Neuroblastoma

Neuroblastoma is a rare and aggressive cancer that primarily affects children, typically under the age of 5. It originates from neuroblasts—immature nerve cells that are present in the developing fetus. These cells can become cancerous and form tumours in various parts of the body, most commonly in the adrenal glands, which are located above the kidneys. Neuroblastoma can also develop in nerve tissue along the neck, chest, abdomen, or pelvis.

This article aims to provide a comprehensive overview of neuroblastoma, covering its types, causes, symptoms, diagnosis, treatment options, and more. Understanding this condition is crucial for early detection and effective management.

Neuroblastoma is the most common extracranial solid tumour in children, accounting for approximately 8–10% of all childhood cancers. It arises from neuroblasts, which are precursor cells of the sympathetic nervous system. These tumours can develop anywhere along the sympathetic nervous system, but they most commonly occur in the adrenal glands, located above the kidneys. Neuroblastoma can also develop in nerve tissue along the neck, chest, abdomen, or pelvis.

The behaviour of neuroblastoma can vary widely. Some tumours may spontaneously regress without treatment, while others can be highly aggressive and spread rapidly to other parts of the body.

Worldwide

Globally, neuroblastoma is a significant health concern. In 2021, the incidence of neuroblastoma in children was approximately 5,560 cases, with 1,977 deaths, and 174,186 disability-adjusted life years (DALYs) attributed to the disease. The incidence rate has shown an overall increase of 12.6% from 1990 to 2021, with the highest annual percentage change observed in low-to-middle sociodemographic index regions. Central Asia exhibited the fastest annual increase in incidence, with an estimated average annual percentage change of 2.76% .

India

India reported the highest number of neuroblastoma cases globally in 2021, with 685 cases. This high number may be attributed to factors such as increased awareness, improved diagnostic facilities, and better reporting mechanisms. However, the incidence rate per 100,000 children is still relatively low compared to some Western countries .

Neuroblastoma can be classified into several types based on its location, histology, and genetic features:

• Localized Neuroblastoma: Confined to its original site without spread to other parts of the body.
• Metastatic Neuroblastoma: Has spread to other areas, such as lymph nodes, bones, liver, or bone marrow.
• High-Risk Neuroblastoma: Characterised by rapid growth and a high likelihood of spreading, often requiring aggressive treatment.
• Low-Risk Neuroblastoma: Tends to grow slowly and may spontaneously regress without treatment.
• Ganglioneuroblastoma: A tumour that contains both neuroblastic (immature nerve cells) and ganglionic (mature nerve cells) components.
• Ganglioneuroma: A benign tumour composed of mature nerve cells.

The exact cause of neuroblastoma remains unknown. However, several factors may contribute to its development:

• Genetic Mutations: Changes in certain genes, such as the MYCN gene, can increase the risk of neuroblastoma.
• Familial Factors: In rare cases, neuroblastoma can run in families, suggesting a genetic predisposition.
• Environmental Factors: Exposure to certain chemicals or radiation may increase the risk, though evidence is limited.
• Age and Gender: Neuroblastoma is more common in infants and young children, with a slight male predominance.

Symptoms of neuroblastoma vary depending on the tumour's location and whether it has spread. Common signs and symptoms include:

• Abdominal Mass: A lump or swelling in the abdomen, often noticed by parents during routine activities.
• Pain: Persistent pain in the abdomen, chest, or bones.
• Fatigue: Unusual tiredness or weakness.
• Fever: Unexplained fevers.
• Weight Loss: Unintentional weight loss.
• Changes in Skin Colour: Dark circles under the eyes or bluish skin.
• High Blood Pressure: Due to tumour secretion of hormones.
• Bulging Eyes or Proptosis: If the tumour affects the area around the eyes.
• Difficulty Breathing or Swallowing: If the tumour is located in the chest area.

Diagnosing neuroblastoma involves a combination of clinical evaluation, imaging studies, and laboratory tests:

• Physical Examination: A thorough examination to check for signs of a tumour.
• Imaging Tests:
  
  • Ultrasound: To detect abdominal masses.
  • CT Scan/MRI: To determine the size and spread of the tumour.
  • MIBG Scintigraphy: A special scan that detects neuroblastoma cells.
  • PET Scan: To assess metabolic activity and detect metastasis.
• Biopsy: Removal of a tissue sample for microscopic examination to confirm the diagnosis.
• Bone Marrow Aspiration: To check for spread to the bone marrow.
• Urine Tests: Measurement of catecholamine metabolites (vanillylmandelic acid and homovanillic acid) that are often elevated in neuroblastoma.

Treatment for neuroblastoma depends on the tumour's stage, risk category, and the child's overall health. Common treatment modalities include:

• Surgery: Removal of the tumour, if feasible.
• Chemotherapy: Use of drugs to kill cancer cells or stop their growth.  (Brand: Oncogem 200mg Injection)
• Radiation Therapy: High-energy rays to target and destroy cancer cells.
• Stem Cell Transplant: To restore bone marrow function after high-dose chemotherapy.
• Immunotherapy: Use of the body's immune system to fight cancer, including monoclonal antibodies like dinutuximab. (Brand: X-MAB 500mg Injection)
• Targeted Therapy: Drugs that specifically target cancer cells with minimal damage to normal cells.
• Retinoid Therapy: Use of vitamin A derivatives to promote differentiation of neuroblastoma cells.

