Tests for Non-Hodgkin Lymphoma

This is the 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 your skin to remove the lymph node.

• Excisional biopsy: The entire lymph node is removed.
• Incisional biopsy: A small part of a larger tumor or node is removed.

If the enlarged node is just under the skin, this is a fairly simple operation. It can often be done with local anesthesia (numbing medicine).

If the node is inside your chest or abdomen, you will also be given medicine to make you drowsy and relaxed (sedated). Or you might be given medicine to put you into a deep sleep (general anesthesia).

A needle biopsy is less invasive than an excisional or incisional biopsy, but it might not remove enough of a sample to diagnose lymphoma or figure out which type you have.

However, you might get a needle biopsy for a few reasons:

As a first step if your healthcare team suspects something other than NHL. Your care team might start with a needle biopsy if they think your lymph node is enlarged for a different reason. For example, if they think it might be enlarged because of an infection or the spread of cancer from your breast, lungs, thyroid, or other organs. You might still need an excisional biopsy later, to diagnose and classify lymphoma.

If you’ve already been diagnosed with NHL. You might get a needle biopsy to check an unusual area in another part of your body if your care team thinks it may be caused by the lymphoma spreading or coming back.

There are 2 main types of needle biopsies:

• Fine needle aspiration (FNA) biopsy uses a very thin, hollow needle attached to a syringe to take out (aspirate) a small amount of tissue from an enlarged lymph node or a tumor.
• Core needle biopsy uses a larger needle to remove a slightly larger piece of tissue.

To biopsy an enlarged node just under the skin, the doctor can often aim the needle while feeling the node. If the node or tumor is deep inside your body, the doctor can guide the needle using a computed tomography (CT) scan or ultrasound.

You might get this procedure so doctors can see if lymphoma has reached your bone marrow.

PET/CT has largely replaced bone marrow biopsy for staging some types of NHL, such as diffuse large B-cell lymphoma. But it is still used for certain subtypes, including follicular lymphoma, CLL/SLL, and mantle cell lymphoma. PET/CT is less reliable for detecting marrow involvement in these types. 

Bone marrow aspiration and biopsy are often done at the same time. The samples are usually taken from the back of your pelvic bone (hip), but sometimes they are taken from other bones.

How is this procedure done?

For this procedure you lie on a table, either on your side or your belly. After cleaning the skin over your hip, the doctor numbs the skin and the surface of the bone by injecting a local anesthetic (numbing medicine). This may cause a brief stinging or burning feeling.

The doctor pushes a thin, hollow needle into the bone and uses a syringe to remove a small amount of liquid bone marrow. Even with the anesthetic, most people have some brief discomfort when the marrow is pulled out.

A bone marrow biopsy is usually done just after the aspiration. A small piece, or core, of bone and marrow is removed with a slightly larger needle pushed into the bone. The biopsy may also cause some brief discomfort.

This test looks for lymphoma cells in cerebrospinal fluid (CSF). CSF is the liquid that bathes your brain and spinal cord. Most people with lymphoma do not need this test. But a cancer care team may order it for certain types of lymphoma or if symptoms suggest lymphoma may have reached the brain.

You either lie on your side or sit up for this test. The doctor first numbs an area in the lower part of your back, over your spine. Next, they remove some of the fluid with a small, hollow needle placed between the bones of your spine.

All biopsy samples and fluids are looked at in the lab by a pathologist. This is a doctor specially trained to recognize cancer cells.

The pathologist can often learn if a person has lymphoma based on the size and shape of the cells and how they are arranged. Sometimes, they can also see what type of lymphoma a person has. But other lab tests are usually needed as well.

For both of these tests, a biopsy sample is coated with lab-made immune proteins (antibodies) that will only stick to certain proteins on cells. The cells are then looked at to see if the antibodies have attached to them. This is done either in the lab (immunohistochemistry) or with a special machine (flow cytometry).

These tests can help determine whether a lymph node is swollen because of lymphoma, a different type of cancer, or another disease that is not cancer.

The tests can also be used to see if the lymphoma cells have certain proteins, or markers. This is called immunophenotyping. It can help determine what type of lymphoma a person has.

Some of these markers are very important. They are a big part of how doctors choose treatment for a person. They also help doctors confirm that the lymphoma can respond to some modern treatments like CAR T-cells or antibody treatments.

These tests look at the chromosomes in lymphoma cells.

