Neuroblastoma in Children: Signs, Diagnosis, and Treatment

Neuroblastoma is one of the most common solid tumors found outside the brain in babies and young children, arising from immature nerve cells that are part of the sympathetic nervous system. Although hearing the word “cancer” is frightening, understanding how neuroblastoma is found and treated can help parents make informed decisions and feel more in control.

What Is Neuroblastoma?

Neuroblastoma is a childhood cancer that begins in early nerve cells called neuroblasts. These cells normally mature into nerve cells and cells of the adrenal glands. In neuroblastoma, the cells grow in an uncontrolled way and form a tumor.

The tumor most often develops in or near the:

• Adrenal glands (small glands above each kidney)
• Neck
• Chest
• Abdomen (belly)
• Pelvis

Because the sympathetic nervous system extends throughout the body, neuroblastoma can also spread (metastasize) to the lymph nodes, bones, bone marrow, liver, skin, or other organs.

How Common Is It and Who Gets It?

Neuroblastoma is rare overall, but among cancers in childhood, it is one of the most frequent solid tumors in infants. It most often affects children under age 5 and is especially common in babies and toddlers.

• Most diagnoses occur before age 5.
• It is rarely diagnosed in teenagers and adults.

Possible Causes and Risk Factors

For most families, there is no clear reason why a child developed neuroblastoma. Researchers know that the cancer starts when changes (mutations) occur in the DNA of developing nerve cells, but exactly why these changes occur is often unknown.

Inherited vs. Non-inherited Cases

• Sporadic (non-inherited) cases are by far the most common. These happen by chance and are not passed down in families.
• Hereditary (inherited) neuroblastoma is rare. In these families, changes in certain genes, such as ALK or PHOX2B, can be passed from a parent to a child and increase the risk.

Children with known predisposing gene changes may be monitored more closely for early signs of the disease.

Signs and Symptoms Parents Might Notice

Neuroblastoma symptoms vary widely. They depend on the size of the tumor, where it started, and whether it has spread. Many early signs can be vague and similar to common childhood illnesses.

Common General Symptoms

• A lump or swelling that can be felt, often in the belly, neck, or chest
• Pain or tenderness, including bone pain that may cause limping
• Loss of appetite and weight loss
• Fatigue, low energy, or irritability
• Fever without a clear cause

Symptoms by Tumor Location

Any persistent, unusual swelling, unexplained pain, or change in a child’s usual behavior should be discussed with a pediatrician. Most children with these symptoms do not have cancer, but serious problems need to be ruled out.

How Neuroblastoma Is Diagnosed

If a doctor suspects neuroblastoma, several tests are used to confirm the diagnosis and to see how far the disease has spread.

Initial Evaluation

• Detailed medical history and physical exam
• Blood tests to check blood counts, organ function, and certain chemicals released by tumor cells
• Urine tests to measure catecholamine breakdown products (such as HVA and VMA), which are often high in neuroblastoma

Imaging Tests

• Ultrasound for a quick look at the abdomen or pelvis
• CT or MRI scans to define the size, location, and spread of the tumor
• MIBG scan, in which a small amount of radioactive material that is taken up by neuroblastoma cells is injected, then images are taken to find tumors throughout the body
• Sometimes a bone scan or PET scan is also used

Biopsy and Bone Marrow Tests

• Tumor biopsy: a surgeon removes a small piece of the tumor to be examined under a microscope and to test for specific genetic and molecular features.
• Bone marrow aspiration and biopsy: samples of bone marrow (the soft tissue inside certain bones) are checked for neuroblastoma cells.

Staging and Risk Groups

Once neuroblastoma is confirmed, doctors determine the stage (how far it has spread) and assign a risk group (low, intermediate, or high risk). These factors guide treatment choices and help estimate the chance of cure.

Staging Systems

The International Neuroblastoma Risk Group Staging System (INRGSS) is widely used. It considers:

• Imaging-defined risk factors, such as whether the tumor is wrapped around major blood vessels or organs
• Whether the cancer has spread to lymph nodes, bone, bone marrow, liver, or skin

Risk Categories

• Low risk: localized tumors, often in younger children, with favorable biology; many are cured with surgery alone or even careful observation.
• Intermediate risk: tumors that may be larger or more complex, often requiring a combination of chemotherapy and surgery.
• High risk: widely spread disease or tumors with high-risk biologic features; treatment is intensive and usually involves multiple therapies over many months.

