title: Congenital glioblastoma: a clinicopathologic and genetic analysis.
abstract: Congenital central nervous system (CNS) tumors are uncommon, accounting for 1% of all childhood brain tumors. They present clinically either at birth or within the first 3 months. Glioblastoma (GBM) only rarely occurs congenitally and has not been fully characterized. We examined clinicopathologic features and genetic alterations of six congenital GBMs. Tumors were seen by neuroimaging as large, complex cerebral hemispheric masses. All showed classic GBM histopathology, including diffuse infiltration, dense cellularity, GFAP-positivity, high mitotic activity, endothelial proliferation and pseudopalisading necrosis. Neurosurgical procedures and adjuvant therapies varied. Survivals ranged from 4 days to 7.5 years; two of the three long-term survivors received chemotherapy, whereas the three short-term survivors did not. Paraffin-embedded tissue sections were used for FISH analysis of EGFR, chromosomes 9p21 (p16/CDKN2A) and 10q ( PTEN/DMBT1); sequencing of PTEN and TP53; and immunohistochemistry for EGFR and p53. We uncovered 10q deletions in two cases. No EGFR amplifications, 9p21 deletions, or mutations of TP53 or PTEN were noted; however, nuclear p53 immunoreactivity was strong in 5/6 cases. Tumors were either minimally immunoreactive (n = 3) or negative (n = 3) for EGFR. We conclude that congenital GBMs show highly variable survivals. They are genetically distinct from their adult counterparts and show a low frequency of known genetic alterations. Nonetheless, the strong nuclear expression of p53 in these and other pediatric GBMs could indicate that p53 dysregulation is important to tumorigenesis.
authors.affiliation: Departments of Pathology and Laboratory Medicine and Winship Cancer Institute, Emory University School of Medicine, 1364 Clifton Road NE, Atlanta, GA 30322, USA. dbrat@emory.edu
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Brat
authors.forename: Bahig M
authors.initials: BM
authors.lastname: Shehata
authors.forename: Amilcar A
authors.initials: AA
authors.lastname: Castellano-Sanchez
authors.forename: Cynthia
authors.initials: C
authors.lastname: Hawkins
authors.forename: Robert B
authors.initials: RB
authors.lastname: Yost
authors.forename: Claudia
authors.initials: C
authors.lastname: Greco
authors.forename: Claire
authors.initials: C
authors.lastname: Mazewski
authors.forename: Anna
authors.initials: A
authors.lastname: Janss
authors.forename: Hiroko
authors.initials: H
authors.lastname: Ohgaki
authors.forename: Arie
authors.initials: A
authors.lastname: Perry
mesh_terms: D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D002879:Chromosomes, Human, Pair 10; D002899:Chromosomes, Human, Pair 9; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005909:Glioblastoma / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009154:Mutation; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism
chemical_list: D005904:Glial Fibrillary Acidic Protein; D016159:Tumor Suppressor Protein p53; D051059:PTEN Phosphohydrolase