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neuroblastoma

Neuroblastoma

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What is Neuroblastoma ? 

Neuroblastoma is a form of cancer that starts in certain types of very early forms of nerve cells found in an embryo or fetus. (The term neuro refers to nerves, while blastoma refers to a cancer that affects immature or developing cells). This type of cancer occurs in infants and young children. It is rarely found in children older than 10 years.

To understand neuroblastoma, it helps to know something about the sympathetic nervous system, which is where these tumors start.
 
About the sympathetic nervous system
The nervous system consists of the brain, spinal cord, and the nerves that reach out from them to all areas of the body. The nervous system is essential for thinking, sensation, and movement, among other things.
Part of the nervous system also controls body functions we are rarely aware of, such as heart rate, breathing, blood pressure, digestion, and other functions. This part of the nervous system is known as the autonomic nervous system.
The sympathetic nervous system is part of the autonomic nervous system. It includes:
Nerve fibers that run along either side the spinal cord.
Clusters of nerve cells called ganglia (plural of ganglion) at certain points along the path of the nerve fibers.
Nerve-like cells found in the medulla (center) of the adrenal glands. The adrenals are small glands that sit on top of each kidney. These glands make hormones such as adrenaline (epinephrine).
The main cells that make up the nervous system are called nerve cells or neurons. These cells interact with other types of cells in the body by releasing tiny amounts of chemicals (hormones). This is important, because neuroblastoma cells often release certain hormones that can cause symptoms.
 
Neuroblastomas
Neuroblastomas are cancers that start in early nerve cells of the sympathetic nervous system (sympathetic neuroblasts), so they can be found anywhere along this system.
A little more than 1 out of 3 neuroblastomas start in the adrenal glands. About 1 out of 4 begin in sympathetic nerve ganglia in the abdomen. Most of the rest start in sympathetic ganglia near the spine in the chest or neck or in the pelvis.
In rare cases, a neuroblastoma may have spread so widely by the time it is found that doctors can’t tell exactly where it started.
There is a wide spectrum of how neuroblastomas can behave. Some grow and spread quickly, while others grow slowly. Sometimes, in very young children, the cancer cells die without any cause and the tumor goes away on its own. In other cases, the cells sometimes mature on their own into normal ganglion cells and stop dividing. This causes the tumor to become a ganglioneuroma.
 
What are the risk factors for neuroblastoma?
A risk factor is anything that affects your chance of getting a disease such as cancer. Different cancers have different risk factors.
Lifestyle-related risk factors such as body weight, physical activity, diet, and tobacco use play a major role in many adult cancers. But these factors usually take many years to influence cancer risk, and they are not thought to play much of a role in childhood cancers, including neuroblastomas.
No environmental factors (such as exposures during the mother’s pregnancy or in early childhood) are known to increase the chance of getting neuroblastoma.
 
Age
Neuroblastoma is most common in very young children, but it is still rare even in this age group. It is very rare in people over the age of 10 years.
 
Heredity
In about 1% to 2% of all neuroblastomas, children may have inherited an increased risk of developing neuroblastoma. But the vast majority of neuroblastomas do not seem to be inherited.
Children with the familial form of neuroblastoma (those with an inherited tendency to develop this cancer) usually come from families with one or more affected members who had neuroblastoma as infants. The average age at diagnosis of familial cases is earlier than the age for sporadic (not inherited) cases.
Children with familial neuroblastoma may develop 2 or more of these cancers in different organs (for example, in both adrenal glands or in more than one sympathetic ganglion). It is important to distinguish neuroblastomas that start in more than one organ from neuroblastomas that have started in one organ and then spread to others (metastatic neuroblastomas). When tumors develop in several places at once it suggests a familial form. This may mean that other family members should consider genetic counseling and testing. Metastases can occur with either the familial or sporadic forms.
 
How is neuroblastoma diagnosed?
Neuroblastomas are usually found as a result of signs or symptoms that a child is having. If a tumor is suspected, tests will be needed to confirm the diagnosis.
 
Signs and symptoms
The signs and symptoms of neuroblastoma can vary widely, depending on the size and location of the tumor, the extent of spread to other parts of the body, and whether or not the tumor cells secrete hormones.
Many of the signs and symptoms below are more likely to be caused by something other than neuroblastoma. Still, if your child has any of these symptoms, check with your doctor so that the cause can be found and treated, if needed.
 
