- Donate
- Understanding Rare Disease
- Living with a Rare Disease
- Community Support
- Advancing Research
- Driving Policy
- Get Involved
- Rare Disease News
- Resource Library
- About Us
- For Clinicians & Researchers
- For Patient Organizations
Last updated: 6/4/2025
Years published: 2025
NORD gratefully acknowledges Rochelle Bagatell, MD, Professor of Pediatrics (Division of Oncology), Children’s Hospital of Philadelphia, for assistance in the preparation of this report.
Neuroblastoma is a type of cancerous tumor in children that starts in cells of the sympathetic nervous system. It is the most common cancer in infants and the third most common childhood cancer behind leukemia/lymphoma and brain cancer. It is the most common solid tumor to occur outside of the brain in children.1
Neuroblastoma is an overgrowth of immature nerve cells known as neural crest cells.1 These cells are present in embryos and under normal circumstances, develop into functioning tissue of the sympathetic nervous system. This part of the nervous system is outside of the brain and spinal cord and is responsible for preparing a person to deal with stressful situations or fight-or-flight responses, including release of hormones from the adrenal glands. Neuroblastoma can form in the adrenal glands and in sympathetic nervous system tissue elsewhere in the abdomen, chest, neck and pelvis.2 It can spread to the bone, bone marrow and lymph nodes and can sometimes spread to the skin or liver. The lungs and brain are less commonly involved at the time of diagnosis but may be involved at the time of relapse.3
The symptoms of neuroblastoma depend on the tumor’s location and whether it has spread.2 The tumor’s behavior varies quite a bit between individual patients — it can be aggressive, spreading to more than one part of the body; it can grow in its original location but not spread to other body parts; it can mature into a benign tumor; or it can spontaneously disappear without any treatment.4
How neuroblastoma is treated depends on whether the tumor is in one location or in multiple sites in the body (metastatic) at diagnosis (disease stage), the patient’s age at diagnosis and other factors such as the appearance under the microscope and the genetic and molecular features of the tumor. Treatment ranges from observation alone to a combination of surgery, chemotherapy, radiation, high dose chemotherapy with stem cell transplantation, immunotherapy and other medications designed to eliminate small amounts of residual disease.5
Most neuroblastomas form in the abdomen, usually in the adrenal glands that sit atop the kidneys. Neuroblastomas can also start in the chest, neck and pelvis and can spread to the bone, bone marrow and lymph nodes. Sometimes it can spread to the skin or liver. The lungs and brain are less commonly involved at the time of diagnosis but may be involved at the time of relapse.3,4 Because neuroblastomas can occur in various regions of the body, the signs and symptoms can vary quite a bit. Some people with neuroblastoma have no symptoms. Other people with more widespread disease have bone pain, fatigue and fevers. If a tumor involves the region near the spinal cord, the person can have neurological problems.2
Some general symptoms of neuroblastoma include a mass where the neuroblastoma formed, pain, weight loss, irritability and fever. A neuroblastoma in the chest can cause respiratory symptoms.3 Other possible symptoms based on the most common areas where neuroblastoma forms include:2,3
Abdominal masses
Chest and neck masses
Pelvic masses
Neuroblastomas can also form near the spine or spread to the bones near the spine, causing neurological problems like difficulty feeling or moving body parts.2 Other signs and symptoms of neuroblastoma are associated with the tumor’s spread (metastasis) to other areas of the body, such as the bones near the eyes, bone marrow, skin, liver and lymph nodes, and less commonly to the lungs or brain.2,6 Spread of the tumor around the eyes leads to signs of eye bulging and bruising. Metastasis to the bone marrow can lead to anemia, pallor, fatigue and less commonly easy bruising or bleeding.2,6 Bluish lumps underneath the skin are associated with metastasis to the skin, most commonly seen in infants.6 Symptoms of neuroblastoma in the brain include headaches, dizziness and changes in consciousness; this is more common at the time of disease recurrence than at the time of diagnosis.3
Children with neuroblastoma may also have symptoms related to syndromes that can accompany these tumors; these syndromes are called paraneoplastic syndromes. A well-described paraneoplastic syndrome associated with neuroblastoma is a condition known as opsoclonus myoclonus ataxia syndrome.7 This syndrome is an autoimmune response in which a person’s immune system attacks healthy nerve tissue as a response to neuroblastoma. Signs and symptoms of this condition include rapid eye movements, muscles spasms, jerking of the limbs or trunk, irritability and discoordination.2,3 Vasoactive intestinal peptide (VIP) syndrome is a rarer paraneoplastic syndrome associated with neuroblastoma. People with VIP syndrome have profuse watery diarrhea that can cause severe electrolyte imbalances.8
The exact causes of neuroblastoma are unknown.6
A small percentage of neuroblastoma cases (1%-2%) are hereditary.1 This happens when a child’s normal cells have a gene change (variant) that increases the chance for the child to develop neuroblastoma. Variants in the ALK gene (most hereditary cases) and the PHOX2B gene (a minority of hereditary cases) can be inherited from a parent or occur for the first time (de novo) in the affected child.
