Brain tumor
Encyclopedia
A brain tumor is an intracranial
Human skull
The human skull is a bony structure, skeleton, that is in the human head and which supports the structures of the face and forms a cavity for the brain.In humans, the adult skull is normally made up of 22 bones...

 solid neoplasm, a tumor
Tumor
A tumor or tumour is commonly used as a synonym for a neoplasm that appears enlarged in size. Tumor is not synonymous with cancer...

 (defined as an abnormal growth of cells) within the brain
Human brain
The human brain has the same general structure as the brains of other mammals, but is over three times larger than the brain of a typical mammal with an equivalent body size. Estimates for the number of neurons in the human brain range from 80 to 120 billion...

 or the central spinal canal
Spinal canal
The spinal canal is the space in vertebrae through which the spinal cord passes. It is a process of the dorsal human body cavity. This canal is enclosed within the vertebral foramen of the vertebrae...

.

Brain tumors include all tumors inside the cranium
Human skull
The human skull is a bony structure, skeleton, that is in the human head and which supports the structures of the face and forms a cavity for the brain.In humans, the adult skull is normally made up of 22 bones...

 or in the central spinal canal. They are created by an abnormal and uncontrolled cell division
Mitosis
Mitosis is the process by which a eukaryotic cell separates the chromosomes in its cell nucleus into two identical sets, in two separate nuclei. It is generally followed immediately by cytokinesis, which divides the nuclei, cytoplasm, organelles and cell membrane into two cells containing roughly...

, usually in the brain itself, but also in lymph
Lymph
Lymph is considered a part of the interstitial fluid, the fluid which lies in the interstices of all body tissues. Interstitial fluid becomes lymph when it enters a lymph capillary...

atic tissue, in blood vessel
Blood vessel
The blood vessels are the part of the circulatory system that transports blood throughout the body. There are three major types of blood vessels: the arteries, which carry the blood away from the heart; the capillaries, which enable the actual exchange of water and chemicals between the blood and...

s, in the cranial nerves, in the brain envelopes (meninges
Meninges
The meninges is the system of membranes which envelopes the central nervous system. The meninges consist of three layers: the dura mater, the arachnoid mater, and the pia mater. The primary function of the meninges and of the cerebrospinal fluid is to protect the central nervous system.-Dura...

), skull
Human skull
The human skull is a bony structure, skeleton, that is in the human head and which supports the structures of the face and forms a cavity for the brain.In humans, the adult skull is normally made up of 22 bones...

, pituitary gland, or pineal gland
Pineal gland
The pineal gland is a small endocrine gland in the vertebrate brain. It produces the serotonin derivative melatonin, a hormone that affects the modulation of wake/sleep patterns and seasonal functions...

. Within the brain itself, the involved cells may be neuron
Neuron
A neuron is an electrically excitable cell that processes and transmits information by electrical and chemical signaling. Chemical signaling occurs via synapses, specialized connections with other cells. Neurons connect to each other to form networks. Neurons are the core components of the nervous...

s or glial cells (which include astrocyte
Astrocyte
Astrocytes , also known collectively as astroglia, are characteristic star-shaped glial cells in the brain and spinal cord...

s, oligodendrocyte
Oligodendrocyte
Oligodendrocytes , or oligodendroglia , are a type of brain cell. They are a variety of neuroglia. Their main function is the insulation of axons in the central nervous system of some vertebrates...

s, ependymal cells, and myelin
Myelin
Myelin is a dielectric material that forms a layer, the myelin sheath, usually around only the axon of a neuron. It is essential for the proper functioning of the nervous system. Myelin is an outgrowth of a type of glial cell. The production of the myelin sheath is called myelination...

-producing Schwann cell
Schwann cell
Schwann cells or neurolemmocytes are the principal glia of the peripheral nervous system . Glial cells function to support neurons and in the PNS, also include satellite cells, olfactory ensheathing cells, enteric glia and glia that reside at sensory nerve endings, such as the Pacinian corpuscle...

s). Brain tumors may also spread from cancer
Cancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...

s primarily located in other organs (metastatic tumors
Metastasis
Metastasis, or metastatic disease , is the spread of a disease from one organ or part to another non-adjacent organ or part. It was previously thought that only malignant tumor cells and infections have the capacity to metastasize; however, this is being reconsidered due to new research...

).

Any brain tumor is inherently serious and life-threatening because of its invasive
Invasive
Invasive may refer to:*A military invasion*An invasive species*An invasive medical procedure*The invasively progressive spread of disease from one organ in the body to another, especially in reference to cancer...

 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 only occurs 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
Posterior cranial fossa
The posterior cranial fossa is part of the intracranial cavity, located between the foramen magnum and tentorium cerebelli. It contains the brainstem and cerebellum.This is the most inferior of the fossae. It houses the cerebellum, medulla and pons....

 in child
Child
Biologically, a child is generally a human between the stages of birth and puberty. Some vernacular definitions of a child include the fetus, as being an unborn child. The legal definition of "child" generally refers to a minor, otherwise known as a person younger than the age of majority...

ren and in the anterior two-thirds of the cerebral hemispheres in adults, although they can affect any part of the brain
Human brain
The human brain has the same general structure as the brains of other mammals, but is over three times larger than the brain of a typical mammal with an equivalent body size. Estimates for the number of neurons in the human brain range from 80 to 120 billion...

.

Signs and symptoms

The 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).

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
    Edema
    Edema or oedema ; both words from the Greek , oídēma "swelling"), formerly known as dropsy or hydropsy, is an abnormal accumulation of fluid beneath the skin or in one or more cavities of the body that produces swelling...

    ) inevitably lead to elevated intracranial pressure
    Intracranial pressure
    Intracranial pressure is the pressure inside the skull and thus in the brain tissue and cerebrospinal fluid . The body has various mechanisms by which it keeps the ICP stable, with CSF pressures varying by about 1 mmHg in normal adults through shifts in production and absorption of CSF...

     (intracranial hypertension), which translates clinically into headaches, vomiting
    Vomiting
    Vomiting is the forceful expulsion of the contents of one's stomach through the mouth and sometimes the nose...

     (sometimes without nausea
    Nausea
    Nausea , is a sensation of unease and discomfort in the upper stomach with an involuntary urge to vomit. It often, but not always, precedes vomiting...

    ), altered state of consciousness
    Consciousness
    Consciousness is a term that refers to the relationship between the mind and the world with which it interacts. It has been defined as: subjectivity, awareness, the ability to experience or to feel, wakefulness, having a sense of selfhood, and the executive control system of the mind...

     (somnolence
    Somnolence
    Somnolence is a state of near-sleep, a strong desire for sleep, or sleeping for unusually long periods . It has two distinct meanings, referring both to the usual state preceding falling asleep, and the chronic condition referring to being in that state independent of a circadian rhythm...

    , coma
    Coma
    In medicine, a coma is a state of unconsciousness, lasting more than 6 hours in which a person cannot be awakened, fails to respond normally to painful stimuli, light or sound, lacks a normal sleep-wake cycle and does not initiate voluntary actions. A person in a state of coma is described as...

    ), dilation of the pupil on the side of the lesion (anisocoria
    Anisocoria
    -Causes:In the absence of the iris or eyeball proper, anisocoria is usually the result of a defect in efferent nervous pathways controlling the pupil traveling in the oculomotor nerve or the sympathetic pathways...

