Epidemiology

Brain tumours occur in approximately 7-21 persons per 100 000 per year. They are responsible for 2% of cancer deaths and 2% of reported neoplasms. 

  • Metastases are the most common intracranial tumours
  • Astrocytomas are the most common primary brain tumours
  • Meningiomas are the commonest benign tumours together with acoustic neuromas

    Pathological classification

    WHO Classification of intra-cranial tumours (Kleihus & Cavenee, 2000) is based on their tissue of origin.

    Tumours of Neuroepithelial Tissue

     - Astrocytomas are the most common primary brain tumours. They are classified into 4 grades (see table).

    N.B. Grade IV tumours (GBM) are the most malignant type and have a poor prognosis. Patients usually die within several months.

      - Oligodendrogliomas are usually slow-growing, sharply defined tumours that originate from oligodendrocytes.

        WHO classification of Astrocytomas

        Tumours of the Nerve Sheath

        • A schwannoma is a non-invasive, slowly growing tumour of the Schwann cells that surround cranial nerve roots or peripheral nerves. The most common is a vestibular schwannoma (acoustic neuroma), which grows around the root of CN VIII at the cerebellopontine angle.
        • Neurofibromas originate from Schwann cells, fibroblasts or perineural-like cells (cells that form and support the nerve sheath). They involve spinal nerve roots or peripheral nerves but rarely cranial nerves and have a greater tendency to undergo malignant change than Schwannomas.

          Lymphomas

          •  Primary CNS lymphoma (PCNSL): forms around periventricular parenchymal blood vessels. It may be solitary or multifocal and generally occurs in immunocompromised patients.

           

           Germ Cell Tumours

          •  A germinoma is a primitive spheroidal cell tumour comparable to seminoma of the testis
          • A teratoma is a tumour containing a mixture of well differentiated tissues – dermis, muscle, bone.

           

          Tumours of the Sellar Region

          - Pituitary adenomas are benign tumours and often secrete pituitary hormones:

          • Prolactinomas are the most common, accounting for 40-50%
          • GH-secreting tumours account for 20% (associated with acromegaly)
          • ACTH-secreting tumours form 10-15% (associated with Cushing's disease)
          • TSH-secreting tumours are the least common pituitary adenomas (associated with both hypo- and hyperthyroidism)
          • Gonadotropin-secreting adenomas rarely cause a clinical syndrome and account for 20% of non-functioning pituitary adenomas.

           - Craniopharyngiomas arise from the embryonic remnants of Rathke’s cleft and lie in close proximity to the pituitary stalk. They are usually nodular tumours with cystic areas containing greenish fluid and cholesteatomous material

           

          Tumours of the Meninges

          •  Meningiomas are tumours that arise from the arachnoid granulations, usually closely related to the venous sinuses.
          • They are mostly benign but some undergo sarcomatous change and present in similar ways to malignant neoplasms. 
          • Meningiomas compress rather than invade the adjacent brain.

           

          Metastatic Tumours

          • These may arise from any primary site but most commonly arise from bronchial or breast tumours.
          • Nervous system metastases occur in 25% of patients with disseminated cancer

            Classification according to site



            Presentation

             

            Supratentorial Tumours

             - Raised intracranial pressure (ICP)

            • Headache, vomiting, depressed conscious level

            - Focal neurological deficit

            - Usually relentlessly progressive

            - Seizures

             

            Posterior Fossa Tumours

             - Never present with seizures

            - Focal deficits

            • CN lesions (e.g. diplopia, facial numbness/weakness, dysphagia)
            • Cerebellar lesions (ataxic gait, dysarthria, dysmetria)
            • Brainstem compression (decreased consciousness/coma)

            - Relentless progression

            - Obstructive hydrocephalus causes symptoms of raised ICP, which may develop rapidly.

             

               

              Pituitary Tumours

               - Focal neurological deficit

              • Chiasmatic compression - bitemporal hemianopia
              • Cavernous sinus syndrome - diplopia, facial numbness

              - Hydrocephalus from compression of the third ventricle from below

              - CSF leak

              - Pituitary apoplexy (resulting from either acute haemorrhage or ischaemic necrosis)

              - Endocrine presentation; panhypopituitarism, amenorrhoea, impotence, acromegaly (adults), gigantism (paediatrics), Cushing’s disease

                Paediatric brain tumours are not covered in depth in this article. They are almost always in the posterior fossa and may be one of the following:

                • Pilocytic astrocytoma
                • Medulloblastoma
                • Ependymoma

                  They present with failure to thrive, developmental delay and hydrocephalus.

                  Management is with surgery followed by radio- and chemotherapy.

                   

                  Investigations

                  The following tests may confirm the presence of a brain tumour and find its location:

                  • CT scan - will detect >90% of tumours. However, it is not very sensitive for: 

                  • Small pituitary tumours
                  • Tumours adjacent to bone 
                  • Brain stem tumours
                  • Low grade astrocytomas
                  • Small metastases

                  • Gadolinium-enhanced cranial MRI - preferred study for the initial anatomic evaluation of CNS tumours. Most tumours are hypointense on T1-weighted images and hyperintense on fluid-attenuated inversion recovery, T2-weighted, and proton-weighted images.

