This is not a original work of mine based on Various text books, Journals and also Power Point presentations too This is a WHO Classification 2021 Update and with brief about all tumor types.also added are the changes that are made in this classification helpful for Neurology and Neurosurgery Residents This Power Point Presentation is useful to revise the final exam

1. WHO CLASSIFICATION
OF CNSTUMOR 2021
Dr Sachin Biradar
Final year Resident
MCh Neurosurgery
Thanjavur Medical College

2. Epidemiology
• It’s the 20th most common malignancy worldwide and 14th most common in
india according to GLOBOCAN 2020 data
• White s and Males (Except Meningioma/ Schwanoma )
• High Mortality Rate
• Dramatic Improvement in Childrens andYoung Adult
• Tumors that have Propensity for CSF Spread
 Medulloblastoma
 CNS Lymphoma
 Germ CellTumor

3. Non Malignant CNSTumors
Site Pathology
CBTRUS 2022

4. CBTRUS 2022
Malignant Primary Brain & Other CNSTumors
Site Pathology

5. Primary Brain & Other CNS Gliomas
Site Pathology
CBTRUS 2022

6. IARC
• The internationalAgency for Research on Cancer (IARC) is the specialized
cancer agency of theWorld Health Organisation.
• The objective of the IARC is to promote international collaboration in cancer
research.
• The publication programme of the IARC is an integral part of its mission to
promote international collaboration in cancer research.
• Several renowned and authoritative series, handbooks, textbooks and manual
reflect the wide range of AgencyActivities.
• WHO Press is the exclusive distributor of IARC Publications in print format.
Electronic formats of IARC publications are available , for free and for
purchase, through this site.

7. Evolution of Brain tumor Classification byWHO

10. 1. Gliomas, glioneuronal tumors, and neuronal tumors
2. Choroid plexus tumors
3. Embryonal tumors
4. Pineal tumors
5. Cranial and paraspinal nerve tumors
6. Meningiomas
7. Mesenchymal, non-meningothelial tumors
8. Melanocytic tumors
9. Hematolymphoid tumors
10. Germ cell tumors
11. Tumors of the sellar region
12. Metastases to the CNS

11. 1. Gliomas, GlioneuronalTumors & Neuronal
Tumors
Adult-type diffuse gliomas
• Astrocytoma, IDH-mutant
• Oligodendroglioma, IDH-mutant, and 1p/19q-codeleted
• Glioblastoma, IDH-wildtype
Pediatric-type diffuse low-grade gliomas
• Diffuse astrocytoma, MYB- or MYBL1-altered
• Angiocentric glioma
• Polymorphous low-grade neuroepithelial tumor of the
young
• Diffuse low-grade glioma, MAPK pathway-altered

12. Pediatric-type diffuse high-grade gliomas
• Diffuse midline glioma, H3 K27-altered
• Diffuse hemispheric glioma, H3 G34-mutant
• Diffuse pediatric-type high-grade glioma, H3-wildtype &
IDH-wildtype
• Infant-type hemispheric glioma
Circumscribed astrocytic gliomas
• Pilocytic astrocytoma
• High-grade astrocytoma with piloid features
• Pleomorphic xanthoastrocytoma
• Subependymal giant cell astrocytoma (SEGA)
• Chordoid glioma
• Astroblastoma, MN1-altered

13. Glioneuronal and neuronal tumors
• Ganglioglioma
• Desmoplastic infantile ganglioglioma / desmoplastic infantile
astrocytoma
• Dysembryoplastic neuroepithelial tumor
• Diffuse glioneuronal tumor with oligodendroglioma-like features and
nuclear clusters
• Papillary glioneuronal tumor
• Rosette-forming glioneuronal tumor
• Myxoid glioneuronal tumor
• Diffuse leptomeningeal glioneuronal tumor
• Gangliocytoma
• Multinodular and vacuolating neuronal tumor
• Dysplastic cerebellar gangliocytoma (Lhermitte-Duclos disease)
• Central neurocytoma
• Extraventricular neurocytoma
• Cerebellar liponeurocytoma

14. Ependymal tumors
• Supratentorial ependymoma
• Supratentorial ependymoma, ZFTA fusion-positive
• Supratentorial ependymoma, YAP1 fusion-positive
• Posterior fossa ependymoma
• Posterior fossa ependymoma, group PFA
• Posterior fossa ependymoma, group PFB
• Spinal ependymoma
• Spinal ependymoma, MYCN-amplified
• Myxopapillary ependymoma
• Subependymoma

