymal tumors. However, the specific types...
SMARCB1 biallelic inactivation resulting in SMARCB1/INI1 deficiency drives a wide range of malignancies, including many mesenchymal tumors. However, the specific types of SMARCB1 alterations and spectrum of cooperating mutations among various types of sarcomas has not been well investigated. We profiled SMARCB1 genetic alterations by targeted DNA sequencing and fluorescence in situ hybridization (FISH) in a large cohort of 118 soft tissue and bone tumors, including SMARCB1-deficient sarcomas (78, 66%): epithelioid sarcomas, epithelioid peripheral nerve sheath tumors, poorly differentiated chordomas, malignant rhabdoid tumors, and soft tissue myoepithelial tumors, as well as non-SMARCB1-deficient sarcomas (40, 34%) with various SMARCB1 genetic alterations (mutations, copy number alterations). SMARCB1 loss by immunohistochemistry was present in 94% SMARCB1 pathogenic cases. By combined sequencing and FISH assays, 80% of SMARCB1-deficient tumors harbored homozygous (biallelic) SMARCB1 loss, while 14% demonstrated heterozygous SMARCB1 loss-of-function (LOF) alterations, and 6% showed no demonstrable SMARCB1 alterations. FISH and sequencing were concordant in the ability to detect SMARCB1 loss in 48% of cases. Epithelioid sarcomas most commonly (75%) harbored homozygous deletions, while a subset showed focal intragenic deletions or LOF mutations (nonsense, frameshift). In contrast, most soft tissue myoepithelial tumors (83%) harbored SMARCB1 nonsense point mutations without copy number losses. Additionally, clinically significant, recurrent co-occurring genetic events were rare regardless of histotype. By sequencing, extended 22q copy number loss in genes flanking the SMARCB1 locus (22q11.23) occurred in one-third of epithelioid sarcomas and the majority of poorly differentiated chordomas. Poorly differentiated chordomas and soft tissue myoepithelial tumors showed significantly worse overall and disease-free survival compared to epithelioid sarcomas. Overall, SMARCB1 LOF alterations predominate and account for SMARCB1 protein loss in most cases: majority being biallelic but a subset were heterozygous. In contrast, SMARCB1 alterations of uncertain significance can be seen in diverse sarcomas types and does not indicate a SMARCB1-deficient entity.
Topics: Humans; SMARCB1 Protein; In Situ Hybridization, Fluorescence; Myoepithelioma; Chordoma; DNA-Binding Proteins; Transcription Factors; Chromosomal Proteins, Non-Histone; Rhabdoid Tumor; Neoplasms, Connective and Soft Tissue; Sarcoma; Soft Tissue Neoplasms
PubMed: 36088476
DOI: 10.1038/s41379-022-01148-x -
Frontiers in Oncology 2022Malignant myoepithelioma of the head and neck (HNMM) is a rare malignancy, and its characteristics and survival rates have not been well-defined. This study aimed to...
Malignant myoepithelioma of the head and neck (HNMM) is a rare malignancy, and its characteristics and survival rates have not been well-defined. This study aimed to define the epidemiology of HNMM and identify the prognostic factors associated with the disease. Data on all patients diagnosed with HNMM between 1991 and 2016 were gathered from the Surveillance Epidemiology and End Results (SEER) database. The demographics, clinicopathological characteristics, treatment, and prognoses of the patients were described. Cox regression analysis was used to identify the prognostic factors, and the prognostic nomograms for overall survival (OS) and disease-specific survival (DSS) were constructed. A total of 333 cases of HNMM were identified. The average age at diagnosis was 60.6 years, and 50.1% of the patients were men. After diagnosis, 46.2% of patients underwent surgery alone, 43.5% of patients underwent surgery and radiotherapy, and 3.6% of patients received only radiotherapy. Survival analysis showed that the 5-year OS and DSS for all HNMM patients were 69.7 and 82.1%, respectively. In the multivariate analysis model, the undifferentiated pathological grade (P <0.05) and M1 in the M category (P <0.01) were independent prognostic factors for poor OS and DSS, whereas the use of surgical resection was an independent favorable prognostic factor for both OS and DSS (P <0.05). The prognostic nomograms for OS and DSS prediction were constructed; the C-index values for OS and DSS prediction were 0.78 (95% CI 0.70-0.86) and 0.79 (95% CI 0.67-0.90), respectively. In conclusion, this SEER data-based study demonstrated that HNMM patients often had a favorable prognosis, and distant metastasis, pathological grade, and the use of surgery contributed to their survival. Furthermore, we developed a prognostic nomogram to predict OS and DSS for HNMM patients to aid physicians in the clinical management of this rare disease.
