PATH-88. Glioneuronal tumor with ATRX alterations, kinase fusion, and anaplastic features (GTAKA) in a young adult male: Review of molecular features and treatment implications

Glioneuronal tumors with ATRX alteration, kinase fusion, and anaplastic features (GTAKA) are a recently identified, rare subset of glioneuronal tumors characterized by distinct molecular alterations, most notably NTRK gene fusions, ATRX mutations, and CDKN2A/B homozygous deletions. These tumors display more aggressive clinical behavior compared to typical low-grade glioneuronal tumors. We report the case of a 21-year-old male who presented with headaches, nausea, and vomiting. Brain MRI revealed a cystic, enhancing mass in the right basal ganglia extending to the midbrain, with hydrocephalus. Resection was performed, with histopathology and molecular profiling revealed a high-grade glioneuronal tumor with CCDC85::NTRK2 fusion, ATRX mutation, and CDKN2A/B deletion. These characteristics are consistent with the recently classified Glioneuronal tumors with ATRX alteration, kinase fusion, and anaplastic features (GTAKA). The patient completed 6 weeks of IMRT (60 Gy) with concurrent temozolomide and will proceed with adjuvant temozolomide. NTRK inhibitor therapy will be considered upon recurrence. There is a paucity of data in the management of this newly classified and molecularly distinct glioneuronal tumor. The median progression-free survival of 12.5 months is based on a limited series. While current treatment approaches are like any high-grade glioma, NTRK inhibitors may represent a promising option, particularly in the recurrent setting. Optimal timing, including possible use in the newly diagnosed setting, remain to be seen. GTAKA is a rare, high-grade glioneuronal tumor with distinct molecular features. Given its likely aggressive nature and possible actionable targets, molecular profiling is crucial. Further studies are needed to guide targeted treatment strategies.