15. 2. Choroid PlexusTumors
• Choroid plexus papilloma
• Atypical choroid plexus papilloma
• Choroid plexus carcinoma

16. 3. Embryonal tumors
A. Medulloblastoma
Medulloblastomas,
molecularly defined
Medulloblastoma,WNT-
activated
Medulloblastoma, SHH-activated
and TP53-wildtype
Medulloblastoma, SHH-activated
and TP53-mutant
Medulloblastoma, non-
WNT/non-SHH
Medulloblastomas,
histologically defined
B. Other CNS embryonal tumors
• Atypical teratoid/rhabdoid tumor
• Cribriform neuroepithelial tumor
• Embryonal tumor with
multilayered rosettes
• CNS neuroblastoma, FOXR2-
activated
• CNS tumor with BCOR internal
tandem duplication
• CNS embryonal tumor

17. 4. Pineal Tumors
• Pineocytoma
• Pineal parenchymal tumor of intermediate differentiation
• Pineoblastoma
• Papillary tumor of the pineal region
• Desmoplastic myxoid tumor of the pineal region, SMARCB1-
mutant

18. 5. Cranial And Paraspinal Nerve Tumors
• Schwannoma
• Neurofibroma
• Perineurioma
• Hybrid nerve sheath tumor
• Malignant melanotic nerve sheath tumor
• Malignant peripheral nerve sheath tumor
• Paraganglioma
6. Meningiomas
• Meningioma

19. 7. Mesenchymal, non-meningothelial tumors
A. Soft tissue tumors
Fibroblastic and myofibroblastic
tumors
Solitary fibrous tumor
Vascular tumors
Hemangiomas and vascular
malformations
Hemangioblastoma
Skeletal muscle tumors
Rhabdomyosarcoma
Uncertain differentiation
Intracranial mesenchymal tumor,
FET-CREB fusion-positive
CIC-rearranged sarcoma
Primary intracranial
sarcoma, DICER1-mutant
Ewing sarcoma
B. Chondro-osseous tumors
Chondrogenic tumors
Mesenchymal chondrosarcoma
Chondrosarcoma
Notochordal tumors
Chordoma (including poorly
differentiated chordoma)

20. 8. MelanocyticTumors
• Diffuse meningeal melanocytic neoplasms
Meningeal melanocytosis and meningeal melanomatosis
• Circumscribed meningeal melanocytic neoplasms
Meningeal melanocytoma and meningeal melanoma

21. 9. Hematolymphoid Tumors
• Lymphomas
CNS lymphomas
Primary DLBCL of CNS
Immunodeficiency associated
CNS Lymphoma
Lymphomatoid granulomatosis
Intravascular large B cell
lymphoma
Miscellaneous rare lymphomas in
the CNS
MALT lymphoma of the Dura
other low grade B cell
Anaplastic large cell
T cell and NK/T cell
Histiocytic tumors
• Erdheim-Chester disease
• Rosai-Dorfman disease
• Juvenile
xanthogranuloma
• Langerhans cell
histiocytosis
• Histiocytic sarcoma

22. 10. Germ CellTumors
• Mature teratoma
• Immature teratoma
• Teratoma with somatic-type malignancy
• Germinoma
• Embryonal carcinoma
• Yolk sac tumor
• Choriocarcinoma
• Mixed germ cell tumor

23. 11.Tumors of the sellar region
• Adamantinomatous craniopharyngioma
• Papillary craniopharyngioma
• Pituicytoma, granular cell tumor of the sellar region,
and spindle cell oncocytoma
• Pituitary adenoma/PitNET
• Pituitary blastoma
12. Metastases to the CNS
• Metastases to the brain and spinal cord
parenchyma
• Metastases to the meninges

