Diagnostic utility of dual-color EWS break-apart fluorescence in-situ hybridization probe in the diagnosis and differential diagnosis of pediatric Ewing family of tumors

Background The Ewing family of tumors (EFTs) is a group of tumors that share to a great extent the same morphology, immunophenotyping, and molecular rearrangement. Unfortunately, such tumors may present with atypical morphology especially in soft tissue and organ-based lesions. Small biopsy material with inadequate morphology, inconclusive immunostains may further complicate the problem. The use of EWSR1 break-apart rearrangement by fluorescence in-situ hybridization (FISH) flanking the EWS break-apart region can determine whether a rearrangement has involving the EWS region has occurred and can score positive in EFTS as well as other tumors sharing the same break-apart rearrangement. Materials and methods A retrospective study, where cases were diagnosed morphologically and immunohistochemically as EFTs in the Children Cancer Hospital Egypt during the period from 2011 to 2015 as well as cases of desmoplastic small round cell tumor (DSRCT) and clear cell sarcoma (CCS) of soft tissue were included in the study for the detection of EWSR1 by FISH. Results Out of 321 cases, 267 (83.2%) cases gave informative results, 209 (93.7%) cases out of 223 cases of EFT showed positive break-apart rearrangement. Of the positive cases, 165 (73.9%) cases were of bony origin, 44 were soft tissue primitive neuroectodermal tumors, eight DSRCT, and six CCS of soft tissue. The 14 cases that were negative showed 10 cases being of bony origin while four cases were of soft tissue primitive neuroectodermal tumors. All cases diagnosed as DSRCT and CCS of soft tissue were positive for rearrangement. Cases with established diagnosis of neuroblastoma, Wilms’ tumor, rhabdomyosarcoma, and lymphoma were all negative for break-apart translocation. Conclusion EWSR1 break-apart probe is a sensitive and specific marker for the detection of EWSR1 rearrangement in EFT as well as case sharing the same break-apart region.