Brain Tumor Malignancy, Type, and Grade
Medically reviewed by Dr. C.H. Weaver M.D. Medical Editor 1/2021
The results from diagnostic tests provide detailed information from which a team of healthcare providers can make an accurate diagnosis. The diagnosis includes identifying whether the tumor is benign or malignant, the type of brain tumor, and the tumor grade, or the extent to which the cells have mutated and invaded nearby brain tissue. An accurate diagnosis is critical for determining optimal treatment.
Benign or Malignant?
Brain tumors are designated as benign or malignant based on how cells from the biopsy sample appear under a microscope. Typically, benign tumors are less aggressive and more treatable than malignant tumors.
Benign Brain Tumors
A benign brain tumor consists of cells that have a normal or almost normal appearance when viewed under a microscope. The tumor is very slow-growing, has distinct borders that form a capsule, and does not spread into adjacent brain tissue. Benign brain tumors grow like a balloon being blown up, with an intact capsule and no direct invasion of brain tissue. However, benign brain tumors can cause brain damage or be considered life-threatening due to their ability to encroach into areas of the brain occupied by normal cells, causing increased pressure on and dysfunction in these cells.
Surgery alone is often curative for benign tumors that are located where complete removal is possible. The most common benign brain tumors are meningiomas and neural sheath tumors (neurilemmoma).
Malignant Brain Cancers
A malignant, or cancerous, brain tumor grows into and invades adjacent normal brain tissue but rarely spreads outside the brain. Malignant brain tumors can be slow- or fast-growing and are usually life threatening due to their ability to invade and destroy normal brain tissue. Malignant brain tumors can spread to other locations in the brain and spine because they lack distinct borders and are difficult to remove without prohibitive damage to normal brain tissue. Cells from malignant brain tumors can also break away from the initial site and travel to distant parts of the brain and spine by way of the cerebrospinal fluid. However, most malignant brain tumors remain localized, in the area where they began.
There are two types of malignant brain tumors, primary and metastatic. Primary brain tumors originate from cells in the brain and there are many types of these. The most common type of malignant primary brain tumor is glioblastoma multiforme (grade IV astrocytoma ), which make up approximately 20% of all primary brain tumors.
Metastatic brain tumors are any cancers that have spread from another area of the body to the brain. Cancers that commonly spread to the brain include breast and lung cancers.
The grade of a tumor is determined by the degree to which the tumor cells appear different from normal cells when viewed under the microscope. Grade is an important factor because the extent to which the cancer has differentiated, or mutated compared to normal cells, may help determine the best possible treatment option.
- Grade I tumors: Grade I tumors are the least malignant, meaning they appear almost normal when viewed under a microscope. These tumors grow slowly and are usually associated with good long-term survival. Surgery alone can be an effective treatment for this grade of tumor. Pilocytic astrocytoma, craniopharyngioma, and many tumors of neurons, such as gangliocytoma and ganglioglioma, are examples of grade I tumors.
- Grade II tumors (well-differentiated): Grade II tumors have a slightly abnormal appearance when viewed under a microscope and are relatively slow growing. While the cells in grade II tumors are not normal, they are still well-differentiated, which means they have distinct boundaries, and thus are not as aggressive as high-grade tumors. However, they can invade adjacent normal tissue, and sometimes these tumors recur as a higher grade.
- Grade III tumors (anaplastic): Grade III tumors are, by definition, malignant, although there isn’t always a sharp distinction between a grade II and a grade III tumor. The cells of a grade III tumor are actively reproducing abnormal cells and spreading into adjacent normal brain tissue. These tumors tend to recur, often as a higher grade.
- Grade IV tumors (blastomas): The most malignant tumors are designated as grade IV. They have a bizarre appearance when viewed under the microscope, reproduce rapidly, and permeate adjacent normal brain tissues. These tumors induce the formation of new blood vessels so that they can maintain their rapid growth. They also have areas of dead cells in their center. The World Health Organization (WHO) designates grade IV tumors as ‘blastomas’. Glioblastoma multiforme is a grade IV glioma, and the most common example of a grade IV tumor.
Types of Brain Tumors
The main distinction for brain tumors is whether they originated in the brain or spread from another location to the brain such as the breast or lung. The latter are called secondary or metastatic brain tumors and the cells are identical to the cancer cells from the original location.
Cancers that originate in the brain are called primary brain tumors. There are many different kinds of primary brain tumors and they are classified by the type of tissue in which they begin. The most common brain tumors are gliomas, which begin in the glial cells located in the brain that perform supportive functions for the cells that conduct neural impulses. There are also many types of non-glial brain tumors that arise from other types of cells in the brain; however, most of these tumors are rare. The main types of primary brain tumors include the following:
Primary Brain Cancers
- Gliomas Astrocytomas Ependymomas Oligodendroglioma Mixed gliomas
- Non-glial Brain Tumors Craniopharyngiomas Germ cell tumors Meningiomas Pineal tumors Pituitary adenomas Primitive neuroectodermal tumors (PNET) Schwannomas
Metastatic Brain Cancers
Metastatic brain tumors are cancers that have spread from their site of origin to the brain. CNS metastases usually occur by way of the bloodstream. A cancer cell may break away from the original location in the body and travel in the circulatory system until it gets lodged in a small capillary network in brain tissue. Metastatic brain tumors are the most common brain tumor, occurring as much as four times more frequently than primary brain tumors. The cancers that most commonly metastasize to the brain are breast and lung cancer.
- Gliomas: About half of all primary brain tumors and about one-fifth of all primary spinal cord tumors are gliomas, meaning that they grow from glial cells. Glial cells provide supportive functions for the neurons, the brain cells that conduct nerve impulses.
