Introduction: Who Should Seek Diagnostic Testing

Diagnostic testing for metastatic glioma becomes necessary when a person experiences symptoms that suggest something may be wrong with the brain or nervous system. If you have already been diagnosed with a glioma and later develop new symptoms in other parts of your body, your healthcare provider may recommend additional testing to check if the cancer has spread beyond the brain or spinal cord.^[2]

Anyone experiencing persistent headaches that are worse in the morning, sudden vision changes, seizures that occur for the first time, or problems with balance and coordination should seek medical attention promptly. Other warning signs include memory problems, personality changes, confusion, nausea and vomiting, or weakness on one side of the body.^[1] These symptoms don’t always mean cancer is present, but they indicate that the brain or nervous system needs to be evaluated by a medical professional.

For individuals already living with a diagnosed glioma, regular follow-up care and monitoring are essential. If you notice new symptoms developing in areas outside the brain—such as unexplained bone pain, breathing difficulties, or swollen lymph nodes—it’s important to inform your healthcare team right away. While gliomas rarely spread outside the brain and spinal cord, awareness of this possibility helps doctors catch any changes early.^[2]

Classic Diagnostic Methods for Identifying Gliomas

When a healthcare provider suspects a brain tumor, the diagnostic process typically begins with a neurological exam. This is a physical examination where your doctor checks how well your brain and nervous system are working. During this exam, the provider will test your vision, hearing, balance, coordination, strength, and reflexes. Problems in any of these areas can give clues about where in the brain a tumor might be located. For example, if you have trouble moving your arm, the tumor may be in the part of the brain that controls arm movement.^[7]

After the neurological exam, imaging tests are used to create detailed pictures of the inside of your brain. The most common and important imaging test for diagnosing glioma is magnetic resonance imaging (MRI). An MRI uses powerful magnets and radio waves to create detailed images of your brain tissue. During the test, you lie still inside a large tube-shaped machine while images are taken. Sometimes a special dye called contrast material is injected into a vein in your arm before or during the MRI. This contrast material makes certain parts of the brain show up more clearly on the images. High-grade, aggressive gliomas tend to “light up” brightly on MRI scans when contrast is used, which helps doctors identify them.^[6][7]

A computed tomography (CT) scan, also called a CAT scan, may be used as well. This test uses X-rays and a computer to create cross-sectional images of your brain. CT scans are faster than MRIs and can be helpful in emergency situations or when an MRI cannot be performed.^[7]

Another specialized imaging test that may be ordered is positron emission tomography (PET). A PET scan creates images that show how tissues and organs in your body are functioning. Before the scan, you receive a small amount of radioactive sugar through an IV. Cancer cells, which use more energy than normal cells, absorb more of this sugar and show up as bright spots on the scan.^[7]

Magnetic resonance spectroscopy (MRS) is an imaging technique based on MRI technology that provides information about the chemical makeup of brain tissue. This test measures the levels of different chemicals in the brain. Normal brain tissue has certain chemical patterns, while tumor tissue has different patterns. For example, normal brain tissue has high levels of a chemical called NAA, while tumor tissue has high levels of a chemical called choline. MRS can help doctors determine whether an abnormal area seen on MRI is likely to be a tumor without needing to take a tissue sample right away.^[6]

Functional MRI (fMRI) may be used to map important areas of the brain that control movement, speech, vision, and other critical functions. This information helps surgeons plan the safest way to remove a tumor while avoiding damage to vital brain tissue.^[6]

To confirm the diagnosis and determine exactly what type of glioma is present, doctors need to examine actual tumor tissue under a microscope. This is done through a procedure called a biopsy. During a biopsy, a small sample of the tumor is removed and sent to a laboratory for testing. There are two main ways this can be done. One method is a stereotactic needle biopsy, where a thin needle is guided through a small hole in the skull to reach the tumor and remove a tissue sample. The other method is to take a biopsy during surgery when the tumor is being removed.^[7]

