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Clinical presentation and diagnosis of brain tumors

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Official reprint from UpToDate


www.uptodate.com 2015 UpToDate

Clinical presentation and diagnosis of brain tumors


Authors
Eric T Wong, MD
Julian K Wu, MD

Section Editors
Jay S Loeffler, MD
Patrick Y Wen, MD

Deputy Editor
April F Eichler, MD, MPH

Disclosures: Eric T Wong, MD Nothing to disclose. Julian K Wu, MD Nothing to disclose. Jay S Loeffler, MD Nothing to
disclose. Patrick Y Wen, MD Grant/Research/Clinical Trial Support: Agios; Angiochem; AstraZeneca; Exelixis;
GlaxoSmithKline; Karyopharm; Novartis; Sanofi-Aventis; Regeneron Pharmaceuticals, Inc.; Vascular Biogenics

All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Oct 2015. | This topic last updated: Sep 26, 2014.
INTRODUCTION Brain tumors are a diverse group of neoplasms arising from different cells within the
central nervous system (CNS) or from systemic tumors that have metastasized to the CNS. Brain tumors
include a number of histologic types with markedly different tumor growth rates (table 1 and table 2).
(See "Classification of gliomas" and "Overview of the clinical manifestations, diagnosis, and
management of patients with brain metastases".)
Brain tumors can produce symptoms and signs by local brain invasion, compression of adjacent
structures, and increased intracranial pressure (ICP). In addition to the histology of the tumor, the clinical
manifestations are determined by the function of the involved areas of the brain. The proper evaluation
of the patient with a suspected brain tumor requires a detailed history, comprehensive neurologic
examination, and appropriate diagnostic neuroimaging studies [1].
The clinical manifestations and diagnosis of primary brain tumors will be reviewed here. Aspects of the
various primary brain tumors are discussed in the specific topics, and the presentation and approach to
patients with brain metastases is presented separately. (See "Overview of the clinical manifestations,
diagnosis, and management of patients with brain metastases".)
CLINICAL MANIFESTATIONS Patients with primary or metastatic brain tumors may present with
either generalized or focal signs and/or symptoms (table 3).
Generalized
Headaches Headache is a common manifestation of brain tumors and is the worst symptom in
about one-half of patients [2]. The headaches are usually dull and constant, but occasionally throbbing.
Severe headaches are infrequent, unless obstructive hydrocephalus or meningeal irritation is present.
The "classic" early morning brain tumor headache appears to be uncommon. (See "Evaluation of
headache in adults".)
Features suggestive of a brain tumor in a patient complaining of headaches include nausea and vomiting
(present in about 40 percent), a change in prior headache pattern, and an abnormal neurologic
examination [2]. In addition, many patients with a brain tumor report worsening of headache after a
change in body position, such as bending over, or with maneuvers that raise intrathoracic pressure, such
as coughing, sneezing, or the Valsalva maneuver [2]. These activities lead to a period of raised ICP,
which uncommonly can cause a loss of consciousness (see 'Syncope' below).
The headache can be localizing. In the above series, the typical headache was bifrontal, but worse on
the same side as the tumor [2]. Alternatively, a generalized headache may result from increased
intracranial pressure (ICP), which can arise either from a large mass or from restriction of cerebrospinal
fluid outflow causing hydrocephalus. Increased ICP may lead to the classic triad of headache, nausea,