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 in the child’s abdomen, causing it to swell. The child may not want to eat (which can lead to weight loss). If the child is old enough, he or she may complain of feeling full or having belly pain. But the lump itself is usually not painful to the touch. Lumps can also occur in other places such as the neck.
Sometimes, swelling from a tumor in the abdomen may affect parts of the body that do not contain cancer, especially the legs and, in boys, the scrotum. This happens when a tumor presses against or invades and clogs the blood and lymph vessels, preventing fluids from getting back to the heart.
In some cases the pressure from a growing tumor can affect the child’s bladder or bowel, which can cause problems with urination, diarrhea, or constipation.
If the tumor is in the chest, it may press on the superior vena cava (the large vein in the chest that returns blood from the head and neck to the heart). This can cause swelling in the face, neck, arms, and upper chest (sometimes with a bluish-red skin color). It can also cause headaches, dizziness, and a change in consciousness if it affects the brain. The tumor may also press on the throat or windpipe, which may cause coughing and trouble breathing or swallowing.
Neuroblastomas that press on certain nerves in the chest or neck can sometimes cause other symptoms, such as a drooping eyelid and small pupil (the black area in the center of the eye). 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 the lymph nodes or other parts of the body by the time they are found.
Lymph nodes are bean-sized collections of immune cells found throughout the body. Cancer that has spread to the lymph nodes may cause them to swell. These nodes can sometimes be felt as lumps under the skin, especially in the neck, above the collarbone, under the arm, or in the groin. Enlarged lymph nodes in children are much more likely to be a sign of infection than cancer, but they should be checked by a doctor.
Neuroblastoma frequently spreads to bones. 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 press on the spinal cord and cause weakness, numbness, or paralysis in the arms or legs. Spread to the bones around the eyes is common and can lead to bruising around the eyes or cause an eyeball to stick out slightly. The cancer can also spread to other bones in the skull, causing bumps under the scalp.
If the cancer spreads to the bone marrow (the inner part of certain bones that makes blood cells), 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 excess bruising or bleeding from small cuts or scrapes.
Rarely, large tumors can start to break down, leading to a loss of clotting factors in the blood. This can result in a high risk of serious bleeding, which 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). Blue or purple bumps that look like small blueberries may be a sign of spread to the skin. The liver can become very large and can be felt as a mass on the right side of the belly. Despite the fact that the cancer is already widespread when it is found, stage 4S neuroblastoma is very treatable, and often shrinks or goes away on its own. Almost all children with this form of neuroblastoma can be cured.
 
Signs or symptoms caused by hormones from the tumor
Neuroblastoma is one of the few cancers in children that release hormones that can cause problems with distant tissues and organs, even though the cancer has not spread to those tissues or organs. These problems are called paraneoplastic syndromes.
 
Symptoms of paraneoplastic syndromes can include:
Constant diarrhea
Fever
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 reasons that are not clear, neuroblastomas 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 learn more about the symptoms. A physical exam can provide information about signs of a neuroblastoma and other health problems. For example, the doctor may be able to see or feel an abnormal mass 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, so the doctor may pay close attention to movement and strength in the child’s arms and legs.
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 may look for other signs of infection at first.
If symptoms or the results of the physical exam suggest a child might have a neuroblastoma (or another type of tumor), other tests will 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 diseases, such as infections, or even other types of cancer.
 
Blood and urine tests
Blood or urine catecholamine tests
Neuroblastoma can often be found by detecting catecholamines in the blood or urine. 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 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
If neuroblastoma is suspected or has been found, your child’s doctor will probably also 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 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
To help determine if treatment has been effective
Most patients who have or may have neuroblastoma will have one or more of these tests.
Neuroblastoma patients are generally quite young, so it can be hard to do some of these tests. Parents and medical staff need to be very patient.
 
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 and does not use radiation. This test uses sound wave echoes to create pictures of internal organs or masses. A small wand-like instrument called a transducer gives off 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 on a computer screen.
For an ultrasound exam, the child simply lies on a table (or the parent holds the child) and a technician moves the transducer across the skin over the part of the body being examined. Usually, the skin is lubricated with gel first.
Ultrasound is used most often to look at masses in the abdomen. (It’s not used in the chest because the ribs block the sound waves.) 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 will likely still be needed.
Ultrasound can also detect if kidneys have become swollen because the outflow of urine has been blocked by enlarged lymph nodes or a mass. Ultrasound 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.
 
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 may 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 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 the first test 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.
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 any allergies or 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 slides 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. Many medical centers now use spiral CT (also known as helical CT), which uses a faster machine that reduces the dose of radiation and gives more detailed pictures.
CT-guided needle biopsy: CT scans can also be used to help guide a biopsy needle into a tumor. For this procedure, the patient 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 fine needle biopsy sample or a larger core needle 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. But 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 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 assessing the extent of neuroblastoma, especially around the spine, but this test can be harder to do in children.
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 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 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.
 