24. Gliomas
• Most heterogeneous groups of brain tumors and the most common overall malignant brain
tumor.
• Tumors of putative glial cell origin were originally called "gliomas" (because of their supposed
derivation from glue-like glial cells).
• The neuropil contains several subtypes of glial cells: astrocytes, oligodendrocytes, ependymal
cells, and modified ependymal cells that form the choroid plexus.
• Primary neoplasms of the brain parenchyma are now thought to arise from pluripotential
neural stem cells.
• These NSCs persist in two areas of the postnatal brain: the subventricular zone ,the region
located under the ependyma of the brain ventricles and the dentate gyrus of the hippocampus.
• Data from The Cancer Genome Atlas identified a mutation in isocitrate dehydrogenase (IDH)
as an early "driver mutation" in gliomagenesis. Mutated IDH converts a normal metabolite, α-
ketoglutarate, to D-2-hydroxyglutarate (2-HG). 2-HG is an "oncometabolite" that alters
cellular epigenetic profiles and induces "broad metabolic reprogramming.

25. ASTROCYTOMA
• Astrocytomas can be relatively localized (and generally
behave more benignly) or diffusely infiltrating with an
inherent tendency to malignant degeneration
• Diffuse astrocytomas are now divided into IDH-mutant
and IDH-wild-type tumors.
• Diffuse astrocytomas are designated as WHO grade II
neoplasms with the caveat that an IDH wild-type grade II
astrocytoma behaves more like a III (anaplastic) or IV
astrocytoma (i.e., glioblastoma).
• Two of the localized tumors, pilocytic astrocytoma (PA)
and subependymal giant cell astrocytoma (SEGA), are
designated WHO grade I neoplasms. Neither displays a
tendency to malignant progression although a variant of
PA, pilomyxoid astrocytoma, may behave more
aggressively.

26. Adult-Type Diffuse Gliomas
A.G. Osborn et al. AJNR Am J Neuroradiol
doi:10.3174/ajnr.A7462

27. NON ASTROCYTIC GLIAL NEOPLASM
OligodendroglialTumors: Oligodendroglial tumors are IDH mutant
and have a category-defining mutation, 1p19q codeletion.Two grades
are recognized: a well-differentiated WHO grade II neoplasm
(oligodendroglioma) and aWHO grade III neoplasm (anaplastic
oligodendrogliomas).
EpendymalTumors: Ependymal tumors vary fromWHO grade I to III.
Subependymoma, a benign-behaving neoplasm of middle-aged and
older adults that occurs in the frontal horns and fourth ventricle, is a
WHO grade I tumor.
Myxopapillary ependymoma, a tumor of young and middleaged adults
that is almost exclusively found at the conus, cauda equina, and filum
terminale of the spinal cord.
Ependymoma, generally a slow-growing tumor of children and young
adults, is a WHO grade II neoplasm that may arise anywhere along the
ventricular system and in the central canal of the spinal cord.

28. ZFTA fusion–positive ependymoma in an 11-year-old girl.
A.G. Osborn et al. AJNR Am J Neuroradiol doi:10.3174/ajnr.A7462

29. Anaplastic ependymomas are biologically more aggressive, have poorer
prognosis, and are designatedWHO grade III neoplasms.
Infratentorial ependymomas, typically arising within the fourth ventricle,
occur predominantly in children.
Supratentorial ependymomas are more common in the cerebral
hemispheres than the lateral ventricle and are usually tumors of young
children.
Choroid PlexusTumors.
Choroid plexus tumors are papillary intraventricular neoplasms derived from
choroid plexus epithelial cells.
Almost 80% of choroid plexus tumors are found in children and are one of
the most common brain tumors in children under the age of 3 years.
Choroid plexus tumors are divided into choroid plexus papillomas (CPPs),
which are WHO grade I tumors, atypical choroid plexus papilloma (WHO
grade II), and choroid plexus carcinomas (CPCas), designatedWHO grade III.

30. NEURONALAND MIXED NEURONAL-GLIALTUMORS
• This group includes dysembryoplastic neuroepithelial tumor (DNET), and
ganglion cell neoplasms include gangliocytoma, ganglioglioma, and
dysplastic cerebellar gangliocytoma (Lhermitte-Duclos disease).
• Other tumors in this category are desmoplastic infantile astrocytoma and
ganglioglioma, neurocytoma, papillary glioneuronal tumor, rosette-forming
glioneuronal tumor, and cerebellar liponeurocytoma.

