CNS neoplasia I: Intracranial tumours

Published on 10/04/2015 by admin

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Last modified 22/04/2025

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CNS neoplasia I

Intracranial tumours

In adults, primary intracranial tumours represent only 3% of tumour-related deaths, and have an annual incidence of 4–7 per 100 000. Intracranial metastases are more common. Intracranial tumours are the second most common tumour in childhood with an annual incidence of 2–3 per 100 000.

Pathology

Intracranial tumours can be divided into intrinsic and extrinsic (Table 1).

Table 1 Approximate frequency of different intracranial tumours

Tumour	Percentage of total	Comments
Intrinsic
Glioblastoma multiforme	20	High-grade glioma; poor prognosis
Astrocytoma	10 (48 in children)	Lower-grade glioma
Metastases	10*	Often multiple
Oligodendroglioma	5	Slow growing. Often frontal or temporal and calcifies
Ependymoma^†	5 (10 in children)	Arise from ependymal lining, usually of 4th ventricle
Medulloblastoma^†	5 (45 in children)	Arise from cerebellum. May metastasize within CNS
Primary CNS lymphoma	Rare except in AIDS	May be multifocal
Extrinsic
Meningioma^†	15	Arise from meninges and indent brain, may erode bone
Pituitary adenoma^†	7	Chiasmatic visual disturbance and endocrine effects
Schwannoma, e.g. of acoustic nerve^†	7	Benign
Other	16	Includes teratomas, pinealomas, etc.

Estimates are taken from a combination of series

† Potentially curable

* Metastases are much more common. This estimate is of those with solitary intracranial metastases

Intrinsic

Intrinsic tumours are within the substance of the brain, either primary or secondary. Primary intracranial tumours do not metastasize outside the CNS, and thus lack a central feature of malignant tumours elsewhere in the body. The concept of malignancy in primary intrinsic CNS tumours is therefore different from tumours elsewhere in the body. Malignancy in cerebral tumours is only a relative term and they are graded according to histopathological appearance (high = more malignant). They can arise from different cell lineages of neuroectodermal origin; gliomas arise from glial cells, and can be divided into specific cell types such as astrocytes (leading to astrocytomas and glioblastoma multiforme), oligodendrocytes (leading to oligodendrogliomas) and ependymal cells (leading to ependymomas). The histological type and grade are the primary determinants of prognosis. Different parts of a tumour may have different grades and a low-grade tumour may suddenly become more aggressive, in association with a change in histological characteristics.

The pattern of tumours differs in adults and children. In adults (see Table 1), 70% of tumours are supratentorial; in children, 70% of tumours are infratentorial.

Secondary intracranial tumours (or intracerebral metastases) occur in up to 20% of patients with cancer at postmortem examination. In most of these patients the primary tumour is known. The difficulty arises when intracranial metastases is the presentation. These most commonly arise from carcinoma of the lung and breast, and melanoma.

Extrinsic

Extrinsic tumours arise from intracranial structures outside the brain substance, most commonly from the meninges, resulting in meningioma, the cranial nerve, producing a Schwannoma or neurofibroma, or the pituitary (p. 96).

Aetiology

The aetiology of most brain tumours is unknown. Hypotheses include the pathological activation of embryonic cell rests, for example in primitive tumours such as teratomas, or the dedifferentiation of mature cells to more primitive cells and neoplastic transformation. The importance of genetic changes is supported by the large number of inherited syndromes of CNS tumours, for example neurofibromatosis (p. 97). There are changes at specific sites of the genome in many tumours, including chromosome 22 loss in up to 70% of meningiomas, P53 gene (involved in DNA repair) in up to 40% of astrocytomas and epidermal growth factor receptor gene amplification in up to 40% of glioblastoma multiforme (GBM). These changes represent an exciting development in understanding but their exact role is unclear; because none is seen in 100% of the appropriate tumour type, other factors must also be important. Endocrine factors are important in some tumours; meningiomas are more common in females, grow more rapidly in pregnancy and may express oestrogen receptors.

Clinical features

Intracranial tumours present with four types of symptoms.

Focal neurological deficit

This is the most common presentation. Tumours may interfere with the function of adjacent neural tissue. As the tumour enlarges, this effect increases, resulting in a progressive focal neurological deficit, depending on the site of the lesion. More malignant tumours usually expand more rapidly and cause a more rapid progression of symptoms.

Raised intracranial pressure

This is the presenting feature in 20% of patients with intracranial tumours and occurs at some stage in 60% of cases. The typical headache of raised intracranial pressure is worse on lying down, bending down or straining and is associated with nausea and vomiting. Initially it may be present each morning and clears after rising. Many patients do not have the classical headache, but there are usually other features: unsteadiness, dulled mentation or drowsiness. Signs include gait ataxia, papilloedema (may be absent), failure of upgaze and false localizing signs: 3rd and 6th nerve palsies. Drowsiness is an ominous sign, suggesting a critically elevated intracranial pressure. Occasionally tumours within the ventricles may cause a sudden, intermittent obstruction to CSF outflow. This causes a sudden severe headache, sometimes with collapse or loss of consciousness.

