A brain tumor is any mass created by an abnormal and uncontrolled growth of cells either found in the brain (neurons, glial cells, epithelial cells, myelin producing cells, etc.) or spread from elsewhere (metastasis). Brain tumors are usually located in the posterior third of the brain in childhood and in the anterior two-thirds of the brain in United States in 2000, it was estimated that there were 16 500 new cases of brain tumors¹, which accounted for 1.4% of all cancers, 2.4% of all cancer deaths², and 20%-25% of pediatric cancers^2,3. Ultimately, it is estimated that there are 13 000 deaths/year as a result of brain tumors¹.

Causes

Tumors in the brain are either benign or malignant. Benign tumors include:

• pituitary adenoma
• meningioma
• acoustic neuroma

Malignant tumors are:

• glioma (60% of new cases)³
• glioblastoma multiforme (WHO Grade IV glioma)
• astrocytoma (WHO Grade II glioma)
• metastasis from elsewhere (e.g., breast cancer, colorectal cancer, lung cancer)

Some lesions can mimic tumors of the central nervous system. These include tuberculosis of the brain and cerebral abscess.

Primary brain tumors

Primary brain tumors are those tumors that originate in the brain, and are named for the cell types from which they originated. Frequently encountered histologic brain tumor types are glioma, glioblastoma, astrocytoma, oligodendroglioma, medulloblastoma, meningioma and neuroglioma. Tumors can be benign and are usually, but not necessarily, localized to a small area. They can also be malignant and invasive (i.e., spreading to neighbouring areas). Brain cells can be damaged by tumor cells by (i) directly being compressed from growth of the tumor; (ii) indirectly being affected from inflammation ongoing in and around the tumor mass, (iii) brain edema (swelling); or (iv) increased pressure in the skull (due to brain edema or to the blockage of the circulation of the cerebrospinal fluid).

Local tissue damage (either by direct or indirect mechanisms) causes focal neurologic symptoms, which vary due to the location of the brain tumor. Hemiparesis, aphasia, difficulty speaking, ataxia, hemihypoesthesia (numbness and decreased sensation of touch on one side of the body) and localized headache are some of the symptoms occurring due to the local effects of the brain tumor. Increased pressure in the skull or brain edema cause more generalized symptoms like generalized headache, nausea and vomiting, loss of consciousness (stupor or coma) and intellectual decline. Seizures due to the local irritating effect of the brain tumor or metabolic changes caused by the cancer are also frequently observed. Since the development of the skull is incomplete during infancy, infants with brain tumor may have increased head perimeter, bulging fontanelles or separated sutures.

Neurologic examination reveals local (specific to the location of the tumor) or generalized neurologic changes. Slowly progressive nature of the neurologic symptoms is suggestive of a possible brain tumor and the diagnosis is confirmed by CT scan or magnetic resonance imaging (MRI) of the head. Angiography, electroencephalography (EEG) or brain biopsy may aid in diagnosis in difficult cases. Although slow progression is an important hallmark of the disease, some brain tumors may enlarge very quickly and thus may cause sudden neurologic changes. Treatment includes the surgical removal of the tumor mass or the destruction of the tumor cells by radiation (radiotherapy) and/or drugs (chemotherapy) in cases with contraindications for a surgical operation.

Secondaries

Secondary or metastatic brain tumors take their origins from tumor cells which spread to the brain from another location in the body. They are more frequent than primary brain tumors, and are mainly a problem in adults, though children may also have secondary tumors. Approximately one quarter of metastatic cancers spread to brain. Lung cancer and breast cancer are the most common causes of secondary brain tumors. Tumor cells may travel to the brain by blood vessels. Since the brain has no lymphatic drainage system like other organs (cerebrospinal fluid system acts like lymphatic system in the brain), spreading of tumor cells by the lymphatic route (which is very typical for cancers of other organs) is impossible in the brain. In contrast to primary brain tumors, metastatic tumor masses may occur in various remote locations in the brain. Highly aggressive brain tumors like glioblastomas may also be observed in more than one location, but usually in the advanced stages of the disease. Symptoms, diagnosis and treatment are quite similar to those of primary tumors, however in the case of secondary tumors the initial location of the tumor cells must be identified and treated as well.

Primary or secondary, brain tumors may cause herniation of the brain (displacement of one part of the brain tissue due to mass effect of a lesion, usually causing the compression of the neurons controlling the respiratory system in the brainstem and eventually death) and permanent neurologic changes including intellectual decline.

Tumors located in distant locations may affect the nerve cells and cause neurologic changes by mechanisms other than direct invasion of brain tissue. Diseases caused by the remote effects of tumor cells are called paraneoplastic diseases. Tumors may affect brain cells from a distance by consuming too much food and energy that is crucial for neurons, by secreting endocrine substances altering nerve cell functions or – in the majority of the cases – by causing the immune system of the body to develop antibodies (autoantibodies) directed against nerve cells. In the latter mechanism, antibodies developed to kill tumor cells are suggested to accidentally (probably due to molecular similarities between tumor cells and normal nerve cells) bind neurons and destroy them. Paraneoplastic diseases due to autoantibodies are not confined to brain cells (e.g. Lambert-Eaton myasthenic syndrome). Most frequent paraneoplastic diseases are cerebellar ataxia, peripheral sensory neuropathy, limbic encephalitis and brainstem encephalitis. The neuroimaging studies are usually not helpful in paraneoplastic diseases and diagnosis is established by immunological methods.

References

1. Greenlee RT et al. CA Cancer J Clin. 2000;50:7-33.
2. American Cancer Society (http://www.cancer.org/). Accessed June 2000.
3. Chamberlain MC, Kormanik PA. West J Med. 1998;168:114-120.
4. Oncology Channel (http://www.oncologychannel.com/braincancer/)