A brain tumor is any intracranial tumor created by abnormal and uncontrolled cell division, normally either in the brain itself (neurons, glial cells (astrocytes, oligodendrocytes, ependymal cells), lymphatic tissue, blood vessels), in the cranial nerves (myelin-producing Schwann cells), in the brain envelopes (meninges), skull, pituitary and pineal gland, or spread from cancers primarily located in other organs (metastatic tumors).

 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. In the United States in the year 2005, it was estimated that 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 that there are 13,000 deaths/year as a result of brain tumors.
 

Classification
 

 Primary tumors
 
Tumors occurring in the brain include: astrocytoma, pilocytic astrocytoma, dysembryoplastic neuroepithelial tumor, oligodendrogliomas, ependymoma, glioblastoma multiforme, mixed gliomas, oligoastrocytomas, medulloblastoma, retinoblastoma, neuroblastoma, germinoma and teratoma.

Most primary brain tumors originate from glia (gliomas) such as astrocytes (astrocytomas), oligodendrocytes (oligodendrogliomas), or ependymal cells (ependymoma). There are also mixed forms, with both an astrocytic and an oligodendroglial cell component. These are called mixed gliomas or oligoastrocytomas. Plus, mixed glio-neuronal tumors (tumors displaying a neuronal, as well as a glial component, e.g. gangliogliomas, disembryoplastic neuroepithelial tumors) and tumors originating from neuronal cells (e.g. gangliocytoma, central gangliocytoma) can also be encountered.

Other varieties of primary brain tumors include: primitive neuroectodermal tumors (PNET, e.g. medulloblastoma, medulloepithelioma, neuroblastoma, retinoblastoma, ependymoblastoma), tumors of the pineal parenchyma (e.g. pineocytoma, pineoblastoma), ependymal cell tumors, choroid plexus tumors, neuroepithelial tumors of uncertain origin (e.g. gliomatosis cerebri, astroblastoma), etc.

From a histological perspective, astrocytomas, oligondedrogliomas, oligoastrocytomas, and teratomas may be benign or malignant. Glioblastoma multiforme represents the most aggressive variety of malignant glioma. At the opposite end of the spectrum, there are so-called pilocytic astrocytomas, a distinct variety of astrocytic tumors. The majority of them are located in the posterior cranial fossa, affect mainly children and young adults, and have a clinically favorable course and prognosis. Teratomas and other germ cell tumors also may have a favorable prognosis, although they have the capacity to grow very large.

Another type of primary intracranial tumor is primary cerebral lymphoma, also known as primary CNS lymphoma, which is a type of non-Hodgkin's lymphoma that is much more prevalent in those with severe immunosuppression, e.g. AIDS.

In contrast to other types of cancer, primary brain tumors rarely metastasize, and in this rare event, the tumor cells spread within the skull and spinal canal through the cerebrospinal fluid, rather than via bloodstream to other organs.

There are various classification systems currently in use for primary brain tumors, the most common being the World Health Organization (WHO) brain tumor classification, introduced in 1993.
 

 
Secondary tumors and non-tumor lesions

 Secondary or metastatic brain tumors originate from malignant tumors (cancers) located primarily in other organs. Their incidence is higher than that of primary brain tumors. The most frequent types of metastatic brain tumors originate in the lung, skin (malignant melanoma), kidney (hypernephroma), breast (breast carcinoma), and colon (colon carcinoma). These tumor cells reach the brain via the blood-stream.

Some non-tumoral masses and lesions can mimic tumors of the central nervous system. These include tuberculosis of the brain, cerebral abscess (commonly in toxoplasmosis), and hamartomas (for example, in tuberous sclerosis and von Recklinghausen neurofibromatosis).

Symptoms of brain tumors may depend on two factors: tumor size (volume) and tumor location. The time point of symptom onset in the course of disease correlates in many cases with the nature of the tumor ("benign", i.e. slow-growing/late symptom onset, or malignant (fast growing/early symptom onset).

