Introduction

This article begins with a general overview of brain tumours, including epidemiology, clinical presentation, investigations and management options. It then moves on to discuss a selection of brain tumour sub-types in some more detail.

 

Definition

The term brain tumour refers to an intracranial tumour affecting the brain, meninges, pituitary gland, pineal gland, cranial nerves and/or skull.

 

Epidemiology

Brain tumours accounted for 3% of total cancers in 2015, but their incidence has been rising.

For adults, the highest incidence occurs in those aged between 85-89 years old.

In children less than 15 years old, brain tumours are the second most common form of cancer (acute lymphoblastic leukaemia is the most common).

Secondary brain tumours are almost three times more common than their primary counterparts.

Brain metastases can originate from cancer in many different organs:

  • Lung (most common)
  • Breast
  • Thyroid
  • Testicular
  • Renal
  • Colorectal
  • Skin (malignant melanoma)

 


Risk Factors

There are a variety of risk factors that can predispose an individual to develop a brain tumour.

The most widely recognised risk factors include:

  • Familial syndromes (Neurofibromatosis type 1 and 2, von Hippel-Lindau and Li-Fraumeni)
  • Ionising radiation/X-ray exposure
  • Multiple endocrine neoplasia type 1 (MEN-1)
  • Immunosuppression/EBV/HIV (primary CNS lymphoma)
  • Previous history of cancer

 


Overall Clinical Presentation

A brain tumour’s presentation is typically progressive and subacute in nature.

Signs and symptoms typically relate to the area of the central nervous system affected by the tumour.

 

Signs related to increased intracranial pressure (ICP) are common

  • Headache (worse on waking, lying down, bending forward or coughing)
  • Nausea and vomiting
  • Papilloedema

 

Focal neurological signs

  • Paresis of limbs (very common)
  • Speech disorders/dysphasia (very common)
  • Seizures
  • Cerebellar signs – think DASHING (dysdiadochokinesis and dysmetria, ataxia, slurred speech, hypotonia, intention tremor, nystagmus, gait abnormality)
  • Visual symptoms (bitemporal hemianopia)
  • Personality changes
  • Cranial nerve 5 palsy (common due to its long intracranial course)

 

Coma

  • Coma is a late stage feature of brain tumours, secondary to raised intracranial pressure.

 


Investigations

History

  • A comprehensive clinical history is essential.

 

Physical examination

  • A comprehensive neurological assessment should be performed (including cranial nerves, upper and lower limbs)
  • Clinical examination of other systems should be performed, particularly when brain metastases are suspected (looking for the primary source).

 

Routine blood tests

  • Full Blood Count
  • Urea & Electrolytes
  • Calcium
  • Liver Function Tests
  • C-Reactive Protein (raised in infection and malignancy)

 

Imaging

  • Both CT and MRI are used to help assess tumour size, adjacent structures, surrounding oedema, mass effect and secondary haemorrhage
  • A CT chest, abdomen and pelvis (CAP) should be performed if metastases are suspected

 

Biopsy

  • A biopsy is the only definitive way to diagnose a tumours tissue type (histology and cytogenetics)
  • This information can be useful in determining treatment options and prognosis

Lumbar puncture

  • Lumbar puncture should be avoided until neuroimaging has ruled out evidence of raised intracranial pressure.
  • This reduces the risk of brain herniation (commonly referred to as coning).

 


Management

Management varies depending on a variety of factors, including brain tumour type, stage of disease, patient preference and current clinical condition.

Multi-disciplinary team approach

A multi-disciplinary team approach is essential, which may involve some, or all, of the specialties below:

  • Neurosurgery
  • Neurology
  • Clinical nurse specialists
  • Oncology
  • Radiology
  • Palliative care

 

Surgery, Radiotherapy and Chemotherapy combination therapy

  • The use of surgery, radiotherapy and chemotherapy varies depending on the type of brain tumour diagnosed.
  • Some brain tumours are particularly sensitive to chemotherapy (e.g. oligodendroglioma codeletion), whereas, for others, the only option may be complete surgical excision.
  • Often, a combination of different therapies is used to achieve the best possible outcome (e.g. adjuvant radiotherapy/chemotherapy with surgical excision).

