Neuroblastoma: Understanding Your Pathology Report

by Jason Wasserman MD PhD FRCPC
September 11, 2026

Neuroblastoma is a cancer that develops from neuroblasts, immature nerve cells that are present while a baby is developing before birth. It starts in tissues that develop from neural crest cells, most often in the adrenal glands above the kidneys. It can also start in the chest, the abdomen, the pelvis, or the chain of nerves running alongside the spine.

It is the most common solid tumor outside the brain in children. The median age at diagnosis is about 17 months, and roughly 9 in 10 children are diagnosed before age 10. Neuroblastoma occurs very rarely in adults, where it tends to grow more slowly but is harder to control over time.

Neuroblastoma behaves more variably than almost any other childhood cancer. Some tumors in infants shrink and disappear without any treatment at all, while others need intensive multi-part treatment. This article explains what appears on a neuroblastoma pathology report. It also explains how those findings, along with the stage and the child’s age, determine which situation applies.

What are the symptoms of neuroblastoma?

The symptoms of neuroblastoma depend on where the tumor started and whether it has spread. Many are vague at first and are mistaken for common childhood illnesses.

A lump or swelling in the abdomen. The commonest presentation, often noticed by a parent or during a routine examination.
Difficulty breathing or a persistent cough. From a mass in the chest.
Bone pain or limping. From spread to bone, which is common at diagnosis in older children.
Bruising or dark circles around the eyes. Sometimes called raccoon eyes, and caused by spread to the bones around the eye socket.
Swollen lymph nodes, or bluish lumps under the skin. Skin lumps are seen mainly in babies.
Weakness in the legs or trouble walking. This happens when a tumor beside the spine grows into the spinal canal and presses on the spinal cord.
A drooping eyelid and a smaller pupil on one side. This can be from a tumor in the neck or upper chest affecting nearby nerves.

Neuroblastoma can also cause paraneoplastic syndromes, meaning symptoms produced by substances the tumor releases rather than by the tumor itself. These include severe watery diarrhea, high blood pressure, and a condition causing rapid jerking eye movements and unsteadiness, sometimes called dancing eye syndrome. Children with that condition often have a tumor with a favorable outlook.

What causes neuroblastoma?

Neuroblastoma develops when neuroblasts acquire genetic changes that keep them dividing instead of maturing into working nerve cells. These changes usually happen by chance during the rapid cell division of normal development. They are not linked to diet, activity, infection, or anything in the home environment.

Several genes are involved. Changes in MYCN and ALK are the best known, along with changes affecting telomeres, the protective caps on the ends of chromosomes that normally shorten as cells age. Most of these changes are present only in the tumor. A small number of children inherit a change that makes the tumor more likely, which is covered in its own section below.

How is the diagnosis made?

Diagnosing neuroblastoma combines imaging, laboratory tests, and tissue examination. Several of these happen at the same time, because the same tests that confirm the diagnosis also establish how far the tumor has spread.

Imaging. Ultrasound, CT, or MRI shows the tumor and its relationship to nearby organs and blood vessels. A special scan called MIBG uses a substance that neuroblastoma cells take up, and it finds tumor anywhere in the body. Roughly 1 in 10 neuroblastomas do not take up MIBG, and a PET scan is used instead.
Urine tests. Most neuroblastomas release breakdown products of adrenaline-like hormones, measured in the urine as HVA and VMA. These are elevated in most children at diagnosis and are also used to monitor response to treatment.
Tumor biopsy. A pathologist examines tumor tissue under the microscope. Molecular tests also require enough tissue, so a core or open biopsy is usually preferred over a fine needle.
Bone marrow biopsy. Samples are taken from both hips, because neuroblastoma commonly spreads to the marrow and can involve one side and not the other.

In some children, the diagnosis can be made from tumor cells in the bone marrow together with raised urine catecholamines, without a biopsy of the main tumor. Even then, doctors usually still obtain tissue because they need molecular results to plan treatment.

The neuroblastic tumor family

Neuroblastoma belongs to a family of tumors that all arise from neuroblasts but differ in how far the cells have matured. Your report may name one of the others, and the difference matters a great deal.

Neuroblastoma. Made almost entirely of immature neuroblasts, with little of the supporting tissue called Schwannian stroma. This is the cancerous end of the family.
Ganglioneuroblastoma, intermixed. Contains areas of maturing tumor cells within abundant supporting tissue. It behaves favorably.
Ganglioneuroblastoma, nodular. Contains one or more distinct nodules of immature neuroblastoma within otherwise maturing tissue. The nodule determines treatment, so this type is treated like a neuroblastoma.
Ganglioneuroma. Made entirely of mature nerve cells and supporting tissue. It is not cancer.