Epileptic seizures

These occur in 20–50% of tumours affecting the cerebral hemispheres and are focal in onset (p. 74). Low-grade tumours, for example oligodendroglioma or meningioma, may cause seizures 10 or more years before other symptoms.

Endocrine disturbance

This may result from tumours in the region of the pituitary gland (p. 96).

Differential diagnosis

The differential diagnosis depends on the presentation. Other space-occupying lesions can share all the characteristics described above and constitute the main differential diagnoses. These include chronic subdural haematomas, intracranial abscesses and giant aneurysms. Obstructive hydrocephalus from non-malignant causes can closely mimic an intracranial tumour. Other differential diagnoses are considered in the sections on headache and epilepsy.

Investigation

MRI shows over 95% of intracranial tumours. A CT scan may miss small lesions. Often, the differential diagnosis can be narrowed considerably by the site and appearance of the lesion. Multiple lesions suggest metastases and investigations for an extracranial primary source may establish the diagnosis. For single lesions, and sometimes with multiple lesions, intracranial biopsy will be required to achieve a histological diagnosis.

Management of intracranial tumours

Treatment differs depending on the clinical situation, site of the tumour, the eloquence of the related part of the brain and the type of tumour. The objective of treatment will vary, from curative resection of a meningioma (Fig. 1) to palliation in a glioma (Fig. 2). Some rarer tumours have different treatment objectives (p. 96).

Fig. 1 Meningioma. Meningiomas arise from the meninges and have a component attached to the meninges, and may cause bony erosion. They typically have a smooth boundary and they may be calcified. They enhance diffusely with contrast. Common sites are parasagittal, attached to the falx cerebri, in the posterior fossa, attached to the tentorium and at the sphenoid ridge.

Fig. 2 Glioblastoma multiforme. An intrinsic lesion, often with a heterogeneous appearance due to necrosis and cyst formation and considerable oedema. They enhance patchily or may show ring enhancement. The main differential diagnoses are cerebral abscess and metastasis.

The optimum management for most kinds of intracranial tumours has not been established by prospective randomized clinical trials. Especially difficult is the management of low-grade gliomas whose natural history is only being observed following the advent of improved brain imaging.

Presurgical management

The cerebral oedema related to the tumour may respond temporarily to steroid therapy: usually dexamethasone. Intravenous mannitol may achieve a rapid but transient reduction if the intracranial pressure is critically elevated. The arterial blood pressure should be maintained to overcome raised intracranial pressure and maintain cerebral perfusion. Adequate fluid balance and sometimes inotropes may be needed. Artificial ventilation with hyperventilation may produce hypocarbia, causing cerebral vasodilatation and increasing brain tissue perfusion.

Seizures are treated as focal epilepsy (p. 76). In the emergency situation, a loading dose of intravenous phenytoin is often used.

Surgical treatment

Resective surgery

Certain tumour types may be cured by resection, especially extrinsic tumours, for example meningioma.

Palliative surgery

This may be undertaken where the tumour cannot be resected. Intrinsic tumours do not have a clear margin to allow resection and a purely surgical cure is not possible. There are two types of procedure:

1. Biopsy, aiming to establish the diagnosis with minimum brain damage; image-guided techniques are helpful.

2. Debulking procedures.

The success of any debulking procedure depends on the site. Tumours in ‘silent’ areas are more accessible to debulking than eloquent areas, such as the motor cortex. Debulking tumours has been shown to improve prognosis for GBM and astrocytoma. Removal of a large cystic component may be of particular benefit. Obstructive hydrocephalus may be treated by ventriculoperitoneal shunts or by ventriculostomy (opening a hole from the third ventricle to the basal cisterns). This may be undertaken as a palliative procedure or as an emergency, prior to more definitive tumour surgery.

Radiotherapy

Primary radiotherapy

is the main mode of palliation for metastatic disease, including meningeal infiltration, and may be effective primary treatment in some rarer tumours, for example primary cerebral lymphoma or pineal region germinoma.

Adjunctive radiotherapy

has been shown to improve the prognosis of GBM by an average of 5 months and the 10-year survival of astrocytoma from 11% to 40%. It is used to prevent seeding of tumour for medulloblastoma or ependymoma.

Chemotherapy

Chemotherapy can prolong survival in some patients with some tumour types. For example, temozolomide with radiotherapy in patients with GBM and oligodendroglioma. Some rarer tumours are more sensitive to chemotherapeutic regimes, for example medulloblastoma.

CNS neoplasia I Intracranial tumours

In adults, metastases are more common than primary intracranial tumours.

Intracranial tumours commonly present with progressive focal neurological deficit, raised intracranial pressure or seizures.

Emergency treatment is directed at reducing cerebral oedema and treating seizures.

The operability of tumours depends on their location as well as their type.

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