Dramatic response to entrectinib in a rare glioneuronal tumor harboring an NTRK2 fusion.

Glioneuronal tumors are rare CNS neoplasms that can exhibit overlapping histological features with embryonal tumors, posing diagnostic and therapeutic challenges. We report a case of a 19-year-old Tunisian woman with a large right frontal tumor and contralateral extension. Initial partial resection suggested CNS neuroblastoma, and the patient underwent chemoradiotherapy with temporary disease control. Upon progression, a second partial resection was followed by DNA methylation profiling, which reclassified the tumor as a glioneuronal tumor with ATRX alteration, kinase fusion, and anaplastic features (GTAKA), harboring a KANK1::NTRK2 fusion. Entrectinib therapy was initiated, leading to a complete radiological response at 14 months, with marked clinical improvement and no serious adverse effects. This case highlights the essential role of DNA methylation profiling in resolving diagnostic ambiguity and guiding targeted treatment in CNS tumors. It further supports the potential efficacy of entrectinib in NTRK fusion-positive glioneuronal tumors.