31. TUMORS OFTHE PINEAL REGION
• Pineal region neoplasms account for less than 1% of all intracranial
neoplasms and can be germ cell tumors or pineal parenchymal tumors.
• Pineocytoma is a very slowly growing, well-delineated pineal
parenchymal tumor that is usually found in adults. Pineocytomas are
WHO grade I.
• Pineal parenchymal tumor of intermediate differentiation (PPTID) is
intermediate in malignancy. PPTIDs can be either WHO grade II or III
neoplasms.
• Pineoblastoma is a highly malignant primitive embryonal tumor mostly
found in children. Highly aggressive and associated with early CSF
dissemination, pineoblastomas are WHO grade IV neoplasms.

32. EMBRYONALTUMORS
• The embryonal tumor group includes medulloblastoma, embryonal tumors,
and atypical teratoid/rhabdoid tumors (AT/RTs). All are highly malignant
invasive tumors.
• All are WHO grade IV and are mostly tumors of young children.
• The term "primitive neuroectodermal tumor" has been eliminated, and a new
tumor, embryonal tumor with multilayered rosetted, C19MC-altered, has
been recognized.
Embryonal tumor
with multilayered
rosettes in a 1-year-
old girl.

33. MENINGEALTUMORS
• Meningeal tumors are the second largest
category of primaryCNS neoplasms.They are
divided into meningiomas and mesenchymal,
nonmeningothelial tumors (i.e., tumors that
are not meningiomas).
• Meningiomas: Meningiomas arise from
meningothelial (arachnoidal) cells.
• Most are attached to the dura but can occur in
other locations (e.g., choroid plexus of the
lateral ventricles). Most meningioma subtypes
are benign, have a low risk of grade II tumors.
Anaplastic (malignant) meningiomas, including
the papillary and rhabdoid subtypes,
correspond toWHO grade III.

34. Mesenchymal Nonmeningothelial Tumors
Both benign and malignant nonmeningothelial mesenchymal tumors can
originate in the CNS. Most correspond to tumors of soft tissue or bone.
Generally, both a benign and malignant (sarcomatous) type occur.
Lipomas and liposarcomas, chondromas and chondrosarcomas, osteomas
and osteosarcomas are examples.
Primary melanocytic neoplasms of the CNS are rare.They arise from
leptomeningeal melanocytes and can be diffuse or circumscribed, benign or
malignant.

35. Tumors of Cranial and Spinal Nerves
Schwannoma
Schwannomas are benign encapsulated nerve sheath tumors that consist of
well-differentiated Schwann cells.
They can be solitary or multiple. Multiple schwannomas are associated with
neurofibromatosis type 2 (NF2) and schwannomatosis, a syndrome
characterized by multiple schwannomas but lacking other features of NF2.
Neurofibroma
Neurofibromas (NFs) are diffusely infiltrating extraneural tumors that
consist of Schwann cells and fibroblasts.
Solitary scalp neurofibromas occur, and multiple NFs or plexiform NFs occur
as part of neurofibromatosis type 1. NFs correspond histologically toWHO
grade I.
Plexiform NFs may degenerate into malignant peripheral nerve sheath
tumors (MPNSTs). MPNSTs are graded from WHO II to IV, the same three-
tiered system used for soft tissue sarcomas.

36. Lymphomas and HistiocyticTumors
• With the onset of the HIV/AIDS era and increasing drug induced immunocompromised
states, some neuropathologists predicted that lymphoma would soon become the most
common malignant intracranial neoplasm, surpassing glioblastoma.
• Intracranial germ cell tumors (GCTs) are morphologic and
immunophenotypic homologs of germinal neoplasms that arise in the
gonads and extragonadal sites. From 80-90% occur in adolescents. Most
occur in the midline (pineal region, around the third ventricle).
• Germinomas are the most common intracranial GCT.
• Teratomas differentiate along ectodermal, endodermal, and
mesodermal lines.They can be mature, immature, or occur as teratomas
with malignant transformation.
• Other miscellaneous GCTs include the highly aggressive yolk sac tumor,
embryonal carcinoma, and choriocarcinoma.
Germ CellTumors

37. Sellar RegionTumors
• The sellar region is one of the most
anatomically complex areas in the
brain.
• The sellar region contains many
structures besides the
craniopharyngeal duct and infundibular
stalk that give rise to masses seen on
imaging studies.The most common of
these masses—pituitary adenoma
• Pituitary Adenoma: Pituitary
adenomas account for the majority of
sellar/suprasellar masses in adults and
the third most common overall
intracranial neoplasm in this age group.
Pituitary adenomas are classified by
size as microadenomas (≤ 10 mm) and
macroadenomas (≥ 11 mm).

