Benign and Malignant Intracranial Tumours in Adults

Radiological Investigations in Intracranial Tumours

Brain tumours are a leading cause of death in young adults, but they occur at all ages with a variable prognosis depending on lesion type. The aim of imaging at first diagnosis is to localise the tumour, to exclude differentials and to decide whether urgent surgical intervention is required. The choice of imaging protocol will depend on the patient's symptoms, their systemic condition and scanner availability.

The best investigation for patients with suspected intracranial tumours is magnetic resonance imaging (MRI). This shows excellent anatomical detail and soft-tissue contrast, which is helpful for lesion characterisation and to guide operative planning. Advanced MR imaging techniques, which aim to identify specific pathophysiological and metabolic tumour properties, have become increasingly available in clinical practice, including diffusion-weighted imaging (DWI), perfusion-weighted imaging (PWI) and magnetic resonance spectroscopy (MRS). CT retains an important role in the imaging of acutely unwell brain tumour patients, and also in situations where bone integrity is of concern. Presurgical angiography can be valuable where the planned operative approach passes near main vessels; this is usually achieved through cross-sectional techniques (computed tomographic angiography [CTA], magnetic resonance angiography [MRA]). Occasionally, endovascular tumour embolisation is advisable to reduce the intraoperative bleeding risk of highly vascular lesions.

Computed Tomography

Although it provides limited information, CT remains the most rapid and widely available test to identify haemorrhage, critical mass effect or hydrocephalus in a neurologically deteriorating patient.

Many clinically symptomatic brain tumours are detectable on CT, either due to mass effect and/or altered attenuation. Intra-axial tumours may produce variable, often heterogenous image signal on non-enhanced CT images, featuring low attenuation in areas of necrosis and with vasogenic oedema. Certain masses, for example lymphoma, may appear isodense to hyperdense compared with surrounding brain parenchyma. Lesions that are isoattenuating, small or in the midline can be easily overlooked on CT. Depending on Hounsfield unit values, increased attenuation within a tumour can indicate recent haemorrhage or calcification. Brain tumours, which frequently exhibit high attenuation, are listed in Table 55.1 .

TABLE 55.1
Commonly Calcified and Haemorrhagic Lesions
Commonly Calcified Lesions Commonly Haemorrhagic Lesions
Oligodendrogliomas (90%) Glioblastoma (grade 4 glioma)
Choroid plexus tumours Oligodendroglioma
Ependymoma Metastases

  • Melanoma

  • Lung

  • Breast

Central neurocytoma

It is important to review CT bone-window settings, because these may reveal features, such as benign hyperostosis or erosions, that may signify a more aggressive lesion, thereby narrowing the differential diagnosis. CT post contrast is rarely beneficial to characterise brain tumours, as this will not determine the need for surgical intervention, provided that MRI can follow within a clinically acceptable time frame.

Magnetic Resonance Imaging

Structural Magnetic Resonance Imaging

A standard clinical MRI protocol for brain tumour imaging should include T 2 weighted, fluid-attenuated recovery (FLAIR) sequences, DWI, T 1 weighted images before and after the intravenous (IV) administration of gadolinium contrast medium. Brain tumour patients generally require long-term follow-up, with intervals scheduled according to the expected tumour growth rate and whether recent changes have been observed.

To ensure accurate serial imaging comparisons, MR image parameters (e.g. contrast dosage and timing) should be kept as consistent as possible. Where available, 3D imaging increases small lesion visibility ( Fig. 55.1 ) and can support volumetric tumour measurements.

Fig. 55.1, Cortical Metastasis.

T 1 and T 2 signals vary amongst brain tumour types dependent on tissue density, solid versus cystic components, haemorrhage and/or mineralisation. On FLAIR images, intrinsic lesions often stand out from surrounding brain parenchyma. This additional contrast is valuable but non-specific, and in some cases, FLAIR demonstrates grey-white matter detail less well than T 2 . Intratumoural blood product and calcification are most conspicuous and hypointense on T 2 * or susceptibility-weighted images (SWI), where magnetic susceptibility effects are stronger. Hyperintensities on T 1 images can be due to haemorrhage, atypical calcification, melanin (in metastatic melanomas) or fat. A typical combination of brain tumour site, morphology and signal composition will often substantially reduce the list of differential possibilities, or even generate a single diagnosis.

