In most individuals, CNS lymphoma is not diagnosed until symptoms appear. A medical history and physical examination are usually the first steps toward diagnosis. This may include a neurological examination to evaluate brain and nerve function for muscle strength, coordination and mental status.

This initial exam may be performed by a general physician. If abnormalities are found, the patient probably will be referred to a neurologist or a neurosurgeon for more detailed testing.

Blood tests may be performed to determine the patient's white blood cell count, as well as to identify cancer cells. These findings may indicate the need for more in-depth testing. Additional blood tests may be conducted to diagnose the following conditions due to their close association with CNS lymphoma:

• HIV test. HIV antibodies (substance produced by the body as a defense to invaders) are measured in the blood.
  
  
• Epstein-Barr virus (EBV) test. EBV antibodies are measured in the blood or cerebrospinal fluid (CSF).

Imaging tests to help diagnose CNSL may include:

• CAT scan. Cross-sectional images are taken of the body from different angles using computer technology. CAT scans may be performed with contrast medium (a dye) to help locate cancer cells in the body. For primary CNS lymphoma, CAT scans focus on the brain, spinal cord, chest, abdomen and pelvis.
  
  
•  Magnetic resonance imaging (MRI). Magnetic field and radio waves are used to create detailed images of internal organs to locate cancer in the CNS. A contrast material may also be used. This diagnostic test is very useful in locating cancer along spinal fluid pathways.

• Positron emission tomography (PET) scan.  A radioactive sugar is injected into the bloodstream and is rapidly absorbed by the cancer cells, creating hot spots. These spots are detectable images and are strong indicators of cancer.
  
  
• X-rays. The use of radiation to create images of organs in the body.
  
  
• Magnetic resonance spectroscopic imaging (MRSI). Magnetic and radio waves are used to interact with atomic features of the cancer to create detailed images of the tumors that are not visible by MRI. This test is used experimentally at this time.
  
  
•  Angiography. A dye is injected into the bloodstream to show the blood vessels in and around the cancer cells while images are taken of the brain and spinal cord. This test provides useful details prior to surgery to help the surgeon plan for surgical procedures.
  
  
• Lumbar puncture (spinal tap). A sample of cerebrospinal fluid (CSF) is taken from the spinal canal and observed under a microscope to detect cancer cells and nervous system infections. Also, high levels of protein and other substances in the CSF may indicate the presence of cancer. This is typically performed after CT and MRI scans indicate cancer cells are present especially along the spinal fluid pathway.

If tumors in or near the nerves of the eyes are found, the following tests may be performed:

• Slit lamp eye exam. Narrow bands of light are beamed into the eye to check for abnormalities.
  
  
• Vitrectomy. Thin incisions are made in the eye to extract vitreous humor (gel-like fluid) from the eyeball to be examined under a microscope for cancer cells.

Diagnosis of CNS lymphoma is dependent on a biopsy which can be obtained by several methods, including:

• Biopsy. Biopsies (samples of tissue taken by using an invasive method with anesthesia) of the brain, spinal cord, lymph node or bone marrow tissue can be taken. The sample is analyzed by a pathologist to determine the type and stage of the cancer.  
  
  
• Stereotactic biopsy and surgery. In this procedure, a neurosurgeon with use of anesthesia drills a hole in the skull and removes a small piece of tumor tissue guided by CT and MRI scans. If the neurosurgeon determines it is partially treatable with surgery, as much as possible of the tumor is surgically removed (debulking).