Brain Tumor

Definition of Brain Tumor

A brain tumor, or tumour, is an intracranial solid neoplasm, a tumor (defined as an abnormal growth of cells) within the brain or the central spinal canal.

Brain tumors include all tumors inside the cranium or in the central spinal canal. They are created by an abnormal and uncontrolled cell division, usually in the brain itself, but also in lymphatic tissue, in blood vessels, in the cranial nerves, in the brain envelopes (meninges), skull, pituitary gland, or pineal gland. Within the brain itself, the involved cells may be neurons or glial cells (which include astrocytes, oligodendrocytes, and ependymal cells). Brain tumors may also spread from cancers primarily located in other organs (metastatic tumors).

Any brain tumor is inherently serious and life-threatening because of its invasive and infiltrative character in the limited space of the intracranial cavity. However, brain tumors (even malignant ones) are not invariably fatal, especially lipomas which are inherently benign. Brain tumors or intracranial neoplasms can be cancerous (malignant) or non-cancerous (benign); however, the definitions of malignant or benign neoplasms differs from those commonly used in other types of cancerous or non-cancerous neoplasms in the body. Its threat level depends on the combination of factors like the type of tumor, its location, its size and its state of development. Because the brain is well protected by the skull, the early detection of a brain tumor occurs only when diagnostic tools are directed at the intracranial cavity. Usually detection occurs in advanced stages when the presence of the tumor has caused unexplained symptoms.

Primary (true) brain tumors are commonly located in the posterior cranial fossa in children and in the anterior two-thirds of the cerebral hemispheres in adults, although they can affect any part of the brain.

Cause of Brain Tumor

Aside from exposure to vinyl chloride or ionizing radiation, there are no known environmental factors associated with brain tumors. Mutations and deletions of so-called tumor suppressor genes are thought to be the cause of some forms of brain tumors. People with various inherited diseases, such as Von Hippel-Lindau syndrome, multiple endocrine neoplasia, neurofibromatosis type 2 are at high risk of developing brain tumors.

Although studies have not shown any link between cell phone radiation and brain tumors, the World Health Organization has classified mobile phone radiation on the IARC scale into Group 2B – possibly carcinogenic. That means that there “could be some risk” of carcinogenicity, so additional research into the long-term, heavy use of mobile phones needs to be conducted.

Signs and Symptoms of Brain Tumor

Visibility of signs and symptoms of brain tumors mainly depends on two factors: tumor size (volume) and tumor location. The moment that symptoms will become apparent, either to the person or people around him (symptom onset) is an important milestone in the course of the diagnosis and treatment of the tumor. The symptom onset – in the timeline of the development of the neoplasm – depends in many cases on the nature of the tumor but in many cases is also related to the change of the neoplasm from “benign” (i.e. slow-growing/late symptom onset) to more malignant (fast growing/early symptom onset). Brain evolution is an intricate weave of species similarities and differences, kept together by different rules and principles.

Symptoms of solid neoplasms of the brain (primary brain tumors and secondary tumors alike) can be divided in 3 main categories:

-Consequences of intracranial hypertension: The symptoms that often occur first are those that are the consequences of increased intracranial pressure: Large tumors or tumors with extensive perifocal swelling (edema) inevitably lead to elevated intracranial pressure (intracranial hypertension), which translates clinically into headaches, vomiting (sometimes without nausea), altered state of consciousness (somnolence, coma), dilation of the pupil on the side of the lesion (anisocoria), papilledema (prominent optic disc at the funduscopic eye examination). However, even small tumors obstructing the passage of cerebrospinal fluid (CSF) may cause early signs of increased intracranial pressure. Increased intracranial pressure may result in herniation (i.e. displacement) of certain parts of the brain, such as the cerebellar tonsils or the temporal uncus, resulting in lethal brainstem compression. In very young children, elevated intracranial pressure may cause an increase in the diameter of the skull and bulging of the fontanelles.

