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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 -
Radiology Case Reports Mar 2023Myoepithelioma-like hyalinizing epithelioid tumors are rare neoplasms that share morphological characteristics of myoepitheliomas but lack traditional immunophenotypic...
Myoepithelioma-like hyalinizing epithelioid tumors are rare neoplasms that share morphological characteristics of myoepitheliomas but lack traditional immunophenotypic findings. Though little is known about these tumors at present, a handful of recent studies have confirmed that they harbor a novel fusion gene known as "OGT-FOXO." Though closely resembling myoeptheliomas, Myoepithelioma-like hyalinizing epithelioid tumors are considered a distinct tumor entity, and few studies have explored their clinical characteristics or their potential for malignancy. Furthermore, literature describing imaging findings of these tumors is virtually non-existent. Understanding the radiological and pathological differences between Myoepithelioma-like hyalinizing epithelioid tumors and myoepitheliomas is helpful in developing a comprehensive differential for soft tissue neoplasms of the foot. We describe a case of MHET of the foot and correlate MRI findings with pathology in addition to describing surgical technique and implications to care.
PubMed: 36593918
DOI: 10.1016/j.radcr.2022.12.014 -
Cold Spring Harbor Molecular Case... Dec 2022Myoepithelial carcinomas (MECs) of soft tissue are rare and aggressive tumors affecting young adults and children, but their molecular landscape has not been...
Myoepithelial carcinomas (MECs) of soft tissue are rare and aggressive tumors affecting young adults and children, but their molecular landscape has not been comprehensively explored through genome sequencing. Here, we present the whole-exome sequencing (WES), whole-genome sequencing (WGS), and RNA sequencing findings of two MECs. Patients 1 and 2 (P1, P2), both male, were diagnosed at 27 and 37 yr of age, respectively, with shoulder (P1) and inguinal (P2) soft tissue tumors. Both patients developed metastatic disease, and P2 died of disease. P1 tumor showed a rhabdoid cytomorphology and a complete loss of INI1 (SMARCB1) expression, associated with a homozygous deletion. The tumor from P2 showed a clear cell/small cell morphology, retained INI1 expression and strong S100 positivity. By WES and WGS, tumors from both patients displayed low tumor mutation burdens, and no targetable alterations in cancer genes were detected. P2's tumor harbored an rearrangement, whereas the tumor from P1 showed a novel fusion. WGS evidenced a complex genomic event involving mainly Chromosomes 17 and 22 in the tumor from P1, which was consistent with chromoplexy. These findings are consistent with previous reports of rearrangements (50% of cases) in MECs and provide a genetic basis for the loss of SMARCB1 protein expression observed through immunohistochemistry in 10% of 40% of MEC cases. The lack of additional driver mutations in these tumors supports the hypothesis that these alterations are the key molecular events in MEC evolution. Furthermore, the presence of complex structural variant patterns, invisible to WES, highlights the novel biological insights that can be gained through the application of WGS to rare cancers.
Topics: Child; Young Adult; Humans; Male; Myoepithelioma; Soft Tissue Neoplasms; Carcinoma; Biomarkers, Tumor
PubMed: 36577525
DOI: 10.1101/mcs.a006227 -
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 2022Salivary gland neoplasms pose considerable diagnostic difficulty owing to their diverse histological features in individual lesions and the presence of a number of types...
Salivary gland neoplasms pose considerable diagnostic difficulty owing to their diverse histological features in individual lesions and the presence of a number of types and variants & similar histological features with other tumor entities. Myoepithelial and basal cells play a significant role in the pathogenesis of salivary gland neoplasm. p63 and smooth muscle actin are more reliable markers for identifying these cells and not studied much comparing their reliability in the diagnosis of salivary gland neoplasms. Hence, the aim of this study is to evaluate and compare the diagnostic reliability of immunohistochemical markers such as p63 and smooth muscle actin (SMA) in the diagnosis of various benign and malignant salivary gland neoplasms. The study comprises of 18 samples categorized into two groups: Group I comprised 9 cases, of which 4 cases were Pleomorphic adenoma, 2 cases were Myoepithelioma, 2 cases of Basal cell adenoma and 1 case was Warthin's tumor; and Group II consisted of 9cases, of which 3 was Mucoepidermoid carcinoma, 1 cases were Myoepithelial carcinoma and 5 cases were Adenoid cystic carcinoma. The selected cases were subjected to immunohistochemistry (IHC) procedure to assess the expression pattern of p63 and smooth muscle actin. The obtained data was analysed statistically by using Mann-Whitney test. In SMA, strong positivity for epithelial and connective tissue components of benign salivary neoplasm is about 22.2%respectively. In malignant salivary neoplasm, SMA was strongly positive for the epithelial and connective tissue component of about 77.7% and 88.8% cases respectively. The difference in the connective tissue components was found to be statistically significant ( = 24, = 0.032). P63 was strongly positive for the epithelial and connective tissue component of benign salivary neoplasm of about 33.3% and 11.1% cases respectively.In malignant salivary neoplasm, p63 was strongly positive for the epithelial component of about 66.6% cases and connective tissue is completely negative. Alpha-SMA can be utilized as reliable IHC markers for salivary gland neoplasms due to its diagnostic importance in tumors with myoepithelial origin indicative of the histogenesis of salivary gland tumors and even p63 can be used as specific markers for differentiation of malignant salivary gland tumors.
