Summary of 2021 WHO Classification of CNS Tumors

Summary of 2021 WHO Classification of CNS Tumors

1. Summary of 2021 WHO Classification of CNS Tumors
Dr.SeenaTresaSamuel
Pathologist

2. General Changes

3. CNS TumorTaxonomy
•WHO CNS5 incorporates numerous molecular changes
•Hybrid taxonomy
•To standardize with other editions of Blue Books-
“type” is used instead of “entity”
“subtype” is used instead of “variant.”
Eg. Meningioma-Single type

4. CNS TumorNomenclature
•Tumor nomenclature more consistent and simple
•Only location, age, or genetic modifiers with clinical utility have
been used
•Tumorswith highly characteristic features are included in tumor
definitions and even if they are not part of a tumor name
Eg. Chordoidgliomas occur in the third ventricle
•Modifier terms like “anaplastic” are not routinely included -do
not appear in this classification.

5. CNS TumorGrading
1.Arabic vs Roman numerals.
a.Avoid typographical error
b. Uniform approaches to grading
Arabic numerals is currently done for all the other organ
systems.
•Romanic numerical e.g.I,II.III,IV
•Arabicnumerical- e.g.1,2,3,4

6. 2.Neoplasms are graded within types
(Rather than across different tumor types).
•Anaplastic astrocytoma-automatically WHO grade III
•No option to grade an anaplastic astrocytoma as WHO
grade I, II, or IV.
•Anaplastic meningioma -assigned to WHO grade III
•Biologically unrelated, WHO grade III tumors were expected to have idealized
clinical-biological behaviour.

7. 1. To provide more flexibility in using grade relative to the
tumor type
2.To emphasize biological similarities within tumor types
rather than approximate clinical behavior, and
3.To conform with WHO grading in non-CNS tumortypes.

9. 3.Combined histological and molecular grading
•Traditionally, CNS tumor grading has been based exclusively on histological
features
•Molecular markers provide prognostic information
•Molecular parameters added as biomarkers of grading

10. •WHO Grade 2 or 3 IDH mutant diffuse astrocytomas
CDKN2A/B homozygous deletion
Astrocytoma IDH mutant CNS grade 4
•WHO grade 2 or 3 IDH-wild type adult diffuse glioma
1.TERT promoter mutation
2.EGFR amplification and/or
3.+7/−10 copy number changes
•Glioblastoma IDH Wild type, CNS Grade 4

11. NOS (Not Otherwise Specified) and NEC (Not
Elsewhere Classified) Diagnoses

12. NOS (Not Otherwise Specified)
•Diagnostic information (histological or molecular)
necessary to assign a specific WHO diagnosis is not available
1. Molecular testing is not available (Low resource setting)
2. Was performed but didn’t yield adequate result( assay failure)
3.Deliberately not done( IDH status in elderly patient with
Glioblastoma bcozlack of implications for therapeutic
management

13. NEC (Not Elsewhere Classified)
•Necessary diagnostic testing has been successfully performed but
the results do not readily allow for a WHO diagnosis
•If there is a mismatch between clinical, histological, IHC, and/or
genetic features.
Eg.Oligodendroglialhistology; but IDH Wild type
DD alternatives not good to fit –OligodendrogliomaNEC

14. Essential diagnosticcriteria and
Desirable diagnosticcriteria

15. •Easier to evaluate whether the key diagnostic criteria
are present.
•Essential diagnosticcriteria-Must have features
•Desirable diagnosticcriteria-Nice to have features

16. Integrated and Layered Diagnoses

17. Integrated and Layered Diagnoses-
To display the full range of diagnostic information available

18. Specific Changes

19. Newly recognized tumortypes -22

20. Revised nomenclature in the WHO CNS tumor
classification-13

21. Gliomas

22. 1.Division of diffuse gliomas into adult-type and pediatric type.
•Recognizes the clinical and molecular distinctions between those diffuse gliomas
that primarily occur in adults (termed “adult-type”) and those that occur
primarily in children.
•Separating these prognosticallyand biologically distinct groups of tumors.

