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Glioblastoma Multiforme (GBM) – Common Malignant Brain Tumor

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glioblastoma multiforme scan
An MRI image showing glioblastoma multiforme in the temporal lobe of the right cerebral hemisphere

Malignant glioma, or glioblastoma, represents the most common form of malignant brain tumors in adults. Moreover, glioblastoma multiforme comprises about 20% of all primary brain tumors. Malignant glioma, or glioblastoma multiforme, is the most aggressive form of the astrocytoma group of brain tumors and represents more than 66% of all cases of brain astrocytoma. The survival rate of this tumor is extremely low because of its high grade status and aggressiveness.

glioblastoma multiforme mri scan
An MRI image showing glioblastoma multiforme in the temporal lobe of the right cerebral hemisphere

Epidimiology:

Glioblastoma is considered the most common primary brain tumor as it accounts for more than 12% of all brain tumors. In the USA and Europe, 2-3 new cases are diagnosed annually in every 100,000 people.

Race:

Glioblastoma multiforme is more common in whites.

Sex:

Malignant glioblastoma is more common in males when compared to females with a male to female ration of 3:2.

Age:

Glioblastoma multiforme can affect a person of any age; however, it is rather more common between 45 and 70 years. Less than 9% of all patients diagnosed with malignant glioblastoma are children.

 

glioblastoma multiforme under the microscope image
Appearance of glioblastoma multiforme under the microscope

Clinical Picture:

Patients start to complain less than 3 months before diagnosis is established in about 50% of cases, except if the tumor is the result of a transformation of a low grade astrocytoma which has been present for some time.

–       A gradually progressing neurological deficit is the most commonly presenting complaint of patients with malignant glioblastoma. This is mostly in the form of muscular weakness. On the other hand, headache is the most common symptom experienced by most patients.

–       Occasionally, patients present with manifestations of increased intracranial tension such as cognitive impairment, nausea, vomiting and headache.

–       Seizures are also common in some patients.

–       Headaches are usually severe early in the morning or shortly after waking.

–       Changes in mood, personality, mental abilities and concentration can be observed early on, or may be the only symptoms present.

–       Occasionally, a patient complains of focal neurologic deficits that reflect the site of the tumor. Focal manifestations include weakness, paralysis, loss of vision, sensory loss or aphasia.

Imaging Studies:

CT scanning can show the tumor and its extension; nevertheless, it can miss small tumors, so it is not an accurate tool in establishing the diagnosis of glioblastoma multiforme. It must be kept in mind that a missed low-grade glioma can progress to more aggressive forms of glioblastoma multiforme.

MRI is much more sensitive to the existence of the tumor. Furthermore, MRI can help visualize edema around the tumor, when present. Accordingly, MRI is the imaging study of choice when a diagnosis of glioblastoma multiforme is suspected. Malignant glioma is a highly infiltrating tumor, so tumor cells are often present beyond the margins delineated by an MRI scan. Metastasis (spread of the tumor outside its primary location) is frequent in other parts of the central nervous system (CNS).

Post-operatively, MRI is not accurate in differentiating scar tissue from recurrent tumors, while positron emission tomography (PET) is very helpful in this regard.

Malignant glioblastoma can assume different shapes, so it can be confused with other disorders such as an abscess, an infarction or lesions associated with multiple sclerosis, which can lead to delay in establishing diagnosis. The following generalizations are very helpful in differentiating glioblastoma multiforme from low-grade astrocytoma:

–       The incidence of calcified lesions is higher in low astrocytoma when compared to glioblastoma multiforme.

–       The incidence of increased enhancement (special appearance due to absorption of brain tissues of a dye used during MRI scanning) is higher in glioblastoma multiforme when compared to low grade astrocytoma.

–       The incidence of necrosis, hemorrhage, edema and mass effects follow the same pattern as that of enhancement.

A few forms of malignant glioblastoma can be considered variants. For instance, monstrocellular glioblastoma, or giant cell glioblastoma, is often considered a variant of malignant glioblastoma, although it has the same MRI findings of malignant glioblastoma.

Radiography:

X-rays are not often used in the workup of a patient with a malignant glioblastoma. Nevertheless, when the tumor is very aggressive, with invasion of the skull bones, skull erosive changes can be demonstrated on a skull x-ray. Very rarely, the tumor sends metastasis to limb bones which can be also visualized on plain x-rays.

CT Scanning:

CT scans are often helpful in the diagnosis of malignant glioma. On the other hand, the CT appearance of some brain lesions may mimic that of malignant glioblastoma such as tumors other than malignant glioblastoma, infarction with hemorrhage and brain abscess. Glioblastoma multiforme can sometimes assume a multi-focal distribution which can be indistinguishable on CT images from diffuse forms of multiple sclerosis.

The findings of malignant glioblastoma on a non-enhanced CT scan include the following:

–       A mass with poorly defined margins.

–       A lesion with areas of fluid attenuation which is present in about 95% of cases.

–       A calcified lesion which is rather rare except if the tumor is the result of the transformation of another tumor such as low grade astrocytoma.

–       Marked mass effects and edema.

Enhanced CT scans findings include inhomogeneity and irregularity, solid enhancement, ring enhancement and little enhancement when the tumor assumes a diffuse form.

Magnetic Resonance Imaging:

MRI is the best imaging modality in the diagnosis of malignant glioblastoma; however, brain lesions with hemorrhagic parts can resemble malignant glioblastoma on MRI.

On MRI, glioblastoma multiforme shows heteregnous masses with areas of cystic changes, edema in the tissues surrounding the tumor, areas of necrosis, new vessel formation and pressure effects on the nearby brain structures.

Nuclear Imaging:

Positron emission tomography (PET) imaging is a useful imaging modality in the evaluation of glioblastoma multiforme, especially after surgical resection. In such situations, differentiation of non-excised tumor residual or recurrent tumor from scarring or postoperative edema is possible. Malignant glioblastoma is viewed during PET scanning because of the high metabolic rate and glucose consumption of the tumor cells.

Whenever a recurrent tumor is suspected, increased tracer tissue uptake at the site of previous surgical resection is often diagnostic. Nevertheless, following radiotherapy increased uptake at the surgical site can occur regardless of tumor recurrence. Epiliptogenic activity near the site of surgery can exhibit increased tracer uptake, especially when high epileptic activity is noted.

Treatment:

Treating malignant glioblastoma is not easy, especially since there is no curative treatment for it at the present time.

After establishing the diagnosis of glioblastoma multiforme, the treatment plan should include:

–       Maximal surgical resection.

–       Radiotherapy.

–       Adjuvant and concomitant chemotherapy with temozolomide.

If the patient is older than 70 years, less aggressive lines of treatment are recommended such as temozolomide or radiation therapy.

Radiotherapy after surgery or combining radiotherapy with chemotherapy and surgery has been proven to increase the survival rate of patients with malignant glioblastoma. Radiotherapy following surgery has been proven to increase the survical rate from 3 months to up to 12 months.

Research is now investigating the possibility of using focal radiation, which is directly delivered to the site of the tumor using an implanted balloon that contains the radioactive substance.

Bevacizumab is an anti-angiogenic agent that has been recently approved by the US Food and Drug Administration for the treatment of recurrent glioblastoma multiforme.

There are other lines of treatment that are still under research, including dendritic cell and peptide vaccines, gene therapy, radiolabelled drugs, synthetic chlorotoxins and radiolabelled antibodies.

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