Many low-grade (benign) tumors can remain asymptomatic (symptom-free) for years and they may accidentally be discovered by imaging exams for unrelated reasons (such as a minor trauma).

New onset of epilepsy is a frequent reason for seeking medical attention in brain tumor cases.

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), dilatation of the pupil on the side of the lesion (anisocoria), papilledema (prominent optic disc at the funduscopic 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 young children, elevated intracranial pressure may cause an increase in the diameter of the skull and bulging of the fontanelles.

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, personality changes, hemiparesis, (hemi) hypesthesia, aphasia, ataxia, visual field impairment, facial paralysis, double vision, tremor etc. 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 disfunction—either hypopituitarism or hyperproduction of pituitary hormones and hyperprolactinemia is suggestive of a pituitary tumor.

 
Brain tumors in infants and children
 
In 2000 approximately 2.76 children per 100,000 will be affected by a CNS tumor in the United States each year. This rate has been increasing and by 2005 was 3.0 children per 100,000. This is approximately 2,500-3,000 pediatric brain tumors occurring each year in the US. The tumor incidence is increasing by about 2.7% per year. The CNS Cancer survival rate in children is approximately 60%. However, this rate varies with the age of onset (younger has higher mortality) and cancer type.

In children under 2, about 70% of brain tumors are medulloblastoma, ependymoma, and low-grade glioma. Less commonly, and seen usually in infants, are teratoma and atypical teratoid rhabdoid tumor.

Diagnosis
 

Although there is no specific clinical symptom or sign for brain tumors, slowly progressive focal neurologic signs and signs of elevated intracranial pressure, as well as epilepsy in a patient with a negative history for epilepsy should raise red flags. However, a sudden onset of symptoms, such as an epileptic seizure in a patient with no prior history of epilepsy, sudden intracranial hypertension (this may be due to bleeding within the tumor, brain swelling or obstruction of cerebrospinal fluid's passage) is also possible.

Symptoms include phantom odors and tastes. Often, in the case of metastatic tumors, the smell of vulcanized rubber is prevalent. 

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 modalities, such as computed tomography (CT) and especially magnetic resonance imaging (MRI). 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. Perifocal edema also appears hyperintense on T2-weighted MRI. Contrast agent uptake, sometimes in characteristic patterns, can be demonstrated on either CT or MRI-scans in most malignant primary and metastatic brain tumors. This is due to the fact that these tumors disrupt the normal functioning of the blood-brain barrier and lead to an increase in its permeability.

Electrophysiological exams, such as electroencephalography (EEG) play a marginal role in the diagnosis of brain tumors.

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 histologic examination is essential for determining the appropriate treatment and the correct prognosis.

Treatment and prognosis

Meningiomas, with the exception of some tumors located at the skull base, can be successfully removed surgically, but the chances are less than 50%. In more difficult cases, stereotactic radiosurgery, such as Gamma Knife radiosurgery, remains a viable option.

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 the inoperable cases.

Although there is no generally accepted therapeutic management for primary brain tumors, a surgical attempt at tumor removal or at least cytoreduction (that is, removal of as much tumor as possible, in order to reduce the number of tumor cells available for proliferation) is considered in most cases. However, due to the infiltrative nature of these lesions, tumor recurrence, even following an apparently complete surgical removal, is not uncommon. 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.

Survival rates in primary brain tumors depend on the type of tumor, age, functional status of the patient, the extent of surgical tumor removal, to mention just a few factors.

Patients with benign gliomas may survive for many years while survival in most cases of glioblastoma multiforme is limited to a few months after diagnosis.

The main treatment option for single metastatic tumors is surgical removal, followed by radiotherapy and/or chemotherapy. Multiple metastatic tumors are generally treated with radiotherapy and chemotherapy. Stereotactic radiosurgery, such as Gamma Knife radiosurgery, remains a viable option. However, the prognosis in such cases is determined by the primary tumor, and it is generally poor.

A shunt operation is used not as a cure but to relieve the symptoms. The hydrocephalus caused by the blocking drainage of the cerebrospinal fluid can be removed with this operation.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

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