This document discusses central nervous system (CNS) tumors. It begins by dividing CNS tumors into primary tumors, which originate in the brain, and secondary tumors, which have metastasized from other parts of the body. It then covers various types and grading systems of CNS tumors, including gliomas, the most common primary malignant brain tumors. Specific low-grade gliomas such as astrocytomas, oligodendrogliomas, and oligoastrocytomas are discussed in detail. Treatment options mentioned include observation, supportive care, surgery such as biopsy or resection, and chemotherapy or radiation.

1. Dr. Parag Moon
Senior resident,
Dept. of Neurology
GMC, Kota

2.  CNS tumors can primarily be divided into
 Primary -originates in the brain (solitary, nodular)
 Secondary-made up of cells that have spread (metastasized)
to the brain from somewhere else in the body.
 Multiple in number, prior h/o cancer , edema +, located at
gray white interface.
 May lodge into
- Brain parenchyma – most common area of metastases
- Leptomeninges – pia mater & arachnoid mater
- Dural space

3.  Tumors of Neuroepithelial Tissue
 Tumors of Cranial and Spinal Nerves
 Tumors of Meninges
 Lymphomas and Hematopoietic
Neoplasm
 Germ Cell Tumor
 Tumors of Sellar Regions (pituitary
/craniopharyngioma)
 Metastatic Tumors

4.  Many grading systems (e.g., Kernohan, St.
Anne-Mayo, and Ringertz systems)
 Most of these grading systems share an
assessment of nuclear abnormalities,
mitoses, endothelial proliferation, and
necrosis

5.  WHO grade I – low proliferative potential.
Possible cure with surgery alone
 WHO grade II – infiltrating, but low in mitotic
activity. Can recur and progress to other
grades
 WHO grade III – Histologic evidence of
malignancy (mitotic activity), infiltrative,
anaplastic
 WHO grade IV – mitotically active, necrosis,
rapid pre and post-surgical progression

6. Cell of origin can be
1. Astrocytes
2. Oligodendrocytes
3. Ependymal cells
4. Mixed
 Identified by glial fibrillary acidic protein
(GFAP) and S100

7.  Gliomas-Most common (80%) primary
malignant brain tumours.
 Gliobastoma accounts for 54%.
 Most common is astrocytoma (including
gliobastoma)-76%.
 Slight male preponderance.
 More common in whites.

8.  Exposure to ionizing radiations is the only
definite risk factor
 They are common in;
 NF type I (15 – 20% develop LGGs)
 NF type II
 Tuberous sclerosis
 Li-Fraumeni syndrome
 Environmental exposure to Nitrites/Nitrates
(nitrosamines/amides)
 Radiofrequency radiation.
 Electromagnetic field radiation(EMF)

9.  Allergies/IgE levels association
 Vit. E and C consumption.
 Head trauma
 Tobacco, alcohol consumption
 p53 gene mutation (a consistent finding)
 1p/19q mutations in tumours transforming
to high grade

10. Genetics

11.  Well circumscribed both grossly and
radiologically.
 More common in cerebellum, third ventricle,
hypothalamus, optic nerve, spinal cord,
dorsal brainstem.
 Cerebellar-large fluid filled cyst with
enhancing nodule.
 Hyothalamus, optic nerve- solid tumours.
 Outcome excellent (80% 20-year survival)

12.  Biphasic pattern- compact pilocytic areas
with interspersed microcytic, loose and
spongy areas.
 Rosenthal fibres
 Mulberry shaped eosinophilic granular
inclusion
 Pilomyxoid astrocytoma-variant, more
aggressive, affects children younger than 3
years

13. Fig 2.4B: Axial T1 Wtd. MRIFig 2.4A: Axial T2 Wtd. MRI Fig 2.4C: Post-Contrast Axial T1 Wtd. MRI
A large cystic tumor (yellow arrow) with a mural enhancing nodule (red arrow) is seen within the left cerebellar
hemisphere.
DIAGNOSIS: PILOCYTIC ASTROCYTOMA
• Grade I Astrocytoma (WHO Classification)
• Children and young adults
• Imaging Features: cyst within enhancing tumor nodule.

14.  Well differentiated, low grade, simply
astrocytoma.
 Median age at diagnosis-35 years.
 Brainstem gliomas-childhood
 Ill defined non enhancing cerebral masses.
 Grossly poorly circumscribed.
 Lacks mitotic activity, microvascular
proliferation and necrosis
 Low MIB(Ki-67) proliferative index.

