EWSR1-rearranged renal neoplasia: Clinicopathologic and molecular characterization of 39 cases from a single...

We report the clinicopathologic features of EWSR1-rearranged renal neoplasia from our institution. A retrospective cohort of 39 EWSR1-rearranged renal tumors was identified using fluorescence in situ hybridization (FISH) and RNA-based next generation sequencing (NGS). A final diagnosis of Ewing sarcoma (EWS) was established in 34 of 39 cases (87%), with the remaining cases diagnosed as desmoplastic small round cell tumor (DSRCT; n = 2), sclerosing epithelioid fibrosarcoma (SEF; n = 2), and thyroid-like follicular renal cell carcinoma (TLFRCC; n = 1). Fusion partners identified in EWS included FLI1 (n = 17) and ERG (n = 2). WT1 (n = 2), CREB3L1 (n = 1) and CREB3L2 (n = 1), and PATZ1 (n = 1) fusions were found in DSRCT, SEF, and TLFRCC, respectively. The mean age at EWS diagnosis was 31.4 years (range 6-73), with a similar sex distribution (18 females, 16 males), and a mean tumor size of 10.7 cm (range 3-24 cm). Both DSRCT cases occurred in males aged 6 and 29 years, diagnosed on renal biopsy and brain metastasis, respectively. The SEF cases involved primary tumors in 22-year-old and 43-year-old females. The one case of TLFRCC was identified in a 41-year-old female that underwent radical nephrectomy. Cases with available immunohistochemistry showed most EWS tumors (24/26, 92%) expressed a combination of CD99, FLI1, and ERG, while both SEF cases were positive for MUC4. Our results highlight the importance of molecular testing in providing an integrated diagnosis and are informative regarding the spectrum of renal neoplasia that harbor EWSR1 rearrangements, including EWS, DSRCT, SEF, and TLFRCC as these tumors can exhibit significant clinicopathologic heterogeneity.