stem cells is generally not known, but they may derive from a stem cell, a transient amplifying cell, or even a terminally differentiated cell that have acquired mutations that free them from the normal control on their proliferation and/or that give them stem cell characteristics, notably, by hijacking the capacity to self-renew and thereby creating a cancer cell that renews indefinitely.
Causes and Risk Factors
The exact mechanisms by which any given cancer has arisen are difficult to pinpoint. However, many studies have shown that primary cancer develops in the brain because cells, possibly stem cells, have acquired mutations in their DNA which allow them to undergo unchecked and uncontrollable division. Secondary cancers (cancers that develop elsewhere, for example, the lungs and then spreading to the brain), are far more common compared to primary brain cancers.
Multiple risk factors are known to play a role in enhancing the chance of developing a brain tumor or accelerating the process. Some people with several risk factors may never develop a brain cancer. Conversely, some people with no known risk factors have presented with brain tumors. Complex interactions between environmental and genetic factors contribute to the development of brain tumors.
Environmental triggers for the brain tumor have been identified through epidemiologic studies that examine patterns of distribution of cancer in patients. Although brain tumors can develop at any age, they are more common in children and older adults. Men are more likely to develop brain tumors, however, meningiomas are more common in women. Recent investigations of mortality among workers employed in petroleum refineries and petrochemical plants have revealed an association between increased brain tumor risk and employment in the chemical industries and petroleum. Occupational groups having an elevated risk of brain tumors are suggested by literature review. The most eminent associations have been noted among white-collar professional groups and workers in occupations in which there is potential contact with lubricating oils, polycyclic aromatic hydrocarbons, organic solvents, polyvinyl chloride, formaldehyde, acrylonitrile, and phenolic compound. Moreover, employment in textile industry maintenance jobs and exposure to wool products may also be associated with an increased risk of brain tumor as suggested by another study. Exposure to radiation at an early age increases the risk of brain tumor. Ionizing radiation appears to be more strongly associated with meningioma risk than with glioma risk.
Genetics also play an important role as a risk factor. The genetic syndromes including neurofibromatosis, tuberous sclerosis, and Turcot’s and Li-Fraumeni syndromes are important risk factors in the development of brain cancers. In these syndromes, individuals inherit a germ-line mutation in a tumor suppressor gene. Tumor is initiated when the remaining copy of the gene is spliced or mutated, giving rise to uncontrolled growth of cells.
Because every cell in these individuals has a preexisting mutation the risk of tumorogenesis through the accumulation of other mutations is greatly increased.
Li-Fraumeni syndrome is caused by mutations in the cell checkpoint genes CHEK2 and TP53. Mutations in genes involved in DNA repair results in Turcot’s syndrome. It is plausible that in Li-Fraumeni syndrome and Turcot’s syndrome that the risk for brain tumors is increased by an accelerated rate of DNA mutation, leading to uncontrolled growth. Tuberous sclerosis is caused by mutations in TSC1 or TSC2, and neurofibromatosis is caused by mutations in NF1 or NF2. NF1, NF2, TSC1, and TSC2 are all involved in down-regulation of growth-promoting signal transduction pathways in the cell. It is therefore likely that, in tuberous sclerosis and neurofibromatosis, the risk for brain tumors is increased because brain cells are prepared for excessive growth and then develop additional mutations that allow cancer to form.
In addition, it has also been observed that brain tumors can cluster within families with no known risk factors, suggesting that these families might be carrying unknown susceptibility genes.
Meta-analyses have shown that people with HIV or AIDS have around double the risk of being diagnosed with a brain tumor in comparison with the general population.
Types of Brain Cancer
The common primary brain tumors in adults include:
Glioblastoma multiforme: Most common and highly malignant primary tumor of the brain involving astrocytes.
Meningioma: Typically benign and the second most common primary tumor.
Schwannoma: Third most common, with a good prognosis after surgical resection.
Pituitary adenoma.
The common childhood brain tumors are:
Pilocytic astrocytoma: Benign tumor with good prognosis.
Medulloblastoma: Cerebellar tumor that is highly malignant.
Ependymoma: Causes hydrocephalus and has poor prognosis.
Craniopharyngioma: Benign tumor that often calcifies.
Metastatic tumors that spread from other sites in the body are mostly from lung, breast, or genitourinary cancers. Osteosarcoma, melanoma, and gastrointestinal malignancies can also metastasize to the brain.
Signs and Symptoms
Patients with primary brain cancers may remain asymptomatic for many years before the onset of symptoms. The variety of signs and symptoms caused by the brain cancers depend on the type, size, and location of the tumors. Benign tumors are slow growing and have a late symptom onset. Malignant tumors are infiltrative and are associated with an early onset of symptoms. People with brain cancer usually present with:
Headaches accompanied by nausea and vomiting. These headaches are worse during the night and are associated with intracranial hypertension. Other signs may include papilledema, bradycardia, and potential for herniation.
Seizures in more than 30% of the patients.
Loss of vision or hearing.
Sensory and motor problems that can manifest as numbness/tingling, muscle twitching, balance, and walking problems.
Cognitive and behavioral dysfunction.
Personality changes.
Endocrine abnormalities including hypo- or hyperpituitarism.
Fatigue and depression.
Diagnosis
Proper medical interview from the patient, neurological examination, and other tests can aid in diagnosing brain cancers. In a neurological examination, the doctor looks for signs involving vision, hearing, muscle strength, sensation, balance and coordination, reflexes, and mental agility. Careful examination can help in choosing the correct investigation tests. Different tests used include:
Computed axial tomography (CT):
It is a noninvasive technique in which patient lies on a flat table that slides in and out of a cylindrical apparatus. X-rays penetrate the brain from many different angles and then provide computer images revealing the gross features of the brain.
Magnetic resonance imaging (MRI):
This noninvasive imaging technique uses magnetic fields and radio waves to build a detailed picture of the brain. It provides information about the anatomic location of the tumor.
Magnetic resonance spectroscopy (MRS):
MRS measures the biochemical composition and detects any changes. It is sensitive in detecting irregular patterns of tumor cell activity.
Electroencephalogram (EEG):
EEG is an electrical reading of brain activity interpreted by a neurologist. It can