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. 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. The picture is not as detailed as a CT or MRI scan, but it can provide helpful information about the whole body. Younger children may be given medicine to help keep them calm or even asleep during the test.
Some newer machines are able to 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 with the more detailed appearance of that area on the CT.
 
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 used to be a routine test, 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 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. 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 distinguish between these conditions, other imaging tests such as plain x-rays or MRI scans, or even a bone biopsy might be needed.
 
Biopsies
Signs and symptoms, lab tests, and imaging tests may strongly suggest a child has neuroblastoma, but 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. 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 cutting away a piece of the tumor through an opening on 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 hollow needle is placed through the skin and into the tumor. If the tumor is deep within the body, CT scans or ultrasound may be used to help guide the needle into the tumor.
The biopsy samples are then 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 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 attach to substances in neuroblastoma cells but not in other cancers. Chemicals (stains) are then added so that cells containing these substances change color and can be easily seen under a microscope. This lets the pathologist know that the tumor is a neuroblastoma.
Other types of lab tests may also be done on neuroblastoma samples to help determine how quickly the tumor is likely to grow. 
 
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 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 skin over the hip, the doctor numbs the area and the surface of the bone with local anesthetic, which may cause a brief stinging or burning sensation. Even with the local anesthetic, most patients still have some brief pain when the marrow is removed. In most cases, the child is also given other medicines to reduce pain or 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.
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. 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 lab, where they are looked at and tested for the presence of cancer cells.
 
How is neuroblastoma staged?
Staging is the process of finding out how far a cancer has spread. The outlook (prognosis) for people with cancer depends, to a large extent, on the cancer’s stage. The stage of a cancer is one of the most important factors in choosing treatment.
The stage of the neuroblastoma is based on results of physical exams, imaging tests, and biopsies of the main tumor and other tissues as well as the results of surgery.
For neuroblastoma, several other factors also affect prognosis, including a child’s age and certain tests of blood and tumor specimens. While these prognostic factors are not used to determine the stage of the cancer, they are used along with the stage to determine which risk group a child falls into, which in turn affects treatment options. 
 
International Neuroblastoma Staging System
A staging system is a standard way for the cancer care team to sum up the extent of the cancer. Since the mid-1990s, most cancer centers have used the International Neuroblastoma Staging System (INSS) to stage neuroblastoma. In simplified form, the stages are:
Stage 1: The cancer is still in the area where it started. It is on one side of the body (right or left). All visible tumor is totally removed by surgery (although looking at the tumor's edges under the microscope after surgery may show some cancer cells). Lymph nodes enclosed within the tumor may contain neuroblastoma cells, but lymph nodes outside of the tumor are free of cancer.
Stage 2A: The cancer is still in the area where it started and on one side of the body, but not all of the visible tumor could be removed by surgery. Lymph nodes enclosed within the tumor may contain neuroblastoma cells, but lymph nodes outside of the tumor are free of cancer.
Stage 2B: The cancer is on one side of the body, and may or may not be totally removed by surgery. Nearby lymph nodes outside the tumor contain neuroblastoma cells, but the cancer has not spread to lymph nodes on the other side of the body or elsewhere.
Stage 3: The cancer has not spread to distant parts of the body, but one of the following is true:
The cancer cannot be completely removed by surgery and it has crossed the midline (defined as the spine) to the other side of the body. It may or may not have spread to nearby lymph nodes.
The cancer is still in the area where it started and is on one side of the body. It has spread to lymph nodes that are relatively nearby but on the other side of the body.
The cancer is in the middle of the body and growing toward both sides (either directly or by spreading to nearby lymph nodes) and cannot be completely removed by surgery.
Stage 4: The cancer has spread to distant sites such as distant lymph nodes, bone, liver, skin, bone marrow, or other organs (but the child does not meet the criteria for stage 4S).
Stage 4S (also called “special” neuroblastoma): The child is younger than 1 year old. The cancer is on one side of the body. It may have spread to lymph nodes on the same side of the body but not to nodes on the other side. The neuroblastoma has spread to the liver, skin, and/or the bone marrow. However, no more than 10% of marrow cells may be cancerous, and imaging tests such as an MIBG scan do not show spread to the bones and/or the bone marrow.
Recurrent: While not formally part of the staging system, this term is used to describe cancer that has come back (recurred) after it has been treated. The cancer may come back in the area where it first started or in another part of the body.
 
