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.

Quantitative Proteomic Analysis Reveals Effects of Epidermal Growth Factor Receptor (EGFR) on Invasion-promoting Proteins Secreted by Glioblastoma Cells

“…Dysregulation of the EGFR signaling cascade can be caused by EGFR hyperactivity, which can result from genomic amplification (16), over-expression of EGFR, increased translation of the EGFR mRNA (17), increased abundance of associated ligands (17,18), or mutations in EGFR that cause constitutive activity (7, 15, 16, 19 -21). In GBM, dysregulation of the EGFR pathway plays a critical role in tumor initiation and progression.…”

Radiological features of infantile glioblastoma and desmoplastic infantile tumors: British Columbia’s Children’s Hospital experience

“…5,6,10,12,17,18,21,[24][25][26]28,31,[33][34][35][36]41,42 From these publications, there were 29 cases of GBM that met our inclusion criteria. The patients underwent either CT scans or MRI based on the patient's age and the clinical presentation.…”

“…25,28 Between 1.3% and 11% of pediatric brain tumors occur in the 1st year of life, with the majority of tumors occurring supratentorially. 5,17,25,28,33 The pathological types of infantile brain tumors include malignant tumors such as primitive neuroectodermal tumors (PNETs), atypical teratoid and rhabdoid tumors, and glioblastoma multiforme (GBM). However, benign tumors such as desmoplastic infantile tumors (DITs)-i.e., desmoplastic infantile ganglioglioma (DIG) and desmoplastic infantile astrocytoma-do occur in infancy.…”

Congenital glioblastoma coexisting with vascular developmental anomaly

“…Congenital glioblastomas are genetically distinct from adult and TP53 pathway dysregulation is impor tant in their tumourigenesis [7]. Unique molecular features of cGBM include also overexpression of mul tiple genes involved in glucose metabolism and tis sue hypoxia [25].…”