Brain Tumor

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What is Brain Tumor?

The brain and spinal column make up the central nervous system (CNS), where all vital functions, including thought, speech, and body movements are controlled. When a tumor occurs in the CNS, it is especially problematic because of the possible effect on a person's thought processes or movements.                                     

                                                     

A brain tumor begins when normal cells in the brain change and grow uncontrollably, forming a mass. A tumor can be benign (noncancerous) or malignant (cancerous). In general, primary CNS tumors do not spread outside of the CNS. Malignant brain tumors are further classified using a grade: low, intermediate, or high. 

This section describes primary brain tumors, which are tumors that begin in the brain. Secondary brain tumors (also called brain metastases) are much more common than primary tumors. A secondary brain tumor is a cancerous tumor that started in another part of the body (such as the breast, lung, or colon) and then spread to the brain. 

Anatomy of the brain

The brain is made up of four main parts: the cerebrum, the cerebellum, the brain stem, and the meninges.

The cerebrum. This is the largest part of the brain. It contains two cerebral hemispheres and is divided into four lobes where specific functions occur:

The frontal lobe controls reasoning, emotions, problem-solving, expressive speech, and movement

The parietal lobe controls the sensations of touch, such as pressure, pain, and temperature, and parts of speech, visual-spatial orientation, and calculation

The temporal lobe controls memory, the special senses such as hearing, and the ability to understand spoken or written words

The occipital lobe controls vision

The cerebellum. The cerebellum is located at the back part of the brain below the cerebrum. It is responsible for coordination and balance.

The brain stem. This is the portion of the brain that connects to the spinal cord, controls involuntary functions essential for life, such as the beating of the heart and breathing. In addition, messages for all the functions controlled by the cerebrum and cerebellum travel through the brain stem to the connections in the body.

The meninges. These are the membranes that surround and protect the brain and spinal cord. There are three meningeal layers, called the dura mater, arachnoid, and pia mater. The cerebrospinal fluid (CSF) is made near the center of the brain, in the lateral ventricles, and circulates around the brain and spinal cord between the arachnoid and pia layers.

Types of brain tumors

There are more than 100 types of primary brain tumors, and about 5% of all brain tumors cannot be assigned an exact type. For a complete list of the types of brain tumors and how often they are diagnosed, please refer to the Central Brain Tumor Registry of the United States. This section covers brain tumors diagnosed in adults. For practical purposes, this section's coverage is divided into gliomas and non-glioma types of tumors in adults:

Gliomas

As a group, a glioma is one of the most common types of brain tumor. A glioma is a tumor that grows from a glial cell, which is a supportive cell in the brain. There are two main types of supportive cells: astrocytes and oligodendrocytes. Most gliomas are called either astrocytoma or oligodendroglioma, or a mix of both. A glioma is given a grade (a measure of how much the tumor appears like normal brain tissue) from I to IV (one to four) based how likely they are to grow quickly. A grade I glioma is often considered a benign tumor, while grades II through IV are tumors with an increasing likelihood of growing and spreading quickly and are therefore considered possibly cancerous.

Types of gliomas include:

Astrocytoma. Astrocytoma is the most common type of glioma and begins in cells called astrocytes in the cerebrum or cerebellum. There are four grades of astrocytoma.

Grade I or pilocytic astrocytoma is a slow-growing tumor that is most often benign and rarely spreads into nearby tissue. It accounts for about 2% of all brain tumors.

Grade II or low-grade diffuse astrocytoma is a slow-growing tumor that can often spread into nearby tissue and can become a higher grade. It accounts for about 3% of all brain tumors.

Grade III or anaplastic astrocytoma is a cancerous tumor that can quickly grow and spread to nearby tissues. It accounts for about 2% of all brain tumors.

Grade IV or glioblastoma multiforme is a very aggressive form of astrocytoma that accounts for about 16% of all brain tumors.

Oligodendroglioma. Oligodendroglioma is a tumor that develops from cells called oligodendrocytes. These cells are responsible for making the myelin (a substance rich in protein and fatty substances called lipids) that surrounds nerves. Oligodendrogliomas make up about 2% of primary brain tumors and are subclassified as either oligodendrogliomas (considered low grade) or anaplastic oligodendroglioma.

