Adult-type diffuse gliomas …

Neuro-Oncology

Updated 09.18.2024
Released 01.16.2024
Expires For CME 09.18.2027

Adult-type diffuse gliomas [Brief]

Authors: Pouya Jamshidi MD, Nicolas Kostelecky MD

See Contributor Disclosures

Editor: Rimas V Lukas MD

Adult-type diffuse gliomas [Brief]

In This Article

Quick Link

Introduction

Key points

	• Adult-type diffuse gliomas are tumors marked by their infiltration of adjacent parenchyma.
	• Delineation of types is determined by the presence or absence of mutations in IDH1 or IDH2 and the presence or absence of codeletion of chromosomes 1p and 19q.
	• Distinction between types is key to determining clinical outcomes, treatment modalities, and eligibility for clinical trial enrollment.

Discussion

The adult-type diffuse gliomas consist of three entities whose major overlapping histopathologic feature is the infiltrating growth pattern (ie, invasion into the adjacent brain parenchyma). Additionally, key histologic features that play a role in the grading of these lesions include microvascular proliferation and tumor-related necrosis, historically pseudo-palisading necrosis (10). The three entities in question are the following:

Glioblastoma, IDH-wildtype
	An infiltrating glial neoplasm of astrocytic histologic phenotype with no mutations in IDH1 or IDH2 nor histone H3 genes.
	Hallmark molecular alterations include mutation in TERT promoter and/or EGFR gene amplification or gain of chromosome 7 and loss of chromosome 10 (+7/-10 chromosome) (04; 11).
	This tumor is, by definition, WHO grade 4 and has a poor prognosis.
Astrocytoma, IDH-mutant
	An infiltrating glial neoplasm of astrocytic origin that harbors a mutation in either IDH1 or IDH2 (IDH1 R132H accounting for 80% to 85% of the IDH mutations) (06) without 1p/19q-codeletion (12).
	It can be WHO grade 2, 3, or 4, based on morphology or molecular alterations, with higher grades corresponding to worse prognosis (01).
	Much better prognosis overall than glioblastoma, IDH-wildtype, even for grade 4 IDH-mutant astrocytoma.
Oligodendroglioma, IDH-mutant and 1p/19q-codeleted
	An infiltrating glial neoplasm of oligodendroglial histologic phenotype (with classic perinuclear halos on histology) that harbors a mutation in either IDH1 or IDH2 (IDH1 R12H being by far the most common) with concurrent 1p/19q-codeletion.
	It can be WHO grade 2 or 3, based on morphology or mitotic activity, with the higher grade corresponding to a worse prognosis.
	Markedly favorable prognosis compared to glioblastoma, IDH-wildtype.

All three entities are wildtype for mutations in histone-related genes (eg, H3 K27M and H3 G34V). Additional caveats regarding molecular details for these lesions are to be noted.

A diagnosis of glioblastoma, IDH-wildtype, WHO grade 4 (full entity name) can be rendered in the absence of high-grade morphologic features (microvascular proliferation and necrosis) if the following molecular criteria are met: absence of mutation in IDH1 or IDH2, absence of 1p/19q-codeletion, and presence of one (or any combination of) mutation in TERT, polysomy 7 with monosomy 10, or amplification of EGFR. This situation may arise in the case of biopsy specimens where a full spectrum of the tumor may not be sampled.

Astrocytomas, IDH-mutant, show near-universal co-occurrence of mutations in ATRX and TP53 (07; 08; 05). Regarding grading, the presence of high-grade morphologic features (microvascular proliferation and necrosis) would result in WHO grade 4 designation. However, this grade may be assigned even in the absence of these findings if there is a homozygous loss of CDKN2A or CDKN2B (01). Heterozygous loss or haploinsufficiency of CDKN2A or CDKN2B is associated with more aggressive clinical behavior, but this observation is still under active investigation and has not been formally codified in the WHO Classification of Tumors of the Central Nervous System (09).

Oligodendrogliomas, IDH-mutant, 1p/19q-codeleted, in contrast to astrocytomas, IDH-mutant, typically show preserved ATRX and TP53 and instead typically show mutations in CIC and TERT promoter (03; 07; 13; 02). The loss of CDKN2A or CDKN2B does not currently play a role in the grading of these lesions, which relies on morphologic details only.

