Central nervous system tumours

Published on 09/04/2015 by admin

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16 Central nervous system tumours

TV. Ajithkumar

Introduction

Primary central nervous system (CNS) tumours can arise from any structures in the cranial vault. Around 4000 new patients with malignant brain tumours are diagnosed per year in the UK and 22,000 new patients in USA. There is a bimodal distribution with small peak in children (p. 323) and a steady increase starting at the age of 20 years. Males are more commonly affected, particularly with malignant tumours, whereas women have a higher rate of non-malignant tumours, particularly meningiomas.

Aetiology

The majority of brain tumours are sporadic with an unknown cause. A small proportion of tumours are associated with genetic syndromes and other factors.

1 Genetic syndromes – fewer than 5% patients with glioma have a family history of brain tumours:

• Neurofibromatosis type I – neurofibromas, optic nerve glioma and pilocytic astrocytoma.
• Neurofibromatosis type II – meningioma, gliomas and bilateral acoustic neuroma.
• Tuberous sclerosis – subependymal giant cell astrocytoma, hamartomas.
• Turcot syndrome – glioblastoma and medulloblastoma.
• Li–Fraumeni syndrome – astrocytoma and PNET.
• Basal naevus syndrome – medulloblastoma.

2 Prior radiotherapy increases the risk of a second intracranial tumour, particularly meningiomas and gliomas with a typical latent period of 10 years. Immunosuppression increases the risk of primary CNS lymphoma.
3 Brain tumours are not associated with smoking, alcohol intake or mobile phone use.

Pathology

Box 16.1 shows WHO classification of brain tumours. WHO grading system (Box 16.2) is important in deciding management and prognosis. Molecular features can be incorporated in this grading system to yield important prognostic information. Clinico-pathological features of individual tumours are discussed later.

Box 16.1
WHO classification of brain tumours

Tumours of neuroepithelial tissue

1 Astrocytic tumours

• Pilocytic astrocytoma (grade 1)
• Diffuse astrocytoma (grade 2)
• Anaplastic astrocytoma (grade 3)
• Glioblastoma (grade 4)

2 Oligodendroglial tumours

• Oligodendroglioma (grade 2)
• Anaplastic oligodendroglioma (grade 3)

3 Ependymal tumours

• Ependymoma (grade 2)
• Anaplastic ependymoma (grade 2)

4 Mixed glioma

• Oligoastrocytoma (grade 2)
• Anaplastic oligoastrocytoma (grade 3)

Choroid plexus tumours

• Papilloma and carcinoma

Embryonal tumours

• Medulloblastoma and its variants (grade 4)
• Supratentorial primitive neuroectodermal tumour (PNET) (grade 4)

Pineal tumours
Neuronal tumours

• Ganglioglioma
• Anaplastic ganglioglioma
• Neurocytoma

Tumours of cranial/spinal nerves
Tumours of the meninges

• Meningioma (grade 1–3)

Tumours of uncertain histogenesis
Haematopoietic neoplasms
Germ cell tumours
Tumours of sellar region

• Pituitary adenoma and carcinoma
• Craniopharyngioma

Metastatic tumours

Box 16.2
WHO grading of primary CNS tumours

Grade 1 – tumours with low proliferative potential and tumour growth by expansion. Generally curable by surgery alone.
Grade 2 – tumours with low proliferative potential but exhibit infiltration. Surgery alone is rarely curative and these tumours can progress to grade 3–4 tumours.
Grade 3 – tumours with cytological evidence of malignancy such as nuclear atypia, endothelial proliferation and mitotic activity. These are rarely curable.
Grade 4 – highly malignant tumours often with necrosis. These are aggressive.

Presentation

Brain tumour can present with non-specific as well as specific features. Non-specific features are headache (50%) and vomiting due to raised intracranial pressure. Specific features are due to location of the tumour. Lateralizing signs (50%) include hemiparesis, aphasia and visual field defects. Seizure, generalized, partial or focal, can be the presenting symptom in 50% of high-grade and 25% of low-grade gliomas. Stroke-like presentations occur mainly due to bleeding associated with the tumour. It can occur in 5–8% of high-grade and 7–14% of low-grade tumours. Altered mental status can be a presenting feature of primary brain tumour, but is more commonly a presentation of multiple brain metastases.

Investigations

Imaging

CT scan

Contrast enhanced CT scan is usually the initial investigation in patients suspected to have a brain lesion. CT scan is not an ideal investigation for low-grade tumours or tumours in the posterior fossa. CT scan may also show features of oedema, hydrocephalus, haemorrhage and calcification depending on the histological variant of brain tumour. Table 16.1 shows radiological appearance of common tumours.

