NTRK Gene Fusions in Pediatric Soft-Tissue Tumors: Diagnostic Significance and Clinical Decision-making

INTRODUCTION/OBJECTIVE: Neurotrophic Tyrosine Receptor Kinase (NTRK) gene fusion is a newly identified and targetable oncogenic driver in various pediatric soft tissue tumors. This perspective aims to emphasize the diagnostic role and evolving practice of NTRK gene fusion in clinical practice, especially in the context of tumor-agnostic targeted therapy. METHODS: This is a perspective review article based on the published literature on pediatric oncology and pathology, specifically the epidemiology, clinicopathologic features, diagnosis, and therapeutic outcomes of NTRK fusion-positive tumors. Special emphasis is placed on practical diagnostic algorithms and clinical trials of TRK inhibitors. RESULTS: NTRK gene fusion is highly prevalent in certain pediatric tumors, such as infantile fibrosarcoma, congenital mesoblastic nephroma, and secretory carcinomas, and may be used as a defining marker for these tumors. Pan-TRK immunohistochemistry is effective as a screening test for NTRK fusion-positive tumors, while RNA-based next-generation sequencing is used as a confirmatory test. TRK inhibitors such as larotrectinib and entrectinib have shown promising efficacy in pediatric tumors, with response rates of 70-80%. DISCUSSION: Despite advances in the management of pediatric tumors, certain issues remain regarding testing algorithms for NTRK fusion-positive tumors and the management of acquired resistance to TRK inhibitors. The long-term safety of TRK inhibitors in pediatric populations, especially infants, needs to be addressed to enable effective management of NTRK fusion-positive tumors. CONCLUSION: NTRK gene fusions are a critical marker for pediatric soft tissue tumors and are used for precision medicine in these tumors. NTRK gene fusions are used as diagnostic markers for infantile fibrosarcoma, congenital mesoblastic nephroma, and secretory carcinomas, and they play a critical role in the management of these tumors.