Tests for Neuroblastoma

Neuroblastomas are usually found when a child is brought to the doctor because of signs or symptoms they are having. If a neuroblastoma (or another type of tumor) is suspected, tests will be needed to confirm the diagnosis.

If a neuroblastoma is found, other tests will then be needed to learn more about it.

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 ask about the symptoms and how long they have been present. The doctor might also ask if there are any possible risk factors, such as a family history of neuroblastoma.

The doctor will examine your child for possible signs of a neuroblastoma or other health problems. For example, the doctor may feel the abdomen (belly) for any abnormal masses or swelling. The doctor might check for lumps or bumps under the skin and examine your child's eyes closely. They might also check child's blood pressure because sometimes neuroblastoma can cause 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 may 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), more tests will be done. These could include:

• Blood and urine tests
• Imaging tests
• 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

Cells in the body make many different types of hormones. For example, sympathetic nerve cells normally release hormones called catecholamines, such as epinephrine (adrenaline) and norepinephrine, which enter the blood and eventually break down into smaller pieces, called metabolites. The metabolites normally pass out of the body in urine. When epinephrine and norepinephrine are broken down by the body, the two most common metabolites made are:

• Homovanillic acid (HVA)
• Vanillylmandelic acid (VMA)

Neuroblastoma cells also often make these catecholamines, so these same metabolites can be detected in blood and urine. If the neuroblastoma cells are making catecholamines, the amount of HVA and VMA in urine or blood will be higher than expected.

If a child does have neuroblastoma, levels of HVA and VMA can also be followed during treatment to get an idea of how well it is working.

Other blood and urine 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 help 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 cancer
• To learn how far cancer has spread
• To help determine if treatment is working

Most children who have or might have neuroblastoma will get one or more of these tests, but they might not need all of them.

Children with neuroblastoma are often very young, so it can be hard to do some of these tests because the child might need to hold very still. Depending on the child's age and the imaging test being done, they might get medicines to make them drowsy (or even asleep) to help them keep still.

Ultrasound (sonogram)

Ultrasound uses sound waves and their echoes to look inside the body. This might be one of the first tests done in very young 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). Ultrasounds are usually not needed if the child has already had an MRI or CT scan.

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.)

Magnetic resonance imaging (MRI)

MRI scans provide detailed images of soft tissues in the body. These scans may be slightly better than CT scans for seeing the extent of a neuroblastoma tumor, especially around the spine.

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.

Computed tomography (CT or CAT) scan

CT scans combine many x-ray pictures to make detailed cross-sectional images of the inside of the body. These tests are often used to look for neuroblastoma in the abdomen, pelvis, and chest.

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.

CT-guided needle biopsy: CT scans can also be used to help guide a biopsy needle into a tumor. But needle biopsies (described below) aren't often done if neuroblastoma is suspected because the amount of the sample collected might not be enough for all of the tumor tests that are needed.

MIBG scan

This test is often an important part of finding out how far a child's neuroblastoma has spread. It is often done after a CT scan or MRI has been done.

For this test, a form of the chemical meta-iodobenzylguanidine (MIBG) that contains a small amount of radioactive iodine is injected into the blood. MIBG is similar to norepinephrine, a hormone made by sympathetic nerve cells, and in most patients it will attach to neuroblastoma cells anywhere in the body. Between 1 and 3 days later, the body is scanned with a special camera to look for areas that picked up the radioactivity. This helps doctors know where the neuroblastoma is and if it has spread to the bones and/or other parts of the body.

MIBG scans can be repeated after treatment to see if the tumors are responding well. 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 Radiation Therapy for Neuroblastoma).

The thyroid gland can also absorb MIBG, so a medicine containing iodine is sometimes given before, during, and after the test to protect the thyroid.

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 can be seen on a bone scan. This test isn’t often needed for neuroblastoma, because an MIBG scan can usually detect cancer spread to the bone. But if the MIBG scan doesn’t find cancer in the bone and the doctor still suspects it might have spread there, a bone scan might be helpful.

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.

Positron emission tomography (PET) scan

For a PET scan, a radioactive substance (usually a type of sugar called 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 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. They 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.

PET scans usually aren’t needed if an MIBG scan has been done. But a PET scan might be useful for some neuroblastomas, especially if the neuroblastoma cells do not absorb MIBG.

X-rays

X-rays can be used to look at the bones, although they aren’t as good at showing other structures in the body.

The doctor may order an x-ray of part of the body as an early test if a child is having symptoms and it’s not clear what might be causing them. But the pictures might not be good enough to spot tumors.

In children with neuroblastoma, an MIBG, PET, or bone scan is usually better than an x-ray for looking at the bones in the rest of the body and to see if neuroblastoma has spread to the bones, but an x-ray test might still be helpful in some situations.

Biopsies

During a biopsy, a doctor removes one or more pieces (samples) from the tumor for testing.

Exams and imaging tests might strongly suggest a child has neuroblastoma, but a biopsy is usually needed to be sure. (Some very young infants with small adrenal tumors seen on an imaging test might not need a biopsy. Instead, the tumor might be watched closely with further imaging tests, as these tumors often mature or go away on their own.)

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 is the most common type of biopsy for neuroblastoma. It 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 inserted 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. Needle biopsies are not usually helpful when a child might have neuroblastoma because the amount of tumor in the sample is often not enough to do all the special tests that are needed.

Once the biopsy samples have been removed, they are sent to a lab, where they are viewed under a microscope by a pathologist (a doctor with special training in identifying cancer cells). Special lab tests are often done on the samples as well to show if the tumor is a neuroblastoma.

If it is a neuroblastoma, lab tests can also help determine how quickly the tumor might grow or spread, as well as which treatments might work best. Some of these tests are described in Neuroblastoma Stages and Prognostic Markers.

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 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.

For a bone marrow biopsy, 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 Testing Biopsy and Cytology Specimens for Cancer.