Neuroblastoma - Cause, Stages, Diagnosis, Complications, Treatment, and Prevention

What Is Neuroblastoma?

Neuroblastoma is a rare childhood cancer that starts in immature nerve cells called neuroblasts. Around 90% of cases are diagnosed before age 5, with the average age at diagnosis being 1 to 2 years. Although rare, neuroblastoma causes nearly 15 % of childhood cancer deaths.

The term comes from neuro (nerves) and blastoma (cancer starting in immature cells). These cells belong to the sympathetic nervous system, which controls heart rate, blood pressure, breathing, and stress responses. Normally, neuroblasts mature before birth, but in neuroblastoma, some grow abnormally and form tumors.

Where Does Neuroblastoma Start?

Neuroblastoma most often begins in the adrenal glands, located above the kidneys.

However, neuroblastoma can also start in the belly (abdomen), chest, neck, or spine (backbone).

If cancer spreads, common sites include:

• Bone marrow.

• Bones.

• Lymph nodes.

• Liver.

• Skin.

• Rarely, it may affect the brain.

Neuroblastoma by Numbers:

• Neuroblastoma is rare, with about 700 to 800 children diagnosed each year in the United States.

• Around 90% of cases occur in children younger than 5 years, and the average age at diagnosis is 1 to 2 years.

• Only 1 to 2% of cases are inherited, meaning most happen without a family history.

• Although uncommon, neuroblastoma is linked to nearly 15% of childhood cancer deaths, highlighting the importance of early diagnosis and treatment.

What Causes Neuroblastoma?

Parents often ask: "Did I do something wrong?"

Current evidence suggests that most neuroblastoma cases are not caused by parenting choices, pregnancy activities, or something a parent did.

The exact cause is often unknown. Scientists believe neuroblastoma develops when immature nerve cells gain genetic mutations and continue growing instead of maturing normally.

Causes may include:

1. Random Genetic Changes (Most Common): Most cases happen sporadically, meaning by chance. Children often have no family history.

2. Inherited Neuroblastoma (Rare): Only around 1 to 2 out of 100 children inherit mutations associated with neuroblastoma.

Genes linked to inherited neuroblastoma include:

• The ALK (anaplastic lymphoma kinase) gene changes in this gene may increase the risk of developing neuroblastoma.

• The PHOX2B (paired-like homeobox 2B) gene, changes in this gene can affect nerve cell development and may be linked to inherited neuroblastoma.

3. Tumor Gene Changes Affecting Prognosis:

Doctors may test for:

• MYCN amplification.

• ATRX mutation.

• NTRK1 changes.

These help estimate severity and treatment response.

What Are the Symptoms of Neuroblastoma?

Symptoms depend on tumor location and whether the cancer has spread.

1. Symptoms Caused by Tumor Pressure

Children may develop:

• Belly swelling.

• Lump in the neck, chest, or abdomen.

• Constipation.

• Appetite loss.

• Trouble breathing.

• Persistent cough.

2. Symptoms After Cancer Spreads

Possible signs include:

• Bone pain.

• Limping.

• Dark circles around the eyes.

• Bulging eyes.

• Pale skin.

• Weight loss.

• Fatigue.

• Persistent unexplained fever.

3. Hormone-Related Symptoms

Some tumors release chemicals causing:

• High blood pressure.

• Fast heartbeat.

• Sweating.

• Flushed skin.

• Ongoing watery diarrhea.

4. Nervous System Symptoms

Cancer affecting nerves or the spinal cord may cause:

• Weakness.

• Difficulty walking.

• Poor balance.

• Numbness in the legs.

• Coordination problems.

5. . Rare Signs

Horner syndrome:

May cause:

• Small pupil.

• Droopy eyelids.

• Reduced sweating on one side of the face.

When Should Parents Seek Medical Care?

Talk to a doctor if your child has:

• A tummy that stays swollen.

• A bump that does not go away or gets bigger.

• Fever without feeling sick from a cold or infection.

• Pain in the bones or trouble walking normally.

• Sudden weakness.

• Bulging eyes or dark circles around the eyes.

• Fast or unexplained weight loss.

Seek urgent care for:

• Trouble breathing.

• Difficulty walking.

• Sudden paralysis symptoms.

These signs do not always mean cancer, but they need evaluation.

How Is Neuroblastoma Diagnosed?

Doctors use several tests.

1. Physical Examination

Doctors ask about:

• Symptoms.

• Growth changes.

• Family history.

• Behavior changes.

2. Urine Tests

Urine often shows increased:

• Homovanillic acid (HVA).

• Vanillylmandelic acid (VMA).

These markers are elevated in about 90% of cases.

3. Blood Tests: Doctors may do blood tests to check LDH (lactate dehydrogenase), ferritin (a protein that stores iron in the body), and uric acid (a waste substance made when cells break down). Higher levels of these may help doctors understand how the disease is affecting the body.

4. Imaging Tests: Tests may include ultrasound, CT (computed tomography) scan, MRI (magnetic resonance imaging), PET (positron emission tomography) scan, MIBG (Metaiodobenzylguanidine) scan, and X-ray to help find tumors, check their size, and see whether cancer has spread to other parts of the body.

5. Tissue Biopsy: A tissue sample (biopsy) helps doctors confirm the type of cancer, genetic changes in the tumor, and the best treatment options for the child.

6. Bone Marrow Biopsy: Helps determine spread.

What Are the Modern Stages of Neuroblastoma?

