Neuroblastoma

What is neuroblastoma?

Neuroblastoma is a cancer that starts in immature nerve cells called neuroblasts. Neuroblasts are cells that normally develop into part of the sympathetic nervous system, the network of nerves that helps control automatic body functions such as heart rate, blood pressure, and digestion. In neuroblastoma, some of these immature cells do not mature the way they should and instead keep dividing, forming a tumor (an abnormal mass of tissue).

The most common place for neuroblastoma to begin is in the adrenal glands, two small glands that sit on top of the kidneys and produce hormones. It can also start in nerve tissue along the spine in the neck, chest, abdomen, or pelvis. Because the sympathetic nervous system runs through much of the body, the tumor can appear in several different locations.

Neuroblastoma in children is by far the most common form. It is one of the most frequent solid tumors found outside the brain in childhood, and it is often diagnosed in infants and young children under the age of five. It is very rare in older children, teenagers, and adults. In many hospitals, including Acibadem, care for neuroblastoma is coordinated through pediatrics together with pediatric oncology, which is the branch of medicine that treats cancer in children.

Neuroblastoma behaves very differently from one child to another. Some tumors grow slowly, and a small number even shrink or mature into harmless tissue on their own, especially in infants. Others grow quickly and spread to other parts of the body. This wide range is one reason doctors group the disease into risk categories before deciding on treatment.

Neuroblastoma symptoms

Neuroblastoma symptoms depend on where the tumor started, how large it is, and whether it has spread. Early on, many children have few or no obvious signs, and the tumor may be found during an examination for another reason. Common signs and symptoms include:

• A painless lump or swelling in the abdomen, neck, or chest
• A swollen or firm belly that may cause discomfort or a feeling of fullness
• Loss of appetite, poor feeding, or unexplained weight loss
• Persistent tiredness, irritability, or a general sense of being unwell
• Bone pain, limping, or refusing to walk, which may suggest spread to the bones
• Dark circles or bruising around the eyes, sometimes with bulging eyes
• Pale skin or easy bruising, which can occur if the bone marrow is affected
• Fever that does not have a clear cause
• Constipation or difficulty passing urine if the tumor presses on the bowel or bladder
• Weakness or numbness in the legs if the tumor presses on the spinal cord

Less common symptoms can also appear. If a tumor in the neck or upper chest affects certain nerves, a child may develop a drooping eyelid, a smaller pupil in one eye, and reduced sweating on one side of the face; doctors call this Horner syndrome. Some tumors release chemicals called catecholamines (hormones such as adrenaline), which can cause high blood pressure, flushing, sweating, or a fast heartbeat. A small number of children develop rapid, jerky eye movements and unsteady movements, a rare condition known as opsoclonus-myoclonus syndrome, which is linked to the immune system’s reaction to the tumor.

Symptoms often differ by stage. A localized tumor (one that has not spread) may cause only a lump or pressure-related symptoms. In stage 4 neuroblastoma, where the cancer has spread to distant sites such as the bones, bone marrow, liver, or skin, children more often have bone pain, tiredness, pale skin, bruising, fever, or a very enlarged liver. In infants, a special pattern called stage 4S (or stage MS in the newer international system) involves spread mainly to the liver, skin, or bone marrow, yet in many cases behaves less aggressively than other spread disease.

Many of these symptoms are also caused by common, harmless childhood conditions. Having one or more of them does not mean a child has cancer, but persistent or unexplained symptoms should always be checked by a doctor.

Causes and risk factors

Doctors do not fully understand what causes neuroblastoma. It develops when neuroblasts acquire changes (mutations) in their DNA during development, before or shortly after birth. These changes allow the cells to keep dividing instead of maturing into normal nerve cells. In most children, these DNA changes happen by chance and are not inherited.

Several genetic features inside the tumor cells are known to influence how the disease behaves. One of the most studied is extra copies of a gene called MYCN, known as MYCN amplification. Tumors with this change tend to grow more aggressively and are usually classed as high risk. Other changes in chromosomes (the structures that carry genes) can also affect the outlook. These are features of the tumor, not something the child or parents did or could have prevented.

Known or suspected risk factors include:

• Young age: most cases occur in children under five, and many are found in infants.
• Family history: a small proportion of cases run in families, often linked to inherited changes in genes such as ALK or PHOX2B.
• Certain inherited conditions: some rare genetic syndromes that affect nerve development are associated with a higher chance of neuroblastoma.

