-
Human Cell Jan 2023Extraskeletal myxoid chondrosarcoma (EMC) is a malignant mesenchymal neoplasm of uncertain differentiation as classified by the WHO Classification of Tumours 2020....
Extraskeletal myxoid chondrosarcoma (EMC) is a malignant mesenchymal neoplasm of uncertain differentiation as classified by the WHO Classification of Tumours 2020. Although often associated with pronlonged survival, EMC has high rates of distant recurrences and disease-associated death. EMCs are translocation sarcomas and harbor in > 90% of the cases an NR4A3 rearrangement. The molecular consequences of the NR4A3 gene fusions are not yet fully elucidated as well-characterized ex vivo cell models for EMC are lacking. Patient-derived ex vivo models are important and essential tools for investigating disease mechanisms associated with diseases that are rare, that exhibit poor prognosis and for the identification of potential novel treatment options. We established two novel EMC ex vivo models (USZ20-EMC1 and USZ22-EMC2) for functional testing and research purposes. USZ20-EMC1 and USZ22-EMC2 were established and maintained as sarco-sphere cell models for several months in culture. The cells were molecularly characterized using DNA sequencing and methylation profiling. Both cell models represent their native tumor tissue as confirmed by histomorphology and their molecular profiles, suggesting that native tumor cell function can be recapitulated in the ex vivo models. Using a functional screening approach, novel anti-cancer drug sensitivities including potential synergistic combinations were identified. In conclusion, two novel EMC ex vivo cell models (USZ20-EMC1 and USZ22-EMC2) were successfully established and characterized from native tumor tissues. Both cell models will be useful tools for further investigating disease mechanisms and for answering basic and translational research questions.
Topics: Humans; Chondrosarcoma; Neoplasms, Connective and Soft Tissue; Soft Tissue Neoplasms; Sarcoma
PubMed: 36316541
DOI: 10.1007/s13577-022-00818-x -
Translational Cancer Research Sep 2022Intracranial extraskeletal mesenchymal chondrosarcoma (EMCS) is a rare neoplasm and often misdiagnosed before histopathological examination due to its rarity. There were...
BACKGROUND
Intracranial extraskeletal mesenchymal chondrosarcoma (EMCS) is a rare neoplasm and often misdiagnosed before histopathological examination due to its rarity. There were few reports previously on the radiological features of intracranial EMCS. We described a 20-year-old male patient with intracranial EMCS focusing on the imaging characteristics.
CASE DESCRIPTION
The patient was admitted to our hospital due to headache and dizziness for two months, without nausea, vomiting, limb convulsions and loss of consciousness during the illness. Pre-contrast computed tomography (CT) revealed a large slightly hyperdense mass with irregularly lobulated margins in the right parietal and occipital region and multiple patchy calcifications in peripheral of the lesion. The inner table of right parietal bone adjacent to the mass was compressed, thickened, and eroded. Magnetic resonance imaging (MRI) exhibited intermediate and hypo-intensity on T1-weighted images (TWI) and slight hyper-intensity on T2-weighted images (TWI) with extremely high intensity rim of cerebral spinal fluid (CSF) and low intensity flow-void vessel. The mass demonstrated heterogeneous remarkable enhancement and "dural tail" sign also was noted. The important imaging signs of this case are irregular calcifications of soft tissue on CT and "dural tail" sign on MRI. The patient underwent tumor resection and was followed up postoperatively with serial MRI every three months. He was alive without obvious clinical symptoms and evidence of recurrence for 9 months. EMCS is a highly invasive tumor and it is difficult to differentiate EMCS from the other intracranial malignant tumors only by clinical characteristics or findings of CT and conventional MR imaging. Radiotherapy and chemotherapy after radical resection are the best treatment choice. Therefore, postoperative patients should be reviewed routinely.
CONCLUSIONS
A knowledge of the imaging features could facilitate differentiation of intracranial EMCS, but the final diagnosis depends on pathological examinations. This paper focuses on the imaging characteristics of EMCS and fully describes the details of lesions in order to provide clinicians with effective differential diagnosis information and improve clinical decision-making.
PubMed: 36237268
DOI: 10.21037/tcr-21-2547 -
Translational Cancer Research Sep 2022Mesenchymal chondrosarcoma (MCS) is a rare malignant chondrosarcoma with a high propensity for recurrence and distant metastasis. MCS usually arises from bone tissue,...
