Simple Summary
Ewing sarcoma is a rare and aggressive cancer of bone and soft tissue that most often affects teenagers. Because it is uncommon and can arise in many different parts of the body, it can be difficult to recognize—particularly when it occurs outside the typical age range or in unusual anatomical sites. This challenge is especially relevant in regions where molecular diagnostic testing is relatively new or inconsistently available, which can complicate accurate diagnosis. In this study, we compared clinical, anatomical, pathological, molecular, treatment, and outcome features of Ewing sarcoma across three age groups: children (0–18 years), adolescents/young adults (19–39 years), and older adults (≥40 years). We identified clear age-related patterns, including a shift from predominantly bone tumors in younger patients to predominantly soft-tissue tumors in older adults. These insights can improve diagnostic accuracy, guide clinical decision-making, and strengthen regional understanding of this rare malignancy.
Abstract
Background: Ewing sarcoma (ES) is a rare, aggressive small round cell sarcoma (SRCS) that peaks in adolescence. Given its rarity, atypical age or site presentations increase the risk of misclassification. This study examines age-related clinicopathological patterns in molecularly confirmed canonical ES (FET::ETS-fused). Methods: Between 2016 and 2025, 90 tumors diagnosed as ES or Ewing-like SRCSs underwent targeted RNA sequencing and/or EWSR1 break-apart fluorescence in situ hybridization. Patients were stratified into three age groups: 0–18, 19–39, and ≥40 years. Clinical, anatomical, pathological, molecular, and treatment/outcome variables were compared across strata. Results: Canonical ES accounted for 84% (76/90) of SRCSs, dominated by EWSR1::FLI1 (89%). ES comprised 91% of SRCSs in children but declined to 75% in older adults. Tumors arose mainly in bone (63%), with a significant age association (p = 0.016): children and young adults were primarily skeletal (73% and 62%), whereas older adults were predominantly extraskeletal (78%). Renal ES clustered in adults ≥40 years (p = 0.003). Classic histology predominated; atypical patterns were more common in extraskeletal tumors but lacked age specificity. Ewing-like SRCSs (n = 14), with heterogeneous or absent fusions, displayed a broader age distribution—including infants and older adults—and a marked extraskeletal predominance (86%, p = 0.001). Metastatic presentation strongly predicted inferior survival (p = 0.025). Treatment was multimodal, with neoadjuvant chemotherapy more frequent in children (90%, p = 0.029). Conclusions: Age significantly influences anatomic presentation and certain treatment choices in ES, whereas histology and survival remain broadly similar across groups. Age-linked extraskeletal trends reinforce the importance of routine molecular testing, particularly in underreported Middle Eastern populations.
Keywords:
Ewing sarcoma; FET-ETS; Ewing-like; pediatric oncology; old adults; extraskeletal; RNA sequencing