Mixed gliomas. A mixed tumor is made up of more than one of the glial cell types and accounts for about 1% of primary brain tumors.

Ependymomas. Ependymomas begin in the ependyma (the passageways in the brain where CSF is made and stored) and make up about 2% of primary brain tumors. 

Brain stem glioma. A brain stem glioma begins in the glial cells in the brain stem.

Non-glioma tumors

As explained above, this section covers non-glioma tumors, which are tumors that arise from cells in the brain that are not glial (supportive) tissue. Types of non-glioma tumors include:

Meningioma. Meningioma is the most common primary brain tumor, making up about 35% of all primary brain tumors. It begins in the meninges and is most often noncancerous. Meningioma can cause serious symptoms if it grows and presses on the brain or spinal cord or grows into the brain tissue. 

Pineal gland and pituitary gland tumors. About 14% of all brain tumors are located in the pineal gland and pituitary gland.

Primary CNS lymphoma. This is a form of lymphoma (cancer that begins in the lymphatic system) that starts in the brain and can spread to the spinal fluid and eyes. It makes up about 2% of all brain tumors.

Medulloblastoma. Medulloblastoma begins in granular cells in the cerebellum. It is most common in children and is most often cancerous, often spreading throughout the CNS. Medulloblastomas make up about 2% of all brain tumors. Similar tumors can start in other parts of the brain, frequently in the pineal gland region, and are called primitive neuroectodermal tumors (PNET).

Craniopharyngioma. Craniopharyngioma is a benign tumor that begins near the pituitary gland located near the base of the brain. These tumors are rare, making up less than 1% of all brain tumors. 

Acoustic schwannoma. Acoustic schwannoma (also called acoustic neuroma or vestibular schwannomas) is a rare tumor that begins in the vestibular nerve (a nerve in the inner ear that helps control balance) and is typically noncancerous.

Symptoms & Signs

People with a brain tumor may experience the following symptoms or signs. Sometimes, people with a brain tumor do not show any of these symptoms. Or, these symptoms may be caused by a medical condition that is not a brain tumor. If you are concerned about a symptom or sign on this list, please talk with your doctor.

Symptoms of a brain tumor can be general (caused by the pressure of the tumor on the brain or spinal cord) or specific (caused a specific part of the brain not working normally). For many people with a brain tumor, they were diagnosed when they went to the doctor because of certain symptoms.

General symptoms include:

Headaches, which may be severe and may worsen with activity or in the early morning

Seizures. Motor seizures, also called convulsions, are sudden involuntary movements of a person's muscles. People may experience different types of seizures, including myclonic and tonic-clonic (grand mal). Certain drugs can help prevent or control them. The differences between these types of seizures can be found below:

 Myclonic: Single or multiple muscle twitches, jerks, spasms

Tonic-Clonic (Grand Mal): Loss of consciousness and body tone, followed by twitching and relaxing muscles contractions, Loss of control of body functions, May be short period of no breathing (30 seconds) and person may turn a shade of blue, After this type of seizure a person may be sleepy and experience a headache, confusion, weakness, numbness, and sore muscles.

Sensory: Change in sensation, vision, smell, and/or hearing without losing consciousness

Complex partial: May cause a loss of awareness or a partial or total loss of consciousness, May be associated with repetitive, unintentional movements, such as twitching

Personality or memory changes

Nausea or vomiting

Symptoms that may be specific to the location of the tumor include:

Pressure or headache near the tumor

Loss of balance and difficulty with fine motor skills (cerebellum)

Changes in judgment, including loss of initiative, sluggishness, and muscle weakness or paralysis (frontal lobe of the cerebrum)

Partial or complete loss of vision (occipital lobe or temporal lobe of the cerebrum)

Changes in speech, hearing, memory, or emotional state, such as aggressiveness and problems understanding or retrieving words (frontal and temporal lobe of cerebrum)

Altered perception of touch or pressure, arm or leg weakness on one side of the body, or confusion with left and right sides of the body (frontal or parietal lobe of the cerebrum)

Inability to look upward (pineal tumor)

Lactation (secretion of breast milk) and altered menstrual periods in women, and growth in hands and feet in adults (pituitary tumor)

Difficulty swallowing, facial weakness or numbness, or double vision (brain stem)

Vision changes, including loss of part of the vision or double vision (temporal lobe, occipital lobe, or brain stem)

Your doctor will ask you questions about the symptoms you are experiencing to help find out the cause of the problem, called a diagnosis. This may include how long you've been experiencing the symptom(s) and how often.

