Early molecular diagnosis of BRAF status drives the neurosurgical management in BRAF V600E-mutant pediatric low-grade gliomas: a case report

Abstract

Background: To date, this is the only report showing with close and consecutive magnetic resonance images the extremely rapid response of two types of pediatric low-grade gliomas (PLGG) to vemurafenib and its impact on the surgical approach.

Cases presentation: We report two cases of symptomatic PLGG treated with vemurafenib, a BRAF inhibitor: in a 12-year-old girl it was used as first-line medical treatment, reducing the tumor by 45% within a month and stabilizing to 76% after a year; in a 3-year-old boy with no improvement after SIOP LGG 2004 Protocol, vemurafenib induced in only one week a 34% shrinkage and solved the hydrocephalus, avoiding surgical operation. DISCUSSION AND CONCLUSIONS: Our cases demonstrate how an early molecular diagnosis of BRAF mutations through the neurosurgical biopsy is essential to promptly start targeted therapies., whose effect can influence both therapeutic and surgical decisions, hopefully reducing the occurrence of second neurosurgery with associated risks of neurological sequelae.

Keywords: BRAF; Brain tumors; Case report; Neurosurgery; Vemurafenib.

Fig. 1

Brain MRI of the 12-year-old girl with ganglioglioma. T2-weighted axial sequences at baseline (after biopsy) show a heterogeneous mass with epicenter in the hypothalamic-chiasmatic region, prominent involvement of the left basal ganglia and thalamus, and caudal exophytic extension with midbrain compression. Follow-up MRI at 1 month from starting vemurafenib shows quick and evident shrinkage (-45%, according to RANO criteria) with prominent regression of the left prepontine component. Mass reduction continues at 5 months (-70%) and is stable at 12 months (-76%)

Fig. 2

Brain MRI of the 3-year-old boy with pilocytic astrocytoma. Baseline MR and after 2 months in T2-weighted, contrast-enhanced T1-weighted, and FLAIR (FLuid Attenuated Inversion Recovery) show a 61% shrinkage of the mass. MRI at 1 week of therapy (FLAIR) shows a 38% reduction (see small frames, main diameters are reported in millimeters)