Warning Signs of Childhood Cancer and How It Is Diagnosed

There is no single sign that identifies cancer in a child. The warning signs of childhood cancer, such as prolonged fever, swollen lymph nodes, pallor, bone pain or headache, are the same symptoms that common infections produce. What should raise suspicion is persistence, unusual intensity, or a combination of symptoms that does not resolve into a clear diagnosis.

That is the starting point Dr. Arun Singh Danewa, Senior Consultant – Pediatric-Haemato-Oncology & Bone Marrow Transplant (Unit II), Artemis Hospitals, Gurugram, India, gave general paediatricians and physicians. A question that often arises for them is whether there is a sign that, on its own, should make a doctor think of cancer. His answer is no. Detection depends on vigilance, a careful history, a full physical examination and targeted screening tests, followed by a diagnostic workup that in 2026 must go well beyond the microscope.

This article covers the warning signs organ by organ, the first investigations, and the minimum diagnostic standard before treatment starts. The complete guide to childhood cancer gives the wider picture of survival and care.

Why childhood cancer is easy to miss

Childhood cancer hides among ordinary illness. A prolonged fever can mean an infection, or it can mean leukaemia or lymphoma. An enlarged lymph node is usually a response to a viral infection, but leukaemia and lymphoma also enlarge lymph nodes. Because no symptom is specific, Dr. Danewa's rule is to watch the pattern rather than the symptom:

• Persistence. A symptom that lasts for weeks rather than days.
• Intensity. A symptom that is more severe than the usual illness would explain.
• Combination. Several symptoms together, particularly when the working diagnosis does not account for them.

When those features are present and the cause remains unclear, cancer belongs on the list of possibilities.

Warning signs of childhood cancer, head to toe

Dr. Danewa walked through the subtle signs that, in the right pattern, point towards a specific cancer.

Brain tumours

The pattern to recognise is the early morning headache. Pressure inside the skull rises overnight, so the headache is typically worst on waking, and projectile vomiting follows. Either symptom alone is common; together, and persistent, they warrant imaging.

Lymph nodes and the chest

Lymph nodes enlarged by infection are often tender. Painless nodes, or nodes matted together into a mass, are more suggestive of lymphoma. A mass in the mediastinum, the central compartment of the chest, can compress the veins returning blood to the heart. The visible sign is engorgement of the veins in the neck.

Bone tumours

Bone tumour pain differs from the everyday aches of childhood. It begins slowly, is often noticed at night, and continues for weeks. A child who keeps complaining of pain in the same limb over that period needs examination and imaging rather than reassurance.

Leukaemia

Leukaemia replaces normal bone marrow, so the marrow stops producing healthy cells. The signs follow directly. With too few working white cells, the child gets fever after fever. With too few platelets, bleeding spots appear. With too little haemoglobin, the child becomes pale.

Retinoblastoma

One of the simplest signs to spot is a white reflex in the eye, often visible when a child is photographed. In the place of the normal red reflex, the pupil appears white. It can be the first sign of retinoblastoma, a cancer of the retina.

The first tests: what the blood count shows

When leukaemia is suspected, the complete blood count (CBC) is the first step, and it tends to show one of two patterns.

1. A very high white cell count. The total leucocyte count (TLC) may be in the range of 20,000 to 40,000 per microlitre, or even in the lakhs.
2. Low counts across every cell line. Haemoglobin, platelets and white cells are all low.

Either pattern calls for a bone marrow examination, which is how leukaemia is diagnosed.

How leukaemia is diagnosed in children

Leukaemia in a child is diagnosed on a bone marrow sample tested by flow cytometry, genetic testing and cytogenetics, not by the microscope alone. For decades, leukaemia was diagnosed by morphology: a pathologist looking at the cells under a microscope. Dr. Danewa is unequivocal that this is no longer acceptable on its own. Under the microscope, ALL can be mistaken for AML and AML for ALL, and the error matters because the two leukaemias are treated in completely different ways.