If a tumor is diagnosed, relieving symptoms and side effects remains an important part of your care and treatment. This may also be called symptom management, palliative care, or supportive care. Be sure to talk with your health care team about symptoms you experience, including any new symptoms or a change in symptoms. 

Risk Factors

A risk factor is anything that increases a person's chance of developing a brain tumor. Although risk factors often influence the development of a brain tumor, most do not directly cause a brain tumor. Some people with several risk factors never develop a brain tumor, while others with no known risk factors do. However, knowing your risk factors and talking about them with your doctor may help you make more informed lifestyle and health care choices.

Most of the time, the cause of a brain tumor is unknown, but the following factors may raise a person's risk of developing a brain tumor:

Age. Brain tumors are more common in children and older adults, although people of any age can develop a brain tumor.

Gender. In general, men are more likely than women to develop a brain tumor. However, some specific types of brain tumors, such as meningioma, are more common in women.

Home/occupational exposures. Occupational exposures to solvents, pesticides, oil products, rubber, or vinyl chloride may increase the risk of developing a brain tumor, although there is not yet scientific evidence that supports this possible link.

Family history. About 5% of brain tumors may be linked to hereditary (genetic) factors or conditions, includingLi-Fraumeni syndrome, neurofibromatosis, nevoid basal cell carcinoma syndrome, tuberous sclerosis, Turcot syndrome, and von Hippel-Lindau disease. Scientists have also found “clusters” of brain tumors within some families without a link to these known hereditary conditions, and studies are underway to try to find a cause.

Exposure to infections, viruses, and allergens. Infection with the Epstein-Barr virus (EBV) increases the risk of CNS lymphoma; EBV is more commonly known as the virus that causes mononucleosis (sometimes called “mono”). In other research, high levels of a common virus called cytomegalovirus (CMV) have been found in brain tumor tissue; the meaning of this finding is being researched. Several types of other viruses have been shown to cause brain tumors in research on animals; however, more data are needed to determine if exposure to infections, other viruses, or allergens affect the risk of a brain tumor in people.

Electromagnetic fields. Electromagnetic fields, such as energy from power lines or from cell phone use, may or may not increase the risk of developing a brain tumor, as current research has shown conflicting results. The World Health Organization (WHO) recommends limiting cell phone use and promotes the use of a hands-free headset for both adults and children.

Race and ethnicity. In the United States, white people are more likely to develop gliomas but less likely to develop meningiomas than black people. Also, people from northern Europe are more than twice as likely to develop a brain tumor as people in Japan.

Ionizing radiation. Previous treatment to the brain or head with ionizing radiation (including x-rays) has shown, in some cases, to be a risk factor for a brain tumor.

Head injury and seizures. Serious head trauma has long been studied for its relationship to brain tumors. Some studies have shown a link between head trauma and meningioma, but not one between head trauma and glioma. A history of seizures has long been associated with brain tumors, but because a brain tumor can cause seizures, it is not known if seizures increase the risk of brain tumors, if seizures occur because of the tumor, or if anti-seizure medication increases the risk.

N-nitroso compounds. Some studies of diet and vitamin supplementation seem to indicate that dietary N-nitroso compounds may raise the risk of both childhood and adult brain tumors. Dietary N-nitroso compounds are formed in the body from nitrites or nitrates found in some cured meats, cigarette smoke, and cosmetics. However, additional research is necessary before a definitive link can be established.

Exposure to nerve agents. One study has shown that some Gulf War veterans are at increased risk of a brain tumor due to exposure to nerve agents; however, more research is needed before a definitive link can be established.

At this time, there are no known ways to prevent a brain tumor.