38. Craniopharyngioma:
Craniopharyngioma is a benign (WHO grade I),
often partially cystic neoplasm that is the most
common nonneuroepithelial intracranial neoplasm
in children.
It shows a distinct bimodal age distribution with the
cystic adamantinomatous type seen mostly in
children and a smaller peak in middle-aged adults.
The less common papillary type is usually solid and
found almost exclusively in adults.
Miscellaneous Sellar Region Tumors
Granular cell tumor of the neurohypophysis, also
called choristoma, is a rare tumor of adults that
usually arises from the infundibulum.
Pituicytomas are glial neoplasms of adults that also
usually arise within the infundibulum.
Spindle cell oncocytoma of the adenohypophysis is
an oncocytic nonendocrine neoplasm. All of these
rare tumors are WHO grade I.

39. Metastatic Tumours
Metastatic neoplasms represent nearly half
of all CNS tumors.
CNS metastases can arise from both extra
and intracranial primary tumors. Metastases
from extracranial primary neoplasms ("body-
to-brain metastases") most commonly
spread via hematogeneous dissemination.
Primary intracranial neoplasms sometimes
spread from one CNS site to another, causing
brain-to-brain or brain-to-spine metastases.
One typical example is spread of a malignant
astrocytoma (e.g., glioblastoma) to other
CNS sites.
Spread occurs preferentially along compact
white matter tracts such as the corpus
callosum and internal capsule but can also
involve the ventricular ependyma, pia, and
perivascular spaces.

41. Highlights Of 2021 WHO BrainTumor Classification

42. Grading
 Romanic Numerical e.g I,II,III,IV
 Arabic Numerical e.g 1,2,3,4

43. Tumor Grading in Brain Tumors

44. GoodbyeTo Anaplastic Word

45. Grading is No Longer Entirely Histological

46. With inTumorType Grading in IDH Mutant Glioma

47. When will we call as Glioblastoma ?

49. Layered Reporting in BrainTumors

52. CNS Classification – Essential and Desirable Diagnostic
Criteria

55. Newly RecognisedTumorTypes in 2021 WHO Brain Tumor
Classification

56. REVISED NOMENCLATURE INTHE 2021 WHO BRAIN
TUMOR CLASSIFICATION

58. CHANGES IN GLIALTUMOR CLASSIFICATION

59. CIRCUMCISED GLIOMA (SHAPE)

60. CHANGES IN CLASSIFICATION OF GLIOMA

62. NEW ENTRY OF PEDS GLIALTUMOR CLASSIFICATION

64. CHANGES IN SELLARTUMOR CLASSIFICATION

65. CHANGES IN MENINGIOMA CLASSIFICATION

66. CHANGES IN EPENDYMOMA CLASSIFICATION

67. CHANGES IN MEDULLOBLASTOMA CLASSIFICATION

68. CHANGES IN PINEAL GLANDTUMOR

69. HEMANGIOPERICYTOMA GOT RETIRED !!!!!

70. To Summaries
•Long way to go
•Metastasis from a SystemicCancer are the most common
BrainTumors in Adults
•Among BrainTumors, Meningioma and Gliomas together
account for more thanTwoThird of all Adult Primary Brain
Tumors
•MRI with Contrast is Optimal Study of Choice
•Better understanding is required for clinical
implementation
•Very few centers are doing the molecular marking
•Over the time some molecular markers will act as
predictive markers

71. References
•Central Nervous SystemTumours ,WHO Classification of
Tumours, 5th Edition,Volume 6
•Louis DN, PerryA,Wesseling P, Brat DJ, Cree IA, Figarella-
Branger D, Hawkins C, Ng HK, Pfister SM, Reifenberger G,
Soffietti R, von Deimling A, Ellison DW.The 2021WHO
Classification ofTumors of the Central Nervous System: a
summary. Neuro Oncol. 2021Aug 2;23(8):1231-1251. doi:
10.1093/neuonc/noab106. PMID: 34185076; PMCID:
PMC8328013.
•Youmans andWinn , Neurological Surgery 8th Edition
•Osborn s Brain, 2nd Edition: Imaging, Pathology andAnatomy