What Makes a Brain Tumor High-Grade or Low-Grade?

Medically reviewed by David Reardon, MD

Brain tumors are graded on a scale of 1 to 4, based on how malignant, or cancerous, they are – that is, how abnormal their cells appear under a microscope. A grade of 1 is the least malignant, and 4 is the most malignant. A tumor may contain cells of different grades, but it is classified by its highest-grade cells.

The purpose of the brain tumor grading system is to indicate the tumor’s likely growth rate and how likely it is to spread within the brain– information used in predicting outcomes and treatment planning. Brain tumors are graded and classified by the World Health Organization (WHO).

Grades are often assigned to gliomas, which are tumors that develop in the supporting glial cells of the brain or spine. Gliomas make up about 30 percent of all brain and central nervous system tumors, and about 80 percent of all malignant brain tumors.  The most common malignant brain tumors are glioblastomas.

Patrick Wen, David Reardon, brain tumors
Patrick Wen, MD (seated), and David Reardon, MD, of Dana-Farber’s Center for Neuro-Oncology.

Gliomas classified as grades 1 and 2 are termed low-grade, because their cells are well-differentiated, exhibit less aggressive tendencies and have a better prognosis.  Grade 3 and 4 gliomas are considered high-grade: their cells are undifferentiated and highly malignant, and have a worse prognosis.

Grade 1 tumors are usually associated with long-term survival and are most common in children. They grow slowly and look almost normal under a microscope. Grade 1 tumors often do not need additional therapy after surgery. An example of a grade I tumor is pilocytic astrocytoma.

Grade 2 tumors are relatively slow-growing. Some of them can spread into nearby normal tissue and can transform into a higher-grade tumor.  Grade 2 tumors may or may not require additional therapy after surgery. An example is a grade 2 astrocytoma.

Grade 3 tumors are by definition are malignant because they actively reproduce abnormal cells that invade nearby tissue. They tend to recur, potentially as a grade 3 or grade 4 tumor. Grade 3 and 4 tumors always require additional therapy after surgery that typically involves radiation and chemotherapy.  An example of a grade 3 tumor is an anaplastic astrocytoma.

Grade 4 tumors are the most malignant and aggressive brain tumors.  Their cells are highly abnormal when viewed under a microscope. They recruit new blood vessels to maintain their rapid growth. Glioblastoma is the most common grade 4 brain tumor.