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

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

A Broniscer  1 , R G Tatevossian, N D Sabin, P Klimo Jr, J Dalton, R Lee, A Gajjar, D W Ellison
Affiliations

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

A Broniscer et al. Neuropathol Appl Neurobiol. 2014 Apr.

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.

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Conflict of interest statement

Conflict of Interests: The authors have no conflicts of interest to declare in regards to this study.

Figures

Figure 1
Figure 1
Intra-tumoral hematoma and spread of hemorrhage inside the ventricular system at diagnosis in patient 4
Figure 2
Figure 2
Neoplastic ascites (white arrow) and peritoneal tumor deposits (white arrowhead), and multiple liver metastases (black arrowheads) as the sites of first progression in patient 3
Figure 3
Figure 3
Histopathological characteristics of epithelioid glioblastoma (e-GB) in children. Several cytological phenotypes characterize these tumors, including epithelioid (a), rhabdoid (b), and astrocytic/gemistocytic (c). e-GBs resemble classic glioblastomas in some areas (d; all H&E, ×200). Immunoreactivity for GFAP was variable in tumor cells (e; anti-GFAP antibody, ×200). Homozygous deletion of CDKN2A was evident in two patients (f; iFISH: green and red fluorochromes targeted CDKN2A and the control locus on 9q, respectively)
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