The presence and pattern of gadolinium uptake can give additional information about the nature of brain tumours, but in many cases this is not specific. Assessing for contrast uptake is also important in post therapy assessment to identify recurrent enhancing disease, and whenever infection is a possible differential. For repeated examinations, potential risks of gadolinium deposition need to be considered; however, there is currently no evidence against the serial use of macrocyclic agents in this situation.

In challenging cases, the visibility of contrast enhancement on MR can be improved by doubling or tripling the gadolinium dose, or by using high-relaxivity gadolinium compounds. In addition, post-contrast FLAIR sequences are excellent for identifying subtle leptomeningeal disease.

MRI can be integrated into neurosurgical navigation systems; furthermore, some institutions possess intraoperative MRI facilities to monitor the resection extent in near real time while preserving eloquent regions of the brain.

Advanced Physiological and Molecular Imaging Methods

Advanced MRI modalities aim to detect specific pathophysiological or metabolic processes that provide complementary information about brain masses, either to predict tumour type ± malignant potential or to assess treated lesions when there is a question regarding tissue viability. To maximise the value of such additional imaging time, the choice of test(s) must be tailored to the clinical situation.

Magnetic Resonance Perfusion-Weighted Imaging

A number of primary intracranial tumours and some metastases exhibit increased vascularity. This does not always equal malignancy, but it can be associated with rapid proliferation if this induces new vessel formation.

There are three methods of PWI:

  • 1.

    Dynamic susceptibility-weighted contrast-enhanced (DSC) imaging exploits the susceptibility effects of gadolinium, which (because of its paramagnetic properties) causes a transient signal reduction on T 2 * weighted images during the passage of a gadolinium bolus. With DSC, a volume of T 2 * images is repeatedly acquired at rapid (1 to 2 seconds) intervals before and during the contrast injection.

  • 2.

    Dynamic contrast-enhanced (DCE) imaging measures the increase of signal intensity on a series of T 1 weighted images before and during gadolinium administration.

  • 3.

    Arterial spin labelling (ASL) uses magnetically labelled blood as endogenous tracer to assess blood flow and does not require an injection of a contrast medium.

DSC is currently the most widely used and best validated perfusion technique in brain tumours. DSC-derived cerebral blood volume (CBV) measurements have been shown to consistently correlate with angiographic and histological markers of tumour neovascularity ( Fig. 55.2 ). For example, DSC is useful to distinguish glioblastoma from slow growing gliomas. To avoid erroneously low measurements due to gadolinium leakage in tumours with blood-brain barrier breakdown, CBV is mathematically normalised (relative cerebral blood volume [‘rCBV’]) relative to normal brain tissue. In addition to this mathematical leakage correction, the administration of a ‘preload’ bolus and the choice of a suitable flip angle can help minimise leakage errors. Underestimation of rCBV may also occur due to susceptibility effects; therefore rCBV measurement should be avoided in such areas. If susceptibility is present in the area of concern (e.g. after surgical intervention), an alternative perfusion technique should be considered in addition.

Fig. 55.2, Dynamic Susceptibility-Weighted Contrast-Enhanced Imaging in Malignant Glioma.

In DCE PWI, T 1 weighted images are repeatedly acquired beyond the duration of the first pass of a gadolinium bolus, typically for about 5 minutes. The shape of the time–signal intensity curve is influenced by tissue perfusion, vascular permeability and the extravascular-extracellular space. Several mathematical models (e.g. ‘extended Tofts’) can be used to quantify contrast leakage into the extravascular space as a measure of microvascular permeability. The most frequently used parameter is the transfer coefficient K trans , which is influenced by endothelial permeability, vascular surface area and flow. DCE images also can be analysed using a model-free approach by looking at the slope of the time–signal intensity curve. DCE quantification is more challenging and therefore it is less widely used than DSC, but DCE has greater spatial resolution and is not hampered by susceptibility effects.

ASL uses labelling of blood hydrogen and requires no contrast injection; therefore it is suitable for children and patients in whom gadolinium is contraindicated. It is the only perfusion technique that directly measures regional cerebral blood flow (rCBF). As hydrogen is freely diffusible and crosses the blood–brain barrier immediately, it is not possible to measure tissue blood volume in the same way as with DSC PWI where the tracer (gadolinium) stays (or is assumed to stay) predominantly in the intravascular compartment. A good correlation between rCBF measurements obtained with ASL and rCBV measurements derived from DSC has been demonstrated so that the use of ASL in neuro-oncology is likely to increase.

