Certain signs and symptoms might suggest that a child may have non-Hodgkin lymphoma, but tests are needed to confirm the diagnosis.

Signs and symptoms

Childhood non-Hodgkin lymphoma may cause many different signs and symptoms, depending on the location of the tumors. In some cases it may not cause any symptoms until it grows quite large.

Lymph nodes near the skin: Non-Hodgkin lymphoma may grow in lymph nodes close to the surface of the body (on the sides of the neck, in the groin or underarm areas, above the collar bone, etc.). This causes the nodes to enlarge, which are often seen or felt as lumps under the skin. These are often noticed by the child, parent, or a health care professional. Enlarged lymph nodes are more often caused by infections than by non-Hodgkin lymphoma.

Abdomen: If the lymphoma grows inside the abdomen, it can become swollen and tender. There may also be a buildup of fluid that causes even more swelling. When lymphoma causes swelling near the intestines, the passage of feces may be blocked, which may lead to abdominal pain. The pressure or blockage can also cause nausea or vomiting.

The lymphoma may block urine from leaving the kidney. This can lead to kidney failure, which may cause low urine output, tiredness, loss of appetite, nausea, or swelling in the hands or feet.

Chest: When the lymphoma starts in the thymus or lymph nodes in the chest, enlargement of these organs can compress the nearby trachea (windpipe). This can lead to coughing, shortness of breath, and trouble breathing.

The superior vena cava (SVC) is a large vein that carries blood from the head and arms back to the heart. It passes next to 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.

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

• fever and chills
• sweating (particularly at night)
• unexplained weight loss

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

The diagnosis of lymphoma in a child may be delayed or difficult because enlarged lymph nodes in infants and children are commonly caused by infections. Indeed, there is usually little cause for concern unless the lymph nodes are very enlarged (greater than 1 inch across).

Even in these instances, the child is usually given a course of antibiotics first to see if the nodes shrink. If not, further testing is needed, usually by removing a small piece of the node, or possibly the whole node, in a biopsy (see next section). But if the lymph nodes seem to be growing quickly or the child's health seems to be getting worse, immediate action is needed.

Biopsies to diagnose non-Hodgkin lymphoma

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. The main types of childhood non-Hodgkin lymphoma can cause many of the same signs and symptoms, but they require slightly different treatments, so it is important to tell them apart.

For these reasons, an accurate diagnosis is needed, and the only way to do this is to remove some or all of the abnormal lymph nodes for viewing under a microscope and other lab tests. This is called a biopsy.

Types of biopsies used to diagnose non-Hodgkin lymphoma

There are several types of biopsies. Doctors choose which one to use based on the unique aspects of each patient's situation. The goal is to obtain enough tissue to make an accurate diagnosis as quickly as possible, with as few side effects as possible.

Fine needle aspiration (FNA) 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 a tumor mass. If the enlarged node is near the surface of the body, the doctor can aim the needle while feeling the node. If the enlarged node is deep inside the body (including the thymus or nodes of the abdomen), the doctor can guide the needle while viewing it on a CT scan (see discussion of imaging tests later in this section).

The main advantage of FNA is that it does not require surgery. The disadvantage is that in some cases the needle may not 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.

Many 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 identifying nodes swollen by infection that don't need to be removed.

Excisional or incisional biopsy: In these procedures, 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 often can be done with local anesthesia (numbing medicine used only at the biopsy site). But if the node is inside the chest or abdomen, then general anesthesia is used (where the child is asleep). This method almost always provides enough of a sample to make a diagnosis of the exact type of non-Hodgkin lymphoma.

Other types of biopsies

These types of biopsies may be done to diagnose lymphoma, but more often they are done to help determine the extent of spread of a lymphoma that has already been diagnosed.

Bone marrow aspiration and biopsy: These procedures help determine if a lymphoma has reached the bone marrow. The 2 tests are usually 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, the skin over the hip and the surface of the bone can be numbed with local anesthetic to make the procedure less uncomfortable. In most cases, children will be given other medicines to make them drowsy or brief general anesthesia so they are asleep during the procedure. 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.

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. 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 (the process used to see how far the cancer has spread).

Lumbar puncture (spinal tap): This procedure is used to look for lymphoma cells in the cerebrospinal fluid (CSF), which is the liquid that bathes the brain and spinal cord.

For this test, the doctor first numbs an area in the lower part of the back near the spine. The doctor may also recommend that the child be given medicine to make him or her sleep so the child won't squirm during the procedure. Squirming may keep the spinal tap from being done correctly. A small, hollow needle is then placed between the bones of the spine to withdraw some of the fluid.