 

Anticonvulsant medication

  • Anticonvulsant medication is commenced if seizure activity is present or if the tumour is in a highly epileptogenic area
  • Examples of anticonvulsant medications include Phenytoin and Levetiracetam

 

Mannitol

  • Mannitol is sometimes used to reduce intracranial pressure

 

Analgesia

  • Typically analgesia is used to reduce the severity of headaches

 

Dexamethasone

  • Dexamethasone is commonly used to reduce cerebral oedema around the tumour site
  • This can help reduce intracranial pressure temporarily
  • Common side effects include sleep disturbance, increased appetite, weight gain and gastro-oesophageal reflux

 

Ventriculo-peritoneal (VP) shunt

  • A ventriculo-peritoneal shunt may be needed if the patient presents with raised intracranial pressure secondary to hydrocephalus (a build-up of CSF in the brain)
  • This is a surgical procedure which allows diversion of CSF into the peritoneal cavity, to prevent rising intracranial pressure
  • Risks include intracerebral haemorrhage, infection and the need for further surgery if the shunt blocks

 


Complications

Radiation complications

  • Cognitive impairment
  • Bone growth retardation
  • Endocrine disruption
  • Hair loss
  • Nausea
  • Skin problems
  • Tissue healing problems

 

Neurosurgical complications

  • Paralysis
  • Seizures
  • Altered personality
  • Hydrocephalus

 

Chemotherapy complications

  • Nausea/vomiting
  • Anorexia
  • Alopecia
  • Pain
  • Headaches
  • Nerve damage
  • Cognitive dysfunction
  • Increased susceptibility to infections

 


Prognosis

  • The majority of benign tumours will be curable by excision.
  • Prognosis, however, is ultimately dependent on type and grade of a tumour.
  • Even with excision, GBM (glioblastoma multiforme) tumours are incurable and carry the worst prognosis of all brain tumours.

 


Meningioma

  • Usually, a slow-growing tumour that forms from the arachnoid cell cap found on the meninges
  • Incidence peak at 45
  • Usually benign and surgically viable
  • 2:1 female to male ratio
  • Includes malignant anaplastic meningioma (grade III meningioma)
  • Rarely metastasise into the body

Presentation

  • Dependent on tumour size and location (can lead to mass effect symptoms)
  • Asymptomatic
  • Headache
  • Seizures
  • Spastic weakness or numbness in both legs
  • Gait abnormalities
  • Visual loss if the optic nerve is compressed

Investigations

  • MRI with gadolinium contrast +/- CT
  • Angiography
CT Scan with contrast of a left-sided meningioma

Figure 1: CT Scan with contrast of a left-sided meningioma 8

Management

  • Conservative measures unless symptomatic
  • Repeat imaging every 6-23 months
  • Surgical excision and/or radiotherapy
  • Chemotherapy has little benefit

 

Prognosis

  • 91% 5-year survival rate

 


Pituitary Adenoma

  • 15% of primary brain tumours
  • Occur in the pituitary gland
  • Can be functional and secrete hormones
  • Others are non-functional and cause symptoms by mass effect
  • Most are benign
  • Larger tumours (>1cm) are usually non-functional
  • Pituitary macroadenomas are the most common cause of hypopituitarism

 

Presentation

  • Cushingoid symptoms
  • Acromegaly
  • Diabetes insipidus
  • Hyperpituitarism
  • Bitemporal hemianopia
  • Hydrocephalus
  • Amenorrhea/galactorrhea/impotence
  • Diplopia

 

Investigations

  • Endocrine evaluation
  • MRI with gadolinium contrast +/- CT
MRI of a Pituitary adenoma

Figure 2: MRI of a pituitary adenoma 9

Management

  • Dopamine agonists to treat prolactinomas
  • Surgery
  • Radiation

Complications

Pituitary apoplexy:

  • Sudden haemorrhage causes a rapid increase in the size of the lesion and surrounding vasogenic oedema
  • Because of mass effect, surrounding tissue necrosis occurs
  • This can result in sudden onset visual loss, headache and hydrocephalus

 