Magnetic Resonance Spectroscopy

MRS analyses the metabolite distribution within a chosen volume of brain tissue, thereby providing semiquantitative information. The commonest pattern in brain tumours is a decrease in N -acetylaspartate (NAA), a neuron-specific marker, and creatine, accompanied by elevation of choline, without the presence of lactate, or lipids ( Fig. 55.3 ). The concentration of choline reflects the turnover of cell membranes (due to accelerated synthesis and destruction) and is amplified in tumour regions with high mitotic activity. Lactate is the end product of non-oxidative glycolysis, which is a hallmark of cancerous metabolism that can be exacerbated by hypoxia in fast growing tumours. Tumour hypoxia has been recognised as a major promoter of tumour angiogenesis and invasion. Lactate is probably associated with viable but hypoxic tissue, whereas mobile lipids are thought to indicate tissue necrosis with the breakdown of cell membranes.

Fig. 55.3, Magnetic Resonance Spectroscopy in Malignant Glioma.

The choice of echo time (TE) is an important technical consideration for performing MRS. TE can be short (20 to 40 ms), intermediate (135 to 144 ms) or long (270 to 288 ms). MRS with a short TE has the advantage of demonstrating additional metabolites, which may improve tumour characterisation, such as myo -inositol, glutamate/glutamine and lipids, but is susceptible to baseline distortion and artefactual NAA peaks. Intermediate echo times produce a better baseline, quantification of NAA and choline is more accurate and reproducible and lactate appears (inconsistently) inverted from the baseline. Long echo times are less commonly used for brain tumour imaging and are inferior at demonstrating some of the minor metabolites.

MRS can be valuable in distinguishing brain tumours from non-neoplastic conditions. It has a less well-defined role in distinguishing tumour types and posttreatment effects. Single voxel spectroscopy is technically easier to achieve good-quality spectra, but it assumes an average of metabolites within the measured area and cannot appreciate tumour spatial heterogeneity. Multivoxel techniques, including chemical shift imaging (CSI), are more challenging but provide 2D or 3D spectra with larger area coverage . With modern 3T MRI systems it is possible to obtain a 16 × 16 × 16 array of spectra with a voxel size of 1 cm 3 in 5 to 10 min.

Magnetic Resonance Diffusion Imaging

DWI measures the movement of water molecules within brain tumours, which is influenced by tissue microstructure, particularly cell density and matrix composition. Standard DWI uses three diffusion directions with two or three b values, typically b0, (± b500) and b1000 mm/s 2 . Through mathematical subtraction of T 2 effects, the apparent diffusion coefficient (ADC) map is calculated that describes the overall water diffusivity in the brain. ADC measurements have been shown to correlate inversely with proliferative indices (Ki-67) in gliomas. There is evidence that lower ADC values (without restricted diffusion) may help identify malignant gliomas, and markedly reduced diffusivity may define certain neoplasms such as lymphoma.

Diffusion tensor imaging (DTI) incorporates additional diffusion directions (6+) to gain information about the directionality of water diffusion. The tendency of water to move in some directions more than others is called anisotropy and can be quantified as fractional anisotropy (FA). With intrinsic tumours, normal white matter tracts show a high degree of anisotropy that can be lost if they become infiltrated with cells destroying the ultrastructural boundaries formed by myelin sheaths.

DTI can be post processed to depict key white matter tracts and their connections (tractography) for display in the form of direction-encoded colour images. Tractography is used widely for preoperative planning, as it helps to depict the relations between intrinsic brain tumours and surrounding neural connections. DTI-based advanced diffusion methods are being trialled in research to enhance the microstructural analysis of certain brain tumours.

Functional Magnetic Resonance Imaging

Functional magnetic resonance imaging (fMRI) is performed by detecting blood oxygen level-dependent (BOLD) imaging changes during various forms of brain activity. The most commonly performed technique is task-based fMRI for presurgical assessment (paradigms using motor tasks, language and speech production, and memory produce activation of relevant cortical areas). fMRI is used almost exclusively for preoperative planning, most commonly for language lateralisation. It also supports the localisation of eloquent (e.g. motor) cortical regions that may have been displaced, distorted or compressed by tumour, and to identify evidence of functional reorganisation. fMRI can improve the safety of surgery and allow for a more radical resection. The BOLD effect is an indirect measure of neuronal activity that may be influenced by numerous physiological factors as well as the MR relaxation properties of soft tissue, such that activation within a tumour may partially reflect angiogenesis rather than eloquent function alone, and susceptibility effects from blood products, for instance, may mask areas of brain activation. Other important caveats include the inability of discriminating between indispensable and expendable brain regions, and limitations in predicting the distance between a lesion and an area of functional activity. Non-BOLD techniques, such as ASL, may potentially reduce these pitfalls in the future. Where relevant, fMRI may be combined with MR tractography to minimise intra-operative injury to white matter tracts connected to the eloquent cortical areas ( Fig. 55.4 ).