These tumors sit on a spectrum, and a neuroblastoma can mature over time into a more favorable member of the family, sometimes without treatment.

What are the types of neuroblastoma?

Neuroblastomas are divided into three types according to how closely the tumor cells resemble normal nerve cells, a process called neuroblastic differentiation. The type appears on the pathology report and feeds into the histology classification described below.

Undifferentiated. Uncommon. The cells are primitive and show no nerve features under the microscope, appearing as small round blue cells. Additional stains are always needed because several other childhood tumors look the same at this stage.
Poorly differentiated. The most common type. The cells show early nerve features, including small extensions called neurites and ring-shaped arrangements called Homer-Wright rosettes, but little maturation beyond that.
Differentiating. The cells are clearly maturing toward normal nerve cells. They are larger, with abundant neurites and nuclei showing signs of maturation. At least 5 percent of the cells must show these changes for this label to be used.

Mitosis-karyorrhexis index and favorable or unfavorable histology

The mitosis-karyorrhexis index, usually written MKI, measures how many neuroblastoma cells are dividing or dying. The pathologist counts cells undergoing mitosis (division) or karyorrhexis (the nucleus breaking apart as the cell dies) among 5,000 tumor cells. The result is reported as low, intermediate, or high.

The MKI is then combined with the type of tumor and with the child’s age at diagnosis to produce a single overall judgment, under the International Neuroblastoma Pathology Classification. The report will describe the tumor as having favorable histology or unfavorable histology.

Age is central to this and often surprises families. The same microscopic appearance can be favorable in a young infant and unfavorable in an older child. A degree of immaturity that is expected at 6 months is not expected at 3 years. A parent comparing their child’s report with another child’s will therefore sometimes find identical microscopic descriptions leading to different conclusions.

Immunohistochemistry

Immunohistochemistry uses antibodies to detect specific proteins inside neuroblastoma cells, and the results confirm the diagnosis and distinguish it from other small round cell tumors.

Neuroblastoma is typically positive for PHOX2B, which is the most specific of these markers, and for synaptophysin, chromogranin, CD56, and tyrosine hydroxylase. All of these are proteins made by nerve cells.

Your report may also mention GD2, a substance on the surface of nearly all neuroblastoma cells. It is not used for diagnosis, but it is the target of the antibody treatments described later in this article.

Molecular tests

Molecular tests on neuroblastoma tissue identify genetic changes that predict how the tumor will behave, and several of them feed directly into the risk group. These results often matter more than the microscopic appearance.

MYCN amplification. Extra copies of the MYCN gene, found in roughly 1 in 5 neuroblastomas and detected by FISH. This is the single strongest unfavorable finding, and on its own it usually places a tumor in the high-risk group, whatever else is present.
Segmental chromosomal changes. Losses or gains of whole sections of a chromosome. Loss of part of chromosome 11q, loss of part of 1p, and gain of part of 17q are the ones most often reported. Each is associated with a higher risk of the tumor returning.
Ploidy. The total amount of DNA in the tumor cells, sometimes reported as the DNA index. Cells with extra whole chromosomes, described as hyperdiploid, are a favorable finding in infants.
ALK. Changes in this gene are found in roughly 1 in 10 neuroblastomas. They are associated with a less favorable outlook, and they are also a treatment target being tested in current trials.
TERT and ATRX. Changes affecting telomeres. Both are linked to a poorer outlook, and ATRX changes are seen mainly in older children and adolescents.

Stage and risk group

Neuroblastoma is not staged with the TNM system used for most adult cancers. It uses the International Neuroblastoma Risk Group Staging System, which is based on imaging performed before any treatment, and which describes whether the tumor can be safely removed by surgery.

Stage L1. The tumor is confined to one body compartment and does not involve vital structures.
Stage L2. The tumor involves one or more vital structures, described as image-defined risk factors, which makes complete removal at the outset unsafe.
Stage M. The tumor has spread to distant sites.
Stage MS. A special stage for children under 18 months, where spread is limited to the skin, liver, and bone marrow. These tumors often regress on their own, and some children are observed.

