Neurology - Brain tumours

Question 1

When are the 2 main peaks of incidence for brain tumours?

Answer 1

• First decade (children)
• Sixth decade (elderly)

In children, brain tumours are the second most common cancer after leukaemia’s

Brain tumours are the sixth most common neoplasm in adults

Question 2

Where are tumours most likely to be located in children and adults?

Answer 2

Children - 70% occur in the posterior fossa and are mostly intrinsic

Adults - 70% occur supratentorially and intrinsic and extrinsic tumours both frequently occur

Question 3

How do brain tumours produce their clinical effects?

Answer 3

There are 2 mechanisms:

1) Mass effect - many tumours present with non specific signs and symptoms of SOLs without any localising signs. Vasogenic oedema around the neoplasm may potentiate the mass effect:
- Headache (worse on coughing, bending, morning)
- Drowsiness (late on)
- Generally brisk reflexes
- False localising signs (III, VI palsy)
- Papilloedema

2) Local effects - depend on the site of growth

Question 4

What are the features of early and late papilloedema?

Answer 4

Early papilloedema:
- Mild venous engorgement + loss of venous pulsation

Late papilloedema:

• Blurred disc margin
• Venous engorgement ++
• Haemorrhage

Question 5

Features of supratentorial tumours

Answer 5

• Mass effect (tumour) - surrounding oedema is very sensitive to steroids
• Herniation of brain through the tentorium
• Ipsilateral III nerve palsy
• VI nerve palsy (either side i.e. “false localising sign”)

Question 6

Features of infratentorial tumours

Answer 6

• Specific defects
• Early hydrocephalus from obstruction of cerebral aqueduct of Sylvius (this produces ++ papilloedema, ++ headache and early reduced GCS)

Question 7

What are intrinsic brain tumours?

Answer 7

These are the commonest group of primary brain tumours and occur within the substance of the brain itself.

They account for almost all primary tumours in children and 65% of primary tumours in adults (majority of which are glial in origin)

Intrinsic tumours occur more frequently in men

Question 8

In what groups of patients are astrocytomas more common?

Answer 8

Astrocytomas are tumours derived from glial cells.

They account for 10% of primary tumours in adults but are more frequent in children.

They are more common in the cerebellum in children and cerebral hemispheres in adults.

Question 9

Features of a well differentiated astrocytoma?

Answer 9

Neoplastic cells have similar features to the normal cell type:
- cells have numerous cytoplasmic processes arranged around blood vessels similar to astrocytic processes in normal grey matter

Question 10

In what patient group are glioblastomas more common?

Answer 10

Glioblastoma accounts for around 30% of all adult primary brain tumours. They are extremely rare in children.

They are mostly found in the cerebral hemispheres.

Question 11

What are the histological features of glioblastomas?

Answer 11

Areas of necrosis are a characteristic feature of this neoplasm. They are usually surrounded by nuclei of small malignant cells.

The neoplastic cell population is pleomorphic (they all appear different) and also includes multinucleate cells.

There is also vascular endothelial proliferation.

Question 12

How are most glioblastomas formed?

Answer 12

Some glioblastomas arise de novo.
Most arise as a consequence of dedifferentiation within a pre-existing astrocytoma.

There are several genetic abnormalities in glioma progression - loss of p53 is an early event, followed by RB inactivation and EGFR amplification.

Question 13

What are oligodendrogliomas?

Answer 13

These are another type of tumour arising from glial cells. They account for 3% of all primary CNS neoplasms in adults but are very rare in children.

They are ill defined, infiltrating neoplasms that often occur in the white matter of cerebral hemispheres.

Question 14

What are the features of a well differentiated oligodendroglioma?

Answer 14

Oligodendrogliomas can be graded similarly to astrocytomas.

Neoplastic cells are small, round and uniform. Small foci of calcification are common and there is also an interweaving vascular pattern.

Question 15

What chromosomal losses occur in oligodendrogliomas?

Answer 15

1p and 19q - detection of these losses is important in determining the most appropriate form of treatment.

Question 16

What is an ependymoma?

Answer 16

Ependymomas are tumours that arise from the ependymal surface - usually in the 4th ventricle and project into a CSF pathway.

Most ependymomas are well differentiated and extensive invasion into adjacent CNS structures is uncommon.

NB - a special variant called the myxopapillary ependymoma occurs in the cauda equina region of adults.

Question 17

Where are choroid plexus papilloma’s most commonly found?

Answer 17

These are most commonly found in the lateral ventricle and usually presents with obstructive hydrocephalus due to their papillary structure.

They tend not to infiltrate locally but can spread within the CSF.

Question 18

What is the most common type of primitive neuroectodermal tumour?

Answer 18

This is the medulloblastoma which arises in the cerebellum in children. Growth of these tumours is rapid and extensive local infiltration is common resulting in obstructive hydrocephalus.

These tumours are composed of poorly differentiated small tumour cells.

5 year survival is around 60%.

Question 19

What is a haemangioblastoma?

Answer 19

This is a rare neoplasm that most commonly arises in the cerebellum and forms well defined, frequently cystic masses.

Histologically the tumours are composed of blood vessels separated by irregular stromal cells.

Question 20

What disease are haemangioblastomas a part of?

Answer 20

They are an important component of von Hippel-Lindau syndrome, an autosomal dominant inherited disease with a genetic locus on chromosome 3p

Question 21

When do CNS lymphomas occur?

Answer 21

These are uncommon tumours but primary CNS lymphoma occurs at increased frequency in immunosuppressed patients - e.g. AIDS, renal transplant etc.

