Signs and Symptoms

Childhood non-Hodgkin lymphoma may cause many different signs and symptoms, depending on the location of the tumors.

If the lymphoma grows 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.) and causes the nodes to enlarge, the child, parent, or health care professional usually notice this.

When the lymphoma grows inside the abdomen, the abdomen can become swollen. There may also be a buildup of fluid that causes even more swelling.

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. The lymphoma may also block feces moving through the bowel. This bowel obstruction can cause nausea, vomiting, and severe abdominal pain.

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, or even suffocation.

The superior vena cava (SVC), a large vein that carries blood from the head and arms back to the heart, passes next to the thymus. Growth of the lymphoma may compress the SVC, causing swelling and bluish-red discoloration of the head, arms, and upper chest. This is known as SVC syndrome, and it can affect the brain and threaten the child's life. Children with SVC syndrome need immediate treatment.

In addition to symptoms and signs resulting from local effects of cancer growth, non-Hodgkin lymphoma can produce generalized symptoms such as fever, chills, or sweating (particularly at night). Weight loss is another sign. Oncologists sometimes call these effects of lymphoma "B symptoms."

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

Even in these instances, the child is usually given 2 weeks of antibiotics 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, for biopsy (examination of a tissue sample under the microscope and by other laboratory tests). But if the lymph nodes seem to be expanding quickly or the child’s health seems to be deteriorating, immediate action is needed.

Types of Biopsy Used to Diagnose Non-Hodgkin Lymphoma

Many of the symptoms of non-Hodgkin lymphoma are not unique enough to say for certain if cancer is present. Most of these symptoms can also be caused by noncancerous problems, like infections, or by other kinds of cancers. Also, the main types of childhood non-Hodgkin lymphoma have slightly different treatments but can cause the same signs and symptoms.

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 node and examining it under a microscope. This is called a biopsy.

There are several biopsy procedures, and doctors choose one 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 biopsy: Fine needle aspiration (FNA) biopsy uses a very thin needle and an ordinary syringe to withdraw a small amount of tissue from the lymph node. The doctor can aim the needle while feeling the enlarged node near the surface of the body. 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 cannot remove enough tissue for a definite diagnosis. However, advances in diagnostic techniques such as flow cytometry and molecular genetics (discussed later in this section) and the growing experience of many doctors with FNA have increased the success of this procedure.

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 can be done with local anesthesia (numbing medication used only at the biopsy site). But if the node is inside the chest or abdomen, then the child requires general anesthesia (the child is asleep). This method almost always provides enough tissue to make a diagnosis of the exact type of non-Hodgkin lymphoma.

Other Biopsy Procedures

These types of biopsies are more commonly done to help determine the extent of spread once a lymphoma has been diagnosed. However, they may also be used to initially diagnose the lymphoma.

Bone marrow aspiration and biopsy: These procedures help determine if a lymphoma is in the bone marrow. Bone marrow aspiration removes small bits of bone marrow tissue and fluid. Usually the sample is taken from the back of the pelvic (hip) bone.

First, the bone is numbed with a local anesthetic. In some cases, the child is also given medicine to reduce pain or put her or him to sleep during the procedure. A thin needle attached to a syringe is then put through the outer bone into the marrow space, where some marrow is sucked out (aspirated).

A biopsy follows, during which a small cylindrical piece of bone and bone marrow (about ¹/16-inch in diameter and ¹/2-inch long) is removed. Both samples are usually taken at the same time. 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 done to determine if the lymphoma has reached the brain or spinal cord. The doctor inserts a small needle between the bones in the child's spine in the lower back (below the level of the spinal cord to avoid nerve damage) to withdraw cerebrospinal fluid and look for lymphoma cells. Before inserting the needle, the doctor uses a local anesthetic to numb the skin.

Pleural or peritoneal fluid examination: Spread of lymphoma to the thin membranes that line the chest and abdominal cavities can cause fluid to accumulate. Pleural fluid (inside the chest) or peritoneal fluid (inside the abdomen) can be removed by placing a 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 examined under the microscope to check for lymphoma cells.

Laboratory Tests on Biopsy Specimens to Diagnose and Classify Non-Hodgkin Lymphoma

All biopsy specimens are examined 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 determines whether they all look the same. Sometimes this exam does not provide a definite answer and other laboratory tests are needed.

Flow cytometry: Flow cytometry may be used to examine the cells of a biopsy sample. It can help determine whether the lymph node is enlarged because of non-Hodgkin lymphoma, a benign growth (a noncancerous disease), or some other cancer. It also can help doctors determine the exact type of non-Hodgkin lymphoma so that they can select the proper treatment.

The cells being examined are treated with special laboratory antibodies and are passed in front of a laser beam. Each antibody sticks only to certain lymphoid cells. If the sample contains those cells, the laser light will cause them to give off light of a different color, which is measured exactly and analyzed by a computer.

Immunohistochemistry (IHC): As in flow cytometry, a part of the biopsy sample is treated with special laboratory antibodies. But instead of using a laser and computer for analysis, the cells are treated so that certain types of cells change color. The color change is seen under a microscope. Like flow cytometry, IHC is helpful in distinguishing different types of non-Hodgkin lymphoma from one another and from other diseases.

