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Pathology Mar 2023Mesenchymal tumours with melanocytic expression can pose a diagnostic challenge because they frequently demonstrate both morphological and immunohistochemical overlap... (Review)
Review
Mesenchymal tumours with melanocytic expression can pose a diagnostic challenge because they frequently demonstrate both morphological and immunohistochemical overlap with other cutaneous melanocytic neoplasms. Therefore, they present potential pathological pitfalls that may lead to a misdiagnosis of malignant melanoma. Mesenchymal neoplasms that closely mimic melanoma include malignant melanotic nerve sheath tumour (melanotic schwannoma), epithelioid schwannoma, malignant peripheral nerve sheath, cutaneous syncytial myoepithelioma, clear cell sarcoma of soft tissue, and perivascular epithelioid cell tumour. Awareness of these melanoma mimics is necessary for establishing the correct diagnosis so that the appropriate clinical management can be rendered to the patient. This in-depth review highlights key diagnostic features and molecular genetics and also discusses the differential diagnosis and treatment of mesenchymal tumours that exhibit melanocytic expression.
Topics: Humans; Diagnosis, Differential; Melanoma; Skin Neoplasms; Melanocytes; Melanoma, Cutaneous Malignant
PubMed: 36639332
DOI: 10.1016/j.pathol.2022.12.340 -
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 -
BMJ Case Reports Dec 2022A woman in her 70s presented with a small subcutaneous retrosacrococcygeal mass and a history of elevated erythrocyte sedimentation rate present for several years. It...
A woman in her 70s presented with a small subcutaneous retrosacrococcygeal mass and a history of elevated erythrocyte sedimentation rate present for several years. It was misdiagnosed as an inflammatory process of unclear origin. She underwent further investigation with the appearance of weight loss and weakness. A sacrococcygeal mass was noted on CT scan. A core needle biopsy was inconclusive for chordoma versus myoepithelioma. Wide surgical resection of the tumour including the coccygeal bone was performed. Following surgery, all the systemic symptoms resolved with normalisation of inflammatory markers. The pathological examination showed a relatively circumscribed multinodular myxoid tumour with lymphatic tissue cuff. Pan-sarcoma fusion analysis detected an EWSR1 (Exon7)-CREB1 (Exon7) fusion gene. The lesion was diagnosed as angiomatoid fibrous histiocytoma with paraneoplastic syndrome presentation of several years' duration.
Topics: Female; Humans; Histiocytoma, Benign Fibrous; Histiocytoma, Malignant Fibrous; Soft Tissue Neoplasms; Paraneoplastic Syndromes
PubMed: 36593607
DOI: 10.1136/bcr-2022-250946 -
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 -
Journal of Oral Pathology & Medicine :... Feb 2023In this systematic review, we aimed to evaluate the clinicopathological and prognosis data of patients with salivary gland myoepithelial carcinoma. (Review)
Review
OBJECTIVES
In this systematic review, we aimed to evaluate the clinicopathological and prognosis data of patients with salivary gland myoepithelial carcinoma.
MATERIALS AND METHODS
MEDLINE/PubMed, Scopus, and Embase search was performed with the keywords "myoepithelial carcinoma" "malignant myoepithelioma," and "salivary glands." Primary salivary glands myoepithelial carcinoma that fulfilled the World Health Organization diagnostic criteria were included. The Joanna Briggs Institute tool was used to assess the risk of bias.
RESULTS
Forty-three studies (71 patients) met the inclusion criteria. The patients showed a mean age of 56.4 ± 19.6 years with no sex predilection. The parotid was the most affected gland (49.3%). The tumor presented as an asymptomatic (65.1%) mass (84%). The most common histological findings were the presence of clear tumor cells (39.7%) and multinodular growth patterns (60.7%). Multivariate analysis showed plasmacytoid cell type (p = 0.010) and solid growth pattern (p = 0.003) were related to decreased disease-free survival. Surgery alone was the most used treatment (53.5%). Patients with a combination of treatments showed a longer disease-free survival (p = 0.049). The 2-year and 5-year overall survival rates were 67.5% and 46.1%, respectively.
CONCLUSION
Salivary gland myoepithelial carcinoma showed no sex predilection, with a higher incidence in the parotid gland. Cell type, growth pattern, and treatment type may be related to a lower disease-free survival. Overall, salivary gland myoepithelial carcinoma presented low recurrence and metastasis rates. Registration and protocol: This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 checklist and registered in the International Prospective Register of Systematic Reviews (PROSPERO) database (CRD42022311512).
Topics: Humans; Adult; Middle Aged; Aged; Myoepithelioma; Salivary Gland Neoplasms; Salivary Glands; Disease-Free Survival; Carcinoma
PubMed: 36504414
DOI: 10.1111/jop.13395 -
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