PubMed: 36452668
DOI: 10.1007/s12070-020-02237-6 -
A novel IRF2BP2::CDX2 Gene fusion in digital intravascular myoepithelioma of soft tissue: An enigma!Genes, Chromosomes & Cancer Mar 2023Soft tissue myoepitheliomas (STM) are benign myoepithelial neoplasms (of nonsalivary gland origin) arising, most commonly within subcutaneous and deep soft tissues of...
Soft tissue myoepitheliomas (STM) are benign myoepithelial neoplasms (of nonsalivary gland origin) arising, most commonly within subcutaneous and deep soft tissues of the extremities and rarely within bones. To the best of our knowledge, the intravascular location of STM as well as the identification of a novel IRF2BP2::CDX2 fusion have not been previously reported. Herein, we report a case of spindle cell myoepithelioma arising within the intravascular space of the right index finger in a 52-year-old male of more than 20 years duration. Histopathology demonstrated an intravascular tumefactive lesion composed of predominantly plump banal spindle cells in a fascicular arrangement within a mixed collagenous and chondromyxoid stroma colliding with papillary endothelial hyperplasia (Masson tumor). By immunohistochemistry, the lesional cells were positive for keratin-AE1/3, epithelial membrane antigen, S100, SOX10, glial fibrillary acid protein, calponin and negative for CD34, smooth muscle actin, desmin, p63, and ERG. Fluorescence in situ hybridization for EWSR1 gene rearrangement was negative. Next-generation sequencing detected a novel IRF2BP2::CDX2 fusion involving Exon 1 of the IRF2BP2 gene and Exon 2 of the CDX2 gene confirmed by reverse transcriptase polymerase chain reaction and Sanger sequencing. Further, clinical evaluation for a salivary gland mass in the head and neck region and magnetic resonance imaging (MRI) of the chest, abdomen, and pelvis was performed with no evidence of tumor elsewhere. Taken together, the overall features were considered diagnostic of STM. Our current case underscores the novelty of the IRF2BP2::CDX2 gene fusion in STM and its exceptionally rare intravascular location.
Topics: Male; Humans; Middle Aged; Myoepithelioma; In Situ Hybridization, Fluorescence; Biomarkers, Tumor; Immunohistochemistry; Gene Fusion; Soft Tissue Neoplasms; DNA-Binding Proteins; Transcription Factors; CDX2 Transcription Factor
PubMed: 36448218
DOI: 10.1002/gcc.23108 -
Biomolecules Nov 2022The Serum Response Factor (SRF) is a transcription factor that regulates the expression of a wide set of genes involved in cell proliferation, migration, cytoskeletal...
The Serum Response Factor (SRF) is a transcription factor that regulates the expression of a wide set of genes involved in cell proliferation, migration, cytoskeletal organization and myogenesis. Accumulating evidence suggests that may play a role in carcinogenesis and tumor progression in various neoplasms, where it is often involved in different fusion events. Here we investigated rearrangements in soft tissue tumors, along with a gene expression profile analysis to gain insight into the oncogenic mechanism driven by fusion. Whole transcriptome analysis of cell lines transiently overexpressing the SRF::E2F1 chimeric transcript uncovered the specific gene expression profile driven by the aberrant gene fusion, including overexpression of SRF-dependent target genes and of signatures related to myogenic commitment, inflammation and immune activation. This result was confirmed by the analysis of two cases of myoepitheliomas harboring fusion with respect to -fusion positive tumors. The recognition of the specific gene signature driven by rearrangement in soft tissue tumors could aid the molecular classification of this rare tumor entity and support therapeutic decisions.
Topics: Humans; Serum Response Factor; Soft Tissue Neoplasms; Cell Differentiation; Transcription Factors; Muscles
PubMed: 36421692
DOI: 10.3390/biom12111678 -
Asian Journal of Surgery Apr 2023
Topics: Humans; Female; Carcinoma, Intraductal, Noninfiltrating; Myoepithelioma; Breast; Breast Neoplasms
PubMed: 36328843
DOI: 10.1016/j.asjsur.2022.10.070 -
Biomedical and Environmental Sciences :... Sep 2022