Glioblastoma Multiforme

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Diagnosis and reasoning

"Headache" is a very common complaint in primary care. While the vast majority of such cases are benign in nature, it is vital to identify those few which are not. Key to this is searching for "red flag" symptoms and signs that might potentially herald a sinister cause. These include onset over the age of 50 years; new onset headaches in persons who are HIV-positive or at risk of cancer; sudden onset headaches; headaches increasing in severity or frequency; headache following trauma; or, the presence of symptoms of systemic illness, focal neurological signs or symptoms, or papilledema. In this patient's case, several red flags are very much apparent, i.e. the headaches first occurring after >50 years of age; bilateral papilledema; and the presence of focal signs involving the left upper limb. Note in particular that the last of these suggests at a lesion affecting the motor cortex. Neuroimaging is essential, with magnetic resonance imaging (MRI) being a good option. This reveals a lesion of the left parietal lobe, with central necrosis and hemorrhage, and surrounding edema. The use of contrast material further reveals ring enhancement. Note that the above radiographic signs are strongly suggestive of glioblastoma multiforme (GBM), the most common primary tumor of the brain. This patient's age and presentation are also compatible with this diagnosis. Lumbar puncture is both unnecessary and harmful, given the risk of tonsillar herniation. Positron emission tomography (PET) with 18F-FDG is generally not used in the primary evaluation of GBM but may be of value in the follow-up. Furthermore, as his clinical and imaging findings all point towards a primary brain tumor, full-body computed tomography (CT) to identify or exclude a malignancy (based on the assumption that the lesion might be a metastasis) is probably best avoided for now. His definitive management will involve surgical resection of as much of the tumor as is possible, followed by chemo-irradiation. Corticosteroids will be a helpful adjunct to decrease vasogenic edema and thus reduce the intracranial pressure. Note that there is no clear role for antibiotic therapy here.


Glioblastoma multiforme (GBM) are a group of highly malignant, genetically and phenotypically diverse tumors of the central nervous system. They comprise 15% of all primary brain tumors and account for 3% to 4% of all cancer-related deaths. In Europe and North America, the incidence of GBM is around 2 to 3 per 100,000 adults, with a peak at 58 years of age. There is a slight male preponderance, with Caucasians being affected more often than other racial groups. Most cases are sporadic, with only ~1% being familial. Genetic conditions known to confer an increased risk for GBM include tuberous sclerosis, Turcot syndrome, multiple endocrine neoplasia type IIA, and neurofibromatosis type 1. Around 90% of GBM are primary neoplasms that arise from glial cells via multistep tumorigenesis. The remainder are secondary neoplasms that develop from low-grade tumors over several years. GBM usually occur singly, although multifocal, distant, and diffuse disease can occur. Most lesions are found in the cerebrum, brainstem, or cerebellum. Spread outside the brain is rare, possibly due to the protective meningeal layer and short disease course. The clinical presentation varies depending on the location of the tumor, with some patients remaining asymptomatic until very late in the course of the disease. Headaches and seizures are the most common generalized findings. Hemiparesis, visual defects, sensory defects, and personality changes may occur, depending on the exact location of the lesion. Neuroimaging is diagnostic, with gadolinium-enhanced magnetic resonance imaging (MRI) being the technique of choice. This typically shows an irregular, ring-enhancing lesion, with a hypointense central zone of necrosis. Surrounding edema, hemorrhage, and ventricular distortion may also be seen. Determination of the tumor subtype currently requires histological analysis. This is preferably achieved via intraoperative tumor removal, although invasive biopsy is also possible. GBM should be treated using a multidisciplinary approach, including resection of as much of the tumor as is feasible, followed by radiation and chemotherapy. Given the invasiveness of these tumors, complete resection is often impossible. However, partial resection still helps decrease intracranial pressure and thus alleviate symptoms. Complications of surgery include lasting neurological deficits, and iatrogenic seeding of tumor cells may also occur. Temozolomide is the chemotherapeutic agent of choice, although others are under trial. External beam radiation therapy (EBRT) is the standard irradiation technique, although gamma knife therapy may also be employed. Adjunct measures include dexamethasone to decrease peritumoral edema, treatment of seizures as needed, venous thromboembolism prophylaxis, occupational therapy, speech therapy, and emotional and psychological support for transitioning to palliative care. Unfortunately, the prognosis of GBM is poor, with a five-year survival rate of less than 5%. Even with optimal treatment, the mean survival after diagnosis is only 12.6 months.

