Hepatoblastoma

Epidemiology And Risk Factors

Most common primary hepatic neoplasm; constitutes two-thirds of pediatric liver tumors.
Peak incidence <3 years of age; median presentation age 1 year.

Etiology Category	Specific Associated Conditions
Perinatal Factors	Prematurity, very low birth weight.
Overgrowth Syndromes	Beckwith-Wiedemann syndrome, isolated hemihyperplasia, Simpson-Golabi-Behmel syndrome.
Genetic Syndromes	Familial adenomatous polyposis, Trisomy 18, Li-Fraumeni syndrome, Glycogen storage disease type 1, Alagille syndrome.

Epithelial Type: Comprises pure fetal, embryonal, macrotrabecular, and small cell undifferentiated patterns.
Mixed Type: Contains both epithelial and mesenchymal elements.
Histologic Prognostication: Pure fetal histology yields superior outcome; small cell undifferentiated variant predicts poorest prognosis.
Genetics: Driven by WNT pathway activation; CTNNB1 mutations present in 70%.

Clinical Signs: Asymptomatic upper abdominal mass. Systemic symptoms (weight loss, anorexia) present in advanced disease. Jaundice remains uncommon.
Metastasis: Preferentially spreads to lungs and regional lymph nodes.

Diagnostic Modality	Key Findings And Clinical Utility
Tumor Markers	Alpha-fetoprotein (AFP) highly elevated in 90% cases. Low AFP (<100 ng/mL) at diagnosis portends poor prognosis. $β$ -hCG occasional elevation causes pseudoprecocious puberty.
Radiologic Imaging	Abdominal ultrasound, CT, or MRI delineates intrahepatic disease extent. Chest CT mandatory for lung metastasis screening.
Staging System	PRETEXT (Presurgical EXTent of disease) evaluates hepatic quadrant involvement to determine upfront surgical resectability.

Surgical Resection: Complete excision essential for cure; achievable upfront in approximately 30% cases.
Chemotherapy: Platinum-based regimens form therapeutic backbone (Cisplatin, Vincristine, 5-Fluorouracil, Doxorubicin). Utilized as neoadjuvant therapy for unresectable tumors or adjuvant therapy post-resection.
Refractory Disease: Unresectable primary tumors require orthotopic liver transplantation following neoadjuvant chemotherapy.
Prognosis: Overall survival approaches 70-80%. Localized disease curable in >90% cases with multimodal therapy.

Second most common pediatric primary hepatic malignancy.
Median presentation age: 12 years.
Bimodal incidence pattern in endemic regions; correlates with perinatal Hepatitis B infection.
Arises in cirrhotic and noncirrhotic backgrounds.
Multicentric, invasive tumor comprising large pleomorphic epithelial cells.
Fibrolamellar variant: Distinct subtype affecting adolescents and young adults; lacks cirrhosis association; harbors DNAJB1-PRKACA translocation or 400-kB deletion on chromosome 19.

Viral: Perinatal Hepatitis B infection (vaccination reduces incidence), Hepatitis C.
Metabolic: Tyrosinemia, alpha-1 antitrypsin deficiency, glycogen storage disease types 1 and 4, Wilson disease.
Cholestatic: Biliary atresia, Alagille syndrome, progressive familial intrahepatic cholestasis.

Tumor marker: Alpha-fetoprotein (AFP) elevated in 50-60% classical cases; typically normal in fibrolamellar variant.
Imaging: Abdominal ultrasound, CT, MRI delineate intrahepatic extent and resectability; chest CT evaluates pulmonary metastasis.
Histopathology: Liver biopsy essential for definitive diagnosis.

Surgery: Complete surgical resection crucial for survival; feasible in 20-30% at diagnosis.
Chemotherapy: Cisplatin and doxorubicin utilized neoadjuvantly to convert unresectable tumors, or adjuvantly post-resection.
Targeted therapy: Sorafenib (tyrosine kinase inhibitor) demonstrates antitumoral activity.
Liver transplantation: Orthotopic liver transplant indicated for individualized unresectable cases.
Prognosis: Poor overall survival approximating 40%.