Glioblastoma (also known as glioblastoma multiforme, or GBM), is most frequently diagnosed among the elderly, with a median age of diagnosis being 64 years and a significant predilection toward male gender [1] [2]. However, pediatric cases have also been documented, in whom an even stronger male predilection exists [1]. Although glioblastomas are not that common (incidence rate is about 2-5 per 100,000 individuals), they carry a very poor prognosis [1] [2]. Overall survival rarely exceeds 12-14 months from the time of diagnosis, which is why, according to the World Health Organization criteria (WHO), it is classified as a stage IV astrocytoma [3] [4] [5]. One of the reasons why such a poor outcome is expected is that GBM is often missed in its initial stages due to a nonspecific symptomatology and physicians often turn their attention to infections, vascular processes or immunological diseases prior to suspecting neoplastic disorders [1]. The clinical presentation initially includes headaches (due to increased intracranial pressure caused by the tumor), vomiting, nausea, frequent syncope and seizures, which may be the only sign in patients without a previous history of epilepsy [1] [6]. In time, cognitive dysfunction can appear, as well as gait disturbances, cranial nerve palsies, urinary incontinence, hemiparesis, aphasia, and disorientation, while vertigo is described in a minority of cases [1] [2] [6]. Moreover, various psychiatric manifestations have been described in patients with glioblastomas, such as personality disorders, loss of emotional control and anger, mood disorders (depression, mania) and marked anxiety, whereas hallucinations and psychosis, although rare, have also been observed [7].

A complete physical workup is essential in order to place glioblastoma into the differential diagnosis of nonspecific central nervous system (CNS) symptoms and associated features. Firstly, a detailed patient history can reveal a history of epilepsy, the appropriate age for the development of glioblastoma (elderly patients) and a somewhat sudden onset of symptoms. Secondly, a thorough physical examination confirms the presence of neurological deficits and roughly determines the area of the brain that is affected by the underlying disorder. To solidify the diagnosis, imaging studies are the modality of choice, ranging from computed tomography (CT) and magnetic resonance imaging (MRI) to more advanced methods, such as positron emission tomography (PET) and magnetic resonance spectroscopy (MRS) [2]. MRI, and even CT, however, are often sufficient to confirm the tumor, and the mean diameter at the time of diagnosis is about 4 cm [1]. An enhancing heterogeneous mass with areas of central necrosis and surrounding edema is the typical presentation [2]. Despite evident clinical and imaging criteria, a definite diagnosis can only be made after obtaining a valid sample for biopsy and a histopathological examination with immunohistochemistry [1] [2]. Postoperative sampling is mandatory, while in cases when the tumor is not resectable, a fine needle aspiration or stereotactic biopsy can be performed [1] [2]. The decreased presence of glial fibrillary acidic protein (GFAP) in glioma cells, as well as S100 positivity on immunohistochemistry, is important in the diagnosis of glioblastoma [1].

Until this date, there are no available treatment for glioblastoma multiforme that is considered curative [8]. Therefore, all available approaches to GBM like surgical resection, radiotherapy, and chemotherapy are considered palliative.

These options are standard approaches upon the initial diagnosis of GBM coupled with adjuvant chemotherapy with temozolomide [9]. A study conducted among elderly patients with GBM treated with radiotherapy have showed significant improvements on mean survival rate post therapy [10].

The prognosis for glioblastoma multiforme is generally poor with a mean survival rate of only 3 months without treatment. Patients given optimal treatment like radiation therapy, chemotherapy and surgical resection may extend survival by 12 months. Only 25% of the patients may survive up to 2 years and only 10% may survive beyond 5 years.

Complications

The following clinical conditions are common complications associated with glioblastoma multiforme:

• Malignant degeneration:Progression from low grade to high grade glioblastoma occurring in 20-40% of primary tumors
• Metastasis to the spinal cord or other organs
• Acquired hydrocephalus
• Brain edema
• Cerebrovascular disease or stroke
• Tumor lysis syndrome may occur following a chemotherapy 
• Seizures
• Coma
• Death

Glioblastoma multiforme may arise primarily or secondarily in the glial cells of the brain. Primary tumors results from a gene mutation in the glial cells during early development. Secondary GBM arises from low grade glioblastoma which usually start during childhood and later progresses to become an aggressive cancer through malignant degeneration by adulthood. Secondary malignant GBM usually progresses to glioblastoma cancers in 40% of the diagnosed low grade gliomas tumors in childhood. Malignant progression usually ensues in a period range of 1 to 10 years from initial diagnosis.