    ), papilledema
    Papilledema
    Papilledema is optic disc swelling that is caused by increased intracranial pressure. The swelling is usually bilateral and can occur over a period of hours to weeks. Unilateral presentation is extremely rare....

     (prominent optic disc
    Optic disc
    The optic disc or optic nerve head is the location where ganglion cell axons exit the eye to form the optic nerve. There are no light sensitive rods or cones to respond to a light stimulus at this point. This causes a break in the visual field called "the blind spot" or the "physiological blind spot"...

     at the funduscopic eye examination). However, even small tumors obstructing the passage of cerebrospinal fluid
    Cerebrospinal fluid
    Cerebrospinal fluid , Liquor cerebrospinalis, is a clear, colorless, bodily fluid, that occupies the subarachnoid space and the ventricular system around and inside the brain and spinal cord...

     (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
    Uncus
    The anterior extremity of the Parahippocampal gyrus is recurved in the form of a hook, the uncus, which is separated from the apex of the temporal lobe by a slight fissure, the incisura temporalis....

    , resulting in lethal brainstem compression. In very young children, elevated intracranial pressure may cause an increase in the diameter of the skull
    Human skull
    The human skull is a bony structure, skeleton, that is in the human head and which supports the structures of the face and forms a cavity for the brain.In humans, the adult skull is normally made up of 22 bones...

     and bulging of the fontanelle
    Fontanelle
    A fontanelle is an anatomical feature on an infant's skull.-Anatomy:Fontanelles are soft spots on a baby's head which, during birth, enable the bony plates of the skull to flex, allowing the child's head to pass through the birth canal. The ossification of the bones of the skull causes the...

    s.
  • Dysfunction : depending on the tumor location and the damage it may have caused to surrounding brain
    Human brain
    The human brain has the same general structure as the brains of other mammals, but is over three times larger than the brain of a typical mammal with an equivalent body size. Estimates for the number of neurons in the human brain range from 80 to 120 billion...

     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
    Hemiparesis
    Hemiparesis is weakness on one side of the body. It is less severe than hemiplegia - the total paralysis of the arm, leg, and trunk on one side of the body. Thus, the patient can move the impaired side of his body, but with reduced muscular strength....

    , hypoesthesia
    Hypoesthesia
    Hypoesthesia refers to a reduced sense of touch or sensation, or a partial loss of sensitivity to sensory stimuli....

    , aphasia
    Aphasia
    Aphasia is an impairment of language ability. This class of language disorder ranges from having difficulty remembering words to being completely unable to speak, read, or write....

    , ataxia
    Ataxia
    Ataxia is a neurological sign and symptom that consists of gross lack of coordination of muscle movements. Ataxia is a non-specific clinical manifestation implying dysfunction of the parts of the nervous system that coordinate movement, such as the cerebellum...

    , visual field
    Visual field
    The term visual field is sometimes used as a synonym to field of view, though they do not designate the same thing. The visual field is the "spatial array of visual sensations available to observation in introspectionist psychological experiments", while 'field of view' "refers to the physical...

     impairment, impaired sense of smell, impaired hearing, facial paralysis, double vision
    Diplopia
    Diplopia, commonly known as double vision, is the simultaneous perception of two images of a single object that may be displaced horizontally, vertically, or diagonally in relation to each other...

    , dizziness
    Dizziness
    Dizziness refers to an impairment in spatial perception and stability. The term is somewhat imprecise. It can be used to mean vertigo, presyncope, disequilibrium, or a non-specific feeling such as giddiness or foolishness....

    , but more severe symptoms might occur too such as: paralysis on one side of the body hemiplegia
    Hemiplegia
    Hemiplegia /he.mə.pliː.dʒiə/ is total paralysis of the arm, leg, and trunk on the same side of the body. Hemiplegia is more severe than hemiparesis, wherein one half of the body has less marked weakness....

     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
    Stroke
    A stroke, previously known medically as a cerebrovascular accident , is the rapidly developing loss of brain function due to disturbance in the blood supply to the brain. This can be due to ischemia caused by blockage , or a hemorrhage...

    , traumatic brain injury
    Traumatic brain injury
    Traumatic brain injury , also known as intracranial injury, occurs when an external force traumatically injures the brain. TBI can be classified based on severity, mechanism , or other features...

    ). 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
    Visual field
    The term visual field is sometimes used as a synonym to field of view, though they do not designate the same thing. The visual field is the "spatial array of visual sensations available to observation in introspectionist psychological experiments", while 'field of view' "refers to the physical...

     defect (bitemporal hemianopia—due to compression of the optic chiasm
    Optic chiasm
    The optic chiasm or optic chiasma is the part of the brain where the optic nerves partially cross...

    ), often associated with endocrine disfunction—either hypopituitarism
    Hypopituitarism
    Hypopituitarism is the decreased secretion of one or more of the eight hormones normally produced by the pituitary gland at the base of the brain...

     or hyperproduction of pituitary hormones and hyperprolactinemia is suggestive of a pituitary tumor.
  • Irritation : abnormal fatigue, weariness, absences and tremor
    Tremor
    A tremor is an involuntary, somewhat rhythmic, muscle contraction and relaxation involving to-and-fro movements of one or more body parts. It is the most common of all involuntary movements and can affect the hands, arms, eyes, face, head, vocal folds, trunk, and legs. Most tremors occur in the...

    s, but also epileptic seizures
    Epilepsy
    Epilepsy is a common chronic neurological disorder characterized by seizures. These seizures are transient signs and/or symptoms of abnormal, excessive or hypersynchronous neuronal activity in the brain.About 50 million people worldwide have epilepsy, and nearly two out of every three new cases...

    .


The above symptoms are true for ALL types of neoplasm of the brain (including secondary tumors). It is common that a person carry a primary benign neoplasm for several years and have no visible symptoms at all. Many present some vague and intermittent symptoms like headaches and occasional vomiting or weariness, which can be easily mistaken for gastritis
Gastritis
Gastritis is an inflammation of the lining of the stomach, and has many possible causes. The main acute causes are excessive alcohol consumption or prolonged use of nonsteroidal anti-inflammatory drugs such as aspirin or ibuprofen. Sometimes gastritis develops after major surgery, traumatic...

 or gastroenteritis
Gastroenteritis
Gastroenteritis is marked by severe inflammation of the gastrointestinal tract involving both the stomach and small intestine resulting in acute diarrhea and vomiting. It can be transferred by contact with contaminated food and water...

. 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
Skull
The skull is a bony structure in the head of many animals that supports the structures of the face and forms a cavity for the brain.The skull is composed of two parts: the cranium and the mandible. A skull without a mandible is only a cranium. Animals that have skulls are called craniates...

 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.

When a person suffering from a metastasized cancer is diagnosed, a scan of the skull frequently reveals secondary tumors.

In a recent study by the Dutch GP Association, a list of causes of headaches was published, that should alert GP's to take their diagnosis further then to choose for symptomatic treatment of headaches with simple pain medication (note the occurrence of brain tumors as possible cause):
Alarm signals Possible cause
First headache complaint from person over 50 years old brain tumor, arteriïtis temporalis
First migraine attack in person over 40 years old brain tumor
Headache in person under 6 years old brain tumor, hydrocephalus
Hydrocephalus
Hydrocephalus , also known as "water in the brain," is a medical condition in which there is an abnormal accumulation of cerebrospinal fluid in the ventricles, or cavities, of the brain. This may cause increased intracranial pressure inside the skull and progressive enlargement of the head,...

