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Nature Reviews. Cancer Oct 2020Epigenetic regulation is critical to physiological control of development, cell fate, cell proliferation, genomic integrity and, fundamentally, transcriptional... (Review)
Review
Epigenetic regulation is critical to physiological control of development, cell fate, cell proliferation, genomic integrity and, fundamentally, transcriptional regulation. This epigenetic control occurs at multiple levels including through DNA methylation, histone modification, nucleosome remodelling and modulation of the 3D chromatin structure. Alterations in genes that encode chromatin regulators are common among mesenchymal neoplasms, a collection of more than 160 tumour types including over 60 malignant variants (sarcomas) that have unique and varied genetic, biological and clinical characteristics. Herein, we review those sarcomas in which chromatin pathway alterations drive disease biology. Specifically, we emphasize examples of dysregulation of each level of epigenetic control though mechanisms that include alterations in metabolic enzymes that regulate DNA methylation and histone post-translational modifications, mutations in histone genes, subunit loss or fusions in chromatin remodelling and modifying complexes, and disruption of higher-order chromatin structure. Epigenetic mechanisms of tumorigenesis have been implicated in mesenchymal tumours ranging from chondroblastoma and giant cell tumour of bone to chondrosarcoma, malignant peripheral nerve sheath tumour, synovial sarcoma, epithelioid sarcoma and Ewing sarcoma - all diseases that present in a younger patient population than most cancers. Finally, we review current and potential future approaches for the development of sarcoma therapies based on this emerging understanding of chromatin dysregulation.
Topics: Animals; Biomarkers, Tumor; Cell Transformation, Neoplastic; Chromatin; Chromatin Assembly and Disassembly; DNA Methylation; Epigenesis, Genetic; Epigenomics; Gene Expression Regulation, Neoplastic; Genetic Association Studies; Genetic Predisposition to Disease; Humans; Sarcoma
PubMed: 32782366
DOI: 10.1038/s41568-020-0288-4 -
Seminars in Diagnostic Pathology May 2021The SWItch Sucrose Non-Fermentable (SWI/SNF) chromatin remodeling complex is a large multi-subunit protein assembly that orchestrates chromatin compaction and... (Review)
Review
The SWItch Sucrose Non-Fermentable (SWI/SNF) chromatin remodeling complex is a large multi-subunit protein assembly that orchestrates chromatin compaction and accessibility for gene transcription in an ATP-dependent manner. As a key epigenetic regulator, the SWI/SNF complex coordinates gene expression, cell proliferation and differentiation, and its biologic functions, in part, antagonize the polycomb repressive complex 2. The mammalian SWI/SNF complex consists of 15 subunits encoded by 29 genes, some of which are recurrently mutated in human cancers, in the germline or sporadic setting. Most SWI/SNF-deficient tumors share common "rhabdoid" cytomorphology. SMARCB1 (INI1) is the subunit most frequently inactivated in soft tissue neoplasms. Specifically, SMARCB1 deficiency is observed as the genetic hallmark in virtually all malignant rhabdoid tumors, and most cases of epithelioid sarcoma and poorly differentiated chordoma. In addition, subsets of myoepithelial carcinoma (10-40%), extraskeletal myxoid chondrosarcoma (20%), epithelioid schwannoma (40%), and epithelioid malignant peripheral nerve sheath tumor (70%) demonstrate SMARCB1 loss. The gene encoding the SS18 subunit is involved in the SS18-SSX rearrangement, which is pathognomonic of synovial sarcoma and indirectly inactivates SMARCB1. Finally, undifferentiated SMARCA4-deficient thoracic sarcomas are defined by SMARCA4 subunit inactivation, leading to SMARCA4 and SMARCA2 loss. Rarely, inactivation of alternate but biologically equivalent key regulators can substitute for canonical subunit deficiency, such as SMARCA4 inactivation in cases of SMARCB1-retained epithelioid sarcoma. This review briefly highlights SWI/SNF complex biologic functions and its roles in human cancer and provides a detailed update on recent advances in soft tissue neoplasms with canonical SWI/SNF complex deficiency, correlating morphologic, genomic, and immunohistochemical findings.