Diagnosis

Doctors use many tests to diagnose a brain tumor, find out the type of brain tumor, and rarely, find out if it has metastasized (spread). Some tests may also determine which treatments may be the most effective. For most types of tumors, taking a sample of the tumor tissue, either by biopsy (see below) or by removing the entire tumor, is the only way to make a definitive diagnosis of a brain tumor. If this is not possible, the doctor may suggest other tests that will help make a diagnosis. Imaging tests may be used to help determine whether the tumor is a primary brain tumor or if it is another type of cancer from elsewhere in the body that has spread to the brain. Your doctor may consider these factors when choosing a diagnostic test:

Age and medical condition

Type of tumor suspected

Severity of symptoms

Previous test results

Most brain tumors are not diagnosed until after symptoms appear. Often a brain tumor is initially diagnosed by an internist (a doctor who specializes in treating adults) or a neurologist (a doctor who specializes in problems with the brain and central nervous system).

To learn more about the brain tumor, an oncologist (a doctor who specializes in cancer) or neuro-oncologist (a doctor who specializes in treating a brain tumor) can use the patient's symptoms as clues to the location of the tumor. In addition to asking the patient for a detailed medical history and doing a physical examination, the doctor may recommend the tests described below to determine the presence, and perhaps the type or grade, of a brain tumor. Based on the combined results of the different tests, the doctor will recommend treatment options.

Imaging tests

The most effective and common tool for diagnosing a brain tumor is the use of a magnetic resonance imaging (MRI) scan, although computed tomography (CT or CAT) scans are also used. A positron emission tomography (PET) scan is generally used to find out more about a tumor while a patient is being treated or if there is a recurrence (the tumor comes back after treatment).

Once an imaging scan shows that there is a tumor in the brain, the most common way to determine the type of brain tumor is to look at the results from a sample of tissue (called a pathology report or laboratory test results) after a biopsy or surgery (see below).

Each imaging test can provide specific information, but they must be combined with the results of the patient history, physical examination, and neurologic and other tests. The most common imaging tests used for diagnosing a brain tumor include:

MRI. An MRI uses magnetic fields, not x-rays, to produce detailed images of the body. MRIs may create more detailed pictures than CT scans (see below) and are the preferred method of diagnosing a brain tumor. The MRI may be of the brain, spinal cord, or both, depending on the type of tumor suspected and the likelihood that it will spread in the CNS. There are different types of MRI, and the results of a neuro-examination, done by the internist or neurologist, helps determine which type of MRI to use.

Intravenous (IV) gadolinium-enhanced MRI is typically used to help diagnose a brain tumor. This is when a patient first has a regular MRI, and afterwards is given a contrast (a special type of dye called gadolinium) through an IV; a second MRI is then done to get another series of pictures using the dye.

A spinal MRI may be used to diagnose a tumor on or near the spine.

A functional MRI (fMRI) provides information about the location of specific areas of the brain that are responsible for muscle movement and speech. During the fMRI examination, the patient is asked to do certain tasks that cause changes in the brain and can be seen on the fMRI image. This test is often used to plan surgery, so the surgeon can avoid damaging the functional parts of the brain while removing the tumor.

Magnetic resonance spectroscopy (MRS) is a test using MRI that provides information on the chemical composition of the brain. It can help tell the difference between dead (necrotic) tissue caused by previous radiation treatments and new tumor cells in the brain.

CT scan. A CT scan creates a three-dimensional picture of the inside of the body with an x-ray machine. A computer then combines these images into a detailed, cross-sectional view that shows any abnormalities or tumors. A CT scan can help find bleeding and enlargement of the fluid-filled spaces in the brain, called ventricles. Changes to bone in the skull can also be seen on a CT scan. Sometimes, a contrast medium (a special dye) is injected into a patient's vein to provide better detail, particularly if the patient cannot have an MRI (such as if the person has a pacemaker).

PET scan. A PET scan is a way to create pictures of organs and tissues inside the body. A small amount of a radioactive substance is injected into a patient's body. This substance is absorbed mainly by organs and tissues that use the most energy. Because a tumor tends to use energy actively, it absorbs more of the radioactive substance. A scanner then detects this substance to produce images of the inside of the body.

Cerebral arteriogram (also called cerebral angiogram). A cerebral arteriogram is an x-ray, or series of x-rays, of the head that shows the arteries in the brain. X-rays are taken after a contrast medium is injected into the main arteries of the patient's head.

