LAUSR

Simple Summary The aim of this review is to provide an overview of the biological basis of pathogenesis and current research in extraskeletal myxoid chondrosarcoma (EMC), together with the state of the art of treatment for localized and advanced disease. EMC is an ultra-rare sarcoma sub-type, more often arising from the soft tissues, marked by specific molecular features consisting in rearrangement of the NR4A3 gene, identified in recent years and very useful to distinguish EMC from other mimics. Available pharmacological treatments in particular are discussed, with a focus on the most recent results and future perspectives. 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.