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

Area of Science:

• Neuro-oncology
• Molecular Diagnostics
• Precision Medicine

Background:

• Glioneuronal tumors (GTAKA) present diagnostic challenges due to overlapping features with embryonal tumors.
• Accurate classification is vital for effective treatment strategies in rare CNS neoplasms.

Purpose of the Study:

• To report a case of a misdiagnosed glioneuronal tumor (GTAKA) and highlight the utility of advanced diagnostic techniques.
• To demonstrate the efficacy of targeted therapy in a patient with a rare NTRK fusion-positive CNS tumor.

Main Methods:

• Histopathological examination and initial diagnosis of CNS neuroblastoma.
• DNA methylation profiling for molecular subtyping and identification of genetic alterations.
• Treatment with entrectinib, a targeted tyrosine kinase inhibitor.

Main Results:

• DNA methylation profiling reclassified the tumor as a glioneuronal tumor with ATRX alteration, kinase fusion, and anaplastic features (GTAKA), harboring a KANK1::NTRK2 fusion.
• Entrectinib therapy resulted in a complete radiological response at 14 months with significant clinical improvement.
• No serious adverse effects were reported during entrectinib treatment.

Conclusions:

• DNA methylation profiling is essential for accurate diagnosis and treatment guidance in ambiguous CNS tumors.
• Entrectinib demonstrates significant potential as a targeted therapy for NTRK fusion-positive glioneuronal tumors (GTAKA).
• This case underscores the importance of molecular diagnostics in advancing precision oncology for rare brain tumors.