Take home messages

  1. Glioblastoma multiforme (GBM) are the most common tumors of the brain, and also the most deadly.
  2. Magnetic resonance imaging (MRI) with gadolinium contrast allows for the radiographic diagnosis of GBM.
  3. Treatment involves surgical resection of as much tumor as possible, followed by chemotherapy and radiotherapy.
  4. The long-term prognosis of these patients is extremely poor. Even with the best of care, most patients live for a little over a year following diagnosis.

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  1. ALIFIERIS C, TRAFALIS DT. Glioblastoma multiforme: Pathogenesis and treatment. Pharmacol Ther [online] 2015 Aug:63-82 [viewed 04 July 2018] Available from:
  2. BAE SH, PARK MJ, LEE MM, KIM TM, LEE SH, CHO SY, KIM YH, KIM YJ, PARK CK, KIM CY. Toxicity Profile of Temozolomide in the Treatment of 300 Malignant Glioma Patients in Korea J Korean Med Sci [online] 2014 Jul 11, 29(7):980-984 [viewed 10 September 2017] Available from: doi:10.3346/jkms.2014.29.7.980
  3. CARLSSON SK, BROTHERS SP, WAHLESTEDT C. Emerging treatment strategies for glioblastoma multiforme EMBO Mol Med [online] 2014 Oct 13, 6(11):1359-1370 [viewed 10 September 2017] Available from: doi:10.15252/emmm.201302627
  4. GOKDEN M. If it is Not a Glioblastoma, Then What is it? A Differential Diagnostic Review. Adv Anat Pathol [online] 2017 Nov, 24(6):379-391 [viewed 04 July 2018] Available from:
  5. HOLLAND EC. Glioblastoma multiforme: The terminator Proc Natl Acad Sci U S A [online] 2000 Jun 6, 97(12):6242-6244 [viewed 10 September 2017] Available from:
  6. HOLLE D, OBERMANN M. The role of neuroimaging in the diagnosis of headache disorders Ther Adv Neurol Disord [online] 2013 Nov, 6(6):369-374 [viewed 10 September 2017] Available from: doi:10.1177/1756285613489765
  7. IACOB G, DINCA E. Current data and strategy in glioblastoma multiforme J Med Life [online] 2009 Nov 25, 2(4):386-393 [viewed 10 September 2017] Available from:
  8. JACKSON RJ, FULLER GN, ABI-SAID D, LANG FF, GOKASLAN ZL, SHI WM, WILDRICK DM, SAWAYA R. Limitations of stereotactic biopsy in the initial management of gliomas. Neuro Oncol [online] 2001 Jul, 3(3):193-200 [viewed 10 September 2017] Available from:
  9. MABRAY MC, BARAJAS RF JR, CHA S. Modern Brain Tumor Imaging Brain Tumor Res Treat [online] 2015 Apr 29, 3(1):8-23 [viewed 10 September 2017] Available from: doi:10.14791/btrt.2015.3.1.8
  10. URBAńSKA K, SOKOłOWSKA J, SZMIDT M, SYSA P. Glioblastoma multiforme – an overview Contemp Oncol (Pozn) [online] 2014 Aug 4, 18(5):307-312 [viewed 10 September 2017] Available from: doi:10.5114/wo.2014.40559
  11. WALID MS. Prognostic Factors for Long-Term Survival after Glioblastoma Perm J [online] 2008 Fall, 12(4):45-48 [viewed 10 September 2017] Available from:
  12. WILSON TA, KARAJANNIS MA, HARTER DH. Glioblastoma multiforme: State of the art and future therapeutics Surg Neurol Int [online] 2014 May 8:64 [viewed 10 September 2017] Available from: doi:10.4103/2152-7806.132138