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and papilledema. (See "Evaluation and management of elevated intracranial pressure in adults".)
Tumor-related headaches tend to be worse at night and may awaken the patient. This nocturnal pattern
is thought to be due in part to transient increases in PCO2, a potent vasodilator, during sleep. Other
possible physiologic explanations include recumbency and decreased cerebral venous return.
The manifestations of headache in brain tumor patients were illustrated by a retrospective review of 111
patients with brain tumors, in which headaches were present in 48 percent of cases with either primary
or metastatic disease [2]. The headaches were tension-type in 77 percent, migraine-type in 9 percent,
and other types in 14 percent.
Brain tumor headaches are discussed in more detail elsewhere. (See "Brain tumor headache".)
Seizures Seizures are among the most common symptoms of gliomas and cerebral metastases.
Some patients who are seizure-free at diagnosis subsequently develop seizures [3,4], but routine
prophylaxis with anticonvulsant medications is not recommended. (See "Seizures in patients with
primary and metastatic brain tumors".)
The incidence of seizures is higher with primary tumors than with metastatic lesions, and among patients
with primary tumors, seizures are less common with high-grade as opposed to low-grade gliomas [5,6].
This was illustrated in a review of 1028 patients with primary brain tumors: the prevalence of seizures
was 49, 69, and 85 percent among patients with glioblastoma (GBM), anaplastic glioma, and low-grade
glioma, respectively [6].
Seizures may be the presenting symptom or develop subsequently. In two large series of patients with
GBM, seizures were the initial manifestation in 18 percent and were present at the time of diagnosis in
29 percent, for an average duration of one year (table 4) [7,8]. The frequency and onset of seizures in
patients with brain metastases was illustrated in a series of 195 patients, in which seizures were present
at diagnosis in 9 percent and subsequently developed in another 10 percent [4].
Although seizures can be either generalized or focal, any seizure focus can cause a generalized seizure.
In patients who have focal seizures, the clinical presentation is dependent upon the tumor location. As
an example, frontal lobe tumors may cause focal tonic-clonic movements involving one extremity, while
seizures originating within the occipital lobe may cause visual disturbances. Temporal lobe seizures are
the most difficult to diagnose and localize. In this setting, abrupt sudden behavioral changes may occur
with or without typical preseizure auras, such as abnormal smell, taste, or gastrointestinal symptoms.
Tumor-related seizures are typically repetitive and are stereotyped in a given patient. The ictal event
may be preceded by an aura, which is itself a simple partial seizure, and followed by postictal sequelae.
The postictal phase can be manifested as a period of fatigue and an urge to sleep. For patients with
focal seizures, a postictal paresis (also known as a Todd's paralysis) may be present. (See "Overview of
the management of epilepsy in adults".)
Both primary and metastatic brain tumors can cause status epilepticus, which may occur at the time of
tumor diagnosis or subsequently [9]. (See "Convulsive status epilepticus in adults: Classification, clinical
features, and diagnosis".)
Patients who present with seizures usually have smaller primary brain tumors or fewer metastatic lesions
in the brain, compared to those who present with other symptoms. This is probably because the
diagnosis of a seizure is an indication for neuroimaging, which leads to an earlier diagnosis. (See
"Evaluation of the first seizure in adults".)
A seizure should not be confused with a syncopal event that may be caused by an abrupt increase in
ICP. This distinction is important since treatment is different in the two conditions. Patients with seizures
are at risk of subsequent seizures [3,10], and the treatment is anticonvulsants. In contrast, patients with

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increased ICP require urgent corticosteroids, neurosurgical intervention, or both. (See 'Syncope' below
and "Overview of the management of epilepsy in adults" and "Management of vasogenic edema in
patients with primary and metastatic brain tumors".)
Nausea and vomiting Brain tumors can cause nausea and/or vomiting by increasing the ICP at
the area postrema of the medulla. (See "Approach to the adult with nausea and vomiting".)
Several characteristics suggest the possibility of tumor-associated emesis, such as triggering emesis by
an abrupt change in body position. More importantly, neurogenic nausea and vomiting usually occur in
the context of other neurologic symptoms such as headache or focal neurologic deficit; these signs and
symptoms may be subtle [11,12].
Syncope A significant rise in ICP can temporarily cut off cerebral perfusion, leading to loss of
consciousness. Patients with brain tumors are particularly susceptible to this sequence of events in
association with plateau waves.
Plateau waves are sustained pressure waves that occur within the brain and are caused by activities that
transiently raise the ICP [13,14]. As an example, any Valsalva maneuver (eg, coughing, sneezing,
vomiting) that increases the intrathoracic pressure can impede jugular venous drainage, leading to a
transient increase in ICP.
In the presence of a brain tumor, the baseline ICP may be raised to a level that reduces brain
compliance; in this setting, even a further small increase in intracranial fluid volume can result in
dramatic elevations in ICP. The cerebral perfusion pressure is the difference between the mean systemic
arterial pressure and ICP. Thus, a significant rise in ICP can temporarily cut off cerebral perfusion,
leading to loss of consciousness. (See "Evaluation and management of elevated intracranial pressure in
adults".)
A syncopal episode may simulate a seizure, since patients suffer loss of consciousness and may have a
few tonic-clonic jerks. Identification of plateau wave-related episodes of loss of consciousness is critical,
since these events identify patients who require urgent corticosteroids and/or neurosurgical intervention
to reduce elevated ICP rather than treatment with an anticonvulsant. (See "Management of vasogenic
edema in patients with primary and metastatic brain tumors", section on 'Glucocorticoids'.)
Cognitive dysfunction Cognitive dysfunction, which includes memory problems and mood or
personality change, is common among patients with intracranial malignancy.
Most of the neurocognitive deficits associated with brain tumors are subtle. Patients often complain of
having low energy, fatigue, an urge to sleep, and loss of interest in everyday activities. They may
become abulic and show a lack of spontaneity (table 5). This pattern of symptoms can be confused with
depression. (See "Unipolar depression in adults: Assessment and diagnosis".)
Because these symptoms lack specificity, they are often recognized in retrospect by the patient or the
treating physician. Thus, consideration should be given to neuroimaging to rule out a brain tumor in
patients without a prior history of depression who experience new onset of depressive symptoms without
obvious cause.
Focal
Weakness Muscle weakness is a common complaint in patients with brain tumors. The
manifestations may be subtle, particularly in the early stages. For upper motor neuron lesions, weakness
is generally more pronounced in the flexors of the lower extremities than in the extensors, and more
pronounced in the extensors than the flexors in the upper extremities. Transient weakness may
represent a postictal state, as in Todd's paralysis (see 'Seizures' above). (See "The detailed neurologic
examination in adults", section on 'Upper versus lower motor neuron lesions'.)

