Neuroblastoma

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Early Detection, Diagnosis, and Staging TOPICS

How is neuroblastoma diagnosed?

Neuroblastomas are usually found when a child is brought to the doctor because of signs or symptoms he or she is having. If a tumor is suspected, tests will be needed to confirm the diagnosis.

Medical history and physical exam

If your child has signs or symptoms that might be caused by a neuroblastoma (or another tumor), the doctor will want to get a complete medical history to learn more about the symptoms. The doctor might also ask if there’s a family history of any type of cancer.

The doctor will examine your child for possible signs of a neuroblastoma and other health problems. For example, the doctor may be able to see or feel an abnormal mass or swelling in the body or may find a child has lumps or bumps under the skin or high blood pressure. Neuroblastomas can sometimes grow close to the spinal cord, which can affect movement and strength in the child’s arms and legs, so the doctor will pay close attention to these.

Some signs that could be caused by neuroblastoma, such as fever and enlarged lymph nodes, are much more likely to be caused by an infection, so the doctor might look for other signs of infection at first.

If the history and exam suggest a child might have a neuroblastoma (or another type of tumor), other tests will be done. These could 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 diseases, such as infections, or even other types of cancer.

Blood and urine catecholamine tests

Sympathetic nerve cells normally release hormones called catecholamines, such as epinephrine (adrenaline) and norepinephrine, which enter the blood. Eventually the body breaks these down into metabolites (smaller pieces), which then pass out of the body in the urine.

Neuroblastoma cells can also make these hormones. 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

If neuroblastoma is suspected or has been found, your child’s doctor will probably order blood tests to check blood cell counts, liver and kidney function, and the balance of salts (electrolytes) 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 can be done for a number of reasons, including:

  • To help find out if a suspicious area might be cancerous
  • To learn how far cancer has spread
  • To help determine if treatment has been effective

Most children who have or might have neuroblastoma will have one or more of these tests.

Children with neuroblastoma are often very young, so it can be hard to do some of these tests.

Ultrasound

Ultrasound is often one of the first tests done in small children if a tumor is suspected, because it is fairly quick and easy, it does not use radiation, and it can often give the doctor a good view inside the body, especially in the abdomen (belly).

This test uses sound waves to create pictures of organs or masses inside the body. For this test, your child lies on a table (or sits on your lap) while a small wand called a transducer is placed on the skin over the belly (which is first lubricated with gel). The wand gives off sound waves and picks up the echoes as they bounce off organs. The echoes are converted by a computer into a black and white image on a screen. The test is not usually painful, but it might cause some discomfort if the transducer is pressed down hard on the belly.

Ultrasound is used most often to look for tumors in the abdomen. (It’s not used to look in the chest because the ribs block the sound waves.) Ultrasound can detect if kidneys have become swollen because the outflow of urine has been blocked by enlarged lymph nodes or a mass. It can also be used to help guide a biopsy needle into a suspected tumor to get a sample for testing. It is particularly useful in checking to see if tumors in the abdomen are shrinking.

The pictures from ultrasound aren’t as detailed as those from some other tests, so even if a tumor is found, CT or MRI scans (described below) might still be needed.

X-rays

The doctor may order an x-ray of the chest or another part of the body as an early test if a child is having symptoms but it’s not clear what might be causing them. But the images might not always be detailed enough to spot tumors.

If neuroblastoma has already been diagnosed, x-rays can be useful to see if cancer has spread to certain bones. An x-ray of the head may be done to see if cancer has spread to the skull bones. An MIBG scan or 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 these scans 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 are often used 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 showing 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.

Before the test, your child may be asked to drink a contrast solution and/or get an IV (intravenous) injection of a contrast dye. 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 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 scans are being done. During the test, the table slides in and out of the scanner. Younger children may be sedated (given medicine to make them sleepy) before the test to reduce movement and help make sure the pictures come out well.

CT-guided needle biopsy: CT scans can also be used to help guide a biopsy needle into a tumor. For this procedure, the child lies 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. 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. These scans are very helpful in looking at the brain and spinal cord. They may be slightly better than CT scans for seeing the extent of a neuroblastoma tumor, especially around the spine, but this test can be harder to do in small children.