Fig. 55.4, Functional Magnetic Resonance Imaging in a Patient With a Frontal Low-Grade Glioma.

Positron-Emission Tomography

The positron emission tomography (PET) image signal is generated through the administration of a radioactive tracer that accumulates preferentially within tumour tissue. The most widely used PET tracer in oncological imaging is fluorodeoxyglucose [ 18 F] (FDG), which provides a measure of cellular glucose uptake. Its principal limitation in neuro-oncology is the high physiological baseline glucose metabolism of the brain, which may result in a poor lesion to background contrast. Newer PET radiopharmaceuticals for brain tumour imaging include amino acid analogues such as [ 11 C] methionine (MET), [ 18 F]fluoroethyl- l -tyrosine (FET) and, more recently, [ 18 F]-dihydroxyphenylalanine (FDOPA). Radioactively labelled choline, [ 11 C] choline (CHO) or [ 18 F] choline, can be used to assess membrane cell turnover and 68Ga-DOTATOC shows a high uptake in meningiomas due to somatostatin receptor expression.

PET imaging is used in combination with computed tomography (PET/CT) and in the form of PET/MRI systems, allowing simultaneous acquisition and registration of high-resolution MR sequences and molecular information.

World Health Organization Classification of Central Nervous System Tumours 2016

Brain tumours can be classified according to location within (‘intra-axial’) or external to (‘extra-axial’) brain tissue, and by tissue origin (e.g. glial, meningeal, pituitary, etc.). Traditionally, histopathological analysis was limited to a visual assessment of individual cell morphology, combined with grading according to the presence of proliferative features, such as high mitotic rate, cellular atypia and new vessel formation.

The recognition that genetic mutations occur frequently in many human cancer types has led to fundamental changes in brain tumour diagnosis. In 2009, a whole-genome sequencing study (The Cancer Genome Atlas) identified a number of common mutations of key prognostic value in different brain neoplasms. For several tumour types, most notably gliomas, this information is reflected in the updated 2016 World Health Organization (WHO) classification, which now mandates molecular testing as part of an integrated diagnosis. Histological grade is still considered important, but has become complementary to genetic tumour characteristics. With this regrouping according to shared molecular features, a number of entities (e.g. ‘primitive neuroectodermal tumour’) have been discontinued in the 2016 WHO update. Moreover, in the WHO 2016 classification, gliomatosis cerebri is no longer a glioma subtype but instead is considered as a growth pattern. Several new adult brain tumour classes have been introduced, which are highlighted in the relevant sections. With this change, radiological work-up has experienced a corresponding paradigm shift, whereby emphasis is placed on predicting tumour molecular status (‘radiogenomics’) in addition to the WHO grade.

An outline of the WHO 2016 integrated classification for central nervous system (CNS) tumours is shown in Table 55.2 . The upcoming chapters will discuss intra-axial and extra-axial brain tumours, highlighting typical and non-specific imaging appearances on conventional and advanced imaging.

Summary Box: Radiological Investigations in Intracranial Tumours

  • Consider non-contrast CT to exclude haemorrhage, critical mass effect or hydrocephalus in patients with acutely deteriorating neurological status

  • A standard MRI brain tumour protocol should include T 2 , fluid-attenuated recovery, pre- and post-contrast T 1 and diffusion-weighted sequences with parameters kept as consistent as practicable to aid serial comparisons

  • Advanced MRI techniques can be applied selectively or in combination to enhance diagnostic certainty, however, their yield depends on the tumour type and the clinical situation

