If signs or symptoms suggest that a patient has non-Hodgkin lymphoma, exams and tests are done to find out for certain if this disease is present and, if so, to determine the exact type of lymphoma.

Signs and symptoms of non-Hodgkin lymphoma

Non-Hodgkin lymphoma may cause many different signs and symptoms, depending on its location in the body. In some cases it may not cause any symptoms until it grows quite large.

Lymph nodes near the skin

Non-Hodgkin lymphoma can affect lymph nodes close to the surface of the body (such as on the sides of the neck, in the groin or underarm areas, or above the collar bone), which may be seen or felt as lumps under the skin. These are often found by the patient, a family member, or a health care professional. Enlarged lymph nodes are more often caused by infections than by lymphoma.

Abdomen

Lymphomas in the abdomen may cause the abdomen to become swollen and tender. This may be due to either a tumor or to large collections of fluid. When lymphoma causes swelling near the intestines, the passage of feces may be blocked, which may lead to abdominal pain, nausea, or vomiting.

Lymphomas of the stomach often cause pain in the stomach, nausea, and reduced appetite.

Chest

When lymphoma starts in the thymus or lymph nodes in the chest, it may press on the nearby trachea (windpipe), which can cause coughing or trouble breathing.

The superior vena cava (SVC) is the large vein that carries blood from the head and arms back to the heart. It passes near the thymus and lymph nodes inside the chest. Lymphomas in this area may push on the SVC, which can cause the blood to back up in the veins. This is known as SVC syndrome. It can cause swelling (and sometimes a bluish-red color) in the head, arms, and upper chest. It can also cause trouble breathing and a change in consciousness if it affects the brain. The SVC syndrome can be life-threatening, and requires treatment right away.

Brain

Lymphomas of the brain, called primary brain lymphomas, can cause headache, trouble thinking, weakness in certain parts of the body, personality changes, and sometimes seizures.

Skin

Lymphomas of the skin can be seen and felt. They often appear as extremely itchy, red or purple lumps or nodules under the skin. (For more details, see the separate document Lymphoma of the Skin.)

General symptoms

Along with symptoms and signs resulting from local effects of cancer growth, non-Hodgkin lymphoma can cause generalized symptoms, such as:

• unexplained weight loss
• fever
• drenching night sweats (enough to soak clothing)

Doctors sometimes call these B symptoms. The presence of B symptoms is often found in more rapidly growing lymphomas.

Diagnosing non-Hodgkin lymphoma by a biopsy

Many of the symptoms of non-Hodgkin lymphoma are not specific enough to say for certain if cancer is present. Most of these symptoms 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 wait a few weeks to see if they remain large. Sometimes they prescribe antibiotics to see if they cause the nodes to shrink.

If the nodes continue to grow or stay the same size, 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. This procedure is called a biopsy.

A biopsy may be needed right away if the size, texture, or location of the node or the presence of other symptoms strongly suggests cancer is present. But a delay in diagnosis of a few weeks is not likely to be harmful in most instances. The exception to this would be a very rapidly 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 the unique aspects of 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 node is near the skin surface, this is a simple operation that can often be done with local anesthesia (numbing medicine). But if the node is inside the chest or abdomen, general anesthesia is used (where the patient is asleep). This method almost always provides enough of a sample to diagnose the exact type of non-Hodgkin lymphoma. It is preferred, 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 needle attached to a syringe to withdraw (aspirate) a small amount of tissue from a tumor mass. A core needle biopsy uses a larger needle to remove a slightly larger piece of tissue.

For an enlarged node 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 discussion of imaging tests later in this section).

A needle biopsy does not require surgery, but in many cases it may not remove enough of a sample to make a definite diagnosis. Advances in lab tests (discussed later in this section) and the growing experience of many doctors have improved the accuracy of this procedure.

Most doctors do not use needle biopsies to make a diagnosis of lymphoma, but they may use FNA in patients already diagnosed to confirm that an enlarged lymph node or organ in another area also contains lymphoma. FNA can also be used to diagnose cancers that spread to nodes from other organs and to identify nodes swollen by infection that don't need to be removed.

Other types of biopsies

These procedures may be done to diagnose lymphoma, but they are more often done to help stage (determine the 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 two 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.

In 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 may 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 down into the bone. The biopsy may also 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: Spread of lymphoma 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. 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.

Lab tests on biopsy samples to diagnose and classify lymphoma

All biopsy samples and fluids are looked at under a microscope by pathologist (a doctor with special training in recognizing cancer cells), who studies the appearance, size, and shape of the cells and how the cells are arranged. This may reveal not only if the person has a lymphoma, but also what type of lymphoma it is. Because the diagnosis of 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.

