The diagnosis of neuroblastoma often begins when parents see certain abnormal signs or symptoms in their child.

Signs and symptoms

The signs and symptoms of neuroblastoma can vary widely depending on the size and location of the original tumor, the extent of spread to other parts of the body, and whether or not the tumor cells secrete hormones.

Signs or symptoms caused by the main tumor

One of the most common signs of a neuroblastoma is an unusual lump or mass. These are usually found in the child's abdomen, causing it to swell. The child may not want to eat (which can lead to weight loss) or may complain of feeling full or having discomfort or pain. But the lump itself is usually not tender to the touch. Masses can also occur in other places such as the neck.

Sometimes, swelling from the tumor may affect parts of the body that do not contain any cancer cells, especially the legs and, in males, the scrotum. This happens when tumors in the abdomen or chest press against or invade and clog the blood and lymph vessels, preventing fluids from circulating back to the heart.

In some cases the pressure from a growing tumor can cause problems with the child's bladder or bowel.

Pressure from the tumor on, or invasion into, the superior vena cava (the large vein in the chest that returns blood from the head and neck to the heart) can cause swelling in the face or throat. This, in turn, may make it hard for the child to breathe or swallow.

Neuroblastomas that compress certain nerves in the chest or neck can sometimes cause other symptoms, such as drooping eyelids and small pupils (the black areas in the center of the eyes). Pressure on other nerves near the spine may affect the child's ability to feel or move the arms or legs.

Signs or symptoms caused by the spread of the tumor

About 2 out of 3 cases of neuroblastoma have spread to other parts of the body by the time they are found.

Neuroblastoma frequently spreads to bones. If this has occurred, a child who can talk may complain of pain in the bones. The pain may be so bad that the child limps or refuses to walk. If it spreads to the backbone, tumors may compress the spinal cord and cause weakness, numbness, or paralysis.

Blue or purple patches that look like small blueberries may indicate spread to the skin. Sometimes there is bruising around the eyes. In some cases the neuroblastoma may spread to the back of the eye, causing it to protrude (stick out slightly).

If the bone marrow (the inner parts of certain bones that make blood cells) is affected, the child may not have enough red blood cells, white blood cells, or blood platelets. These shortages of blood cells can result in tiredness, irritability, weakness, frequent infections, and excessive bleeding from small cuts or scrapes.

Rarely, bleeding can be caused by loss of clotting factors in the blood, which is due to clotting and excessive breakdown of tissue inside a large tumor. This is known as a consumption coagulopathy and can be life threatening.

A special widespread form of neuroblastoma (known as stage 4S) occurs only during the first few months of life. In this special form, the neuroblastoma has spread to the liver, to the skin, and/or to the bone marrow (in small amounts). The liver can become very large. Despite the fact that the cancer is already widespread when it is found, stage 4S neuroblastoma is very treatable, and almost all children can be cured, usually with minimal treatment.

Signs or symptoms caused by hormones from the tumor

Neuroblastoma is one of the few cancers in children that release hormones that can cause strange changes in the body. These changes are called paraneoplastic syndromes.

Symptoms of paraneoplastic syndromes can include:

• fever (in about 1 out of 4 children)
• constant diarrhea
• high blood pressure (causing irritability)
• rapid heartbeat
• reddening (flushing) of the skin
• sweating

An uncommon symptom is called the opsoclonus-myoclonus-ataxia syndrome or "dancing eyes, dancing feet." In this situation, the child has irregular, rapid eye movements (opsoclonus), twitch-like muscle spasms (myoclonus), and appears uncoordinated when standing or walking (ataxia). He or she may also have trouble speaking. For unknown reasons, neuroblastoma tumors that cause this syndrome tend to be less life-threatening than other forms of the disease.

Medical history and physical exam

If your child has signs or symptoms that may suggest a neuroblastoma, the doctor will want to take a complete medical history to check for more symptoms. A physical exam can provide information about signs of a neuroblastoma and other health problems. For example, the doctor may find a child has high blood pressure or may be able to see or feel an abnormal mass in the body.

If symptoms and/or the results of the physical exam suggest a neuroblastoma (or other tumor) might be present, more involved tests will likely be done. These might include blood and urine tests, imaging tests, and biopsies. These tests are important because many of the symptoms and signs of neuroblastoma can also be caused by other cancers or by non-cancerous diseases.