While conventional treatments are the mainstay for neuroblastoma, some families explore complementary therapies to support overall well-being:

• Acupuncture: May help alleviate pain and nausea.
• Herbal Supplements: Some herbs are believed to boost the immune system, though evidence is limited.
• Mind-Body Techniques: Practices like meditation and yoga to reduce stress.

It's essential to consult with the healthcare team before starting any alternative therapies to ensure they do not interfere with standard treatments.

• Age: Most cases occur in children under 5 years of age, with the majority diagnosed before the age of 2.
• Genetics: Inherited mutations, especially those affecting the ALK (anaplastic lymphoma kinase) gene, are known to increase the risk.
• Family History: Although rare, familial neuroblastoma can occur when multiple cases appear in a family.
• Congenital Abnormalities: Some studies suggest that children born with congenital anomalies may have a slightly increased risk of developing neuroblastoma.

Neuroblastoma can lead to several complications, particularly if diagnosed late or if it is aggressive in nature:

• Metastasis: The cancer can spread to lymph nodes, bone marrow, liver, and skin, complicating treatment and reducing survival chances.
• Spinal Cord Compression: Tumours near the spine can compress the spinal cord, leading to pain, paralysis, or other neurological issues.
• Paraneoplastic Syndromes: These are rare conditions caused by substances produced by the tumour, such as:
  
  • Opsoclonus-myoclonus-ataxia syndrome (characterised by rapid eye movements, muscle jerks, and unsteady gait).
• Treatment Side Effects: Including growth delays, hearing loss, fertility issues, and secondary cancers, particularly in children undergoing high-dose chemotherapy or radiation.

Living with neuroblastoma can be overwhelming, especially for young children and their families. Here are practical tips to help cope with the condition:

• Build a Support Network: Lean on family, friends, support groups, and counsellors. Emotional support is essential.
• Coordinate Care: Assign a care coordinator or keep detailed records of medical visits, treatments, medications, and test results.
• Focus on Nutrition: Work with a paediatric dietitian to ensure the child maintains adequate nutrition, especially during treatment.
• Maintain Routine: Where possible, maintain normal routines such as schooling, playtime, and family activities to provide a sense of stability.
• Manage Side Effects: Open communication with the healthcare team can help manage pain, nausea, fatigue, and other side effects.

Understanding neuroblastoma often involves dispelling myths and misconceptions:

• “Neuroblastoma is caused by poor parenting or bad habits.”
  False. It is primarily a genetic and biological disease with no link to parenting styles or choices.
• “All neuroblastomas are fatal.”
  Not true. Prognosis varies greatly. Low-risk neuroblastoma may resolve on its own or with minimal treatment, while high-risk forms require aggressive therapy.
• “It’s only a tumour in the brain.”
  No. Despite the name, neuroblastoma is not a brain tumour. It originates in nerve tissues outside the brain, often in the adrenal glands.
• “Once treated, it won’t come back.”
  While many cases are cured, some aggressive forms can relapse. Ongoing follow-up care is essential.

Early medical attention is crucial for improving outcomes. Parents should seek medical advice if a child exhibits:

• A persistent lump or swelling in the abdomen, neck, or chest
• Unexplained weight loss or fatigue
• Bone pain or limping
• Bruising around the eyes or drooping eyelids
• Difficulty breathing or swallowing
• High blood pressure or sweating without a clear cause

Prompt evaluation can lead to early diagnosis and more effective treatment.

If your child is diagnosed with neuroblastoma, you may consider asking the following:

1. What type and stage of neuroblastoma does my child have?
2. What is the risk category (low, intermediate, or high)?
3. What treatment options are available, and what do you recommend?
4. Are there any clinical trials we should consider?
5. What are the side effects of the proposed treatment?
6. Will the treatment affect my child’s growth or development?
7. What is the expected prognosis?
8. How often will follow-up appointments be needed?
9. Are there any dietary or lifestyle changes we should make?
10. How can we best support our child emotionally and mentally?

Supporting a child with neuroblastoma involves emotional, physical, and logistical efforts from caregivers and loved ones:

• Offer Emotional Support: Be patient, empathetic, and available. Validate their fears and anxieties.
• Help With Routine Tasks: Offer to cook meals, handle errands, or care for other children in the household.
• Be Present: Simply spending time with the child and their family can be deeply comforting.
• Encourage Play and Joy: Fun and laughter are important for a child’s well-being. Bring games, books, or music.
• Be an Advocate: Help families navigate medical systems, access financial aid, and understand treatment options.

Neuroblastoma is a rare but serious cancer that mainly affects infants and young children. Its wide spectrum of clinical behaviours—from spontaneous regression to aggressive spread—makes early diagnosis and personalised treatment crucial. With advancements in medical science, survival rates for some forms of neuroblastoma have improved significantly, particularly when diagnosed early and treated appropriately.

Families affected by neuroblastoma face emotional and logistical challenges, but with the right support, many children go on to lead healthy, fulfilling lives. Raising awareness, investing in research, and promoting early detection are vital steps toward better outcomes.