Person over 50 years old with pain at temples arteriïtis temporalis
Pregnancy with unknown headache
Headache
A headache or cephalalgia is pain anywhere in the region of the head or neck. It can be a symptom of a number of different conditions of the head and neck. The brain tissue itself is not sensitive to pain because it lacks pain receptors. Rather, the pain is caused by disturbance of the...

pre-eclampsia
Pre-eclampsia
Pre-eclampsia or preeclampsia is a medical condition in which hypertension arises in pregnancy in association with significant amounts of protein in the urine....

Increased headaches after trauma sub/epidural hematoma
Hematoma
A hematoma, or haematoma, is a localized collection of blood outside the blood vessels, usually in liquid form within the tissue. This distinguishes it from an ecchymosis, which is the spread of blood under the skin in a thin layer, commonly called a bruise...

Severe headaches and very high blood pressure malignant hypertension
Malignant hypertension
Malignant hypertension or hypertensive emergency is severe hypertension with acute impairment of an organ system and the possibility of irreversible organ-damage...

Acute severe headache meningitis
Meningitis
Meningitis is inflammation of the protective membranes covering the brain and spinal cord, known collectively as the meninges. The inflammation may be caused by infection with viruses, bacteria, or other microorganisms, and less commonly by certain drugs...

, CVA
CVA
The abbreviation CVA can refer to:Schools* Carrabassett Valley Academy, a ski and snowboard academy based in Carrabassett Valley, Maine* College of Visual Arts, a four-year private college in Minnesota...

 (Cerebrovascular accident or stroke), subarachnoidal hemorrhage
Headache and fever (with reduced consciousness) meningitis
Stiffness of the neck/neurological dysfunction meningitis, brain tumor
Headache with signs of elevated intracranial pressure
Intracranial pressure
Intracranial pressure is the pressure inside the skull and thus in the brain tissue and cerebrospinal fluid . The body has various mechanisms by which it keeps the ICP stable, with CSF pressures varying by about 1 mmHg in normal adults through shifts in production and absorption of CSF...

brain tumor
Focal neurological dysfunction brain tumor
Early morning vomiting or vomiting unrelated to headache or other illness brain tumor
Behavioral changes or rapid decline in school results brain tumor

Cause

Aside from exposure to vinyl chloride
Vinyl chloride
Vinyl chloride is the organochloride with the formula H2C:CHCl. It is also called vinyl chloride monomer, VCM or chloroethene. This colorless compound is an important industrial chemical chiefly used to produce the polymer polyvinyl chloride . At ambient pressure and temperature, vinyl chloride...

 or ionizing radiation
Ionizing radiation
Ionizing radiation is radiation composed of particles that individually have sufficient energy to remove an electron from an atom or molecule. This ionization produces free radicals, which are atoms or molecules containing unpaired electrons...

, there are no known environmental factors associated with brain tumors. Mutations and deletions of so-called tumor suppressor gene
Tumor suppressor gene
A tumor suppressor gene, or anti-oncogene, is a gene that protects a cell from one step on the path to cancer. When this gene is mutated to cause a loss or reduction in its function, the cell can progress to cancer, usually in combination with other genetic changes.-Two-hit hypothesis:Unlike...

s 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
Multiple endocrine neoplasia
The term multiple endocrine neoplasia encompasses several distinct syndromes featuring tumors of endocrine glands, each with its own characteristic pattern. In some cases, the tumors are malignant, in others, benign...

, neurofibromatosis
Neurofibromatosis
Neurofibromatosis is a genetically-inherited disorder in which the nerve tissue grows tumors that may be benign or may cause serious damage by compressing nerves and other tissues...

 type 2 are at high risk of developing brain tumors. Cell phone use does not appear to be related.

Pathophysiology

Anatomy

From the brain
Human brain
The human brain has the same general structure as the brains of other mammals, but is over three times larger than the brain of a typical mammal with an equivalent body size. Estimates for the number of neurons in the human brain range from 80 to 120 billion...

-wikipedia article and for the purpose of understanding this article some summary notes about the brain and its different types of organic tissues will be provided.

When reading the human brain in the picture on the left, only a few of the areas are really of interest to us. The first type of tissue encountered beneath the skullbone in the intracranial cavity is actually not shown on this picture: the meninges. This is what is inflamed in meningitis.

Meninges

Human brains are surrounded by a system of connective tissue
Connective tissue
"Connective tissue" is a fibrous tissue. It is one of the four traditional classes of tissues . Connective Tissue is found throughout the body.In fact the whole framework of the skeleton and the different specialized connective tissues from the crown of the head to the toes determine the form of...

 membranes called meninges
Meninges
The meninges is the system of membranes which envelopes the central nervous system. The meninges consist of three layers: the dura mater, the arachnoid mater, and the pia mater. The primary function of the meninges and of the cerebrospinal fluid is to protect the central nervous system.-Dura...

  that separate the skull
Human skull
The human skull is a bony structure, skeleton, that is in the human head and which supports the structures of the face and forms a cavity for the brain.In humans, the adult skull is normally made up of 22 bones...

 from the brain
Human brain
The human brain has the same general structure as the brains of other mammals, but is over three times larger than the brain of a typical mammal with an equivalent body size. Estimates for the number of neurons in the human brain range from 80 to 120 billion...

. This three-layered covering is composed of (from the outside in) the dura mater
Dura mater
The dura mater , or dura, is the outermost of the three layers of the meninges surrounding the brain and spinal cord. It is derived from Mesoderm. The other two meningeal layers are the pia mater and the arachnoid mater. The dura surrounds the brain and the spinal cord and is responsible for...

 ("hard mother"), arachnoid mater
Arachnoid mater
The arachnoid mater, literally from Latin "spider -like mother", is one of the three meninges, the membranes that cover the brain and spinal cord...

 ("spidery mother"), and pia mater
Pia mater
Pia mater often referred to as simply the pia, is the delicate innermost layer of the meninges, the membranes surrounding the brain and spinal cord. The word finds its roots in Latin, meaning literally "tender mother." The other two meningeal membranes are the dura mater and the arachnoid mater....

 ("soft mother"). The arachnoid and pia are physically connected and thus often considered as a single layer, the pia-arachnoid. Below the arachnoid is the subarachnoid space
Subarachnoid space
In the central nervous system, the subarachnoid cavity is the interval between the arachnoid membrane and pia mater....

 which contains cerebrospinal fluid
Cerebrospinal fluid
Cerebrospinal fluid , Liquor cerebrospinalis, is a clear, colorless, bodily fluid, that occupies the subarachnoid space and the ventricular system around and inside the brain and spinal cord...

, which circulates in the narrow spaces between cells and through cavities called ventricles, and serves to nourish, support, and protect the brain tissue. Blood vessels enter the central nervous system
Central nervous system
The central nervous system is the part of the nervous system that integrates the information that it receives from, and coordinates the activity of, all parts of the bodies of bilaterian animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish...

 through the perivascular space above the pia mater. The cells in the blood vessel walls are joined tightly, forming the blood-brain barrier which protects the brain from toxins  that might enter through the blood.
Tumors of the meninges are meningioma
Meningioma
The word meningioma was first used by Harvey Cushing in 1922 to describe a tumor originating from the meninges, the membranous layers surrounding the CNS ....

 and are often benign neoplasms.

