EWSR1::NFATC2 Rearranged Sarcoma

Ewing sarcoma (ES) is an undifferentiated round cell sarcoma affecting children and young adults. It is characterized by gene fusions involving one of the gene members of FET family ( EWSR1 ) and ETS transcription family members. Recent studies have observed certain undifferentiated round cell sarcomas with EWSR1 –non-ETS fusions, particularly EWSR1::NFATC2 fusion. We identified 5 cases of EWSR1::NFATC2 fusion sarcomas. There was male preponderance and all the patients had a history of trivial trauma. It affected the distal femur and proximal tibia with destructive osteolytic lesions. There was morphologic heterogeneity ranging from round cells in a myxo hyaline stroma to sheets of round-to-spindle cells in a fibrotic stroma. All the cases showed immunopositivity for MIC2, NKX2.2, and NKX3.1, and one showed focal positivity for AE1/AE3 (dot-like) and SATB2. Fluorescence in situ hybridization showed EWSR1 gene rearrangement and amplification (red signals) at 5’ end in all the cases classic of EWSR1::NFATC2 sarcoma. Two of the cases showed multiple relapses despite chemotherapy. Though there is morphologic and immunohistochemical overlap with Ewing sarcoma, this entity has been listed separately within the group of undifferentiated small round cell sarcomas.