The modern standard rests on three tests.

1. Flow cytometry. A machine that reads the markers on the surface of the cancer cells. ALL and AML carry different markers, so flow cytometry separates them reliably. In Dr. Danewa's view, diagnosing leukaemia by morphology alone is no longer correct; flow cytometry is a requirement.
2. Genetic testing by next-generation sequencing (NGS) or PCR. NGS reads many genes at once to identify the mutations driving the cancer. PCR, the polymerase chain reaction, detects specific known genetic changes.
3. Cytogenetics. Examination of the chromosomes of the leukaemia cells, including their number and any rearrangements.

In 2026, Dr. Danewa said, these three are the minimum whether a child is treated in Africa or in India, and treatment should not start without them.

What genetic testing adds

Not all ALL is the same. In some subgroups, response to therapy is 90 to 95%; in others, around 60 to 70%. Genetic testing reveals which subgroup a child falls into, and it helps in two ways.

• Prognosis. It tells the team how the leukaemia is likely to behave, and therefore whether the child needs standard-risk treatment or more intensive high-risk therapy.
• Targets. It shows whether the leukaemia carries a target that a drug can attack, opening the way to targeted therapy alongside chemotherapy.

The same logic applies to AML, brain tumours and other solid tumours, where NGS is increasingly used both to grade risk and to find a treatable target. How those results change treatment is covered in the leukaemia treatment article and the solid tumours article.

Liquid biopsy where surgery cannot reach

Some tumours sit where surgery is not possible. Diffuse intrinsic pontine glioma (DIPG) grows in the brainstem, the vital centre that controls breathing and heart rate, where the tumour cannot be surgically removed and even a needle biopsy carries risk. Liquid biopsy offers an alternative: by sampling the cerebrospinal fluid (CSF) and analysing circulating tumour DNA, the tumour can be diagnosed and its targets identified. Dr. Danewa described liquid biopsy as coming up in a big way in brain tumours.

Bone tumour biopsy: why the incision direction matters

For a suspected bone tumour, the biopsy incision should run along the length of the limb, because its direction can decide whether the limb can later be saved. Diagnosis is not only about tests: the biopsy itself can shape the outcome. Dr. Danewa showed two biopsy scars, one transverse and one longitudinal, and asked which was right. The answer is the longitudinal incision, running along the length of the limb.

The reason is surgical. If limb salvage surgery is needed later, the surgeon must remove the biopsy tract along with the tumour. A transverse scar forces the removal of far more muscle and tissue, and can compromise the chance of saving the limb. A decision made in a few seconds at the biopsy stage can determine whether the child keeps the leg or arm. His advice to every surgeon is to plan the incision with the definitive operation in mind.

What causes cancer in children

Families nearly always ask why. Dr. Danewa's answer is that, in most children, there is no identifiable cause. In his estimate only around 1% of childhood tumours are familial. Germline sequencing studies find an inherited predisposition gene in a somewhat larger share, around 8 to 10% of children with cancer, often without a family history. In his explanation, the rest arise from mutations that occur by chance in the body and escape the immune system's checks. There is no childhood equivalent of smoking or alcohol. Some viral links are established, notably Epstein-Barr virus in certain lymphomas, but for most childhood cancers no preventable cause has been pinned down, so there is no vaccine to offer. For the doctor in front of a worried family, the message is that the parents did nothing to cause it, and that early recognition is the only lever available.

When to refer a child with suspected cancer

The value of early referral lies in getting the diagnosis and the risk group right from the first day. A child whose ALL is stratified correctly at diagnosis receives the intensity of treatment the disease needs: no more, which spares toxicity, and no less, which guards against relapse. Where a hospital cannot run flow cytometry, cytogenetics or NGS, the samples or the child can go to a centre that can, so that the local team knows the risk group before treatment starts. How that diagnose-centrally, treat-locally model works in practice is described in the complete guide.

The questions doctors asked in the session, including on risk factors and recommended textbooks, are answered in the Live Discussion.