Glioblastoma

Glioblastoma, also known as glioblastoma multiforme (GBM), is the most aggressive type of cancer that begins within the brain.
[6]
 Initially, signs and symptoms of glioblastoma are nonspecific.[1] They may include headaches, personality changes, nausea, and
symptoms similar to those of a stroke.[1] Symptoms often worsen rapidly and may progress to unconsciousness.[2]
The cause of most cases of glioblastoma is not known. [2] Uncommon risk factors include genetic disorders, such
as neurofibromatosis and Li–Fraumeni syndrome, and previous radiation therapy.[2][3] Glioblastomas represent 15% of all brain
tumors.[1] They can either start from normal brain cells or develop from an existing low-grade astrocytoma.[7] The diagnosis typically is
made by a combination of a CT scan, MRI scan, and tissue biopsy.[1]
There is no known method of preventing the cancer. [3] Treatment usually involves surgery, after which chemotherapy and radiation
therapy are used.[3] The medication temozolomide is frequently used as part of chemotherapy.[3][4][8] High-dose steroids may be used
to help reduce swelling and decrease symptoms.[1] Greater surgical removal of the tumor is linked to longer survival.[9]
Despite maximum treatment, the cancer usually recurs.[3] The typical duration of survival following diagnosis is 12 to 15 months, with
fewer than 3 to 7% of people surviving longer than five years.[2][5] Without treatment, survival is typically three months.[10] It is the most
common cancer that begins within the brain and the second-most common brain tumor, after meningioma.[6][11] About 3 in 100,000
people develop the disease per year.[3] It most often begins around 64 years of age and occurs more commonly in males than
females.[2][3] Immunotherapy is being studied as treatment for the cancer.[12]

Signs and symptoms

Common symptoms include seizures, headaches, nausea and vomiting, memory loss, changes to personality, mood or
concentration, and localized neurological problems.[13] The kind of symptoms produced depends more on the location of the tumor
than on its pathological properties. The tumor can start producing symptoms quickly, but occasionally is an asymptomatic
condition until it reaches an enormous size.

Risk factors
The cause of most cases is unclear.[2] About 5% develop from another type of brain tumor known as a low-grade astrocytoma. [13]

Genetics
Uncommon risk factors include genetic disorders such as neurofibromatosis, Li–Fraumeni syndrome, tuberous sclerosis, or Turcot
syndrome.[13] Previous radiation therapy is also a risk.[2][3] For unknown reasons, it occurs more commonly in males.[14]

Environmental
Other associations include exposure to smoking, pesticides, and working in petroleum refining or rubber manufacturing.[13]
Glioblastoma has been associated with the viruses SV40,[15] HHV-6,[16][17] and cytomegalovirus.[18]

Other
Research has been done to see if consumption of cured meat is a risk factor. No risk had been confirmed as of 2013. [19] Similarly,
exposure to radiation during medical imaging, formaldehyde, and residential electromagnetic fields, such as from cell phones and
electrical wiring within homes, have been studied as risk factors. As of 2015, they had not been shown to cause GBM.[13][20]
[21]
 However, a meta-analysis published in 2007 found a correlation between the rate of GBMs and use of a cell phone for longer than
10 years, especially among those who always held the phone on one side of their heads. [13]

Pathogenesis
The cellular origin of glioblastoma is unknown. Because of the similarities in immunostaining of glial cells and glioblastoma, gliomas
such as glioblastoma have long been assumed to originate from glial-type cells. More recent studies suggest
that astrocytes, oligodendrocyte progenitor cells, and neural stem cells could all serve as the cell of origin.[22][23]
Glioblastomas are characterized by the presence of small areas of necrotizing tissue that are surrounded by anaplastic cells. This
characteristic, as well as the presence of hyperplastic blood vessels, differentiates the tumor from grade 3 astrocytomas, which do
not have these features.
GBMs usually form in the cerebral white matter, grow quickly, and can become very large before producing symptoms. Fewer than
10% form more slowly following degeneration of low-grade astrocytoma or anaplastic astrocytoma. These are called secondary
GBMs and are more common in younger patients (mean age 45 versus 62 years).[24] The tumor may extend into the meninges
or ventricular wall, leading to high protein content in the cerebrospinal fluid (CSF) (> 100 mg/dl), as well as an
occasional pleocytosis of 10 to 100 cells, mostly lymphocytes. Malignant cells carried in the CSF may spread (rarely) to the spinal
cord or cause meningeal gliomatosis. However, metastasis of GBM beyond the central nervous system is extremely unusual. About
50% of GBMs occupy more than one lobe of a hemisphere or are bilateral. Tumors of this type usually arise from the cerebrum and
may exhibit the classic infiltration across the corpus callosum, producing a butterfly (bilateral) glioma.

Glioblastoma classification
Brain tumor classification has been traditionally based on histopathology at macroscopic level, measured in hematoxylin-
eosin sections.The World Health Organization published the first standard classification in 1979[25] and has been doing so since. The
2007 WHO Classification of Tumors of the Central Nervous System[26] was the last classification mainly based on microscopy
features. The new 2016 WHO Classification of Tumors of the Central Nervous System [27] was a paradigm shift: some of the tumors
were defined also by their genetic composition as well as their cell morphology.
The grading of gliomas changed importantly and glioblastoma was now mainly classified according to the status of isocitrate
dehydrogenase (IDH) mutation: IDH-wildtype or IDH-mutant.