Once the tissue sample reaches the laboratory, specialists called pathologists examine it under a microscope. They look at the shape and appearance of the cells to determine what type of glioma it is and how aggressive it appears. They also perform molecular and genetic testing on the tumor cells to identify specific genetic changes or mutations. These genetic markers help doctors predict how the tumor will behave and which treatments are most likely to work. For instance, some gliomas have mutations in genes called IDH, which can affect prognosis and treatment decisions.^[4][7]

All gliomas are assigned a grade based on how quickly they grow and how abnormal the cells look under the microscope. The grading system ranges from grade 1 (slowest growing and least aggressive) to grade 4 (fastest growing and most aggressive). Glioblastoma, which is always classified as grade 4, is the most aggressive type of glioma in adults.^[5][12]

Diagnostics for Metastatic Glioma: Testing for Cancer Spread

When doctors need to determine whether a glioma has spread outside the brain or spinal cord—which is very rare—additional diagnostic tests may be necessary. Extracranial metastases, meaning cancer spread beyond the skull and spine, occur in only a small number of glioma patients, usually those with high-grade, aggressive tumors who have already had surgery.^[2]

If metastatic spread is suspected, your healthcare team may order imaging tests of other parts of your body. These might include CT scans or PET scans of the chest, abdomen, or other areas where symptoms have developed. The most common sites where gliomas spread outside the nervous system are the spine (along the neural axis), bones (especially the vertebrae in the spine), lungs, liver, and lymph nodes.^[2][8]

If an abnormal area is found outside the brain or spinal cord, a biopsy of that area may be performed to confirm that it contains glioma cells. This helps doctors distinguish between cancer spread and other medical conditions that might cause similar symptoms.^[2]

For patients with known glioma who develop new neurological symptoms, spinal MRI may be ordered to check whether tumor cells have spread within the nervous system to the spinal cord. This is more common than spread to organs outside the nervous system.^[2]

Diagnostic Testing for Clinical Trial Enrollment

Many patients with glioma are encouraged to consider participating in clinical trials, which are research studies that test new treatments. Clinical trials often have specific requirements that patients must meet before they can enroll. These requirements, called eligibility criteria, help researchers make sure the study participants are appropriate for the treatment being tested.^[14]

To determine whether you qualify for a clinical trial, your healthcare team will perform several diagnostic tests. These typically include recent MRI scans to document the size and location of your tumor. Many trials require that these scans be performed within a certain timeframe, such as within the past two to four weeks, to ensure the most current information about your disease.^[14]

Molecular and genetic testing of your tumor tissue is especially important for clinical trial eligibility. Many new treatments target specific genetic mutations found in glioma cells. For example, some trials are testing treatments specifically for gliomas with IDH mutations or EGFRvIII mutations. Your tumor tissue will be tested to see if it has these or other genetic markers that match the requirements of the trial.^[4][14]

Blood tests are usually required before enrolling in a clinical trial. These tests check your overall health, including how well your liver and kidneys are functioning, your blood cell counts, and other factors. Trials have specific standards that your test results must meet to ensure you are healthy enough to participate safely.^[13]

Some clinical trials test immunotherapy approaches, which use the body’s own immune system to fight cancer. For these trials, additional tests may be performed to evaluate your immune system function. Newer approaches like chimeric antigen receptor (CAR) T-cell therapy require specialized testing and preparation before treatment can begin.^[14]

Your healthcare team will also assess your functional status—meaning how well you can perform daily activities—using standardized scales. This helps determine whether you are well enough to participate in the trial and tolerate the experimental treatment.^[13]

The GBM AGILE trial is an example of a platform study designed to test multiple new treatments for glioblastoma more quickly than traditional trials. This trial includes comprehensive testing and tissue collection to better understand which patients respond to which treatments. Participating in such trials often requires extensive diagnostic testing both before and during treatment to monitor how the disease responds.^[14]