CNS & pituitary tumors

Gliomas, glioneuronal tumors, and neuronal tumors

WHO grading of gliomas


Editorial Board Member: Meaghan Morris, M.D., Ph.D.
Deputy Editor-in-Chief: Chunyu Cai, M.D., Ph.D.
Rebecca Yoda, M.D.
P.J. Cimino, M.D., Ph.D.

Last author update: 14 March 2022
Last staff update: 14 March 2022

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PubMed Search: WHO grading of gliomas[TI] 2021 free full text[SB]

Rebecca Yoda, M.D.
P.J. Cimino, M.D., Ph.D.
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Cite this page: Yoda R, Cimino PJ. WHO grading of gliomas. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/cnstumorwhograding.html. Accessed December 3rd, 2022.
Definition / general
  • CNS WHO grading of gliomas according to the WHO Classification of Central Nervous System Tumors, 5th edition, published in 2021
Major updates
  • Standardization with other fifth edition WHO classification systems (Neuro Oncol 2021;23:1231)
    • Switch from Roman to Arabic numeral system
    • The term "type" replaces "entity" and "subtype" replaces "variant"
    • Shift toward within tumor type grading
      • Removal of modifier terms, such as anaplastic
      • IDH mutant astrocytic gliomas were 3 separate entities under the 2016 WHO (diffuse astrocytoma, anaplastic astrocytoma and glioblastoma) but now fall under the single tumor type astrocytoma, IDH mutant, with CNS WHO grade ranging from 2 to 4
      • Oligodendroglioma, IDH mutant and 1p / 19q codeleted, is assigned a CNS WHO grade of 2 or 3
      • Pleomorphic xanthroastrocytoma is assigned a CNS WHO grade of 2 or 3
      • Terms that are no longer recommended include diffuse astrocytoma, anaplastic astrocytoma, glioblastoma IDH mutant, anaplastic oligodendroglioma and anaplastic pleomorphic xanthoastrocytoma
  • To emphasize difference of grading between CNS and non-CNS tumors, the term CNS WHO grade is endorsed
  • Allows designation of not otherwise specified (NOS) or not elsewhere classified (NEC) as modifiers
    • Not otherwise specified (NOS): applied when there is lack of diagnostic information (histological or molecular) necessary to classify glioma as a specific WHO diagnostic entity
    • Not elsewhere classified (NEC): applied when there is sufficient diagnostic information available (histological and molecular) but the results do not allow for the glioma to be classified as a specific WHO diagnostic entity - often ending up more as a descriptive diagnosis
  • New tumor type groupings
    • Adult type diffuse gliomas
    • Pediatric type diffuse low grade gliomas
    • Pediatric type diffuse high grade gliomas
    • Circumscribed astrocytic gliomas
  • New glioma types
    • Diffuse astrocytoma, MYB or MYBL1 altered
    • Polymorphous low grade neuroepithelial tumor of the young
    • Diffuse low grade glioma, MAPK pathway altered
    • Diffuse hemispheric glioma, H3 G34 mutant
    • Diffuse pediatric type high grade glioma, H3 wildtype and IDH wildtype
    • Infant type hemispheric glioma
    • High grade astrocytoma with piloid features
  • Removed glioma types
    • Diffuse astrocytoma, IDH wildtype
    • Anaplastic astrocytoma, IDH wildtype
  • Renamed glioma types
    • Astrocytoma, IDH mutant
      • Eliminates the following previously used terms: diffuse astrocytoma, IDH mutant; anaplastic astrocytoma, IDH mutant; and glioblastoma, IDH mutant
    • Diffuse midline glioma, H3 K27 altered
      • Terminology replaces the term mutant with altered, to include other mechanisms of histone alteration (e.g., EZHIP overexpression)
    • Chordoid glioma
      • Omits "of the third ventricle" anatomical designation
    • Astroblastoma, MN1 altered
      • Adds molecular criterion for diagnosis
  • Changes to existing grading criteria require that either histological or molecular features are present (adult type diffuse gliomas)
    • IDH mutant astrocytoma, CNS WHO grade 4 (Neuro Oncol 2021;23:1231)
      • IDH mutant diffuse astrocytic glioma with CDKN2A / CDKN2B homozygous deletion is assigned a CNS WHO grade 4, even in the absence of microvascular proliferation or necrosis
    • Glioblastoma, IDH wildtype, CNS WHO grade 4 (Acta Neuropathol 2018;136:805)
      • Changes require that either histological or molecular criteria are present in order to obtain diagnosis
      • Requirements: a diffuse astrocytic glioma with any one or more of the following: microvascular proliferation, necrosis, TERT promoter mutation, EGFR amplification, gain of chromosome 7 with concomitant loss of chromosome 10
WHO (2021)



Diagrams / tables

Contributed by P.J. Cimino, M.D., Ph.D.
Adult type IDH mutant gliomas

Adult type IDH mutant gliomas

Adult type IDH wildtype gliomas

Adult type IDH wildtype gliomas

Microscopic (histologic) images

Contributed by P.J. Cimino, M.D., Ph.D.
Astrocytoma lacking mitoses

Astrocytoma lacking mitoses

Increased mitotic activity

Increased mitotic activity

Pseudopalisading necrosis

Pseudopalisading necrosis

Microvascular proliferation

Microvascular proliferation

Molecular / cytogenetics images

Contributed by P.J. Cimino, M.D., Ph.D.
Glioblastoma EGFR amplification

Glioblastoma EGFR amplification

Glioblastoma copy number plot

Glioblastoma copy number plot



Images hosted on other servers:

Glioblastoma TERT promoter mutation

Videos

2021 WHO classification of CNS tumors: update I - gliomas

Board review style question #1

This IDH mutant astrocytoma is from a 40 year old woman. There is no microvascular proliferation or necrosis identified. According to the 5th edition of the WHO classification of CNS tumors (2021), a CNS WHO grade 4 should be applied if which of the following genetic alterations is present?

  1. ATRX loss
  2. CDKN2A homozygous deletion
  3. Chromosome 1p / 19q codeletion
  4. EGFR amplification
  5. TERT promoter mutation
Board review style answer #1
B. CDKN2A homozygous deletion. The presence of CDKN2A or CDKN2B homozygous deletion in an astrocytoma, IDH mutant, necessitates a CNS WHO grade of 4, even in the absence of histologic features (i.e., lacking microvascular proliferation and spontaneous necrosis).

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Reference: WHO grading of gliomas
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