Hepatoblastoma
Content of This Page
1- Introduction
2- Pathophysiology
3- Symptoms
4- Investigations
5- Treatment
6- Prognosis
Introduction
Hepatoblastoma is a rare malignant liver tumor that occurs almost exclusively in children under 3 years of age. It arises from immature liver cells (hepatoblasts) and typically presents as a painless abdominal mass. Unlike adult liver cancers, it is not associated with cirrhosis.
Pathophysiology
1. Cell of Origin
Hepatoblasts are immature liver cells present during fetal development.
In hepatoblastoma, these cells proliferate abnormally and fail to differentiate into mature hepatocytes.
2. Genetic Abnormalities
Common mutations include:
CTNNB1 gene mutations → leads to β-catenin activation, which promotes cell proliferation and survival.
Chromosomal abnormalities (e.g. trisomy 2, 8, or 20) are also reported in some cases.
These mutations disrupt the Wnt/β-catenin signaling pathway, crucial for liver development and regeneration.
3. Tumor Subtypes
Epithelial type: resembles fetal or embryonal liver cells.
Mixed epithelial and mesenchymal type: includes non-liver tissues (e.g. bone, cartilage, muscle), indicating abnormal multilineage differentiation.
4. Tumor Growth
The tumor typically forms a well-circumscribed mass in the liver.
It is often hypervascular and may compress surrounding liver parenchyma.
Metastasis, especially to the lungs, may occur if not detected early.
5. AFP Production
Hepatoblastoma cells often continue producing alpha-fetoprotein (AFP), a fetal plasma protein, which serves as a tumor marker.
High AFP levels reflect active tumor growth and are used for both diagnosis and monitoring.
Symptoms
Abdominal mass or distension
Most frequent presenting sign.
Usually painless and firm, noted incidentally by parents or during routine exam.
Abdominal pain
Less common unless the tumor is large, hemorrhages, or stretches the liver capsule.
Weight loss or failure to thrive
Non-specific but may reflect underlying malignancy.
Anorexia or poor feeding
Reduced appetite, particularly in infants and toddlers.
Nausea and vomiting
Due to mass effect or hepatomegaly.
Fever
Occasionally, due to tumor necrosis or secondary infection.
Jaundice (rare)
Occurs only if bile ducts are compressed or invaded.
Respiratory symptoms
Such as cough or breathlessness if there are lung metastases.
Investigations
1. Laboratory Tests
Alpha-fetoprotein (AFP)
Very high AFP levels are found in over 90% of cases.
Useful for diagnosis, prognosis, and monitoring response to therapy.
Complete blood count (CBC)
May show anemia or thrombocytosis.
Liver function tests (LFTs)
Usually normal unless there’s biliary obstruction or extensive tumor burden.
Renal function and electrolytes
Baseline before chemotherapy.
2. Imaging
Abdominal ultrasound
First-line for detecting a liver mass.
Can assess tumor size, vascularity, and any cystic components.
Contrast-enhanced CT or MRI of the abdomen
Defines the anatomical extent of disease, relation to hepatic vessels, and lobar involvement.
MRI is often preferred for its superior soft tissue contrast.
Chest CT
To identify pulmonary metastases, which are the most common site of spread.
3. Histopathology
Core needle biopsy
Confirms diagnosis and determines histological subtype (e.g. epithelial vs. mixed).
Important before initiating chemotherapy.
4. Staging Assessment
PRETEXT (PRE-Treatment EXTent of Disease) system
Although not included in Davidson’s, it is used internationally to assess tumor involvement across the four liver sectors.
Also evaluates vascular invasion, extrahepatic spread, and metastases.
Treatment
1. Surgical Resection
Definitive and potentially curative if complete (R0) resection is possible.
Options include:
Lobectomy (removal of involved lobe).
Segmentectomy or extended resections, depending on tumor extent.
Surgery is guided by PRETEXT staging (not in Davidson).
2. Chemotherapy
Used as:
Neoadjuvant therapy (before surgery): to shrink tumors and make them operable.
Adjuvant therapy (after surgery): to reduce recurrence risk.
Cisplatin-based regimens are the standard.
Common agents: Cisplatin, sometimes combined with Doxorubicin.
Tumors typically respond well to chemotherapy, especially in early stages.
3. Liver Transplantation
Considered when:
The tumor is unresectable (e.g. involves all lobes or major vessels).
No evidence of extrahepatic metastases.
Transplantation offers good long-term survival if criteria are met.
4. Follow-Up and Surveillance
AFP monitoring: A falling AFP indicates good response; rising levels suggest recurrence.
Regular imaging (CT/MRI) post-treatment.
Prognosis
Tumor Resectability
Complete surgical resection (R0) is the strongest predictor of long-term survival.
Unresectable tumors without transplant access have poorer outcomes.
Alpha-fetoprotein (AFP) Levels
High AFP at diagnosis is typical and expected.
Declining AFP during treatment suggests good response.
Low or normal AFP may indicate an aggressive or poorly differentiated subtype.
Histological Subtype
Fetal-type histology is associated with a better prognosis.
Small cell undifferentiated histology is more aggressive and has worse outcomes.
PRETEXT Stage
Lower PRETEXT stages (I or II) have better outcomes.
Higher stages (III or IV) and involvement of major vessels are associated with poorer survival unless liver transplant is feasible.
Presence of Metastases
Most commonly to the lungs.
Prognosis decreases if metastases are not responsive to chemotherapy.
Response to Chemotherapy
Good responders have high rates of disease-free survival.
Poor response is a poor prognostic marker.