TUMOURS OF THE CENTRAL NERVOUS SYSTEM

FM Brett MD., FRCPath

At the end of this lecture you should be able to:

1. Give basic classification of CNS tumours2. Understand how patients present3. Know the common tumours in children and adults4. Know what is meant by paraneoplastic syndromes5. Know that concept of benign and malignant meaningless when applied to CNS tumours

CLASSIFICATION OF CNS TUMOURS

1. Intrinsic tumours – account for virtually all tumours in children and 60% of primary CNS tumours in adults

2. Extrinsic tumours – arising from cranial and spinal nerves and dura.

3. Tumours arising from adjacent structures i.e pituitary gland and metastatic tumours.

The pathologist and CNS neoplasms

Clinical details of importance~ Age~ Sex~ F/X~ Site of neoplasm

INCIDENCE;

~ Second commonest form of cancer in childrenAccounts for 3.5% of all deaths in the 1-14 year age group

Sixth commonest cause of cancer deaths in adults25% of all tumors in adults are in the brain and 35% are neurectodermal and 40% are metastatic

~ Most primary tumors are sporadic andof unknown aetiology

~ Secondary tumors vary greatly between 14-40%

~ Fewer than 5% are associated with hereditary syndromes that predispose to neoplasia

Syndrome Gene locus Gene Type of CNS tumourNF type 1 17q11 NF1 Neurofibromameningio

ma, optic nerve gliomaNF2 22q12 NF2 Meningioma,

schwannomaTS 9q34,16p13 TSc1/TSC2 SEGAVHL 3p35 VHL HaemangioblastomaLi-Fraumani

17q13 p53 glioma

Gorlin’s syndrome

9q31 PNET

Heritable syndromes with increased risk of CNS tumours

CNS neoplasms present with:

~ epilepsy (focal or generalised)~ focal neurologic deficits~ symptoms and signs of raised ICP~ symptoms and signs of hydrocephalus

SSites of cerebral tumorsSites of cerebral tumors

ADULTSSupratentorial tumors account for 90%

Therefore increased incidence of epilepsy and decreased incidence of headache

Posterior fossa tumours cause headache and vomiting as early features

CHILDRENCerebellum

PonsOptic nerve/chiasm

SUPRATENTORIAL TUMORS ARE RARE

ThereforeHeadache, vomiting, visual disturbances

commonEpilepsy - unusual

DiagnosisDiagnosis

1. Clinical picture

2. CT or MRI scan

3. Biopsy ~ smear~ Frozen section~ paraffin section

Factors in the aetiology of CNS neoplasms1. Sex – gliomas commoner in males

meningiomas commoner in females2. Exposure to ionizing radiation implicated in the genesis of~ meningiomas~ gliomas~ nerve sheath tumors3. Primary CNS lymphoma – is associated with immunodeficiency4. Nitroso compounds cause CNS neoplasms in animals5. No convincing convincing evidence has linked CNS neoplasms

with trauma, occupation, diet, electromagnetic fields

Prognostic factors in CNS tumorsPrognostic factors in CNS tumors

~ Patient characteristics

~ Tumour characteristics

Patient characteristicsPatient characteristics

~ Age

~ General physical characteristics

~ Extent of surgical resection

Tumour characteristicsTumour characteristics

~ Specimen procurement

~ Phenotypic analysis

~ Proliferative capacity

EFFECTS OF TUMOUREFFECTS OF TUMOUR

1. Local destruction of neural tissue2. Oedema3. Distortion of neural tissue4. Raised ICP

Grading of Gliomas (WHO)

Grade 1 – 1V – based on presence of pleomorphism, mitoses, vascular proliferation and necrosis

Median Overall Survival AA – 3-5 yearsOS GBM – 1 year

Secondary GBM – younger patients with pre-existing lower grade glioma

Primary – 60-70

Primary GBM – high frequency of RGFR amplification-p16 loss

-Secondary GBM – TP53 mutations

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

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

Prognosis

Benign and malignant are meaningless

with respect to brain tumors. It is the

technical aspects that determine the

prognosis

Haemorrhage andmidline shift

Raised ICP

~ As neoplasm grows – contents of the skull are compressed~ Within the skull brain occupies 1400mlsCSF 100-200mls and blood 100-150mls~ Displacement of CSF and blood compensate initially for mass effect~ Then ICP rises quickly mass effect compression vascular insufficiency

IC

ICP Herniations

~ Subfalcine herniation~ Tentorial herniation~ Tonsillar herniation

FALSE LOCALISING SIGNSFALSE LOCALISING SIGNS

~ Occulomotor nerve compression~ Abducens nerve compressed againstthe petrous ligament~ Ipsilateral hemiparesis – from compression of the cerebral peduncle against the tentorium~ PCA infarction from compression of the artery against the tentorium

Under the age of 16, 75% occurIn the posterior fossa

~ Pilocytic astrocytoma~ Ependymoma~ Medulloblastoma

Medulloblastoma

ChildhoodMale predominance

Medulloblastoma – seeding down the cord

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

Neuroectodermal tumours

Prognosis depends on

a. Siteb. histology

Meningiomas

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

Meningioms

Clinical presentation depends on:a) Siteb) Rapidity of growth

Prognosis – ~ benign (usually)~ slowly growing~ often can be completelyexcised

Meningiomaarising from the falxcerebri

Spinal cord tumors

1. Extradural – metastatic carcinoma, myeloma, lymphoma

2. Intradural (extramedullary) - meningioma

schwannoma3. Intramedullary - gliomas

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

Case History

~ Patient transferred with a history ofHeadaches and drowsiness

~ Microcytic hypochromic anaemia, Thrombocytopenia

~ CT – hydrocephalus – no known cause

~ EVD inserted

~ IVH

~ RIP

E. O. N

Admitted on 02/10/00 with stridor and Personality changeProgressive deteriorationInfective screen negative

? sCJD? ?

Investigations

CSF – NADMRI - ?EEG - NAD

PM A50/01

Paraneoplastic encephalomyelitis

Tumour mass 8x6x4 cm, wt 120gmsAnterior, inferior and left lateral to the Thyroid

Paraneoplastic encephalomyelitisParaneoplastic 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

Include:

1. Encephalitis2. Cerebellarr cortical degeneration3. Myopathy4. Peripheral neuropathy5. Necrotising myelopathy

AB AntiYo

Anti HU Anti Ri AntiCAR

Neurologicalsynd

Cerebellar deg

Encephalomyelitis

Opsoclonus-ataxia

retinopathy

ICC Cytoplas PC and Ov ca

Nuclei neuronestumors

Nuclei of CNS neurones,breast and lung ca

Retinal neurones, rods, cones

Benign cystic lesions in the brain that may cause sudden death

~ colloid cyst of the third ventricle~ Other cystic lesions

A209/01

CONCLUSION

1. Brain tumours classified into intrinsic,extrinsic and spread from adjacent structures

2. Adults usually present with supratentorial tumours3. Commonest primary tumour in adults gliomas. >65

metastatic tumours common4. Paraneoplastic syndromes – non-metastatic

complications of an underlying malignancy.