Hepatoblastoma

Hepatoblastoma is a very rare type of liver cancer that primarily affects babies and young children, most commonly before their third birthday. While the diagnosis can be frightening for families, advances in treatment combining chemotherapy and surgery have dramatically improved outcomes, with many children achieving complete recovery.

Table of contents

• What is hepatoblastoma?
• Signs and symptoms
• Causes and risk factors
• Diagnosis
• Staging systems
• Treatment approaches
• Prognosis and survival
• Long-term effects of treatment

What is hepatoblastoma?

Hepatoblastoma is the most common primary malignant liver tumor (a cancerous growth in the liver) in children^[1][2]. This cancer is extremely rare, affecting only 1 to 2 children per million in the United States^[1]. The disease most commonly appears in children during the first three years of life, with about half of all cases diagnosed before age one^[1][2].

The tumor develops when healthy liver cells change and begin growing uncontrollably. These cancer cells resemble the cells found in a developing fetal liver^[3]. While hepatoblastoma usually stays within the liver, it can sometimes spread to other parts of the body, most commonly the lungs and nearby lymph nodes^[4].

• Liver
• Lungs (when cancer spreads)
• Lymph nodes (when cancer spreads)

The liver is one of the largest organs in the body. It sits in the upper right side of the belly inside the rib cage and has two main sections called lobes^[2]. The liver performs many critical functions including helping digest fats from food, storing energy in the form of sugar, and filtering harmful substances from the blood^[2].

Signs and symptoms

Hepatoblastoma tumors grow very slowly, which means children may not show any symptoms until the tumor becomes large enough to affect their body^[1]. In many cases, children appear healthy at first, which can make early detection challenging^[3].

The most common sign that brings families to the doctor is a swollen belly or a noticeable lump in the abdomen, particularly on the right side where the liver is located^[1][4]. This swelling happens because the tumor causes the liver to enlarge, and a doctor can sometimes feel this mass during a physical examination.

Other symptoms that may appear include:

• Pain or discomfort in the belly area^[1]
• Loss of appetite and unexplained weight loss^[1]
• Persistent nausea and vomiting^[1]
• Yellowing of the skin or the whites of the eyes, a condition called jaundice^[1]
• Pale skin and fatigue due to anemia (low number of red blood cells)^[4]
• Fever^[4]
• Itchy skin^[4]
• Back pain^[4]

These symptoms can be caused by many conditions other than hepatoblastoma. However, if your child has persistent belly pain, noticeable swelling, or other concerning symptoms, it is important to contact their pediatrician right away^[1].

Causes and risk factors

Medical experts do not know the exact reason why healthy liver cells become cancer cells in hepatoblastoma^[1][2]. Most cases occur sporadically, meaning they happen by chance without a clear cause. However, about one-third of cases may be linked to certain genetic conditions or other factors^[5].

Several conditions and circumstances increase a child’s risk of developing hepatoblastoma:

• Being born prematurely or with very low birth weight (below 5 pounds, 5 ounces)^[1][2]
• Beckwith-Wiedemann syndrome, which affects growth and increases cancer risk^[1][2]
• Familial adenomatous polyposis (FAP), a genetic condition that causes growths in the colon^[1][2]
• Aicardi syndrome, which causes brain and body malformations^[1][2]
• Hemihyperplasia, where one side of the body grows faster than the other^[1][2]
• Simpson-Golabi-Behmel syndrome, which causes organ abnormalities^[1][2]
• Edwards syndrome (trisomy 18), a chromosomal condition^[1][2]
• Biliary atresia, which blocks bile ducts and damages the liver^[1]
• Glycogen storage disease^[2]

Research has shown that genetic mutations, particularly those affecting the Wnt signaling pathway and leading to accumulation of a protein called beta-catenin, are present in many hepatoblastoma cases^[5]. These mutations occur more frequently in sporadic cases that develop without an underlying genetic syndrome.

