Table of Contents
Definition and Epidemiology of Central Nervous System Cancers
Brain tumours are dysfunctional and abnormal growth of tissue in the cranium. They can either be primary or secondary (although are 5x more likely to be secondary).
Most (85%) of CNS tumours will be metastases from other cancers. As such, investigations for a suspected CNS tumour should also include tests for other organs’ function to rule out metastases.
Of primary brain tumours, gliomas account for the significant majority (70%) and glioblastomas make up the largest proportion in this group. Of patients diagnosed with glioblastoma only 3% are still alive in 5 years.
Etiology of CNS Cancers
Tumours will have varying etiology dependent on the specific tumour classification. Around 50% of all tumours are secondary following malignancy elsewhere in the body.
Neurocutaneous syndrome can also cause CNS tumours. These are inherited, autosomal dominant conditions that lead to both benign and malignant tumours. They are caused by mutation in tumour suppressor genes.
Neurocutaneous disorders include neurofibromatosis type I and type II. Type I typically causes meningiomas and optic tract astrocytomas. This is the result of a mutation in the neurofibromin gene. Type II neurofibromatosis results in vestibular schwannomas amongst other manifestations and results from a mutation in the Merlin gene.
Von Hippel-Lindau disease can cause tumours in the CNS (typically hemangioblastomas and ocular angiomas) but also causes a number of renal cancers.
Classification of CNS Cancers
As noted before, brain tumours are far more likely to be secondary to primary malignancies elsewhere in the body. Below are common primary tumours you will be expected to know.
Classification of primary tumours
In the adult
- Glioblastoma multiforme (astrocytoma)
- Schwannoma (e.g. acoustic schwannoma)
- Pituitary adenoma
- Primary CNS lymphoma
- Pilocytic astrocytoma
Gliomas are a group of malignant tumours that include astrocytomas (like glioblastoma multiforme) and oligodendrogliomas. They can be associated with neurofibromatosis but are more regularly idiopathic. They are unlikely to metastasize.
Astrocytomas are graded I-IV. Grade I tumours grow very slowly over years. Grade IV tumours (also known as glioblastoma multiforme) are far faster growing and can cause mortality within a year. Oligodendrocytes are far slower growing.
Meningiomas are benign tumours. They grow over many years from the meninges and are found (usually) below the tentorium. They most regularly form in the pituitary fossa, skull base, parasagittal region, sphenoid ridge and subfrontal region.
Schwannomas arise from the cerebellopontine angle. They are benign tumours of Schwann cells. They can be caused by neurofibromatosis type II but will be bilateral. If you see bilateral vestibular schwannomas of the VIIIth nerve think of neurofibromatosis!
Pathophysiology of CNS Cancers
As with many tumours the biological determinants of the development of symptoms (aka the pathophysiology) is caused by the expanding tumour. Either cancer cells invade normal neuronal tissue or pressure from the growing tumours can cause focal neurological deficits.
Patients will typically present with seizures (epilepsy) and signs of raised intracranial pressure. These include headache, vomiting, intellectual deterioration. The headache can be worse on coughing, bending or in the morning. Patients can also present with focal (localized) deficits due to pressure from the expanding tumours. These can vary dependent on the site of the tumour.
Diagnosis of CNS Cancers
A full history and examination should be taken in any patients presenting with symptoms suggestive of a brain tumour.
As mentioned previously, patients will complain of headache, seizures, vomiting, and focal deficits (for instance cranial nerve VI palsy where patients will complain of diplopia). Asking for specifics about the headache is important. Patients will describe a headache that is worse with coughing, bending or in the morning (typical of raised intracranial pressure).
Patients presenting with headaches is a common occurrence and the majority of patients will have a non-sinister reason behind the headaches. It is therefore important to be able to differentiate sinister from non-sinister presentations.
The headaches are usually constant and dull and patients are unlikely to present with an acute severe pain. Other concerning factors are nausea and vomiting and worsening headache. Patients can report worsening headaches on bending over, coughing or sneezing, all of which are indicators of raised intracranial pressure.
Often patients will complain their headache is worse at night, and if patients are waking from sleep to the headache they have severe pain. This pattern has been suggested to arise from diurnal variations in PCO2 which causes vasodilation, a drop in blood pressure and potentially headache.
Identifying the course of symptoms can also be telling. A direct effect mass lesion will often cause a progressive loss of function and worsening symptoms (as the tumour slowly grows).
On examination, papilloedema may be present (due to raised intracranial pressure). In the early stages of CNS tumour development, you might expect to see a mild venous engorgement and some loss of venous palpation.
Late CNS tumours will have a blurred disc margin, pronounced venous engorgement and signs of haemorrhage. Eye examination is imperative to a good examination when a CNS tumour is suspected. Patients with neurofibromatosis type I can have Lisch nodules in the iris. These patients also have café-au-lait patches and axillary freckling.
CT head is the most common diagnostic investigation. Some tumours are hard to see on an unenhanced CT, so enhanced CT is commonly ordered. Oligodendrogliomas can show calcification on CT.
MRI may also be used (particularly good for diagnosing posterior fossa masses). A stereotactic guided biopsy can also be taken for histology.
Histology of CNS Cancers
- Glioblastoma multiforme (astrocytoma grade IV): tumour cells are “pseudopalisading” and are seen bordering central areas where necrosis and haemorrhage are found.
- Meningioma: Spindle cells are seen arranged in concentric circles. Sometimes known as a “whorled pattern”. Psammoma bodies (calcified areas) are also seen.
- Hemangioblastoma: These are tumours of the capillaries found in the cerebellum. On histological examination, capillaries with minimal parenchyma are seen.
- Oligodendroglioma: Under the microscope, oligodendrocytes are often described as looking like fried eggs. These are calcified in oligodendroglioma.
- Pilocytic astrocytoma (low grade): “Rosenthal” fibers are eosinophilic, corkscrew-like fibers.
- Medulloblastoma: show Homer Wright rosettes where tumour cells surround a neuropil.
- Ependymoma: Show characteristic rosettes perivascularly. Basal ciliary bodies are found near the nucleus of the tumours.
- Craniopharyngioma: calcification is commonly seen.
Therapy of CNS Cancers
Different aspect of the patient’s issues can be treated differently. If the patient has cerebral edema (possibly caused by raised intracranial pressure) steroids (for instance Dexamethasone) can be given orally or IV. If the patient is suffering from epilepsy as a result of the tumour, antiepileptic drugs are recommended.
After the initial management, one should consider whether surgery is a realistic option. In some cases it is not necessary. Slow growing benign tumours like gliomas can often be followed up with frequent imaging and left. Some benign tumours are regularly removed, for instance acoustic neuromas.
Malignant tumours are harder to deal with as they often cannot be totally removed. The surrounding neural tissue will often be infiltrated and cannot be removed as it has functional use in the patient.
Radiotherapy only has a small use in tumours of the CNS. It can improve survival in gliomas and secondary metastases from a primary tumour but not drastically. Chemotherapy has little use, however temozolomide is used in glioblastomas and has been shown to improve survival.
Prognosis of CNS Cancers
Malignant tumours of the CNS typically have a poor prognosis whilst some benign tumours can be left with little loss of quality of life in the patients.
Prognosis for glioblastoma multiforme is poor and most patients die within one year.
Patients with meningioma can have resection. This often depends on the location of the tumours.
Schwannoma patients can have surgery and prognosis is often good.
Oligodendroglioma are slow growing glioma and as such have a good prognosis.