Brain matter

The brains of vertebrates (including humans) are made of very soft tissue, with a texture that has been compared to gelatin. Living brain tissue is pinkish on the outside and mostly white on the inside, with subtle variations in color. Three separate brain areas make up the majority of brain volume:
    • telencephalon
      Telencephalon
      The cerebrum or telencephalon, together with the diencephalon, constitutes the forebrain. The cerebrum is the most anterior region of the vertebrate central nervous system. Telencephalon refers to the embryonic structure, from which the mature cerebrum develops...

       (cerebral hemispheres or cerebrum)
    • mesencephalon
      Mesencephalon
      The midbrain or mesencephalon is a portion of the central nervous system associated with vision, hearing, motor control, sleep/wake, arousal , and temperature regulation....

        (midbrain)
    • cerebellum
      Cerebellum
      The cerebellum is a region of the brain that plays an important role in motor control. It may also be involved in some cognitive functions such as attention and language, and in regulating fear and pleasure responses, but its movement-related functions are the most solidly established...



These areas are composed of two broad classes of cells: neurons and glia. These two types are equally numerous in the brain as a whole, although glial cells outnumber neurons roughly 4 to 1 in the cerebral cortex
Cerebral cortex
The cerebral cortex is a sheet of neural tissue that is outermost to the cerebrum of the mammalian brain. It plays a key role in memory, attention, perceptual awareness, thought, language, and consciousness. It is constituted of up to six horizontal layers, each of which has a different...

. Glia come in several types, which perform a number of critical functions, including structural support, metabolic support, insulation, and guidance of development.

Primary tumors of the glial cells are called Glioma
Glioma
A glioma is a type of tumor that starts in the brain or spine. It is called a glioma because it arises from glial cells. The most common site of gliomas is the brain.-By type of cell:...

 and often are malignant by the time they are diagnosed.

Spinal cord and other tissues

  • The pink area in picture is called the pons
    Pons
    The pons is a structure located on the brain stem, named after the Latin word for "bridge" or the 16th-century Italian anatomist and surgeon Costanzo Varolio . It is superior to the medulla oblongata, inferior to the midbrain, and ventral to the cerebellum. In humans and other bipeds this means it...

     and is a specific region that consists of myelinated axons much like the spinal cord
  • The yellow region is the diencephalon
    Diencephalon
    The diencephalon is the region of the vertebrate neural tube which gives rise to posterior forebrain structures. In development, the forebrain develops from the prosencephalon, the most anterior vesicle of the neural tube which later forms both the diencephalon and the...

     (thalamus
    Thalamus
    The thalamus is a midline paired symmetrical structure within the brains of vertebrates, including humans. It is situated between the cerebral cortex and midbrain, both in terms of location and neurological connections...

     and hypothalamus
    Hypothalamus
    The Hypothalamus is a portion of the brain that contains a number of small nuclei with a variety of functions...

    ) which consist also of neuron and glial cell tissue with the hypophysis (or pituitary gland) and pineal gland
    Pineal gland
    The pineal gland is a small endocrine gland in the vertebrate brain. It produces the serotonin derivative melatonin, a hormone that affects the modulation of wake/sleep patterns and seasonal functions...

     (which is glandular tissue) attached at the bottom; tumors of the pituitary and pineal gland
    Pineal gland
    The pineal gland is a small endocrine gland in the vertebrate brain. It produces the serotonin derivative melatonin, a hormone that affects the modulation of wake/sleep patterns and seasonal functions...

     are often benign neoplasms
  • The turquoise region or medulla oblongata is the end of the spinal cord and is composed mainly of neuron tissue enveloped in Schwann cells and meninges tissue. Our spinal cord
    Spinal cord
    The spinal cord is a long, thin, tubular bundle of nervous tissue and support cells that extends from the brain . The brain and spinal cord together make up the central nervous system...

     is made up of bundles of these axons. Glial cells such as Schwann cells in the periphery or, within the cord itself, oligodendrocytes, wrap themselves around the axon, thus promoting faster transmission of electrical signals and also providing for general maintenance of the environment surrounding the cord, in part by shuttling different compounds around, responding to injury, etc.

Diagnosis

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.

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
Otolaryngology
Otolaryngology or ENT is the branch of medicine and surgery that specializes in the diagnosis and treatment of ear, nose, throat, and head and neck disorders....

 (or ENT) and/or electrophysiological exams. The use of electroencephalography
Electroencephalography
Electroencephalography is the recording of electrical activity along the scalp. EEG measures voltage fluctuations resulting from ionic current flows within the neurons of the brain...

 (EEG) often plays a role in the diagnosis of brain tumors.

Swelling, or obstruction of the passage of cerebrospinal fluid
Cerebrospinal fluid
Cerebrospinal fluid , Liquor cerebrospinalis, is a clear, colorless, bodily fluid, that occupies the subarachnoid space and the ventricular system around and inside the brain and spinal cord...

 (CSF) from the brain may cause (early) signs of increased intracranial pressure
Intracranial pressure
Intracranial pressure is the pressure inside the skull and thus in the brain tissue and cerebrospinal fluid . The body has various mechanisms by which it keeps the ICP stable, with CSF pressures varying by about 1 mmHg in normal adults through shifts in production and absorption of CSF...

 which translates clinically into headaches, vomiting
Vomiting
Vomiting is the forceful expulsion of the contents of one's stomach through the mouth and sometimes the nose...

, or an altered state of consciousness
Consciousness
Consciousness is a term that refers to the relationship between the mind and the world with which it interacts. It has been defined as: subjectivity, awareness, the ability to experience or to feel, wakefulness, having a sense of selfhood, and the executive control system of the mind...

, and in children changes to the diameter of the skull
Human skull
The human skull is a bony structure, skeleton, that is in the human head and which supports the structures of the face and forms a cavity for the brain.In humans, the adult skull is normally made up of 22 bones...

 and bulging of the fontanelle
Fontanelle
A fontanelle is an anatomical feature on an infant's skull.-Anatomy:Fontanelles are soft spots on a baby's head which, during birth, enable the bony plates of the skull to flex, allowing the child's head to pass through the birth canal. The ossification of the bones of the skull causes the...

s. More complex symptoms such as endocrine dysfunctions should alarm doctors not to exclude brain tumors.

A bilateral temporal visual field
Visual field
The term visual field is sometimes used as a synonym to field of view, though they do not designate the same thing. The visual field is the "spatial array of visual sensations available to observation in introspectionist psychological experiments", while 'field of view' "refers to the physical...

 defect (due to compression of the optic chiasm
Optic chiasm
The optic chiasm or optic chiasma is the part of the brain where the optic nerves partially cross...

) 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
Hemiparesis
Hemiparesis is weakness on one side of the body. It is less severe than hemiplegia - the total paralysis of the arm, leg, and trunk on one side of the body. Thus, the patient can move the impaired side of his body, but with reduced muscular strength....

, hypoesthesia
Hypoesthesia
Hypoesthesia refers to a reduced sense of touch or sensation, or a partial loss of sensitivity to sensory stimuli....

, aphasia
Aphasia
Aphasia is an impairment of language ability. This class of language disorder ranges from having difficulty remembering words to being completely unable to speak, read, or write....

, ataxia
Ataxia
Ataxia is a neurological sign and symptom that consists of gross lack of coordination of muscle movements. Ataxia is a non-specific clinical manifestation implying dysfunction of the parts of the nervous system that coordinate movement, such as the cerebellum...