-Dysfunction: depending on the tumor location and the damage it may have caused to surrounding brain structures, either through compression or infiltration, any type of focal neurologic symptoms may occur, such as cognitive and behavioral impairment (including impaired judgment, memory loss, lack of recognition, spatial orientation disorders), personality or emotional changes, hemiparesis, hypoesthesia, aphasia, ataxia, visual field impairment, impaired sense of smell, impaired hearing, facial paralysis, double vision, dizziness, but more severe symptoms might occur too such as: paralysis on one side of the body hemiplegia or impairment to swallow . These symptoms are not specific for brain tumors – they may be caused by a large variety of neurologic conditions (e.g. stroke, traumatic brain injury). What counts, however, is the location of the lesion and the functional systems (e.g. motor, sensory, visual, etc.) it affects. A bilateral temporal visual field defect (bitemporal hemianopia—due to compression of the optic chiasm), often associated with endocrine dysfunction—either hypopituitarism or hyperproduction of pituitary hormones and hyperprolactinemia is suggestive of a pituitary tumor.

-Irritation: abnormal fatigue, weariness, absences and tremors, but also epileptic seizures.

The above symptoms are true for ALL types of neoplasm of the brain (including secondary tumors). It is common that a person carries a primary benign neoplasm for several years and have no visible symptoms at all. Many present some uncertain and intermittent symptoms like headaches and occasional vomiting or weariness, which can be easily mistaken for gastritis or gastroenteritis. It might seem strange that despite having a mass in his skull exercising pressure on the brain the patient feels no pain, but as anyone who has suffered a concussion can attest, pain is felt on the outside of the skull and not in the brain itself. The brain has no nerve sensors in the meninges (outer surface) with which to feel or transmit pain to the brain’s pain center; it cannot signal pain without a sensory input. That is why secondary symptoms like those described above should alert doctors to the possible diagnosis of a neoplasm of the brain.

Risk Factors for Brain Tumor

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 most common in older adults. However, a brain tumor can occur at any age. And certain types of brain tumors, such as medulloblastomas, occur almost exclusively in children.
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. A small portion of brain tumors occur in people with a family history of brain tumors or a family history of genetic syndromes that increase the risk of brain tumors.
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.
Exposure to radiation.People who have been exposed to a type of radiation called ionizing radiation have an increased risk of brain tumor. Examples of ionizing radiation include radiation therapy used to treat cancer and radiation exposure caused by atomic bombs. More common forms of radiation, such as electromagnetic fields from power lines and radiofrequency radiation from cellphones and microwave ovens, have not been proved to be linked to brain tumors.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 general, brain tumors occur more frequently in whites than they do in people of other races.
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 of Brain Tumor

The majority of the brain is separated from the blood by the blood-brain barrier (BBB) which exerts a restrictive control as to which substances are allowed to pass. Therefore many tracers that reach tumors in the body very easily would only reach brain tumors once there is a disruption of the BBB. Therefore the disruption of the BBB (blood-brain-barrier), which can be detected by and MRI and CT, is regarded as the main diagnostic indicator for malignant gliomas, meningiomas, and brain metastases.

Although there is no specific or singular clinical symptom or sign for any brain tumors, the presence of a combination of symptoms and the lack of corresponding clinical indications of infections or other causes can be an indicator to redirect diagnostic investigation towards the possibility of an intracranial neoplasm. Brain tumors have similar characteristics and obstacles when it comes to diagnosis and therapy with tumors located elsewhere in the body. However, they create specific issues that follow closely to the properties of the organ they are in.

The diagnosis will often start with an interrogation of the patient to get a clear view of his medical antecedents, and his current symptoms. Clinical and laboratory investigations will serve to exclude infections as the cause of the symptoms. Examinations in this stage may include the eyes, otolaryngological (or ENT) and/or electrophysiological exams. The use of electroencephalography (EEG) often plays a role in the diagnosis of brain tumors.