PubMed: 35847870
DOI: 10.3389/fonc.2022.754967 -
Journal of Cutaneous Pathology Jun 2020
Topics: 12E7 Antigen; Adult; Carcinoma; Chondrosarcoma; Diagnosis, Differential; Humans; Immunophenotyping; Middle Aged; Myoepithelioma; Oncogene Proteins, Fusion; Repressor Proteins; Sarcoma, Ewing; Soft Tissue Neoplasms; Translocation, Genetic
PubMed: 32166781
DOI: 10.1111/cup.13682 -
The American Journal of Surgical... Sep 2022Cutaneous myoepithelial neoplasms are a heterogenous group of neoplasms with mixed tumors typically affecting the head and myoepitheliomas showing a predilection for the...
Cutaneous myoepithelial neoplasms are a heterogenous group of neoplasms with mixed tumors typically affecting the head and myoepitheliomas showing a predilection for the extremities. Their malignant counterparts, myoepithelial carcinoma, and malignant mixed tumor are exceptionally rare in the skin, and the morphologic criteria for malignancy are only poorly defined. The aim of the present study was to characterize the clinicopathologic features of myoepithelial neoplasms presenting on acral skin. The clinical and histopathologic features of 11 tumors were recorded, and follow-up was obtained. Immunohistochemistry was performed for S100, SOX10, glial fibrillary acidic protein, keratins, epithelial membrane antigen, p63, p40, smooth muscle actin, desmin, and PLAG1. The tumors mainly affected the feet of adults (range: 26 to 78 y; median: 47 y) with a predilection for the great toe and a male predominance of 1.8:1. Most tumors (91%) displayed a lobular architecture composed of solid and nested growth of epithelioid cells with plasmacytoid features in a myxoid or angiomatous stroma. Scattered cytologic atypia and rare duct differentiation were frequently noted. Three tumors with confluent cytologic atypia, infiltrative growth, and lymphovascular invasion were classified as malignant. By immunohistochemistry, the tumors were positive for S100, SOX10, keratins AE1/AE3, CK5/6 and CK7, and PLAG1. Local recurrence and bilateral pulmonary metastasis were observed in a patient presenting with a histopathologically benign-appearing tumor. Two patients with malignant tumors experienced local recurrences, and 1 developed metastasis to soft tissue, lung, and mediastinal lymph nodes. All patients are currently alive, all but 1 with no evidence of disease after a median follow-up interval of 96 months (range: 2 to 360 mo). In conclusion, acral myoepithelial neoplasms show distinctive and reproducible histopathologic and immunohistochemical features. They are best regarded as a distinctive subset of mixed tumors with features reminiscent of their salivary gland counterparts. While most tumors pursue a benign disease course, histopathologic features appear to be a poor indicator of prognosis.
Topics: Adenoma, Pleomorphic; Adult; Aged; Biomarkers, Tumor; Carcinoma; Female; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Myoepithelioma; Skin Neoplasms
PubMed: 35354162
DOI: 10.1097/PAS.0000000000001896 -
Frontiers in Oncology 2022Among sarcomas, which are rare cancers with an incidence of <6 per 100.000/year cases, ultra-rare sarcomas have an incidence of approximately ≤1/1,000,000/year cases...
BACKGROUND
Among sarcomas, which are rare cancers with an incidence of <6 per 100.000/year cases, ultra-rare sarcomas have an incidence of approximately ≤1/1,000,000/year cases and altogether account for ~20% of all soft tissue sarcomas (STS) and bone sarcomas. The Italian Sarcoma Group has recently performed a non-interventional, retrospective TrObs study with data from 512 anthracycline-pretreated patients with advanced multiple STS histologies and treated with trabectedin (Palmerini, 2021; ClinicalTrials.gov Identifier: NCT02793050).
METHODS
A analysis of case series to evaluate the efficacy and safety of trabectedin on patients with ultra-rare and other rare translocation-related sarcomas included in TrObs study was performed. Main outcomes comprised investigator-assessed overall response rate (ORR), disease control rate (DCR), progression-free survival (PFS) and safety.
