How Is Non-Hodgkin Lymphoma Diagnosed?
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 (see the previous section), or they just don’t feel well and go in for a check-up.
If signs or symptoms suggest that a person might have non-Hodgkin lymphoma, exams and tests will be done to find out for certain if they do and, if so, to determine the exact type of lymphoma.
Medical history and physical exam
If your symptoms suggest you might have non-Hodgkin lymphoma, your doctor will want to get a thorough medical history, including information about your symptoms, possible risk factors, family history, 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 involved, including the spleen and liver. Because infections are the most common cause of enlarged lymph nodes, the doctor will look for an infection in the part of the body near the swollen lymph nodes.
If the doctor suspects that non-Hodgkin lymphoma might be causing the symptoms, he or she will recommend a biopsy of the area.
Many symptoms of non-Hodgkin lymphoma are not specific enough to say for certain if they are being caused by cancer. Most of them can also be caused by non-cancerous problems, like infections, or by other kinds of cancers.
For example, enlarged lymph nodes are more often caused by infections than by non-Hodgkin lymphoma. Because of this, doctors often prescribe antibiotics and wait a few weeks to see if the nodes shrink.
If the nodes stay the same or continue to grow, the doctor might then order a biopsy. Either a small piece of a node or, more commonly, the entire node is removed for viewing under the microscope and for other lab tests.
A biopsy might be needed right away if the size, texture, or location of the node or the presence of other symptoms strongly suggests cancer. But delaying the diagnosis for a few weeks is not likely to be harmful unless it’s a very fast-growing lymphoma.
Types of biopsies used to diagnose non-Hodgkin lymphoma
A biopsy is the only way 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 most common type of biopsy if lymphoma is suspected. In this procedure, a surgeon cuts through the skin to remove either the entire node (excisional biopsy) or a small part of a large tumor (incisional biopsy).
If the enlarged node is near the skin surface, this is a simple operation that can often be done with local anesthesia (numbing medicine). But if it is inside the chest or abdomen, the patient will be sedated or given general anesthesia (drugs are used to put the patient into a deep sleep).
This method almost always provides enough of a sample to diagnose the exact type of non-Hodgkin lymphoma. It is the preferred type of biopsy, if it can be done without too much discomfort to the patient.
Fine needle aspiration (FNA) or core needle biopsy: In an 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.
If the enlarged node is near the surface of the body, the doctor can aim the needle while feeling the node. If the 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).
A needle biopsy does not require surgery, but in some cases it might not remove enough of a sample to make a definite diagnosis. 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 to diagnose and classify lymphoma, even after a needle biopsy has been done.
Once lymphoma has been diagnosed, needle biopsies are sometimes used to check areas in other parts of the body that might be 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. They may also be done for symptoms or problems even when lymphoma is not suspected, and lymphoma may be found.
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 the sternum (breast bone) or 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 (about 1 teaspoon). Even with the anesthetic, most patients 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 twisted as it is pushed into the bone. Most patients feel pressure during the biopsy, but it can cause some brief pain. Once the biopsy is done, pressure will be applied to the site to help stop any bleeding.
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.
For this test, the patient may lie on their side or sit up. The doctor first numbs an area in the lower part of the back over the spine. A small, hollow needle is then placed between the bones of the spine to withdraw some of the fluid.
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.
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. Often, ultrasound is used to guide the needle. The doctor uses a local anesthetic to numb the skin before inserting the needle. The fluid is then withdrawn and looked at under the microscope to check for lymphoma cells. When this procedure is used to remove fluid from the area around the lung, it is called a thoracentesis. When it is used to collect fluid from inside the abdomen, it’s known as a paracentesis.
Lab tests on biopsy samples to diagnose and classify lymphoma
All biopsy samples and fluids are looked at under a microscope by a pathologist (a doctor with special training in recognizing cancer cells), who studies the size and shape of the cells and how they are arranged. This may show not only if the person has a lymphoma, but also what type of lymphoma it is. Because diagnosing lymphoma can be tricky, it helps if the pathologist specializes in diseases of the blood.
Pathologists can sometimes tell which kind of lymphoma a patient has by looking at the cells, but usually other types of tests are needed to confirm the diagnosis.
In this test, a part of the biopsy sample is treated with special antibodies (man-made versions of immune system proteins) that attach only to specific molecules on the cell surface. These antibodies cause color changes, which can be seen under a microscope. This test may be helpful in distinguishing different types of lymphoma from one another and from other diseases.
Like immunohistochemistry, this test looks for certain substances on the outside surface of cells that help identify what types of cells they are. But this test can look at many more cells than immunohistochemistry.
