Hepatoblastoma: Understanding Your Pathology Report

Section Editor: Anthea Girdwood MD FRCPC
September 10, 2026

Hepatoblastoma is a cancer that develops from immature liver cells. It is the most common liver cancer in children and accounts for about 1 percent of all childhood cancers. Most children are diagnosed before their third birthday, and almost all before the age of 5. It is different from hepatocellular carcinoma, the liver cancer seen in adults, which arises from mature liver cells that have been damaged over many years.

This article is written for parents and caregivers. It explains what appears on a hepatoblastoma pathology report, why the blood test called alpha-fetoprotein matters so much in this diagnosis, and how clinicians use the findings to plan treatment. Most children with hepatoblastoma are cured, and the sections below explain what the report contributes to that.

What causes hepatoblastoma?

Hepatoblastoma develops when cells that would normally mature into working liver cells acquire genetic changes that keep them dividing instead. 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 situations raise the risk, and some of them explain why a particular child developed this tumor.

Very low birth weight and prematurity. The strongest known association outside of inherited conditions. The risk rises as birth weight falls, and it is highest in babies born weighing under 1,000 grams.
Beckwith-Wiedemann syndrome. An overgrowth condition present from birth. Children with it are screened for liver tumors and for nephroblastoma with regular ultrasound and blood tests during early childhood.
Familial adenomatous polyposis. An inherited condition caused by changes in the APC gene, better known for causing bowel polyps in adolescence and adulthood. It also raises the risk of hepatoblastoma in early childhood, and a small proportion of children with hepatoblastoma turn out to carry an APC change.
Other genetic conditions. Trisomy 18 and Simpson-Golabi-Behmel syndrome are also associated with hepatoblastoma, though less commonly.

Because an inherited condition is found in a meaningful minority of children, genetic assessment is often offered after a hepatoblastoma diagnosis. A finding of familial adenomatous polyposis in particular has consequences for parents, brothers, and sisters that reach well beyond the child’s treatment.

What are the symptoms of hepatoblastoma?

Hepatoblastoma usually causes few symptoms until the tumor is large, which is why many are found late. The commonest presentation is a swelling or firm lump in the abdomen, often noticed by a parent during bathing or dressing, or by a clinician during a routine examination.

An abdominal mass or swelling. Usually painless and on the right side, under the ribs.
Loss of appetite and weight loss. Or a child who is not gaining weight as expected.
Abdominal pain. Usually a later sign, and sometimes sudden if the tumor bleeds.
Nausea and vomiting. From the tumor pressing on the stomach and bowel.
Early puberty in boys. Uncommon, and caused by a hormone that some hepatoblastomas produce.

Yellowing of the skin and eyes is not typical, which surprises many families, because the tumor usually leaves enough healthy liver working normally.

How is the diagnosis made?

The diagnosis of hepatoblastoma is usually suspected from a combination of the child’s age, an ultrasound or MRI showing a liver mass, and a raised alpha-fetoprotein level in the blood. Confirmation requires tissue, and in most children, a biopsy is performed before treatment begins. A needle is passed into the tumor, usually through the skin and under general anesthesia, to take a small core of tissue.

The biopsy serves two purposes. It confirms that the tumor is a hepatoblastoma rather than one of the other liver tumors that occur in children, which look similar on a scan. It also provides material for the molecular and immunohistochemical tests described below, which increasingly guide treatment.

In some children, the surgeon removes the whole tumor at the first operation, and the pathologist then examines the entire specimen. This is more common when the tumor is small and confined to one part of the liver.

Under the microscope, hepatoblastoma is made of cells that resemble the liver at various stages of its development before birth. A pathologist describes which stage the cells resemble, and that description becomes the tumor type.

Alpha-fetoprotein and what the number means

Alpha-fetoprotein, usually shortened to AFP, is a protein made by the developing liver before birth. Most hepatoblastomas produce it in large amounts, so blood levels are high in roughly 9 out of 10 children at diagnosis. AFP is used in three ways in hepatoblastoma: to support the diagnosis, to monitor response to treatment, and to watch for recurrence.

Two features of AFP can be confusing and are worth understanding.