Swelling, or obstruction of the passage of cerebrospinal fluid (CSF) from the brain may cause (early) signs of increased intracranial pressure which translates clinically into headaches, vomiting, or an altered state of consciousness, and in children changes to the diameter of the skull and bulging of the fontanelles. More complex symptoms such as endocrine dysfunctions should alarm doctors not to exclude brain tumors.

A bilateral temporal visual field defect (due to compression of the optic chiasm) or dilatation of the pupil, and the occurrence of either slowly evolving or the sudden onset of focal neurologic symptoms, such as cognitive and behavioral impairment (including impaired judgment, memory loss, lack of recognition, spatial orientation disorders), personality or emotional changes, hemiparesis, hypoesthesia, aphasia, ataxia, visual field impairment, impaired sense of smell, impaired hearing, facial paralysis, double vision, or more severe symptoms such as tremors, paralysis on one side of the body hemiplegia, or (epileptic) seizures in a patient with a negative history for epilepsy, should raise the possibility of a brain tumor.

Imaging

Imaging plays a central role in the diagnosis of brain tumors. Early imaging methods—invasive and sometimes dangerous— such as pneumoencephalography and cerebral angiography, have been abandoned in recent times in favor of non-invasive, high-resolution techniques, especially magnetic resonance imaging (MRI) and computed tomography (CT)-scans. Neoplasms will often show as differently colored masses (also referred to as processes) in CT or MRI results.

Benign brain tumors often show up as hypodense (darker than brain tissue) mass lesions on cranial CT-scans. On MRI, they appear either hypo- (darker than brain tissue) or isointense (same intensity as brain tissue) on T1-weighted scans, or hyperintense (brighter than brain tissue) on T2-weighted MRI, although the appearance is variable.

Contrast agent uptake, sometimes in characteristic patterns, can be demonstrated on either CT or MRI-scans in most malignant primary and metastatic brain tumors.

Perifocal edema, or pressure-areas, or where the brain tissue has been compressed by an invasive process also appears hyperintense on T2-weighted MRI, they might indicate the presence a diffuse neoplasm.

This is because these tumors disrupt the normal functioning of the blood–brain barrier and lead to an increase in its permeability. However it is not possible to diagnose high versus low grade gliomas based on enhancement pattern alone.

Glioblastoma multiforme and anaplastic astrocytoma have been associated[by whom?] with the genetic acute hepatic porphyrias (PCT, AIP, HCP and VP), including positive testing associated with drug refractory seizures. Unexplained complications associated with drug treatments with these tumors should alert physicians to an undiagnosed neurological porphyria.

The definitive diagnosis of brain tumor can only be confirmed by histological examination of tumor tissue samples obtained either by means of brain biopsy or open surgery. The histological examination is essential for determining the appropriate treatment and the correct prognosis. This examination, performed by a pathologist, typically has three stages: interoperative examination of fresh tissue, preliminary microscopic examination of prepared tissues, and follow-up examination of prepared tissues after immunohistochemical staining or genetic analysis.

Pathology

Micrograph of an oligodendroglioma, a type of brain cancer. Brain biopsy. H&E stain.

Tumors have characteristics that allow determination of its malignacy, how it will evolve and it will allow the medical team to determine the management plan.

Anaplasia: or dedifferentiation; loss of differentiation of cells and of their orientation to one another and blood vessels, a characteristic of anaplastic tumor tissue. Anaplastic cells have lost total control of their normal functions and many have deteriorated cell structures. Anaplastic cells often have abnormally high nuclear-to-cytoplasmic ratios, and many are multinucleated. Additionally, the nuclei of anaplastic cells are usually unnaturally shaped or oversized nuclei. Cells can become anaplastic in two ways: neoplastic tumor cells can dedifferentiate to become anaplasias (the dedifferentiation causes the cells to lose all of their normal structure/function), or cancer stem cells can increase in their capacity to multiply (i.e., uncontrollable growth due to failure of differentiation).