Doctors commonly use the INRGSS (International Neuroblastoma Risk Group Staging System) to describe how far neuroblastoma has spread.

• Stage L1 means the tumor is limited to one area and has no major risk features.

• Stage L2 means the tumor is still localized but has risk factors that may make treatment harder.

• Stage M means the cancer has spread to distant parts of the body.

• Stage MS occurs in younger children when cancer has spread in a limited way. Older stage 1 to 4 systems are used less often today.

What Are Neuroblastoma Risk Groups?

Treatment depends on whether the child has low-, intermediate-, or high-risk neuroblastoma.

• Children with low-risk neuroblastoma may need only surgery or careful monitoring. Intermediate-risk neuroblastoma often requires surgery and chemotherapy.

• High-risk neuroblastoma usually needs intensive treatment, including chemotherapy, surgery, stem cell transplant, immunotherapy, or radiation therapy.

Doctors decide the risk group based on factors such as the child’s age, cancer stage, genetic changes, tumor biology, and MYCN (MYCN proto-oncogene) status.

How Is Neuroblastoma Treated?

Treatment for neuroblastoma depends on the child’s age, cancer stage, genetic changes, and risk group.

• Treatment options may include surgery to remove tumors, chemotherapy using medicines to kill cancer cells, and radiation therapy to destroy remaining cancer cells.

• Some children may receive immunotherapy, which helps the immune system attack cancer, or a stem cell transplant after high-dose chemotherapy.

• Some children with relapsed or high-risk neuroblastoma may receive targeted MIBG therapy, which delivers radiation directly to cancer cells while limiting damage to healthy tissues.

What Complications Can Occur?

Possible complications of neuroblastoma or its treatment include pressure on the spinal cord, which may cause weakness or trouble moving, paralysis (loss of movement in parts of the body), and hormonal imbalance, which can affect normal body functions.

Cancer can sometimes spread to other parts of the body and cause serious health problems. After treatment, your child may experience slower growth, hearing difficulties, or changes in how organs like the heart or kidneys function. Some children may also experience growth delay, fertility problems later in life, or, rarely, develop secondary cancers related to previous treatment. Regular follow-up visits with the doctor can help monitor these effects and support your child’s recovery and long-term health.

Regular check-ups can help doctors find and manage these problems early, supporting the child’s health as they grow.

Can Neuroblastoma Be Prevented?

There is no proven way to prevent neuroblastoma.

Unlike many adult cancers, lifestyle changes usually do not prevent childhood neuroblastoma.

Families with inherited mutations may benefit from:

• Genetic counseling.

• Monitoring.

• Early screening discussions.

Evidence does not show that folic acid specifically prevents neuroblastoma.

What Is the Survival Rate for Neuroblastoma?

The chance of surviving neuroblastoma for at least 5 years depends on the child’s risk group, age, cancer stage, tumor genetics, and how well the cancer responds to treatment.

• Children with low-risk neuroblastoma have a survival rate above 95%, meaning most respond well to treatment and recover.

• For intermediate-risk neuroblastoma, survival rates are around 90 to 95%. In high-risk neuroblastoma, the 5-year survival rate is lower, at about 40 to 50%, because the cancer is more aggressive.

• Early diagnosis, timely treatment, and regular follow-up care can improve outcomes and increase the chances of recovery.

What Is the Outlook for Children With Neuroblastoma?

Parents often ask, "Will my child be okay?" The answer depends on several factors, including the child’s age, cancer stage, genetic changes in the tumor, and how well the cancer responds to treatment.

In rare cases, especially in very young infants with stage MS neuroblastoma, tumors may shrink or disappear on their own without intensive treatment. However, close medical monitoring is still necessary.

High-risk neuroblastoma can be more difficult to treat, but new therapies and improved treatments continue to increase survival rates. Regular follow-up care is important because some children may develop long-term health problems related to treatment.

How Can Parents Support a Child With Neuroblastoma?

• Parents often feel scared, confused, or overwhelmed after a neuroblastoma diagnosis.

• It is important to remember that your child’s illness is usually not caused by something you did or did not do.

• Honest and age-appropriate conversations can help children understand and cope with treatment.

• Explaining medical procedures in simple steps may reduce fear. Parents also need emotional support during this time.

• Doctors, nurses, counselors, and social workers can help families manage treatment, answer questions, and provide support throughout the journey.

Conclusion

Neuroblastoma is a rare cancer that usually affects children younger than 5 years. It often starts in the adrenal glands above the kidneys. Early diagnosis, correct staging, and treatment based on your child’s risk level can improve recovery chances.

A diagnosis can feel very frightening for you as a parent, but newer treatments like immunotherapy, stem cell transplantation, and targeted therapy are helping more children recover and live healthier lives. If you notice unusual symptoms in your child, consult a cancer specialist early, so your child can get the right care and support as soon as possible.

Key takeaways:

• Neuroblastoma is a rare cancer of immature nerve cells mainly affecting children under 5 years.

• The average age at diagnosis is 1 to 2 years.

• It often starts in the adrenal glands, but can occur in the chest, neck, abdomen, or spine.

• Symptoms range from abdominal swelling to bone pain and unexplained fever.

• Treatment may include surgery, chemotherapy, immunotherapy, radiation, or stem cell transplant.

• Early diagnosis improves survival. Speak with a pediatric cancer specialist for guidance.