15.  90%-mutation in IDH1 and IDH2 encoding for
isocitrate dehydrogenase in citric acid cycle.
 IDH1 mutation-prognostic significance
 50%- loss of 17p and mutation in TP53.

16. Axial T1 Wtd. MRIAxial Flair MRI Post-Contrast Axial T1 Wtd. MRI
Non-enhancing tumor (arrow) involving the right temporal lobe.
GRADE II ASTROCYTOMA (LOW GRADE)
• Children and young adults
• Imaging Features: Non-enhancing tumors. Calcification can be seen.

17.  Mean age- fouth or fifth decade
 Some contrast enhancement on MRI.
 More cellular than grade II
 Presence of mitotic figures.
 High Ki67/MIB index
 High incidence of progression to GBM
 High frequency of TP53, IDH1, IDH2, RB, PTEN
 EFGR mutation-worse prognosis.
 Relative survival at 2 years-40% and at 5 years-
27%

18. Fig 2.2B: Axial T1 Wtd. MRIFig 2.2A: Axial Flair MRI Fig 2.2C: Post-Contrast Axial T1 Wtd. MRI Fig 2.2D: Post Contrast Coronal T1 Wtd. MRI
An ill-defined non-enhancing tumor (yellow arrows) is seen in the left parietal lobe with spotty areas of
enhancement (red arrows).
DIAGNOSIS: Anaplastic Astrocytoma
• Grade III Astrocytoma (WHO Classification)
• Usually seen between 40 – 60 years of age
• Imaging Features: Ill-defined non-enhancing tumor with or without
feeble enhancement.

19.  Previously known as glioblastoma multiforme
 Peak age of onset is 50-60yrs.
 Common in deep white matter, basal ganglia,
thalamus, rarely in cerebellum
 Grossly may appear circumscribed
 Microscopic infiltrates widely, often to other
hemisphere via corpus callosum.
 Multifocal
 Extracranial metastasis rare.
 Survival 1-1.5 yrs after treatment.

20.  Central yellow or white zone of necrosis and
hemorrhage surrounded by hyperemic ring of
endothelial hyperplasia.
 Surrounded by edematous brain (mixture of
vasogenic edema, tumour infiltrates and
gliosis)
 TP53, IDH1 and IDH2 mutation less common
in primary.
 30-40% have EFGR mutation
 MGMT mutation- favorable prognosis.

21.  Primary GBM
◦ Develops de novo from
glial cells
◦ Accounts for > 90% of
biopsied or resected cases
◦ Clinical history of 6 months
◦ Occurs in older patients
(median age: 60 years)
◦ EFGR mutation
 Secondary GBM
◦ Develops from low-grade or
anaplastic astrocytoma
 ~ 70% of lower grade
gliomas develop into
advanced disease within
5-10 years of diagnosis
◦ Comprises < 5% of GBM
cases
◦ Occurs in younger patients
(median age: 45 years)
◦ TP53, IDH1, IDH2

22. Fig 2.1B: Axial T1 Weighted
(Wtd.) MRI
Fig 2.1A: Axial Flair MRI Fig 2.1C: Post-Contrast Axial T1
Wtd. MRIAn irregular enhancing ring lesion (arrow) is seen involving the left parietal lobe. Tumor is associated with
edema (E) best noticed on FLAIR image (A).
DIAGNOSIS: GLIOBLASTOMA
E
• Grade IV Astrocytoma (WHO Classification)
• Older Patient
•Imaging Features: Tumor with irregular peripheral enhancement with
central necrosis.

23.  Average age of diagnosis-26 yrs.
 Involve cerebral cortex and overlying
meninges most common in temporal lobe.
 Bizzare giant cells
 Xanthomatous cells-foamy lipid filled
astrocytes seen in 1/4th cases.
 15-20% have malignant transformation.
 Survival 81% at 5 yrs and 70% at 10 yrs.

24. large well defined cystic mass in right temporo-parieto-occipital
region with mild vasogenic oedema and mass effects. Post-contrast rim
like enhancement of the cystic mass, with enhancing mural nodule

25.  Associated with tuberous sclerosis
 Gross- elongated, sausage like or lobulated
 Candle guttering-identical smaller masses on
walls of ventricle.
 Rich vascularity
 Pseudo-rosettes
 Hydrocephalus
 TSC1 and TSC2
 Inhibitors of mTOR found effective.

26. Hypo- to isointense to gray matter on T1, heterogeneously hyperintense
on FLAIR , T2 punctate hypointensities corresponding to calcium with
avid contrast enhancement.