BACKGROUND
Mesenchymal chondrosarcoma (MCS) is a rare malignant chondrosarcoma with a high propensity for recurrence and distant metastasis. MCS usually arises from bone tissue, and rarely occurs outside the bone. MCS in the subdural and extramedullary regions of the spinal cord is especially rare. In this article, we report a case of spinal intradural extramedullary MCS with herpes virus infection, which is the first such case reported in East China.
CASE DESCRIPTION
A 13-year-old male complained of intermittent low-grade fever, sweating, progressive constipation with weakness of both lower extremities and bilateral hypoesthesia after a 5-month history of herpes virus infection. Spinal magnetic resonance imaging (MRI) revealed a subdural-extramedullary solid nodular mass with isointensity on T1-weighted imaging and hyperintensity on T2-weighted imaging that was located behind the superior margin of the T5 vertebral body. The patient was initially diagnosed with thoracic meningioma and underwent spinal cord tumour resection followed by adjuvant chemotherapy. Histopathological examination revealed that the tumour was mainly composed of round or oval cells and mesenchymal chondroid matrix, and gene analysis showed the fusion of HEY1 exon 4 to NCOA2 exon 13. Both test results were consistent with the diagnosis of primary intraspinal MCS. At the 1-year follow-up, the patient received adjuvant chemotherapy, and the reexamination images revealed no evidence of tumour tumour recurrence or distant metastasis.
CONCLUSIONS
As more research has been done on MCS, it has been found that the disease is more likely to occur in adolescents, but is often overlooked due to its lack of imaging characterization. Therefore, the misdiagnosis rate can be reduced only by closely considering clinical manifestations with pathology and imaging findings. Although MCS is a highly malignant tumour, early primary spinal intradural extramedullary MCS can cause neurological symptoms, early detection and treatment can achieve basic total surgical resection. Postoperative adjuvant chemoradiotherapy can further reduce recurrence.
PubMed: 36237254
DOI: 10.21037/tcr-21-2703 -
Translational Cancer Research Sep 2022Primary mesenchymal chondrosarcoma (PMC) is a relatively rare malignancy that can occur in bone or soft tissue, but rarely in the lumbar spine; there is currently no...
BACKGROUND
Primary mesenchymal chondrosarcoma (PMC) is a relatively rare malignancy that can occur in bone or soft tissue, but rarely in the lumbar spine; there is currently no unified treatment. We report a case of mesenchymal chondrosarcoma originating from the L1 vertebra.
CASE DESCRIPTION
A 47-year-old female patient was admitted to the hospital with intermittent low back pain for 20 years, accompanied by intermittent headache and radiating pain in both lower limbs. After admission, magnetic resonance imaging (MRI) showed bone destruction of the L1 vertebral body and accessories and a surrounding soft tissue mass. Enhanced MRI revealed significant enhancement of the L1 vertebral body and soft tissue mass. Technetium 99 m-methylene diphosphonate (99 m Tc-MDP) bone scan showed abnormally high metabolism in the L1 vertebral body, which is highly suspicious of malignancy, and vertebral biopsy revealed a soft tissue malignancy originating from the mesenchymal tissue. Total vertebrectomy combined with postoperative adjuvant radiotherapy was planned, but the patient refused radiotherapy for financial reasons. Intraoperative frozen sections indicated mesenchymal chondrosarcoma, as confirmed by postoperative pathological examination. After 1 year of outpatient follow-up, the patient had no related symptoms, and normal motor and sensory function, and her condition had improved.
CONCLUSIONS
Total tumor resection is an effective treatment for PMC, and increased attention to this disease in the clinic is essential.
PubMed: 36237229
DOI: 10.21037/tcr-22-122 -
Frontiers in Oncology 2022Hepatic carcinosarcoma (HCS) is defined as a tumor that contains cancer from the epithelium and sarcoma from mesenchymal tissue. HCS has a low incidence rate and is...
Hepatic carcinosarcoma (HCS) is defined as a tumor that contains cancer from the epithelium and sarcoma from mesenchymal tissue. HCS has a low incidence rate and is composed of osteosarcoma, chondrosarcoma, or angiosarcoma. Though surgery is the main treatment for HCS, it has proven unsatisfactory, resulting in a very poor prognosis of HCS. Currently, the reports on HCS are mainly about the description of clinical pathological phenomena, imaging features, and mutation sites of related genes, the underlying molecular mechanism of HCS remains undefined. Through the dynamic process of epithelial-mesenchymal transition (EMT), cancer cells acquire a mesenchymal phenotype, simultaneously losing epithelial properties. Zinc finger E-box binding homeobox 1 (ZEB1) is an EMT-inducing transcription factor; its main regulatory target is E-cadherin in EMT process. Esophageal carcinosarcoma (ECS) is associated with EMT. The current study showed that EMT might promote the development of ECS and uterine carcinosarcoma (UCS), and ZEB1 was highly expressed in the sarcomatous components. In the current study, three cases were collected, and the clinicopathological features were compared with those of corresponding cases. The expression level, and subcellular localization of ZEB1 were detected using immunohistochemistry. The expression of the ZEB1 in the nucleus was found to be significantly higher in sarcomatous components than that in cancer components in all three cases, suggesting an association of HCS with EMT.
