Details of WHO classification of brain tumours for Neurology and neurosurgery residents

1. WHO CLASSIFICATION OF
BRAIN TUMOURS
DR SAMEEP KOSHTI

4. ASTROCYTES
• Most abundant cells in CNS
• Three common types:
• Radial glia
• White matter –Fibrous astrocytes
• Gray matter –Protoplasmic astrocytes
• Site specific Astrocytes: many types
• Bergmann glia in the cerebellum,
• Müller cells in the retina, and
• tanycytes in the brain and spinal cord

6. RADIAL GLIA
• First glia to appear in developing brain
• Kind of Neuronal stem cell
• Differentiate into the Astrocytes of white or gray matter.
• Site specific Astrocytes:
• Bergmann glia in the cerebellum,
• Müller cells in the retina, and
• tanycytes in the brain and spinal cord
retain many characteristics of radial glia in the adult brain
• Bipolar

8. WHITE MATTER ASTROCYTES
• Higher content of intermediate filaments (that contains GFAP) so stains more by
GFAP antibody.
• The astrocyte is the major homeostatic regulator of the CNS microenvironment.
• help restrict the entry of serum factors into the CNS by extending processes that terminate
in specialized “end-feet” that surround almost all blood vessels in the CNS  induces and
maintains the tight junctions between neighboring endothelial cells, an essential element
for the formation and maintenance of the BBB.
• Types:
• TYPE I -- Structural
• TYPE II -- Associated with blood vessels and nodes

9. GRAY MATTER ASTROCYTES
• More abundant than white matter astrocytes

10. ROLE
• The astrocyte is the major regulator of energy metabolism in the brain.
• One key to understanding this role is the
• physical connection between astrocytic processes and
• (1) capillaries, the external source of glucose; and
• (2) the synapse, a major energy consumer of the brain
• REACTIVE ASTROCYTES:
• Another important feature of astrocytes is their reaction to CNS pathology induced by
trauma, neurotoxicity, neurodegeneration, infection, and inflammation.
• Astrocytes react by becoming hypertrophic and, in a few cases, hyperplastic.

11. OLIGODENDROCYTES
• Myelin is a specialized extension of the plasma membrane of the
oligodendrocyte in the CNS and of the Schwann cell in the PNS.
• The only known functions of oligodendrocytes are myelination and
axonal support.

14. MICROGLIA
• Innate immune cells in the CNS.
• Two functions :
• they fight off and phagocytize viruses, bacteria, and other foreign invaders,
and
• they remove cellular debris to facilitate wound repair.

16. WHO CLASSIFICATION OF TUMOURS (2016,Revised 4th EDITION)
1. Difffuse astrocytic and oligodendroglial tumours
2. Other Astrocytic tumours
3. Ependymal tumours
4. Other Gliomas
5. Choroid plexus tumours
6. Neuronal and mixed Neuronal glial tumours
7. Tumours of the pineal region
8. Embryonal tumours
9. Tumours of the cranial and paraspinal nerves
10. Meningioma
11. Mesenchymal,Non meningothelial tumours
12. Melanocytic tumours
13. Lymphomas
14. Histiocytic tumours
15. Germ cell tumours
16. Tumours of the sellar region
17. Metastatic tumours

27. Nomenclature and HPE reporting of tumour
• CNS tumor diagnoses should consist of :
• a histopathological name followed by the genetic features following a comma and as adjectives,
• E.g
• Diffuse astrocytoma, IDH-mutant and
• Medulloblastoma, WNT-activated.
• For those entities with more than one genetic determinant, the multiple necessary
molecular features are included in the name:
• E.g
• Oligodendroglioma, IDH-mutant and 1p/19q-codeleted.
• For a tumor lacking a genetic mutation,
• the term wildtype can be used if an official “wildtype” entity exists:
• E.g.Glioblastoma, IDH-wildtype.
• For tumor entities in which a specific genetic alteration is present or absent,
• the terms “positive” can be used if the molecular characteristic is present:
• E.g. Ependymoma, RELA fusion–positive.

28. Contd..
• If formal wildtype diagnosis is not available, and a tumor lacking a diagnostic
mutation
• is given an NOS designation
• For sites lacking any access to molecular diagnostic testing,
• a diagnostic designation of NOS (i.e., not otherwise specified) is permissible for some tumor types.
• NOS designation thus represents those cases about which :
• we do not know enough pathologically, genetically and clinically and which should, therefore, be subject
to future study before additional refinements in classification can be made.
• WHO grades are written in Roman numerals:
• (e.g., I, II, III and IV; not 1, 2, 3 and 4)

29. Definition of tumours
• EXAMPLE:
• the definition of oligodendroglioma, IDH-mutant and 1p/19q-codeleted includes
• a first sentence: “A diffusely infiltrating, slow-growing glioma with IDH1 or IDH2 mutation and codeletion
of chromosomal arms 1p and 19q” (which is the italicized, entity-defining criteria),
• followed by sentences such as
• “Microcalcifications and a delicate branching capillary network are typical”
• (findings that are highly characteristic of the entity, but not necessary for the diagnosis).

31. IDH : Mutant vs Wild type
• If
• immunohistochemistry for mutant R132H IDH1 protein and
• sequencing for IDH1 codon 132 and for IDH2 codon 172 gene mutations are both negative,
or
• if sequencing for IDH1 codon 132 and IDH2 codon 172 gene mutations alone is negative,
then the lesion can be diagnosed as IDHwildtype.

34. IDH WILD TYPE AND GRADE II / III tumours
• uncommon diagnosis/Rare :
• Diffuse astrocytoma, IDH-wildtype
• anaplastic astrocytoma, IDH-wildtype (most such tumors will feature genetic findings highly
characteristic of IDH-wildtype glioblastoma )
• and that such cases need to be carefully evaluated to avoid misdiagnosis of lower
grade lesions such as gangliogliomas;
• Finally, in the setting of a diffuse astrocytoma or anaplastic astrocytoma,
• if IDH testing is not available or cannot be fully performed (e.g., negative
immunohistochemistry without available sequencing),
• the resulting diagnosis would be diffuse astroctyoma, NOS, or anaplastic astrocytoma, NOS, respectively.

35. Epithelioid Glioblastoma
• More in children and younger adults,
• typically present as superficial cerebral or diencephalic masses, and
• often harbor a BRAF V600E mutation (which can be detected
immunohistochemically).
• There are frequent hemizygous deletions of ODZ3.
• Often lack other molecular features of conventional adult IDHwildtype
glioblastomas:
• such as EGFR amplification and
• chromosome 10 losses;

36. PEDIATRIC DIFFUSE GLIOMA
• group of tumors primarily occurring in children (but sometimes in adults too) is
characterized by :
• K27M mutations in the histone H3 gene H3F3A, or
• Less commonly in the related HIST1H3B gene,
• a diffuse growth pattern, and
• a midline location (e.g., thalamus, brain stem, and spinal cord)
• This newly defined entity is termed diffuse midline glioma, H3 K27M–mutant
• includes tumors previously referred to as diffuse intrinsic pontine glioma (DIPG).

38. Contd..