27.  Seen in young to middle aged adults.
 Most common in frontal lobe
 Histopath- uniform round nuclei, bland
chromatin, perinuclear halo-Fried egg
 Rich branching capillary network-Chicken
wire
 50-80%-loss of 1p and 19q
 Favorable response to chemotherapy
 IDH1 and IDH2 mutation in grade II (84%) and
grade III (94%).

28. Hypointense on T1 hyperintense on T2 with no contrast enhancement
mass in rt. Frontal lobe.

29.  Most difficult to define
 Survival between astrocytoma and
oligodendroglioma.
 Usually grade and treated as
oligodendroglioma.

30.  Most common in first decade.
 Age<3 years have worse prognosis
 Children-infratentorial
 Adult-spinal
 Well circumscribed mass that compresses and
not infiltrates surrounding parenchyma
 May seed subarachnoid space in 5%
 Perivascular rosettes
 22q deletion in NF2 mutation-spinal
ependymoma.

32.  Seen in filum terminale
 More common in adults
 Thin collagenous capsule
 Prognosis excellent if capsule intact
 May metastasize to lungs

33. Hypointense mass on T1 and hyperintense with some hypointense signal
within due to hemorrhage within on T2

34.  Seen in adults
 Small and incidental
 Glistening pearly white lobulated
intraventricular proteburance
 Most often in fourth ventricle
 May cause hydrocephalus
 Low proliferative index

35.  Presenting symptoms determined by
 Tumour’s size,
 Location
 Rate of growth

36.  Classically (17%) starts in early morning and
disappears soon after pt. gets up
 Initially mild, becomes progressively more
severe, frequent and of longer duration
 Worse with Valsalva manoeuvre
 Associated with nausea,vomiting
 Forsyth, Posner(1993) showed tension-type
headache(77%), migraine-like headache
(9%),14% had mixture of headaches could not
be easily classified

37.  Forsyth (1993)- commonest headache site
was frontal region (68%) seen primarily in
supratentorial tumours or with raised ICT.
 73% of patients with infratentorial tumours
had frontal, temporal or parietal headaches
and 24% had nuchal and occipital.
 Related to size of tumour and amount of
midline shift.
 Produced due to traction on pain-sensitive
structures such as blood vessels, dura or
obstruction of CSF pathways

38. Recommendation Level
A patient with new onset or recurrent headache
uncharacteristic for that patient should also be
imaged, particularly if there are focal neurological
symptoms and signs.
III

39. Other symptoms
 Limb weakness
 Language disturbances
 Apraxia, agnosia
 Amnesia
 Depression
 Seizures- most common partial motor often
with secondary generalization
 Plateau waves- paroxysmal neurological
symptoms on standing

41. ◦ A discrete or diffuse hypodense to isodense mass
lesion
◦ Minimal or no enhancement (except in 15 – 30%
patients)
◦ Calcifications
(Oligodendrogliomas/Oligoastrocytomas)
◦ Cystic changes (any histologic type)

43. ◦ Hypo- to Iso-intense on T1WI
◦ Hyperintense on T2WI
◦ Minimal- to NO gadolinium enhancement
 (25 – 50% oligodendrogliomas are somewhat enhanced)
◦ No significant mass effect
◦ Tendency to invade & reside in white matter
 Oligodendrogliomas expands along gyri
◦ Calcifications (20% lesions)

45.  T1-weighted MRI with contrast may
underestimate the extent of an LGG
 The true extent is shown on the T2-
weighted sequences,
 Diffusion tensor MRI used as a marker of
glioma infiltration

46.  Reduced NAA peaks
 Increased choline peak
 Increased choline/creatinine ratio
 Choline/creatinine peak>3:1 predicts high
grade tumour.

48. Malignant Transformation:
LGG transformation ranges from 17% to 73% in
clinical studies
Risk of progression increases with tumour
burden
Growth rate of ≥ 8 mm per year  Median
survival of 5.16 years
Growth rate ≤ 8 mm/year  median survival of
≥ 15 years
Residual tumour after surgery is an important
determinant

49. Observation:
 Advantages:
 No surgical morbidity
 Lesser cost of follow up treatment
 Disadvantages:
 Loss of histological diagnosis
 Loss to follow up (quite frequent than reported)
 Risk of increased malignant transformation
 Risk of increasing tumour burden/neurodeficits

50.  Supportive treatment
 Antiepileptics- leviteracetam preferred.
Prophylactic antiepileptics not recommended.
 Enzyme inducers avoided.
 Steroids- Dexamethasone most commonly
used.
 Usual dose 8-16mg daily dose.