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A key feature of tumor-related muscle weakness is its frequent responsiveness to high-dose


dexamethasone, particularly with tumors that are near the motor cortex or its descending fibers. A
response to dexamethasone usually means that the weakness is caused by edema and not by direct
tumor involvement. In such a patient, craniotomy can be considered to relieve mass effect and lessen
the corticosteroid requirement, even if the patient is not resectable for cure. (See "Management of
vasogenic edema in patients with primary and metastatic brain tumors", section on 'Glucocorticoids'.)
Sensory loss Cortical sensory deficits (abnormalities in graphesthesia or stereognosis) can
develop in patients whose tumors invade the primary sensory cortex (table 5). These sensory deficits
usually do not respect a dermatomal or peripheral nerve distribution. (See "The detailed neurologic
examination in adults", section on 'Sensory examination'.)
The type of deficit varies in part with location of the tumor. As an example, visual-spatial disconnection
syndromes can be found in patients with tumors located in the visual association cortex (see 'Visual
spatial dysfunction' below). Some of the other cortically-based sensory deficits include loss of spatial
orientation, tingling, and lack of coordination.
Aphasia Aphasia is a disorder of language function, not of vocalization, as in dysarthria or
hoarseness. It is a specific sign of a lesion in the dominant hemisphere (usually left frontal or parietal); in
comparison, lesions in the nondominant hemisphere may produce apraxia, which refers to an inability to
perform purposeful movements (table 5).
Patients who are aphasic may be confused with those who have dementia or other psychiatric disorders
such as psychosis or depression. Subacute psychosis in a patient without an antecedent psychiatric
history is a diagnosis of exclusion that requires diagnostic neuroimaging studies to rule out an organic
cause.
Visual spatial dysfunction The visual pathway courses through the brain from the retina and
optic chiasm to the occipital poles of the cerebral cortex. Because of its long course through the brain,
the visual pathway can be affected by brain tumors that involve any of these areas.
Examination of the retina, particularly the optic discs, is an important component of the initial
examination of a patient suspected of having a brain tumor. The optic nerve head can be a good
measure of ICP, although papilledema is often not present in the elderly despite an increase in ICP.
Although gross papilledema is easy to diagnose, evolving papilledema can be difficult to recognize.
As an example, only the medial portion of the optic disk may be blurred initially in early
papilledema. Venous engorgement and the absence of venous pulsations are also important
diagnostic clues. (See "Overview and differential diagnosis of papilledema".)
Tumor-related compression of the optic chiasm usually manifests as a bitemporal hemianopsia.
However, there may be a unilateral hemianopsia with a central scotoma in the contralateral eye in
the early stages, particularly when the compression is on one side. The latter results from partial
compression of the Wilbrand's knee in the contralateral optic nerve. (See "Causes, presentation,
and evaluation of sellar masses" and "Optic pathway glioma".)
Postchiasmatic lesions also may present with visual abnormalities. Because of the somatotopic
representation of the visual pathways, the more anterior the lesion, the more asymmetric the
hemianopsia.
DIAGNOSTIC NEUROIMAGING The differential diagnosis of an adult presenting with signs and
symptoms suggesting a brain tumor includes both neoplastic and nonneoplastic conditions (table 6) [15].
Neuroradiologic imaging is the major diagnostic modality in the evaluation of brain tumors. These studies
are critical for preoperative planning, and they often provide information about the etiology of a mass
lesion.