Genetic conditions caused by variants in RAS pathway genes can increase the risk of neuroblastoma including Costello syndrome, Noonan syndrome and neurofibromatosis type 1.1 Beckwith-Weidemann syndrome is also associated with the development of neuroblastoma. Li-Fraumeni syndrome (due to variants in the p53 gene), Weaver syndrome (due to variants in the EZH2 gene) and familial pheochromocytoma/paraganglioma (associated with SDH2 gene variants) have also been associated with an increased risk for neuroblastoma and related tumors. Genetic changes that have been linked to Fanconi anemia have also been linked to neuroblastoma predisposition. Although the genetic basis for ROHHAD (rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation) syndrome has not been identified, people with this syndrome are also at increased risk for neuroblastoma and related tumors.
Neuroblastoma affects slightly more boys than girls and appears to occur with the same frequency in all countries and ethnic groups.1 It occurs in 1/70,000 children per year in the United States (approximately 700 to 800 people are diagnosed each year in the U.S.).9,10
Neuroblastoma affects mostly young children — 90% are diagnosed in children younger than 5 years old, with 40% diagnosed before they reach 1 year of age.1,9 The average age of neuroblastoma diagnosis is between 1 and 2 years old.11 Children with an inherited form of neuroblastoma are more likely to develop the disease at a younger age.11 However, neuroblastoma can occur in teenagers and, in very rare cases, may not be diagnosed until adulthood.6
A diagnosis of neuroblastoma is suspected based on the detection of the tumor on imaging like ultrasound, CT, or MRI.9 The diagnosis is confirmed based on examination of a tumor or bone marrow sample under a microscope.2
Most neuroblastomas release hormones called catecholamines. Adrenaline, the hormone responsible for the fight-or-flight response, is an example of a catecholamine. Catecholamines are broken down into the chemicals vanillylmandelic acid (VMA) and homovanillic acid (HVA). These byproducts are detected in the blood and urine of 70%- 90% of people with neuroblastoma and may support the diagnosis of neuroblastoma.
Abdominal neuroblastomas are often first investigated with ultrasound imaging. Sometimes, prenatal ultrasound can detect a neuroblastoma in a developing fetus.2,10 CT scans or MRI studies may also be used to detect masses and allow for clarity regarding the relationship of tumors to nearby normal structures in the body. MRI is especially useful when neuroblastomas are suspected to be near the spine.2
After a tumor is found on ultrasound, CT, or MRI, another imaging study known as an MIBG scan is used to see if the neuroblastoma has spread to other sites in the body.2 For this test, a radioactive substance that neuroblastoma cells absorb is injected into the patient. The scan is then performed the following day to detect the locations of neuroblastoma cells and the extent of spread. When positive, MIBG scans can be repeated during and after a patient’s treatment to monitor the response to treatment.14 In some people, a neuroblastoma may not take up the radioactive substance used during an MIBG scan, and they may have a negative MIBG scan. If the doctor still suspects neuroblastoma after the patient has a negative MIBG scan, they may order a PET scan to see if cancer cells can be detected in other areas of the body. PET scans use another radioactive substance, usually a sugar, that cancer cells will absorb.2,14
If laboratory and imaging tests are highly suggestive of neuroblastoma, a biopsy of the tumor or the bone marrow (for patients whose cancer has spread to the bone marrow) must be done to both confirm that the tumor is a neuroblastoma and to allow for testing that provides information needed to plan therapy. Biopsy is usually performed on the most accessible site of disease. This may be the primary site (where the neuroblastoma may have originated) or may be a lymph node or other type of tissue that is safe to sample.
After the diagnosis is confirmed, the neuroblastoma must be staged or defined in terms of how far the cancer has spread from where it started. This staging process is important because it determines the course of treatment.15 Based on the cancer’s stage, its genetic makeup and the person’s age, the patient is assigned a risk level that describes the likelihood of recurrence.15 Staging involves performing the scans mentioned above as well as sampling of the bone marrow.