Table 16.1 Radiological appearance of common brain tumours

Type of tumour Imaging characteristic
Pilocystic astrocytoma Well-circumscribed, contrast enhancing tumour with a cystic or enhancing mural nodule.
Grade II astrocytoma Isodense or hypodense on CT. Hypointense on T1W image and hyperintense on T2W and FLAIR images. No contrast enhancement and if present suggest malignant transformation. No associated cerebral oedema.
Oligodendroglioma Same CT/MRI as grade II astrocytoma; but can be associated with areas of contrast enhancement, calcification and haemorrhage.
Anaplastic astrocytoma and GBM
CT – irregular hypodense lesions with varying degree of contrast enhancement and associated oedema and pressure effect. Ring-like enhancement surrounding an irregular shaped necrosis suggests GBM. Some of the high-grade tumours can be non-enhancing particularly in the elderly.
MRI – irregular hypointense on T1W and irregular contrast enhancement and hyperintense on T2W and FLAIR, representing tumour and oedema.

Anaplastic oligodendroglioma Contrast enhancing heterogeneous mass with frequent cystic components, calcifications and necrosis. Medulloblastoma
CT – hyperdense midline mass with associated hydrocephalus. Marked contrast enhancement. Sometimes show calcification cysts, haemorrhage and nodular seedling.
MRI – heterogeneous hypo or isointense on T1W with slightly heterogeneous contrast enhancement. Iso-hyperintense on T2W.

Ependymoma Heterogeneously enhancing lesion with cystic component. There may be associated calcification and haemorrhage. Primary CNS lymphoma Solitary or multiple periventricular homogenously enhancing diffuse lesions (‘cotton wool’ appearance). Ring enhancement common in immunocompromised patients. Meningioma Homogenously contrast enhancing lesion arising from the dura. There is little associated brain oedema. There will be enhancement of dura (’dural tail’ sign). Craniopharyngioma Solid and cystic lesion on CT scan. MRI appearance depends on the composition of tumour. T1W can be hypo, iso or hyperintense with variable contrast enhancement. T2W can also be hypo, iso or hyperintense. Pituitary Contrast enhancing seller/suprasellar lesion on CT. T1W iso-hypointense and T2W hyperintense. Metastasis Solitary or multiple irregularly contrast enhancing lesion which may be solid or cystic at the junction of grey and white matter. Location and characteristic depends on type of tumour.

MRI scan

MRI scan with gadolinium and FLAIR (fluid-attenuated inversion recovery) sequence is the standard investigation for brain tumours. T1W imaging demonstrates anatomy and areas of contrast enhancement and T2W and FLAIR images are useful in demonstrating oedema. Appearance of tumour on T1W image is similar to that on CT, but better delineated on MRI. Tumour and oedema demonstrate increased signal on T2 and the area of increased T2 signal on MRI usually includes the hypodense area on CT (Figure 16.1).

image

Figure 16.1 MRI scan of diffuse astrocytoma. Scan shows hypointense lesion on left parieto-occipital region (A) without contrast enhancement (B) on T1W image. T2W image (C) shows a hyperintense lesion. Since low-grade tumours are not associated with oedema, this hyperintense lesion represents just the tumour.

Various MR imaging techniques are being evolved to improve the diagnostic ability in the imaging of brain tumours.

Magnetic resonance spectroscopy (MRS)

MRS is clinically useful in distinguishing high-grade glioma and metastases from abscess, assessing tumour recurrence and radiation necrosis, and identification of atypical meningioma as a true meningioma.

Diffusion tensor imaging (DTI)

In radiotherapy planning for high-grade gliomas, conventional methods of imaging cannot distinguish oedema from peritumoural white matter infiltration, resulting in large target volumes. DTI shows white matter abnormalities resulting from tumour infiltrating, and thereby reducing the target volume, which would allow significant dose escalation to the tumour with acceptable damage to the normal tissue.

Evaluation of the craniospinal axis

MRI of the craniospinal axis and CSF evaluation is needed for tumours with a high risk of CSF dissemination such as medulloblastoma, germ cell tumours, CNS lymphoma, PNET and ependymoma (Figure 16.2). CSF evaluation includes CSF biochemistry (typically elevated protein >40 mg/dL and reduced glucose <50 mg/mL), cytology and in cases of suspected germ cell tumours, the estimation of tumour markers (AFP and beta hCG) in CSF and serum. Evaluation of the craniospinal axis is best done prior to surgery or >3 weeks after surgery to avoid false positive results.

image

Figure 16.2 Multiple contrast-enhancing tumour nodules in ependymoma suggesting leptomeningeal disease.

Tissue diagnosis

Histologic confirmation is necessary in all patients prior to definite treatment. Biopsy is obtained by either stereotactic guided techniques or open biopsy. In intrinsic brainstem tumours, biopsy may cause neurologic damage and hence may be avoided. Biopsy is avoided in patients with multiple brain metastases from a known primary, optic meningioma and CNS lymphoma in HIV positive patients showing typical radiological findings.