PubMed: 36172159
DOI: 10.3389/fonc.2022.972650 -
Frontiers in Oncology 2022Craniofacial bones may be the site of origin of various sarcomas. We review the various malignancies affecting this region of the body and attempt to put systemic... (Review)
Review
INTRODUCTION
Craniofacial bones may be the site of origin of various sarcomas. We review the various malignancies affecting this region of the body and attempt to put systemic treatment approaches into perspective.
MATERIAL AND METHODS
Non-systematic literature review.
RESULTS
Conventional types of osteosarcoma, Ewing sarcoma, and chondrosarcoma are the most frequent bone sarcomas occurring in craniofacial region, but variants may occur. The tumors' biologies and the resulting treatment strategies vary distinctly. As a general rule, local control remains paramount regardless of histology. The efficacy of antineoplastic chemotherapy varies by type of malignancy. It is clearly indicated in Ewing sarcoma and related tumors, potentially of benefit in high-grade osteosarcoma, undifferentiated pleomorphic sarcoma, dedifferentiated and mesenchymal chondrosarcoma, and of no proven benefit in the others.
CONCLUSIONS
Various histologies demand various and distinct treatment approaches, with local control remaining paramount in all. The efficacy of systemic treatments varies by type of tumor. Prospective trials would help in all of these to better define systemic treatment strategies.
PubMed: 36158667
DOI: 10.3389/fonc.2022.966073 -
Asian Journal of Neurosurgery Jun 2022Intracranial extraskeletal mesenchymal chondrosarcomas (IEMCs) are malignant aggressive neoplasms. IEMCs originate from the meninges or parenchyma. In the current...
Intracranial extraskeletal mesenchymal chondrosarcomas (IEMCs) are malignant aggressive neoplasms. IEMCs originate from the meninges or parenchyma. In the current study, we aimed to figure out the importance of gross total resection (GTR) and adjuvant radiotherapy (RT) by evaluating all reported IEMCs through the literature that included our two patients. We presented two IEMC patients who were treated at our institutions and followed up for a long duration. To understand the appropriate management for IEMC, we conducted a systematic literature review for previously reported series and cases of IEMCs. We surgically treated two young males with IEMC initially diagnosed at their age of 18 and 20 years. The patients were initially treated with GTR and GTR followed by RT, and followed-up for 218 and 73 months, respectively. Through both the patients, we obtained 83 reported IEMC patients from the literature. The mean age of the reported cases was 24.5 ± 16.0 years (2 months-71 years). Female predominance was 54.2%. The mean progression-free and overall survivals were 27.9 and 39.0 months, respectively. The progressiveness rate was 56%. The presence of progressiveness was a poor prognostic factor ( = 0.0008). GTR was achieved in 53.0% of the patients. There was a significant difference between patients who received GTR compared with those who did not receive GTR ( = 0.035). Regarding their malignancy and progressiveness, we recommended the maximal surgical resection with wide margins followed by RT as appropriate management for IEMCs with close follow-up. The timely treatment provides high life quality and avoids life-threatening complications.
PubMed: 36120627
DOI: 10.1055/s-0042-1750804 -
Comparative Medicine Oct 2022Osteosarcoma (OSA) is the most common primary bone tumor in both dogs and humans. The dog is an important research model for OSA, yet dogs have much higher prevalence of...