For this test, a sample of cells is treated with special antibodies that stick to the cells only if certain substances are present on their surfaces. The cells are then passed in front of a laser beam. If the cells now have antibodies attached to them, the laser will make them give off light, which can be measured and analyzed by a computer. Groups of cells can be separated and counted by these methods.
This is the most commonly used test for immunophenotyping (classifying lymphoma cells according to the substances (antigens) on their surfaces. Different types of lymphocytes have different antigens on their surface. These antigens may also change as each cell matures.
Flow cytometry can help determine whether the lymph node is swollen because of lymphoma, some other cancer, or a non-cancerous disease. It has also become very useful in helping doctors determine the exact type of lymphoma so that they can select the best treatment.
This technique allows doctors to evaluate the chromosomes (long strands of DNA) in the lymphoma cells. The cells are looked at under a microscope to see if the chromosomes have any abnormalities. Some lymphoma cells may have too many chromosomes, too few chromosomes, or other changes such as a translocation (where part of one chromosome has broken off and is now attached to another chromosome. These changes can help identify the type of lymphoma.
Cytogenetic testing usually takes about 2 to 3 weeks because the lymphoma cells must grow in lab dishes for a couple of weeks before their chromosomes are ready to be viewed under the microscope.
Molecular genetic tests
These tests look more closely at lymphoma cell DNA. They can detect most changes that are visible by microscope in cytogenetic tests, as well as others that can’t be seen. The disadvantage is that they can only be used to look for specific changes, so the doctor has to know what he or she is looking for.
Fluorescent in situ hybridization (FISH): FISH uses special fluorescent dyes that only attach to specific genes or parts of chromosomes. FISH can find most chromosome changes (such as translocations) that can be seen under a microscope in standard cytogenetic tests, as well as some gene changes too small to be seen with usual cytogenetic testing.
FISH can be used on regular blood or bone marrow samples. It is very accurate and can usually provide results within a couple of days, which is why this test is now used in many medical centers.
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. .
Blood tests measure the amounts of certain types of cells and chemicals in the blood. They are not used to diagnose lymphoma, but they can sometimes help determine how advanced the lymphoma is.
Patients with known or suspected lymphoma will have a complete blood count (CBC). This test measures the different cells in the blood, such as the red blood cells, the white blood cells, and the platelets. In patients already known to have lymphoma, low blood cell counts can mean that the lymphoma is growing in the bone marrow and affecting new blood cell formation.
Many patients will also have blood chemistry tests run, to look at kidney and liver function. If lymphoma has been diagnosed, another blood test called lactate dehydrogenase (LDH) may be checked. LDH levels are often increased in patients with lymphomas.
For some types of lymphoma or if certain treatments may be used, your doctor may also advise you to have other blood tests to see if you have been infected with certain viruses, such as the hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV). Infections with these viruses may affect your treatment.
Imaging tests use x-rays, sound waves, magnetic fields, or radioactive particles to produce pictures of the inside of the body. In someone with known or suspected lymphoma, these tests might be done to look more closely at an abnormal area that might contain lymphoma, to learn how far the lymphoma might have spread, or to find out if treatment has been effective.
The chest might be x-rayed to look for enlarged lymph nodes in this area.
Computed tomography (CT) scan
The CT scan is an x-ray test that produces detailed, cross-sectional images of your body. Instead of taking one picture, like a regular x-ray, a CT scanner takes many pictures as it rotates around you. A computer then combines these pictures into an image of a slice of your body.
A CT scanner has been described as a large donut, with a narrow table in the middle opening. You will need to lie still on the table while the scan is being done. CT scans take longer than regular x-rays, and you might feel a bit confined by the ring while the pictures are being taken.
Unlike a regular x-ray, CT scans can show the detail in soft tissues (such as internal organs). 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.
Before the test, you may be asked to drink a contrast solution and/or get an intravenous (IV) injection of a contrast dye that helps better outline abnormal areas in the body. You may need an IV for the contrast dye injection. The injection can cause some flushing (a feeling of warmth, especially in the face). Some people are allergic and get hives or, rarely, more serious reactions like trouble breathing and low blood pressure. Be sure to tell the doctor if you have any allergies or have ever had a reaction to any contrast material used for x-rays.
CT-guided needle biopsy: In some cases, CT can be used to guide a biopsy needle into a suspicious area. For this procedure, called a CT-guided needle biopsy, you remain on the CT scanning table while a radiologist moves a biopsy needle through the skin and toward the location of the mass. CT scans are repeated until the needle is within the mass. A biopsy sample is then removed to be looked at under a microscope.
Magnetic resonance imaging (MRI) scan
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.