                  • Biopsy of the tumour during surgery or CT-scan may confirm the type of tumour

                      • EEG - used primarily to complement CT and MRI by evaluating functional changes in the patient's condition. It demonstrates aspects of brain physiology that are not reflected in structural neuroimaging.

                      • CSF analysis - Lumbar puncture contraindicated in many patients with brain tumours, but may be useful in some where it may show cancerous changes.

                      Many other imaging techniques (see table below), including MR spectroscopy, diffusion and perfusion imaging, single photon emission computed tomography (SPECT) and positron emission tomography (PET) may help to identify foci of high-grade tumour prior to surgery, thereby improving the accuracy of histopathological evaluation.



                      Management

                      The aims of management is diagnosis, symptomatic relief and tumour control (with minimal morbidity for malignant disease and maximal aggression for benign disease).

                       

                      Conservative Management

                       - Immediate introduction of palliative care may be appropriate when there is no doubt regarding diagnosis and if the patient is in extremis.

                      - Asymptomatic lesions may be left alone, especially in the elderly and in surgically difficult spots.

                      - Watch and wait with serial imaging for:

                      • Small acoustic neuroma - 66% show no growth
                      • Small meningiomata - mean doubling time of 26 years
                      • Low grade glioma - radiation and (for oligodendrogliomas) chemotherapy both have a role, but it may not matter when they are given

                       

                      Medical Management

                       - Corticosteroids (Dexamethasone) for ↑ ICP (reduces vasogenic oedema). Steroids may also temporarily improve focal neurological deficits by treating brain oedema.

                      - Anti-epileptic drugs for epilepsy. Carbamazepine, lamotrigine, oxcarbazepine, sodium valproate, and topiramate are the drugs of choice for partial (focal) seizures.

                      • Phenytoin first line anti-epileptic in neurosurgery as it can be given quickly

                        - Prolactinomas respond well to dopamine agonists and these are the treatment of choice. Acromegaly can be treated with Octreotide and Pegvisomant.

                         

                        Radiation Therapy

                         - Postsurgical radiation is the standard treatment for high-grade gliomas.

                         - Stereotactic radiosurgery used to palliate small, well-demarcated recurrent glioblastoma multiforme and as a boost after conventional external beam radiotherapy. 

                         - Interstitial radiotherapy (brachytherapy) involves surgically implanting radioactive material directly inside the tumour.

                         

                        Chemotherapy

                         - Combining Temozolomide therapy with radiation improves survival in patients with high-grade gliomas. 

                         - Irinotecan and targeted agents such as Bevacizumab, which inhibits vascular endothelial growth factor; and Gefitinib, Erlotinib, and Imatinib, which inhibit the epidermal and platelet-derived growth factor receptors, have shown some promise in the treatment of recurrent malignant gliomas.

                          Surgical Management

                          Most patients with intracranial tumours require one of the following surgical approaches (as shown in the diagram):



                          The surgical procedure may involve biopsy, debulking/cytoreduction or complete removal of the tumour. However this depends upon the nature of the tumour and its site. 

                          • Primary malignant tumours are infiltrative in nature and hence surgery is restricted to partial removal (debulking) or biopsy.
                          • Benign tumours such as meningiomas or craniopharyngiomas have better prospects following complete removal.

                          It is important to note, that if any of the tumour tissue is overlooked, or if fragments remain attached to deep structures, recurrence may be seen.

                          Prognosis

                          • Craniotomy and radiotherapy prolong prognosis for glioblastoma multiforme from 4 to 14 months.
                          • Surgery can prolong survival with single metastasis from 15 to 40 weeks.
                          • For low grade glioma, prognosis is 5-7 years with inevitable deterioration associated with tumour progression.

                            References

                            Lindsay KW, Bone I, Fuller G. Neurology and Neurosurgery Illustrated. 5th ed. Edinburgh; New York: Churchill Livingstone; 2010.

                            Ginsberg L. Lecture Notes: Neurology. 9th ed. UK: Wiley-Blackwell; 2010.

                            Jasmin L. Brain tumor - primary - adults [online] 2011. Available from: http://www.nlm.nih.gov/medlineplus/ency/article/007222.htm [accessed 19/05/2012]. 

                            Chandana SR, Movva S, Arora M, Singh T. Primary Brain Tumors in Adults. American Family Physician 2008; 77(10): 1423-30

                            NICE. Guidance on Cancer Services: Improving Outcomes for People with Brain and Other CNS Tumours - The Manual. June 2006: Developed by the National Collaborating Centre for Cancer.

                            Bromfield EB, Benbadis SR et al. EEG in Brain Tumors [online] 2009. Available from:http://emedicine.medscape.com/article/1137982-overview [accessed 19/05/2012]. 

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