PEDIATRIC BITHALAMIC GLIOMA H3K27M NEGATIVE AND EGFR POSITIVE: A DISTINCT ENTITY WITH POTENTIAL SENSIBILITY TO EGFR INHIBITORS

Abstract INTRODUCTION: Brain tumors are the most common solid tumors of childhood and optimal therapeutic strategies for many subtypes remain unknown. Bithalamic gliomas, in contrast with unilateral, have frequent mutations in the EGFR oncogene and only rare Histone H3 mutation. These EGFR mutations are small inframe insertions within exon 20 or missense mutations within exon 7 and occur in absence of gene amplification. CASE REPORT: A previously healthy 10-years-old boy with adequate neuropsychomotor development was admitted with a 5-day-long headache. A brain magnetic resonance imaging (MRI) showed an expansive midline lesion with thalamic extension. The tumor showed no diffusion restriction or contrast enhancement. An endoscopic septostomy and biopsy were performed.The histopahotology showed a diffused astrocytoma grade II. The immunohistochemistry was negative for IDH1 and 2, BRAF mutation, P53 and H3K27M. Next generation sequencing (NGS) ruled out histone H3K27M mutation and showed EGFR mutation in exon 7. The patient experimented clinical and radiological disease progression in a few weeks, confirming the high grade glioma despite the histopahological diagnosis.He received radiotherapy (Total dose 54Gy) and after radiation he started target therapy with Osimertinib, a third generation tirosin kinase inhibitor. As a toxiticy, he experienced neutropenia Grade 2. Disease evaluation performed after 2 cycles showed stable disease. DISCUSSION: Our case report represents a distintc molecular class of pediatric-type bithalamic glioma characterized by EGFR alteration and absence of H3K27M mutation. EGFR inhibition may represent a potential therapeutic strategy in these highly aggressive gliomas.