Tests for Non-Hodgkin Lymphoma

Most people with non-Hodgkin lymphoma (NHL) see their doctor because they have felt a lump that hasn’t gone away, they develop some of the other symptoms of NHL, or they just don’t feel well and go in for a check-up.

If you have signs or symptoms that suggest you might have lymphoma, exams and tests will be done to find out for sure and, if so, to determine the exact type of lymphoma.

Medical history and physical exam

Your doctor will want to get a complete medical history, including information about your symptoms, possible risk factors, and other medical conditions. 

Next, the doctor will examine you, paying special attention to the lymph nodes and other areas of the body that might be affected, including the spleen and liver. Because infections are the most common cause of enlarged lymph nodes, the doctor will look for an infection near the swollen lymph nodes. 

The doctor also might order blood tests to look for signs of infection or other problems. Blood tests aren't used to diagnose lymphoma, though. If the doctor suspects that lymphoma might be causing your symptoms, they might recommend a biopsy of a swollen lymph node or other affected area.

Biopsy

For a biopsy, a small piece of a lymph node or, more often, an entire lymph node is removed for testing in a lab.

A biopsy is the only way to confirm a person has NHL. But it's not always done right away because many symptoms of NHL can also be caused by other problems, like an infection, or by other kinds of cancer. For example, enlarged lymph nodes are more often caused by infections than by lymphoma. Because of this, doctors often prescribe antibiotics and wait a few weeks to see if the lymph nodes shrink. If the nodes stay the same or continue to grow, the doctor might order a biopsy.

A biopsy might be needed right away if the size, texture, or location of a lymph node or the presence of other symptoms strongly suggests lymphoma.

Biopsies to diagnose non-Hodgkin lymphoma

There are several types of biopsies. Doctors choose which one to use based on each person’s situation.

Excisional or incisional biopsy: This is the preferred and most common type of biopsy if lymphoma is suspected, because it almost always provides enough of a sample to diagnose the exact type of NHL.

In this procedure, a surgeon cuts through the skin to remove the lymph node. 

• If the doctor removes the entire lymph node, it is called an excisional biopsy. 
• If a small part of a larger tumor or node is removed, it is called an incisional biopsy. 

If the enlarged node is just under the skin, this is a fairly simple operation that can often be done with local anesthesia (numbing medicine). But if the node is inside the chest or abdomen, you will be sedated (given drugs to make you drowsy and relaxed) or given general anesthesia (drugs to put you into a deep sleep).

Needle biopsy: Needle biopsies are less invasive than excisional or incisional biopsies, but the drawback is that they might not remove enough of a sample to diagnose lymphoma (or to determine which type it is). Most doctors do not use needle biopsies to diagnose lymphoma. But if the doctor suspects that your lymph node is enlarged because of an infection or by the spread of cancer from another organ (such as the breast, lungs, or thyroid), a needle biopsy may be the first type of biopsy done. An excisional biopsy might still be needed even after a needle biopsy has been done, to diagnose and classify lymphoma.

There are 2 main types of needle biopsies:

• In a fine needle aspiration (FNA) biopsy, the doctor uses a very thin, hollow needle attached to a syringe to withdraw (aspirate) a small amount of tissue from an enlarged lymph node or a tumor mass. 
• For a core needle biopsy, the doctor uses a larger needle to remove a slightly larger piece of tissue.

To biopsy an enlarged node just under the skin, the doctor can aim the needle while feeling the node. If the node or tumor is deep inside the body, the doctor can guide the needle using a computed tomography (CT) scan or ultrasound (see descriptions of imaging tests later in this section).

If lymphoma has already been diagnosed, needle biopsies are sometimes used to check abnormal areas in other parts of the body that might be from the lymphoma spreading or coming back after treatment.

Other types of biopsies

These procedures are not normally done to diagnose lymphoma, but they might be used to help determine the stage (extent) of a lymphoma that has already been diagnosed. 

Bone marrow aspiration and biopsy: These procedures are often done after lymphoma has been diagnosed to help determine if it has reached the bone marrow. The 2 tests are often done at the same time. The samples are usually taken from the back of the pelvic (hip) bone, although in some cases they may be taken from other bones.