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Although neuroimaging cannot definitively establish the specific histology, the characteristic appearance
of dural-based meningiomas often can allow a tentative diagnosis. Treatment of meningiomas without a
histologic diagnosis may be warranted in carefully selected cases for lesions in a surgically inaccessible
location. (See "Meningioma: Clinical presentation and diagnosis", section on 'Neuroimaging'.)
Magnetic resonance imaging Gadolinium-enhanced magnetic resonance imaging (MRI) is usually
the only test needed to suggest a brain tumor. MRI may also provide information that indicates the
specific tumor type:
High-grade gliomas are typically hypointense on T1-weighted images, and enhance
heterogeneously following contrast infusion. Enhancing tumor can be distinguished from the
surrounding hypointense signal of edema on T1-weighted sequences (image 1).
Regardless of the histologic grade, astrocytomas generally show increased T2 and FLAIR signal
intensity; however, some astrocytomas do not manifest contrast enhancement [16].
Low-grade gliomas generally present as an infiltrating hemispheric lesion that produce little mass
effect. The MRI appearance of focal brainstem gliomas is discussed elsewhere. (See "Focal
brainstem glioma", section on 'Clinical presentation'.)
In addition to permitting visualization of the tumor and its relationship to the surrounding normal
parenchyma, MRI is also superior to computed tomography (CT) for evaluation of the meninges,
subarachnoid space, and posterior fossa, and for defining the vascular distribution of the abnormality.
(See 'Computed tomography' below.)
Magnetic resonance spectroscopy Magnetic resonance spectroscopy (MRS) is increasingly being
utilized as a diagnostic technique in patients with suspected brain tumors [17-20]. This technique may
improve the differentiation of locally infiltrative brain tumors from other types of well-circumscribed
intracranial lesions by analyzing the chemical composition in an area of interest selected by the
radiologist. Important spectroscopic signals include N-acetylaspartate, choline, lactate, and
2-hydroxyglutarate (table 7):
N-acetylaspartate, a byproduct of the ubiquitous neurotransmitter glutamate, signals the presence
of neurons since it localizes to the synaptic terminals, and is decreased in gliomas.
Choline, a component of cell membranes, is increased in tumors.
Lactate, a product of anaerobic respiration, can be present in necrotic tumor, infection, or stroke.
Mutations in IDH1 and IDH2 result in accumulation of 2-hydroxyglutarate [21-23].
MRS cannot differentiate the types of infiltrative or circumscribed lesions, and it cannot replace histologic
diagnosis of malignancy [19]. However, it can help differentiate between neoplasm and other central
nervous system processes [24]. The utility of MRS was illustrated in a study of 26 patients with
intracranial masses who underwent MRI, proton MRS, and stereotactic biopsy [19]. For patients with
gliomas and lymphomas, pathologic spectra were present outside the area of contrast enhancement,
suggesting infiltration beyond the borders suggested by MRI. In comparison, four circumscribed tumors
(meningioma, pineocytoma, metastasis, and germinoma) showed no pathologic spectra outside the
region of enhancement.
MRS spectroscopy signals are degraded by bone and cerebrospinal fluid. As a result, MRS is less useful
for skull base and periventricular lesions.
Functional MRI When a region of the brain is activated (eg, the language center during phonation or
the motor cortex when moving a limb), blood flow to that region increases. Functional MRI (also known
as echoplanar MRI) permits the measurement of differences in blood flow though particular regions of

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the brain and has several advantages in patients with brain tumors:
Functional MRI is an important adjunct in the preoperative planning for patients whose tumor is
located near eloquent areas of the brain [25]. In such areas, imaging after activation of sensory and
motor areas by appropriate stimuli may permit separation of tumor from normal brain preoperatively
(functional brain imaging) [26,27].
Functional MRI may permit better resolution of tumor versus surrounding edema at the tumor
borders [28,29].
Ultrafast acquisition of MRI images by echoplanar imaging is free from motion artifact and may be
useful in patients who are unable to cooperate with standard MRI scanning [30].
Perfusion MRI Perfusion MRI is the imaging of blood flow in brain tumors. This is done either with a
bolus of gadolinium as in dynamic contrast MRI [31] or dynamic susceptibility contrast MRI [32], or with
magnetic pulsation of water molecules as they pass through carotid and vertebral arteries as in arterial
spin labeling [33,34]. Increased perfusion can be seen in newly diagnosed or recurrent brain tumors,
usually reflecting the presence of hypervascularity.
Computed tomography CT has largely been replaced by cranial MRI as the imaging modality of
choice for brain tumors. However, CT retains utility in selected situations:
To detect bone or vascular involvement
To detect metastases to the skull base, clivus, or regions near the foramen magnum
In an emergency situation (eg, an unstable patient with a suspected intratumoral hemorrhage),
when CT can be faster to perform than MRI
In patients for whom MRI is contraindicated, either because of an iron-containing implant or
because of claustrophobia
PET scans Positron emission tomography (PET) with fluorodeoxyglucose (FDG) can be used to
detect malignant tumors with high metabolic rates. Such lesions take up greater amounts of glucose
than surrounding tissues or tumors with slower metabolic rates.
FDG-PET may be useful in the following situations:
To localize the areas of maximum glucose utilization within the tumor. This information can guide
the neurosurgeon to biopsy tumor locations with the most aggressive biologic behavior [35-37].
To permit the mapping of functional areas of the brain prior to surgery or radiation, in conjunction
with functional MRI, in order to minimize injury to eloquent areas [26,38,39].
To differentiate recurrent tumor from radiation necrosis [40-44].
To help differentiate high-grade (glucose hypermetabolizing) from low-grade (glucose
hypometabolizing) brain tumors [45,46]. In patients with low-grade gliomas, FDG-PET images that
show diffuse hypometabolism may support a decision to defer treatment, while the presence of
hypermetabolic areas may indicate a high-grade tumor and signal the need for biopsy or treatment.
(See "Diagnosis and classification of low-grade gliomas".)
Because of high basal uptake of FDG by normal brain tissues, the low signal-to-noise ratio of FDG-PET
may result in false negative data [47], sensitivity of 71 percent and specificity of 80 percent [44]. As a
result, FDG-PET is not an FDA-approved diagnostic study for evaluating malignancies in the brain, even
though it is approved for systemic malignancies. 18F-fluorothymidine-PET (18F-FLT-PET) has a higher
signal-to-noise ratio than FDG-PET [48]. But its exact utility in the brain tumor population await further

