Bone Sarcoma With <i>EWSR1-NFATC2</i> Fusion: Sarcoma With Varied Morphology and Amplification of Fusion Gene Distinct From Ewing Sarcoma

Abstract

Ewing sarcomas are typified by <i>EWSR1</i> fusion to <i>ETS</i> gene family members. Tumors with fusion partners other than <i>ETS</i> family members and atypical histologic features pose significant diagnostic challenges and controversies as to their classification. In this article, we report a tumor with <i>EWSR1-NFATC2</i> fusion in the left femur of a 43-year-old man and with unusual morphologic features that resemble undifferentiated high-grade sarcoma. Analysis together with reported cases in the literature shows that tumors with <i>EWSR1-NFATC2</i> exhibit distinctive clinicopathologic features, including predilection for young male adults, highly variable histology that varies from round cell tumors frequently associated with nuclear irregularity, short spindle cells with nuclear pleomorphism, to myoepithelial tumor-like with or without myxohyaline matrix. They show variable positivity to CD99, frequent expression of cytokeratins, and consistent high-level amplification of <i>EWSR1-NFATC2</i> fusion gene with distinctive gene expression profile. These tumors thus deserve classification separate from Ewing sarcoma.