Prognostic factors

The outcome of brain tumours depends on the following factors:

1 Pathology – outcome depends on pathologic type and grade. High-grade tumours have poor prognosis. Recently molecular factors are shown to be important in certain tumour types.
2 Age – increased age is associated with poorer outcome.
3 Performance status – is an important factor in outcome and guiding treatment.
4 Extent of surgical resection – based on observational studies, patients with less residual disease after surgery have a better prognosis.

Principles of management

General medical management

Steroids

Steroids may improve symptoms by reducing intracranial pressure. The most commonly used agent is dexamethasone which is started at a dose of 2–16 mg daily (low doses given once daily and higher doses as 2–4 equally divided doses) and titrated against the patient’s symptoms. The optimal dose is just above that at which symptomatic deterioration occurs. If there is no symptomatic improvement, steroids should be stopped.

Anti-epileptics

All patients who have had a seizure should be treated with an anti-epileptic drug (AED); prophylactic use of anti-epileptics is not recommended. Many anti-epileptics are enzyme-inducers, and hence should be carefully monitored when they need to be used concurrently with drugs metabolized by cytochrome p450 enzyme system.

Analgesics

Patients requiring pain control are managed according to the WHO analgesic ladder (p. 66).

Surgical management

Surgery in brain tumours helps in pathological diagnosis, symptom control and definite treatment.

Biopsy can be either stereotactic guided or an open biopsy. Surgery is useful in relieving pressure symptoms as well as decreasing the frequency and intensity of seizures. Surgical resection is constantly evolving in brain tumours. It is common practice to confirm the diagnosis with an intraoperative frozen section or smear prior to attempting a full resection. Complete or maximal resection with minimal injury to neighbouring critical structures is the aim of surgery. The importance of surgical resection in specific tumours is discussed later. The various resection techniques are:

1 Image guided stereotactic resection – is useful in technically challenging locations such as the peri-thalamic region, to minimize critical structure injury.
2 Neuronavigation guided resection – distortion of brain anatomy by tumour and oedema makes surgical resection according to conventional landmarks difficult. Neuronavigation systems allow registration of stored imaging data which can be incorporated with real time intra-operative imaging using intra-operative ultrasound or MRI. This helps surgeons to guide resection based on real time shift of structures during operation.
3 Cortical mapping awake craniotomy – is useful in resection of tumours inside or adjacent to functional brain areas. Intraoperative cortical or subcortical stimulation helps to map functional areas. Initial craniotomy and preliminary stimulation are done with the patient asleep. After arousal, under sedative/hypnotic anaesthesia, the patient responds to motor or language commands but with subsequent amnesia.
4 Fluorescent guided surgery – an evolving technique for malignant gliomas.

Radiotherapy in brain tumours

Radiotherapy has a major role in the management of CNS tumours. Radiotherapy is proven to improve local control and/or survival in grade 3–4 tumours whereas its role in grade 2 tumours is doubtful and has limited role for grade 1 tumours. Radiotherapy is delivered by the following methods:

1 External beam radiotherapy is commonest mode of delivery of radiotherapy to the brain. Immobilization and proper localization is important in the delivery of EBRT. Target volume depends on the type of tumour and intention of treatment.
2 Stereotactic technique – this technique involves improved localization of tumour and precision. Treatment is delivered either as multiple fractions using linear accelerator (called stereotactic radiotherapy) or as single fraction (called radiosurgery) using gamma knife, a special machine for cranial radiosurgery.
3 Charged particle radiotherapy – mainly protons, which deposit the energy only at a depth and hence useful in skull base tumours.

A summary of radiotherapy details for common tumours are given in Table 16.2.

Table 16.2 Radiotherapy for common brain tumours

image

Radiation tolerance and reactions

Radiation to the brain can cause structural damage to critical structures if attention is not paid not to exceed the tolerance dose of individual structures.

Acute radiation reactions may manifest up to 6 weeks following completion of irradiation. These reactions are generally those of raised intracranial pressure, fatigue and worsening of neurology. Vomiting is particularly common in patients receiving radiotherapy to the brainstem region.

Early delayed (intermediate) side effects usually appear from 6 weeks to 6 months following radiotherapy and are due to changes in capillary permeability and transient demyelination. Symptoms include headache, somnolence syndrome, lethargy and frequently recurrence of the original presenting features. Recovery is spontaneous but can be accelerated by steroids.

Delayed radiation reaction develops 6 months after radiotherapy. This is thought to be due to white matter injury secondary to vascular injury, demyelination and necrosis. The most serious form of this is radiation necrosis which peaks at 3 years. Conventional imaging fails to distinguish this from recurrent tumour and special imaging is therefore needed (p. 265). Treatment is with steroids and debulking. Other late effects include, depending on the area irradiated, memory problems, pituitary failure, hearing loss, visual changes and second malignancies.

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