MRI scans use radio waves and strong magnets to create the images instead of x-rays, so there is no radiation. A contrast material called gadolinium may be injected into a vein before the scan to better see details, but this is needed less often than with a CT scan. It usually does not cause allergic reactions, but it can cause other problems in children with kidney disease, so doctors are careful when they use it.

MRI scans take longer than CT scans, often up to an hour. For most MRI machines, your child has to lie inside a narrow tube, which is confining and can be distressing. Newer, more open MRI machines may be an option in some cases, but they still require the child to stay still for long periods of time. The MRI machine also makes loud buzzing and clicking noises that may be disturbing. Younger children are often given medicine to help keep them calm or even asleep during the test.

MIBG scan

This scan uses a form of the chemical meta-iodobenzylguanidine (MIBG) that contains a small amount of radioactive iodine. MIBG is similar to norepinephrine, a hormone made by sympathetic nerve cells. It is injected into a vein and travels through the blood, 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 helps doctors tell where the neuroblastoma is and whether it has spread to the bones and/or other parts of the body.

This test is preferred by many doctors as a standard test in 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).

Positron emission tomography (PET) scan

For a PET scan, a radioactive substance (usually a type of sugar related to glucose, known as 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 cancer cells in the body are growing quickly, they absorb large amounts of the radioactive 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. Younger children may be given medicine to help keep them calm or even asleep during the test. The picture from a PET scan is not as detailed as a CT or MRI scan, but it can provide helpful information about the whole body.

Some newer machines can do 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.

Bone scan

A bone scan can help show if a cancer has spread to the bones, and can provide a picture of the entire skeleton at once. Neuroblastoma often causes bone damage, which a bone scan can find. This test used to be done routinely, but in some centers it has been replaced by use of MIBG or PET scans.

For this test, a small amount of low-level radioactive material (technetium-99) is injected into a vein. (The amount of radioactivity used is very low and will pass out of the body within a day or so.) The substance settles in areas of damaged bone throughout the 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. Younger children may be given medicine to help keep them calm or even asleep during the test.

Areas of active bone changes attract the radioactivity and appear as “hot spots” on the skeleton. These areas may suggest cancer, but other bone diseases can also cause the same pattern. To help tell these apart, other imaging tests such as plain x-rays or MRI scans, or even a bone biopsy might be needed.

Biopsies

Exams and tests might strongly suggest a child has neuroblastoma, but a biopsy (removing some of the tumor for viewing under a microscope and other lab testing) is often done to be sure.

During a biopsy, the doctor removes a sample of the tumor mass. In adults, 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). There are 2 main types of biopsies:

  • Incisional (open or surgical) biopsy: This type of biopsy is done by removing a piece of the tumor through an incision (cut) in the skin. For tumors deep in the body this may be done laparoscopically using long, thin surgical tools inserted through small cuts in the skin.
  • Needle (closed) biopsy: For this type of biopsy, a thin, hollow needle is placed through the skin and into the tumor to remove a small sample. If the tumor is deep within the body, CT scans or ultrasound can be used to help guide the needle into the tumor.

The biopsy samples are sent to a lab, where they are viewed under a microscope by a pathologist (a doctor with special training in identifying cancer cells). Some neuroblastomas are easily recognized when looked at by experienced doctors. But some may be hard to tell apart from other types of children’s cancers. In these cases, special lab tests must be done to show the tumor is a neuroblastoma.

Other lab tests may also be done on neuroblastoma samples to help determine how quickly the tumor is likely to grow. Some of these are described in the section, “How is neuroblastoma staged?

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 (without getting a biopsy of the main tumor). If neuroblastoma has already been diagnosed by a biopsy done elsewhere in the body, bone marrow tests are 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.

Even when the area is numbed with local anesthetic, these tests can be painful, so in most cases the child is also given other medicines to reduce pain or even be asleep during the procedure.

For a bone marrow aspiration, a thin, hollow needle is 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 pushed down into the bone. Once the biopsy is done, pressure is applied to the site to help stop any bleeding.

Samples from the bone marrow are sent to a lab, where they are looked at and tested for the presence of cancer cells. You can read more about testing tissue samples in our document Testing Biopsy and Cytology Specimens for Cancer.


Last Medical Review: 03/14/2014
Last Revised: 03/17/2014