Supratentorial High-grade Gliomas

Chapter 11 - Classification and Treatment of Paediatric Brain Tumours

Supratentorial HGGs represent 7%–11% of childhood CNS tumours. The median age at diagnosis is 9–10 years.

HGGs occur most frequently in the cerebral hemisphere, in contrast to LGGs, which occur in cerebellar and deep midline locations. These tumours are clinically aggressive and regionally invasive.

Paediatric high-grade diffuse gliomas, i.e. glioblastoma and anaplastic astrocytoma (WHO Grade 3/4) represent a single category.

Although histologically similar to their adult equivalents, the two groups present distinct genetic alterations. Commonly altered genes in hemispheric high-grade astrocytomas of childhood are TP53 (in 30%–50% of cases), ATRX (in ~25%), SETD2 (in ~15%), CDKN2A (deletion; in ~30%), and PDGFRA (Amplification and/or mutation; in ~30%).

Mutations of the histone genes H3 (H3.1/H3.3) K27M are found exclusively in midline tumours as diffuse intrinsic pontine gliomas (DIPG) or thalamic lesions, whereas H3.3 G34 mutations are found exclusively in tumours of the cerebral hemispheres, more frequently seen in teenagers and young adults. In contrast, hemispheric glioblastomas in infants harbour NTRK fusions in approximately 40% of cases, and histone mutations have not been reported.

Surgery followed by RT is the standard treatment of patients with HGG. Surgery has prognostic significance in patients with near-total resection and is at present the strongest indicator of prognosis in paediatric HGG. Focal RT is used as first-line therapy except in children <3 years. The role of ChT is evolving.

Revision Questions

  1. What is the median age at diagnosis for HGG?
  2. What is the standard treatment of children with HGG?
  3. In which paediatric tumour can the H3.3 K27 mutation be observed?

« Previous Page Next Page »

Last update: 18 September 2017