Children with a neuroblastoma that has not spread to other areas of the body are predicted to have a better disease outcome (prognosis) than children with a neuroblastoma that has spread (metastatic disease).16 Unfortunately, however, more than half of children with neuroblastoma have metastatic disease at the time of diagnosis.9 Children who have the best survival rates and are most likely to have their tumor go away on its own are young infants with small neuroblastoma tumors limited to the adrenal gland. Children older than 18 months of age who have metastatic disease have the worst prognosis.10 An exception to the rule of children with metastatic disease having worse outcomes is a special form of neuroblastoma known as stage MS (previously known as 4S) neuroblastoma. Stage MS neuroblastoma is a type of neuroblastoma that has spread to the liver, skin, or bone marrow (to a limited extent). MS disease usually occurs in very young infants. However, it tends to respond well to treatment and can usually be cured. In some babies, stage MS neuroblastoma even goes away on its own.3,13
Molecular genetic (DNA) testing is very important in determining prognosis for patients with newly diagnosed neuroblastoma. The presence of extra copies of the MYCN gene in tumor cells (referred to as MYCN amplification) is associated with more aggressive disease. Patients who would have been classified as having non-high-risk disease based on age and stage at diagnosis are instead classified as having high-risk disease if MYCN amplification is detected in tumor cells. In certain groups of patients, gain or loss of chromosomal material (referred to as segmental chromosome aberrations or SCAs) can also change the prognosis.17 Researchers around the world are actively studying other tests that may help in risk classification for children with neuroblastoma.
Blood tests that can also help predict the prognosis for children with neuroblastoma include tests for ferritin and lactate dehydrogenase levels. In many countries, the use of DNA testing has replaced the use of these blood tests, but the levels may still be helpful in areas of the world in which DNA testing is less widely available.
Treatment
The National Comprehensive Cancer Network (NCCN) has published guidelines for the treatment of neuroblastoma.18
Treatment for neuroblastoma varies widely among patients and is based on the patient’s age at diagnosis, the tumor’s location and relationship to surrounding normal structures, whether it has spread to distant parts of the body, the appearance of the tumor under the microscope (favorable or unfavorable histology), the number of copies of the MYCN gene in tumor cells (MYCN amplification status) and the presence or absence of changes in chromosomal material in tumor cells (SCA status).19 Newborns with a small neuroblastoma that has not spread may be observed with close monitoring to see if their tumor resolves on its own or grows and eventually needs treatment. For people with a neuroblastoma that has not spread or has spread to only nearby lymph nodes, surgery alone may be recommended.20 Patients in this low-risk category have an excellent prognosis. If their neuroblastoma recurs in the future, they can potentially undergo surgery again or be treated with chemotherapy.15
Chemotherapy may be used as the initial treatment instead of surgery to shrink tumors that have not spread to other body parts but would be difficult to remove at the time of diagnosis.20 Chemotherapy is also the recommended initial form of treatment when a neuroblastoma is near the spinal cord.13 For tumors that grow after they were initially removed by surgery, chemotherapy may also be indicated. The chemotherapy drugs used for patients in these situations may include carboplatin, cyclophosphamide, doxorubicin and etoposide.5
Patients over 18 months of age at diagnosis with neuroblastoma that has spread to distant body parts (i.e. patients with high-risk disease) have a chance of surviving for 5 years after diagnosis of just over 50% compared with the 90% to 95% 5-year survival rate of patients with low or intermediate risk neuroblastoma.19 Other children with neuroblastoma may also be considered high risk, including patients whose tumors have too many copies of the MYCN gene and children with tumors that cannot be fully removed at the time of diagnosis. Additional smaller subsets of patients may also be considered to have high-risk disease, depending on risk factors outlined above. Patients in these high-risk groups are treated more aggressively and receive a combination of chemotherapy, surgical removal of the main tumor, high dose chemotherapy with infusion of the patient’s own blood forming cells (autologous stem cell transplantation), external beam radiation and therapy that uses the body’s own immune system to eliminate cancer cells (immunotherapy).5
Chemotherapy drugs typically used for high-risk patients during the first treatment phase (known as induction) may include cisplatin, etoposide, vincristine, cyclophosphamide, doxorubicin and topotecan.19 After several months of chemotherapy, patients usually have surgery to remove the main (primary) tumor. Patients who have a good response to chemotherapy and surgery then proceed to the next phase of treatment. Those who do not have a good response to induction may receive second-line treatment to improve response.
Patients who do move on to the next phase of treatment (known as consolidation) commonly undergo high-dose chemotherapy. To reduce recovery time from the high dose chemotherapy, patients receive infusions of their own blood forming cells, known as stem cells. In North America, the vast majority of centers administer two rounds of high dose chemotherapy with stem cell rescue because the results from a large clinical trial indicated that survival rates were better in patients who underwent this very intensive therapy. Decision-making around the administration of high dose chemotherapy with stem cell rescue can be complicated, especially in children who have been very ill due to their cancer or its treatment. Upon recovery from high dose chemotherapy with stem cell rescue, patients receive radiation to the site where the primary tumor used to be. They may also receive radiation to other specific sites, depending on the response they had to initial treatment.
