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.
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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.