Chromosomes are long strands of DNA. Human cells usually have 23 pairs of chromosomes. Each pair is a certain size and looks a certain way in the lab. But some types of lymphoma cells have chromosome changes. The lymphoma cells might have abnormal chromosomes, or they might have too many or too few chromosomes.

These changes can often help identify the type of lymphoma.

Cytogenetic testing (karyotyping)

In this lab test, the cells are checked for any abnormalities in the chromosomes. The cells need to be grown in the lab first, so the results can take a week or more.

Fluorescent in situ hybridization (FISH)

This test looks more closely at lymphoma cell DNA using fluorescent dyes that only attach to certain genes or parts of chromosomes.

FISH can find most chromosome changes that are seen in standard cytogenetic tests. It can also find some gene changes that are too small to be seen with those tests. It is very accurate, and results are usually ready within a couple of days.

Polymerase chain reaction (PCR)

PCR is a very sensitive DNA test. Even when a testing sample has very few lymphoma cells, this test can find gene changes and certain chromosome changes that are too small to be seen with a microscope.

Next-generation sequencing and other molecular tests may also be done on the lymphoma cells. These tests look for specific gene changes (mutations). For some lymphoma types, the results can help guide treatment decisions.

For example, changes in the MYD88 and CD79B genes of certain B-cell lymphomas can affect which treatments are most likely to work. The same is also true for BTK mutations in mantle cell lymphoma.

A chest x-ray might be done to look for enlarged lymph nodes in this area. This test is not needed if a CT of the chest is done.

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

To get the clearest pictures of the lymph nodes, a contrast dye is usually put into a vein (IV) before the scan. Let your healthcare team know if you have kidney problems or if you've ever had a reaction to contrast dye.

When looking for lymphoma in the body, CT scans are often combined with a PET scan. This is known as a PET/CT scan.

CT-guided needle biopsy

A CT scan 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 your skin and toward the area.

CT scans are repeated until the needle is in the right place. The doctor then removes a biopsy sample and sends it to the lab to be looked at under a microscope.

Like a CT scan, an MRI shows detailed images of soft tissues in your body. But an MRI uses radio waves and strong magnets instead of x-rays.

This test is not used as often as CT scans for lymphoma. But MRI can be very useful for looking at the spinal cord and brain, if your cancer care team is concerned about lymphoma spread to these areas.

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 your skin and moved over the part of your body being checked. It gives off sound waves and picks up the echoes as they bounce off your organs. Gel is used to help the sound waves travel back and forth. The echoes are converted by a computer into an image on a screen.

Ultrasound can be used to:

• Look at lymph nodes near the surface of your body.
• Check inside your abdomen for enlarged lymph nodes or organs such as the liver and spleen.
• See if your kidneys are swollen because enlarged lymph nodes are blocking the outflow of urine.

For a PET scan, you are injected with a slightly radioactive form of sugar. This sugar collects mainly in cancer cells. A camera takes pictures showing where the sugar has gathered in your body. The picture is not detailed like a CT scan or MRI, but it can provide helpful information about your whole body.

If you have lymphoma, a PET scan might be used 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 lymphoma is responding to treatment. Some doctors will repeat the PET scan after 2 to 4 cycles of chemotherapy. If it’s working, the lymph nodes will no longer absorb the radioactive sugar.
• Help decide whether an enlarged lymph node still contains lymphoma or if it is just scar tissue after treatment.

PET scans are helpful for most types of lymphoma, but some slow-growing types don't show up well on them.

PET/CT scan

Many clinics and hospitals have machines that combine a PET scan with a CT scan. This lets doctors 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 areas of lymphoma better than a CT scan alone.

This test measures the levels of different cells in your blood. If you have lymphoma, low blood cell counts might mean the cancer is growing in your bone marrow and affecting new blood cell formation.

Blood chemistry tests are often done to look at how well the kidneys and liver are working.

If you are diagnosed with lymphoma, your cancer care team might check your LDH level. LDH levels are often increased in people with lymphomas. 

High LDH levels can be a sign of a larger amount of cancer in the body or faster-growing disease. Doctors use this test as one factor in judging how advanced or aggressive the lymphoma may be.

LDH is also one of the measures used to help predict prognosis and plan treatment.  However, this test may come back elevated for other reasons. An elevated LDH does not always mean that you have lymphoma. 

Depending on the type of lymphoma you have and your treatment plan, your cancer care team might test to see if you’ve been infected with certain viruses, such as:

• Hepatitis B virus (HBV)
• Hepatitis C virus (HCV)
• Human immunodeficiency virus (HIV)

Infection with these viruses may affect your treatment.