Extraskeletal Myxoid Chondrosarcoma: State of the Art and Current Research on Biology and Clinical Management

Abstract

Extraskeletal myxoid chondrosarcoma (EMC) is an ultra-rare mesenchymal neoplasm with uncertain differentiation, which arises mostly in the deep soft tissue of proximal extremities and limb girdles. EMC is marked by a translocation involving the NR4A3 gene, which can be fused in-frame with different partners, most often EWSR1 or TAF1. Although EMC biology is still poorly defined, recent studies have started shedding light on the specific contribution of NR4A3 chimeric proteins to EMC pathogenesis and clinical outcome. Standard treatment for localized disease is surgery, plus or minus radiation therapy with an expected prolonged survival even though the risk of relapse is about 50%. In advanced cases, besides the standard chemotherapy currently used for soft tissue sarcoma, antiangiogenic agents have recently shown promising activity. The aim of this review is to provide the state of the art of treatment for localized and advanced disease, with a focus on pharmacological treatments available for EMC. The biological basis of current research and future perspectives will be also discussed.

Extraskeletal myxoid chondrosarcoma: a case report with adjuvant intraoperative treatment

“…Of note, there was some asymmetry between the lesions, with the pelvic one showing more inhomogeneity on T2-weighted imaging and less intense contrast-enhancement as compared to the extrapelvic one. Overall, MR findings were in line with previously reported findings [ 5 ]. At radiological scans, no distant metastases were documented in the liver or lungs.…”

“…Myxoid chondrosarcoma shows an indolent behavior but, after a long-term follow-up, local and distant progressions of disease are demonstrated in more than 40% of patients with a 10 years survival of 65–88% [ 4–6 ]. The most common site of distant metastases is the lung, but soft tissues and lymph nodes also can be involved [ 1 , 5 , 7 ]. To treat distant metastatic disease or local recurrence, surgery, radiotherapy and/or systemic chemotherapy have been proposed [ 6–9 ].…”

Chondrosarcoma-from Molecular Pathology to Novel Therapies

“…Identified fusions with diagnostic potential, participating in several cellular processes such as cell divisions, differentiation, and apoptosis, were also found in extraskeletal myxoid CHS [ 32 ]. The following translocations in extraskeletal myxoid CHS were observed: t(9;22) (q31;q12) in EWS RNA binding protein 1 ( EWSR1 ) and NR4A3 genes, t(9;17)(q31;q12) in TATA-binding protein-associated factor 2N ( TAF15 ) and NR4A3 genes, t(9;3)(q31;q12) in trafficking from ER to Golgi regulator ( TFG ) and NR4A3 genes, t(9;15)(q31;q21) in transcription factor 12 ( TCF12 ) and NR4A3 genes, t(9;11)(q31;q24) in heat shock protein family A (Hsp70) member 8 ( HSPA8 ) and NR4A3 genes, and t(9;16)(q31;q11) in FUS RNA binding protein ( FUS / TLS ) and NR4A3 genes [ 32 , 95 ].…”

Biological Heterogeneity of Chondrosarcoma: From (Epi) Genetics through Stemness and Deregulated Signaling to Immunophenotype

“…In the cytogenetics of sarcomas, gene fusions are significant and are essential markers in diagnostics [ 69 ]. Among ChSs, the best-known translocations, based on many studies [ 70 , 71 , 72 , 73 , 74 ], are defined for extraskeletal myxoid ChS (excluded from this review), while only a few translocations have been discovered in mesenchymal ChS [ 75 , 76 ] ( Table 1 ).…”