If your healthcare provider thinks you may have non-Hodgkin lymphoma, certain exams and tests will need to be done to be sure. Diagnosing non-Hodgkin lymphoma starts with your healthcare provider asking you questions. You will be asked about your health history, your symptoms, risk factors, and family history of disease. Your healthcare provider will also give you a physical exam.

A biopsy is a small sample of tissue that’s removed and checked for cancer cells. A biopsy is the only way for your healthcare provider to know for sure if you have non-Hodgkin lymphoma. For a biopsy, the doctor removes a sample of tissue. The sample is sent to a lab. A doctor called a pathologist checks it under a microscope for cancer cells. Several types of biopsies can be done to look for non-Hodgkin lymphoma.

The different types of biopsies include:

• Excisional or incisional biopsy. This is the preferred type of biopsy to diagnose non-Hodgkin lymphoma. For an excisional biopsy, a surgeon takes out a whole lymph node. For an incisional biopsy, the surgeon takes out only part of the lymph node or tumor. You may be given medicine to numb the area first. Or you may have medicine to sleep through the procedure. This kind of biopsy almost always gives the pathologist enough tissue to make a full diagnosis.

• Fine needle aspiration (FNA) or core needle biopsy. For FNA, the doctor uses a very thin, hollow needle. For core needle, the doctor uses a slightly larger needle. If the tumor is deep inside your body, the surgeon may guide the needle with the help of ultrasound or CT. A CT scanner is a kind of X-ray imaging machine. This method avoids surgery, but doesn’t always remove enough tissue for a definite diagnosis. But it can help to check for other problems. For example, it can check for an infection in the lymph nodes.

• Bone marrow aspiration and biopsy. Bone marrow is the soft, inner part of certain bones. Non-Hodgkin lymphoma can spread to the bone marrow. So some people who are diagnosed will have a sample of the bone marrow checked for cancer. For this method, the doctor uses a needle to take out small amounts of your liquid bone marrow. This is called aspiration. A small piece of the bone is also taken. This is the biopsy. The aspiration and biopsy is usually done in the bone in the back of your hip (pelvic) bone.

A pathologist can often see if a person has non-Hodgkin lymphoma by using a microscope to check the tissue taken with the biopsy. But in many cases, other types of lab tests may be needed. The tests help to:

• Make sure the diagnosis is correct

• Show the type of lymphoma

This information helps determine your treatment plan and gives a sense of your prognosis.

Biopsy samples may be tested with:

Immunohistochemistry. This test can help show different types of non-Hodgkin lymphoma. For this test, your doctor treats part of the biopsy sample with special antibodies that attach to the cell surface. These cause color changes seen under a microscope.

Flow cytometry. This is another test that can help tell the type of non-Hodgkin lymphoma. It looks at more cells than immunohistochemistry. It uses a special analyzer to determine the types of proteins on the outside of the cancer cells. This helps classify the type of lymphoma.

Cytogenetic analysis. This test is done on a tumor sample or a bone marrow sample. The cells are then grown in a lab. After about 2 to 3 weeks, a pathologist looks at a cell’s chromosomes (pieces of DNA) under a microscope. Some lymphomas have characteristic chromosome changes that help classify them.

Molecular genetic tests. These tests may also be used to look for chromosome changes at a more detailed genetic or molecular level. They usually take less time than cytogenetic tests, so many doctors now prefer to use them. These tests include:

• FISH, or fluorescent in situ hybridization. This test uses special fluorescent dyes that only link to specific parts of chromosomes. FISH can find most chromosome changes that can be seen with standard cytogenetic tests. It can also find some changes too small to be seen with usual cytogenetic testing. It can be used on blood, biopsy, or bone marrow samples. 

• PCR or polymerase chain reaction. This is a very sensitive DNA test. It can also find some chromosome changes too small to be seen under a microscope. It can do this even if there are very few lymphoma cells in a sample.

Your healthcare provider will contact you with your test results. Your provider will talk with you about other tests that may be needed if non-Hodgkin lymphoma is found. Make sure you understand the results and what follow-up is needed.