How Is Non-Hodgkin Lymphoma Diagnosed in Children?
Non-Hodgkin lymphoma (NHL) is usually found when a child is brought to a doctor because of signs or symptoms he or she is having. The doctor might suspect a child could have a lymphoma based on the signs and symptoms, but tests are needed to confirm the diagnosis. The exams and tests below are used to diagnose the disease, to find out what type of lymphoma it is, and to learn how advanced it is.
Medical history and physical exam
If any signs and symptoms suggest a child might have lymphoma, the doctor will want to get a thorough medical history to learn more about the symptoms and how long they have been present. The doctor might also ask if there is any history of possible risk factors, such as immune system problems.
During the physical exam, the doctor will probably focus on any enlarged lymph nodes or other areas of concern. For example, the abdomen may be felt for signs of an enlarged spleen or liver. Enlarged lymph nodes in children are usually caused by infections, so the doctor will look for an infection in the part of the body near any swollen lymph nodes.
Because infections are the most common cause of enlarged lymph nodes, this is often what doctors think of first, so the diagnosis of NHL in a child can sometimes be delayed. There is usually little cause for concern in children with swollen lymph nodes unless they are very large (more than 1 inch across). Even in these instances, the child is usually watched closely for a time or given a course of antibiotics first to see if the nodes will shrink. If not, more tests are done, usually a biopsy removing a swollen node (or a large portion of it) (see next section). But if the lymph nodes seem to be growing quickly or the child’s health seems to be getting worse, a biopsy may be needed right away.
A doctor can’t make a diagnosis of NHL in a child based only on symptoms or a physical exam. Most of the symptoms NHL can cause are more often caused by non-cancerous problems, like infections. They may also be caused by other kinds of cancers. If a child does have NHL, it’s important to tell which type it is, because each type is treated slightly differently.
For these reasons, an accurate diagnosis is needed, and the only way to do this is to remove some or all of an abnormal lymph node (or tumor) 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 situation. The goal is to get a sample large enough to make an accurate diagnosis as quickly as possible, with as few side effects as possible.
Excisional or incisional biopsy: These are the most common types of biopsy done if lymphoma is suspected. An exception might be for large tumors in chest, for which a needle biopsy (described below) might be used instead.
In these procedures, a surgeon cuts through the skin to remove either an entire lymph node (excisional biopsy) or a small part of a large tumor (incisional biopsy).
If the node is near the skin surface, this is an operation that might be done with either local anesthesia (numbing medicine used only at the biopsy site) and sedation or with general anesthesia (where the child is in a deep sleep). If the node is inside the chest or abdomen, then general anesthesia is usually needed.
This method almost always provides enough of a sample to diagnose the exact type of NHL.
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 an enlarged lymph node is near the surface, the doctor can aim the needle while feeling the node. If the enlarged node or tumor is deep in the body (such as in the chest or abdomen), the doctor can guide the needle while watching it on a CT scan or ultrasound (see discussion of imaging tests later in this section).
The main advantage of a needle biopsy is that it does not require surgery. This can be especially important for tumors in the chest, because general anesthesia (where the child is in a deep sleep) can sometimes be dangerous for these children. It is also useful when the lymphoma is in other sites outside of the lymph nodes, such as the bones.
In children, needle biopsies can often be done using local anesthesia to numb the area, along with sedation to make the child sleepy. General anesthesia is needed less often.
The main drawback of needle biopsies (especially FNA) is that in some cases the needle might not remove enough of a sample to make a definite diagnosis. Most doctors don’t use needle biopsies if they strongly suspect lymphoma (unless other types of biopsies can’t be done for some reason). But if the doctor suspects that lymph node swelling is caused by an infection (even after antibiotics), a needle biopsy may be the first type of biopsy done. If a biopsy is needed, doctors typically prefer to do a core biopsy instead of FNA. 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 other types of biopsies are not normally used to diagnose lymphoma, but they might be done to help determine the extent of spread if a lymphoma has already been diagnosed.
Bone marrow aspiration and biopsy: These tests help determine if a lymphoma has reached the bone marrow. The 2 tests are usually done at the same time. The biopsy samples are usually taken from the back of the pelvic (hip) bones, although in some cases they may be taken from the front of the hip bones or from other bones.
For a bone marrow aspiration, the skin over the hip and the surface of the bone is numbed with local anesthetic. In most cases, children will be given other medicines to make them drowsy or brief general anesthesia so they are asleep during the biopsy. 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 is removed with a slightly larger needle that is put into the bone. Once the biopsy is done, pressure will be applied to the site to help stop any bleeding.
Lumbar puncture (spinal tap): This test 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 usually also gives the child medicine to make him or her sleep during the procedure. A small, hollow needle is then placed between the bones of the spine to withdraw some of the fluid.
In children already diagnosed with lymphoma, a lumbar puncture can also be used to put chemotherapy drugs into the CSF to try to prevent or treat the spread of lymphoma to the spinal cord and brain.
Pleural or peritoneal fluid sampling: If lymphoma spreads to the thin membranes that line the inside of the chest and abdomen it can cause fluid to build up. Pleural fluid (inside the chest) or peritoneal fluid (inside the abdomen) can be removed using a hollow needle put through the skin into the chest or abdomen.
Before the procedure, the doctor uses a local anesthetic to numb the skin and may give the child other medicines so they are drowsy or asleep during the procedure. The fluid is then drawn out and looked at under the microscope to check for lymphoma cells.
When this procedure is used to remove fluid from the chest, it’s 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 using lab tests to identify cancer cells). The doctor looks at the size and shape of the cells and how they are arranged. This may reveal not only if a child has 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 child has by looking at the cells, but usually other types of lab 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 can help distinguish different types of NHL from one another and from other diseases.