Children at high risk due to genetic syndromes may benefit from regular monitoring. Those with Beckwith-Wiedemann syndrome, hemihyperplasia, Simpson-Golabi-Behmel syndrome, and trisomy 18 may have abdominal ultrasound examinations every three months from birth until age four to check for cancer before symptoms appear^[2].

Diagnosis

When a child shows signs that might suggest hepatoblastoma, the healthcare team will perform several tests to determine whether cancer is present and to understand its extent. The diagnostic process begins with a detailed medical history and physical examination focused on the abdomen^[1].

One of the most important diagnostic tools is a blood test that measures alpha-fetoprotein (AFP), a protein produced by the liver^[1][2]. Babies naturally have high levels of AFP at birth, which normally decrease to adult levels by age two. In hepatoblastoma, AFP levels are often significantly elevated, typically above 500 nanograms per milliliter^[3]. This test is valuable not only for diagnosis but also for monitoring how well treatment is working. When treatment successfully removes the cancer, AFP levels should return to normal^[3].

It is important to note that some rare variants of hepatoblastoma do not produce elevated AFP levels, and these cases may have a worse prognosis^[3][4].

Additional blood tests help assess overall health and liver function:

• Complete blood count (CBC) measures and counts different types of blood cells^[1]
• Comprehensive metabolic panel (CMP) checks liver function and other important substances in the blood^[1]
• Tests for blood clotting problems, kidney function, and genetic changes^[4]

Imaging tests create detailed pictures of the liver and surrounding areas to see the tumor and determine its size and location:

• Ultrasound uses sound waves to create images and is often one of the first tests performed to look at the liver^[1][4]
• CT scan (computed tomography) uses X-rays taken from different angles to create detailed cross-sectional images^[1][4]
• MRI (magnetic resonance imaging) uses powerful magnets and radio waves to produce very clear images of organs and blood vessels^[1][4]
• Vascular ultrasound or Doppler ultrasound shows the network of blood vessels entering and leaving the liver^[1]

A biopsy involves removing a small piece of the tumor tissue to examine it under a microscope. This confirms the diagnosis and identifies the specific type of hepatoblastoma^[4]. The biopsy can be done using a needle or during surgery, and the child receives anesthesia so they do not feel pain during the procedure^[4].

Staging systems

After diagnosis, doctors use staging systems to describe how much the cancer has spread within the liver and to other parts of the body. This information is crucial for planning treatment. Two main staging systems are used for hepatoblastoma^[4].

The PRETEXT (pre-treatment extent of disease) staging system was developed by the International Society for Paediatric Oncology and is based on imaging of the liver before any surgery is attempted^[4]. The liver has four main sections called lobes. PRETEXT assigns a stage from I (one) to IV (four) based on how many lobes contain tumor. Stage I means one lobe is involved, while Stage IV means all four lobes have tumor^[4].

The Children’s Oncology Group (COG) staging system considers additional information including imaging of other body parts and the results of surgery if performed at diagnosis^[4]. This system reflects how much tumor was removed and whether the cancer has spread:

• Stage I: The tumor has been completely removed by surgery, and there are no cancer cells at the edges of the removed tissue. No spread of cancer is found outside the liver^[4].
• Stage II: The tumor has been removed, but cancer cells are present at the edges of the removed tissue. No spread is found outside the liver^[4].
• Stage III: The tumor cannot be completely removed, or cancer cells have spread to nearby lymph nodes, or the tumor has ruptured^[4].
• Stage IV: The cancer has spread to distant parts of the body, most commonly the lungs^[4].

The most common sites where hepatoblastoma spreads are the lungs and lymph nodes around the belly^[4].

Treatment approaches

The most important advance in treating hepatoblastoma has been the development of effective chemotherapy^[5][12]. Complete surgical removal of the tumor combined with chemotherapy offers the best chance for cure. Over the past three decades, survival rates have improved dramatically from about 30 percent in the 1970s to approximately 70 percent or higher today^[5][11].

Chemotherapy uses powerful medicines that interfere with cancer cells’ ability to grow and reproduce^[6]. The medicines travel through the bloodstream to reach cancer cells throughout the body. The most effective single drug for hepatoblastoma is cisplatin^[12]. Doctors typically combine cisplatin with other chemotherapy drugs such as doxorubicin, fluorouracil (5-FU), and vincristine^[12].

