title: Clinical, radiological, histological and molecular characteristics of paediatric epithelioid glioblastoma.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Oncology, St. Jude Children's Research Hospital, Memphis, TN, USA; Department of Pediatrics, University of Tennessee Health Science Center, Memphis, TN, USA.
authors.forename: A
authors.initials: A
authors.lastname: Broniscer
authors.forename: R G
authors.initials: RG
authors.lastname: Tatevossian
authors.forename: N D
authors.initials: ND
authors.lastname: Sabin
authors.forename: P
authors.initials: P
authors.lastname: Klimo
authors.forename: J
authors.initials: J
authors.lastname: Dalton
authors.forename: R
authors.initials: R
authors.lastname: Lee
authors.forename: A
authors.initials: A
authors.lastname: Gajjar
authors.forename: D W
authors.initials: DW
authors.lastname: Ellison
mesh_terms: D001932:Brain Neoplasms / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000235:genetics / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D005260:Female; D005909:Glioblastoma / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000235:genetics / Q000473:pathology; D006801:Humans; D008297:Male; D011859:Radiography
keywords: BRAF; epithelioid; glioblastoma; paediatric; rhabdoid