Neuroblastoma is a cancer that develops from immature nerve cells found in several areas of the body.
Neuroblastoma most commonly arises in and around the adrenal glands, which have similar origins to nerve cells and sit atop the kidneys. However, neuroblastoma can also develop in other areas of the abdomen and in the chest, neck and near the spine, where groups of nerve cells exist.
Neuroblastoma most commonly affects children age 5 or younger, though it may rarely occur in older children.
Some forms of neuroblastoma go away on their own, while others may require multiple treatments. Your child’s neuroblastoma treatment options will depend on several factors.
Signs and symptoms of neuroblastoma vary depending on what part of the body is affected.
Neuroblastoma in the abdomen — the most common form — may cause signs and symptoms such as:
- Abdominal pain
- A mass under the skin that isn’t tender when touched
- Changes in bowel habits, such as diarrhea or constipation
Neuroblastoma in the chest may cause signs and symptoms such as:
- Chest pain
- Changes to the eyes, including drooping eyelids and unequal pupil size
Other signs and symptoms that may indicate neuroblastoma include:
- Lumps of tissue under the skin
- Eyeballs that seem to protrude from the sockets (proptosis)
- Dark circles, similar to bruises, around the eyes
- Back pain
- Unexplained weight loss
- Bone pain
The cause of neuroblastoma is not well understood. The great majority of cases are sporadic and nonfamilial. About 1–2% of cases run in families and have been linked to specific gene mutations.
Occasionally, neuroblastoma may be due to a mutation inherited from a person’s parents. Environmental factors have not been found to be involved. Diagnosis is based on a tissue biopsy. Occasionally it may be found in a baby by ultrasound during pregnancy. At diagnosis, the cancer has usually already spread. The cancer is divided into low-, intermediate-, and high-risk groups based on a child’s age, cancer stage, and what the cancer looks like.
Cancer cells grow and multiply out of control. The accumulating abnormal cells form a mass (tumor).
Neuroblastoma begins in neuroblasts — immature nerve cells that a fetus makes as part of its development process.
As the fetus matures, neuroblasts eventually turn into nerve cells and fibers and the cells that make up the adrenal glands. Most neuroblasts mature by birth, though a small number of immature neuroblasts can be found in newborns. In most cases, these neuroblasts mature or disappear. Others, however, form a tumor — a neuroblastoma.
It isn’t clear what causes the initial genetic mutation that leads to neuroblastoma.
Children with a family history of neuroblastoma may be more likely to develop the disease. Yet, familial neuroblastoma is thought to comprise a very small number of neuroblastoma cases. In most cases of neuroblastoma, a cause is never identified.
Tests and procedures used to diagnose neuroblastoma include:
Physical exam. Your child’s doctor conducts a physical exam to check out any signs and symptoms. The doctor will ask you questions about your child’s habits and behaviors.
- Urine and blood tests. These may indicate the cause of any signs and symptoms your child is experiencing. Urine tests may be used to check for high levels of certain chemicals that result from the neuroblastoma cells producing excess catecholamines.
- Imaging tests. Imaging tests may reveal a mass that can indicate a tumor. Imaging tests may include an X-ray, ultrasound, computerized tomography (CT) scan, metaiodobenzylguanidine (MIBG) scan and magnetic resonance imaging (MRI), among others.
- Removing a sample of tissue for testing. If a mass is found, your child’s doctor may want to remove a sample of the tissue for laboratory testing (biopsy). Specialized tests on the tissue sample can reveal what types of cells are involved in the tumor and specific genetic characteristics of the cancer cells. This information helps your child’s doctor devise an individualized treatment plan.
- Removing a sample of bone marrow for testing. Your child may also undergo bone marrow biopsy and bone marrow aspiration procedures to see if neuroblastoma has spread to the bone marrow — the spongy material inside the largest bones where blood cells are formed. In order to remove bone marrow for testing, a needle is inserted into your child’s hipbone or lower back to draw out the marrow.
Once neuroblastoma is diagnosed, your child’s doctor may order further testing to determine the extent of the cancer and whether it has spread to distant organs — a process called staging. Knowing the cancer’s stage helps the doctor decide what treatment is most appropriate.
