Table 3. Childhood Astrocytomas and Other Tumors of Glial Origin and Preferential Central Nervous System (CNS) Location continued...
Molecular features of pediatric high-grade astrocytomas show some similarities to the genetic aberrations seen in adult glioblastomas that arise from pre-existing lower-grade gliomas (so-called secondary glioblastoma).[29,30,31] These include a high incidence of TP53 mutations, a low incidence of PTEN and P16INK4A mutations, and the presence of PDGF/PDGFR overexpression. However, the IDH1 mutations that have been identified in a high proportion of adults with secondary glioblastoma are rarely seen in pediatric glioblastoma.[32,33] While the incidence of IDH1 mutations is low in children, it increases with age in the adolescent and young adult population. Mutations in histone H3.3 (H3F3A) are present in approximately one-third of non–brain stem pediatric high-grade astrocytomas,[33,34] and most of these cases also have TP53 mutations. Pediatric high-grade astrocytomas with H3F3A mutations often additionally have somatic mutations in ATRX, a gene coding for a protein involved in chromatin remodeling. Diffuse intrinsic pontine gliomas show an even higher frequency of H3F3A mutations than do non–brain stem pediatric high-grade astrocytomas, with approximately three-fourths of cases showing mutations.[34,35] Diffuse intrinsic pontine gliomas show a comparably high frequency of TP53 mutations, but IDH1 and IDH2 mutations are rare. These findings suggest that a substantial proportion of pediatric high-grade astrocytomas are associated with processes required for establishing normal chromatin architecture.
The molecular profile of pediatric patients with oligodendroglioma does not demonstrate deletions of 1p or 19q, as found in 40% to 80% of adult cases. Pediatric oligodendroglioma harbors MGMT gene promoter methylation in the majority of tumors.
Gliomatosis cerebri is a diffuse glioma that involves widespread involvement of the cerebral hemispheres in which it may be confined, but it often extends caudally to affect the brain stem, cerebellum, and/or spinal cord. It rarely arises in the cerebellum and spreads rostrally. The neoplastic cells are most commonly astrocytes, but in some cases, they are oligodendroglia. They may respond to treatment initially, but overall have a poor prognosis.
Low-grade astrocytomas (grade I [pilocytic] and grade II) have a relatively favorable prognosis, particularly for circumscribed, grade I lesions where complete excision may be possible.[39,40,41,42,43,44] Tumor spread, when it occurs, is usually by contiguous extension; dissemination to other CNS sites is uncommon, but does occur.[45,46] Although metastasis is uncommon, tumors may be of multifocal origin, especially when associated with NF1.
Unfavorable prognostic features include young age, fibrillary histology, and inability to obtain a complete resection. Elevated MIB-1 labeling index, a marker of cellular proliferative activity, is associated with shortened PFS in patients with pilocytic astrocytoma. A BRAF-KIAA fusion, found in pilocytic tumors, confers a better clinical outcome.