Most children receive chemotherapy before surgery, an approach called neoadjuvant chemotherapy^[5][11]. This treatment shrinks the tumor, making it easier and safer to remove surgically. In some cases, preoperative chemotherapy can completely eliminate disease that has spread to the lungs or reduce multiple tumors in the liver^[12].

Children with very small tumors that are completely contained within one or two sections of the liver may have surgery first, followed by chemotherapy^[12]. After surgery, chemotherapy usually begins about two to four weeks later to allow the liver time to heal and regenerate^[12].

Surgery is essential for curing hepatoblastoma regardless of the stage^[9][11]. The goal is to remove all visible tumor tissue. Depending on the tumor’s size and location, surgeons may remove a portion of the liver (called a partial hepatectomy or liver resection) or, in cases where the tumor affects the entire liver, perform a liver transplant^[1][3].

The liver has a remarkable ability to regenerate. Even when a large portion is removed, the remaining healthy liver tissue can grow back to nearly normal size within a few months.

Liver transplantation may be recommended when the tumor is too large or widespread within the liver to be safely removed while leaving enough healthy liver tissue behind^[3][13]. This procedure involves removing the entire diseased liver and replacing it with a healthy liver from a donor. Liver transplantation can provide high long-term survival rates, around 80 percent, when the tumor is completely removed and followed by chemotherapy^[3].

Newer treatments being studied include specialized procedures that deliver treatment directly to the liver tumor. Radioembolization (Y90) delivers high-dose radiation through the bloodstream directly to the tumor, protecting normal liver tissue^[7]. Transarterial chemoembolization (TACE) delivers chemotherapy drugs directly into the artery feeding the tumor while blocking the blood supply^[7]. These treatments may be used when tumors do not respond well to standard chemotherapy or when they return after initial treatment.

Prognosis and survival

The outlook for children with hepatoblastoma depends on several important factors. Early diagnosis and the ability to completely remove the tumor surgically lead to the best outcomes^[1].

Key factors that influence prognosis include:

• AFP levels at diagnosis – higher levels generally indicate a better response to treatment^[5]
• Age at diagnosis^[5]
• Whether the tumor can be completely removed^[5]
• The stage of disease^[5]
• Whether cancer has spread to other parts of the body – this is the strongest predictor of poorer outcomes^[3]

With modern treatment combining chemotherapy and surgery, many children with hepatoblastoma can be cured. Children with early-stage disease that can be completely removed have particularly good outcomes, with cure rates approaching 90 to 100 percent^[11][12].

Even children with more advanced disease or cancer that has spread can achieve good outcomes with aggressive treatment including liver transplantation when appropriate^[13]. Treatment at specialized centers with experience in complex liver surgery and pediatric cancer care may provide the best results for children with large or extensive tumors^[9].

Long-term effects of treatment

While treatment can cure hepatoblastoma, cancer therapies may cause health problems that appear months or even years after treatment ends. These are called late effects^[1][2].

Children who have been treated for hepatoblastoma need ongoing medical care and monitoring to watch for and manage potential late effects. These health issues can affect:

• Thinking, learning, and memory^[1]
• Growth and development^[1]
• Mood, feelings, and mental health^[1]
• Various organs and tissues^[1]
• Hearing, particularly with cisplatin chemotherapy which can cause hearing loss^[12]

One serious late effect is the development of a second cancer, which is a completely new and different type of cancer that appears months or years after completing hepatoblastoma treatment^[1][2].

Children who receive liver transplants need to take medications that suppress the immune system for the rest of their lives to prevent rejection of the transplanted organ. These medicines require careful monitoring and management by specialized healthcare teams.

Regular follow-up appointments with the healthcare team are essential. During these visits, doctors will monitor your child’s overall health, check for any signs of cancer returning, and watch for potential late effects. Your child’s medical team will create a personalized follow-up care plan based on the specific treatments your child received^[2].