, visual field
Visual field
The term visual field is sometimes used as a synonym to field of view, though they do not designate the same thing. The visual field is the "spatial array of visual sensations available to observation in introspectionist psychological experiments", while 'field of view' "refers to the physical...

 impairment, impaired sense of smell, impaired hearing, facial paralysis, double vision
Diplopia
Diplopia, commonly known as double vision, is the simultaneous perception of two images of a single object that may be displaced horizontally, vertically, or diagonally in relation to each other...

, or more severe symptoms such as tremor
Tremor
A tremor is an involuntary, somewhat rhythmic, muscle contraction and relaxation involving to-and-fro movements of one or more body parts. It is the most common of all involuntary movements and can affect the hands, arms, eyes, face, head, vocal folds, trunk, and legs. Most tremors occur in the...

s, paralysis on one side of the body hemiplegia
Hemiplegia
Hemiplegia /he.mə.pliː.dʒiə/ is total paralysis of the arm, leg, and trunk on the same side of the body. Hemiplegia is more severe than hemiparesis, wherein one half of the body has less marked weakness....

, or (epileptic) seizures in a patient with a negative history for epilepsy, should raise the possibility of a brain tumor.

Imaging plays a central role in the diagnosis of brain tumors. Early imaging methods —invasive and sometimes dangerous— such as pneumoencephalography
Pneumoencephalography
Pneumoencephalography is a medical procedure in which most of the cerebrospinal fluid is drained from around the brain and replaced with air, oxygen, or helium to allow the structure of the brain to show up more clearly on an X-ray image...

 and cerebral angiography, have been abandoned in recent times in favor of non-invasive, high-resolution techniques, such as computed tomography
Computed tomography
X-ray computed tomography or Computer tomography , is a medical imaging method employing tomography created by computer processing...

 (CT)-scans and especially magnetic resonance imaging
Magnetic resonance imaging
Magnetic resonance imaging , nuclear magnetic resonance imaging , or magnetic resonance tomography is a medical imaging technique used in radiology to visualize detailed internal structures...

 (MRI). 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 (unclear outline)


This is because these tumors disrupt the normal functioning of the blood-brain barrier
Blood-brain barrier
The blood–brain barrier is a separation of circulating blood and the brain extracellular fluid in the central nervous system . It occurs along all capillaries and consists of tight junctions around the capillaries that do not exist in normal circulation. Endothelial cells restrict the diffusion...

 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
Glioblastoma multiforme
Glioblastoma multiforme is the most common and most aggressive malignant primary brain tumor in humans, involving glial cells and accounting for 52% of all functional tissue brain tumor cases and 20% of all intracranial tumors. Despite being the most prevalent form of primary brain tumor, GBMs...

 and anaplastic astrocytoma
Astrocytoma
Astrocytomas are a type of neoplasm of the brain. They originate in a particular kind of glial-cells, star-shaped brain cells in the cerebrum called astrocytes. This type of tumor does not usually spread outside the brain and spinal cord and it does not usually affect other organs...

 have been associated with the genetic acute hepatic porphyria
Porphyria
Porphyrias are a group of inherited or acquired disorders of certain enzymes in the heme bio-synthetic pathway . They are broadly classified as acute porphyrias and cutaneous porphyrias, based on the site of the overproduction and accumulation of the porphyrins...

s (PCT
Porphyria cutanea tarda
Porphyria cutanea tarda is the most common subtype of porphyria. The disorder results from low levels of the enzyme responsible for the fifth step in heme production. Heme is a vital molecule for all of the body's organs...

, AIP
Acute intermittent porphyria
Acute intermittent porphyria is a rare autosomal dominant metabolic disorder affecting the production of heme, the oxygen-binding prosthetic group of hemoglobin. It is characterized by a deficiency of the enzyme porphobilinogen deaminase. Acute intermittent porphyria is the second most common...

, HCP
Hereditary coproporphyria
Hereditary coproporphyria is a type of acute porphyria that is associated with a deficiency of the enzyme coproporphyrinogen III oxidase....

 and VP
Variegate porphyria
Variegate porphyria is an autosomal dominant porphyria that can have acute symptoms along with symptoms that affect the skin...

), 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
Medical diagnosis
Medical diagnosis refers both to the process of attempting to determine or identify a possible disease or disorder , and to the opinion reached by this process...

 of brain tumor can only be confirmed by histological examination
Histology
Histology is the study of the microscopic anatomy of cells and tissues of plants and animals. It is performed by examining cells and tissues commonly by sectioning and staining; followed by examination under a light microscope or electron microscope...

 of tumor
Tumor
A tumor or tumour is commonly used as a synonym for a neoplasm that appears enlarged in size. Tumor is not synonymous with cancer...

 tissue
Biological tissue
Tissue is a cellular organizational level intermediate between cells and a complete organism. A tissue is an ensemble of cells, not necessarily identical, but from the same origin, that together carry out a specific function. These are called tissues because of their identical functioning...

 samples obtained either by means of brain biopsy
Biopsy
A biopsy is a medical test involving sampling of cells or tissues for examination. It is the medical removal of tissue from a living subject to determine the presence or extent of a disease. The tissue is generally examined under a microscope by a pathologist, and can also be analyzed chemically...

 or open surgery
Surgery
Surgery is an ancient medical specialty that uses operative manual and instrumental techniques on a patient to investigate and/or treat a pathological condition such as disease or injury, or to help improve bodily function or appearance.An act of performing surgery may be called a surgical...

. The histological examination is essential for determining the appropriate treatment and the correct prognosis
Prognosis
Prognosis is a medical term to describe the likely outcome of an illness.When applied to large statistical populations, prognostic estimates can be very accurate: for example the statement "45% of patients with severe septic shock will die within 28 days" can be made with some confidence, because...

. This examination, performed by a pathologist, typically has three stages: interoperative examination of fresh tissue, preliminary microscopic examination of prepared tissues, and followup examination of prepared tissues after immunohistochemical staining or genetic analysis.

Pathology

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

Anaplasia
Anaplasia
Anaplasia refers to a reversion of differentiation in cells and is characteristic of malignant neoplasms . Sometimes, the term also includes an increased capacity for multiplication. Lack of differentiation is considered a hallmark of aggressive malignancies. The term anaplasia literally means "to...

: 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
Atypia
Atypia is a clinical term for abnormality in a cell. The term is medical jargon for an atypical cell. Atypia: Etymology: Gk, a + typos, without type; a condition of being irregular or nonstandard....

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

Neoplasia
Neoplasia
Neoplasm is an abnormal mass of tissue as a result of neoplasia. Neoplasia is the abnormal proliferation of cells. The growth of neoplastic cells exceeds and is not coordinated with that of the normal tissues around it. The growth persists in the same excessive manner even after cessation of the...

: 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
Parenchyma
Parenchyma is a term used to describe a bulk of a substance. It is used in different ways in animals and in plants.The term is New Latin, f. Greek παρέγχυμα - parenkhuma, "visceral flesh", f. παρεγχεῖν - parenkhein, "to pour in" f. para-, "beside" + en-, "in" + khein, "to pour"...

. 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
Necrosis
Necrosis is the premature death of cells in living tissue. Necrosis is caused by factors external to the cell or tissue, such as infection, toxins, or trauma. This is in contrast to apoptosis, which is a naturally occurring cause of cellular death...

: 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
Hypoxia (medical)
Hypoxia, or hypoxiation, is a pathological condition in which the body as a whole or a region of the body is deprived of adequate oxygen supply. Variations in arterial oxygen concentrations can be part of the normal physiology, for example, during strenuous physical exercise...

, 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.