23. 2.Simplification of the classification of common, adult type,diffuse
gliomas
•CNS classification from 2016, the common diffuse gliomas of
adults were divided into 15 entities
(Because different grades were assigned to different entities)
Eg. Anaplastic oligodendrogliomawas considered a different
type from Oligodendroglioma

24. ADULT diffuse glioma
IDH-mutant IDH-mutant & IDH-wildtype
1p/19q-codeleted;
Astrocytoma OligodendrogliomaGlioblastoma
(IHC: ATRX and p53)
ATR
X
IDH IDH

25. Diffuse Glioma
Adult-type Pediatric-type

26. •IDH and H3 Wild type diffuse glioma in children
•MYB or MYBL1 gene rearrangement,FGFR1
mutation ,BRAF V600E mutation or another
MAPK pathway alteration
Favourable prognosis
Molecular defect-Potential therapeutic target

27. Polymorphous low-grade neuroepithelialtumor of the
young
•History of epilepsy in young people
•Diffuse growth patterns
•Oligodendroglioma-like appearance and calcification
•CD34 immunoreactivity
CD3
4

28. Diffuse hemispheric glioma, H3 G34-mutant
•Malignant infiltrative glioma
•High-grade anaplastic features, sometimes with an
embryonal appearance
•Missense mutation in the H3F3A gene
•Positive nuclear staining with H3 G34
H3G34

29. Circumscribed Glioma
circumscribed”referstotheir moresolidgrowth pattern

30. Neuronal and glioneuronaltumors

31. Myxoidglioneuronaltumor
•Arise in the septal region and involve the lateral ventricle.
•Proliferation of oligodendrocyte-like tumorcells
•Prominent myxoidstroma
•Neurocyticrosettes

32. Multinodular and vacuolatingneuronal tumor
•Benign tumor
•Discrete and coalescent nodules
•Vacuolar changes both in tumor cells and the neuropil

33. Ependymoma
•Based on Anatomic site, histology & molecular features
•Papillary, clear cell & tanycyticvariant of classic ependymoma
–No specific clinical utility
•Myxopapillaryependymomaof spinal cord-Grade 2
•Anaplastic ependymoma-No longer used

34. EPENDYMOMA
Supratentorial Posterior fossa Spinal Ependymoma
Ependymoma Ependymoma SE,MYCN Amplified
•STE,ZFTA fusion+ PFE, Group PFA
•STE,YAP1fusion+ PFE, Group PFB
(H3K27Me3 +/-)
Subependymoma MyxopapillaryEpendymoma
Classified based on Anatomic site, histopathological &molecular features

35. Choroid Plexus Tumors
•Remains unchanged
•Separated from the category of primary neuroepithelialtumors

36. Embryonal Tumors

37. CNS tumor with BCOR internal tandem duplication
1. High-grade neoplasm with perivascular rosettes
2. Strong, diffuse nuclear staining on BCOR IHC
BCO
R

38. Pineal Tumors
Loss of INI 1

39. Meningioma
•A single type with 15subtypes
•Criteria defining atypical or anaplastic meningioma should
be applied regardless of the underlying subtype
Rhabdoidand papillary morphology –CNS WHO grade 3
Chordoidand clear cell meningioma-CNS WHO grade 2
•Molecular biomarkers-classification of Meningiomas
SMARCE1-Clear cell subtype
BAP1-Rhabdoidand papillary subtypes

40. Tumors of the SellarRegion
1. Adamantinomatouscraniopharyngiomaand Papillary
craniopharyngioma-subtypes of craniopharyngioma
2. Pituicytoma, Granular cell tumor, and Spindle cell oncocytoma
are included in 1 section as a related group of tumortypes
3.New term Pituitary neuroendocrine tumor(PitNET)
4.Pituitary blastoma–New entity

41. Mesenchymal, Non-MeningothelialTumors

42. Cranial and ParaspinalNerve Tumors
1.Paragangliomas are now included with the nerve tumors
2.Paraganglioma of the cauda equina/filum terminaleregion –
Distinct subtype
3. Melanoticschwannoma-Malignant melanoticnerve sheath
tumor.
4. New subtype added to the neurofibromasection:
Atypical neurofibromatousneoplasm of unknown biological
potential –ANNUBP (NF1-associated tumor)

43. Conclusion
•It is hoped that these more precisely defined entities will allow for
1.Improved tailoring of patient therapy
2.Better classification for clinical trials
3.Lead to improvements in the lives of patients with brain tumors

44. THANK YOU