Imaging tests used to stage cancer include X-rays, bone scans, and CT, MRI and MIBG scans, among others.
The stages of neuroblastoma are indicated by Roman numerals that range from 0 to IV, with the lowest stages indicating cancer that is limited to one area. By stage IV, the cancer is considered advanced and has spread to other areas of the body.
When the lesion is localized, it is generally curable. However, long-term survival for children with advanced disease older than 18 months of age is poor despite aggressive multimodal therapy (intensive chemotherapy, surgery, radiation therapy, stem cell transplant, differentiation agent isotretinoin also called 13-cis-retinoic acid, and frequently immunotherapy with anti-GD2 monoclonal antibody therapy).
Biologic and genetic characteristics have been identified, which, when added to classic clinical staging, has allowed patient assignment to risk groups for planning treatment intensity. These criteria include the age of the patient, extent of disease spread, microscopic appearance, and genetic features including DNA ploidy and N-myc oncogene amplification (N-myc regulates microRNAs , into low, intermediate, and high risk disease. A recent biology study (COG ANBL00B1) analyzed 2687 neuroblastoma patients and the spectrum of risk assignment was determined: 37% of neuroblastoma cases are low risk, 18% are intermediate risk, and 45% are high risk. (There is some evidence that the high- and low-risk types are caused by different mechanisms, and are not merely two different degrees of expression of the same mechanism.)
The therapies for these different risk categories are very different.
- Low-risk disease can frequently be observed without any treatment at all or cured with surgery alone.
- Intermediate-risk disease is treated with surgery and chemotherapy.
- High-risk neuroblastoma is treated with intensive chemotherapy, surgery, radiation therapy, bone marrow / hematopoietic stem cell transplantation, biological-based therapy with 13-cis-retinoic acid (isotretinoin or Accutane) and antibody therapy usually administered with the cytokines GM-CSF and IL-2.
With current treatments, patients with low and intermediate risk disease have an excellent prognosis with cure rates above 90% for low risk and 70–90% for intermediate risk. In contrast, therapy for high-risk neuroblastoma the past two decades resulted in cures only about 30% of the time. The addition of antibody therapy has raised survival rates for high-risk disease significantly. In March 2009 an early analysis of a Children’s Oncology Group (COG) study with 226 high-risk patients showed that two years after stem cell transplant 66% of the group randomized to receive ch14.18 antibody with GM-CSF and IL-2 were alive and disease-free compared to only 46% in the group that did not receive the antibody. The randomization was stopped so all patients enrolling on the trial will receive the antibody therapy.
Chemotherapy agents used in combination have been found to be effective against neuroblastoma. Agents commonly used in induction and for stem cell transplant conditioning are platinum compounds (cisplatin, carboplatin), alkylating agents (cyclophosphamide, ifosfamide, melphalan), topoisomerase II inhibitor (etoposide), anthracycline antibiotics (doxorubicin) and vinca alkaloids (vincristine). Some newer regimens include topoisomerase I inhibitors (topotecan and irinotecan) in induction which have been found to be effective against recurrent disease.
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Between 20% and 50% of high-risk cases do not respond adequately to induction high-dose chemotherapy and are progressive or refractory. Relapse after completion of frontline therapy is also common. Further treatment is available in phase I and phase II clinical trials that test new agents and combinations of agents against neuroblastoma, but the outcome remains very poor for relapsed high-risk disease.
Most long-term survivors alive today had low or intermediate risk disease and milder courses of treatment compared to high-risk disease. The majority of survivors have long-term effects from the treatment. Survivors of intermediate and high-risk treatment often experience hearing loss. Growth reduction, thyroid function disorders, learning difficulties, and greater risk of secondary cancers affect survivors of high-risk disease. An estimated two of three survivors of childhood cancer will ultimately develop at least one chronic and sometimes life-threatening health problem within 20 to 30 years after the cancer diagnosis.
Disclaimer: This information is not meant to be a substitute for professional medical advise or help. It is always best to consult with a Physician about serious health concerns. This information is in no way intended to diagnose or prescribe remedies.This is purely for educational purpose.