Approximately 5% of malignant gliomas arise from familial glioma while 1% are associated with genetic syndromes like neurofibromatosis, and Li-Fraumeni syndrome [1]. A multinational study revealed that electromagnetic field from cell phones may pose a significant risk in the development of brain tumors [2]. Because of this, some European nations have taken active steps in limiting the use of cellular phones among children.

In the United States, an annual rate of 17,000 new cases of brain tumors are diagnosed. Of these number, approximately 15% or about 2,550 are glioblastoma multiforme. GBM is slightly more common in the United States, Scandinavia, and Israel compared to their Asian counterparts. In European nations, the relative incidence of GBM reaches 2-3 cases per 100,000 population annually.

The mean survival time of GBM varies directly with the patient’s age. There is a slight male preponderance in GBM with a ratio of 3:2 compared to the females [3]. Glioblastoma multiforme occurs in all ages but is more prevalent among adults from 45 to 70 years of age. Only 8.8% of Glioblastoma multiforme are diagnosed among children [4].

Among the glioma brain neoplasm, glioblastoma contains the most genetic mutation in its gene sequence. They may occur as a primary brain tumor arising from glial cells representing 60% of the primary glial cell tumors. They may also progress a secondary malignant tumor arising from low grade gliomas with a mean time of progression between 4 to 5 years from time of diagnosis.

The more common genetic abnormalities seen in GBM include the loss of heterozygosity in chromosome arm 10q. This abnormality is commonly seen in both primary and secondary GBM’s with incidence rate of up to 60-90% of all GBM cases. The mutation related to the deletion of p53 chromosome happens in at least 25% of GBM cases which are more commonly seen in secondary GBMs. The p53 gene is believed to function as a tumor suppressor gene in normal subjects. Activation and mutation of the epidermal growth factor receptor (EGFR) gene that controls the cell proliferation is eminent in primary tumors [5]. In the same way, the phosphatase and tensin analog (PTEN) mutation has been found in 20% of cases of primary glioblastoma multiforme cases [6].

The majority of cases of glioblastoma multiforme has been dubbed to be familial in origin, thus; genetic counselling is a good approach in the prevention of GBM among offspring.

Recent trends in the implication of electromagnetic field in the causation of brain tumors suggests that chronic exposure to electronic gadgets like cellular phones and laptops may predispose children to the development of brain tumors.

Glioblastoma multiforme (GBM), also known as grade IV astrocytoma, is an aggressive primary carcinoma of the glial cells in the brain. Glioblastoma multiforme has the reputation of growing fast in a given site and rapidly metastasizing to a distant site, that is why it is sometimes referred to as a “grow and go” brain tumor.

GBM is considered the most common primary glial cell tumor and the most malignant glioma in the brain parenchyma. This tumor usually evolves from the cerebral hemispheres but may rarely arise from the brainstem and spinal cord in some cases.

Definition

Glioblastoma multiforme (GBM) is an aggressive primary carcinoma of the glial cells in the brain.

Cause

Familial tendencies, genetic mutations, malignant degeneration of primary tumors and electromagnetic radiations are possible causes. 

Symptoms

Headache, progressive neurologic deficits, weakness, cognitive dysfunction and seizures are common symptoms of GBM.

Diagnosis

CT scan, MRI, and electroencephalogram may be used to diagnose the condition.

Treatment and follow-up

Surgical resection, chemotherapy, and radiotherapy are the most common treatment options.

1. Urbańska K, Sokołowska J, Szmidt M, Sysa P. Glioblastoma multiforme – an overview. Contemporary Oncology. Contemp Oncol (Pozn). 2014;18(5):307-312.
2. Mesti T, Ocvirk J. Malignant gliomas: old and new systemic treatment approaches. Radiol Oncol. 2016;50(2):129-138.
3. Louis DN, Ohgaki H, Wiestler OD, et al. The 2007 WHO Classification of Tumours of the Central Nervous System. Acta Neuropathologica. 2007;114(2):97-109.
4. Aster, JC, Abbas, AK, Robbins, SL, Kumar, V. Robbins basic pathology. Ninth edition. Philadelphia, PA: Elsevier Saunders; 2013.
5. Porter RS, Kaplan JL. Merck Manual of Diagnosis and Therapy. 19th Edition. Merck Sharp & Dohme Corp. Whitehouse Station, N.J; 2011.
6. Sanli AM, Turkoglu E, Dolgun H, Sekerci Z. Unusual manifestations of primary Glioblastoma Multiforme: A report of three cases. Surg Neurol Int. 2010;1:87.
7. Boele FW, Rooney AG, Grant R, Klein M. Psychiatric symptoms in glioma patients: from diagnosis to management. Neuropsychiatric Disease and Treatment. 2015;11:1413-1420.