Atypia: is an indication of abnormality of a cell (which may be indicative for malignancy). Significance of the abnormality is highly dependent on context.

Neoplasia: is the (uncontrolled) division of cells; as such neoplasia is not problematic but its consequences are: the uncontrolled division of cells means that the mass of a neoplasm increases in size, and in a confined space such as the intracranial cavity this quickly becomes problematic because the mass invades the space of the brain pushing it aside, leading to compression of the brain tissue and increased intracranial pressure and destruction of brain parenchyma. Increased Intracranial pressure (ICP) may be attributable to the direct mass effect of the tumor, increased blood volume, or increased cerebrospinal fluid (CSF) volume may in turn have secondary symptoms

Necrosis: is the (premature) death of cells, caused by external factors such as infection, toxin or trauma. Necrotic cells send the wrong chemical signals which prevents phagocytes from disposing of the dead cells, leading to a build up of dead tissue, cell debris and toxins at or near the site of the necrotic cells.

Arterial and venous hypoxia, or the deprivation of adequate oxygen supply to certain areas of the brain, occurs when a tumor makes use of nearby blood vessels for its supply of blood and the neoplasm enters into competition for nutrients with the surrounding brain tissue.

More generally a neoplasm may cause release of metabolic end products (e.g., free radicals, altered electrolytes, neurotransmitters), and release and recruitment of cellular mediators (e.g., cytokines) that disrupt normal parenchymal function.

Classification

-Secondary brain tumors

Secondary tumors of the brain are metastatic tumors that invaded the intracranial sphere from cancers originating in other organs. This means that a cancerous neoplasm has developed in another organ elsewhere in the body and that cancer cells have leaked from that primary tumor and then entered the lymphatic system and blood vessels. These are most common among brain tumors. They then circulate through the bloodstream, and are deposited in the brain. There, these cells continue growing and dividing, becoming another invasive neoplasm of the primary cancer’s tissue. Secondary tumors of the brain are very common in the terminal phases of patients with an incurable metastasized cancer; the most common types of cancers that bring about secondary tumors of the brain are lung cancer, breast cancer, malignant melanoma, kidney cancer and colon cancer (in decreasing order of frequency).

Secondary brain tumors are the most common cause of tumors in the intracranial cavity.

The skull bone structure can also be subject to a neoplasm that by its very nature reduces the volume of the intracranial cavity, and can damage the brain.

-By behavior

Brain tumors or intracranial neoplasms can be cancerous (malignant) or non-cancerous (benign). However, the definitions of malignant or benign neoplasms differs from those commonly used in other types of cancerous or non-cancerous neoplasms in the body. In cancers elsewhere in the body, three malignant properties differentiate benign tumors from malignant forms of cancer: benign tumors are self-limited and do not invade or metastasize. Characteristics of malignant tumors include:

uncontrolled mitosis (growth by division beyond the normal limits)
anaplasia: the cells in the neoplasm have an obviously different form (in size and shape). Anaplastic cells display marked pleomorphism. The cell nuclei are characteristically extremely hyperchromatic (darkly stained) and enlarged; the nucleus might have the same size as the cytoplasm of the cell (nuclear-cytoplasmic ratio may approach 1:1, instead of the normal 1:4 or 1:6 ratio). Giant cells – considerably larger than their neighbors – may form and possess either one enormous nucleus or several nuclei (syncytia). Anaplastic nuclei are variable and bizarre in size and shape.
invasion or infiltration (medical literature uses these terms as synonymous equivalents. However, for clarity, the articles that follow adhere to a convention that they mean slightly different things; this convention is not followed outside these articles):

