Glioblastoma is most malignant and most frequent primary brain tumor. Glioblastoma Multiforme ( GBM) is also called WHO grade IV astrocytoma and it is the most malignant of the astrocytomas.
Incidence
It accounts for 12-15% of all intracranial neoplasms and 60-75% of all astrocytic tumors.
Age
It may manifest at any age, but preferentially affects adults, with a peak incidence at between 45 and 75 years of age. About 1% of patients are younger than 20 years old. primary GBM is more common in older adults between 60-75 years.
Secondary GBMs which constitute about 5% of all GBMs , usually occur about a decade or two decade earlier.
Location
Cerebral hemispheres are the most common site in adults. Glioblastoma occurs most often in the subcortical white matter and deep periventricular white matter of the cerebral hemispheres. Most affectected sites are temporal, parietal frontal and occipital lobes. Combined fronto-temporal location is particularly typical.
Tumor infiltration often extends into the adjacent cortex and through the corpus callosum into the contralateral cerebral hemisphere. Glioblastoma is notorious for its rapid invasion of neighbouring brain structures. A very common feature is extension of the tumor through the corpus callosum into the contralateral hemisphere, creating the image of a bilateral, symmentrical lesion ( Butterfly glioma).
Glioblastoma of the basal ganglia and thalamus is not uncommon, especially in children. Glioblastoma of the brain stem( malignant brain stem glioma)is infrequent and often affects children.
20% of GBM are multifocal and of which 2-5% are synchronous.
Types of Glioblastoma and clinical features
Two forms of GBM are currently recognized: Primary ("de novo") GBM and secondary glioblastoma. Primary glioblastoma constitute majority, about more than 90%, , which arise de novo.
Secondary glioblastoma arise from a previously pre-existing lower grade glioma. While the two types share similar histology, they differ genetically. Neurofibromatosis type 1 ( NF1), Li Fraumeni and Turcot syndrome demonstrate an enhanced propensity to develop GBM.
The clinical history of the disease is usually short ( less than 3 months in more than 50% of cases). Unless the neoplasm has developed from a lower grade astrocytoma ( secondary glioblastoma).
Symptoms and signs of raised intracranial pressure ( headache, vomiting, papilledema) are common. Seizures , focal neurological deficits are common. Sometimes patients may present with sudden stroke like features due to acute intratumoral hemorrhage ( in about 2% patients).
Histopathology
Glioblastoma on gross appearance look like Reddish-gray " rind of tumor, with necrotic core with marked peritumoral edema. It shows increased vascularity, and intra-tumoral hemorrhage.
The histopathological features include nuclear atypia, cellular pleomorphism, mitotic activity, vascular thrombosis, microvascular proliferation, and necrosis.
As the term glioblastoma " multiforme " suggests , the histopathology is extremely variable. The varied tumor cells include: pleomorphic fibrillary astrocytes, gemistocytes, bipolar bland appearing but mitotically active small cells ( including " microglia")and large bizzare multinucleated giant cells. While some lesions show a high degree of cellular and nuclear polymorphism with numerous multinucleated giant cells, others are highly cellular, but rather monotonous.
GBMs generally have a high proliferation index (MIB-1), usually exceeding 10%.
Immunohistochemistry shows GFAP and olig 2 positivity. IDH-1 is very helpful in distingushing secondary GBM (positive) from primary GBM ( negative).
Radiology of Glioblastoma
At least 90 -95% of GBM demonstrate a thick, irregular, enhancing "rind" of tumor surrounding a necrotic core.
CT scan of brain: Most GBMs demonstrate a hypodense central mass surrounded by an iso-to moderately hyperdense rim on non-enhanced CT scan. Hemorrhage is common but calcification are rare. marked mass effect and significant hypodense peritumoral edema are typical ancillary findings.
Contrast Enhanced Computerized Tomography (CECT) of Brain reveals strong but heterogenous irregular rim enhancement. In highly vascular GBMs prominant vessels are seen as linear enhancing foci adjacent to the mass.
MRI of Brain: T1W1 image shows poorly marginated mass with mixed signal intensity . Subacute hemorrhage is common. T2/FLAIR image shows heterogenous intensity with extensive vasogenic edema. Necrosis, cysts, hemorrhage at various stages of evolution are seen. Fluid-debris level is seen in some cases.
Contrast Enhanced magnetic Resonance Imaging ( CE MRI) of brain shows strong but irregular contrast enhancement with central non-enhancing core.
DWI MR : most GBMs do not restrict on diffusion weighted imaging.
DTI may show increased fractional anisotropy and disrupted white matter tracts from tumor invasion.
MR spectroscopy (MRS) may show elevated choline peak and decreased NAA.
On imaging the differential diagnosis of GBM is usually Metastasis and Abscess. Metastasis is usually multiple and occur at gray-white matter junction and non-infiltrating. Intracranial abscess is usually thinner with more regular rim which usually restrict on DWI.
Treatment of Glioblastoma
Neurosurgery and Radiation Oncology intervention: Craniotomy and tumor decpmpression. The cytoreductive surgery followed by chemo and radiotherapy.
