Ewing Sarcoma and Ewing-Like Sarcoma and the Role of NKX2.2 Immunoreactivity

Ewing sarcoma (ES) belongs to the family of “small round blue cell” tumors and its diagnosis currently involves a combination of immunostaining and molecular analysis. However, due to significant histological overlap with other tumors of the same family, accurate diagnosis has historically involved combining these results with clinical correlation. Recently, multiple studies have analyzed the role of NKX2.2 immunopositivity in the diagnosis of ES. NKX2.2, a downstream target of the Ewing sarcoma breakpoint region-Friend leukemia integration 1 (EWSR1-FLI1) fusion, has been identified as a potential stain to differentiate ES and Ewing-like sarcoma from other small round blue cell tumors. In this study, we examine the histopathological interpretation of five patients. Four cases showed fluorescent in situ hybridization (FISH)-identified EWSR1 rearrangement. In one case, rearrangements of EWSR1 or FUS could not be detected, and a diagnosis of Ewing-like sarcoma was rendered. NKX2.2 was immunopositive in all five cases. Based on this limited dataset, NKX2.2 immunopositivity can significantly support the diagnosis of ES and has the potential to support the diagnosis of fusion-undetected Ewing-like sarcoma in appropriate clinical and histologic settings.