Pleural or peritoneal fluid sampling: Spread of lymphoma to the thin membranes that line the chest and abdominal cavities 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 child's 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 a pathologist (a doctor with special training in identifying cancer cells). The doctor looks at the size and shape of the cells and how they are arranged. This may reveal not only if the child has a lymphoma, but also what type of lymphoma it is.

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 can.

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 doctors to evaluate the chromosomes (long strands of DNA) in the lymphoma cells. They look at the 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 chromosome abnormalities. 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): This procedure 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.

Polymerase chain reaction (PCR): This is a very sensitive DNA test that 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 determining how advanced the lymphoma is.

In patients already known to have lymphoma, if the blood cell counts are low, it might indicate that the lymphoma is growing in the bone marrow and damaging normal blood cell production.

Levels of a chemical called 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 the blood is clotting properly.

Imaging tests used to diagnose and stage non-Hodgkin lymphoma

Imaging tests use x-rays, sound waves, magnetic fields, or radioactive substances to create pictures of the inside of the body. Imaging 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

A chest x-ray may be done to look for enlarged lymph nodes inside the chest.

Computed tomography (CT or CAT) scan

The CT scan is an x-ray procedure that produces detailed cross-sectional images of the body. Instead of taking one picture, like a conventional x-ray does, a CT scanner takes many pictures as it rotates around the patient. A computer then combines these pictures into images of slices of the part of the body being studied.

CT scans are useful for looking at enlarged lymph nodes or other masses in the chest, abdomen, or pelvis.

Before the scan, your child 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. Your child may need an IV line through which the contrast dye will be injected. The injection can cause some flushing (redness and warm feeling). 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 your child has ever had a reaction to any contrast material used for x-rays.

Your child will need to lie still on a table while the scan is being done. Some younger children may be given medicine to help keep them calm or even asleep during the test. For the exam itself, the table moves in and out of the scanner, a ring-shaped machine that completely surrounds the table.

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.

CT scans can also be used to guide a biopsy needle precisely into a suspected tumor or metastasis. For this procedure, called a CT-guided needle biopsy, the child remains asleep on the CT scanning table, while a radiologist advances a biopsy needle through the skin and toward the mass. CT scans are repeated until the needle is within the mass. A biopsy sample is then removed and looked at under a microscope.

Ultrasound (ultrasonography)

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). The transducer gives off 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 on a computer screen.

This is an easy test to have done, and it uses no radiation. Your child simply lies on a table, and a technician moves the transducer over the part of the body being looked at.

Ultrasound is useful for looking at lymph nodes near the surface of the body. It can also be used to find masses in the abdomen or to detect if kidneys have become swollen because the outflow of urine has been blocked by enlarged lymph nodes.

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 and then released in a pattern formed by the type of body tissue and by certain diseases. A computer translates the pattern into very detailed images 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 most useful in looking the brain and spinal cord, and they may be done if a child has symptoms that might be caused by problems in the nervous system.

MRI scans take longer than CT scans, often up to an hour. Your child may have to lie inside a narrow tube, which is confining and can be distressing, so sedation is sometimes needed. Newer, more open MRI machines may be another option. The MRI machine makes loud buzzing and clicking noises that your child may find disturbing. Some places provide headphones or earplugs to help block this noise out.

Nuclear medicine tests

For these tests, a slightly radioactive solution is injected into the blood. It travels throughout the body and, depending on the substance used, collects in a specific area. A special type of camera is then used to get a picture of the active areas. These tests can often give information about how active tumors are, as opposed to just creating a picture of their structure.

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 are growing rapidly, they absorb large amounts of the 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 the whole body.

PET scans can also 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.

Some newer machines are able to perform both a PET and CT scan at the same time (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 areas of lymphatics in the body. A special camera can detect the radioactivity, showing the location of the gallium. These tests 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 lymphoma deposits that the PET scan may miss. Although the gallium scan does not detect most slow-growing lymphomas, it does recognize the more highly aggressive lymphomas. It can also be useful in distinguishing an infection from lymphoma when the diagnosis is uncertain.

Bone scan: For bone scans, a different radioactive substance (technetium) is used. After it is injected into a vein, it travels to areas of the bone that are damaged. Lymphoma in bone often causes damage, which a bone scan will detect. But a bone scan may also pick up non-cancerous problems, such as arthritis and fractures. This test is not usually done unless a child is having bone pain or has lab test results that suggest the lymphoma may have reached the bones.

Last Medical Review: 07/08/2009
Last Revised: 07/08/2009