Immunohistochemistry

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.

Flow cytometry

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 cause them to 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 lymph node swelling is due to 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.

Cytogenetics

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 translocations (where part of one chromosome has broken off and is now attached to another chromosome), as happens in certain types of lymphoma. Some lymphoma cells may have too many chromosomes, too few chromosomes, or other chromosome abnormalities. 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 studies

These tests look more closely at lymphoma cell DNA. They can detect most changes that are visible under a microscope in cytogenetic tests, as well as others that can't be seen.

Fluorescent in situ hybridization (FISH): FISH is similar to cytogenetic testing. It uses special fluorescent dyes that only attach to specific 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 changes too small to be seen with usual cytogenetic testing.

FISH can be used to look for specific changes in chromosomes. It 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 also find some chromosome changes too small to be seen under a microscope, even if very few lymphoma cells are present in a sample.

These tests can also detect certain genes that have been "turned on" and are contributing to the lymphoma cells' abnormal growth. As researchers learn more about lymphomas, these may become even more important.

Other lab tests

Blood tests may be used to 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. In patients already known to have lymphoma, if the blood counts are low, it might mean that the lymphoma is growing in the bone marrow and affecting new blood cell formation. Results of another blood test that measures levels of lactate dehydrogenase (LDH) will often be abnormally high in the blood of patients with fast-growing lymphomas.

Other blood tests can help detect liver or kidney problems caused by the spread of lymphoma or due to the side effects of certain chemotherapy drugs. Blood tests can also help determine if treatment is needed to correct low or high blood levels of certain minerals. Tests may also be done to make sure blood is clotting properly.

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 may be done for a number of reasons, including to help find a suspicious area that might be cancerous, to learn how far a cancer may have spread, and to help determine if treatment has been effective..

Chest x-ray

X-rays of the chest are often done to look for enlarged lymph nodes in this area.

Computed tomography (CT) scan

The CT scan is a type of x-ray that produces detailed, cross-sectional images of your body. 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.

Instead of taking one picture, as does a regular x-ray, a CT scanner takes many pictures as it rotates around you. A computer then combines these pictures into detailed images of the part of your body that is being studied.

Before the scan, 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 line through which the contrast dye is injected. 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 ever had a reaction to any contrast material used for x-rays.

CT scans take longer than regular x-rays. You need to lie still on a table while they are being done. During the test, the table moves in and out of the scanner, a ring-shaped machine that completely surrounds the table. You might feel a bit confined by the ring you have to lay in when the pictures are being taken.

Spiral CT (also known as helical CT) is now available in many medical centers. This type of CT scan uses a faster machine. The scanner part of the machine rotates around the body continuously, allowing doctors to collect the images much more quickly than standard CT. This lowers the chance of blurred images occurring as a result of body movement. It also lowers the dose of radiation received during the test. The slices it images are thinner, which yields more detailed pictures.

In some cases, CT can be used to guide a biopsy needle precisely 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

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 is often injected into a vein before the scan to better see details. The contrast material usually does not cause allergic reactions.

MRI scans are very helpful in looking at the brain and spinal cord.

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 out.

Ultrasound

Ultrasound uses sound waves and their echoes to produce a picture of internal organs or masses. For this test, 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 organs or 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. 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, glucose (a form of sugar) containing a radioactive atom is injected into the blood. Because cancer cells in the body grow rapidly, they absorb large amounts of the radioactive sugar. A special camera can then create a picture of areas of radioactivity in the body.

PET scans can help tell if an enlarged lymph node contains lymphoma or is benign. The picture is not finely detailed like a CT or MRI scan, but it provides helpful information about your whole body.

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 glucose. PET scans can also be used after treatment in helping decide whether an enlarged lymph node still contains lymphoma or is merely scar tissue.

Recently, newer devices have been developed that combine the PET scan with a CT scan (PET/CT scan). This allows the doctor to compare areas of higher radioactivity on the PET scan with the more detailed appearance of that area on the CT.

Gallium scan

For this test, a solution containing slightly radioactive gallium is injected into a vein. It is attracted to lymph tissue in the body. A special camera can then detect the radioactivity, showing the location of the gallium. This test can find lymphoma tumors in bones and other organs.

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. The gallium scan will not detect most slow-growing lymphomas but will find many fast-growing (aggressive) lymphomas. It can also help distinguish an infection from a lymphoma when the diagnosis is not clear.

Bone scan

For bone scans, a different radioactive substance (technetium) is used. After it is injected, it travels to areas of the bone that are damaged. 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.

Last Medical Review: 07/17/2009
Last Revised: 07/17/2009