Newborns normally have very high AFP. Levels are high at birth and fall steadily over the first months of life, reaching adult levels at around 8 months. A number that would be alarming in a 3-year-old can be entirely normal in a 2-month-old. Laboratories therefore compare the result against a range for the child’s age, and a raised AFP in a young infant needs interpretation rather than reaction.

A low AFP is concerning, not reassuring. A small number of hepatoblastomas have an AFP below 100 nanograms per milliliter at diagnosis. This has long been recognized as a poor sign, and the reason has only recently become clear. Many tumors in that group turn out on modern testing not to be hepatoblastoma at all, but a different and more difficult tumor called a rhabdoid tumor of the liver. This is why a low AFP prompts additional testing rather than reassurance.

What are the types of hepatoblastoma?

Hepatoblastoma is divided into types according to which stage of normal liver development the tumor cells resemble. Most tumors contain more than one pattern, and the report describes each pattern present. The type matters because it influences how the tumor is expected to respond to treatment.

Well-differentiated fetal. Cells closely resembling the fetal liver, arranged in orderly plates, with few dividing cells. When a tumor is entirely of this type, has a low mitotic count, and is completely removed at the first operation, it is the most favorable situation in hepatoblastoma. Some of these children are cured with surgery alone and need no chemotherapy.
Embryonal. Cells resembling an earlier stage of liver development, smaller and more crowded than the fetal type. Frequently found mixed with a fetal component.
Macrotrabecular. Tumor cells growing in thick plates many cells wide.
Small cell undifferentiated. Small cells with no resemblance to liver at all. Even a small amount of this pattern within an otherwise ordinary tumor lowers the chance of cure, and it always prompts the additional test described in the next section.
Cholangioblastic and pleomorphic. Less common patterns, described when present.
Mixed epithelial and mesenchymal. The tumor contains supporting tissue such as cartilage or bone alongside the liver-like cells. When other tissue types such as skin or nerve are present as well, the report may add the phrase “with teratoid features.”

Molecular and immunohistochemical testing

Tests beyond the microscope are now routine in hepatoblastoma diagnosis. Immunohistochemistry uses antibodies to detect specific proteins in the tumor cells, and molecular tests look for changes in genes.

Beta-catenin. Most hepatoblastomas carry a change in a gene called CTNNB1, which controls a growth pathway in liver cells. The change causes the beta-catenin protein to accumulate in the nucleus of tumor cells, where a stain can detect it. This supports the diagnosis, and the same pathway is disrupted in children with familial adenomatous polyposis.
INI1, also called SMARCB1. The most important test when a small cell undifferentiated pattern is present. Normal cells make the INI1 protein and stain positive. If the stain is negative, meaning the protein has been lost, the tumor is not a hepatoblastoma but a rhabdoid tumor of the liver, which is treated differently. This single stain can completely change the diagnosis.
Glypican-3 and alpha-fetoprotein stains. Used to confirm that the tumor cells are of liver origin when the appearance is unclear.
Gene panels. Next-generation sequencing reads many genes at once. In hepatoblastoma, it is used mainly to confirm the CTNNB1 change and to look for findings that suggest an inherited condition.

PRETEXT, and how the risk group is assigned

Hepatoblastoma is not staged with the TNM system used for most adult cancers. It uses a system called PRETEXT, short for PRE-Treatment EXTent of disease, which is determined from imaging before treatment starts rather than from the pathology report.

The liver is divided into four sections. The PRETEXT group records how many of those sections are free of tumor.

PRETEXT I. Three sections are free of tumor.
PRETEXT II. Two sections are free.
PRETEXT III. One section is free.
PRETEXT IV. Tumor involves all four sections.

Letters are added for features that make surgery harder or the outlook less favorable. These include involvement of the major veins, growth outside the liver, more than one tumor, rupture of the tumor, and spread to lymph nodes or distant sites. Imaging is repeated after chemotherapy, and the reassessment is called POST-TEXT.

The PRETEXT group is then combined with the child’s age, the AFP level, and whether the tumor has spread. Together, these place the child in a risk group of very low, low, intermediate, or high. The system used internationally comes from the Children’s Hepatic Tumors International Collaboration, published in 2017. The risk group determines how much chemotherapy is given and whether a liver transplant needs to be considered early.