Lumbar puncture (spinal tap). A lumbar puncture is a procedure in which a doctor uses a needle to take a sample of CSF to look for tumor cells, blood, or tumor markers. Typically an anesthetic is given to numb the patient's lower back before the procedure.

Myelogram. Because some specific types of brain tumors can spread to the spinal fluid, other parts of the brain, or the spinal cord, the doctor may recommend a myelogram to look for areas where the tumor may have spread. A myelogram uses a dye injected into the CSF that surrounds the spinal cord. The dye shows up on an x-ray and can outline the spinal cord to help the doctor look for a tumor. This is rarely done; a lumbar puncture (see above) is more common.

Tissue sampling/biopsy/surgical removal of a tumor

As explained above,imaging tests are useful, but a sample of the tumor's tissue is typically needed for the final diagnosis.A biopsy is the removal of a small amount of tissue for examination under a microscope and is the only definitive way a brain tumor diagnosis can be made. The sample removed from the biopsy is analyzed by a pathologist (a doctor who specializes in interpreting laboratory tests and evaluating cells, tissues, and organs to diagnose disease). A biopsy can be done as part of surgery to remove the entire tumor or as a separate procedure (if surgical removal of the tumor is not possible because of its location or the health of the patient.)

Molecular testing of the tumor

Your doctor may recommend running laboratory tests on a tumor sample to identify specific genes, proteins, and other factors, such as tumor markers, unique to the tumor. Tumor markers (also called biomarkers) are substances found in higher than normal amounts in the blood, urine, spinal fluid, plasma or other bodily fluids of people with certain types of cancer. Researchers are examining biomarkers to find ways to diagnose a brain tumor before symptoms begin. Results of these tests may help decide whether your treatment options include a type of treatment called targeted therapy.

Neurological, vision, and hearing tests

These tests help determine if a tumor is affecting how the brain functions. An eye examination can detect changes to the optic nerve.

Neurocognitive assessment

This consists of a detailed assessment of all major functions of the brain, such as storage and retrieval of memory, expressive and receptive language abilities, calculation, dexterity, and the overall well-being of the patient. These tests are done by a licensed clinical neuropsychologist, who will write a formal report to be used for comparison with future assessments or to identify specific problems that can be helped through treatment.

Electroencephalography (EEG)

An EEG is a noninvasive test in which electrodes are attached to the outside of a person's head to measure electrical activity of the brain. It is used to monitor for possible seizures.

Evoked potentials

Evoked potentials involve the use of electrodes to measure the electrical activity of nerves and can often detect acoustic schwannoma, a noncancerous brain tumor. This test can be used as a guide during surgical removal of a tumor that is growing around important nerves.

Test results

After these diagnostic tests are done, your doctor will review all of the results with you. If the diagnosis is a tumor, these results also help the doctor describe the tumor; this is called staging.

Staging and Prognostic Factors

Staging is a way of describing where the tumor is located, if or where it has spread, and whether it is affecting the functions of other organs in the body. A staging system is used for most other types of cancer. There is a formal staging system for adult brain tumors; however, the grading system described below is always used instead.

After a brain tumor has been diagnosed, additional tests will be done to learn more about the tumor. If the tumor is a glial brain tumor, the pathologist will assign a “grade” using a number from I to IV (one to four). The grade indicates how different the tumor cells are from healthy cells, with a higher grade tumor having cells that are the least like healthy cells. The characteristics of the tumor, as seen under the microscope, help determine how cancerous a tumor is. Generally, the lower the grade, the better the prognosis (chance of recovery or long-term control of the tumor).

Prognostic factors

There are several other factors that help doctors determine the appropriate brain tumor treatment plan and determine prognosis:

Tumor histology. As outlined under Diagnosis, a sample of the tumor is removed for analysis. How a tumor looks under a microscope is called tumor histology.

Normal brain tissue usually has differentiated tissue (different types of cells grouped together). Brain tissue that is cancerous is usually made up of cells that look more alike. In general, the more differentiated the brain tissue (and the lower the grade), the better the prognosis.

