Gliomas are central nervous system tumors. If you know someone who’s had breast or colon cancer, you’ve probably heard them mention their “stage.” Staging describes a tumor’s size and how far it has spread.

Gliomas rarely spread beyond the brain and spinal cord, so doctors don’t stage them. They grade them instead, from 1 (slowest-growing) to 4 (fastest-growing). Doctors often call grade 1 and 2 tumors “low-grade” and grade 3 and 4 tumors “high-grade.”

How Glioma Grade is Determined

Grading happens after surgery or a biopsy, a procedure that removes a small tissue sample.

“After the surgery, we would take the tissue out, we would give it to the pathologist,” Dr. Mandel explains. A pathologist diagnoses disease by studying tissue under a microscope.

Most adult gliomas are “diffuse,” meaning they grow into the surrounding brain. For these tumors, the pathologist looks for specific warning signs, including:

• Odd-looking cells: “If there were different sizes and shapes of cells or the nucleus, then those would often be graded as grade two for gliomas,” Dr. Mandel says. The nucleus is the cell’s control center and stores its DNA.
• Cells dividing: “If there was mitosis or cells actively dividing those often would be characterized as a grade three,” Dr. Mandel explains. Mitosis is cell division. More dividing cells usually means faster growth.
• New blood vessels or dead tissue: “If there were new blood vessels forming or areas of necrosis where the brain is not getting enough oxygen, those often would be grade four depending upon the different types of tumors,” Dr. Mandel says. Necrosis means areas of dead tissue. It’s a sign the tumor is growing faster than its blood supply can keep up.

Your Tumor’s Genes Matter, Too

One of the most important molecular markers in gliomas is an IDH (isocitrate dehydrogenase) gene mutation. In fact, IDH status has become one of the main factors doctors use to classify gliomas and to predict how these tumors tend to behave over time.

Over the past decade, research has shown that gliomas are not all the same, even when they look similar under a microscope. Some grow slowly and respond well to treatment, while others are more aggressive.

Molecular markers like IDH help explain these differences. As a result, the World Health Organization updated its glioma classification in 2021, placing much greater importance on genetic and molecular features than on appearance alone. This shift has allowed doctors to provide more accurate diagnoses and more personalized care.

Another key marker is called 1p/19q codeletion, the loss of pieces of two chromosomes. Together with an IDH mutation, it identifies a type of glioma called oligodendroglioma.

“It’s more important to be characterized by the molecular features than what it looks like under the microscope,” Dr. Mandel explains. This is because gene changes can show that a tumor is more dangerous than it looks.

“For astrocytoma, sometimes they can look, under the microscope, like a tumor that may not be very aggressive, may not have higher-grade features, but if they have certain molecular mutations, they may need to be graded higher,” he explains.

The same is true for glioblastoma, the most aggressive glioma. A tumor without an IDH mutation can be classified as grade 4 based on its genes alone, even if it doesn’t show the warning signs above.

If your report doesn’t mention molecular testing, be sure to ask your doctor about it.

Questions to Ask Your Doctor

• Has my tumor been tested for genetic markers like the IDH mutation?
• What are my treatment options based on these markers?
• What are the potential side effects of my recommended treatment path?
• Are there any clinical trials I should consider joining?

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