Cytogenetics: This test helps in identifying certain types of non-Hodgkin lymphoma by looking at cells’ chromosomes (pieces of DNA and protein that control the cells’ growth and metabolism). In certain types of lymphoma, part of one chromosome may be attached to part of a different chromosome (DNA translocation). This can be seen under a microscope or, as is more common now, detected by chemical methods (see next test).

Molecular genetic studies: Tests of lymphoma cell DNA can also detect translocations and other gene defects. DNA tests such as polymerase chain reaction (PCR) or fluorescent in situ hybridization (FISH) can find some translocations involving parts of chromosomes too small to be seen with usual cytogenetic testing under a microscope. This sophisticated test is not needed to diagnose most childhood lymphomas, but it is sometimes helpful in lymphoma classification because some subtypes of lymphoma have distinctive translocations.

Imaging Studies Used in Diagnosis and Staging of Non-Hodgkin Lymphoma

Imaging tests are used to find tumors inside the body. These tests are an important part of staging (the process of finding out how far a cancer has spread).

Chest x-ray: A chest x-ray is 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 an image of a slice of the body. The machine creates multiple images of the part of the body being studied. A CT scan is useful for looking at lymphoma in the abdomen, pelvis, and chest.

If the child is having a CT scan of the abdomen, after the first set of pictures is taken the child may be asked to drink 1 to 2 pints of a radiocontrast agent, or dye. This helps outline the intestine so that it is not mistaken for tumors. The child may also receive an intravenous (IV) injection of a radiocontrast material. This helps better outline structures in the body. The child will need an IV line through which the contrast dye is injected. A second set of pictures is then taken.

The injection can cause some flushing (redness and warm feeling). Some people are allergic to the dye and get hives or, rarely, more serious reactions like trouble breathing and low blood pressure can occur. Be sure to tell the doctor if your child has ever had a reaction to any contrast material used for x-rays.

CT scans take longer than regular x-rays. The child needs to lie still on a table while the part of the body to be examined is placed within the scanner, a doughnut-shaped machine that encircles the table.

A newer kind of CT, known as a spiral CT, uses a rapid scanner that takes quicker images. This reduces the chances that body movement caused by the patient taking breaths will distort the images, and therefore can provide greater detail.

CT scans can also be used to precisely guide a biopsy needle into an enlarged lymph node. For this procedure, called a CT-guided needle biopsy, the child remains asleep on the CT scanning table while a radiologist moves a biopsy needle toward the mass. CT scans are repeated until the doctors are sure that the needle is within the mass. A biopsy sample is then removed and examined under a microscope.

Magnetic resonance imaging (MRI) scan: 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 tissue and by certain diseases. A computer translates the pattern of radio waves given off by the tissues into a very detailed image of parts of the body. Not only does this produce cross-sectional slices of the body like a CT scanner, it also produces slices that are parallel with the length of your body. A contrast material might be injected just as with CT scans but is used less often. This contrast material usually does not cause allergic reactions.

MRI scans are helpful in examining the brain and spinal cord. MRI scans are a little more uncomfortable than CT scans. They take longer -- about an hour -- which may be too long for some children to lie in a confined space, so sedation is sometimes offered. The machine itself is also more constricting -- being in one can seem like being in a narrow tunnel. The machine also produces a humming or thumping noise, and some centers provide headphones with music to block this out.

Positron emission tomography (PET) scan: PET scans use glucose (a form of sugar) that contains a slightly radioactive atom. The glucose solution is injected into a vein and travels throughout the body. Cancer cells absorb high amounts of the radioactive sugar because of their high rate of metabolism. A special camera can then detect the radioactivity.

A PET scan can be more helpful than several different x-rays because it scans for lymphoma throughout the whole body. It can also tell if an enlarged lymph node contains lymphoma or is benign. Some centers are now combining it with CT scans to get a better quality image.

PET is also used after treatment in helping decide whether an enlarged lymph node still contains lymphoma or is merely scar tissue. Although this test is relatively new, it is becoming widely used to examine people with lymphomas.

Gallium scan: During this procedure, the radiologist injects a tiny amount of radioactive gallium 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 tumors that might be non-Hodgkin lymphoma in bones and other organs.

Although the gallium scan does not detect most slow-growing lymphomas, it does recognize the more highly aggressive lymphomas. It was used before PET scans and can still be useful in finding lymphoma deposits that the PET scan may miss. It is also useful in distinguishing an infection from lymphoma when the diagnosis is uncertain.

Bone scan: For bone scans, a different radioactive substance 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 noncancerous problems, such as arthritis and fractures. It is not generally used in the early staging process for non-Hodgkin lymphoma.

Ultrasound (ultrasonography): Ultrasound uses the echoes from sound waves to produce a picture of internal organs or masses. A small microphone-like instrument called a transducer emits sound waves. These high-frequency sound waves are transmitted into the area of the body being studied and echo back. The echoes are picked up by the transducer and converted by a computer into an image, which is displayed on a computer screen.

Ultrasound is an easy procedure. It uses no radiation, which is why it is often used to look at the developing fetuses of pregnant women. To have an ultrasound exam, the child simply lies on a table and a technician moves the transducer along the skin over the part of the body being examined. Usually, the skin is first lubricated with oil.

Sometimes an ultrasound is used to find masses in the abdomen. It can also detect if kidneys have become swollen because the outflow of urine has been blocked by enlarged lymph nodes. Last Revised: 03/08/2007