Resident University of Iowa Department of Neurosurgery Iowa City, Iowa, United States
Introduction: Glioneuronal tumors (GNTs) comprise a rare class of central nervous system (CNS) neoplasms with varying degrees of neuronal and glial differentiation that predominately affect children and young adults. Within the current 2021 WHO Classification of CNS Tumors, GNTs encompass 14 distinct tumor types. Recently, utilization of whole-genome DNA-methylation profiling has allowed for more precise classification of this tumor group.
Methods: A 3-year-old male patient presented with a 3-month history of increasing head circumference, regression of developmental milestones and speech delay. Magnetic resonance imaging of the brain was notable for a large left hemispheric multiseptated mass with significant mass effect and midline shift that was treated with near-total resection. Subsequently, histologic and molecular assessment demonstrated a glioneuronal tumor harboring a MYO5A::NTRK3 fusion.
Results: By DNA-methylation profiling, this tumor matched to a provisional methylation class “glioneuronal tumor kinase-fused” (GNT kinase-fused). The patient was later initiated on targeted therapy with Larotrectinib.
Conclusion : This is the first report of a MYO5A::NTRK3 fusion in a pediatric GNT. “GNT kinase-fused” is a provisional methylation class, not currently included in the WHO Classification of CNS Tumors. This case highlights the impact of thorough molecular characterization of CNS tumors, especially with the increasing availability of novel gene targeting therapies.