Unlike many adult cancers, neuroblastoma has not been clearly linked to lifestyle or environmental exposures. Researchers continue to study whether factors during pregnancy play a role, but no firm conclusions have been established. Because the cause is usually unknown, there is no proven way to prevent it.

Diagnosis

Diagnosis usually starts with a physical examination and a careful history of the child’s symptoms. If the doctor suspects a tumor, several tests are used to confirm the diagnosis, find out where the tumor is, and check whether it has spread. Common steps include:

• Blood and urine tests: most neuroblastomas release catecholamines, and their breakdown products can be measured in urine. Raised levels support the diagnosis. Blood tests also check blood cell counts, kidney and liver function, and other markers.
• Ultrasound: often the first imaging test, using sound waves to show a mass in the abdomen or elsewhere.
• CT or MRI scans: detailed imaging that shows the tumor’s exact size, location, and relationship to nearby blood vessels and organs. MRI is especially useful for checking the spine.
• MIBG scan: a nuclear medicine test in which a small amount of a radioactive tracer that is taken up by neuroblastoma cells is injected, allowing doctors to see the main tumor and any spread throughout the body. In some cases a PET scan is used instead.
• Biopsy: a sample of tumor tissue is removed, usually under general anesthesia, and examined under a microscope. This is the definitive way to confirm neuroblastoma.
• Bone marrow aspiration and biopsy: samples of bone marrow (the soft tissue inside bones where blood cells are made) are taken, usually from the hip bones, to see whether cancer cells have spread there.

Tumor tissue is also tested for genetic features such as MYCN amplification and other chromosome changes. Together with the child’s age, the stage of the disease, and how the cells look under the microscope, these results are used to place the child into a risk group: low, intermediate, or high risk. Staging systems describe how far the cancer has spread. The traditional system uses stages 1 to 4 (with 4S for the special infant pattern), while the International Neuroblastoma Risk Group system uses stages L1, L2, M, and MS based on imaging findings. Doctors may refer to both.

This risk grouping is central to planning care, because children in different risk groups receive very different types and amounts of treatment.

Neuroblastoma treatment options

Neuroblastoma treatment is tailored to the risk group. The overall goal is to remove or destroy the cancer while limiting long-term side effects in a growing child. Care is provided by a team that may include pediatric oncologists, pediatric surgeons, radiation specialists, nurses, and supportive care staff. Main options include:

• Observation (watchful waiting): for some infants with low-risk tumors, doctors may recommend close monitoring with regular scans rather than immediate treatment, because these tumors can shrink or mature on their own.
• Surgery: removing the tumor is often the main treatment for low-risk disease and is usually part of treatment for other risk groups. If the tumor is wrapped around important blood vessels or nerves, the surgeon may remove as much as is safely possible.
• Chemotherapy: medicines that kill fast-dividing cells. It may be given before surgery to shrink a tumor, or after surgery to treat remaining cancer cells. Intermediate- and high-risk disease usually requires chemotherapy.
• High-dose chemotherapy with stem cell rescue: in high-risk neuroblastoma, very strong chemotherapy is given, followed by an infusion of the child’s own previously collected blood-forming stem cells to help the bone marrow recover.
• Radiation therapy: high-energy beams directed at the tumor site or areas of spread. It is commonly used in high-risk disease and sometimes for tumors causing urgent problems, such as pressure on the spinal cord.
• Immunotherapy: treatments that help the immune system recognize and attack neuroblastoma cells, often using antibodies directed against a molecule on the tumor’s surface. It is now a standard part of high-risk treatment in many centers.
• Retinoid therapy: medicines related to vitamin A that encourage remaining cancer cells to mature, typically given after other treatment for high-risk disease.

For high-risk neuroblastoma, these approaches are usually combined in phases over many months: induction chemotherapy and surgery, then consolidation with high-dose therapy and radiation, then maintenance with immunotherapy and retinoids. Treatment is demanding, and children need close monitoring for side effects such as infection, nausea, hearing changes, and effects on growth and organ function.

Supportive care and rehabilitation are important throughout. This may include nutrition support, physical therapy if muscle weakness has developed, hearing checks, and psychological support for the child and family. Clinical trials testing newer targeted drugs may be offered in some centers, and your child’s medical team can explain whether any are suitable.

Living with neuroblastoma and outlook

The neuroblastoma prognosis (the likely course of the disease) varies more than for almost any other childhood cancer. Several factors influence it, including the child’s age at diagnosis, the stage, the tumor’s genetic features such as MYCN status, and how well the disease responds to initial treatment. In general, infants and children with low-risk or intermediate-risk disease have a favorable outlook, and many are treated successfully with limited therapy.