TABLE 55.2
The 2016 World Health Organization Classification of Tumours of the Central Nervous System
Overview of the WHO 2016 classification for central nervous system tumours, adapted from Louis DN, Perry A, Reifenberger G, et al. The 2016 World Health Organization Classification of Tumors of the Central Nervous System: a summary. Acta Neuropathol . 2016;131(6):803–820. doi: 10.1007/s00401-016-1545-1.
Diffuse Astrocytic and Oligodendroglial Tumours
Diffuse astrocytoma, IDH-mutant 9400/3
Gemistocytic astrocytoma, IDH-mutant 9411/3
Diffuse astrocytoma, IDH-wildtype 9400/3
Diffuse astrocytoma, NOS 9400/3
Anaplastic astrocytoma, IDH-mutant 9401/3
Anaplastic astrocytoma, IDH-wildtype 9401/3
Anaplastic astrocytoma, NOS 9401/3
Glioblastoma, IDH-wildtype 9440-3
Giant cell glioblastoma 9441/3
Gliosarocma 9442/3
Epithelioid glioblastoma 9440/3
Glioblastoma, IDH-mutant 9445/3*
Glioblastoma, NOS 9440/3
Diffuse midine glioma, H3 K27M-mutant 9385/3*
Oligodendroglioma, IDH-mutant and 1p/19q-codeleted 9450/3
Oligodendroglioma, NOS 9450/3
Anaplastic oligodendroglioma, IDH-mutant and 1p/19q-codeleted 9451/3
Anaplastic oligodendroglioma, NOS 9451/3
Oligoastrocytoma, NOS 9382/3
Anaplastic oligoastrocytoma, NOS 9382/3
Other Astrocytic Tumours
Pilocytic astrocytoma 9421/1
Pilomyxoid astrocytoma 9425/3
Subependymal giant cell astrocytoma 9384/1
Pleomorphic xanthoastrocytoma 9424/3
Anaplastic pleomorphic xanthoastrocytoma 9424/3
Ependymal Tumours
Subependymoma 9383/1
Myxopapillary ependymoma 9394/1
Ependymoma 9391/3
Papillary ependymoma 9393/3
Clear cell ependymoma 9391/3
Tanycytic ependymoma 9391/3
Ependymoma, RELA fusion–positive 9396/3*
Anaplastic ependymoma 9392/3
Other Gliomas
Chordoid glioma of the third ventricle 9444/1
Angiocentric glioma 9431/1
Astroblastoma 9430/3
Choroid Plexus Tumours
Choroid plexus papilloma 9390/0
Atypical choroid plexus papilloma 9390/1
Choroid plexus carcinoma 9390/3
Neuronal and Mixed Neuronal-Glial Tumours
Dysembryoplastic neuroepithelial tumour 9413/0
Gangliocytoma 9492/0
Ganglioglioma 9505/1
Anaplastic ganglioglioma 9505/3
Dysplastic cerebellar gangliocytoma (Lhermitte-Duclos disease) 9493/0
Desmoplastic infantile astrocytoma and ganglioglioma 9412/1
Papillary glioneuronal tumour 9509/1
Rosette-forming glioneuronal tumour 9509/1
Diffuse leptomeningeal glioneuronal tumour
Central neurocytoma 9506/1
Extraventricular neurocytoma 9506/1
Cerebellar liponeurocytoma 9506/1
Paraganglioma 8693/1
Tumours of the Pineal Region
Pineocytoma 9361/1
Pineal parenchymal tumour of intermediate differentiation 9362/3
Pineoblastoma 9362/3
Papillary tumour of the pineal region 9395/3
Embryonal Tumours
Medulloblastomas, genetically defined
Medulloblastoma, WNT-activated 9475/3*
Medulloblastoma, SHH-activated and TP53 -mutant 9476/3*
Medulloblastoma, SHH-activated and TP53 -wildtype 9471/3
Medulloblastoma, non-WNT/non-SHH 9477/3*
    • Medulloblastoma, group 3

    • Medulloblastoma, group 4

Medulloblastomas, histologically defined
Medulloblastoma, classic 9470/3
Medulloblastoma, desmoplastic/nodular 9471/3
Medulloblastoma with extensive nodularity 9471/3
Medulloblastoma, large cell / anaplastic 9474/3
Medulloblastoma, NOS 9470/3
Embryonal tumour with multilayered rosettes, C19MC-altered 9478/3*
Embryonal tumour with multilayered rosettes, NOS 9478/3
Medulloepithelioma 9501/3
CNS neuroblastoma 9500/3
CNS ganglioneuroblastoma 9490/3
CNS embryonal tumour, NOS 9473/3
Atypical teratoid/rhabdoid tumour 9508/3
CNS embryonal tumour with rhabdoid features 9508/3
Tumours of the Cranial and Paraspinal Nerves
Schwannoma 9560/0
Cellular schwannoma 9560/0
Plexiform schwannoma 9560/0
Note that the WHO classifications use spellings that are hybrid between American and British English. The present review, however, has used American English spellings.

