Neuroblastoma

Neuroblastoma (NB) is a type of cancer that forms in certain types of nerve tissue. It most frequently starts from one of the adrenal glands but can also develop in the head, neck, chest, abdomen, or spine. Generally affecting children under five years old, neuroblastoma is the most common cancer in babies and the third-most common cancer in children.

Signs and Symptoms

The first symptoms of neuroblastoma are often vague, making diagnosis difficult. Common symptoms include fatigue, loss of appetite, fever, and joint pain. Symptoms depend on the primary tumour location and metastases:

• Abdominal Tumours: May cause abdominal distension and constipation.
• Chest Tumours: May cause breathing problems.
• Spinal Cord Compression: May result in weakness and inability to stand, crawl, or walk.
• Bone Lesions: Particularly in the legs and hips, causing pain and limping.
• Orbital Tumours: May cause distinct bruising and swelling around the eyes.
• Bone Marrow Infiltration: May cause anaemia-related pallor.

Neuroblastoma often spreads to other parts of the body before symptoms appear, with 50-60% of cases presenting with metastases.

Causes

The exact cause of neuroblastoma is not well understood, but it is generally due to a genetic mutation occurring in the first trimester of pregnancy. Most cases are sporadic and nonfamilial, although about 1-2% of cases run in families and are linked to specific gene mutations such as the ALK, PHOX2B, or KIF1B genes. Amplification of the MYCN oncogene within the tumour is a common finding and is associated with advanced stages of disease.

Diagnosis

Diagnosis is typically confirmed by a surgical pathologist via tissue biopsy, considering clinical presentation and microscopic findings. In about 90% of cases, elevated levels of catecholamines or their metabolites are found in urine or blood.

Imaging

Meta-iodobenzylguanidine (mIBG) scans are highly effective, with 90-95% of neuroblastomas being mIBG-avid. Fluoro-deoxy-glucose positron emission tomography (F-FDG-PET) is used when mIBG is not effective.

Histology

On microscopy, neuroblastoma cells are typically small, round, blue, and often form rosettes (Homer Wright pseudorosettes). Various immunohistochemical stains help distinguish neuroblastomas from other histological mimics.

Staging

The International Neuroblastoma Staging System (INSS) classifies neuroblastoma from Stage 1 (localised tumour) to Stage 4 (disseminated tumour). A newer system, the International Neuroblastoma Risk Group Staging System (INRGSS), further refines risk assignment based on various clinical and genetic factors.

Treatment

Treatment and outcomes depend on the risk group. Options include observation, surgery, radiation, chemotherapy, and stem cell transplantation. Low-risk disease often has a good outcome with surgery or observation alone. High-risk disease, despite aggressive treatment, has a long-term survival rate of less than 40%.

• Low-risk: Often cured with surgery alone or observation.
• Intermediate-risk: Treated with surgery and chemotherapy.
• High-risk: Requires intensive chemotherapy, surgery, radiation therapy, stem cell transplantation, and biological-based therapy.

In recent years, monoclonal antibody therapy, such as dinutuximab, has significantly improved survival rates in high-risk cases.

Prognosis

The overall five-year survival rate is around 67%, but varies significantly based on risk category. Low and intermediate-risk cases have excellent prognosis, while high-risk cases have poorer outcomes despite aggressive treatment.

Cytogenetic Profiles

Genomic patterns predict outcomes in neuroblastoma. Tumours with whole chromosome copy number changes have excellent survival rates, while those with segmental alterations have a high risk of relapse. Specific cytogenetic profiles, such as N-myc amplification and deletions on chromosomes 1p and 11q, correlate with poorer prognosis.

Epidemiology

Neuroblastoma accounts for 6-10% of all childhood cancers and 15% of cancer deaths in children. It predominantly affects those under five years old, with the highest number of cases in the first year of life. Adult cases are very rare.

History

Neuroblastoma was first described by Rudolf Virchow in 1864, with further understanding developed by Felix Marchand, William Pepper, and James Homer Wright, who identified its origin from primitive neural cells.

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Self-assessment MCQs (single best answer)

Which of the following is the most common location for neuroblastoma to originate?

Which symptom is specifically associated with neuroblastoma in the abdomen?

What is a common histological feature of neuroblastoma cells?

Which of the following genetic markers is commonly associated with advanced stages of neuroblastoma?

What imaging technique is most effective for diagnosing neuroblastoma, with 90-95% sensitivity?

Which treatment modality is often sufficient for low-risk neuroblastoma?

What percentage of neuroblastoma cases typically present with metastases at diagnosis?

Which of the following is NOT a common symptom of neuroblastoma?

What is the overall five-year survival rate for neuroblastoma?

Which historical figure first described an abdominal tumour in a child as a "glioma"?