First, a physician will obtain the patient’s medical history and perform a complete physical examination. Because infections are the most common cause of enlarged lymph nodes, the physician will examine the area surrounding the swollen lymph nodes for an infection. The physician may prescribe antibiotics and re-examine the lymph nodes in one to two weeks to determine if the lymph nodes have shrunk. If they are still enlarged or have become more swollen, a biopsy of the area may be ordered. A biopsy is the definitive method for diagnosing whether cancer is present and if so, its type and stage.

Biopsies are required to diagnose and classify non-Hodgkin’s lymphoma. The procedure involves removing a sample of lymph node tissue and sending it to a pathologist for examination. Excisional and incisional biopsies are the two procedures used to diagnose NHL. In these procedures, the physician makes an incision through the skin to remove an entire lymph node (excisional biopsy), or a small section of a large tumor (incisional biopsy). When the lymph node is located near the skin surface, the procedure is relatively simple, and can be done with local anesthesia. However, when the lymph node is inside the chest or abdomen general anesthesia is required.

A fine needle aspiration (FNA) biopsy is another type of biopsy that may be ordered. In this procedure, a thin needle and a syringe are used to remove a small amount of fluid and tissue. This procedure is useful because it does not require surgery. However, there are some disadvantages. One disadvantage is that in some situations the needle cannot remove the amount of tissue needed for a diagnosis. Advances are being made to counteract this problem. FNA is also helpful in diagnosing cancers that have spread to lymph nodes from other organs, and in distinguishing lymph nodes that are swollen by infection. 

After a diagnosis has been confirmed, the disease will be staged. Staging is the process of determining how far the cancer has spread and is necessary to determine treatment. Additional tests also may be necessary for diagnosis and treatment planning. These tests may be ordered by a medical oncologist, a physician who specializes in the diagnosis and treatment of cancers. Imaging tests that may be used during the staging of non-Hodgkin’s lymphoma include:

• Chest x-ray. This test uses low doses of radiation to produce images of the chest on film paper or fluorescent screens. With non-Hodgkin’s lymphoma, enlarged lymph nodes may be detected in the chest.
  
  
• CAT scan (computed axial tomography). This test allows for multiple x-rays to be taken from different angles around the patient. The cross-sectional images of the patient’s body are analyzed by a computer.  CAT scans give a physician an enhanced look at the lymph nodes in the head, neck, chest, abdomen and pelvis. They can also reveal enlarged organs, such as the liver and the spleen. CAT scans also may be used to guide a biopsy needle into an enlarged lymph node located deep in the body. This procedure is known as a CAT-guided needle biopsy.

• MRI (magnetic resonance imaging). This test uses a powerful magnetic field to create images of structures and organs within the body allowing a computer to produce very clear cross-sectional or three-dimensional images. It may be ordered to determine if the disease has spread to the spinal cord or brain.
  
  
• PET scan (positron emission tomography). In this procedure, the patient receives an injection of glucose (sugar) containing a small amount of radioactive material. Once in the body, the radioactive glucose is absorbed by the cancer cells. A camera then scans the patient and detects where the radioactive glucose was absorbed.
  
  This test is useful when a physician wants to look for lymphoma throughout the entire body. Areas where the cancer cells are present appear as hot spots. They are brighter than noncancerous areas because they absorb more radioactive glucose. PET scan can also be useful in determining whether an enlarged lymph node contains cancer or is benign.
  
  
• Gallium scan. A patient receives an injection of gallium-67, a radioactive substance that is often absorbed by areas of the body where non-Hodgkin’s lymphoma is present. A few days after the injection, the patient is placed under a scanner that detects where the gallium has accumulated in the body and the image is recorded on film. These tests are useful for locating the disease in bones and organs. It is also useful in differentiating lymphomas from an infection.
  
  
• Bone scan. In this procedure, a mildly radioactive substance is injected into the bloodstream where it travels to areas where bone is damaged. The test is helpful in locating bone damage due to lymphoma in the bones.
  
  
• Ultrasound. This procedure uses harmless high-frequency sound waves to produce images of internal organs. This test is useful for uncovering masses in the abdomen and for detecting kidneys or other organs that have swollen as the result of enlarged lymph nodes.    

Additional tests that may be ordered include:

• Bone marrow biopsy and aspiration. Usually performed together during the same procedure, a bone marrow biopsy and a bone marrow aspiration may be ordered for initial diagnosis. It also may be used to determine how far the disease has spread. A bone marrow aspiration uses a long thin needle attached to a syringe to remove small amounts of liquid bone marrow. During the biopsy, a larger needle is used to remove a narrow piece of bone. The samples are usually taken from the back of the pelvic bone after the patient has received local anesthesia.
  
  
• Lumbar puncture. Also known as a spinal tap, this procedure uses a needle to remove a sample of cerebrospinal fluid (CSF) from between the bones in the lower spine. The sample is then examined for lymphoma cells.
  
  
• Immunohistochemistry. Part of a biopsy sample is treated with special antibodies. The antibodies attach themselves to specific molecules on the cell surface and cause color changes that are detectable under a microscope. This test may be ordered to distinguish the various types of NHL from one another and from other diseases.
  
  
• Flow cytometry. Fluorescent antibodies are used to detect certain molecules on the surface of lymphoma cells. The cells are treated with the antibodies, each of which attach themselves to certain types of cells. The cells are then passed in front of a laser beam which causes the cells to give off light of a different color. The color is then measured and analyzed by a computer. This test may be ordered to determine if lymph node enlargement is due to NHL or another form of cancer or disease. It is also useful in diagnosing the exact type of NHL.
  
  
• Cytogenetics. This test uses a microscope to evaluate the characteristics of specially treated cells including their nuclear structure. It may be ordered to determine if the cells have too many chromosomes, or if the chromosomes have any translocations (the transfer of DNA from one chromosome to another).
  
  
• Molecular genetic studies. These tests may be ordered to spot translocations of cell DNA that are not detectable under a microscope during cytogenetic testing. The tests can also detect oncogenes (genes that speed up cell division) that have been “turned on” and are contributing to the abnormal growth of the lymphoma cells.
  
  
• Blood tests. A complete blood count and blood chemistry studies may be ordered. A complete blood count measures the number of red blood cells, white blood cells and platelets in a sample of blood, as well as the amount of hemoglobin in the red blood cells and a number of other factors. Blood chemistry studies measure the amounts of specific substances released into the blood by organs and tissues.