Pediatric-type diffuse high-grade gliomas …

Neuro-Oncology

Updated 09.18.2024
Released 01.16.2024
Expires For CME 09.18.2027

Pediatric-type diffuse high-grade gliomas [Brief]

Authors: Pouya Jamshidi MD, Nicolas Kostelecky MD

See Contributor Disclosures

Editor: Rimas V Lukas MD

Pediatric-type diffuse high-grade gliomas [Brief]

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Introduction

Key points

	• These are the pediatric counterparts to the adult-type diffuse high-grade gliomas.
	• Pediatric-type diffuse high grade gliomas are universally aggressive tumors with a short overall survival.
	• They have distinct molecular profiles and somewhat specific localization.

Discussion

These tumors form the pediatric counterpart to the adult-type diffuse gliomas and are universally aggressive. Outcome data for all but the infant-type hemispheric glioma suggest a median survival of less than 2 years from diagnosis. They occur in the breadth of childhood classically, but a subset affects young adults as well (10).

Diffuse midline glioma, H3 K27-altered. Diffuse midline gliomas, H3 K27-altered, occur in the midline and most frequently in mid-childhood (5 to 8 years of age) but can occur in adolescence and early adulthood. They occur most frequently in the brainstem (commonly the pons, hence the terminology of “diffuse infiltrating pontine glioma”), bithalamic, unilaterally thalamic, or unilaterally in the spinal cord, with unilateral presentations being more common in adolescence and young adulthood (12; 14). The tumors show a diffusely infiltrative histology, with tumor cells being generally small and showing varied differentiation patterns, including astrocytic and epithelioid (15). Irrespective of their histologic appearance, these tumors are WHO grade 4 by definition, in keeping with their aggressive behavior (11; 06). From a molecular perspective, they show four major subtypes: H3.3 p.K28M (K27M)-mutant, H3.1 or 3.2 p.K28M (K27M)-mutant, H3-wildtype with EZHIP overexpression, and EGFR-mutant (02; 01; 13).

Diffuse hemispheric glioma, H3 G34-mutant. Diffuse hemispheric gliomas, H3 G34-mutant, are cerebral hemispheric tumors arising in adolescents and young adults and are assigned a WHO grade 4 designation due to their aggressive behavior (11). They show an infiltrating growth pattern, with astrocytic tumor cells and frequent necrosis, mitotic activity, and perivascular pseudorosettes akin to those seen in the higher-grade adult-type diffuse gliomas. The key molecular finding is a mutation in the H3-3A gene (07).

Diffuse pediatric-type high-grade glioma, H3-wildtype and IDH-wildtype. Diffuse pediatric-type high-grade gliomas, H3-wildtype and IDH-wildtype, are aggressive infiltrating gliomas affecting children, adolescents, and young adults. They arise anywhere but the spinal cord and have several molecular subtypes. The pHGG RTK1 subtype is notably the most frequent type among those associated with germline tumor predisposition syndromes and post-radiation gliomas. The other two subtypes are pHGG RTK2 and pHGG MYCN. Histologically, they show an infiltrating astrocytic tumor with high-grade morphologic features (microvascular proliferation and necrosis) (08; 11; 09).

Infant-type hemispheric glioma. Infant-type hemispheric glioma is a pediatric-type high-grade glioma notable for its occurrence chiefly in the first year of life. They are supratentorial and typically hemispheric. They frequently harbor receptor tyrosine kinase alterations or mutations in ROS1, ALK, or MET. They have an astrocytic histology and frequent high-grade morphologic features (microvascular proliferation, necrosis, and elevated mitotic activity) (05). Comprehensive outcome data are lacking due to the scarcity of this tumor, but targeted therapies may be available if an RTK fusion is present (04; 16; 03).