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clinical trials.
SPECT imaging Single photon emission CT (SPECT) utilizes various isotopes to detect
abnormalities in the blood brain barrier. Preoperative SPECT using thallium-201 is useful to distinguish
benign from malignant brain lesions, predict the histologic grade of brain tumors, and select areas for
biopsy [49]. The uptake of 201-Tl is unaffected by steroid treatment [50].
There appears to be a correlation between early and delayed tumor uptake of 201-Tl and the
subsequent grade of the surgically resected tumor, allowing a distinction between low- and high-grade
astrocytomas [50-53].
DIAGNOSTIC NEUROSURGICAL INTERVENTION Accurate diagnosis of a brain tumor requires an
adequate tissue sample for histologic study. This may be obtained by stereotactic biopsy or open
surgery.
Corticosteroid use should be avoided prior to biopsy or surgery if either a primary central nervous
system lymphoma or an infectious process is part of the differential diagnosis. (See 'CNS lymphomas'
below.)
Preoperative assessment The likelihood that a lesion is metastatic should be assessed prior to
proceeding to biopsy. Brain metastases are more common than primary brain tumors. Although brain
metastases usually present in the context of overt systemic disease, they can occur as the initial
manifestation of a systemic malignancy.
If any aspect of the clinical or neurodiagnostic evaluation suggests that a brain tumor is a metastatic
rather than a primary lesion, systemic evaluation, particularly of the thorax, should be carried.
Neurosurgical intervention in a patient with a presumed brain metastasis should balance the risks of the
procedure versus the potential benefits (ie, tissue diagnosis, resection of a solitary lesion, relief of
neurological symptoms). (See "Overview of the clinical manifestations, diagnosis, and management of
patients with brain metastases".)
Surgical exploration or biopsy Technical advances have improved the safety of both surgical
resection and stereotactic biopsy. Improved diagnostic neuroimaging permits better preoperative
localization of the lesion and separation of the lesion from adjacent normal brain tissue, particularly in
eloquent areas of the brain. Techniques such as intraoperative MRI facilitate improved surgical
navigation for lesion biopsy and resection.
For most patients, tissue for histologic confirmation is obtained at the time of surgical exploration for
resection. In those patients with large, nonresectable lesions or those whose lesions are in a critical
location, stereotactic biopsy is an alternative. In some patients with a meningioma with a lesion that is
either difficult or impossible to access, the characteristic appearance of a dural-based tumor may be
sufficient to permit treatment. (See "Treatment of benign (WHO grade I) meningioma", section on 'RT
alone for nonresectable meningiomas'.)
Glial tumors For patients with primary glial tumors, maximum surgical resection is usually
recommended. (See appropriate topic reviews).
There are two exceptions to this approach:
Low-grade glioma For patients with low-grade glial tumors, the role of maximal resection
remains uncertain. Retrospective studies suggest that more extensive tumor resection is
associated with delay in tumor progression and malignant degeneration, as well as improved
survival. (See "Management of low-grade glioma", section on 'Surgery'.)
Immediate surgery is generally required for patients presenting with a large mass or extensive