-Invasion or invasiveness is the spatial expansion of the tumor through uncontrolled mitosis, in the sense that the neoplasm invades the space occupied by adjacent tissue, thereby pushing the other tissue aside and eventually compressing the tissue. Often these tumors are associated with clearly outlined tumors in imaging.
-Infiltration is the behavior of the tumor either to grow (microscopic) tentacles that push into the surrounding tissue (often making the outline of the tumor undefined or diffuse) or to have tumor cells “seeded” into the tissue beyond the circumference of the tumorous mass; this does not mean that an infiltrative tumor does not take up space or does not compress the surrounding tissue as it grows, but an infiltrating neoplasm makes it difficult to say where the tumor ends and the healthy tissue starts.

metastasis (spread to other locations in the body via lymph or blood).

Of the above malignant characteristics, some elements do not apply to primary neoplasms of the brain:

Primary brain tumors rarely metastasize to other organs; some forms of primary brain tumors can metastasize but will not spread outside the intracranial cavity or the central spinal canal. Due to the blood–brain barrier cancerous cells of a primary neoplasm cannot enter the bloodstream and get carried to another location in the body. (Occasional isolated case reports suggest spread of certain brain tumors outside the central nervous system, e.g. bone metastasis of glioblastoma multiforme.)
Primary brain tumors generally are invasive (i.e. they will expand spatially and intrude into the space occupied by other brain tissue and compress those brain tissues), however some of the more malignant primary brain tumors will infiltrate the surrounding tissue.

Prevention from Brain Tumor

Follow the steps to prevent from Brain Tumor:

Ask about family medical history. About 5% of brain tumors may be linked to hereditary (genetic) factors or conditions. Becoming educated on the history of brain cancer or other diseases in family members can help prevent cancer. Understanding family history of brain cancer can help with identification of symptoms and treatment options. Life expectancy is almost always extended when cancer is detected in patients early.
Note environmental conditions. Molecular and cellular mutations in the brain can cause brain tumors and lead to cancer. Exposure to certain environmental elements can also increase the risk. To prevent brain cancer, avoid vinyl chloride and other cancer causing chemicals. Be aware of any therapeutic radiation treatments to the head. Low dosage radiation to the head could be happening currently, if other cancers are being treated, or from childhood, if radiation occurred to combat a fungal infection to the scalp.
Check for immune system problems or other health issues. Certain immune system disorders have led to a rare type of brain cancer called central nervous system lymphoma. Loss of vision and muscle weakness are symptoms to get checked by a doctor.
Pay attention to cell phone usage. The World Health Organization (WHO) recommends limiting cell phone use and promotes the use of a hands-free headset for both adults and children. There is no evidence that using a cell phone causes brain cancer. But to prevent brain cancer, it is important to understand that cell phones do emit radiation energy to parts of the body.
Eat healthily. Work to prevent brain cancer and all types of cancer by exercising, eating healthy and nutritious foods, not smoking, eliminating stress, and drinking in moderation.

Treatment of Brain Tumor

When a brain tumor is diagnosed, a medical team will be formed to assess the treatment options presented by the leading surgeon to the patient and his/her family. Given the location of primary solid neoplasms of the brain in most cases a “do-nothing” option is usually not presented. Neurosurgeons take the time to observe the evolution of the neoplasm before proposing a management plan to the patient and his/her relatives. These various types of treatment are available depending on neoplasm type and location and may be combined to give the best chances of survival:

surgery: complete or partial resection of the tumor with the objective of removing as many tumor cells as possible
radiotherapy: the most commonly used treatment for brain tumors; the tumor is irradiated with beta, x rays or gamma rays.
chemotherapy: is a treatment option for cancer, however it is seldom used to treat brain tumors as the blood and brain barrier prevents the drugs from reaching the cancerous cells. Chemotherapy can be thought of as a poison that prevents the growth and division of all cells in the body including cancerous cells. Thus the significant side effects associated and experienced by patients undergoing chemotherapy.
A variety of experimental therapies are available through clinical trials

Survival rates in primary brain tumors depend on the type of tumor, age, functional status of the patient, the extent of surgical tumor removal and other factors specific to each case.

