Abstract
Extraskeletal Ewing sarcoma (also known as extraosseous Ewing sarcoma) is the soft tissue counterpart of Ewing sarcoma of the bone. This malignant tumor displays varying degrees of neuroectodermal differentiation, but the cell of origin is unknown. Lesions arising in the chest wall are also known as Askin tumor.
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Notes
- 1.
EWSR1 is a “promiscuous” gene because it can fuse with different partner genes in phenotypically similar neoplasms or with the same genes in morphologically and behaviorally different tumors. In fact, EWSR1-based chimeric genes can be found not only in Ewing and Ewing-like sarcomas but also in other tumors such as angiomatoid fibrous histiocytoma, clear cell sarcoma, low-grade fibromyxoid sarcoma, sclerosing epithelioid fibrosarcoma, hemangioma of the bone, desmoplastic small round cell tumor, extraskeletal myxoid chondrosarcoma, myoepithelial tumor of soft tissue, and myxoid liposarcoma.
It must be underscored that fluorescence in situ hybridization (FISH) analysis has a significant risk of false-negative results, making next-generation sequencing (NGS)-based diagnostic tools more sensitive for detecting EWSR1 rearrangements.
- 2.
ETS gene family: the erythroblastosis transforming sequence (ETS) family includes (among others) the following genes (encoding transcription factors): FLI1, ERG, ETV1, ETV4, FEV.
- 3.
EWSR1-FLI1 fusion gene: EWSR1 (Ewing sarcoma breakpoint region 1) encodes a multifunctional protein that is involved in various cellular processes, including gene expression, cell signaling, and RNA processing and transport. FLI1 (Friend leukemia integration 1) encodes a transcription factor containing an ETS DNA-binding domain. EWSR1-FLI1 chimeric protein is believed to act as an oncoprotein playing a key role in Ewing sarcoma pathogenesis; for instance, its activity leads to upregulation of c-Myc and GLI expression and inhibition of the transcriptional activity of p53, as well as blockage of the ability of Runx2 to induce osteoblast differentiation.
- 4.
Cabozantinib: small molecule tyrosine kinase inhibitor targeting the following: VEGFR2, RET, KIT, MET.
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Mocellin, S. (2021). Extraskeletal Ewing Sarcoma. In: Soft Tissue Tumors . Springer, Cham. https://doi.org/10.1007/978-3-030-58710-9_93
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