1. TUMOURS OF THE CENTRAL NERVOUS SYSTEM
FM Brett MD., FRCPath

2. At the end of this lecture you should be able to:
Give basic classification of CNS tumours
Understand how patients present
Know the common tumours in children and adults
Know what is meant by paraneoplastic syndromes
Know that concept of benign and malignant
meaningless when applied to CNS tumours

3. CLASSIFICATION OF CNS TUMOURS
Intrinsic tumours – account for virtually all tumours in children and 60% of primary CNS tumours in adults
Extrinsic tumours – arising from cranial and spinal nerves and dura.
Tumours arising from adjacent structures i.e pituitary gland and metastatic tumours.

4. The pathologist and CNS neoplasms Clinical details of importance
~ Age
~ Sex
~ F/X
~ Site of neoplasm

5. INCIDENCE; ~ Second commonest form of cancer in children
Accounts for 3.5% of all deaths in the 1-14
year age group
Sixth commonest cause of cancer deaths in adults
25% of all tumors in adults are in the brain and 35%
are neurectodermal and 40% are metastatic

6. ~ Most primary tumors are sporadic and
of unknown aetiology
~ Secondary tumors vary greatly
between 14-40%
~ Fewer than 5% are associated with
hereditary syndromes that predispose
to neoplasia

7. Heritable syndromes with increased risk of CNS tumours
Gene locus
Gene
Type of CNS tumour
NF type 1
17q11
NF1
Neurofibromameningioma, optic nerve glioma
NF2
22q12
Meningioma, schwannoma TS
9q34,16p13
TSc1/TSC2
SEGA
VHL
3p35
Haemangioblastoma
Li-Fraumani
17q13
p53
glioma
Gorlin’s syndrome
9q31
PNET

8. CNS neoplasms present with:
~ epilepsy (focal or generalised)
~ focal neurologic deficits
~ symptoms and signs of raised ICP
~ symptoms and signs of hydrocephalus

9. SSites of cerebral tumors
ADULTS
Supratentorial tumors account for 90%
Therefore increased incidence of epilepsy and decreased incidence of headache
Posterior fossa tumours cause headache
and vomiting as early features
SSites of cerebral tumors

10. CHILDREN Cerebellum Pons Optic nerve/chiasm
SUPRATENTORIAL TUMORS ARE RARE
Therefore
Headache, vomiting, visual disturbances common
Epilepsy - unusual

11. Diagnosis 1. Clinical picture 2. CT or MRI scan Biopsy ~ smear
~ Frozen section
~ paraffin section

13. Factors in the aetiology of CNS neoplasms
1. Sex – gliomas commoner in males
meningiomas commoner in females
Exposure to ionizing radiation implicated
in the genesis of
~ meningiomas
~ gliomas
~ nerve sheath tumors
Primary CNS lymphoma – is associated with
immunodeficiency
Nitroso compounds cause CNS neoplasms in animals
No convincing evidence has linked CNS neoplasms with trauma, occupation, diet, electromagnetic fields

14. Prognostic factors in CNS tumors
~ Patient characteristics
~ Tumour characteristics

15. Patient characteristics
~ Age
~ General physical characteristics
~ Extent of surgical resection

16. Tumour characteristics
~ Specimen procurement
~ Phenotypic analysis
~ Proliferative capacity

17. EFFECTS OF TUMOUR Local destruction of neural tissue Oedema
Distortion of neural tissue
Raised ICP

18. Grading of Gliomas (WHO)
Grade 1 – 1V – based on presence of pleomorphism,
mitoses, vascular proliferation and necrosis
Median Overall Survival AA – 3-5 years
OS GBM – 1 year
Secondary GBM – younger patients with pre-existing
lower grade glioma
Primary – 60-70

19. Primary GBM
– high frequency of RGFR amplification
p16 loss
Secondary GBM – TP53 mutations

20. Oligodendroglioma
~ Concurrent deletion of 1p and 19q
In AO – good response to DXT and chemo
~ Criteria for anaplasia – nuclear pleomorphism,
mitotic activity, endothelial vascular hyperplasia
and necrosis
~ For anaplasia 2 features – one of which frequent
mitoses or VEH