Secondary brain tumors

Secondary tumors of the brain are metastatic tumors
Metastasis
Metastasis, or metastatic disease , is the spread of a disease from one organ or part to another non-adjacent organ or part. It was previously thought that only malignant tumor cells and infections have the capacity to metastasize; however, this is being reconsidered due to new research...

 that invaded the intracranial sphere from cancer
Cancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...

s 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
Lymphatic system
The lymphoid system is the part of the immune system comprising a network of conduits called lymphatic vessels that carry a clear fluid called lymph unidirectionally toward the heart. Lymphoid tissue is found in many organs, particularly the lymph nodes, and in the lymphoid follicles associated...

 and blood vessels. 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
Lung cancer
Lung cancer is a disease characterized by uncontrolled cell growth in tissues of the lung. If left untreated, this growth can spread beyond the lung in a process called metastasis into nearby tissue and, eventually, into other parts of the body. Most cancers that start in lung, known as primary...

, breast cancer
Breast cancer
Breast cancer is cancer originating from breast tissue, most commonly from the inner lining of milk ducts or the lobules that supply the ducts with milk. Cancers originating from ducts are known as ductal carcinomas; those originating from lobules are known as lobular carcinomas...

, malignant melanoma
Melanoma
Melanoma is a malignant tumor of melanocytes. Melanocytes are cells that produce the dark pigment, melanin, which is responsible for the color of skin. They predominantly occur in skin, but are also found in other parts of the body, including the bowel and the eye...

, kidney cancer
Kidney cancer
Kidney cancer is a type of cancer that starts in the cells in the kidney.The two most common types of kidney cancer are renal cell carcinoma and urothelial cell carcinoma of the renal pelvis...

 and colon cancer (in decreasing order of frequency).

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

The skull
Human skull
The human skull is a bony structure, skeleton, that is in the human head and which supports the structures of the face and forms a cavity for the brain.In humans, the adult skull is normally made up of 22 bones...

 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
    Anaplasia
    Anaplasia refers to a reversion of differentiation in cells and is characteristic of malignant neoplasms . Sometimes, the term also includes an increased capacity for multiplication. Lack of differentiation is considered a hallmark of aggressive malignancies. The term anaplasia literally means "to...

    : the cells in the neoplasm have an obviously different form (in size and shape). Anaplastic cells display marked pleomorphism
    Pleomorphism (cytology)
    Pleomorphism is a term used in histology and cytopathology to describe variability in the size and shape of cells and/or their nuclei. It is a feature characteristic of malignant neoplasms....

    . The cell nuclei are characteristically extremely hyperchromatic (darkly stained) and enlarged; the nucleus might have the same size as the cytoplasm
    Cytoplasm
    The cytoplasm is a small gel-like substance residing between the cell membrane holding all the cell's internal sub-structures , except for the nucleus. All the contents of the cells of prokaryote organisms are contained within 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 formed 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 (so readers should note that this convention is not kept 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 doesn't mean that an infiltrative tumor doesn't take up space or doesn't 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
    Metastasis
    Metastasis, or metastatic disease , is the spread of a disease from one organ or part to another non-adjacent organ or part. It was previously thought that only malignant tumor cells and infections have the capacity to metastasize; however, this is being reconsidered due to new research...

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


Of the above malignant characteristics, some elements don't 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
    Blood-brain barrier
    The blood–brain barrier is a separation of circulating blood and the brain extracellular fluid in the central nervous system . It occurs along all capillaries and consists of tight junctions around the capillaries that do not exist in normal circulation. Endothelial cells restrict the diffusion...

     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
    Glioblastoma multiforme
    Glioblastoma multiforme is the most common and most aggressive malignant primary brain tumor in humans, involving glial cells and accounting for 52% of all functional tissue brain tumor cases and 20% of all intracranial tumors. Despite being the most prevalent form of primary brain tumor, GBMs...

    .)
  • 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.


Of numerous grading systems
Grading of the tumors of the central nervous system
The concept of grading of the tumors of the central nervous system, agreeing for such the regulation of the "progressiveness" of these neoplasias , dates back to 1926 and was introduced by P. Bailey and H...

 in use for the classification of tumor of the central nervous system, the World Health Organization
World Health Organization
The World Health Organization is a specialized agency of the United Nations that acts as a coordinating authority on international public health. Established on 7 April 1948, with headquarters in Geneva, Switzerland, the agency inherited the mandate and resources of its predecessor, the Health...

 (WHO) grading system is commonly used for astrocytoma. Established in 1993 in an effort to eliminate confusion regarding diagnoses, the WHO system established a four-tiered histologic grading guideline for astrocytomas that assigns a grade from 1 to 4, with 1 being the least aggressive and 4 being the most aggressive.

Treatment

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 ressection of the tumor with the objective of removing as many tumor cells as possible
  • radiotherapy
  • chemotherapy, with the aim of killing as many as possible of cancerous cells left behind after surgery and of putting remaining tumor cells into a nondividing, sleeping state for as long as possible
  • 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
Craniotomy
A craniotomy is a surgical operation in which a bone flap is temporarily removed from the skull to access the brain. Craniotomies are often a critical operation performed on patients recording, brain imaging, and for neurological manipulations such as electrical stimulation and chemical...

. 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 adenoma
Pituitary adenoma
Pituitary adenomas are tumors that occur in the pituitary gland, and account for about 15% of intracranial neoplasms. Tumors which exceed 10 mm in size are defined as macroadenomas, and those smaller than 10 mm are referred to as microadenomas...

s can be removed surgically, often using a minimally invasive approach through the nasal cavity
Nasal cavity
The nasal cavity is a large air filled space above and behind the nose in the middle of the face.- Function :The nasal cavity conditions the air to be received by the other areas of the respiratory tract...

 and skull base (trans-nasal, trans-sphenoidal approach). Large pituitary adenoma
Pituitary adenoma
Pituitary adenomas are tumors that occur in the pituitary gland, and account for about 15% of intracranial neoplasms. Tumors which exceed 10 mm in size are defined as macroadenomas, and those smaller than 10 mm are referred to as microadenomas...

s require a craniotomy
Craniotomy
A craniotomy is a surgical operation in which a bone flap is temporarily removed from the skull to access the brain. Craniotomies are often a critical operation performed on patients recording, brain imaging, and for neurological manipulations such as electrical stimulation and chemical...

 (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 a chemical (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
Epilepsy
Epilepsy is a common chronic neurological disorder characterized by seizures. These seizures are transient signs and/or symptoms of abnormal, excessive or hypersynchronous neuronal activity in the brain.About 50 million people worldwide have epilepsy, and nearly two out of every three new cases...

. 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. 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
Brachytherapy
Brachytherapy , also known as internal radiotherapy, sealed source radiotherapy, curietherapy or endocurietherapy, is a form of radiotherapy where a radiation source is placed inside or next to the area requiring treatment...

, and in more difficult cases, stereotactic radiosurgery
Radiosurgery
Radiosurgery is a medical procedure that allows non-invasive treatment of benign and malignant tumors. It is also known as stereotactic radiotherapy, when used to target lesions in the brain, and stereotactic body radiotherapy when used to target lesions in the body...

, such as Gamma knife, Cyberknife
Cyberknife
The CyberKnife is a frameless robotic radiosurgery system used for treating benign tumors, malignant tumors and other medical conditions. The system was invented by John R. Adler, a Stanford University Professor of Neurosurgery and Radiation Oncology, and Peter and Russell Schonberg of Schonberg...

 or Novalis Tx radiosurgery
Radiosurgery
Radiosurgery is a medical procedure that allows non-invasive treatment of benign and malignant tumors. It is also known as stereotactic radiotherapy, when used to target lesions in the brain, and stereotactic body radiotherapy when used to target lesions in the body...