International Neuroblastoma Risk Group Staging System
A risk-group staging system now coming into use is known as the International Neuroblastoma Risk Group Staging System (INRGSS). It is similar to the INSS, but it does not use the results of surgery to help define the stage. This lets doctors determine a stage before surgery, based on the results of imaging tests (usually a CT or MRI scan, and an MIBG scan), as well as exams and biopsies. The stage can then be used to help predict how resectable the tumor is – that is, how much of it can be removed with surgery.
The INRGSS uses image-defined risk factors (IDRFs), which are factors seen on imaging tests that might mean the tumor will be harder to remove. This includes things like the tumor growing into a nearby vital organ or growing around important blood vessels.
 
The INGRSS divides neuroblastomas into 4 stages:
L1: A tumor that has not grown from where it started and does not involve vital structures as defined by the list of IDRFs. It is confined to one body compartment, such as the neck, chest, or abdomen.
L2: A tumor that has not grown far from where it started (for example, it may have grown from the left side of the abdomen into the left side of the chest), but that has at least one IDRF.
M: A tumor that has spread (metastasized) to a distant part of the body (except tumors that are stage MS).
MS: Metastatic disease in children younger than 18 months with spread only to skin, liver, and/or bone marrow. No more than 10% of marrow cells may be cancerous, and an MIBG scan does not show spread to the bones and/or the bone marrow.
 
Prognostic markers
Prognostic markers are features that help predict whether the child's outlook for cure is better or worse than would be predicted by the stage alone. The following markers are used to help determine a child's prognosis.
 
Age
Younger children (under 12-18 months) are more likely to be cured than older children.
 
Tumor histology
Tumor histology is based on how the neuroblastoma cells look under the microscope. Tumors that contain more normal-looking cells and tissues tend to have a better prognosis and are said to have a favorable histology. Tumors whose cells and tissues look more abnormal under a microscope tend to have a poorer prognosis and are said to have an unfavorable histology.
 
DNA ploidy
The amount of DNA in each cell, known as ploidy or the DNA index, can be measured by special lab tests, such as flow cytometry or imaging cytometry. Neuroblastoma cells with about the same amount of DNA as normal cells (a DNA index of 1) are classified as diploid. Cells with increased amounts of DNA (a DNA index higher than 1) are termed hyperdiploid.
In infants, hyperdiploid cells tend to be associated with earlier stages of disease, respond better to chemotherapy, and usually predict a more favorable prognosis (outcome) than diploid cells. Ploidy is not as useful a factor in older children.
 
MYCN gene amplifications
MYCN is an oncogene, a gene that helps regulate cell growth. Changes in oncogenes can make cells grow and divide too quickly, as with cancer cells.
Neuroblastomas with too many copies (amplification) of the MYCN oncogene tend to grow quickly and are less likely to mature. Children whose neuroblastomas have this feature tend to have a worse prognosis than other children with neuroblastoma.
 
Other markers
These markers are not used to help determine risk groups at this time, but they are still important and may influence a doctor's decision on how to treat a child with neuroblastoma.
Chromosome changes: Tumor cells that are missing certain parts of chromosomes 1 or 11 (known as 1p deletions or 11q deletions) may predict a less favorable prognosis. It is thought that these chromosome parts, which are missing in many neuroblastomas, may contain important tumor suppressor genes, but more studies are needed to verify this.
Having an extra part of chromosome 17 (17q gain) is also linked with a worse prognosis. This probably means that there is an oncogene in this part of chromosome 17.
Understanding the importance of chromosome deletions/gains is an active area of neuroblastoma research.
Neurotrophin (nerve growth factor) receptors: These are substances on the surface of normal nerve cells and on some neuroblastoma cells. They normally allow the cells to recognize neurotrophins – hormone-like chemicals that help the nerve cells to mature.
Neuroblastomas that have more of certain neurotrophin receptors, especially the nerve growth factor receptor called TrkA, may have a better prognosis.
Serum markers: Serum (blood) levels of certain substances can be used to help predict prognosis.
Neuroblastoma cells release ferritin, a chemical that is an important part of the body's normal iron metabolism, into the blood. Patients with high ferritin levels tend to have a worse prognosis.
Neuron-specific enolase (NSE) and lactate dehydrogenase (LDH) are made by some types of normal cells as well as by neuroblastoma cells. Increased levels of NSE and LDH in the blood are often linked with a worse outlook in children with neuroblastoma.
A substance on the surface of many nerve cells known as ganglioside GD2 is often increased in the blood of neuroblastoma patients. Although the usefulness of GD2 in predicting prognosis is unknown, it may turn out to be more important in treating neuroblastoma.

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