51. Surgical intervention:
 Open resection
 Open/stereotactic biopsy
 Guided by patient’s clinical status, location of tumour &
surgeon’s preference
 Goals of surgery:
 Establishing a diagnosis
 Symptoms alleviation
 Decompression
 Tumour cytoreduction

52. Biopsy:
 Open/Image guided or stereotactic (if available)
 Indicated in high risk patients or when open surgery is
declined/deferred
 Advantages:
 Minimally invasive
 Early identification of histologic type
 Disadvantages:
 Morbidity/mortality with open biopsy
 Image guided biopsy may sample wrong site
 Stereotactic biopsy may be too small for a diagnosis

53. Surgical Resection:
 It is the principle mode of treatment in the following;
 Whenever possible
 Mass effect
 Raised ICT
 Steroid resistant edema
 Threat of herniation
 CSF flow obstruction
 Seizure control
 Smaller tumours are less aggressive & better surgical
candidates

54. Surgery has limited role in following;
 Disseminated tumours
 Multifocal tumours
 Eloquent location
Extent of Resection:
◦ Recent evidence favouring early extensive resection
◦ Good life expectancy
◦ Influencing malignant transformation
◦ Progression free survival & overall survival both
improves

55.  Radiation for Pilocytic astrocytoma after surgery may be
reserved until recurrence or deep lesions
 Fractionated radiation of up to 45-60 Gy (more
focussed, more good)
 Hyperfraction protocol
 Provided to T2 abnormality and margin of 1.5 to 2 cm
 In sharply demarcated tumour 0.5cm margin suffice
 Adjvunt to surgery
 Malignant transformation may be treated with radiation
 Steriotactic radiosurgery-useful in well circumscribed
tumour.
 Brachytherapy

56. Chemotherapy:
 PCV (Procarbazine, Lomustine, Vincristine) may have a
role in stabilising tumour growth
 Temozolomide may have a role for progressive
astrocytoma
 Oligodendroglioma- chemosensitive
 Recurrence of anaplastic astrocytoma and glioblastoma
multiforme

57.  Methylating agent
 Principal mechanism is causing damage to DNA
of tumour cell, leading to cell death
 Taken orally, rapidly absorbed
 Penetrates the blood-brain barrier
 TMZ 75 mg/m2 PO QD for 6 weeks, then 150-
200 mg/m2 PO QD on Days 1-5 every 28 days
for 6 cycles
 Used with radiotherapy

58.  No consensus
 Low dose temozolomide (+/- procarbazine)
 Carboplatin
 BCNU/CCNU
 Bevacizumab (+/- Irinotecan)
 EFGR inhibitors (geftinib)
 PDGFR inhibitors (imatinib)
 Clinical trials if possible

59.  BCNU(carmustine)-
infused wafers
 Implanted to tumour
bed at time of surgery
 Chemotherapy
released to
surrounding brain
tissue over a period of
2 to 3 weeks
 Clinical trials showed
survival benefit

60.  Prognosis
◦ Extremely young patients<3yrs or patients > 50 y
◦ Large tumours that enhance
◦ Short clinical history
◦ Absent of mental changes
◦ Cerebellar location
◦ High grade
◦ Completeness of surgical lesion
◦ Evidence of progression on imaging studies

61.  Clinical course is by no means benign as is manifested
by histology & radiologic appearance
 Aggressive early resection advised but NOT on the
expense of patient’s quality of life
 Diagnosis purely on the basis of radiology has a failure
rate of up to 50%
 Early histologic evidence of the diagnosis is paramount
both for the surgeon & the patient
 Chemo-radiotherapy can be delayed until recurrence
or progression in low grade gliomas.

62. Thanks

63.  Clinical practice guidelines for management
of gliomas: Clinical oncological society of
Australia; Aug2009.
 Malignant Gliomas in Adults;Patrick Y. Wen,
Santosh Kesari:N Engl J Med 2008; 359:492-
507
 Guidelines on management of low-grade
gliomas: report of an EFNS–EANO* Task
Force; European Journal of Neurology 2010,
17: 1124–1133

64.  High Grade Gliomas: Pathogenesis,
Management And Prognosis;ACNR :VOLUME
12 NUMBER 4 ;SEPTEMBER/OCTOBER 2012
 Practical Guidelines for the Treatment of
Malignant Gliomas;Marc C., Patty A., WJM,
February 1998-Vol 168, No. 2