Surgery

The primary and most desired course of action described in medical literature is surgical removal (resection) via craniotomy. Minimally invasive techniques are being studied but are far from being common practice. The prime remediating objective of surgery is to remove as many tumor cells as possible, with complete removal being the best outcome and cytoreduction (“debulking”) of the tumor otherwise. In some cases access to the tumor is impossible and impedes or prohibits surgery.

Many meningiomas, with the exception of some tumors located at the skull base, can be successfully removed surgically. Most pituitary adenomas can be removed surgically, often using a minimally invasive approach through the nasal cavity and skull base (trans-nasal, trans-sphenoidal approach). Large pituitary adenomas require a craniotomy (opening of the skull) for their removal. Radiotherapy, including stereotactic approaches, is reserved for inoperable cases.

Several current research studies aim to improve the surgical removal of brain tumors by labeling tumor cells with 5-aminolevulinic acid that causes them to fluoresce. Postoperative radiotherapy and chemotherapy are integral parts of the therapeutic standard for malignant tumors. Radiotherapy may also be administered in cases of “low-grade” gliomas, when a significant tumor burden reduction could not be achieved surgically.

Any person undergoing brain surgery may suffer from epileptic seizures. Seizures can vary from absences to severe tonic-clonic attacks. Medication is prescribed and administered to minimize or eliminate the occurrence of seizures.

Multiple metastatic tumors are generally treated with radiotherapy and chemotherapy rather than surgery and the prognosis in such cases is determined by the primary tumor, but is generally poor.

Radiation therapy

The goal of radiation therapy is to selectively kill tumor cells while leaving normal brain tissue unharmed. In standard external beam radiation therapy, multiple treatments of standard-dose “fractions” of radiation are applied to the brain. This process is repeated for a total of 10 to 30 treatments, depending on the type of tumor. This additional treatment provides some patients with improved outcomes and longer survival rates.

Radiosurgery is a treatment method that uses computerized calculations to focus radiation at the site of the tumor while minimizing the radiation dose to the surrounding brain. Radiosurgery may be an adjunct to other treatments, or it may represent the primary treatment technique for some tumors.

Radiotherapy may be used following, or in some cases in place of, resection of the tumor. Forms of radiotherapy used for brain cancer include external beam radiation therapy, brachytherapy, and in more difficult cases, stereotactic radiosurgery, such as Gamma knife, Cyberknife or Novalis Tx radiosurgery.

Radiotherapy is the most common treatment for secondary brain tumors. The amount of radiotherapy depends on the size of the area of the brain affected by cancer. Conventional external beam ‘whole brain radiotherapy treatment’ (WBRT) or ‘whole brain irradiation’ may be suggested if there is a risk that other secondary tumors will develop in the future. Stereotactic radiotherapy is usually recommended in cases involving fewer than three small secondary brain tumors.

Chemotherapy

Patients undergoing chemotherapy are administered drugs designed to kill tumor cells. Although chemotherapy may improve overall survival in patients with the most malignant primary brain tumors, it does so in only about 20 percent of patients. Chemotherapy is often used in young children instead of radiation, as radiation may have negative effects on the developing brain. The decision to prescribe this treatment is based on a patient’s overall health, type of tumor, and extent of the cancer. The toxicity and many side effects of the drugs, and the uncertain outcome of chemotherapy in brain tumors puts this treatment further down the line of treatment options with surgery and radiation therapy preferred.

Other

A shunt is used not as a cure but to relieve symptoms by reducing hydrocephalus caused by blockage of cerebrospinal fluid.
Researchers are presently investigating a number of promising new treatments including gene therapy, highly focused radiation therapy, immunotherapy and novel chemotherapies. A variety of new treatments are being made available on an investigational basis at centers specializing in brain tumor therapies.