Sources:
1. WHO classification of Tumours of the central nervous system Edited by David N.Louis, Hiroko Ohgaki, Otmar D. Wiestler , Webster K.Cavene
2. Handbook of Neurosurgery by Mark S. Greenberg
Incidence
It accounts for 12-15% of all intracranial neoplasms and 60-75% of all astrocytic tumors.
Age
It may manifest at any age, but preferentially affects adults, with a peak incidence at between 45 and 75 years of age. About 1% of patients are younger than 20 years old. primary GBM is more common in older adults between 60-75 years.
Secondary GBMs which constitute about 5% of all GBMs , usually occur about a decade or two decade earlier.
Location
Cerebral hemispheres are the most common site in adults. Glioblastoma occurs most often in the subcortical white matter and deep periventricular white matter of the cerebral hemispheres. Most affectected sites are temporal, parietal frontal and occipital lobes. Combined fronto-temporal location is particularly typical.
Tumor infiltration often extends into the adjacent cortex and through the corpus callosum into the contralateral cerebral hemisphere. Glioblastoma is notorious for its rapid invasion of neighbouring brain structures. A very common feature is extension of the tumor through the corpus callosum into the contralateral hemisphere, creating the image of a bilateral, symmentrical lesion ( Butterfly glioma).
Glioblastoma of the basal ganglia and thalamus is not uncommon, especially in children. Glioblastoma of the brain stem( malignant brain stem glioma)is infrequent and often affects children.
20% of GBM are multifocal and of which 2-5% are synchronous.
Types of Glioblastoma and clinical features
Two forms of GBM are currently recognized: Primary ("de novo") GBM and secondary glioblastoma. Primary glioblastoma constitute majority, about more than 90%, , which arise de novo.
Secondary glioblastoma arise from a previously pre-existing lower grade glioma. While the two types share similar histology, they differ genetically. Neurofibromatosis type 1 ( NF1), Li Fraumeni and Turcot syndrome demonstrate an enhanced propensity to develop GBM.
The clinical history of the disease is usually short ( less than 3 months in more than 50% of cases). Unless the neoplasm has developed from a lower grade astrocytoma ( secondary glioblastoma).
Symptoms and signs of raised intracranial pressure ( headache, vomiting, papilledema) are common. Seizures , focal neurological deficits are common. Sometimes patients may present with sudden stroke like features due to acute intratumoral hemorrhage ( in about 2% patients).
Histopathology
Glioblastoma on gross appearance look like Reddish-gray " rind of tumor, with necrotic core with marked peritumoral edema. It shows increased vascularity, and intra-tumoral hemorrhage.
The histopathological features include nuclear atypia, cellular pleomorphism, mitotic activity, vascular thrombosis, microvascular proliferation, and necrosis.
As the term glioblastoma " multiforme " suggests , the histopathology is extremely variable. The varied tumor cells include: pleomorphic fibrillary astrocytes, gemistocytes, bipolar bland appearing but mitotically active small cells ( including " microglia")and large bizzare multinucleated giant cells. While some lesions show a high degree of cellular and nuclear polymorphism with numerous multinucleated giant cells, others are highly cellular, but rather monotonous.
GBMs generally have a high proliferation index (MIB-1), usually exceeding 10%.
Immunohistochemistry shows GFAP and olig 2 positivity. IDH-1 is very helpful in distingushing secondary GBM (positive) from primary GBM ( negative).
Radiology of Glioblastoma
At least 90 -95% of GBM demonstrate a thick, irregular, enhancing "rind" of tumor surrounding a necrotic core.
CT scan of brain: Most GBMs demonstrate a hypodense central mass surrounded by an iso-to moderately hyperdense rim on non-enhanced CT scan. Hemorrhage is common but calcification are rare. marked mass effect and significant hypodense peritumoral edema are typical ancillary findings.
Contrast Enhanced Computerized Tomography (CECT) of Brain reveals strong but heterogenous irregular rim enhancement. In highly vascular GBMs prominant vessels are seen as linear enhancing foci adjacent to the mass.
MRI of Brain: T1W1 image shows poorly marginated mass with mixed signal intensity . Subacute hemorrhage is common. T2/FLAIR image shows heterogenous intensity with extensive vasogenic edema. Necrosis, cysts, hemorrhage at various stages of evolution are seen. Fluid-debris level is seen in some cases.
Contrast Enhanced magnetic Resonance Imaging ( CE MRI) of brain shows strong but irregular contrast enhancement with central non-enhancing core.
DWI MR : most GBMs do not restrict on diffusion weighted imaging.
DTI may show increased fractional anisotropy and disrupted white matter tracts from tumor invasion.
MR spectroscopy (MRS) may show elevated choline peak and decreased NAA.
On imaging the differential diagnosis of GBM is usually Metastasis and Abscess. Metastasis is usually multiple and occur at gray-white matter junction and non-infiltrating. Intracranial abscess is usually thinner with more regular rim which usually restrict on DWI.
Treatment of Glioblastoma
Neurosurgery and Radiation Oncology intervention: Craniotomy and tumor decpmpression. The cytoreductive surgery followed by chemo and radiotherapy.
Sources:
1. WHO classification of Tumours of the central nervous system Edited by David N.Louis, Hiroko Ohgaki, Otmar D. Wiestler , Webster K.Cavene
2. Handbook of Neurosurgery by Mark S. Greenberg
