Brain and spinal cord -
This article was last reviewed and updated on January 15, 2019
by Jane Barron, MD FRCPC
Glioblastoma is a type of cancer that can develop in the brain or spinal cord.
It is the most common brain tumour in adults.
Your pathology report for glioblastoma will include important information such as the IDH and MGMT status of the tumour.
The normal brain and spinal cord
The brain is an organ that is found within the skull. It is part of a system known as the central nervous system which includes the brain and spinal cord. The brain is divided into the cerebrum, cerebellum, and brainstem. The spinal cord is a long thin structure that sits in the spinal column at the back of the body. The spinal cord starts in the neck and ends in the lower back.
The brain and spinal cord are made up of specialized cells called glial cells and neurons. The glial cells are further divided into cells called astrocytes, oligodendrocytes, ependymal cells, and microglial.
What is glioblastoma?
Glioblastoma is made up of abnormal astrocytes. Glioblastoma is the most common astrocytic derived tumor and the most common brain tumor found in adults. It can occur at any age, including childhood.
World Health Organization (WHO) Grade
Pathologists use the word grade to describe how different the cancer cells in glioblastoma look compared the cells normally found in the brain or spinal cord.
Brain and spinal cord tumors are given a World Health Organization grade of I to IV. For glioblastoma, the grade can only be determined after your pathologist has examined the tissue under the microscope.
Your pathologist will look for the following features in order to determine the grade:
Nuclear atypia – The nucleus is the part of the cell that contains genetic material or DNA. Cells with nuclear atypia have nuclei that are darker, larger, or more irregular in shape compared to normal glial cells. The tumour cells in glioblastoma show significant nuclear atypia.
Cellular pleomorphism – Pleomorphism is a word pathologists use to describe a tumour where the cells within the tumour look very different from one and other. For example, one tumour cell may be five times larger than the tumour cell right next to it. The tumour cells in glioblastoma are very pleomorphic.
Mitotic activity – A tumour cell that is in the process of dividing to create new tumour cells is called a mitotic figure. Mitotic activity is a measure of how many tumour cells are dividing to create new tumour cells. The mitotic activity for most glioblastomas is high.
Microvascular proliferation – Tumours require lots of blood in order to grow. Glioblastoma creates new blood vessels and pathologists call this process microvascular proliferation. Glioblastoma can show microvascular proliferation.
Necrosis – Necrosis is a form of cell death. Fast growing tumours such as glioblastoma often contain many dead tumour cells. As a result, necrosis is very commonly seen in glioblastoma. Necrosis may also be seen after a tumour has been treated with radiation or chemotherapy.
Why is this important? Grade is important, as the higher grade tumors, grade III and IV, have a worse prognosis compared to the lower grades. Glioblastoma is a World Health Organization (WHO) grade IV tumor.
Your pathologist may perform a test called immunohistochemistry which allows your pathologist to see the proteins being made by the tumour cells. If the tumour cells are making a protein, the result will be described as positive or reactive.
The results can be variable for each marker but usually glioblastoma tumour cells are usually positive for glial fibrillary acidic protein (GFAP), S100, vimentin, and p53.
Isocitrate Dehydrogenase (IDH)
Isocitrate dehydrogenase (IDH) is a special protein that can be found inside glioblastoma tumour cells. There are two forms of the IDH protein made by the genes IDH1 and IDH2.
A genetic alteration, called a mutation, can occur in either of these genes which causes the cell to produce an abnormal IDH protein.
Why is this important? A glioblastoma that has a mutation in IDH1 or IDH2 (a mutant glioblastoma) is associated with a better prognosis compared to a glioblastoma that does not possess a mutation (IDH-wildtype).
O6-Methylguanine-DNA Methyltransferase (MGMT) Methylation
MGMT is a special protein found in all cells. In some glioblastomas, the MGMT protein can undergo a change, called methylation. This change causes the tumour cell to produce less MGMT protein.
Why is this important? Your pathologist can perform a test to see if the MGMT in your tumour shows methylation. If testing shows that a glioblastoma is methylated it could be associated with a better response to certain chemotherapy drugs compared to a tumor that is not methylated.