Osteosarcoma (OSA) is the most common primary bone tumor in both dogs and humans. The dog is an important research model for OSA, yet dogs have much higher prevalence of bone tumors than do humans, a disparity that has yet to be explained. Neoplastic transformation of cells within or adjacent to bone infarcts into primary bone tumors has been described in humans but only sparsely characterized in the veterinary literature. In this study, 653 cases of canine bone infarcts were received through a referral veterinary osteopathology service over a 14-y period. We identified an idiopathic disorder affecting the nutrient artery, termed canine idiopathic arteriopathy (CIA), which to our knowledge has no direct counterpart in human medicine. This disorder was documented alongside ischemic necrosis of the medullary cavity in 114 bone infarcts in 108 dogs. We hypothesize that CIA precipitated an ischemic environment, resulting in development of a bone infarct down- stream of the abnormal artery. In 52% (59 of 114) of cases, bone infarcts demonstrated evidence of repair (termed reparative bone infarcts [RBI]), while in 48% (55 of 114) of infarcts, a bone tumor was also present, including pleomorphic sarcoma, OSA, fibrosarcoma, and chondrosarcoma. In some cases, a spectrum of tumors was present. We hypothesize that the ischemic infarct environment provoked bone marrow mesenchymal stem cells (MSCs) to attempt repair of the stroma, and in approximately half of cases, MSCs underwent neoplastic transformation (BINT) to produce tumors. The most common sites of bone infarcts were the distal femur, distal radius, proximal humerus, and distal tibia, coinciding with common sites of canine OSA. The authors propose that CIA leading to bone infarcts and infarct-derived tumors, in combination with possible underdiagnosis of canine bone infarcts and misdiagnosis of some RBI as neoplasia, may contribute to the higher reported proportion of bone tumors in dogs compared with humans.
Topics: Animals; Dogs; Humans; Bone Neoplasms; Dog Diseases; Infarction; Osteosarcoma; Wolves
PubMed: 36113969
DOI: 10.30802/AALAS-CM-22-000037 -
Evidence-based Complementary and... 2022Currently, developing therapeutic strategies for chondrosarcoma (CS) remains important. Sennoside A (SA), a dianthrone glycoside from Senna and Rhubarb, is widely used...
Currently, developing therapeutic strategies for chondrosarcoma (CS) remains important. Sennoside A (SA), a dianthrone glycoside from Senna and Rhubarb, is widely used as an irritant laxative, weight-loss agent, or dietary supplement, which possesses various bioactive properties such as laxative, antiobesity, and hypoglycemic activities. For the first time, our results suggested that cell proliferation and metastasis were inhibited by SA in CS SW1353 cells. SA induced cell growth arrest by inhibiting cell proliferation. The changes of N-cadherin and E-cadherin levels, the markers associated with epithelial mesenchymal transition (EMT), suggested the EMT-related mechanism of SA in inhibiting cell metastasis. Besides, SA significantly stimulated apoptosis in CS SW1353 cells, leading to cell death. The increase of Bax/Bcl2 ratio confirmed that the internal mitochondrial pathway of apoptosis was regulated by SA. In addition, the prediction of network pharmacology analysis suggested that the possible pathways of SA treatment for CS included the Wnt signaling pathway. Notably, the protein levels of the components in the Wnt pathway, such as Wnt3a, -catenin, and c-Myc, were downregulated by SA in CS SW1353 cells. To sum up, these results demonstrated that the suppression of the growth, metastasis and the stimulation of cytotoxicity, and apoptosis mediated by SA in CS SW1353 cells were possibly caused by the inhibition of the Wnt/-catenin pathway, indicating an underlying therapeutic prospect of SA for chondrosarcoma.
PubMed: 36091590
DOI: 10.1155/2022/8063497 -
Thoracic Cancer Oct 2022Extraskeletal myxoid chondrosarcoma (EMCS) is an undifferentiated mesenchymal malignancy; however, its immune microenvironment remains to be elucidated. The case of a...
Extraskeletal myxoid chondrosarcoma (EMCS) is an undifferentiated mesenchymal malignancy; however, its immune microenvironment remains to be elucidated. The case of a 34-year-old woman who developed EMCS metastasizing to the pleura is presented here. The pleural EMCS showed hypervascularity, absent PD-L1 expression, and a lack of tumor mutational burden and pathogenic variants. Immunohistological examination of the pleural lesions showed predominant M2 macrophages and sparse CD8 T cells. EMCS and the tumor stroma were positive for transforming growth factor-β1 (TGF-β1) and vascular endothelial growth factor (VEGF). In contrast, a small number of the stromal vessels were positive for hypoxia inducible factor-1α (HIF-1α). TGF-β1 and VEGF in the tumor stroma and low antigenicity of the tumor cells may help explain how EMCS induced the immunosuppressive microenvironment. These findings may encourage investigators to explore novel combined immunotherapy for EMCS, such as TGF-β1 and VEGF inhibitors, and specific therapy for enhancing tumor antigens.
Topics: Adult; Antigens, Neoplasm; B7-H1 Antigen; CD8-Positive T-Lymphocytes; Chondrosarcoma; Female; Humans; Neoplasms, Connective and Soft Tissue; Pleura; Transforming Growth Factor beta1; Tumor Microenvironment; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors
PubMed: 35974707
DOI: 10.1111/1759-7714.14613