Neuroblastoma is a solid tumor or cancer that occurs in the developing cells of the sympathetic nervous system, which aids in the control of the body’s internal organs. The cells that make up neuroblastoma tumors are called neuroblasts. The majority of tumors (65%) begin in the adrenal glands, which are located on top of each kidney. However, tumors can begin anywhere in the body. Other common sites for neuroblastoma are the chest, neck and pelvis. While neuroblastoma may be found in only one spot in the body at the time of diagnosis in some patients, in others this cancer may have spread (metastasized) from its primary location to the lymph nodes, bone marrow or bones.
Many researchers believe that neuroblastoma develops when normal neuroblasts (the immature cells of the sympathetic nervous system) fail to mature into normal nerve cells. Instead, the neuroblasts grow and divide without the usual controls, leading to the growth of a cancerous mass of cells, also called a tumor.
Researchers have started to identify mistakes, or "mutations," that occur in genetic material – the DNA – of neuroblastoma cells. Why these mutations happen in the first place is still unknown. Many scientists believe that neuroblastoma and other children’s cancers are caused by a random mutation or mistake that happens during cell division.
Symptoms of NeuroblastomaThere are no symptoms of neuroblastoma that are common to all children with the disease. Rather, the symptoms are related to the location of the tumor. Common locations for neuroblastoma include the abdomen, the neck and chest. Some of the more common symptoms include:
- Abdominal swelling, pain, constipation or difficulty urinating if a tumor is present in the abdomen.
- A lump or bump in the neck that can sometimes be accompanied by drooping of the eyelid, a small pupil, and lack of sweating on the same side of the face.
- Bone pain
- Fatigue, if the disease has spread to the bone marrow
- Bleeding and bruising
- High blood pressure
- Rapid heartbeat
- Persistent diarrhea
There are many procedures and tests that might be done to see if and where cancer cells are present in the body. The exact combination of testing that will be used to diagnose a child is dependent upon the symptoms that are present and the suspected type of cancer.Quite often, some type of x-ray may have been done by your child’s primary care doctor. These exams are often repeated by the specialist. If there is a suspicion of neuroblastoma, it is important to be diagnosed and treated by a team with experience specific to children with cancer.
- Imaging tests are done to produce pictures of the inside of the body to determine the location and size of the neuroblastoma tumor. There are multiple types of exams that can be done to collect this information. Your doctor will choose those that will provide the best information regarding the extent of disease. Some of the most likely tests include:
- In about 90% of neuroblastoma cases, tumor cells produce elevated levels of hormones. The hormones are broken down by the body into acids called HVA and VMA, which are eliminated from the body in the urine. Your child will need to give a urine sample for the test to be done. If the HVA and VMA are elevated, the healthcare team may use urine tests to follow your child's disease and response to treatment. These urine tests can also be used later on to monitor your child for signs of recurrence of neuroblastoma.
- A complete blood count (CBC) will be done to check for low blood counts which may result from tumor growth in the bone marrow. A chemistry panel will also be done to check kidney and liver function.
- Once the tumor has been located, a sample of the tumor will be needed to make the diagnosis of neuroblastoma and to develop the best treatment plan. Doctors will perform surgery to remove either part (a biopsy) or all, of the tumor. The decision will be made based on the size and location of the tumor. Following surgery, the tumor that is removed will be reviewed by the pathologist and sent for special testing. Your healthcare team will identify the exact type of tumor and its particular characteristics. These factors are very important in determining the best treatment for your child.
- In some children, neuroblastoma will have spread to the bone marrow by the time of diagnosis. To evaluate your child, the healthcare team will perform a bone marrow aspirate and a bone marrow biopsy on both hips.
Determining Treatment and Risk of RelapseAfter your child undergoes testing to identify the extent of tumor present and to learn about the biology or characteristics of the tumor cells, the information gathered will determinethe likelihood of a recurrence of disease after treatment. Neuroblastoma is classified as low-, intermediate- or high-risk disease. The risk of relapse of neuroblastoma tumor is determined by the basic biology of the cancer cells, not on when the diagnosis is made. Factors for determining risk for relapse are:
- The age of the child at diagnosis: Many children under 18 months have "low risk" or “intermediate risk” disease, and the cancer is less likely to recur in these children.
