Ewing Sarcoma and Atypical Teratoid Rhabdoid Tumor: A FISH and Immunohistochemical Comparison

Ewing sarcoma (ES)/primitive neuroectodermal tumor (PNET) and atypical teratoid rhabdoid tumor (ATRT) are high-grade malignancies of childhood, each of which is associated with genetic abnormalities on chromosome 22. ES is typically characterized by rearrangement of the EWSR1 locus and ATRT by deletion of SMARCB1. We report a case with an unusual FISH signal pattern consistent with EWSR1 rearrangement that was shown to have loss of INI1 expression by immunohistochemistry due to deletion in the long arm of one chromosome 22. In light of the unusual findings in this case as well as the proximity of the EWSR1 locus and SMARCB1 locus on chromosome 22 and frequent CD99 staining in both tumors, we examined 16 ES cases and 17 ATRT, renal rhabdoid tumor (RRT), and extrarenal rhabdoid tumor (ERRT) cases for CD99 and INI1 staining and for EWSR1 rearrangement. Staining with INI1 was negative in ATRT, RRT, and ERRT and positive in ES cases; CD99 was positive in ES cases and variable in ATRT cases. All but 2 cases of ES, and no cases of ATRT, showed rearrangement of EWSR1. The present case appears to be best classified as a unique variant of ATRT based on immunohistochemistry, EWSR1 FISH and RT-PCR, and SMARCB1 gene sequencing.

Pediatric and developmental pathology : the official journal of the Society for Pediatric Pathology and the Paediatric Pathology Society. 2016 Jul 28 [Epub ahead of print]

M Cristina Pacheco, Michelle Dolan, Anne Bendel

1 Monroe Carell Jr. Children's Hospital at Vanderbilt Pathology, Microbiology & Immunology., 2 Universtiy of Minnesota Medical School Department of Laboratory Medicine and Pathology., 3 Children's Hospitals and Clinics of Minnesota Cancer and Blood Disorders Program.