Blood and urine tests

Blood or urine catecholamine tests: Neuroblastoma can often be found by detecting substances called catecholamines in the blood or urine. Sympathetic nerve cells normally release certain chemicals called catecholamines, such as epinephrine (adrenaline). Eventually the body breaks these down into metabolites (smaller pieces), which are then passed out of the body in the urine.

In most cases, neuroblastoma cells make enough catecholamines to be detected by blood or urine tests. The 2 catecholamine metabolites most often measured are:

• homovanillic acid (HVA)
• vanillylmandelic acid (VMA)

Other lab tests: Your child's doctor will probably also order blood tests to check blood cell counts, liver and kidney function, and the salt balance in the body. A urinalysis (urine test) may also be done to further check kidney function.

Imaging tests

Imaging tests use x-rays, magnetic fields, sound waves, 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 out whether a suspicious area might be cancerous, to learn how far cancer may have spread, and to help determine if treatment has been effective. Most patients who have or may have cancer will have one or more of these tests.

Neuroblastoma patients are generally quite young, so it can be difficult to perform some of these tests. Parents and medical staff need to be very patient.

X-rays: X-rays can be useful for looking for cancer spread to the bones. An x-ray of the head may be done to be see if cancer has spread to the skull bones. A bone scan (described below) is usually better for looking at the bones in the rest of the body, but x-rays may be used in infants, where a bone scan might not be possible. A standard chest x-ray may be done if doctors suspect that the tumor has invaded the lungs, but a CT or MRI scan of the chest can show the area in more detail.

Computed tomography (CT or CAT) scan: CT scans can be useful to look for neuroblastoma in the abdomen, pelvis, and chest.

The CT scan is an x-ray test that produces detailed cross-sectional images of parts of the body. Instead of taking one picture, like a regular x-ray, a CT scanner takes many pictures as it rotates around your child while he or she lies on a table. A computer then combines these pictures into images of slices of the part of the body being studied. Unlike a regular x-ray, a CT scan creates detailed images of the soft tissues in the body.

Your child may be asked to drink a contrast solution and/or receive an IV (intravenous) line through which a contrast dye is injected. This helps better outline structures in the body. The contrast may cause some flushing (a feeling of warmth, especially in the face). Some people are allergic and get hives. Rarely, more serious reactions like trouble breathing or 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, but not as long as MRI scans. Your child will 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. Some people feel a bit confined by the ring they have to lie in while the pictures are being taken. In some cases, your child may be sedated (given medicine to make them sleepy) before the test to reduce movement and help make sure the pictures come out well.

In recent years, spiral CT (also known as helical CT) has become 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 with a standard CT. This lowers the chance of "blurred" images occurring as a result of breathing motion. It also lowers the dose of radiation received during the test. The biggest advantage may be that the "slices" it images are thinner, which yields more detailed pictures and allows doctors to look at suspicious areas from different angles.

CT-guided needle biopsy: CT scans can also be used to precisely guide a biopsy needle into a tumor. For this procedure, the patient remains 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 doctors are sure that 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 1/2-inch long and less than 1/8-inch in diameter) is then removed and looked at under a microscope. In children, this procedure is always done under general anesthesia (where the child is asleep).

Magnetic resonance imaging (MRI) scan: MRI scans provide detailed images of soft tissues in the body. But MRI scans use radio waves and strong magnets instead of x-rays, so there is no radiation involved. 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 may be injected into a vein before the scan to better see details, but contrast is needed less often than with a CT scan.

MRI scans are most helpful in looking at the brain and spinal cord. MRI may be slightly better than CT at evaluating the extent of neuroblastoma, but it can be more difficult for the child. MRI scans may take up to an hour to have done. For most MRI machines, your child has to lie inside a narrow tunnel, which can be confining. While newer "open" MRI machines can help with this, the test still requires a person to stay still for long periods of time. The machines also make buzzing and clicking noises that may be disturbing. This may require that the child is sedated before testing.

Ultrasound: Ultrasound uses sound waves whose echoes produce a picture of internal organs or masses. A small microphone-like instrument called a transducer emits sound waves and picks up the echoes as they bounce off body tissues. The echoes are converted by a computer into a black and white image that is displayed on a computer screen.

