About CNS tumors Dr Atta Gillani

1. WHO CNS Classification of
Tumors 2021

2. INTRODUCTION
• Tumor classification systems provide a framework to rationally subdivide
the broad spectrum of tumors into specific types with similar pathologic
characteristics, natural history, and patient demographics.
• This subdivision is useful in both practice and research, allowing clinicians
to offer accurate prognostic predictions and tumor-specific treatments,
clinical researchers to design trials enriched with the patient populations
most likely to benefit, and basic science researchers to focus their
investigations on specific tumor types.

3. “Big Picture” Changes in comparison to 2016 CNS
tumor classification
1-Increased emphasis on molecular diagnostics
The 2021 fifth edition continues to expand the role of molecular features in tumor diagnosis, with a much larger
number of tumor types defined by molecular features. In other tumors, molecular features impact grading, even if
not part of the definition of the tumor.
In comparison to 2016 classification system in which emphasis was given on molecular diagnostics but that was
not enough to classify tumors or to grade them.
Although molecular methods are used more frequently now than in the past, they have not displaced traditional
techniques such as histologic analysis and immunohistochemistry, and many tumor types are adequately
classified with these tools, with molecular testing supportive although not required for tumor diagnosis.

4. 2-TUMOR GRADING
Roman numerals are replaced by Arabic numerals i.e. 1,2,3..
A more fundamental change in the 2021 fifth edition is the move
to assigning grade within rather than across tumor types.
For example, in previous versions of the WHO classification
system, WHO grade I, II, and III meningiomas were separate
tumor types, with WHO grade II meningioma representing
“atypical” meningioma and WHO grade III
representing “anaplastic” or “malignant” meningioma
• NOTE: This change does not imply that multiple grade options
exist for all tumor types; some tumor types with predictably
favorable or aggressive natural histories may only be assigned
CNS WHO grades of 1 or 4, respectively, and other tumors may
be assigned a limited range of grades.

5. 3-Molecular diagnostic methods
• IMMUNOHISTOCHEMISTRY
• Fluorescence in situ hybridization
• Genome wide copy number arrays
• Methylation array
• DNA methylation profile

8. Adult Type Diffuse Gliomas

9. ADULT

10. Glioblastoma
• Previously classified as IDH mutant and non mutant. Newer classification labelled IDH mutant as astrocytomas.
Required criteria:
IDH wild type both canonical(IDH1 p.R132H)and non canonical(IDH1 p.R1372),
H3 wild type and one of the following:
1. Microvascular proliferation
2. Necrosis
3. EGFR amplification
4. TERT promoter mutation
5. +7/-10 chromosomal copy number changes
Additional desirable criteria:
DNA methylation profile of glioblastoma, IDHwildtype
NOTE:
In patients older than 54 years with a histologic diagnosis of glioblastoma, a negative IDH1 R132H immunostain is
sufficient for an IDH-wildtype designation.
While in younger patients or lower-grade tumors, assessment for noncanonical IDH1/IDH2(i.e., non-IDH1 R132H)

11. tT1 CEMRI
Ring
enhancement
Vasogenic edema
T2 FLAIR
DWI
Restricted
diffusion
Periventricular

12. TERT promoter mutation Activates telomerase to maintain telomere length
EGFR amplification Activates receptor tyrosine kinase pathway
+7/-10 chromosomal copy number changes

13. Key points
• Absence of gadolinium enhancement on MRI scan has never excluded
the possibility of high grade glioma.
• Molecular gliomas are commonly non enhancing.

15. ASTROCYTOMA
Required criteria:
Diffusely infiltrating glioma AND
IDH mutation AND
Loss of nuclear ATRX expression or ATRX mutation
OR
NO 1p/19q codeletion
CDKN2A/B homozygous deletion (Determines the grade of astrocytoma if present CNS WHO grade 4
aggressive tumor)
ADDITIONAL DESIRABLE CRITERIA:
TP53 mutation or strong p53 nuclear expression
(>10%)
DNA methylation profile of astrocytoma, IDH mutant
Astrocytic differentiation by morphology

16. IDH1 p.R132 or IDH2
p.R172 mutation
IDH mutations generate the oncometabolite 2-hydroxyglutarate, resulting in DNA hypermethylation
(G-CIMP phenotype)
ATRX mutation Activates alternative lengthening of telomeres (ALT) pathway to maintain telomere length
CDKN2A/B homozygous deletion Results in loss of tumor suppressor and cell cycle regulator p16

18. T2-FLAIR mismatch sign

19. T2 FLAIR Mismatch
• Occur in well circumscribed tumors
• Shows homogenous hyperintensity in T2 images with central signal
drop out, with
• Rim of residual hyperintensity in T2 FLAIR
• T1 gadolinium enhanced scan shows hypointensity with lack of
enhancement.
• Highly specific and moderately sensitive for Astrocytoma IDH mutant

20. Key point
• Can be CNS WHO grade 2-4
• CKN2A/B homozygous deletion is sufficient to indicate CNS WHO
grade4 even without microvascular proliferation and necrosis.
• Tumor enhancement is frequently seen in grade 3-4

22. Oligodendrogliomas
Required criteria:
Diffusely infiltrating glioma AND
IDH mutation* AND
1p/19q codeletion
CDKN2A/B homozygous deletion(Again a marker of poor prognosis and if present Labelled as CNS
WHO grade 3 tumor)
Additional desirable criteria:
TERT promoter mutation
Retained nuclear ATRX expression
Methylation profile of oligodendroglioma IDHmutant
and 1p/19q codeleted.