Surgical margins

Complete surgical removal of a hepatoblastoma is necessary for cure, so margins are among the most important findings in the report after surgery. The margin is the edge of tissue cut by the surgeon. The pathologist inks it and examines it under the microscope.

A negative margin means no tumor cells were seen at the inked edge. A positive margin means the tumor reaches the edge and some may have been left behind, which usually leads to further treatment.

Margin

Most children receive chemotherapy before surgery, which shrinks the tumor and makes complete removal possible in many cases that looked impossible at diagnosis. When the tumor still involves too much of the liver, a liver transplant can be curative. Referral to a transplant center is made early rather than after an attempted removal has failed. The report on a liver removed at transplant describes how much tumor remained after chemotherapy, which is useful information about how well the treatment worked.

What is the prognosis?

Most children with hepatoblastoma are cured. Overall, roughly 80 percent are alive five years after diagnosis, and for children whose tumor is confined to the liver and completely removed, the figure is above 90 percent.

Outcome depends mainly on how far the tumor has spread and on whether it can be completely removed.

PRETEXT group. In a large trial cohort, five-year survival was roughly 89 percent for PRETEXT I, 85 percent for PRETEXT II, 72 percent for PRETEXT III, and 31 percent for PRETEXT IV. Surgical technique and transplantation have improved considerably since those children were treated, and current results for the higher groups are better.
Risk group. In a recent multicenter study, four-year survival was 100 percent for very low risk, 97 percent for low risk, 94 percent for intermediate risk, and 87 percent for high risk. The proportion who never relapsed was lower in each group, particularly high risk at 51 percent, because some children whose cancer returns are cured with further treatment.
Spread at diagnosis. Historically the hardest situation, with survival around 27 percent in the 1990s. With modern chemotherapy, surgery to remove secondary tumors, and transplantation, reported survival has risen to around 79 percent.
Tumor type. A completely removed tumor that is entirely well-differentiated fetal with a low mitotic count carries the best outlook of all. Any small cell undifferentiated component lowers it substantially, even when the tumor is otherwise small and confined.
A low AFP at diagnosis. Associated with a poorer outcome, partly because some of these tumors are rhabdoid tumors rather than hepatoblastoma.

These figures come from groups of children treated over many years and cannot predict what will happen to one child—the gap between the proportion who never relapse and the proportion who survive matters. A relapse is a setback rather than an ending, and many children in that position are still cured. The oncology team can provide figures that match your child’s PRETEXT group, risk group, and tumor type.

What happens after the diagnosis?

A team that includes a pediatric oncologist, a liver surgeon, a radiologist, and a pathologist manages hepatoblastoma at a center that regularly treats children’s liver tumors. Because surgery is essential to cure and some children need a transplant, referral to a center with a pediatric liver transplant program is often made at the outset.

Most children receive chemotherapy before surgery, built around a drug called cisplatin. The aim is to shrink the tumor enough for complete removal. Surgery follows, either removing part of the liver or, when the tumor cannot be removed any other way, replacing the liver entirely. More chemotherapy is usually given afterward. Children with a completely removed, entirely well-differentiated fetal tumor may need no chemotherapy at all.

AFP is measured throughout. A falling level during chemotherapy shows the tumor is responding. The level is followed for years afterward, because a rise can signal a recurrence before anything is visible on a scan. Follow-up also covers the late effects of treatment, particularly hearing loss and kidney function, which cisplatin can affect. Genetic assessment is offered where an inherited condition is suspected.

Questions to ask your doctor

What type or types of hepatoblastoma are described on the report?
Was any small cell undifferentiated component found?
If so, was the INI1 stain performed, and did it confirm this is a hepatoblastoma rather than a rhabdoid tumor?
What was my child’s AFP level at diagnosis, and how does it compare with the normal range for their age?
What PRETEXT group was assigned, and were any of the additional letters applied?
Which risk group is my child in, and what determined it?
Is the tumor removable now, or is chemotherapy needed first to shrink it?
Should we be referred to a liver transplant center, and when?
If surgery has already happened, were the margins negative?
How will AFP be used to follow the response to treatment?
Should my child have genetic testing, and does this diagnosis have implications for our other children or for us?
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?