Definition:
Hepatoblastoma is a type of liver cancer which is seen in young children. Surgical resection is usually required for cure, but not all tumors are removable.

Incidence (How common is Hepatoblastoma?):
Hepatoblastoma occurs in approximately 1 per million children. It is more common in males than females in children younger than 5 years (1.2:1 to 3.6:1), but the incidence is equal in children older than 5. It does, however, occur 4 to 5 times more frequently in white children than African-American children.

Associated Syndromes:
Beckwith-Wiedemann syndrome and Familial Adenomatous Polyposis.

Risks:
Maternal exposure to metals, paints, and oil products, prematurity with prolonged hospitalization

Clinical Presentation:

• 35% of patients have bilateral (both sides of the liver) disease
• 20% have distant metastasis at time of diagnosis
• Most common site for spread is lung. Other common sites include brain and bone.

Histology (microscopic appearance)

• 56% epithelial origin
• 31% pure fetal
• 19% embryonal
• 3% macrotrabecular
• 3% small cell undifferentiated

Epithelial tumors (Fetal or Embryonal) usually have a homogeneous appearance (all the cells look the same).

Pathophysiology:

• 44% mixed epithelial and mesenchymal origin:  heterogeneous appearance
• May contain areas of osteoid, cartilage, calcification, fibrosis, necrosis, and hemorrhage

Prognosis:

• Long-term survival rates are 75-80%
• Ppure fetal tumors have the best prognosis (outcome)
• Small cell undifferentiated/anaplastic tumors have the worst prognosis

Diagnosic studies:

• Labs: AFP (alpha fetoprotein) level
  • AFP abnormally elevated in 80% of newly diagnosed cases
  • Poorer prognosis if AFP is extremely high or low
  • Low AFP associated with small cell undifferentiated type, especially unresponsive to chemotherapy
  • Large, early fall after chemotherapy is a good prognostic indicator
• Imaging
  • Ultrasound – preliminary imaging study
  • CT – quick and easy, usually without sedation, good for detecting pulmonary metastasis
  • MRI – More accurate at showing tumor margins, evaluating portal vein, and detecting residual tumor after surgical resection
  • MRA – demonstrates vascular anatomy and segmental involvement

Treatment:

• Primary goal of treatment is surgical resection
• 30-60% of patients present with resectable tumors clear margins
• Of the initially unresectable tumors, 60-75% will decrease in size after chemotherapy and allow for surgical resection

Unresectable at presentation if:

• Tumor crosses planned margins of resection
• Resection may result in excessive bleeding
• Invasion of hepatic blood vessels or the IVC
• Disease is diffuse and multifocal

Chemotherapy:

• Vincristine
• Adriamycin
• Cyclophosphamide
• 5-Fluorouracil

After Chemotherapy:
Monitor with CT and AFP after 2 to 4 cycles and resect if clear margins can be obtained.

Transplantation:

• Indicated for those patients with unresectable tumors after chemotherapy
• Can be done with cadaveric liver donor or living liver donor
• 1 year survival – 79%
• 5 year survival – 69%
• 10 year survival – 66%

Staging:

• Old Staging (CCG/POG) (post surgery staging)
  • Stage I – completely resected
  • Stage II – microscopic residual at margins of resected specimen
  • Stage III – partially resected, unresected specimen confined to liver, tumor spill during surgery, or + lymph nodes
  • Stage IV – distant metastatic disease
• Current Staging – SIOP/PRETEXT (pre-surgical staging)
  • PRETEXT system
  • Divides liver into 4 sectors or quadrants
  • PRETEXT 1 involves 1 sector of the liver
  • PRETEXT 2 involves 2 sectors, etc.
  • PRETEXT 3  Tumor involves 3 sectors and 1 sector is free of tumor
  •       or tumor involves 2 sectors and 2 nonadjoining sectors are free of tumor
  • PRETEXT 4 Tumor involves all four sectors; there is no sector free of tumor.
  • V – involves the hepatic vein
  • P – involves the portal vein
  • C – involves the caudate lobe of liver
  • E – extrahepatic extension
  • M – distant metastasis

References:
Emre S, McKenna GJ. “Liver Tumors in children”
Pediatr Transplantation 2004:8:632-38

Evans AE, Land VJ, Newton WA, Randolf JG, Sather HN, Tefft M. “Combination chemotherapy (vincristine, adriamycin, cyclophosphamide, and 5-fluorouracil) in the treatment of children with malignant hepatoma”
Cancer1982;50:821-6

Mann JR, Kasthuri N, Raafat F, Pincott JR, Parkes SE, MuirKR, et al “Malignant hepatic tumours in children: incidence, clinical features and aetiology”
Paediatr Perinat Epidemiol 1990;4:276-89

Penn I. “Hepatic transplantation for primary and metastatic cancers of the liver”
Surgery 1991;110:726-34

Molmenti EP, Nagata D, Roden J, Squires R, Molmenti H, Casey D, et al. “Liver transplantation for hepatoblastoma in the pediatric population”
Transplant Proc 2001;33:1749

Raney B.
J Ped Hematol Oncol 1997;19:418-22

Tiao et al. “The current management of hepatoblastoma: a combination of chemotherapy, conventional resection, and liver transplantation”
J Pediatr 2005;146:204-11