Superficially located CIC::DUX4-rearranged sarcomas in children: insights from a long-term survival case series

Soft tissue sarcomas account for approximately 10% of all cancers in the pediatric population, with undifferentiated round cell sarcomas-historically referred to as Ewing-like sarcomas-forming a notable subset. Recent molecular profiling has reclassified these tumors into distinct subtypes, including CIC::DUX4-rearranged sarcomas. While CIC::DUX4 sarcomas are more commonly found in adults, they are rarer in children and are typically located in deep soft tissues. The current study focuses on pediatric cases of superficially located CIC::DUX4 sarcomas, aiming to describe their clinical, morphological, and molecular features. This retrospective study includes pediatric patients diagnosed with superficial CIC::DUX4-rearranged sarcoma from January 2018 to December 2024. Relevant clinical data, including patient demographics, tumor location, and follow-up outcomes, were extracted from medical records. Tumor samples were examined histologically, and RNA sequencing was performed to confirm the presence of the CIC::DUX4 fusion. For survival analysis, we compared our series with 27 pediatric deep-seated CIC::DUX4 sarcomas. Five cases of superficial CIC::DUX4 sarcoma were identified. The patients ranged from 4 to 18 years old, with a mean age of 10.6 years. Only one patient presented with pulmonary metastases at diagnosis. All patients underwent excisional biopsies. Follow-up revealed complete remission in all cases and a statistically significant difference in OS (p = 0.00256) and DFS (p = 0.0239) compared to deep-seated CIC::DUX4 sarcoma. This study presents the first pediatric case series of superficial CIC::DUX4 sarcomas. While CIC::DUX4 sarcomas in adults are known for their aggressive behavior, our findings suggest that superficial tumors with well-defined margins in children may have a more favorable prognosis. These results highlight the need for further research into the biological behavior and long-term outcomes of these rare pediatric tumors.