Topics: Chromosomal Proteins, Non-Histone; DNA Helicases; Humans; Immunohistochemistry; Nuclear Proteins; Rhabdoid Tumor; Soft Tissue Neoplasms; Sucrose; Transcription Factors
PubMed: 32646614
DOI: 10.1053/j.semdp.2020.05.005 -
Indian Journal of Otolaryngology and... Dec 2022Mass lesions of the larynx are one of the most common clinical entity which we come across in routine otorhinolaryngology and head neck practice with varied...
Mass lesions of the larynx are one of the most common clinical entity which we come across in routine otorhinolaryngology and head neck practice with varied symptomatology. Among all the mass lesions of the larynx, Epithelial neoplasms constitute up to 97%. Mesenchymal tumours of the larynx constitute only 0.3-1.0% of all the laryngeal tumors. Abundance of cartilage structures in the larynx made it a spot for mesenchymal tumors [chondromas and chandrosacrcomas]. The spectrum of mesenchymal neoplasms can vary from chondromas, chondroblastoma to chondrosarcoma. Here we want to share our experience of a mesenchymal tumour of the larynx. This case is reported for the rarity and ambiguity in diagnosis. Though these are slow-growing tumours with an early presentation, in our case, the patient had a supportive tracheostomy without definitive treatment for more than 2 years. We managed this patient by excising the mass by lateral pharyngotomy with the preservation of larynx followed by successful Decannulation in 20 days.
PubMed: 36742506
DOI: 10.1007/s12070-020-02308-8 -
International Journal of Particle... 2016To review the treatment and outcomes of patients with mesenchymal chondrosarcomas (MC). (Review)
Review
PURPOSE
To review the treatment and outcomes of patients with mesenchymal chondrosarcomas (MC).
MATERIALS AND METHODS
Review of the pertinent literature.
RESULTS
MC is a rare aggressive small round blue cell malignancy that may arise in either bone or soft tissue. It usually presents in the 2 or 3 decade of life and exhibits an approximately equal gender predilection. Patients usually present with pain and swelling. The majority of MCs arise in either the trunk or extremities. Distant metastases are present at diagnosis in about 15% of patients. The most common sites for distant metastases are lung and bone. The optimal treatment is surgery. Although the role of adjuvant chemotherapy is unclear, an anthracycline-based chemotherapy regimen combined with ifosfamide or cisplatin, may be considered. Adjuvant radiation therapy (RT) is employed for patients with close (<5 mm) or positive margins as well as those with incompletely resectable tumors. The most common mechanism of recurrence is hematogenous dissemination. Although most recurrences are observed within 5 years of treatment, late recurrences are not unusual. The likelihood of successful salvage in the event of a recurrence is modest. The overall survival rates for all patients are approximately 50% at 5 years and 40% at 10 years. The overall survival rates for the subset of patients with localized disease that is resected are approximately 70% to 80% at 5 years and 60% at 10 years.
CONCLUSION
Patients with MCs are optimally treated with surgery. The role of adjuvant chemotherapy is uncertain. However, given the relatively high risk of recurrence, adjuvant chemotherapy should be considered in medically fit patients. Radiation therapy should be considered for those with incompletely resectable tumors and those with inadequate margins.
PubMed: 31772981
DOI: 10.14338/IJPT-16-00019.1 -
Archives of Pathology & Laboratory... Nov 2018Extraskeletal mesenchymal chondrosarcoma is a rare soft tissue sarcoma arising from soft tissues, mainly of the lower extremities, meninges, and orbits. It usually... (Review)
Review
Extraskeletal mesenchymal chondrosarcoma is a rare soft tissue sarcoma arising from soft tissues, mainly of the lower extremities, meninges, and orbits. It usually presents during the second to third decades of life, and has a slight predominance in females. Histologically, it has a typical biphasic pattern comprising small cells and islands of hyaline cartilage. It can pose a diagnostic challenge in small biopsy specimens where 1 of the 2 components can be absent. The prognosis is extremely variable; survival varies depending on the location of the tumor.