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neurologic symptoms, both to establish the diagnosis and to debulk the tumor. However, for
patients with a small tumor not creating a mass effect and only transient symptoms or tumors in
eloquent cortex, careful observation may be an alternative to immediate surgery.
Diffuse pontine glioma As long as characteristic radiologic features are present, a tissue
diagnosis of a pontine gliomas not required prior to treatment (image 2) [54]. In equivocal cases,
the clinician must weigh the risks of a surgical biopsy versus the diagnostic uncertainty. (See
"Diffuse pontine glioma".)
CNS lymphomas Patients with primary central nervous system lymphoma are typically not offered
surgical debulking, since the extent of surgical resection does not influence patient survival. Stereotactic
biopsy is usually recommended, providing a high rate of positive tissue diagnosis with a low rate (<2
percent) of morbidity and mortality. Definitive treatment is usually chemotherapy, radiation, or a
combination of these modalities. (See "Clinical presentation, pathologic features, and diagnosis of
primary central nervous system lymphoma" and "Treatment and prognosis of primary central nervous
system lymphoma".)
Corticosteroids should be avoided whenever possible prior to biopsy or surgery if primary CNS
lymphoma is part of the differential diagnosis. These agents are lymphocytotoxic. A single dose can alter
the histopathologic evaluation, and a short course of treatment may cause the lymphoma to disappear
temporarily.
Brain metastases Biopsy is not necessary for patients with multiple brain metastases if there is a
preexisting primary cancer known to have a propensity for brain metastases. If, however, a patient has a
primary tumor that does not usually metastasize to the brain (eg, prostate cancer), there is no known
primary, or neuroimaging is not typical for metastasis, biopsy may be indicated to define the etiology of a
brain lesion. The importance of biopsy in such situations was illustrated in a randomized trial of surgery
for the treatment of solitary brain metastases, in which 11 percent of patients had a second primary
malignancy, inflammatory process, or infection rather than metastasis [55].
The management of patients with brain metastases is dependent upon the overall condition of the
patient, as well as the number, size, and location of brain metastases. The management of patients with
brain metastases is discussed separately. (See "Treatment of brain metastases in favorable prognosis
patients" and "Treatment of brain metastases in poor prognosis patients".)
Neuropathology Histologic examination of the biopsy specimen remains the most important
component of the diagnostic evaluation of brain tumors. A smear or frozen section can be performed in
the operating room for a preliminary interpretation of the histologic subtype. With this information, the
neurosurgeon can make a decision whether or not to proceed with a more extensive resection.
A definitive diagnosis requires examination of the permanent tissue sections stained by hematoxylin and
eosin. Important information may be derived from additional analyses that include the following:
Proliferative index, using the MIB-1 monoclonal antibody
Immunohistochemical stains
Electron microscopy may be necessary to ascertain the correct diagnosis
Molecular markers, including deletions of chromosome 1p/19q or the presence or absence of
promoter methylation of the DNA repair enzyme O6-methylguanine-DNA methyltransferase
(MGMT), isocitrate dehydrogenase (IDH), and p53
Caution should be exercised in interpreting the tissue diagnosis when the tissue is derived only from a
biopsy specimen. This is particularly true for glial tumors, because regional heterogeneity and sampling
error may underestimate the histologic grade of malignancy [56].

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In patients suspected of having a primary central nervous system lymphoma, corticosteroid use should
be avoided prior to biopsy, as these drugs are lymphocytotoxic and can affect the histopathologic
evaluation. (See "Clinical presentation, pathologic features, and diagnosis of primary central nervous
system lymphoma", section on 'Diagnosis'.)
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Basics topics (see "Patient information: Brain cancer (The Basics)")
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Basics)" and "Patient information: High-grade glioma in adults (Beyond the Basics)" and "Patient
information: Meningioma (Beyond the Basics)")
SUMMARY Brain tumors can produce symptoms and signs by local brain invasion, compression of
adjacent structures, and increased intracranial pressure (ICP). In addition to the histology of the tumor,
the clinical manifestations are determined by the function of the involved areas of brain. The proper
evaluation of the patient with a suspected brain tumor requires a detailed history, a comprehensive
neurologic examination, and appropriate diagnostic neuroimaging studies.
Although newer imaging techniques often provide information suggesting a specific histology, an
adequate tissue sample should generally be obtained, either at the time of neurosurgical resection or by
stereotactic biopsy, to optimize treatment.
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REFERENCES
1. Gutin PH, Posner JB. Neuro-oncology: diagnosis and management of cerebral gliomas--past,
present, and future. Neurosurgery 2000; 47:1.
2. Forsyth PA, Posner JB. Headaches in patients with brain tumors: a study of 111 patients.
Neurology 1993; 43:1678.
3. Moots PL, Maciunas RJ, Eisert DR, et al. The course of seizure disorders in patients with
malignant gliomas. Arch Neurol 1995; 52:717.
4. Cohen N, Strauss G, Lew R, et al. Should prophylactic anticonvulsants be administered to patients
with newly-diagnosed cerebral metastases? A retrospective analysis. J Clin Oncol 1988; 6:1621.
5. Pace A, Bove L, Innocenti P, et al. Epilepsy and gliomas: incidence and treatment in 119 patients.
J Exp Clin Cancer Res 1998; 17:479.
6. Lote K, Stenwig AE, Skullerud K, Hirschberg H. Prevalence and prognostic significance of epilepsy
in patients with gliomas. Eur J Cancer 1998; 34:98.
7. FRANKEL SA, GERMAN WJ. Glioblastoma multiforme; review of 219 cases with regard to natural
history, pathology, diagnostic methods, and treatment. J Neurosurg 1958; 15:489.

