An Unusual High-Grade Sarcoma of the Kidney with TPM4::NTRK1 Fusion, CDKN2A/B Deletion, SDHD and NOTCH3 Variants: The First Case Report in Pediatric Population

Background NTRK-rearranged spindle cell neoplasms (NTRK-RSCNs) are an emerging entity, molecularly characterized by NTRK rearrangements. Advances in molecular testing have revealed that NTRK fusions are prevalent in various tumor types, particularly in soft tissue tumors.Case report A 5-year-old boy presented with frequent urination and a low fever. Imaging studies showed a large mass in the right kidney. Laboratory tests revealed hypophosphatemia and hypercalcemia. The patient received chemotherapy and radiation followed by nephrectomy. The tumor exhibited diverse high-grade sarcomatous morphological features distinct from common NTRK-RSCNs and was initially diagnosed as a malignant phosphaturic mesenchymal tumor (PMT) without molecular alteration evidence. Subsequent upgraded next-generation sequencing identified a TPM4::NTRK1 fusion, CDKN2A/B deletion, SDHD and NOTCH3 variants. Based on these molecular findings, the diagnosis was confirmed as an NTRK-rearranged high-grade sarcoma with an unusual histomorphological phenotype.Conclusion This case highlights novel molecular characteristics of NTRK-rearranged high-grade sarcoma and underscores the critical role of comprehensive molecular profiling in diagnosing challenging cases.