Like CT scans, MRI scans provide detailed images of soft tissues in the body. But MRI scans use radio waves and strong magnets instead of x-rays. The energy from the radio waves is absorbed by the body and then released in a pattern formed by the type of body tissue and by certain diseases. A computer translates the pattern into a very detailed image of parts of the body.
A contrast material called gadolinium may be injected into a vein before the scan to better see details. This material is different from what is used for CT scans, so being allergic to one doesn’t mean you are allergic to the other. This material should be used with caution (if at all) in people on dialysis (for kidney failure).
MRI scans take longer than CT scans – often up to an hour. You may have to lie inside a narrow tube, which is confining and can be distressing to some people. Newer, more open MRI machines may be another option. The MRI machine makes loud buzzing and clicking noises that you may find disturbing. Some places provide headphones or earplugs to help block this noise out.
Ultrasound uses sound waves and their echoes to produce a picture 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 emits sound waves and picks up the echoes as they bounce off the organs. The echoes are converted by a computer into a black and white image that is displayed 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. (It can’t be used to look at lymph nodes in the chest because the ribs block the sound waves.)
This is an easy test to have done, and it uses no radiation. For most ultrasounds, you simply lie on a table, and a technician moves the transducer over the part of your body being looked at.
Positron emission tomography (PET) scan
For a PET scan, a form of radioactive sugar (known as fluorodeoxyglucose or FDG) is injected into the blood. Because cancer cells in the body grow rapidly, they absorb large amounts of the radioactive sugar. After about an hour, you will be moved onto a table in the PET scanner. You lie on the table for about 30 minutes while a special camera creates a picture of areas of radioactivity in the body. The picture is not finely detailed like a CT or MRI scan, but it can provide helpful information about your whole body.
- PET scans can help tell if an enlarged lymph node contains lymphoma.
- It can also help spot small areas that might be lymphoma, even if the area looks normal on a CT scan.
- PET scans can be used to tell 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 take up the radioactive sugar.
- PET scans can also be used after treatment in helping decide whether an enlarged lymph node still contains lymphoma or is merely scar tissue.
Often, for patients with lymphoma, a machine that combines the PET scan with a CT scan (PET/CT scan) is used. This lets the doctor compare areas of higher radioactivity on the PET scan with the more detailed appearance of that area on the CT.
For this test, a solution containing slightly radioactive gallium is injected into a vein. It is attracted to lymph tissue in the body. A few days later a special camera is used to detect the radioactivity, showing the location of the gallium. The gallium scan will not detect most slow-growing lymphomas but will find many fast-growing (aggressive) lymphomas.
This test is not used as much now as in the past, as many doctors may do a PET scan instead. It can still sometimes be useful in finding areas of lymphoma that the PET scan may miss. It can also help distinguish an infection from a lymphoma when the diagnosis is not clear.
For bone scans, a radioactive substance called technetium is used. After being injected into a vein, it travels to damaged areas of the bone. Lymphoma often causes bone damage, and a bone scan will find it. But a bone scan may also pick up non-cancerous problems, such as arthritis and fractures.
This test is not usually done unless a person is having bone pain or has lab test results that suggest the lymphoma may have reached the bones.
Tests of heart and lung function
These tests are not used to help diagnose non-Hodgkin lymphoma, but they may be done if you are going to get certain chemotherapy drugs commonly used to treat lymphoma that may 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.
Freedman AS, Jacobson CA, Mauch P, Aster JC. Chapter 103: Non-Hodgkin’s lymphoma. In: DeVita VT, Lawrence TS, Rosenberg SA, eds. DeVita, Hellman, and Rosenberg’s Cancer: Principles and Practice of Oncology. 10th ed. Philadelphia, Pa: Lippincott Williams & Wilkins; 2015.
Roschewski MJ, Wilson WH. Chapter 106: Non-Hodgkin Lymphoma. In: Niederhuber JE, Armitage JO, Doroshow JH, Kastan MB, Tepper JE, eds. Abeloff’s Clinical Oncology. 5th ed. Philadelphia, Pa: Elsevier; 2014.
Last Medical Review: August 26, 2014 Last Revised: February 29, 2016
- Can Non-Hodgkin Lymphoma Be Found Early?
- Signs and Symptoms of Non-Hodgkin Lymphoma
- How Is Non-Hodgkin Lymphoma Diagnosed?
- How Is Non-Hodgkin Lymphoma Staged?
- Survival Rates and Factors That Affect Prognosis (Outlook) for Non-Hodgkin Lymphoma
- What Should You Ask Your Doctor About Non-Hodgkin Lymphoma?