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8. ROTH JG, ELVIDGE AR. Glioblastoma multiforme: a clinical survey. J Neurosurg 1960; 17:736.
9. Cavaliere R, Farace E, Schiff D. Clinical implications of status epilepticus in patients with
neoplasms. Arch Neurol 2006; 63:1746.
10. Cascino GD. Epilepsy and brain tumors: implications for treatment. Epilepsia 1990; 31 Suppl
3:S37.
11. Keane JR. Neurologic symptoms mistaken for gastrointestinal disease. Neurology 1998; 50:1189.
12. Squires RH Jr. Intracranial tumors. Vomiting as a presenting sign. A gastroenterologist's
perspective. Clin Pediatr (Phila) 1989; 28:351.
13. Hayashi M, Handa Y, Kobayashi H, et al. Plateau-wave phenomenon (I). Correlation between the
appearance of plateau waves and CSF circulation in patients with intracranial hypertension. Brain
1991; 114 ( Pt 6):2681.
14. Hayashi M, Kobayashi H, Handa Y, et al. Brain blood volume and blood flow in patients with
plateau waves. J Neurosurg 1985; 63:556.
15. Anderson MD, Colen RR, Tremont-Lukats IW. Imaging mimics of primary malignant tumors of the
central nervous system (CNS). Curr Oncol Rep 2014; 16:399.
16. Scott JN, Brasher PM, Sevick RJ, et al. How often are nonenhancing supratentorial gliomas
malignant? A population study. Neurology 2002; 59:947.
17. Poptani H, Gupta RK, Roy R, et al. Characterization of intracranial mass lesions with in vivo proton
MR spectroscopy. AJNR Am J Neuroradiol 1995; 16:1593.
18. Warren KE, Frank JA, Black JL, et al. Proton magnetic resonance spectroscopic imaging in
children with recurrent primary brain tumors. J Clin Oncol 2000; 18:1020.
19. Burtscher IM, Skagerberg G, Geijer B, et al. Proton MR spectroscopy and preoperative diagnostic
accuracy: an evaluation of intracranial mass lesions characterized by stereotactic biopsy findings.
AJNR Am J Neuroradiol 2000; 21:84.
20. Galanaud D, Chinot O, Nicoli F, et al. Use of proton magnetic resonance spectroscopy of the brain
to differentiate gliomatosis cerebri from low-grade glioma. J Neurosurg 2003; 98:269.
21. Pope WB, Prins RM, Albert Thomas M, et al. Non-invasive detection of 2-hydroxyglutarate and
other metabolites in IDH1 mutant glioma patients using magnetic resonance spectroscopy. J
Neurooncol 2012; 107:197.
22. Andronesi OC, Kim GS, Gerstner E, et al. Detection of 2-hydroxyglutarate in IDH-mutated glioma
patients by in vivo spectral-editing and 2D correlation magnetic resonance spectroscopy. Sci
Transl Med 2012; 4:116ra4.
23. Choi C, Ganji SK, DeBerardinis RJ, et al. 2-hydroxyglutarate detection by magnetic resonance
spectroscopy in IDH-mutated patients with gliomas. Nat Med 2012; 18:624.
24. Quan D, Hackney DB, Pruitt AA, et al. Transient MRI enhancement in a patient with seizures and
previously resected glioma: use of MRS. Neurology 1999; 53:211.
25. Lehricy S, Duffau H, Cornu P, et al. Correspondence between functional magnetic resonance
imaging somatotopy and individual brain anatomy of the central region: comparison with
intraoperative stimulation in patients with brain tumors. J Neurosurg 2000; 92:589.
26. Bittar RG, Olivier A, Sadikot AF, et al. Presurgical motor and somatosensory cortex mapping with
functional magnetic resonance imaging and positron emission tomography. J Neurosurg 1999;
91:915.
27. Schulder M, Maldjian JA, Liu WC, et al. Functional image-guided surgery of intracranial tumors
located in or near the sensorimotor cortex. J Neurosurg 1998; 89:412.
28. Pardo FS, Aronen HJ, Kennedy D, et al. Functional cerebral imaging in the evaluation and
radiotherapeutic treatment planning of patients with malignant glioma. Int J Radiat Oncol Biol Phys

10 of 12

11/19/15 6:54 PM

Clinical presentation and diagnosis of brain tumors

http://www.uptodate.com/contents/clinical-presentation-and-d...