.

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.

In 2008 a study published by the University of Texas M. D. Anderson Cancer Center indicated that cancer patients who receive stereotactic radiosurgery (SRS) and whole brain radiation therapy (WBRT) for the treatment of metastatic brain tumors have more than twice the risk of developing learning and memory problems than those treated with SRS alone.

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.

UCLA Neuro-Oncology publishes real-time survival data for patients with a diagnosis of glioblastoma multiforme. They are the only institution in the United States that displays how brain tumor patients are performing on current therapies. They also show a listing of chemotherapy agents used to treat high grade glioma tumors.

Other

A shunt
Shunt (medical)
In medicine, a shunt is a hole or a small passage which moves, or allows movement of fluid from one part of the body to another. The term may describe either congenital or acquired shunts; and acquired shunts may be either biological or mechanical.* Cardiac shunts may be described as...

 is used not as a cure but to relieve symptoms by reducing hydrocephalus caused by blockage of cerebrospinal fluid
Cerebrospinal fluid
Cerebrospinal fluid , Liquor cerebrospinalis, is a clear, colorless, bodily fluid, that occupies the subarachnoid space and the ventricular system around and inside the brain and spinal cord...

.

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.

Prognosis

The prognosis of brain cancer varies based on the type of cancer. Medulloblastoma has a good prognosis with chemotherapy, radiotherapy, and surgical resection while glioblastoma multiforme has a median survival of only 12 months even with aggressive chemoradiotherapy
Chemoradiotherapy
Chemoradiotherapy is the combination of chemotherapy and radiotherapy to treat cancer. Chemoradiotherapy in the Neoadjuvant therapy has been shown to be effective in rectal cancer....

 and surgery. Brainstem gliomas have the poorest prognosis of any form of brain cancer, with most patients dying within one year, even with therapy that typically consists of radiation to the tumor along with corticosteroids. However, one type of brainstem glioma, a focal seems open to exceptional prognosis and long-term survival has frequently been reported.

Glioblastoma multiforme

Glioblastoma multiforme is the deadliest and most common form of malignant brain tumor. Even when aggressive multimodality therapy consisting of radiotherapy, chemotherapy, and surgical excision is used, median survival is only 12–17 months. Standard therapy for glioblastoma multiforme consists of maximal surgical resection
Resection
Resection may refer to:*Segmental resection , the partial removal of an organ or other body structure*Resection , a means of establishing a location...

 of the tumor, followed by radiotherapy between two and four weeks after the surgical procedure
Craniotomy
A craniotomy is a surgical operation in which a bone flap is temporarily removed from the skull to access the brain. Craniotomies are often a critical operation performed on patients recording, brain imaging, and for neurological manipulations such as electrical stimulation and chemical...

 to remove the cancer. This is followed by chemotherapy
Temozolomide
Temozolomide Temozolomide Temozolomide (brand names Temodar and Temodal is an oral alkylating agent which can be used for the treatment of Grade IV astrocytoma — an aggressive brain tumor, also known as glioblastoma multiforme as well as melanoma, a form of skin cancer...

. Most patients with glioblastoma take a corticosteroid
Corticosteroid
Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex. Corticosteroids are involved in a wide range of physiologic systems such as stress response, immune response and regulation of inflammation, carbohydrate metabolism, protein catabolism, blood electrolyte...

, typically dexamethasone
Dexamethasone
Dexamethasone is a potent synthetic member of the glucocorticoid class of steroid drugs. It acts as an anti-inflammatory and immunosuppressant...

, during their illness to palliate symptoms. Experimental treatments include gamma-knife radiosurgery, boron neutron capture therapy
Boron Neutron Capture Therapy
Boron neutron capture therapy is an experimental form of radiotherapy that uses a neutron beam that interacts with boron injected into a patient...

 and gene transfer.

Oligodendrogliomas

Oligodendroglioma is an incurable but slowly progressive malignant brain tumor. They can be treated with surgical resection, chemotherapy
Chemotherapy
Chemotherapy is the treatment of cancer with an antineoplastic drug or with a combination of such drugs into a standardized treatment regimen....

, and/or radiotherapy. For suspected low-grade oligodendrogliomas in select patients, some neuro-oncologists opt for a course of watchful waiting, with only symptomatic therapy. Tumors with the 1p/19q co-deletion have been found to be especially chemosensitive, and one source reports oligodendrogliomas to be "among the most chemosensitive of human solid malignancies". A median survival of up to 16.7 years has been reported for low grade oligodendrogliomas.

Epidemiology

The incidence of low-grade astrocytoma has not been shown to vary significantly with nationality. However, studies examining the incidence of malignant CNS tumors have shown some variation with national origin. Since some of these high-grade lesions arise from low-grade tumors, these trends are worth mentioning. Specifically, the incidence of CNS tumors in the United States, Israel, and the Nordic countries is relatively high, while Japan and Asian countries have a lower incidence. These differences probably reflect some biological differences as well as differences in pathologic diagnosis and reporting.
Worldwide data on incidence of cancer can be found at the WHO
Who
Who may refer to:* Who , an English-language pronoun* who , a Unix command* Who?, one of the Five Ws in journalism- Art and entertainment :* Who? , a 1958 novel by Algis Budrys...

 (world health organisation) and is handled by the AIRC (Agency for Interanctional Research on Cancer) located in France.
Figures for incidences of cancers of the brain show a significant difference between more and less developed countries (i.e. the less-developed countries have lower incidences of tumors of the brain) this could be explained by undiagnosed tumor-related deaths (patient in extreme poor situations don't get diagnosed simply because they don't have access to the modern diagnostic facilities required to diagnose a brain tumor) and by deaths caused by other poverty related causes that preempt a patients life before tumors develop or tumors become life threatening. Nevertheless studies have been made that certain forms of primary brain tumors are more prevalent among certain groups of the population.

United Kingdom

From the British national statistics data about new diagnosis of malignant neoplasms of the brain for the year 2007 (in absolute figures and in rates per 100.000)
Measures Gender DASR All ages Under 1 1-4 5-9 10-14 15-19 20-24 25-29 30-34 35-39 40-44 45-49 50-54 55-59 60-64 65-69 70-74 75-79 80-84 85+
Absolute figures M 2.13 7 34 40 31 37 33 48 61 87 100 116.1 142 242 264 258 237 193 128 73
F 1.598 7 42 39 37 28 25 37 50 42 73 87 99 140 191 166 169 158 111 97
Rates per 100.000 inhabitants M 7,7 8,5 2,1 2,8 2,7 2,0 2,1 1,9 2,8 3,7 4,6 5,1 6,6 9,3 15,7 18,6 24,0 25,8 26,7 26,6 21,2
F 5,3 6,2 2,2 3,6 2,8 2,5 1,7 1,5 2,2 3,0 2,2 3,7 4,9 6,3 8,8 12,9 14,3 16,2 17,1 15,1 12,8

United States

In the United States in the year 2005, it was estimated there were 43,800 new cases of brain tumors (Central Brain Tumor Registry of the United States, Primary Brain Tumors in the United States, Statistical Report, 2005–2006), which accounted for 1.4 percent of all cancers, 2.4 percent of all cancer deaths, and 20–25 percent of pediatric cancers. Ultimately, it is estimated there are 13,000 deaths per year in the United States alone as a result of brain tumors.