RESULTS
Thirty-six patients (18 women) with ultra-rare and other rare sarcoma and a median age of 53.0 years (range: 22-81) were included. Most patients had solitary fibrous tumor (SFT; n=11) followed by epithelioid sarcoma (n=5), malignant peripheral nerve sheath tumor (MPNST; n=4), extraskeletal myxoid chondrosarcoma (EMC; n=3), desmoplastic small round cell tumor (DSRCT; n=3), and alveolar soft part sarcoma (ASPS), rhabdomyosarcoma and clear cell sarcoma (n=2 each). Thirty-five patients had metastatic disease and 23 patients received trabectedin as a second-line treatment. Among 35 patients evaluable for response, two patients with SFT and ASPS had a partial response and one patient with DSRCT obtained a complete response, reaching an ORR of 8.6% (95% CI: 2.8-23.4%). Among patients with an ORR, 6-months PFS was 100% in patients with ASPS, 45.7% in patients with SFT and 33.3% in those with DSRCT. Two patients with epithelioid sarcoma and myoepithelioma had disease stabilization lasting >24 months. Nine patients had at least one grade 3/4 adverse event, mostly being bone marrow toxicity (n=6).
CONCLUSIONS
Trabectedin has some anti-tumor activity in some ultra-rare and other rare sarcomas, particularly translocation-related sarcomas, with the well-known manageable safety profile.
PubMed: 36568164
DOI: 10.3389/fonc.2022.1042479 -
Indian Journal of Otolaryngology and... Oct 2019Myoepitheliomas are rare tumours of salivary glands arising from myoepithelial cells, which are normal constituent of the salivary acini and ducts and are found between...
Myoepitheliomas are rare tumours of salivary glands arising from myoepithelial cells, which are normal constituent of the salivary acini and ducts and are found between the epithelial cells and the basement membrane. The most common site of origin of Myoepitheliomas are the salivary glands and rarely other sites in the head and neck have been described in literature. Myoepithelioma arising from parapharyngeal space provide both a diagnostic and therapeutic challenge. We present such a case and discuss its diagnostic and therapeutic aspects.
PubMed: 31742043
DOI: 10.1007/s12070-018-1488-z -
Human Pathology Oct 2023Myoepithelial neoplasms comprise a histologically and immunophenotypically diverse spectrum of entities. The following review is a comprehensive summary of acral lesions...
Myoepithelial neoplasms comprise a histologically and immunophenotypically diverse spectrum of entities. The following review is a comprehensive summary of acral lesions demonstrating myoepithelial-like and chondroid histomorphology, as well as recently described mimics that are diagnostically challenging to distinguish. The salient clinicopathologic, immunophenotypic, and molecular features of each entity are described.
PubMed: 37054781
DOI: 10.1016/j.humpath.2023.04.003 -
Head and Neck Pathology Mar 2023Myoepithelial neoplasms of the salivary gland are benign or malignant neoplasms composed exclusively of neoplastic myoepithelial cells. These tumors, including the... (Review)
Review
BACKGROUND
Myoepithelial neoplasms of the salivary gland are benign or malignant neoplasms composed exclusively of neoplastic myoepithelial cells. These tumors, including the benign myoepithelioma and the malignant counterpart myoepithelial carcinoma, exhibit a wide range of cytomorphologic features and architectural patterns.
METHODS
Review.
RESULTS
Myoepithelial cells can be epithelial, plasmacytoid, clear cell, spindle cell, and/or oncocytic cell, arranging as trabeculae, solid sheets, nests, cords, and/or single cells. A stromal component is commonly but not universally present, Therefore, their differential diagnoses are quite broad, including salivary gland neoplasms especially those with a myoepithelial component, plasmacytoma, melanoma, and various mesenchymal tumors.
CONCLUSION
In this review, we summarize the characteristic histologic features, useful immunohistochemical panel, and common molecular alterations of myoepithelial tumors and their top differential diagnoses. A logical stepwise algorithmic approach and an immunohistochemical panel to include multiple myoepithelial markers are essential to establish the correct diagnosis.