21. Predictive Markers in Malignant Gliomas
~ 1p19q loss in AO associated with
enhanced chemosensitivity and longer
overall survival
~ MGMT status in GBM inc responsivness to temezolamide
~ EGFR – inc in GBM

22. Prognosis Benign and malignant are meaningless
with respect to brain tumors.
It is the
technical aspects that
determine the
prognosis

24. Haemorrhage and
midline shift

25. Raised ICP ~ As neoplasm grows – contents of the skull are compressed
~ Within the skull brain occupies 1400mls
CSF mls and blood mls
~ Displacement of CSF and blood compensate
initially for mass effect
~ Then ICP rises quickly mass effect
compression vascular insufficiency

26. ICP Herniations IC ~ Subfalcine herniation ~ Tentorial herniation
~ Tonsillar herniation

27. FALSE LOCALISING SIGNS
~ Occulomotor nerve compression
~ Abducens nerve compressed against
the petrous ligament
~ Ipsilateral hemiparesis – from
compression of the cerebral peduncle against
the tentorium
~ PCA infarction from compression of the
artery against the tentorium

29. Under the age of 16, 75% occur In the posterior fossa
~ Pilocytic astrocytoma
~ Ependymoma
~ Medulloblastoma

30. Medulloblastoma
Childhood
Male predominance

31. Medulloblastoma – seeding down the cord

32. Ependymoma
~ childhood
~ Often occur in areas where complete surgical excision is
impossible

33. Neuroectodermal tumours
Prognosis depends on
Site
histology

34. Meningiomas ~ Older adults usually female
~ Increased incidence in Von Recklinhausen disease
~ Association between meningiomas and breast cancer

35. Meningioms Clinical presentation depends on: Site Rapidity of growth
Prognosis – ~ benign (usually)
~ slowly growing
~ often can be completely
excised

36. Meningioma
arising from the falx
cerebri

38. Spinal cord tumors
Extradural – metastatic carcinoma,
myeloma, lymphoma
Intradural (extramedullary) meningioma
schwannoma
3. Intramedullary - gliomas

39. Metastatic tumours in Adults
~ Common
~ Over the age of 65 – commonest variety of intracerebral neoplasm
~ Mets in children uncommon but CNS well recognised site for relapse of ALL

42. Case History ~ Patient transferred with a history of
Headaches and drowsiness
~ Microcytic hypochromic anaemia,
Thrombocytopenia
~ CT – hydrocephalus – no known cause
~ EVD inserted
~ IVH
~ RIP

44. E. O. N Admitted on 02/10/00 with stridor and Personality change
Progressive deterioration
Infective screen negative
? sCJD
? ?

45. Investigations
CSF – NAD
MRI - ?
EEG - NAD

51. PM A50/01 Paraneoplastic encephalomyelitis
Tumour mass 8x6x4 cm, wt 120gms
Anterior, inferior and left lateral to the
Thyroid

52. Paraneoplastic encephalomyelitis
~ neurological disorders of unknown cause
associated with systemic malignancy
~ Subacute progressive course over mths – years
~ May precede follow or occur simultaneously
with a systemic cancer

53. Include: Encephalitis Cerebellarr cortical degeneration Myopathy
Peripheral neuropathy
Necrotising myelopathy

54. AB Anti Yo Anti HU Anti Ri CAR Neurological synd ICC Cerebellar deg
Encephalo
myelitis
Opsoclonus-ataxia
retinopathy
ICC
Cytoplas PC and Ov ca
Nuclei neurones
tumors
Nuclei of CNS neurones,breast and lung ca
Retinal neurones, rods, cones

55. Benign cystic lesions in the brain that may cause sudden death
~ colloid cyst of the third ventricle
~ Other cystic lesions

56. A209/01

57. CONCLUSION 1. Brain tumours classified into intrinsic,
extrinsic and spread from adjacent structures
Adults usually present with supratentorial tumours
Commonest primary tumour in adults gliomas. >65
metastatic tumours common
Paraneoplastic syndromes – non-metastatic complications of an underlying malignancy.