The stage is then combined with the child’s age, histology classification, MYCN result, 11q result, and ploidy. Together, these assign a risk group of very low, low, intermediate, or high, under the International Neuroblastoma Risk Group classification. Some centers use a revised version from the Children’s Oncology Group that also accounts for other segmental chromosomal changes.

The risk group, not the pathology report alone, determines the treatment. Age 18 months is the usual dividing line, and a child under that age with the same findings as an older child is often placed in a lower-risk group.

What is the prognosis?

Outcomes in neuroblastoma vary more widely than in most childhood cancers, and the risk group is what matters for an individual child. A single figure for the disease as a whole would be misleading.

Low risk. Roughly 98 percent of children are alive five years after diagnosis, with about 91 percent having had no return of the tumor. Many need little or no treatment.
Intermediate risk. Roughly 96 percent are alive at five years, with about 85 percent free of any return.
High risk. Roughly 63 percent are alive at five years, with about 51 percent free of any return. This group accounts for close to half of all children diagnosed and is where current research is concentrated.

Features linked to a less favorable outcome include MYCN amplification, age over 18 months, unfavorable histology, spread at diagnosis, and loss of chromosome 11q. Features linked to a more favorable outcome include young age, favorable histology, hyperdiploid tumor cells, and stage MS disease.

These figures come from large groups of children treated over many years and cannot predict what will happen to one child. Outcomes for high-risk disease have improved considerably over the past two decades, particularly since antibody treatment became part of standard care.

What happens after the diagnosis?

The risk group decides treatment for neuroblastoma, and the range is wider than for almost any other childhood cancer. A children’s cancer center plans care, usually using a protocol developed by a cooperative research group.

For very low and low risk disease, treatment may be surgery alone, and for some infants, including many with stage MS, careful observation without any treatment. These tumors frequently mature or disappear on their own.

For intermediate risk disease, a moderate course of chemotherapy is given to shrink the tumor, usually followed by surgery.

For high-risk disease, treatment has several phases over roughly 18 months. Induction chemotherapy is followed by surgery, then high-dose chemotherapy with the child’s own blood stem cells returned afterward to rebuild the bone marrow, then radiation to the original tumor site. Maintenance treatment follows, combining isotretinoin with an antibody that targets GD2 on the tumor cell surface.

The FDA has approved two GD2 antibodies. Dinutuximab was approved in 2015 for use after the intensive phase of treatment, given with isotretinoin and two immune-stimulating drugs. In the trial supporting that approval, about 63 percent of children were free of tumor recurrence at two years, compared with about 46 percent with isotretinoin alone. Naxitamab received accelerated approval in 2020 for neuroblastoma in the bone or bone marrow that has come back or not responded. A related antibody, dinutuximab beta, is approved in the European Union.

An ALK inhibitor called lorlatinib is being tested in current trials for children whose tumors carry an ALK change, as an addition to standard treatment. It is not yet an approved treatment for neuroblastoma, and access is generally through a clinical trial.

Long-term follow-up continues for years and covers hearing, kidney function, growth, hormone function, and fertility, all of which the intensive treatments can affect.

Can neuroblastoma be inherited?

Most neuroblastomas are not inherited. The genetic changes found in the tumor developed in that tumor during the child’s lifetime and are not present in the rest of the body’s cells.

Roughly 1 to 2 percent of children have an inherited change that makes the tumor more likely, most often in the ALK or PHOX2B genes. Features that raise this possibility include more than one tumor in the same child and a tumor in both adrenal glands. Others include a family history of neuroblastoma and a very young age at diagnosis. PHOX2B changes can also occur alongside Hirschsprung disease or a breathing condition present from birth.

We offer genetic testing on a blood or saliva sample when any of these features are present. You can read more in our article What is a hereditary cancer syndrome?

Questions to ask your doctor

What type of neuroblastoma is described on the report, and is any part of it maturing?
Is the histology favorable or unfavorable, and how did my child’s age affect that?
What was the MKI result?
Was MYCN amplification found?
Were segmental chromosome changes looked for, particularly loss of 11q?
Was an ALK change found, and does that open a treatment option or a trial?
What stage was assigned, and what does that letter mean?
Which risk group is my child in, and what determined it?
Given the risk group, is observation an option, or is treatment needed now?
Was tumor found in the bone marrow on both sides?
Will antibody treatment be part of the plan, and at what stage?
Should my child have genetic testing for an inherited change?
Is treatment being given on a cooperative group protocol or a clinical trial?
What long-term follow-up will be needed, particularly for hearing and kidney function?