Like immunohistochemistry, this test looks for certain substances on the outer 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 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.
Doctors use this technique 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. Some lymphoma cells may also have too many chromosomes, too few chromosomes, or other chromosome changes. These changes can be used to 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 can be seen under a microscope on cytogenetic tests, as well as others that can’t be seen.
Fluorescent in situ hybridization (FISH): FISH is similar to cytogenetic testing. It uses pieces of DNA that only attach to specific parts of chromosomes. The DNA is linked to fluorescent dyes that can be seen with a special microscope. FISH can find most chromosome changes (such as translocations) that can be seen under a microscope on 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): This is a very sensitive DNA test that can also find some chromosome changes too small to be seen under a microscope, even if there are very few lymphoma cells 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 might be one of the first types of tests done in children with symptoms to help the doctor determine what is going on.
If a child has been diagnosed with lymphoma, these tests can also sometimes help determine how advanced the lymphoma is.
The complete blood count (CBC) is a test that measures the levels of different cells in the blood, such as the red blood cells, the white blood cells, and the platelets. In children already known to have lymphoma, low blood cell counts might mean that the lymphoma is growing in the bone marrow and damaging new blood cell production.
Blood levels of a chemical called LDH will often be abnormally high in patients with fast-growing lymphomas.
Blood chemistry tests can help detect liver or kidney problems caused by the spread of lymphoma cells or 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.
For some types of lymphoma, the doctor might also want to order other blood tests to see if the child has been infected with certain viruses, such as the Epstein-Barr virus (EBV), hepatitis B virus (HBV), or human immunodeficiency virus (HIV). Infections with some of these viruses can affect your child’s treatment.
Imaging tests 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. In a child with known or suspected lymphoma, these tests might be done to look more closely at an abnormal area that might be lymphoma, to learn how far the lymphoma may have spread, or to find out if treatment has been effective. Children with NHL usually get some (but not all) of the following imaging tests.
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 test that produces detailed, cross-sectional images of the body. Unlike a regular x-ray, CT scans can show the detail in soft tissues (such as internal organs). They can help tell if any lymph nodes or organs in the body are enlarged. CT scans can be used to look for enlarged lymph nodes or other masses in the chest, abdomen, pelvis, head, and neck.
Instead of taking one picture, like a standard x-ray does, a CT scanner takes many pictures as it rotates around the child. A computer then combines these pictures into images of slices of the part of the body being studied.
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 any allergies or has ever had a reaction to any contrast material used for x-rays.
CT scans take longer than regular x-rays. A CT scanner has been described as a large donut, with a narrow table in the middle opening. Your child will need to lie still on the table while the scan is being done. During the test, the table slides in and out of the scanner. Some younger children may be given medicine to help keep them calm or even asleep during the test to help make sure the pictures come out well.
CT-guided needle biopsy: CT scans can also be used to guide a biopsy needle precisely into a suspected tumor or enlarged lymph node. For this procedure, 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 uses sound waves and their echoes to produce a picture of internal organs or masses.
Ultrasound can be used to look at lymph nodes near the surface of the body or to look inside the abdomen (belly) for enlarged lymph nodes or organs such as the liver, spleen, and kidneys. (It can’t be used to look inside the chest because the ribs block the sound waves.) It is also sometimes used to help guide a biopsy needle into an enlarged lymph node.
For this test, a small wand called a transducer is moved around 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 usually an easy test to have, 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. The test is not usually painful, but it might be uncomfortable if the transducer is pressed down hard on the abdomen.
Magnetic resonance imaging (MRI) scan
An MRI scan, like a CT scan, gives detailed images of soft tissues in the body. This test is not used as often as CT scans for lymphoma, but MRI is very useful for looking at the brain and spinal cord if a child has symptoms that might be caused by problems in the nervous system.
MRI scans use radio waves and strong magnets instead of x-rays, so there is no radiation. 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 take longer than CT scans, often up to an hour. Your child may have to lie inside a narrow tube, which can be distressing, so sedation is sometimes needed. Newer, more open MRI machines may be another option, although your child will still have to lie still. 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.
Positron emission tomography (PET) scan
For a PET scan, a form of radioactive sugar (known as fluorodeoxyglucose or FDG) is injected into the blood. (The amount of radioactivity used is very low and will pass out of the body within a day or so.) Because lymphoma cells grow quickly, they absorb large amounts of the sugar. After about an hour, your child will be moved onto a table in the PET scanner. He or she will 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 provides helpful information about the whole body.
PET scans can be used for many reasons in a child with lymphoma:
- They can help tell if an enlarged lymph node contains lymphoma or is benign.
- They can help spot small areas in the body that might be lymphoma, even if the area looks normal on a CT scan.
- They can help 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 as much of the radioactive sugar.
- They can be used after treatment in helping decide whether an enlarged lymph node still contains lymphoma or is merely scar tissue.
Some newer machines can do both a PET and CT scan at the same time (PET/CT scan). This lets the doctor compare areas of higher radioactivity on the PET scan with the more detailed appearance of that area on the CT scan.
This test is not usually needed unless a child is having bone pain or has lab test results that suggest the lymphoma might have reached the bones.
For a bone scan, a radioactive substance called technetium is injected into the blood. (The amount of radioactivity used is very low and will pass out of the body within a day or so.)
The substance travels to damaged areas of the bone over a couple of hours. Your child then lies on a table for about 30 minutes while a special camera detects the radioactivity and creates a picture of the skeleton. Younger children may be given medicine to help keep them calm or even asleep during the test.
A bone scan can detect bone damage from lymphoma. But a bone scan may also pick up non-cancerous problems, so other tests might be needed to be sure.
Last Medical Review: March 7, 2014 Last Revised: January 27, 2016
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