Vesicular stomatitis virus

In 2000, researchers at the University of Ottawa
University of Ottawa
The University of Ottawa is a bilingual, research-intensive, non-denominational, international university in Ottawa, Ontario. It is one of the oldest universities in Canada. It was originally established as the College of Bytown in 1848 by the Missionary Oblates of Mary Immaculate...

, led by John Bell PhD., discovered that the vesicular stomatitis virus
Vesicular stomatitis virus
Vesicular stomatitis Indiana virus is a virus in the family Rhabdoviridae; the well-known Rabies virus belongs to the same family. VSIV can infect insects, cattle, horses, pigs and humans. It has particular importance to farmers in certain regions of the world where it can infect cattle...

, or VSV, can infect and kill cancer cells, without affecting healthy cells if coadministered with interferon
Interferon
Interferons are proteins made and released by host cells in response to the presence of pathogens—such as viruses, bacteria, or parasites—or tumor cells. They allow communication between cells to trigger the protective defenses of the immune system that eradicate pathogens or tumors.IFNs belong to...

.

The initial discovery of the virus' oncolytic properties were limited to only a few types of cancer. Several independent studies have identified many more types susceptible to the virus, including glioblastoma multiforme
Glioblastoma multiforme
Glioblastoma multiforme is the most common and most aggressive malignant primary brain tumor in humans, involving glial cells and accounting for 52% of all functional tissue brain tumor cases and 20% of all intracranial tumors. Despite being the most prevalent form of primary brain tumor, GBMs...

 cancer cells, which account for the majority of brain tumors.

In 2008, researchers artificially engineered strains of VSV that were less cytotoxic to normal cells. This advance allows administration of the virus without coadministration with interferon. Consequently administration of the virus can be given intravenously or through the olfactory nerve
Olfactory nerve
The olfactory nerve, or cranial nerve I, is the first of twelve cranial nerves. It is instrumental in the sense of smell. Derived from the embryonic nasal placode, the olfactory nerve is capable of regeneration.-Anatomy:...

. In the research, a human brain tumor was implanted into mice
Mouse
A mouse is a small mammal belonging to the order of rodents. The best known mouse species is the common house mouse . It is also a popular pet. In some places, certain kinds of field mice are also common. This rodent is eaten by large birds such as hawks and eagles...

 brains.

Research on virus treatment like this has been conducted for some years, but no other viruses have been shown to be as efficient or specific as the VSV mutant strains. Future research will focus on the risks of this treatment, before it can be applied to humans.

Retroviral replicating vectors

Led by Prof. Nori Kasahara, researchers from USC, who are now at UCLA, reported in 2001 the first successful example of applying the use of retroviral replicating vectors towards transducing cell lines derived from solid tumors. Building on this initial work, the researchers applied the technology to in vivo models of cancer and in 2005 reported a long-term survival benefit in an experimental brain tumor animal model. Subsequently, in preparation for human clinical trials, this technology was further developed by Tocagen, Inc. and is currently under clinical investigation in a Phase I/II trial for the potential treatment of recurrent high grade glioma including glioblastoma multiforme (GBM) and anaplastic astrocytoma.

In children

In the US, about 2000 children and adolescents younger than 20 years of age are diagnosed with malignant brain tumors each year. Higher incidence rates were reported in 1975–83 than in 1985–94. There is some debate as to the reasons; one theory is that the trend is the result of improved diagnosis and reporting, since the jump occurred at the same time that MRIs
Magnetic resonance imaging
Magnetic resonance imaging , nuclear magnetic resonance imaging , or magnetic resonance tomography is a medical imaging technique used in radiology to visualize detailed internal structures...

 became available widely, and there was no coincident jump in mortality
Mortality rate
Mortality rate is a measure of the number of deaths in a population, scaled to the size of that population, per unit time...

. The central nervous system
Central nervous system
The central nervous system is the part of the nervous system that integrates the information that it receives from, and coordinates the activity of, all parts of the bodies of bilaterian animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish...

 (CNS) cancer survival rate in children is approximately 60%. The rate varies with the type of cancer and the age of onset: younger patients have higher mortality.

In children under 2, about 70% of brain tumors are medulloblastoma
Medulloblastoma
Medulloblastoma is a highly malignant primary brain tumor that originates in the cerebellum or posterior fossa.Previously, medulloblastomas were thought to represent a subset of primitive neuroectodermal tumor of the posterior fossa...

, ependymoma
Ependymoma
Ependymoma is a tumor that arises from the ependyma, a tissue of the central nervous system. Usually, in pediatric cases the location is intracranial, while in adults it is spinal. The common location of intracranial ependymoma is the fourth ventricle...

, and low-grade glioma
Glioma
A glioma is a type of tumor that starts in the brain or spine. It is called a glioma because it arises from glial cells. The most common site of gliomas is the brain.-By type of cell:...

. Less commonly, and seen usually in infants, are teratoma
Teratoma
A teratoma is an encapsulated tumor with tissue or organ components resembling normal derivatives of all three germ layers. There are rare occasions when not all three germ layers are identifiable...

 and atypical teratoid rhabdoid tumor. Germ cell tumor
Germ cell tumor
A germ cell tumor is a neoplasm derived from germ cells. Germ cell tumors can be cancerous or non-cancerous tumors. Germ cells normally occur inside the gonads...

s, including teratoma
Teratoma
A teratoma is an encapsulated tumor with tissue or organ components resembling normal derivatives of all three germ layers. There are rare occasions when not all three germ layers are identifiable...

, make up just 3% of pediatric primary brain tumors, but the worldwide incidence varies significantly.

See also

  • Craterization
    Craterization
    Craterization is an old medical procedure in which doctors would drill holes into people's heads to remove a foreign mass . It gets its name from the crater-like holes it leaves behind....

  • List of notable brain tumor patients
  • Radiosurgery
    Radiosurgery
    Radiosurgery is a medical procedure that allows non-invasive treatment of benign and malignant tumors. It is also known as stereotactic radiotherapy, when used to target lesions in the brain, and stereotactic body radiotherapy when used to target lesions in the body...

  • Stereotactic surgery
    Stereotactic surgery
    Stereotactic surgery or stereotaxy is a minimally invasive form of surgical intervention which makes use of a three-dimensional coordinates system to locate small targets inside the body and to perform on them some action such as ablation, biopsy, lesion, injection, stimulation, implantation,...

  • Radiation therapy
    Radiation therapy
    Radiation therapy , radiation oncology, or radiotherapy , sometimes abbreviated to XRT or DXT, is the medical use of ionizing radiation, generally as part of cancer treatment to control malignant cells.Radiation therapy is commonly applied to the cancerous tumor because of its ability to control...

  • Grading of the tumors of the central nervous system
    Grading of the tumors of the central nervous system
    The concept of grading of the tumors of the central nervous system, agreeing for such the regulation of the "progressiveness" of these neoplasias , dates back to 1926 and was introduced by P. Bailey and H...

  • Visualase
    Visualase
    Visualase, Inc. founded in 2005 as a spin-off from BioTex, Inc., is focused on laser and image-guided technologies for thermal ablation. They developed the Visualase Laser Thermal Ablation System referred to as "Visualase" in which energy is delivered directly into a lesion. Light is delivered...

     Laser Technology for Tumor Ablation (LITT)

External links

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