Acoustic Neuroma

  • Benign tumour of vestibulocochlear Schwann cells (aka vestibular schwannoma)
  • Approximately 5% of intracranial tumours
  • Presents in those over 30 years old
  • Bilateral acoustic neuromas are seen in younger patients and in those with NF type 2
  • Tumour suppressor gene abnormalities on chromosome p22 are thought to cause tumour growth

Presentation

  • Gradual onset of unilateral sensorineural deafness due to compression of CN VIII
  • Headache
  • Vertigo
  • Dizziness
  • Unilateral face numbness
  • Absent corneal reflex
  • Nystagmus and gait abnormalities in larger tumours

 

Investigations

  • Routine hearing examination useful
  • MRI with gadolinium contrast +/- CT
MRI with contrast of a right-sided acoustic neuroma

Figure 3: MRI with contrast of a right-sided acoustic neuroma (shown by arrows) 10

Management

  • Due to the slow onset, small tumours can be monitored with annual MRI head
  • If deemed necessary, tumours can be removed surgically or with Gamma Knife radiosurgery

Complications

  • Facial palsy post-operatively
  • CSF fluid leakage after surgery – greatly reduced since the introduction of microsurgical techniques

 


Craniopharyngioma

  • 6-13% of all childhood brain tumours and 1-3% of all adult brain tumours
  • Derived from residual cells of Rathke’s pouch
  • Bimodal onset: age 5-14 and 50-70
  • Arises in the pituitary stalk
  • Can affect the hypothalamus and pituitary

Presentation

  • Growth failure in children
  • Diabetes insipidus
  • Sexual dysfunction in adults
  • Hydrocephalus
  • Bitemporal hemianopia
  • Pituitary insufficiency
  • Headache

Investigations

  • MRI with gadolinium contrast +/- CT
  • Endocrine testing
MRI of a Craniopharyngioma

Figure 4: MRI of a Craniopharyngioma 11

Management

  • Surgical removal is the treatment of choice
  • Radiotherapy can be considered
  • Chemotherapy is usually of no use

 


Primary CNS Lymphoma

  • This is usually diffuse large B cell lymphoma
  • It accounts for <1% of all non-Hodgkin’s lymphoma sub-types

 

Presentation

  • Seizures
  • Headache
  • Altered mental status
  • Systemic symptoms – Fever / Night sweats / Unintentional weight loss
  • Diplopia
  • Vertigo
  • Dysphagia

 

Investigations

HIV testing:

  • CD4 count
  • Viral load

 

Imaging:

  • MRI
  • CT may be done additionally

 

Lumbar puncture (LP):

  • May show increased WCC /cytology positive for lymphoma

 

EBV PCR:

  • This may identify Epstein-Barr virus if it is present

 

Management

Chemotherapy:

  • Usually with Methotrexate
  • Cytarabine may be used as well
  • Chemotherapy is typically used alongside whole-brain radiation therapy

 

Steroids:

  • Typically dexamethasone

 

Surgery:

  • Tumours are typically not resectable
  • However, if mass effect is present, resection may be considered as a life-sparing procedure

 

Prognosis

  • Usually quite poor
  • In patients co-diagnosed with AIDs, median survival is 4 months with radiotherapy
  • With methotrexate-based chemotherapy, median survival is 10-18 months

 


Medulloblastoma

  • The most common malignant tumour in children
  • Thought to arise from cerebellar stem cells between the brainstem and cerebellum near the fourth ventricle
  • Malignant primitive neuroectodermal tumour
  • Tends to seed within CSF pathways giving rise to its high metastatic propensity
  • Metastatic disease is classified by the Chang system

 

Presentation

Hydrocephalus:

  • Worsening headaches and reducing level of consciousness
  • Dilated ventricles on CT head

 

Cerebellar signs:

  • Incoordination of limbs
  • Gait abnormalities

Mass effect symptoms:

  • Speech abnormalities
  • Vision abnormalities
  • Unilateral weakness
  • Headaches
  • Drowsiness
  • Nausea/vomiting

 

Extraocular muscle palsies:

  • Typically presents as diplopia

 

Investigations

Lumbar puncture (LP):

  • This can be useful for staging
  • Only done post-operatively as it can result in brain herniation if done pre-operatively

 

MRI +/- CT including spinal imaging

MRI of a medulloblastoma (as indicated by arrows)

