Glioblastomas are high-grade Astrocytomas.
They form from star-shaped cells, astrocytes, that support nerve cells.
Are generally aggressive, resistant to therapy & have a corresponding poor prognosis.
Terminology
- Previously known as glioblastoma multiforme
- Sometimes still referred to as GBM
Epidemiology
- Most common and most malignant adult primary intracranial brain tumour
- Accounts for 15% of all brain tumours and 50% of all Astrocytomas
- Mainly sporadic but can be radiation-induced
- Any age, usually over 40 with peak incidence at 65-75 years
- 3:2 M:F ratio
- Most frequently in Caucasians
Genetic Predispositions
- Turcot Syndrome: development of primary cancers in the CNS, particularly a combination of gastrointestinal adenomatous polyps and primary brain tumours
- Neurofibromatosis Type 1: NF1 is a condition that follows an Autosomal dominant inheritance pattern and affects nerve cell tissue, causing the growth of small tumours throughout the nervous system
- Li-Fraumeni Syndrome: inherited familial predisposition to a wide range of certain, often rare, cancers due to a mutation of the tp53 tumour-suppressor gene
- Ollier Disease & Maffucci Syndrome: Diseases characterised by enchondromas and an increased association with gliomas
Primary Vs Secondary
- Primary
90% of Glioblastomas
Considered “IDH wild-type”
No pre-existing lower grade astrocytoma
Occur in older patients
Have amplification of Epidermal growth factor receptor (EGFR), Phosphatase and tensin homolog (PTEN) mutation that causes cancer & Murine Double Minute-2 (MDM2) mutation causing an increase in MDM2 reducing the p53 availability
- Secondary
10% of Glioblastomas
Considered “IDH mutant”
Arise from pre-existing lower grade diffuse Astrocytomas
Occur in younger patients and are less aggressive
Predilection for frontal lobes
Show p53 mutation, amplification of Platelet-derived Growth Factor (PDGF) (genes that drive tumour progression), loss of heterozygosity on chromosomes 10q, 17p & 19q (suggested of tumour progression), shortening of telomeres, increased telomerase activity and hTERT expression (telomeres uphold genomic integrity, their shortening leads to chromosomal instability, cancer initiation and tumour survival)
*Isocitrate dehydrogenase (IDH) gene mutations
Clinical Presentation
- Focal neurological deficits
- Symptoms of increased intracranial pressure
- Seizures
- Stroke-like signs and symptoms
- For example: headaches, vomiting, trouble thinking, changes in mood or personality, double or blurred vision, trouble speaking
Imaging Differential Diagnosis
- Metastasis
May look identical
Metastases are usually centred on grey-white matter junction and spare the overlying cortex
CBV in the oedema will be reduced
- Primary CNS Lymphoma
Especially in patients with AIDS (due to very common central necrosis)
Homogenous enhancement
- Cerebral Abscess
Dual rim sign
Presence of smooth and complete SWI low-intensity rim
Central restricted diffusion
- Tumefactive demyelinating lesion
Ring pattern of enhancement
Usually in younger patients
- Anaplastic Astrocytoma
No central necrosis
- Subacute Cerebral Infarction
No relevated choline
No elecated CBV
- Cerebral Toxoplasmosis
Infection common in AIDS patients
Immunophenotype
- Glial fibrillary acid protein (GFAP): positive but of variable intensity
- S100 (cytoplasmic calcium-binding proteins): positive
- Nestin (filament protein in nerves for radial growth): positive
- tp53 protein (tumour suppressor gene): positive if TP53 mutated
- Epidermal growth factor receptor (EGFR): positive in 40-98% of cases
- IDH-1 R132H: negative (by definition, otherwise not an IDH wild-type GBM, but rather a secondary IDH mutant tumour)
- H3 K27M mutation: negative (if positive then diffuse midline glioma H3 K27M-mutant)
Macroscopic Appearance
- Poorly marginated
- Diffusely infiltrating
- Multilobulated appearance
- Necrotic
- Haemorrhagic
- Most common in supratentorial white matter
- Variable in size
- Infiltration beyond tumour margin
Locations
- Hemispheric