Ultrasound is a fairly quick and easy procedure that involves no radiation, which is why it is often one of the first tests done if an internal mass is suspected. To have an ultrasound exam, the child simply lies on a table (or the parent holds the child) and a technician moves the transducer over the skin overlying the part of the body being examined. Usually, the skin is lubricated with gel first.

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 or a mass. It is particularly useful in checking to see if internal tumors are shrinking.

MIBG scan: This scan uses a form of the chemical meta-iodobenzylguanidine (MIBG) that contains radioactive iodine. MIBG is similar to norepinephrine, a chemical made by sympathetic nerve cells. It is injected into a vein and travels through the bloodstream, and in most patients it will attach to neuroblastoma cells anywhere in the body. Several hours or days later, the body is scanned with a special camera to look for areas that picked up the radioactivity. This allows doctors to find the neuroblastoma and spot whether it has spread to the bones and/or other parts of the body.

This test is preferred by many doctors as a standard way to evaluate children with neuroblastoma. It can be repeated after treatment to see if it has been effective. It is also good to know if the tumor takes up the MIBG because in some cases, this radioactive molecule can be used (at higher doses) to treat the neuroblastoma (see the radiation therapy section in "How is neuroblastoma treated?").

Positron emission tomography (PET) scan: PET scans involve injecting a chemical like glucose (a form of sugar) that contains a radioactive atom into the blood. The amount of radioactivity used is very low. Because cancer cells in the body are growing rapidly, they absorb large amounts of the radioactive sugar. A special camera can then create a picture of areas of radioactivity in the body. The picture is not finely detailed like a CT or MRI scan, but it can provide helpful information about the whole body.

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 with the appearance of that area on the CT.

Bone scan: A bone scan can help show if a cancer has metastasized (spread) to the bones, and can provide a picture of the entire skeleton at once.

For this test, a small amount of low-level radioactive material (technetium-99) is injected into a vein (intravenously, or IV). The substance settles in areas of damaged bone throughout the entire skeleton over the course of 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. (This may require sedation fro smaller children.)

Areas of active bone changes appear as "hot spots" on the skeleton -- that is, they attract the radioactivity. These areas may suggest the presence of cancer, but other bone diseases can also cause the same pattern. To distinguish between these conditions, other imaging tests such as plain x-rays or MRI scans, or even a bone biopsy might be needed.

Neuroblastoma often causes bone damage, which a bone scan will find. This used to be a standard test, but it has been largely replaced by the MIBG scan.

Biopsies

Signs and symptoms, lab tests, and imaging tests may strongly suggest that a neuroblastoma is present, a biopsy (removing some of the tumor for viewing under a microscope and other lab testing) is the only way to be certain.

During a biopsy, the doctor removes a sample of the tumor mass. This is done either during an operation by cutting away a piece of the tumor through an opening on the skin (known as an incisional biopsy or open biopsy) or by placing a large, hollow needle through the skin and into the tumor (known as a needle biopsy or closed biopsy). In adults such biopsies are sometimes done using local anesthetic (numbing medicine), but in children they are more often done while the child is under general anesthesia (asleep).

The sample is then viewed under a microscope by a pathologist. Some cases of neuroblastoma are easily recognized when looked at by doctors experienced in testing children's tumor samples. But some cases may be hard to tell apart from other types of children's cancers. In these situations, special tests such as immunohistochemistry must be done. For this test, a portion of the sample is treated with special proteins (antibodies) that specifically attach to substances in neuroblastoma cells but not other cancers. Chemicals (stains) are then added so that cells containing these substances change color and can be easily recognized under a microscope. This lets the pathologist know that the tumor is a neuroblastoma.

Bone marrow aspiration and biopsy: Neuroblastoma often spreads to the bone marrow (the soft inner parts of certain bones). If blood or urine levels of catecholamines are increased, then finding cancer cells in a bone marrow sample is enough to diagnose neuroblastoma. If neuroblastoma has already been diagnosed by a biopsy done elsewhere in the body, bone marrow testing is done to help determine the extent of the disease.

A bone marrow aspiration and biopsy are usually done at the same time. In most cases the samples are taken from the back of both of the pelvic (hip) bones.

For a bone marrow aspiration, the child lies on a table (on his or her side or 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. In many cases, the child is also given other medicines to reduce pain or may even be 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. 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.

Samples from the bone marrow are sent to a pathology lab, where they are looked at and tested for the presence of cancer cells.

Last Medical Review: 10/22/2008
Last Revised: 10/22/2008