The neuroblastoma survival rate is considerably lower for children with high-risk disease, including most children with stage 4 neuroblastoma diagnosed after infancy. Even so, outcomes for high-risk disease have improved over time with intensive combined treatment, and a substantial proportion of children do survive long term. Statistics describe groups of patients, not individuals, and your child’s doctors can explain what the numbers may mean in your child’s particular situation.

Children who complete treatment are followed for years with regular check-ups, scans, and blood or urine tests to detect any return of the disease (relapse) and to monitor for late effects of treatment. These can include hearing loss, problems with growth or hormones, dental issues, heart or kidney effects, fertility concerns later in life, and, rarely, second cancers. Long-term follow-up in a survivorship program helps identify and manage these problems early.

Living with neuroblastoma affects the whole family. Parents often face emotional strain, disrupted routines, and financial pressure. Social workers, psychologists, and parent support groups can help. Siblings may also need attention and reassurance. Many families find it helpful to keep a written record of treatments, medicines, and test results, and to ask the care team to explain anything that is unclear.

Frequently asked questions

What is neuroblastoma in simple terms?

Neuroblastoma is a childhood cancer that develops from immature nerve cells left over from a baby’s development. It most often begins in the adrenal glands above the kidneys or along the spine, and it can range from tumors that disappear on their own to tumors that spread widely and need intensive treatment.

What are the first neuroblastoma symptoms parents usually notice?

Often the first sign is a lump or swelling in the belly, or a child who seems generally unwell, tired, or has lost their appetite. Other early clues can include bone pain or limping, dark circles around the eyes, or unexplained fever. These symptoms are common in many harmless conditions, so a doctor’s assessment is needed to find the cause.

What does stage 4 neuroblastoma mean?

Stage 4 neuroblastoma means the cancer has spread from where it started to distant parts of the body, such as the bones, bone marrow, liver, or lymph nodes far from the tumor. In older children this usually places the disease in the high-risk group, although infants with a specific pattern of spread (stage 4S or MS) often have a much better outlook.

What is high-risk neuroblastoma?

High-risk neuroblastoma is a category that doctors assign based on age, stage, and tumor genetics, especially MYCN amplification. It indicates a tumor that is likely to grow and spread aggressively and therefore needs intensive, multi-phase treatment combining chemotherapy, surgery, high-dose therapy with stem cell rescue, radiation, immunotherapy, and retinoid medicines.

What is the neuroblastoma survival rate?

Survival varies greatly by risk group. Children with low- and intermediate-risk disease generally have a very favorable outlook, while survival for high-risk disease is lower, though it has improved with modern combined treatment. Because averages do not predict any single child’s outcome, your child’s oncology team is the best source for individualized information.

Can neuroblastoma be cured?

Many children with neuroblastoma are treated successfully and go on to live full lives, particularly those with low- or intermediate-risk disease. For high-risk disease, cure is possible but less certain, and relapse remains a concern. Doctors usually speak of remission and long-term survival rather than offering guarantees.

Is neuroblastoma inherited?

In most children neuroblastoma is not inherited and occurs by chance. A small proportion of cases are familial, linked to inherited changes in genes such as ALK or PHOX2B. If more than one family member has been affected, doctors may suggest genetic counseling to discuss testing for other children in the family.

When to see a doctor

Any lump, swelling, or symptom in a child that persists or cannot be explained should be evaluated by a doctor. Most will turn out to have a benign cause, but early assessment matters. Seek medical care promptly if a child has:

• A lump or firm swelling in the abdomen, neck, or chest
• A swollen belly with discomfort, or a belly that is growing quickly
• Ongoing bone pain, limping, or refusal to walk without a clear injury
• Unexplained weight loss, poor appetite, or persistent tiredness
• Dark circles or bruising around the eyes, or bulging eyes
• Pale skin, unusual bruising, or bleeding that is hard to explain
• A fever that keeps returning without an obvious infection

Seek urgent or emergency care if a child develops sudden weakness or numbness in the legs, difficulty walking, loss of bladder or bowel control, severe breathing difficulty, or rapid, jerky eye movements with unsteady movements, as these can indicate pressure on the spinal cord or other complications that need immediate attention. For a child already being treated for neuroblastoma, fever, signs of infection, uncontrolled vomiting, or unusual bleeding should be reported to the treating team without delay, following the instructions they have provided.