For a bone marrow aspiration, you lie on a table (either on your side or on your belly). After cleaning the skin over the hip, the doctor numbs the area and the surface of the bone with local anesthetic, which can cause a brief stinging or burning sensation. A thin, hollow needle is then inserted into the bone and a syringe is used to suck out a small amount of liquid bone marrow. Even with the anesthetic, most people still have some brief pain when the marrow is removed.

A bone marrow biopsy is usually done just after the aspiration. A small piece of bone and marrow is removed with a slightly larger needle that is pushed into the bone. The biopsy can also cause some brief pain.

Lumbar puncture (spinal tap): This test looks for lymphoma cells in the cerebrospinal fluid (CSF), which is the liquid that bathes the brain and spinal cord. Most people with lymphoma will not need this test. But doctors may order it for certain types of lymphoma or if a person has symptoms that suggest the lymphoma may have reached the brain.

For this test, you may lie on your side or sit up. The doctor first numbs an area in the lower part of your back over the spine. A small, hollow needle is then placed between the bones of the spine to withdraw some of the fluid. 

Pleural or peritoneal fluid sampling: Lymphoma that has spread to the chest or abdomen can cause fluid to build up. Pleural fluid (inside the chest) or peritoneal fluid (inside the abdomen) can be removed by placing a hollow needle through the skin into the chest or abdomen.

• When this procedure is used to remove fluid from the area around the lung, it’s called a thoracentesis. 
• When it is used to collect fluid from inside the abdomen, it’s known as a paracentesis. 

The doctor uses a local anesthetic to numb the skin before inserting the needle. The fluid is then taken out and checked in the lab for lymphoma cells. 

Lab tests on biopsy samples

All biopsy samples and fluids are looked at in the lab by a pathologist (a doctor specially trained to recognize cancer cells). The size and shape of the cells and how they are arranged may show not only if the person has a lymphoma, but also what type of lymphoma it is. But usually other types of lab tests are needed as well. 

Flow cytometry and immunohistochemistry: For both flow cytometry and immunohistochemistry, the biopsy samples are treated with antibodies that stick to certain proteins on cells. The cells are then looked at in the lab (immunohistochemistry) or with a special machine (for flow cytometry), to see if the antibodies attached to them.

These tests can help determine whether a lymph node is swollen because of lymphoma, some other cancer, or a non-cancerous disease. The tests can also be used for immunophenotyping – determining which type of lymphoma a person has, based on certain proteins in or on the cells. Different types of lymphocytes have different proteins on their surface, which correspond to the type of lymphocyte and how mature it is.

Chromosome tests: Normal human cells have 23 pairs of chromosomes (strands of DNA), each of which is a certain size and looks a certain way in the lab. But in some types of lymphoma, the cells have changes in their chromosomes, such as having too many, too few, or abnormal chromosomes. These changes can often help identify the type of lymphoma.

• Cytogenetics: In this lab test, the cells are checked for any abnormalities in the chromosomes.
• Fluorescent in situ hybridization (FISH): This test looks more closely at lymphoma cell DNA using special fluorescent dyes that only attach to specific genes or parts of chromosomes. FISH can find most chromosome changes that can be seen in standard cytogenetic tests, as well as some gene changes too small to be seen with cytogenetic testing. FISH is very accurate and can usually provide results within a couple of days.
• Polymerase chain reaction (PCR): PCR is a very sensitive DNA test that can find gene changes and certain chromosome changes too small to be seen with a microscope, even if very few lymphoma cells are present in a sample.

For more information, see Testing Biopsy and Cytology Specimens for Cancer.

Imaging tests

Imaging tests use x-rays, sound waves, magnetic fields, or radioactive particles to produce pictures of the inside of the body. These tests might be done for a number of reasons, including:

• To look for possible causes of certain symptoms (such as enlarged lymph nodes in the chest in someone having chest pain or trouble breathing)
• To help determine the stage (extent) of the lymphoma
• To help show if treatment is working
• To look for possible signs of lymphoma coming back after treatment

Chest x-ray

The chest might be x-rayed to look for enlarged lymph nodes in this area.