1994; 30:663.
29. Aronen HJ, Glass J, Pardo FS, et al. Echo-planar MR cerebral blood volume mapping of gliomas.
Clinical utility. Acta Radiol 1995; 36:520.
30. Brning R, Seelos K, Yousry T, et al. Echo-planar magnetic resonance imaging (EPI) with
high-resolution matrix in intra-axial brain tumors. Eur Radiol 1999; 9:1392.
31. Wong ET, Jackson EF, Hess KR, et al. Correlation between dynamic MRI and outcome in patients
with malignant gliomas. Neurology 1998; 50:777.
32. Batchelor TT, Sorensen AG, di Tomaso E, et al. AZD2171, a pan-VEGF receptor tyrosine kinase
inhibitor, normalizes tumor vasculature and alleviates edema in glioblastoma patients. Cancer Cell
2007; 11:83.
33. Alsop DC, Detre JA. Multisection cerebral blood flow MR imaging with continuous arterial spin
labeling. Radiology 1998; 208:410.
34. Alsop DC, Detre JA. Reduced transit-time sensitivity in noninvasive magnetic resonance imaging
of human cerebral blood flow. J Cereb Blood Flow Metab 1996; 16:1236.
35. Hanson MW, Glantz MJ, Hoffman JM, et al. FDG-PET in the selection of brain lesions for biopsy. J
Comput Assist Tomogr 1991; 15:796.
36. Herholz K, Pietrzyk U, Voges J, et al. Correlation of glucose consumption and tumor cell density in
astrocytomas. A stereotactic PET study. J Neurosurg 1993; 79:853.
37. Levivier M, Goldman S, Pirotte B, et al. Diagnostic yield of stereotactic brain biopsy guided by
positron emission tomography with [18F]fluorodeoxyglucose. J Neurosurg 1995; 82:445.
38. Kaplan AM, Bandy DJ, Manwaring KH, et al. Functional brain mapping using positron emission
tomography scanning in preoperative neurosurgical planning for pediatric brain tumors. J
Neurosurg 1999; 91:797.
39. Hamilton RJ, Sweeney PJ, Pelizzari CA, et al. Functional imaging in treatment planning of brain
lesions. Int J Radiat Oncol Biol Phys 1997; 37:181.
40. Thiel A, Pietrzyk U, Sturm V, et al. Enhanced accuracy in differential diagnosis of radiation necrosis
by positron emission tomography-magnetic resonance imaging coregistration: technical case
report. Neurosurgery 2000; 46:232.
41. Barker FG 2nd, Chang SM, Valk PE, et al. 18-Fluorodeoxyglucose uptake and survival of patients
with suspected recurrent malignant glioma. Cancer 1997; 79:115.
42. Doyle WK, Budinger TF, Valk PE, et al. Differentiation of cerebral radiation necrosis from tumor
recurrence by [18F]FDG and 82Rb positron emission tomography. J Comput Assist Tomogr 1987;
11:563.
43. Janus TJ, Kim EE, Tilbury R, et al. Use of [18F]fluorodeoxyglucose positron emission tomography
in patients with primary malignant brain tumors. Ann Neurol 1993; 33:540.
44. Chao ST, Suh JH, Raja S, et al. The sensitivity and specificity of FDG PET in distinguishing
recurrent brain tumor from radionecrosis in patients treated with stereotactic radiosurgery. Int J
Cancer 2001; 96:191.
45. Sasaki M, Kuwabara Y, Yoshida T, et al. A comparative study of thallium-201 SPET, carbon-11
methionine PET and fluorine-18 fluorodeoxyglucose PET for the differentiation of astrocytic
tumours. Eur J Nucl Med 1998; 25:1261.
46. Borgwardt L, Hjgaard L, Carstensen H, et al. Increased fluorine-18 2-fluoro-2-deoxy-D-glucose
(FDG) uptake in childhood CNS tumors is correlated with malignancy grade: a study with FDG
positron emission tomography/magnetic resonance imaging coregistration and image fusion. J Clin
Oncol 2005; 23:3030.
47. Olivero WC, Dulebohn SC, Lister JR. The use of PET in evaluating patients with primary brain

11 of 12

11/19/15 6:54 PM

Clinical presentation and diagnosis of brain tumors

http://www.uptodate.com/contents/clinical-presentation-and-d...

tumours: is it useful? J Neurol Neurosurg Psychiatry 1995; 58:250.


48. Chen W, Cloughesy T, Kamdar N, et al. Imaging proliferation in brain tumors with 18F-FLT PET:
comparison with 18F-FDG. J Nucl Med 2005; 46:945.
49. Sun D, Liu Q, Liu W, Hu W. Clinical application of 201Tl SPECT imaging of brain tumors. J Nucl
Med 2000; 41:5.
50. Black KL, Hawkins RA, Kim KT, et al. Use of thallium-201 SPECT to quantitate malignancy grade
of gliomas. J Neurosurg 1989; 71:342.
51. Kaplan WD, Takvorian T, Morris JH, et al. Thallium-201 brain tumor imaging: a comparative study
with pathologic correlation. J Nucl Med 1987; 28:47.
52. Slizofski WJ, Krishna L, Katsetos CD, et al. Thallium imaging for brain tumors with results
measured by a semiquantitative index and correlated with histopathology. Cancer 1994; 74:3190.
53. Vertosick FT Jr, Selker RG, Grossman SJ, Joyce JM. Correlation of thallium-201 single photon
emission computed tomography and survival after treatment failure in patients with glioblastoma
multiforme. Neurosurgery 1994; 34:396.
54. Barkovich AJ, Krischer J, Kun LE, et al. Brain stem gliomas: a classification system based on
magnetic resonance imaging. Pediatr Neurosurg 1990-1991; 16:73.
55. Patchell RA, Tibbs PA, Walsh JW, et al. A randomized trial of surgery in the treatment of single
metastases to the brain. N Engl J Med 1990; 322:494.
56. Jackson RJ, Fuller GN, Abi-Said D, et al. Limitations of stereotactic biopsy in the initial
management of gliomas. Neuro Oncol 2001; 3:193.
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