Neuroblastoma – Causes, Symptoms and Treatment

What is Neuroblastoma?

Neuroblastoma is a malignant (cancerous) tumor that develops from immature nerve cells of the sympathetic nervous system. It is one of the most common solid extracranial tumors in childhood, accounting for approximately 8–10% of all childhood cancers. The tumor most frequently arises in the adrenal medulla, but it can develop anywhere along the sympathetic nerve chain — including the abdomen, chest, or neck.

Causes and Risk Factors

The exact causes of neuroblastoma are not yet fully understood. In most cases, the disease occurs sporadically, without a family history. In approximately 1–2% of cases, a hereditary form is present, associated with mutations in the ALK gene (Anaplastic Lymphoma Kinase) or the PHOX2B gene.

• Genetic predisposition (familial neuroblastoma)
• Mutations in the ALK or PHOX2B genes
• Amplification of the MYCN oncogene (associated with more aggressive disease)

Symptoms

Symptoms depend on the location of the tumor and its extent of spread. Neuroblastoma is often not detected until it has already metastasized (spread to other parts of the body).

• Palpable lump or swelling in the abdomen
• Abdominal pain or a sensation of fullness
• Bone pain (due to metastases)
• High blood pressure and rapid heartbeat (due to catecholamine secretion)
• Pallor, fatigue, and weight loss
• Periorbital bruising (so-called raccoon eyes) when metastases affect the eye socket
• Breathing difficulties with thoracic (chest) tumors

Diagnosis

Diagnosis of neuroblastoma involves a combination of investigative methods:

Imaging Studies

• Ultrasound: Initial investigation for a suspected abdominal mass
• CT (Computed Tomography) and MRI (Magnetic Resonance Imaging): For precise localization and assessment of extent
• MIBG scintigraphy (Meta-Iodobenzylguanidine): A specialized nuclear medicine scan that reliably detects neuroblastoma cells
• PET-CT: Used for MIBG-negative tumors

Laboratory Tests

• Measurement of catecholamines and their metabolites (vanillylmandelic acid, homovanillic acid) in urine
• NSE (Neuron-Specific Enolase) and LDH (Lactate Dehydrogenase) in blood as tumor markers

Tissue Biopsy

A biopsy of the tumor tissue is obtained for definitive diagnosis and tumor typing, including histological (microscopic tissue) examination. MYCN amplification status is also determined, as it has significant implications for treatment and prognosis.

Staging

Neuroblastomas are classified using the international INRG (International Neuroblastoma Risk Group) system into risk categories: very low, low, intermediate, and high. This classification is based on age, tumor stage, MYCN status, histology, and additional molecular markers.

Treatment

Treatment is guided by the patient's risk group and may include the following approaches:

Low-Risk Neuroblastoma

In very young infants with low-risk disease, a watchful waiting approach may be sufficient, as some tumors regress spontaneously. Surgical removal is performed if necessary.

Intermediate Risk

• Surgical removal of the tumor (resection)
• Moderate chemotherapy

High-Risk Neuroblastoma

• Intensive induction chemotherapy to reduce tumor size
• Surgical resection of residual tumor
• High-dose chemotherapy followed by autologous stem cell transplantation
• Radiotherapy to the tumor bed
• Immunotherapy with the antibody Dinutuximab (targeting the ganglioside GD2 on neuroblastoma cells)
• Isotretinoin (13-cis-retinoic acid) as differentiation therapy

Prognosis

Prognosis depends strongly on the risk group. Children with low-risk neuroblastoma have excellent survival rates of over 90%. In high-risk neuroblastoma, long-term survival rates remain approximately 40–50% despite intensive therapy. Ongoing clinical trials are investigating new approaches such as targeted therapies (ALK inhibitors) and CAR-T cell therapies to further improve outcomes.

References

1. Brodeur GM, Bagatell R. Mechanisms of neuroblastoma regression. Nature Reviews Clinical Oncology, 2014; 11(12): 704–713.
2. Matthay KK et al. Neuroblastoma. Nature Reviews Disease Primers, 2016; 2: 16078.
3. Maris JM. Recent advances in neuroblastoma. New England Journal of Medicine, 2010; 362(23): 2202–2211.