Treatment Options for Neuroblastoma

Treatment is tailored to each child based on age, stage, risk group, and tumor biology. A team that may include pediatric oncologists, surgeons, radiation oncologists, nurses, and supportive care specialists works together to design the best plan.

Surgery

Surgery aims to remove as much of the tumor as safely possible.

• For low-risk tumors, complete surgical removal may be the only treatment needed.
• For intermediate- and high-risk cases, chemotherapy often comes first to shrink the tumor, followed by surgery to remove remaining disease.
• Sometimes only a biopsy is done initially if the tumor is too entangled with vital organs or blood vessels.

Chemotherapy

Chemotherapy uses powerful medicines that travel through the bloodstream to destroy cancer cells. It is a key part of treatment for most children, especially those with intermediate- or high-risk disease.

• Used before surgery to shrink tumors
• Used after surgery to kill any remaining cancer cells
• Given at very high doses before stem cell transplant in high-risk cases

Commonly used drugs include combinations such as cisplatin, carboplatin, cyclophosphamide, etoposide, vincristine, doxorubicin, and topotecan.

Radiation Therapy

Radiation therapy uses high-energy beams to target and destroy cancer cells in specific areas.

• May be used after surgery and chemotherapy for high-risk neuroblastoma to treat the primary tumor site or other involved areas
• Sometimes used for pain relief or to control disease pressing on vital structures

Stem Cell (Bone Marrow) Transplant

For many children with high-risk neuroblastoma, treatment includes high-dose chemotherapy followed by autologous stem cell rescue (the child’s own blood-forming stem cells are collected in advance and returned after intensive chemotherapy).

• High-dose chemotherapy aims to wipe out remaining cancer cells.
• Reinfused stem cells help the bone marrow recover and make new blood cells.

Immunotherapy and Targeted Therapies

Newer treatments focus on helping the immune system recognize and attack neuroblastoma cells or on targeting specific molecules on tumor cells.

• Immunotherapy: monoclonal antibodies such as dinutuximab bind to markers on neuroblastoma cells and help the immune system destroy them. These are often used after stem cell transplant in high-risk disease.
• Retinoid therapy: medicines like isotretinoin help remaining cancer cells mature and are used as maintenance therapy following intensive treatment for high-risk cases.
• Radiolabeled MIBG therapy: delivers targeted radiation directly to neuroblastoma cells using a radioactive iodine-labeled molecule.

Observation for Very Low-Risk Tumors

Some infants with small adrenal tumors and no symptoms may be carefully monitored with regular imaging instead of starting treatment right away, because some of these tumors can shrink or mature on their own.

Side Effects and Long-Term Follow-Up

Because treatment for neuroblastoma can be intensive, both short-term side effects and long-term health issues (late effects) are possible. Ongoing follow-up care is essential.

Possible Short-Term Side Effects

• Nausea, vomiting, and loss of appetite
• Hair loss
• Infections, bleeding, or anemia from low blood counts
• Fatigue and weakness
• Skin changes or soreness at radiation sites

Potential Long-Term or Late Effects

• Growth and developmental issues
• Learning or memory difficulties
• Hearing loss (especially with certain chemotherapy drugs)
• Kidney, heart, or lung problems
• Hormone or fertility issues
• Risk of second cancers later in life

Survivorship clinics and long-term follow-up programs help monitor for late effects and manage any health issues that arise.

Living With Neuroblastoma: Support for Families

Caring for a child with neuroblastoma affects the entire family emotionally, physically, and financially. Support is an important part of treatment.

• Emotional support: psychologists, social workers, child life specialists, and support groups can help children and parents cope with stress and fear.
• Practical help: social work teams often assist with transportation, housing near treatment centers, school planning, and financial resources.
• Education: understanding the disease and its treatment can reduce anxiety and help parents partner effectively with the care team.

Frequently Asked Questions (FAQs)