After completion of radiation, patients undergo another evaluation of their response to treatment. Those who continue to have a good response go on to receive the next phase of treatment, known as post-consolidation. This includes immunotherapy, a form of therapy that harnesses the immune system to eliminate residual tumor cells and prevent recurrence. The cornerstone of immunotherapy is medication directed at a specific molecule that is found on the surface of neuroblastoma cells. This molecule is called GD2, and there are several medications known as antibodies that have been developed that attach to GD2 specifically. These antibodies make neuroblastoma cells more “visible” to the body’s own immune system, making it possible for the immune system to destroy the cancer cells. In North America, these antibodies are given with stimulators of the immune system to increase this effect. Another medication called isotretinoin is also given during this phase of treatment. Isotretinoin is a type of vitamin A that is thought to help cancer cells mature into less aggressive cells.
In 2023, the U.S. Food and Drug Administration (FDA) approved another medication known as eflornithine for patients who have responded to prior treatment and have completed post-consolidation immunotherapy. Eflornithine may be taken for up to 2 years.
Relapsed neuroblastoma
It is unusual for patients who were initially diagnosed with low- or intermediate-risk neuroblastoma to have a recurrence of the disease. Neuroblastomas that have returned but have not spread or have spread only to nearby lymph nodes can sometimes be treated again with surgery only or surgery with chemotherapy. Detailed information is needed for patients like this so that an appropriate treatment plan can be made. For patients with high-risk disease at diagnosis, disease recurrence is seen more frequently. At the time of recurrence of high-risk neuroblastoma, careful evaluation of the sites of the disease, the molecular features of the tumor cells and the patient’s organ function is needed. Doctors will often spend a great deal of time with patients and families discussing treatment options in this setting, as decision-making can be complex.
Late effects of neuroblastoma therapy
Because of treatment advances, many children with neuroblastoma now survive into adulthood. Patients who received treatment for low or intermediate risk disease are expected to have far fewer long term side effects than patients who received treatment for high-risk disease. Important research regarding long term effects of high-risk neuroblastoma treatment is ongoing, but it is important that children treated for high-risk neuroblastoma be monitored for problems with growth, abnormalities in thyroid function, hearing loss, fertility issues, musculoskeletal problems, social and emotional challenges and cancers related to prior treatment. Doctors who specialize in late effects after cancer therapy can partner with primary care doctors and other specialists to provide the services and support that survivors need.
Research is being done to develop new treatment options for patients with neuroblastoma. For patients with low and intermediate-risk neuroblastoma, researchers are evaluating reductions in treatment with the goal of continuing to address the cancer appropriately while minimizing long term side effects.
Different treatment regimens are being studied for patients with aggressive neuroblastoma as well, including targeted therapies and new combinations of existing therapies. The use of agents that target variants in specific genes in tumor cells (such as variants in the ALK gene and other genes that are altered in neuroblastoma cells) are of great interest.
In addition, the use of combinations of new drugs with immunotherapy and the use of immunotherapy at different points in the treatment course are also being studied.
Another immunotherapy treatment being explored for neuroblastoma is chimeric antigen receptor (CAR) T-cell therapy. CAR T-cell therapy is a type of cell-based gene therapy that involves taking a patient’s immune cells called T cells, genetically altering them in a lab to recognize specific receptors on cancer cells and then administering them back to the patient to attack their cancer cells.21
In addition to CAR T-cell therapy, vaccines that train a patient’s immune system to recognize and attack neuroblastoma cells are being evaluated.
Information on current clinical trials is posted on the Internet at https://clinicaltrials.gov/ All studies receiving U.S. Government funding, and some supported by private industry, are posted on this government web site.
For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
Tollfree: (800) 411-1222
TTY: (866) 411-1010
Email: [email protected]
Some current clinical trials also are posted on the following page on the NORD website:
https://rarediseases.org/living-with-a-rare-disease/find-clinical-trials/
For information about clinical trials sponsored by private sources, contact:
http://www.centerwatch.com/
For information about clinical trials conducted in Europe, contact:
https://www.clinicaltrialsregister.eu/
NORD strives to open new assistance programs as funding allows. If we don’t have a program for you now, please continue to check back with us.
NORD and MedicAlert Foundation have teamed up on a new program to provide protection to rare disease patients in emergency situations.
Learn more https://rarediseases.org/patient-assistance-programs/medicalert-assistance-program/Ensuring that patients and caregivers are armed with the tools they need to live their best lives while managing their rare condition is a vital part of NORD’s mission.
Learn more https://rarediseases.org/patient-assistance-programs/rare-disease-educational-support/This first-of-its-kind assistance program is designed for caregivers of a child or adult diagnosed with a rare disorder.
Learn more https://rarediseases.org/patient-assistance-programs/caregiver-respite/