Topics: Humans; Biomarkers, Tumor; Immunohistochemistry; Salivary Gland Neoplasms; Salivary Glands; Myoepithelioma; Carcinoma
PubMed: 36928733
DOI: 10.1007/s12105-022-01502-0 -
Japanese Journal of Clinical Oncology Mar 2024Salivary gland-type tumors of the lung are thought to originate from the submucosal exocrine glands of the large airways. Due to their rare occurrence, reports of their... (Review)
Review
Salivary gland-type tumors of the lung are thought to originate from the submucosal exocrine glands of the large airways. Due to their rare occurrence, reports of their study are limited to small-scale or case reports. Therefore, daily clinical practices often require a search for previous reports. In the last 20 years, several genetic rearrangements have been identified, such as MYB::NF1B rearrangements in adenoid cystic carcinoma, CRTC1::MAML2 rearrangements in mucoepidermoid carcinoma, EWSR1::ATF1 rearrangements in hyalinizing clear cell carcinoma and rearrangements of the EWSR1 locus or FUS (TLS) locus in myoepithelioma and myoepithelial carcinoma. These molecular alterations have been useful in diagnosing these tumors, although they have not yet been linked to molecularly targeted therapies. The morphologic, immunophenotypic, and molecular characteristics of these tumors are similar to those of their counterparts of extrapulmonary origin, so clinical and radiologic differential diagnosis is required to distinguish between primary and metastatic disease of other primary sites. However, these molecular alterations can be useful in differentiating them from other primary lung cancer histologic types. The management of these tumors requires broad knowledge of the latest diagnostics, surgery, radiotherapy, bronchoscopic interventions, chemotherapy, immunotherapy as well as therapeutic agents in development, including molecularly targeted agents. This review provides a comprehensive overview of the current diagnosis and treatment of pulmonary salivary gland tumors, with a focus on adenoid cystic carcinoma and mucoepidermoid carcinoma, which are the two most common subtypes.
Topics: Humans; Carcinoma, Adenoid Cystic; Carcinoma, Mucoepidermoid; Salivary Gland Neoplasms; Carcinoma; Myoepithelioma; Salivary Glands; Lung Neoplasms
PubMed: 38018262
DOI: 10.1093/jjco/hyad160 -
Veterinary Pathology May 2020Feline mammary tumors are usually malignant and aggressive carcinomas. Most cases are simple monophasic carcinomas (1 epithelial population), and additional phenotyping...
Feline mammary tumors are usually malignant and aggressive carcinomas. Most cases are simple monophasic carcinomas (1 epithelial population), and additional phenotyping is usually not needed. In this study, we describe 10 malignant mammary tumors from 9 female cats that had unusual histomorphology: they appeared biphasic, with 2 distinct cell populations. Initially, they were morphologically diagnosed as either carcinosarcoma (1/10) or malignant pleomorphic tumor (9/10) of the mammary gland, as the latter did not match any previously described histological subtype. Immunohistochemistry (IHC) was performed for pancytokeratin, cytokeratins 8 and 18, cytokeratin 14, cytokeratins 5 and 6, vimentin, p63, calponin, alpha-smooth muscle actin, Ki-67, ERBB2, estrogen receptor alpha, and progesterone receptor. In 7 of 10 cases, the biphasic nature was confirmed and, on the basis of the IHC results, they were classified as carcinoma and malignant myoepithelioma (4/10), ductal carcinoma (1/10), and carcinosarcoma (2/10). The other 3 of 10 cases were monophasic based on IHC. In the cases of carcinoma and malignant myoepithelioma, the malignant myoepithelial cells were 100% positive for vimentin (4/4) and variably positive for p63, calponin, and cytokeratins (4/4). These findings show that, although rare, biphasic mammary carcinomas do occur in cats. In dogs and humans, tumors composed of malignant epithelial and myoepithelial cells have a less aggressive behavior than certain simple carcinomas, and therefore, their identification might also be clinically significant in the cat.
Topics: Animals; Biomarkers, Tumor; Calcium-Binding Proteins; Carcinoma; Carcinoma, Ductal; Carcinosarcoma; Cat Diseases; Cats; Dogs; Female; Immunohistochemistry; Keratins; Mammary Neoplasms, Animal; Microfilament Proteins; Myoepithelioma; Sarcoma; Vimentin; Calponins
PubMed: 32100640
DOI: 10.1177/0300985820908792