A is any intracranial mass created by an abnormal and uncontrolled growth of cells either normally found in the s,
Glia l cells (
Astrocyte s,
Oligodendrocyte s,
Ependymal Cell s),
Lymph atic tissue,
Blood Vessel s), in the
Cranial Nerve s (
Myelin -producing
Schwann Cell s), in the brain envelopes (
Meninges ),
Skull ,
Pituitary and
Pineal Gland , or spread from
Cancer s 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 tumorsGreenlee RT, Murray T, Bolden S, Wingo PA. ''Cancer statistics, 2000.'' CA Cancer J Clin 2000;50:7-33.
PDF . PMID 10735013., which accounted for 1.4% of all cancers, 2.4% of all cancer deaths
American Cancer Society . Accessed June 2000., and 20%–25% of pediatric cancers
,Chamberlain MC, Kormanik PA. ''Practical guidelines for the treatment of malignant gliomas.'' West J Med 1998;168:114-120. PMID 9499745.. Ultimately, it is estimated that there are 13,000 deaths/year as a result of brain tumors.
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 Gene s 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.
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
Meninge s (
Meningiomas ; about 95% are benign),
Pituitary Gland (
Pituitary Adenoma s) and the
Myelin Sheath of
Cranial Nerve s (
Neuromas or
Schwanomas , e.g.
Acoustic Neuroma ).
Most primary brain tumors (), 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.
Ganglioglioma s,
Disembryoplastic Neuroepithelial Tumor s) and tumors originating from neuronal cells (e.g.
Gangliocytoma ,
Central Gangliocytoma ) can also be encountered.
Other varieties of primary brain tumors include:
Primitive Neuroectodermal Tumor s (PNET, e.g.
Medulloblastoma ,
Medulloepithelioma ,
Neuroblastoma ,
Retinoblastoma ,
Ependymoblastoma ), tumors of the
Pineal Parenchyma (e.g.
Pineocytoma ,
Pineoblastoma ),
Ependyma l 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 Astrocytoma s, 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 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 .
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 Lopez MBS, Laws ER Jr. Neurosurgical Focus 12(2), Article 1, 2002. 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
Fontanelle s.
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 Symptom s 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.
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 caracteristic 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.
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 Adenoma s can be removed surgically, often using a minimally invasive approach through the
Nasal Cavity and
Skull Base (
Trans-nasal, Trans-sphenoidal Approach ). Large
Pituitary Adenoma s 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 casesNakamura M, Konishi N, Tsunoda S, Nakase H, Tsuzuki T, Aoki H, Sakitani H, Inui T, Sakaki T. ''Analysis of prognostic and survival factors related to treatment of low-grade astrocytomas in adults.'' Oncology 2000;58:108-16. PMID 10705237.. 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 factorsNicolato A, Gerosa MA, Fina P, Iuzzolino P, Giorgiutti F, Bricolo A. ''Prognostic factors in low-grade supratentorial astrocytomas: a uni-multivariate statistical analysis in 76 surgically treated adult patients.'' Surg Neurol 1995;44:208-21; discussion 221-3. PMID 8545771..
Patients with benign gliomas may survive for many yearsJanny P, Cure H, Mohr M, Heldt N, Kwiatkowski F, Lemaire JJ, Plagne R, Rozan R. ''Low grade supratentorial astrocytomas. Management and prognostic factors.'' Cancer 1994;73:1937-45. PMID 8137221.
,Piepmeier J, Christopher S, Spencer D, Byrne T, Kim J, Knisel JP, Lacy J, Tsukerman L, Makuch R. ''Variations in the natural history and survival of patients with supratentorial low-grade astrocytomas.'' Neurosurgery 1996;38:872-8; discussion 878-9. PMID 8727811. 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.
