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Brain tumor
A brain tumor is any intracranial tumor created by abnormal and uncontrolled
cell division, normally either found 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 2000, it was estimated that there were
16,500 new cases of brain tumors, 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.
Causes
Aside from exposure to vinyl chloride or ionizing radiation, there are no
known environmental factors associated with brain tumors. Mutations and
deletions of so-called tumor supressor genes are incriminated in some forms
of brain tumors. Patients with various inherited diseases, such as Von
Hippel-Lindau syndrome, multiple endocrine neoplasia, neurofibromatosis type
2 are at high risk of developing brain tumors.Symptoms
The kind of symptoms brain tumors may cause 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, i.e. 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[4] 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 intracranial
hypertension. Intracranial hypertension 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. It cannot be stressed enough that 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.
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.
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 for each
individual patient.
Classification
Primary tumors
In contrast to tumors originating elsewhere in the body, differentiating
primary "brain tumors"—these are the true brain tumors, arising exclusively
from cells normally present in the brain itself—into benign and malignant is
of relative and limited clinical value, since even histologically-benign
tumors grow by infiltration of healthy brain tissue and, in time, tend to
transform into malignant forms (anaplastic degeneration). True benign
intracranial tumors arise mainly from the meninges (meningiomas; about 95%
are benign), pituitary gland (pituitary adenomas) and the myelin sheath of
cranial nerves (neuromas or Schwanomas, e.g. acoustic neuroma).
Most primary brain tumors (gliomas) originate from glia: astrocytes (astrocytomas),
oligodendrocytes (oligodendrogliomas). There are also mixed forms, with both
an astrocytic and an oligodendroglial cell component. These are called mixed
gliomas or oligoastrocytomas. Additionally, 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, and
oligoastrocytomas 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.
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-tumoral 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 lesions can mimic tumors of the central nervous system.
These include tuberculosis of the brain and cerebral abscess.
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 radiotherapy 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
(i.e., removal of as much tumor as possible, in order to reduce the number
of tumor cells available for proliferation) is considered in most cases[5].
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. However, the prognosis
in such cases is determined by the primary tumor, and it is generally poor.
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