To determine histology of a glial tumor, doctors look at several factors including, but not limited to, the following:

Mitosis (the number of cells dividing)

Hypercellularity (if the tumor contains large numbers of cells)

Vascular proliferation (if blood vessels in the tumor are growing)

Necrosis (if there is any dead tissue in the tumor)

The pathologist can determine the type of tumor and its grade. To decide on the best treatment for a brain tumor, both the type and grade of the tumor must be determined. In general, a tumor is referred to by grade. The higher the grade, the more rapidly growing the tumor is.

Specifically for glial tumors, the grade is determined by its features, as seen under a microscope, according to the following criteria:

Grade I is a separate group of tumors called juvenile pilocytic astrocytoma (JPA). The term juvenile does not refer to the age of the patient, but rather the type of cell. This is a noncancerous, slow-growing tumor that can typically be cured with surgery. It is different from a low-grade astrocytoma or Grade II glioma, which are likely to recur.

A grade II tumor does not have mitosis, vascular proliferation, or necrosis, but shows increased cellularity.

A grade III tumor is hypercellular and has mitosis but no vascular proliferation and no necrosis. It is often called anaplastic astrocytoma

A grade IV tumor (glioblastoma, also called glioblastoma multiforme or GBM) has vascular proliferation and/or necrosis in addition to the factors common to grade II and III tumors.

Age of patient. In adults, the age of the patient (as well as his or her level of functioning, called functional status, see below) when diagnosed is one of the best ways to predict a patient's prognosis. In general, a younger adult has a better prognosis.

Extent of tumor residual. Resection is surgery to remove a tumor, and residual refers to how much of the tumor remains in the body after surgery. Four classifications are used:

Gross total: The entire tumor was removed (microscopic cells may remain).

Subtotal: Large portions of the tumor were removed.

Partial: Only part of the tumor was removed.

Biopsy only: Only a small portion, used for a biopsy, was removed.

A patient's prognosis is better when all of the tumor can be surgically removed.

Tumor location. A tumor can form in any part of the brain. Some tumor locations cause more damage than others, and some tumors are harder to treat because of their location.

Functional neurologic status. The doctor will test how well a patient is able to function and carry out everyday activities by using a functional assessment scale, such as the Karnofsky Performance Scale (KPS), outlined below. A higher score indicates a better functional status. Typically, the better someone is able to walk and care for themselves indicates a better prognosis.

100 Normal, no complaints, no evidence of disease

90 Able to carry on normal activity; minor symptoms of disease

80 Normal activity with effort; some symptoms of disease

70 Cares for self; unable to carry on normal activity or active work

60 Requires occasional assistance but is able to care for needs

50 Requires considerable assistance and frequent medical care

40 Disabled: requires special care and assistance

30 Severely disabled; hospitalization is indicated, but death not imminent

20 Very sick, hospitalization necessary; active treatment necessary

10 Moribund, fatal processes progressing rapidly

0 Dead

Metastatic spread. A tumor that starts in the brain or spinal cord, if cancerous, often spreads within the CNS only and rarely spreads to other parts of the body in adults. For that reason, with few exceptions, tests looking at the other organs of the body are typically not needed. A tumor that does spread to other parts of the brain or spinal cord is associated with a poorer prognosis.

Biogenetic markers. Certain molecular markers found in the tumor tissue can provide information on the tumor's response to treatment. For instance, for oligodendroglioma, the loss of part of chromosome 1 on the p part of the chromosome, and the loss of part of chromosome 19 on the q part of the chromosome (called a 1p and 19q co-deletion) is associated with a much better response to chemotherapy and more successful treatment and can be used to help plan treatment, especially for anaplastic oligodendroglioma. Also, in glioblastoma, whether a gene called MGMT is changed can help understand a patient's prognosis, and it is being tested in clinical trials (research studies).

Recurrent tumor. A recurrent tumor is one that comes back after treatment. If there is a recurrence, the tumor may need to be graded again using the system above.

Currently, the factors listed above are the best indicators of a patient's prognosis. As discussed in Diagnosis, researchers are currently looking for tumor markers in the tumor tissue that could make a brain tumor easier to diagnose and the staging of an adult brain tumor possible in the future. These tools may someday help doctors analyze the possibility that a brain tumor will grow, develop more effective treatments, and more accurately predict prognosis.

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