Gastrointestinal Ewing Sarcoma: A Clinicopathological and Molecular Genetic Analysis of 25 Cases.

Occurrence of extraskeletal Ewing sarcoma (ES) in the gastrointestinal (GI) tract is extremely rare. Here, we report 25 cases of ES arising primarily in the GI tract with a focus on the clinicopathological and molecular features, differential diagnosis, and biological behavior. Thirteen patients (52%) were male, and 12 (48%) were female with age ranging from 9 to 59 years (mean: 36.2 years; median: 38 years). Twenty-one tumors (84%) occurred in the small intestine, 3 (12%) in the stomach, and 1 (4%) in the anal canal. At operation, 8/18 (44.4%) patients presented with abdominopelvic disseminated disease. Tumor size measured from 2 to 25 cm (mean: 8.2 cm; median: 6 cm) in maximum size. Microscopically, the tumors were composed of infiltrative small round, ovoid, or short spindle cells arranged mostly in lobular and solid sheet-like patterns with a rich capillary vasculature. Focal formation of Homer Wright-type rosettes and pseudoalveolar architecture was noted each in 2 (8%) cases and 3 (12%) cases. Besides CD99 (25/25; 100%), Fli-1 (15/15, 100%), and NKX2.2 (14/16; 87.5%), the tumor cells also showed variable staining of CD117 (14/17; 82.4%). Of 25 cases, 23 (92%) demonstrated EWSR1 rearrangement by fluorescence in situ hybridization analysis. The 2 cases with negative fluorescence in situ hybridization results were found to harbor EWSR1::ERG and EWSR1::FLI1 fusion by further RNA sequencing, respectively, with a median follow-up of 12 months (range: 1 to 42 months), 5/19 (26.3%) patients developed visceral metastasis and 12/19 (63.2%) patients died of the disease (range:1 to 33 months; median: 9 months). This study showed that GI ES had a predilection for the small intestine, although other sites of the GI tract could also be involved. GI ES had a poor prognosis with a high rate of mortality, particularly in patients with abdominopelvic disseminated disease. In light of appropriate therapeutic strategies and prognostic considerations, it is essential not to misdiagnose GI ES as gastrointestinal stromal tumor owing to the expression of aberrant CD117.