Computed tomography (CT) scan

A CT scan combines many x-rays to make detailed, cross-sectional images of your body. This scan can help tell if any lymph nodes or organs in your body are enlarged. CT scans are useful for looking for lymphoma in the abdomen, pelvis, chest, head, and neck.

CT-guided needle biopsy: A CT can also be used to guide a biopsy needle into a suspicious area. For this procedure, you lie on the CT scanning table while the doctor moves a biopsy needle through the skin and toward the area. CT scans are repeated until the needle is in the right place. A biopsy sample is then removed to be looked at in the lab.

Magnetic resonance imaging (MRI) scan

Like CT scans, MRI scans show detailed images of soft tissues in the body. But MRI scans use radio waves and strong magnets instead of x-rays. This test is not used as often as CT scans for lymphoma, but if your doctor is concerned about spread to the spinal cord or brain, MRI is very useful for looking at these areas.

Ultrasound

Ultrasound uses sound waves and their echoes to create pictures of internal organs or masses. In the most common type of ultrasound, a small, microphone-like instrument called a transducer is placed on the skin (which is first lubricated with a gel). It gives off sound waves and picks up the echoes as they bounce off the organs. The echoes are converted by a computer into an image on a computer screen. 

Ultrasound can be used to look at lymph nodes near the surface of the body or to look inside your abdomen for enlarged lymph nodes or organs such as the liver and spleen. It can also detect kidneys that have become swollen because the outflow of urine has been blocked by enlarged lymph nodes.

Positron emission tomography (PET) scan

For a PET scan, you are injected with a slightly radioactive form of sugar, which collects mainly in cancer cells. A special camera is then used to create a picture of areas of radioactivity in the body. The picture is not detailed like a CT or MRI scan, but it can provide helpful information about your whole body.

If you have lymphoma, a PET scan might be done to:

• See if an enlarged lymph node contains lymphoma. 
• Find small areas that might be lymphoma, even if the area looks normal on a CT scan.
• Check if a lymphoma is responding to treatment. Some doctors will repeat the PET scan after 1 or 2 courses of chemotherapy. If the chemotherapy is working, the lymph nodes will no longer absorb the radioactive sugar.
• Help decide whether an enlarged lymph node still contains lymphoma or is just scar tissue after treatment.

PET/CT scan: Some machines can do both a PET scan and a CT scan at the same time. This lets the doctor compare areas of higher radioactivity on the PET scan with the more detailed appearance of that area on the CT scan. PET/CT scans can often help pinpoint the areas of lymphoma better than a CT scan alone.

Bone scan

This test is usually done if a person is having bone pain or has lab results that suggest the lymphoma may have reached the bones.

For bone scans, a radioactive substance called technetium is injected into a vein. It travels to damaged areas of bone, and a special camera can then detect the radioactivity. Lymphoma often causes bone damage, which may be seen on a bone scan. But bone scans can’t show the difference between cancers and non-cancerous problems, such as arthritis and fractures, so further tests might be needed. 

Other tests

Blood tests

Blood tests are not used to diagnose lymphoma, but they can sometimes help determine how advanced the lymphoma is. 

• A complete blood count (CBC) measures the levels of different cells in the blood. For a person already known to have lymphoma, low blood cell counts might mean that the lymphoma is growing in the bone marrow and affecting new blood cell formation. 
• Blood chemistry tests are often done to look at how well the kidney and liver function are working. 
• If lymphoma has been diagnosed, the lactate dehydrogenase (LDH) level may be checked. LDH levels are often increased in patients with lymphomas. 
• For some types of lymphoma or if certain treatments might be used, your doctor may also advise you to have tests to see if you’ve been infected with certain viruses, such as hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV). Infections with these viruses may affect your treatment.

Tests of heart and lung function

These tests are not used to diagnose lymphoma, but they might be done if you are going to get certain chemotherapy drugs commonly used to treat lymphoma that could affect the heart or the lungs. 

• Your heart function may be checked with an echocardiogram (an ultrasound of the heart) or a MUGA scan.
• Your lung function may be checked with pulmonary function tests, in which you breathe into a tube connected to a machine.