Intra-Axial Tumours

This tumour category includes lesions arising from different glial cell lineages (oligodendroglioma, astrocytoma, glioblastoma) and those showing a predominantly neuronal phenotype (ganglioglioma, gangliocytoma, dysembryoplastic neuroepithelial tumour [DNT], glioneuronal tumour [GNT] subtypes).


Gliomas are the commonest intra-axial tumours, of which many (50% to 70%) are highly malignant (glioblastoma, WHO grade IV). The DNA mutational profile and gene expression preferentially determine the prognosis of gliomas, in some cases to a greater extent than microscopic features. For this reason, radiological descriptions of masses as probable low- or high-grade gliomas can be misleading, and should be used with caution in diagnostic reports.

Isocitrate Dehydrogenase Wild-Type Astrocytoma (WHO II–III)

Mutations in the isocitrate dehydrogenase (IDH) gene occur early in glioma genesis and are thought to be the key event that distinguishes benign from malignant gliomas. Most (95%) glioblastomas are IDH wild-type (IDH wt ) tumours. Based on a number of shared molecular features, a high proportion of WHO II-III IDH wt tumours that previously fell into the ‘low grade’ glioma category show highly malignant clinical behaviour with survival less than 2 years, and have been hypothesised to represent early glioblastoma. It should be highlighted that IDH wt tumours are not a homogeneous group (a number of benign brain parenchymal tumours would also lack the IDH mutation if tested), therefore IDH testing requires specialist interpretation in conjunction with clinical and imaging markers. The diagnosis of ‘IDH wt glioma’ as defined in WHO 2016 is only made when other molecular features (e.g. overexpression of the epidermal growth factor receptor (EGFR), the presence of a telomerase reverse transcriptase [TERT] mutation ) are consistent with a malignant glioma.

IDH wt gliomas tend to occur in middle-aged patients (40 to 50 years). Research is progressing into imaging biomarkers of IDH wt gliomas in the hope of improved outcomes with an earlier diagnosis. Possible imaging features may include multifocality, ill-defined margins, lower diffusivity (but not necessarily diffusion restriction), increased perfusion (due to neovascularisation) and variable post-contrast signal. A proportion of malignant IDH wt gliomas are non-gadolinium enhancing ( Fig. 55.5 ).

Fig. 55.5, Wild-Type Astrocytoma.

Glioblastoma (WHO IV)

Most (>90%) glioblastomas are primary, lacking the IDH mutation. Secondary glioblastoma is thought to arise on a continuum from lower grade IDH-mutant astrocytoma.

The most common morphology of glioblastoma is that of a centrally necrotic mass with avid, often nodular rim enhancement surrounded by non-enhancing T 2 /FLAIR hyperintense signal abnormality representing vasogenic oedema ( Fig. 55.6 ). This oedema is universally infiltrated by strands of glioblastoma cells, which cannot be delineated on standard MR images. Areas of reduced diffusion (low signal on the ADC map) may be present in solid tumour components, but they are not specific to the disease. Advanced imaging is very useful for the imaging of gliomas as described further on, and can assist both tumour work-up and biopsy planning to target probable malignant components.

Fig. 55.6, Glioblastoma.

Early postoperative MRI is commonly requested following glioblastoma resection; patient condition permitting it is important that this is performed early (ideally within 48 hours), as linear enhancement of the surgical margins may occur quite soon after surgery. The standard treatment for glioblastoma (GBM) consists of maximum safe resection, followed by adjuvant radiotherapy and chemotherapy with temozolomide. Methylation of the DNA repair gene 0-6-methylguanine-DNA-methyltransferase (MGMT) is associated with a better response to temozolomide chemotherapy and improved prognosis in glioblastomas; MGMT methylation is more common in secondary glioblastoma. Even with maximum treatment, the median survival of primary glioblastoma lies in the region of 12 to 14 months.

Isocitrate Dehydrogenase-Mutant Lower Grade Gliomas

In its physiological state, IDH is an enzyme that participates in normal oxidative metabolism by converting isocitrate to α-ketoglutarate. In its mutant form (IDH mut ), D2-hydroxyglutarate (2-HG) is produced instead. 2-HG is thought to represent an oncometabolite, which promotes tumour growth, supported by an increased glioma risk in patients with D2-glutaric aciduria. Despite this, gliomas with an IDH mutation have a better prognosis (up to several years longer survival) than those without. The most common mutation is in the IDH1 gene (R132H); other IDH1 or IDH2 gene mutations occur less frequently (<10%) but should be tested for in IDH1 negative cases to accurately stratify gliomas.

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