Clinical, radiological, histological and molecular characteristics of paediatric epithelioid glioblastoma

Neuropathol Appl Neurobiol. 2014 Apr;40(3):327-36. doi: 10.1111/nan.12093.

Abstract

Aims: A few case series in adults have described the characteristics of epithelioid glioblastoma (e-GB), one of the rarest variants of this cancer. We evaluated clinical, radiological, histological and molecular characteristics in the largest series to date of paediatric e-GB.

Methods: Review of clinical characteristics and therapy, imaging studies and histology was performed in patients younger than 22 years with e-GB seen at our institution over 15 years. Sequencing of hotspot mutations and fluorescence in situ hybridization of relevant genes were undertaken.

Results: Median age at diagnosis of six patients was 7.6 years. Tumours originated in the cerebral cortex (n = 2) or diencephalon (n = 4). Three patients presented with acute, massive haemorrhage and three had leptomeningeal dissemination at diagnosis. Paediatric e-GB had the typical histological characteristics seen in adult tumours. Universal immunoreactivity for INI1 and lack of diverse protein expression were seen in all cases. One tumour had a chromosome 22q loss. Three tumours (50%) harboured a BRAF: p.V600E. One thalamic tumour had an H3F3A p.K27M. All patients received radiation therapy with (n = 3) or without chemotherapy (n = 3). All patients experienced tumour progression with a median survival of 169 days. One patient with nonmetastatic disease had early leptomeningeal progression. Two patients had symptomatic tumour spread outside the central nervous system (CNS) through a ventriculoperitoneal shunt. One additional patient had widespread metastases outside the CNS identified at autopsy.

Conclusions: Paediatric e-GBs are rare cancers with an aggressive behaviour that share histological and genetic characteristics with their adult counterparts. BRAF inhibition is a potential treatment for these tumours.

Keywords: BRAF; epithelioid; glioblastoma; paediatric; rhabdoid.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Brain Neoplasms / diagnosis*
  • Brain Neoplasms / diagnostic imaging
  • Brain Neoplasms / genetics
  • Brain Neoplasms / pathology
  • Child
  • Child, Preschool
  • Female
  • Glioblastoma / diagnosis*
  • Glioblastoma / diagnostic imaging
  • Glioblastoma / genetics
  • Glioblastoma / pathology
  • Humans
  • Male
  • Radiography