- The stage of the disease: Staging refers to the physical location of the primary tumor and the location of any secondary tumors (metastases). Tumors are categorized by the International Neuroblastoma Staging System (INSS).
- Stage 1: Tumor is confined to one area (localized) and can be completely removed through surgery. Nearby lymph nodes do not contain cancer cells.
- Stage 2A: Tumor is localized and confined to one side of the body but cannot be completely removed. Nearby lymph nodes do not contain cancer cells.
- Stage 2B: Tumor is localized and may or may not be completely removed. Nearby lymph nodes show cancer cells. Enlarged lymph nodes on the opposite side of the body do not contain cancer cells.
- Stage 3: Must meet one of these criteria:
- Tumor starts in or crosses the vertical midline of the body (marked by the spine) and cannot be removed surgically. Lymph nodes in the area may or may not contain cancer cells.
- Tumor is restricted to one side of the body but there are enlarged lymph nodes on the opposite side of the body that contain cancer cells.
- Stage 4: The primary tumor(s) has spread to distant lymph nodes, bone, bone marrow, liver, skin and/or other organs.
- Stage 4-S: The “S” stands for “special.” These tumors are unique in that they often disappear on their own (spontaneous regression) without any treatment. Must meet special criteria:
- Child must be less than 12 months of age.
- Localized primary tumor that has spread only to the skin, lymph nodes or liver. Very small amounts of tumor may be seen in the bone marrow, but the disease cannot involve the outer portion of the bone (cortex).
- Tumor Histopathology: Histopathology refers to the evaluation of tumor cells under a microscope. A pathologist will determine the type of cells in the tumor and will decide whether the tumor is neuroblastoma or one of the related, but less aggressive related tumors called ganglioneuroblastoma or ganglioneuroma.
- MYCN Status: MCYN is a gene that is involved in regulation of the growth of some cells, including neuroblasts. Tumor cells are examined to determine the number of copies of the gene within the tumor cell. A single copy (non-amplified) is normal. Multiple copies of the MYCN gene (amplified) are associated with a more aggressive tumor type.
- DNA Index: The DNA content (ploidy) of a tumor cell is compared to that of a normal cell. Normal cells have a DNA index of 1. A DNA index of more than 1 is associated with a better outcome in some groups of children with neuroblastoma.
- Chromosomes: Certain consistent changes have been identified in the chromosomes of neuroblastoma tumor cells and their presence can help to determine a risk classification.
Understanding the risk for relapse is important because there are large differences between the treatments for low-risk, intermediate-risk and high-risk disease. In general, high-risk neuroblastomas are more likely to come back and therefore require stronger treatment than low- or intermediate-risk disease. Stronger treatment selected for high-risk disease has been shown to benefit patients; however, it also has more side effects. Therefore, risk assessment is an essential step in determining appropriate treatment.
International teams of neuroblastoma specialists have developed current treatment plans over several decades to carefully balance the benefits and risks of treatment and the chance that treatment will not be successful. Once your doctor has completed all the necessary tests and has assigned a risk category for your child, focus your attention on that particular risk group’s treatment section.
Risk of Relapse GroupsLow-risk patients have about a 95% probability of survival. Low-risk disease has the following characteristics:
- Any age with Stage I (completely removed) disease
- Stage II disease with non-amplified MYCN and > 50% of the tumor is removed by the surgeon
- Stage IV-S disease with non-amplified MYCN, DNA index >1 and favorable histology
- Stage II disease with non-amplified MYCN but < 50% of the tumor was removed
- Stage III disease in patients < 18 months and non-amplified MYCN
- Stage III disease in patients > 18 months with non-amplified MYCN and favorable histology
- Stage IV disease in patients < 12 months with non-amplified MYCN
- Stage IV disease in patients 12 - 18 months with non-amplified MYCN, favorable histology and DNA index of >1
- Stage IV-S disease, non-amplified MYCN and either unfavorable histology or a DNA index of 1
- Stage II, III, IV or IV-S disease with amplified MYCN
- Stage III disease in patients > 18 months with unfavorable histology
- Stage IV disease in patients 12 - 18 months with non-amplified MYCN, unfavorable histology or DNA index=1
- Stage IV disease in patients >18 months