Thus, ESW-FLI1 inhibition of the microRNA miRNA-145 leads to increased pluripotency and decreased differentiation of cells and increased oncogenesis.A genome-wide association study (GWAS) identified three susceptibility loci located on chromosomes 1, 10 and 15. A continuative study discovered that the Ewing sarcoma susceptibility gene EGR2, which is  located within the chromosome 10 susceptibility locus, is regulated by the EWSR1-FLI1 fusion oncogene via a GGAA-microsatellite.EWS/FLI functions as the master regulator. Other translocations are at t(21;22) and t(7;22). Ewing sarcoma cells are positive for CD99 and MIC2, and negative for CD45. Diagnosis
The definitive diagnosis is based on histomorphologic findings, immunohistochemistry and molecular pathology. Ewing sarcoma is a small-blue-round-cell tumor that typically has a clear cytoplasm on H&E staining, due to glycogen. The presence of the glycogen can be demonstrated with positive PAS staining and negative PAS diastase staining. The characteristic immunostain is CD99, which diffusely marks the cell membrane. However, as CD99 is not specific for Ewing sarcoma, several auxiliary immunohistochemical markers can be employed to support the histological diagnosis. Morphologic and immunohistochemical findings are corroborated with an associated chromosomal translocation, of which several occur. The most common translocation, present in about 90% of Ewing sarcoma cases, is t(11;22)(q24;q12), which generates an aberrant transcription factor through fusion of the EWSR1 gene with the FLI1 gene.The pathologic differential diagnosis is the grouping of small-blue-round-cell tumors, which includes lymphoma, alveolar rhabdomyosarcoma, and desmoplastic small round cell tumor, among others.
Medical imaging
On conventional radiographs, typical findings of Ewing sarcoma consist of multiple confluent lytic bone lesions that have a "moth eaten" pattern due to permeative destruction of bone. There will also be a displaced periosteum as the new sub-periosteal layer of bone begins to grow on top of the tumor. This raised or displaced periosteum is consistent with the classic radiographic finding of the Codman triangle. The proliferative reaction of bone can also create delicate laminations constituting the periosteal layers and giving the radiographic appearance of an onion peel. Plain films add valuable information in the initial evaluation or screening. The wide zone of transition (e.g. permeative) is the most useful plain film characteristic in differentiation of benign versus aggressive or malignant lytic lesions. Magnetic resonance imaging (MRI) should be routinely used in the work-up of malignant tumors. It will show the full bony and soft tissue extent and relate the tumor to other nearby anatomic structures (e.g. vessels). Gadolinium contrast is not necessary as it does not give additional information over noncontrast studies, though some current researchers argue that dynamic, contrast-enhanced MRI may help determine the amount of necrosis within the tumor, thus help in determining response to treatment prior to surgery.Computed axial tomography (CT) can also be used to define the extraosseous extent of the tumor, especially in the skull, spine, ribs, and pelvis. Both CT and MRI can be used to follow response to radiation and/or chemotherapy.