EBV virus has been implicated in the pathogenesis of these tumours. Most are high grade non Hodgkins lymphomas of B cell origin and carry a poor prognosis

Question 22

Give examples of some cystic lesions that occur in the CNS

Answer 22

Not all cystic lesions are neoplastic but they tend to present clinically with similar signs and symptoms as CNS tumours.

• Craniopharyngioma - suprasellar region, causing pituitary dysfunction and visual disturbance
• Colloid cyst - in the third ventricle in young children and young adults, causing intermittent hydrocephalus and sudden death
• Dermoid cyst - posterior fossa and lumbar spine in children and young adults causing cerebellar signs and paraplegia
• Epidermal cyst - cerebellar-pontine angle and pituitary region in adults, causing cerebellar signs and pituitary dysfunction respectively

Question 23

What are extrinsic tumours?

Answer 23

These are tumours arising from the coverings of the brain and spinal cord, and from cranial and spinal nerve roots.

They are less common than intrinsic tumours.

Question 24

Where do meningiomas arise from?

Answer 24

Meningiomas arise from the cells of the arachnoid cap (a component of the arachnoid villi). The most frequent sites are the parasagittal region, sphenoidal wing, olfactory groove, and foramen magnum.

They are more common in females (M:F = 2:1)

Question 25

What are the features of meningiomas?

Answer 25

They are smooth lobulated masses which are adherent to the dura and normally well demarcated from the cerebrum.

Infiltration of the adjacent dura and overlying bone is common, but infiltration into the brain is rare. But the brain can be compressed by the meningioma.

Question 26

What disease are multiple meningiomas common in?

Answer 26

Neurofibromatosis type 2

Question 27

What are “psammoma bodies”?

Answer 27

These are small foci of calcification that are common in meningiomas. Microscopically, meningiomas comprise sheets of fusiform cells in a solid and whorled pattern.

Question 28

What is a schwannoma?

Answer 28

These are tumours derived from Schwann cells in the nerve shealth of the intracranial and intraspinal sensory nerve roots.

Like meningiomas they occur more commonly in females

Question 29

Where do Schwannomas commonly arise?

Answer 29

Vestibular branch of the 8th cranial nerve in the region of the cerebellar-pontine angle - these neoplasms are often known as “acoustic neuromas”

Bilateral 8th nerve tumours are common in neurofibromatosis type 2

Question 30

Neurofibroma

Answer 30

These usually arise on the dorsal nerve roots of the spinal cord and occur mostly in patients with neurofibromatosis types 1 and 2.

Unlike Schwannomas, neurofibromas are not encapsulated but tend to involve the entire nerve root (and occasionally several nerves)

Question 31

Adjacent tumours

Answer 31

Tumours arising in adjacent structures may compress or invade the CNS, producing localising signs or presenting as a SOL. A common example is pituitary adenomas which cause bitemporal hemianopia due to compression of the optic chiasm

Question 32

What tumours commonly metastasise to the CNS?

Answer 32

Commonest metastases occur by haematogenous spread - e.g. carcinomas of the breast, bronchus, kidney, and malignant melanomas

Metastases often occur at the boundary between grey and white matter and present as SOLs with or without localising signs .

They can infiltrate the subarachnoid space producing “carcinomatous meningitis”.

Question 33

What is malignant meningitis?

Answer 33

Spread of tumours to the CNS can be via the bloodstream to the meninges. This can cause diffuse subacute meningitis with headache, stiff neck, and vomiting.

There may also be sequential cranial nerve palsies (especially bulbar palsies)

Question 34

What does CSF show in malignant meningitis?

Answer 34

CSF examination shows:

• Reactive lymphocytosis
• Low glucose
• High protein

CSF serology may show malignant cells

Treatment is usually unsuccessful except in the case of lymphoma

Question 35

What are paraneoplastic disorders?

Answer 35

Loss of genetic regulation in malignant tumours may lead to cell surface expression of proteins normally only found in neurones (“once-neuronal” antigens).

These may initiate an immune response causing damage to the nervous system. Anti neuronal antibodies may be detected but these may not be pathogenic.

Question 36

What are the common features of paraneoplastic disorders?

Answer 36

• Evolution over weeks/ months
• Relentlessly progressive course
• Failure to respond to treatment of the primary tumour or of the immune response (e.g. steroids, IVIg or plasma exchange) - the exceptions being Lambert-Eaton and NMDA receptor antibody associated encephalitis
• Oligoclonal bands in the CSF
• Specific antibodies
• Relatively normal CNS imaging

Question 37

What is neurofibromatosis?

Answer 37

Autosomal dominant inherited condition caused by mutation in a tumour suppressor gene.

It has an incidence of 1 in 3000 and occurs in several patterns. Both types have a 5% association with pheochromocytoma (should be suspected if hypertensive) and Addison’s disease.

Question 38

Features of neurofibromatosis type 1

Answer 38

Type 1 is the peripheral type. It is caused by mutations in the neurofibromin gene and has a very high new mutation rate.

Features:

• Iris hamartoma (lisch nodule)
• Malignant brain tumours (usually astrocytomas of the optic pathway
• Axillary freckling
• Multiple cafe au lait spots (visible by UV light - “Woods lamp”)
• Multiple neurofibroma on peripheral nerves leading to compression neuropathy

Question 39

Features of neurofibromatosis type 2

Answer 39

Type 2 is the central type. It is caused by mutations in the Merlin gene

Features:

• Spinal cord tumour
• Few cafe au lait spots
• Few peripheral neurofibromas
• Bilateral acoustic neuroma/ Schwannoma