Topics: Chondrosarcoma, Mesenchymal; Humans; Sarcoma
PubMed: 30407856
DOI: 10.5858/arpa.2017-0109-RS -
Skeletal Radiology Feb 2021To describe imaging and clinical features of primary mesenchymal chondrosarcoma (MCS) and evaluate for presence of a distinct biphasic pattern on imaging.
OBJECTIVE
To describe imaging and clinical features of primary mesenchymal chondrosarcoma (MCS) and evaluate for presence of a distinct biphasic pattern on imaging.
MATERIAL AND METHODS
Patients with a pathologic diagnosis of MCS were identified along with imaging of their primary tumor. Size, location, appearance (lytic, sclerotic, or mixed), presence, extent and distribution of calcifications, cortical destruction, soft tissue extension, periosteal reaction, contrast enhancement, and radiotracer uptake were recorded. The presence of T2-hyperintense tumor lobules on MRI and a biphasic morphology (distinct calcified and non-calcified components) on CT were assessed. Presence and location of metastases were documented.
RESULTS
Twenty-three patients (mean age 28.0 ± 13.8 years) were reviewed (13 skeletal, 10 extraskeletal). Overall mean tumor size was 10.2 ± 7.2 cm, 7.1 ± 7.3 cm in non-metastatic and 13.2 ± 5.9 cm (p = 0.004) in metastatic cases. Locations were extremities (n = 11), head/neck (n = 4), chest wall (n = 4), pelvis (n = 3), and retroperitoneum (n = 1). Skeletal MCS were aggressive mixed lytic and sclerotic (n = 8), purely lytic (n = 4), or juxtacortical (n = 1) lesions with cortical destruction and soft tissue extension. Chondroid calcifications were common (80%). On MRI, the presence of T2-hyperintense lobules was seen in 35%. A biphasic morphology on imaging was seen in 30%. Metastases were common (52%) with the most common site being the lungs (75%). All tumors were hypermetabolic with a mean SUVmax of 14.3 (5.6-34) on PET/CT.
CONCLUSION
Skeletal MCS commonly present as aggressive lytic bone lesions with chondroid calcifications. A biphasic morphology was seen in one-third of cases. Metastases were common at initial presentation and more commonly seen with larger tumors.
Topics: Adolescent; Adult; Bone Neoplasms; Chondrosarcoma; Chondrosarcoma, Mesenchymal; Humans; Magnetic Resonance Imaging; Positron Emission Tomography Computed Tomography; Retrospective Studies; Young Adult
PubMed: 32734374
DOI: 10.1007/s00256-020-03558-x -
Diagnostics (Basel, Switzerland) Mar 2022Mesenchymal chondrosarcoma is an uncommon malignant mesenchymal tumor with an aggressive behavior. Diagnoses of mesenchymal chondrosarcoma are established based on...
Mesenchymal chondrosarcoma is an uncommon malignant mesenchymal tumor with an aggressive behavior. Diagnoses of mesenchymal chondrosarcoma are established based on histomorphological, immunohistochemical, and molecular findings. Only one case of extraskeletal mesenchymal chondrosarcoma (EMC) of the uterus has been reported. This article presents the second case of primary uterine EMC, occurring in a 33-year-old woman. We describe the histological and immunophenotypical features of EMC. Our observations will help pathologists and clinicians perform accurate histological diagnoses of uterine EMC and plan appropriate treatment strategies for this rare tumor.
PubMed: 35328196
DOI: 10.3390/diagnostics12030643