23. calcification Poorly
circumscribed
margins/edema
Hyperintense lesion
CT Scan
without
contrast
T2 FLAIR T1 CE MRI
CT Scan
Without
contrast
T2 FLAIR
T1 CE MRI
Calcification
Hyperintense
cystic portion

25. Key points
• Can be grade 2- 3
• IDH mutation and 1p/19q codeletion are required for the diagnosis of
oligodendrogliomas.
• Poorly circumscribed
• Internal heterogeneity(96% sensitivity)
• Internal cyst
• Calcification(88% specific)
• Enhancement occurs in roughly half of oligodendrogliomas and is
frequently partial; ring-enhancing or predominantly enhancing
oligodendrogliomas are not typical
• Pathological feature such as perinuclear halos creating fried egg cell
and chicken wire vasculature remain characteristic ,although not
necessary or sufficient for diagnosis.

28. PEDIATRIC TYPE GLIOMAS
Can be classified as:
1. Pediatric type diffuse low grade glioma.
2. Pediatric type diffuse high grade glioma.

29. PEDIATRIC TYPE DIFFUSE LOW GRADE
GLIOMA
( ALL ARE GRADE 1)

31. ANGIOCENTRIC GLIOMA
• Angiocentric glioma is a rare epilepsy-associated neoplasm occurring primarily in
children and young adults and has be.
• Molecularly, angiocentric glioma is characterized by MYB gene alterations.
• This CNS WHO grade 1 tumor is typically peripherally located in the supratentorial
brain Imaging features:
• T2 prolongation,
• Facilitated diffusion,
• Lack of enhancement on MRI scans
• Ribbon-like intrinsic T1 hyperintensity and T2-hyperintense stalk-like extension to the
underlying ventricle .
• Gross total resection typically results in freedom from seizures.

32. Hyperintense
lesion
T1
Hyperintensity
No
Enhancement
T2 Non CE MRI T1 NON CE T1 CE

33. Key points
• T1 hyperintensity in non CE scan.
• Facilitated diffusion.
• Supratentorial
• Peripherally located

34. Diffuse Astrocytoma MYB or MYBL1 Altered
• Grade 1
• No IDH mutation
• No H3 gene mutation
• Highly differentiated.
• Enhancement uncommon.
• T2 hyperintense
• T1 hypointense
• Well circumscribed
• Cyst

36. T2 non CE T1 CE
Hyperintense
non enhancing
Hypointense

37. Polymorphous Low grade Neuroepithelial
Tumor of Young (PLNTY)
• Grade 1
• Molecularly characterized by aberrant Cd34 expression and distinct
methylation signal.
• IDH wild type
• Unequivocal BRAF p.V600E expression
• Superficial cerebral hemispheres with predilection for temporal lobes.
• Well circumscribed
• Heterogenous signal
• Peripheral cyst
• Frequent central coarse calcification.

39. T2 non CE SWI T1 CE
Well circumscribed
with hyperintense
cystic component
Focal central T2 hypointensity
corresponding to dense
calcification
Small enhancement
along tumor margin

41. Diffuse Low Grade Glioma MAPK pathway
Altered

42. • No microvascular proliferation
• No necrosis
• NO IDH mutation
• NO H3 mutation
• No CDKN2A homozygous deletion
• Characterized by MAPK pathway alteration
• May exhibit astrocytic or oligodendroglial morphological
characteristics
• Can occur throughout craniospinal axis
• Heterogenous enhancement and cystic component are often seen,
these are not always present.

44. T2 non CE
Hyperintense mass with poorly
defined margins and cystic c
component
Focal region of solid
enhancement within the
mass

45. PEDIATRIC TYPE DIFFUSE HIGH GRADE
GLIOMA
(All are Grade 4)

46. Pediatric Diffuse High Grade GLIOMA

48. Diffuse Midline Glioma,H3 K27-altered
• IDH wild type.
• Infiltrative tumor harboring a K27M mutation in H3.1 or H3.2
• EGFR altered tumors in children arising in midline may also fall into this group
• loss of expression of H3 K27me3 at immunohistochemistry, presence of this
mutation confers poor prognosis and designate this as CNS WHO grade 4.
• Midline location: Thalamus,brainstem,spinal cord
• Imaging feature are widely variable
• Non enhancing and infiltrative to enhancing and necrotic tumors.

50. T2 FLAIR
Expansile homogenous non enhancing
lesion centered in pons
T1 CE shows lack of enhancement and
effacement of lower 4th ventricle

53. Diffuse hemispheric glioma H3 G34 mutant
• IDH wildtype
• H3.3 p.G34R or p.G34V mutation
• Pathognomic molecular feature is missense mutation at position 34
of histone H3.3 protein
• Hemispheric location, supratentorial nonmidline
• Leptomeningeal contact
• Older children and younger adults

57. Diffuse Pediatric type High grade Glioma H3
Wildtype and IDH wild type
• Aggressive pediatric brain tumor
• NO IDH mutation
• NO histone mutation
• Microvascular proliferation and necrosis
• Most pediatric radiation induced high grade gliomas are H3 wild type
and IDH wild type
• Often resembles glioblastoma

58. Key Molecular features :
1-PDGFRA alteration
2-EGFR alteration
3-MYCN amplification

59. T2 non CE T1 CE
Well circumscribed
solid and cystic mass
Thin
peripheral
enhancement

60. Infant type hemispheric glioma
• Malignant
• 1st year of life
• Supratentorial
• Molecular pathogenesis:

61. CT scan without
contrast
Multiple cystic
spaces and a small
region of dense
calcification
T2 Flair
T1 CE

62. T2 FLAIR
Hyperintense periphery pf tumor cyst which have
proteinaceous content .
Marked enlargement of ventricular system (arrow
heads)
Without periventricular edema
Possibly reflecting longstanding communication
hydrocephalus from tumor seeding and /or
underlying parenchymal volume loss