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 are easily 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 non-Hodgkin lymphoma.

Abdomen: When the lymphoid tissue inside the abdomen is involved, the abdomen can become tender, painful, and/or swollen. 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 discomfort or abdominal pain. The pressure or blockage can also cause 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 irritate or compress 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 in the face and arms and a bluish-red coloration of 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 and moving 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 to 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 produce generalized symptoms, such as:

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

Doctors sometimes call these generalized effects B symptoms. The presence of B symptoms is often related to the presence of more rapidly growing lymphoma cells.

Diagnosing Non-Hodgkin Lymphoma by a Biopsy

The diagnosis of lymphoma may be delayed because 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 the antibiotics cause the nodes to shrink.

If the node continues to grow or stays the same size, either a small piece of the 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 imediately if the size, texture, or location of the node or the presence of other symptoms strongly suggests cancer is present. But there is no evidence that a delay in diagnosis of a few weeks is 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 biopsy procedures, and the doctor's choice is based on the unique aspects of each person's situation.

Excisional or incisional biopsy: This is the most common type of biopsy. 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 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 biopsy: In a fine needle aspiration ( 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. 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 while viewing a computed tomography (CT) scan (see discussion of imaging tests in this section).

The main advantage of FNA is that it does not require surgery. The disadvantage is that in many cases the thin needle cannot remove enough of a sample to make a definite diagnosis. But advances in lab tests (discussed later in this section) and the growing experience of many doctors with FNA have improved the accuracy of this procedure.

Most doctors will use FNA in patients already diagnosed with lymphoma to confirm that an enlarged lymph node or organ in another area also contains lymphoma. FNA is also very useful in diagnosing cancers that spread to nodes from other organs and in identifying 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: Bone marrow samples are obtained from a bone marrow aspiration and biopsy - two tests that 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 (breastbone) or other bones.

In bone marrow aspiration, you lie on a table (either on your side or on your belly). After cleaning the area, the skin over the hip and the surface of the bone are numbed 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 (about 1/16 inch in diameter and 1/2 inch long) 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.

These tests can be used for the initial diagnosis and for staging (to see how far the cancer has spread).

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 near the spine. A small needle is then placed between the bones of the spine to withdraw some of the fluid.

Lab Tests Used to Diagnose and Classify Non-Hodgkin Lymphoma

All biopsy samples and fluids are looked at under a microscope by pathologist (a doctor with special training in recognizing cancer cells). The pathologist looks at 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 is trained and experienced in diagnosing lymphomas.

Pathologists who specialize in diagnosing lymphoma can often tell which kind of lymphoma a patient has, but sometimes this exam does not provide a definite answer. In these cases, one or more of the following lab tests may be needed.

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 non-Hodgkin 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 these 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 non-Hodgkin lymphoma, some other cancer, or a non-cancerous disease. It has also become very useful in helping doctors determine the exact type of non-Hodgkin lymphoma so that they can select the best treatment.

Cytogenetics

This technique allows scientists to evaluate the chromosomes (long strands of DNA) in the lymphoma cells. Scientists look at cells 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. In addition to translocations, some lymphoma cells may have too many chromosomes, too few chromosomes, or other abnormalities of the chromosome. These changes can be used to help identify the type of lymphoma.

Molecular Genetic Studies

Tests of lymphoma cell DNA 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) is similar to cytogenetic testing. It can find most translocations that are visible under a microscope in standard cytogenetic tests, as well as some translocations too small to be seen with usual cytogenetic testing. It uses special fluorescent dyes that only attach to specific parts of chromosomes. 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.

Very sensitive DNA tests such as polymerase chain reaction (PCR) can also find translocations too small to be seen under a microscope, even if there are very few lymphoma cells 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. In the future, as researchers learn more about lymphomas, these may become the most useful tests for determining what kind of lymphoma is present.

Other Lab Tests

Blood tests may be used to measure the amounts of certain types of cells and chemicals in the blood. While they are not used to diagnose lymphoma, they can be helpful in deciding how advanced the lymphoma is. In patients already known to have lymphoma, if the blood counts are low, it might indicate that the lymphoma is growing in the bone marrow and damaging normal blood cell production. Results of another blood test that measures levels of lactate dehydrogenase or 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 cells 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 are used to find and look at tumors inside the body. These tests are an important part of staging (determining if and how much the cancer has spread) non-Hodgkin lymphoma.

Chest X-ray

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

Computed Tomography

The computed tomography (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. A CT scan is 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.

Often after the first set of pictures is taken, you will receive an intravenous (IV) injection of a dye, or radiocontrast agent, which helps better outline structures in your body. You may also be asked to drink 1 to 2 pints of a solution of contrast material. This helps outline the intestine so that it is not mistaken for tumors if your doctor is looking for abnormal areas in your abdomen. A second set of pictures is then taken.

The IV injection of contrast dye 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.

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 fine needle biopsy sample (tiny fragment of tissue) or a core needle biopsy sample (a thin cylinder of tissue about ½-inch long and less than 1/8-inch in diameter) is then removed to be looked at under a microscope.

Magnetic Resonance Imaging

Magnetic resonance imaging (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 might be injected, just as with CT scans, but is used less often.

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 upset people who are afraid of enclosed spaces. Newer, open MRI machines can help with this if needed. The MRI machine makes loud buzzing noises that you may find disturbing. Some places provide headphones to block this out.

Positron Emission Tomography

Positron emission tomography (PET) scans involve injecting glucose (a form of sugar) that contains a radioactive atom 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 scans can help pinpoint the exact location of the lymphoma.

Gallium Scan

During this procedure, the radiologist injects a small dose of radioactive gallium 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. These tests can find tumors that might be non-Hodgkin lymphoma in bones and other organs.

The gallium scan will not detect most slow-growing lymphomas but will recognize many fast-growing (aggressive) lymphomas. It was used before PET scans were available and can still be useful in finding lymphoma deposits that the PET scan may miss. It is also useful in distinguishing infections from lymphomas when the diagnosis is not clear.

Bone Scan

For bone scans, a different radioactive substance 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 will also pick up non-cancerous problems, such as arthritis and fractures. This test is not generally used in the early staging process for non-Hodgkin lymphoma.

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 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 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.

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.