References

01: Appay R, Dehais C, Maurage CA, et al. CDKN2A homozygous deletion is a strong adverse prognosis factor in diffuse malignant IDH-mutant gliomas. Neuro Oncol 2019;21(12):1519-28. PMID 31832685
02: Arita H, Narita Y, Fukushima S, et al. Upregulating mutations in the TERT promoter commonly occur in adult malignant gliomas and are strongly associated with total 1p19q loss. Acta Neuropathol 2013;126(2):267-76. PMID 23764841
03: Bettegowda C, Agrawal N, Jiao Y, et al. Mutations in CIC and FUBP1 contribute to human oligodendroglioma. Science 2011;333(6048):1453-5. PMID 21817013
04: Brat DJ, Aldape K, Colman H, et al. cIMPACT-NOW update 3: recommended diagnostic criteria for "Diffuse astrocytic glioma, IDH-wildtype, with molecular features of glioblastoma, WHO grade IV". Acta Neuropathol 2018;136(5):805-10. PMID 30259105
05: Cancer Genome Atlas Research Network, Brat DJ, Verhaak RG, et al. Comprehensive, integrative genomic analysis of diffuse lower-grade gliomas. N Engl J Med 2015;372(26):2481-98. PMID 26061751
06: Hartmann C, Meyer J, Balss J, et al. Type and frequency of IDH1 and IDH2 mutations are related to astrocytic and oligodendroglial differentiation and age: a study of 1,010 diffuse gliomas. Acta Neuropathol 2009;118(4):469-74. PMID 19554337
07: Jiao Y, Killela PJ, Reitman ZJ, et al. Frequent ATRX, CIC, FUBP1 and IDH1 mutations refine the classification of malignant gliomas. Oncotarget 2012;3(7):709-22. PMID 22869205
08: Kannan K, Inagaki A, Silber J, et al. Whole-exome sequencing identifies ATRX mutation as a key molecular determinant in lower-grade glioma. Oncotarget 2012;3(10):1194-203. PMID 23104868
09: Kocakavuk E, Johnson KC, Sabedot TS, Reinhardt HC, Noushmehr H, Verhaak RG. Hemizygous CDKN2A deletion confers worse survival outcomes in IDHmut-noncodel gliomas. Neuro Oncol 2023;25(9):1721-3. PMID 37329568
10: Louis DN. Chapter 2: Gliomas, glioneuronal tumours, and neuronal tumours. In: Louis DN. WHO Classification of Tumours Editorial Board. Central nervous system tumours. 5th ed. Lyon (France): International Agency for Research on Cancer, 2021:19-55.
11: Tesileanu CM, Dirven L, Wijnenga MM, et al. Survival of diffuse astrocytic glioma, IDH1/2 wildtype, with molecular features of glioblastoma, WHO grade IV: a confirmation of the cIMPACT-NOW criteria. Neuro Oncol 2020;22(4):515-23. PMID 31637414
12: Yan H, Parsons DW, Jin G, et al. IDH1 and IDH2 mutations in gliomas. N Engl J Med 2009;360(8):765-73. PMID 19228619
13: Yip S, Butterfield YS, Morozova O, et al. Concurrent CIC mutations, IDH mutations, and 1p/19q loss distinguish oligodendrogliomas from other cancers. J Pathol 2012;226(1):7-16. PMID 22072542
14: 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.
See Profile
Nicolas Kostelecky MD

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

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.
See Profile

ICD & OMIM codes

ICD: Astrocytoma, IDH-mutant, grade 2: 9400/3

Astrocytoma, IDH-mutant, grade 3: 9401/3

Astrocytoma, IDH-mutant, grade 4: 9445/3

Oligodendroglioma, IDH-mutant and 1p/19q-codeleted, grade 2: 9450/3

Oligodendroglioma, IDH-mutant and 1p/19q-codeleted, grade 3: 9451/3

Glioblastoma, IDH-wildtype: 9440/3

Other specified gliomas of brain and astrocytoma, NOS: 2A00.0Y & XH6PH6

Other specified gliomas of brain and diffuse astrocytoma, IDH-mutant: 2A00.0Y & XH2HK4

Other specified gliomas of brain and oligodendroglioma, IDH-mutant and 1p/19q-codeleted: 2A00.0Y & XH7K31

Glioblastoma of brain and glioblastoma, IDH-wildtype: 2A00.00 & XH5571

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

Nearly 3,000 illustrations, including video clips of neurologic disorders.
Every article is reviewed by our esteemed Editorial Board for accuracy and currency.
Full spectrum of neurology in 1,200 comprehensive articles.
Listen to MedLink on the go with Audio versions of each article.

Questions or Comment?

MedLink®, LLC

3525 Del Mar Heights Rd, Ste 304
San Diego, CA 92130-2122

Toll Free (U.S. + Canada): 800-452-2400

US Number: +1-619-640-4660

Support: service@medlink.com

Editor: editor@medlink.com

ISSN: 2831-9125

Adult-type diffuse gliomas [Brief]

Also Relevant

Glioblastoma, IDH wildtype
IDH-mutated diffuse astrocytomas
Oligodendroglioma
Overview of neuropathology updates for infiltrating gliomas

Clinical Categories

Neuro-Oncology

Adult-type diffuse gliomas …

Adult-type diffuse 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

Adult-type diffuse 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.