Most common in frontal lobe and then temporal lobe
Common in Pons, Thalamus, Quadrigeminal region
- Callosal
“butterfly glioma” may grow into ventricle
- Posterior Fossa
Brainstem
- Extra-axial
- Multifocal
In 2-5% of cases
Spread
- Direct extension along white matter tracts corpus callosum (36%), corona radiata, cerebral peduncles, anterior commissure, arcuate fibres
readily crosses midline = butterfly glioma (invasion of septum pellucidum)
frontal and temporal gliomas tend to invade basal ganglia
may invade pia, arachnoid and dura matter mimicking meningioma
- subependymal carpet after reaching the surface of the ventricles
- via CSF (<2%)
- Hematogenous (extremely rare)
Osteoblastic bone lesion
Radiographic Appearance:
- Large tumours at diagnosis unless incidental finding
- Thick, irregular-enhancing margins with central necrotic core +/- haemorrhagic component
- Surrounded by oedema
- 20% Multifocal – multiple enhancing areas connected by abnormal white matter signal = microscopic spread
CT
Non-Contrast CT
Inhomogeneous (hypodense) low-density mass
Irregular shape poorly defined margins, cavitary necrosis, cystic appearance, peritumoral “fingers of oedema”
Considerable mass effect compression and displacement of ventricles, cisterns, brain parenchyma
Iso- /hyperdense margins (haemorrhagic in 5%)
Contrast Enhanced CT
Microvascular proliferation --> new vessels with bad blood-brain barrier = contrast leakage in extracellular membrane = contrast enhancement
Diffuse homogenous enhancement
Ring pattern (occasionally enhancing mass within the ring)
Low-density lesion with contrast fluid level (leakage of contrast)
Almost always ring blush of variable thickness; multiscalloped and round
Sedimentation level secondary to cellular debris/ haemorrhage/ accumulated contrast material in tumoral cyst
MRI
- Poorly defined lesion with some mass effect/ vasogenic oedema
T1
Hypo to isointense mass within white matter
Central heterogeneous signal (necrosis, intra-tumoural haemorrhage)
T1 C+ (Gd)
Enhancement is variable but is almost always present
Typically, peripheral and irregular with nodular components
Usually surrounds necrosis
T2/FLAIR
Hyperintense
Surrounded by vasogenic oedema
Flow voids are occasionally seen
GE/SWI
Susceptibility artefact on T2* from blood products (or occasionally calcification)
Low-intensity rim from blood product
Incomplete and irregular in 85% when present
Mostly located inside the peripheral enhancing component
Absent dual rim sign
DWI/ADC
Solid component
Elevated signal on DWI is common in solid/enhancing component
Diffusion restriction is typically intermediate similar to normal white matter, but significantly elevated compared to surrounding vasogenic oedema (which has facilitated diffusion)
ADC values correlate with grade
WHO IV (GBM) = 745 ± 135 x 10-6 mm2/s
WHO III (anaplastic) = 1067 ± 276 x 10-6 mm2/s
WHO II (low grade) = 1273 ± 293 x 10-6 mm2/s
Non-enhancing necrotic/cystic component
The vast majority (>90%) have facilitated diffusion (ADC values >1000 x 10-6 mm2/s)
Care must be taken in interpreting cavities with blood product
MR perfusion:
CBV elevated compared to lower grade tumours and normal brain
MR spectroscopy
Typical spectroscopic characteristics include:
Choline: increased
Lactate: increased
Lipids: increased
NAA: decreased
Myoinositol: decreased
PET
- PET demonstrates accumulation of FDG (representing increased glucose metabolism) which typically is greater than or similar to metabolism in grey matter.
Treatment:
- Surgical Removal
- Radiotherapy
- Chemotherapy - Temozolomide
- Immunotherapy
*<70 years of age – Stupp protocol
Follow up
- MRI
- 1-2 days post-surgery to assess residual disease
- 8-12 weeks
- RANO criteria used for response assessment
Prognosis
- Very poor; <2 years
- Dependent on
Degree of necrosis
Degree of enhancement
Location
MGMT not-methylated
Increased age
References:
Dahnert, W. (2008). Radiology Review Manual (6th Edition). Philadelphia: Lippincott Williams & Wilkins
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