Figure 5: MRI of a medulloblastoma (as indicated by arrows) 12

Treatment

  • Surgical removal of the tumour
  • Radiation
  • Chemotherapy

Prognosis

  • The 5-year survival for standard risk patients is around 70%

 


Glioma

  • Gliomas account for 50% of primary brain tumours in adults
  • More common in men and in industrial countries
  • Glioma is an umbrella term for a variety of different tumour sub-types
  • They include astrocytomas, glioblastoma multiforme (GBM), pilocytic astrocytoma (PCA), ependymomas and oligodendrogliomas
  • The mean age of onset is 55 and they account for 20% of all intracranial tumours
  • PCA, on the other hand, is the commonest benign tumour in children
  • All gliomas metastasise via the cerebrospinal fluid

Presentation

  • Headache
  • Vomiting
  • Seizures
  • Focal neurological deficit including visual loss
  • Cranial nerve dysfunction

 

Investigations

  • MRI with gadolinium contrast
MRI with contrast of a GBM

Figure 6: MRI with contrast of a GBM 13

Management

Surgery:

  • For all gliomas, complete excision of the tumour is often difficult
  • This is because the margins between the tumour and the brain are rarely clear
  • Biopsies taken can be used to help make a histological diagnosis
  • Carmustine implants can also be inserted; these are alkylating agents, which can help reduce the rate of tumour spread (however, they do carry a risk of serious cerebral oedema).

 

Radiotherapy:

  • Targeted radiotherapy can be used in an attempt to shrink tumours or to destroy any residual tumour cells after excision

 

Chemotherapy:

  • Temozolomide has been shown to increase survival when given alongside surgery and/or radiotherapy

 

Prognosis

  • Overall, the prognosis is poor as gliomas are rarely curable
  • As an example, GBMs have a mean life expectancy of 1 year
  • PCAs are an exception, with more than  95 % of patients surviving 5 years

 


Edited by

Samantha Strickland

Hull York Medical School

 

Reviewed by

Konstantinos Lilimpakis

Neurosurgical Clinical Fellow


References

  1. DN Louis, A Perry, G Reifenberger, A von Deimling, D Figarella-Branger, W KCavenee et al (2016) ‘The 2016 World Health Organization Classification of Tumours of the Central Nervous System: a summary’, Acta Neuropathologica, 131(6), pp. 803-820.
  2. Whittle IR, Smith C, Navoo P, Collie D (2004), ‘Meningiomas’, Lancet, 363, pp. 1535-1543.
  3. BMJ Best Practice (2017) ‘Overview of brain tumours’, BMJ Best Practice. Available at: https://bestpractice.bmj.com/topics/en-gb/262
  4. Cancer Research UK (2018) ‘Brain, other CNS and intracranial tumours incidence statistics’, Cancer Research UK. Available at: http://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/brain-other-cns-and-intracranial-tumours/incidence#heading-One
  5. National Institute for Health and Care Excellence (2006) ‘Improving outcomes for people with brain and other central nervous system tumours’, NICE guideline (CSG10)
  6. Grant R (2004) ‘Overview: brain tumour diagnosis and management/RoyalCollege of Physicians guidelines’, J Neurol Neurosurg Psychiatry 75(2), pp. 18-23
  7. Hamilton W, Kernick D (2007) ‘Clinical features of primary brain tumours: a case-control study using electronic primary care records’, Br J Gen Pract 57(542), pp. 695-699
  8. Taken from: http://en.wikipedia.org/wiki/Image:Contrast_enhanced_meningioma.jpg
  9. Taken from https://commons.wikimedia.org/wiki/File:Craniopharyngioma-t1corkm-001.jpg
  10. MRT-Bild. 2009. Taken from: https://en.wikipedia.org/wiki/File:Akustikusneurinom_Mrt.jpg
  11. Taken from: https://commons.wikimedia.org/wiki/File:Craniopharyngioma-t1corkm-001.jpg
  12. The Armed Forces Institute of Pathology. Taken from: https://commons.wikimedia.org/wiki/File:AFIP405851R-MEDULLOBLASTOMA.jpg
  13. Christaras A. https://commons.wikimedia.org/wiki/File:Glioblastoma_-_MR_sagittal_with_contrast.jpg

 

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