References

01: Castel D, Kergrohen T, Tauziède-Espariat A, et al. Histone H3 wild-type DIPG/DMG overexpressing EZHIP extend the spectrum diffuse midline gliomas with PRC2 inhibition beyond H3-K27M mutation. Acta Neuropathol 2020;139(6):1109-13. PMID 32193787
02: Castel D, Philippe C, Kergrohen T, et al. Transcriptomic and epigenetic profiling of 'diffuse midline gliomas, H3 K27M-mutant' discriminate two subgroups based on the type of histone H3 mutated and not supratentorial or infratentorial location. Acta Neuropathol Commun 2018;6(1):117. PMID 30396367
03: Clarke M, Mackay A, Ismer B, et al. Infant high-grade gliomas comprise multiple subgroups characterized by novel targetable gene fusions and favorable outcomes. Cancer Discov 2020;10(7):942-63. PMID 32238360
04: Drilon A, Siena S, Ou SI, et al. Safety and antitumor activity of the multitargeted Pan-TRK, ROS1, and ALK inhibitor entrectinib: combined results from two phase i trials (ALKA-372-001 and STARTRK-1). Cancer Discov 2017;7(4):400-9. PMID 28183697
05: Guerreiro Stucklin AS, Ryall S, Fukuoka K, et al. Alterations in ALK/ROS1/NTRK/MET drive a group of infantile hemispheric gliomas. Nat Commun 2019;10(1):4343. PMID 31554817
06: Hoffman LM, Veldhuijzen van Zanten SE, Colditz N, et al. Clinical, radiologic, pathologic, and molecular characteristics of long-term survivors of diffuse intrinsic pontine glioma (DIPG): a collaborative report from the International and European Society for Pediatric Oncology DIPG Registries. J Clin Oncol 2018;36(19):1963-72. PMID 29746225
07: Korshunov A, Capper D, Reuss D, et al. Histologically distinct neuroepithelial tumors with histone 3 G34 mutation are molecularly similar and comprise a single nosologic entity. Acta Neuropathol 2016;131(1):137-46. PMID 26482474
08: Korshunov A, Schrimpf D, Ryzhova M, et al. H3-/IDH-wild type pediatric glioblastoma is comprised of molecularly and prognostically distinct subtypes with associated oncogenic drivers. Acta Neuropathol 2017;134(3):507-16. PMID 28401334
09: Lopez GY, Van Ziffle J, Onodera C, et al. The genetic landscape of gliomas arising after therapeutic radiation. Acta Neuropathol 2019;137(1):139-50. PMID 30196423
10: Louis DN. Chapter 2: Gliomas, glioneuronal tumours, and neuronal tumours. Louis DN, editor. WHO Classification of Tumours Editorial Board. Central Nervous System Tumours. 5th ed. Lyon (France): International Agency for Research on Cancer, 2021:69-82.
11: Mackay A, Burford A, Carvalho D, et al. Integrated molecular meta-analysis of 1,000 pediatric high-grade and diffuse intrinsic pontine glioma. Cancer Cell 2017;32(4):520-37.e5. PMID 28966033
12: Meyronet D, Esteban-Mader M, Bonnet C, et al. Characteristics of H3 K27M-mutant gliomas in adults. Neuro Oncol 2017;19(8):1127-34. PMID 28201752
13: Mondal G, Lee JC, Ravindranathan A, et al. Pediatric bithalamic gliomas have a distinct epigenetic signature and frequent EGFR exon 20 insertions resulting in potential sensitivity to targeted kinase inhibition. Acta Neuropathol 2020;139(6):1071-88. PMID 32303840
14: Roux A, Pallud J, Saffroy R, et al. High-grade gliomas in adolescents and young adults highlight histomolecular differences from their adult and pediatric counterparts. Neuro Oncol 2020;22(8):1190-202. PMID 32025728
15: Solomon DA, Wood MD, Tihan T, et al. Diffuse midline gliomas with histone H3-K27M mutation: a series of 47 cases assessing the spectrum of morphologic variation and associated genetic alterations. Brain Pathol 2016;26(5):569-80. PMID 26517431
16: Ziegler DS, Wong M, Mayoh C, et al. Brief report: potent clinical and radiological response to larotrectinib in TRK fusion-driven high-grade glioma. Br J Cancer 2018;119(6):693-6. PMID 30220707
17: References especially recommended by the author or editor for general reading.

Contributors

All contributors' financial relationships have been reviewed and mitigated to ensure that this and every other article is free from commercial bias.

Authors

Pouya Jamshidi MD

Dr. Jamshidi of Northwestern University, Feinberg School of Medicine has no relevant financial relationships to disclose.
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Nicolas Kostelecky MD

Dr. Kostelecky of Northwestern University, Feinberg School of Medicine has no relevant financial relationships to disclose.
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Editor

Rimas V Lukas MD

Dr. Lukas of Northwestern University Feinberg School of Medicine received honorariums from Novartis and Novocure for speaking engagements, honorariums from Cardinal Health, Novocure, and Merck for advisory board membership, and research support from BMS as principal investigator.
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ICD & OMIM codes

ICD: Diffuse midline glioma, H3 K27-altered: 9385/3

Diffuse hemispheric glioma, H3 G34-mutant: 9385/3

Diffuse pediatric-type high-grade glioma, H3-wildtype and IDH-wildtype: 9385/3

Infant-type hemispheric glioma: 9385/3

Other specified gliomas of brain and diffuse midline glioma, H3 K27M-mutant: 2A00.0Y and XH7692

Other specified gliomas of brain: 2A00.0Y

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Pediatric-type diffuse high-grade gliomas [Brief]

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Pediatric-type diffuse high-grade gliomas …

Pediatric-type diffuse high-grade gliomas [Brief]

Introduction

Key points

Discussion

References

Contributors

Authors

Editor

ICD & OMIM codes

This is an article preview.
Start a Free Account
to access the full version.

Questions or Comment?

Also in This Category

NF2-related schwannomatosis

Tumors of the skull base

Ganglioglioma

Paraneoplastic syndromes

Overview of neuropathology updates for infiltrating gliomas

NTRK-fused tumors of the central nervous system

Anti-LGI1 encephalitis

Brain metastases

Pediatric-type diffuse high-grade gliomas [Brief]

Introduction

Key points

Discussion

References

Contributors

Authors

Editor

ICD & OMIM codes

This is an article preview. Start a Free Account to access the full version.

Questions or Comment?

Also in This Category

NF2-related schwannomatosis

Tumors of the skull base

Ganglioglioma

Paraneoplastic syndromes

Overview of neuropathology updates for infiltrating gliomas

NTRK-fused tumors of the central nervous system

Anti-LGI1 encephalitis

Brain metastases

This is an article preview.
Start a Free Account
to access the full version.