Neuroblastoma — the under-5 nerve cell cancer, explained

Neuroblastoma is a cancer that forms in immature nerve cells called neuroblasts. These cells are part of the sympathetic nervous system, which controls involuntary functions such as heart rate, blood pressure, and digestion. Because neuroblasts are present throughout the body during foetal development, neuroblastoma can appear in several locations — most commonly the adrenal glands (the small glands that sit on top of the kidneys), and also along nerve tissue in the abdomen, chest, neck, and spine. Neuroblastoma is almost exclusively a disease of young children; the large majority of cases are diagnosed before the age of five. The exact cause is not fully understood. Most cases arise spontaneously without any known risk factor or family history. A very small number of cases run in families and are linked to certain inherited gene changes, but this is rare. Neuroblastoma is not caused by anything the parents did before or during pregnancy.

The warning signs of neuroblastoma depend on where the tumour is growing and whether it has spread. The most common early finding is a firm, painless lump or swelling in the abdomen — sometimes noticed by a parent while bathing the child, or found during a routine check. Other signs that sometimes appear include: a swollen belly that makes the child seem unusually full or uncomfortable; unexplained weight loss or a child who has stopped growing as expected; persistent tiredness or paleness that does not improve; bone pain, which may make a young child irritable, reluctant to walk, or limp for no obvious reason; a visible lump in the neck or chest; drooping of one eyelid or one pupil appearing smaller than the other (Horner syndrome, which can occur if the tumour is near certain neck nerves); rapid, involuntary eye movements (opsoclonus); or, in advanced cases, bluish lumps on the skin that may resemble bruising. These signs are not specific to neuroblastoma — each can have many other causes. A doctor’s evaluation is the right step if any of these persist without explanation.

Diagnosing neuroblastoma involves several steps. When a lump or concerning symptom brings a child to the doctor, initial investigations include an ultrasound of the abdomen, followed by cross-sectional imaging (CT scan or MRI) to better define the tumour and check whether it has spread to lymph nodes, bone marrow, or other sites. A urine test looking for catecholamine breakdown products (HVA and VMA) is important because neuroblastoma cells often produce these chemicals in abnormal quantities. A bone marrow biopsy is done to check whether the cancer has reached the marrow. Tissue from the tumour itself is taken (biopsy) and examined under a microscope by a pathologist, who also carries out molecular and genetic tests on the tumour cells — including checking for a gene abnormality called MYCN amplification, which significantly influences risk grouping and treatment planning. An MIBG scan — a specialised nuclear medicine scan — is often used to map neuroblastoma throughout the body, as most neuroblastoma tumours absorb the MIBG tracer. All these results together give the oncology team the information they need to assign a risk group and plan treatment.

In neuroblastoma, the oncology team assigns every child to a risk group — typically low, intermediate, or high risk — based on a combination of factors: the child’s age at diagnosis, the stage of the disease (how far it has spread), the biology and genetic features of the tumour cells (including whether the MYCN gene is amplified), and how the tumour looks under the microscope. Risk grouping matters because it directly determines the intensity of treatment recommended. Children in the low-risk group often do very well with limited treatment, and in some cases a very immature form of the tumour may even be observed without immediate treatment, as it may mature or shrink on its own. Children in the intermediate-risk group receive moderately intensive chemotherapy. Children in the high-risk group require the most intensive treatment programme, which typically involves multiple phases of chemotherapy, surgery, and additional therapies. Understanding the risk group is one of the first conversations the paediatric oncology team will have with you.

Treatment for neuroblastoma is tailored to the child’s risk group. For low-risk disease, treatment may involve surgery alone — removing the tumour — or in some very immature forms, careful observation. For intermediate-risk disease, the treatment programme typically combines chemotherapy to shrink the tumour, followed by surgery to remove it. For high-risk disease — which accounts for a significant proportion of neuroblastoma cases in children over 18 months — treatment is more intensive and multi-phase: induction chemotherapy to reduce the tumour and treat any spread, high-dose chemotherapy with a stem cell rescue (autologous stem cell transplant), surgery to remove the primary tumour, radiation therapy directed at the tumour site, and maintenance therapy using agents that target remaining cancer cells and help prevent relapse. Every step of this journey is planned by a multidisciplinary team including medical oncologists, surgical oncologists, radiation oncologists, and supportive care specialists. At CION, every child’s case is reviewed at a tumour board before any treatment begins — we do not make rushed decisions.

In a small subset of cases — specifically very young infants (under 12 months) with a particular pattern of disease that has a special designation in older staging systems — neuroblastoma tumours can sometimes spontaneously mature into benign cells or shrink without treatment. This remarkable biological behaviour is only seen in certain carefully defined situations. It does not mean that all neuroblastoma is likely to resolve without treatment. Any child suspected of having neuroblastoma needs a full diagnostic evaluation at a specialist paediatric oncology centre so that the tumour biology can be properly assessed. Whether watchful waiting is appropriate is a decision made by the oncology team based on precise criteria — not something to assume without specialist assessment. For the majority of children, especially those with high-risk disease, prompt and comprehensive treatment is essential.