- Astrocytomas: Astrocytomas are the most common form of glioma and the most common type of primary brain tumor. These tumors can develop in any part of the central nervous system: the brain, brain stem, or spinal cord. Astrocytomas are further classified based on how the cells look under a microscope. Cells that are well differentiated mean that they have clear boundaries and structure. They are the least malignant form of brain tumor.
- Non-invasive astrocytoma: Non-invasive astrocytomas are tumors that grow slowly and usually do not grow into the tissues around them. There are two types of non-invasive astrocytomas called juvenile pilocytic and subependymal.
- Diffuse astrocytoma (stage I-II astrocytoma): Diffuse astrocytomas contain cells that are relatively normal and are considered to be low-grade tumors. They grow relatively slowly and may sometimes be completely removed through surgery. However, even well-differentiated astrocytomas can be life-threatening if they are inaccessible. In some cases, these tumors can also progress or recur as higher grade tumors.
- Anaplastic astrocytoma (stage III astrocytoma): Anaplastic astrocytomas grow more rapidly than low-grade tumors and contain cells with malignant traits, meaning they appear very different from normal cells when viewed under a microscope.
- Glioblastoma multiforme (stage IV astrocytoma, GBM): The most advanced stage of astrocytoma is called glioblastoma multiforme, or GBM. These tumors grow rapidly, invade nearby tissue and contain cells that are very malignant. GBM is among the most common and devastating primary brain tumors that affect adults.
- Recurrent glioblastoma multiforme: GBM that has returned or advanced after initial treatment is considered to be recurrent disease. Recurrent GBM may occur after initial treatment of a lower grade astrocytoma, such as diffuse or anaplastic.
Ependymomas: Brain tumors that develop from cells that line the hollow cavities of the brain and the canal containing the spinal cord are called ependymomas. Most of these tumors are usually benign (non-cancerous) and slow growing.
- Well-differentiated ependymoma (stage II): Well-differentiated ependymomas have cells that look very much like normal cells and grow quite slowly.
- Anaplastic ependymoma (stage III): Anaplastic ependymomas are ependymal tumors that do not look like normal cells and grow more quickly than well-differentiated ependymal tumors.
- Ependymoblastoma (stage IV): Ependymoblastomas are rare cancers that usually occur in children. They may grow very quickly.
Oligodendroglioma: Oligodendroglioma tumors begin in the brain cells called oligodendrocytes, which provide support and nourishment for the cells that transmit nerve impulses.
- Well-differentiated oligodendrogliomas are slow-growing tumors that look very much like normal cells.
- Anaplastic oligodendrogliomas grow more quickly, and the cancer cells look very different from normal cells.
Mixed gliomas: Gliomas that occur in more than one type of brain cell are called mixed and may involve astrocytes, ependymal cells, and/or oligodendrocytes. Mixed gliomas include three separate types of tumors: mixed astrocytoma-ependymoma, mixed astrocytoma-oligodendroglioma and mixed astrocytoma-ependymoma-oligodendroglioma.
Non-glial Brain Tumors
Craniopharyngiomas: Another tumor that develops in the region of the pituitary gland near the hypothalamus is called a craniopharyngioma. These tumors are usually benign; however, they are sometimes considered malignant because they can press on or damage the hypothalamus and affect vital functions. These tumors occur most often in children and adolescents.
Germ cell tumors: Germ cell tumors arise from developing sex cells, called germ cells. There are different kinds of germ cells, including germinomas, embryonal carcinomas, choriocarcinomas, and teratomas.
Meningiomas: Meningiomas are very common brain tumors that occur in the membranes that cover and protect the brain and spinal cord (the meninges). Meningiomas usually grow slowly and tend to affect more women than men. Most meningiomas are considered to be benign tumors; however, even benign brain tumors can cause disability and may sometimes be life-threatening. Malignant meningioma is a rare tumor that grows more quickly than benign meningiomas. Types of malignant meningioma include anaplastic meningioma, hemangiopericytoma and papillary meningioma.
Pineal tumors: Pineal region tumors are tumors found in or around the pineal, gland, a tiny organ located near the center of the brain that mediates changes in energy with light and darkness, causing sleepiness with darkness and alertness with increasing light. The tumors can be slow-growing ( pineocytomas ) or fast-growing ( pineoblastomas ). The pineal region is very difficult to reach, and these tumors often cannot be removed.
Pituitary adenomas: The pituitary gland is a small, pea-sized structure located at the base of the brain in the center of the head, behind the eyes. It is very important because it secretes several chemical messengers known as hormones, which help control the body’s other glands and regulate growth, metabolism, maturation, and other essential body processes. Cancers of the pituitary gland are called pituitary adenomas. Almost all adenomas are benign, but their slow expansion compresses normal structures that surround it, suppressing normal pituitary function and sometimes causing headaches or problems with vision. Pituitary adenomas rarely metastasize or spread to other areas of the body. Doctors classify pituitary tumors into two groups—secreting and non-secreting. Secreting tumors release unusually high levels of pituitary hormones, triggering a variety of symptoms.
Primitive neuroectodermal tumors (PNET): PNETs are rare tumors that occur in children and young adults. The most common type of PNET is medulloblastoma, which arises from developing nerve cells that normally do not remain in the body after birth. These brain tumors begin in the lower part of the brain and may spread from the brain to the spine.
Schwannomas: Tumors that begin in Schwann cells, which produce the myelin that protects the acoustic nerve (nerve of hearing), are called schwannomas and are typically benign. Acoustic neuromas are a type of schwannoma. They occur mainly in adults and affect women twice as often as men.
- American Cancer Society. Cancer Facts & Figures 2017.