Introduction

Glioblastoma multiforme is a type of glioma, a group of glia or its precursor

tumors within the central nervous system. Clinically, gliomas are classified into
four grades; unfortunately, the most severe of these is grade 4 or multiforme
glioblastoma (GBM), the most common and aggressive malignant brain tumor in
adults that accounts for approximately 80% of all malignant primary brain tumors.

Because most GBM patients die of their disease in less than a year and basically
none have long-term survival, these tumors have received much interest, and so,
we will provide a clear picture of GBM epidemiology, etiology, pathogenesis,
clinical signs, and treatment.
Epidemiology:

Although GBM is a rare tumor with an incidence rate of less than 10 per
100,000 people, it is a crucial public health issue due to its poor prognosis with a
survival rate of 14-15 months after diagnosis. It accounts for 50 percent of all
gliomas in all age groups. It can happen at any age but the peak incidence ranges
from 55 to 60 years. Malignant gliomas are the cause of 2.5% of cancer deaths and
are the third leading cause of cancer death in people aged 15 to 34. In men, the
ratio of GBM incidence is higher than in women. Few studies have shown that
blacks are less susceptible, and there is a higher incidence of GBM in other ethnic
groups including Asians, Latinos, and Whites.

Etiology:

“The etiology of GBM has not been fully elucidated. Glioblastoma is

believed to be a spontaneous tumor, despite the fact that medical history describes
the development of glioma in related persons. The familial form of this tumor is
described for 1% of cases. However, the genetic background for the development
of this type of glioblastoma is different from those arising spontaneously.
Glioblastoma multiforme may also occur in the course of genetic diseases:
tuberous sclerosis, Turcot syndrome, multiple endocrine neoplasia type IIA, and
neurofibromatosis type I, NF1. In addition, acquired head injuries, which occurred
as a result of a brain contusion, may predispose to the onset of glioblastoma.
Viruses, such as human cytomegalovirus (H-CMV), are also believed
to be among the etiologic agents for glioma development. H-CMV induces
congenital encephalitis and multi-organ changes in immunocompromised adults.
Ionizing radiation is one of the physical factors that increase the likelihood
of developing this type of tumor. The following chemicals are considered as
potentially dangerous: pesticides, polycyclic aromatic compounds, and solvents.”
(Urbańska et al., 2014)
Pathogenesis:
Site:

The cerebral hemispheres are the most common site for GBM, with 95%
arising in the supratentorial region, and less commonly appearing in the brain stem,
cerebellum, and spinal cord. (Nakada et al., 2011)

Macroscopic and Histological Features:

“Macroscopic examination of glioblastomas shows a heterogeneous tumor

with cystic and gelatinous areas, multifocal hemorrhage and necrosis, which can be
a predominant feature. Histological examination shows a markedly pleomorphic
cell population that ranges from small poorly differentiated tumor cells to large
multinucleate cells, with widespread mitotic activity and multifocal necrosis often
surrounded by nuclear pseudo-palisading. Vascular endothelial proliferation is a
prominent feature often with the formation of characteristic glomeruloid structures.
Many, but not all, of the tumor cells will give a positive reaction on
immunohistochemistry for GFAP and cell proliferation studies reveal a high
percentage of cells labelled with the Ki-67 antibody.

A number of subcategories of glioblastoma have been identified, including the

giant cell glioblastoma in which multinucleated giant cells predominate, and
epithelioid glioblastomas, which are formed (at least in part) of large sheet-like
collections of cells with large nuclei and prominent nucleoli. These may mimic a
metastatic carcinoma on routine staining and immunohistochemistry is required for
the diagnosis. Some glioblastomas are composed predominantly of small poorly
differentiated cells (small cell glioblastoma), which can cause diagnostic
confusion with other tumors.” (Smith & Ironside, 2007)
Clinical signs:

Depending on the localization and the increased intracranial pressure, as a

result of the clinical stage of the disease, the most common signs of GBM include
headaches, ataxia, dizziness, vision disturbances (blurred vision, diplopia), and
frequent syncope. Due to these unspecific symptoms, glioma is often misdiagnosed
as infections, inflammatory processes, and circulatory and immunological diseases.
The occurrence of back and leg pain and sciatica may also suggest a herniated
lumbar. The occurrence of seizures in people who have not been previously
diagnosed with epilepsy can also be an indication of neuroimaging because of
glioblastoma suspicion.

Imaging:

Initial diagnostic imaging may include a computed tomography (CT) or

magnetic resonance imaging (MRI) scan. On MRI, nearly all GBMs enhance with
gadolinium contrast and show an irregularly shaped mass with a dense ring of
enhancement and hypointense center of necrosis. Necrosis is a hallmark feature of
GBM, and the presence of necrosis is required for a brain tumor to be grade IV or
to be classified as a GBM on the World Health Organization classification system.
Surrounding vasogenic edema (which may cause a mass effect), hemorrhage, and
ventricular distortion or displacement may also be present on diagnostic imaging.

Treatment:

Treatment of newly diagnosed GBM requires a multidisciplinary approach.

Current standard therapy includes maximal safe surgical resection, followed by
concurrent radiation with temozolomide (TMZ), an oral alkylating chemotherapy
agent, and then adjuvant chemotherapy with TMZ. Extensive and complete
surgical resection of GBM is difficult because these tumors are frequently invasive
and are often in eloquent areas of the brain, including areas that control speech,
motor function, and the senses. Because of the high degree of invasiveness, radical
resection of the primary tumor mass is not curative, and infiltrating tumor cells
invariably remain within the surrounding brain, leading to later disease progression
or recurrence. (Davis, 2016)

Conclusion:

Glioblastoma multiforme is the most malignant type of central nervous

system tumors. Depending on the tumor site patients may present with varying
symptoms. To confirm the presence and the extent of the tumor, imaging
techniques require employment. Although, several treatment options are available,
including surgery, along with adjuvant chemo- and radio-therapy, the disease has a
poor prognosis, and patients generally succumb within 14 months of diagnosis.