The age of onset of liver cancer in children is related to tumor histology. Hepatoblastomas usually occur before the age of 3 years, and approximately 90% of malignant liver tumors in children aged 4 years and younger are hepatoblastomas.
The incidence of hepatocellular carcinoma is negligible in children aged 14 years and younger.[SEER Cancer Statistics Review] In several Asian countries, the incidence of hepatocellular carcinoma in children is 10 times more than that in North America. The high incidence appears to be related to the incidence of perinatally acquired hepatitis B, which can be prevented in most cases by vaccination and administration of hepatitis B immune globulin to the newborn.
The overall survival rate for children with hepatoblastoma is 70%,[9,10,11] but is only 25% for those with hepatocellular carcinoma.[4,12,13]
A biopsy of the tumor is always indicated to secure the diagnosis of a liver tumor except:
- In infants with hepatic hemangiomas or hemangioendotheliomas, which can be diagnosed by imaging.
- In infantile hepatic choriocarcinoma, which can be diagnosed by imaging and markedly elevated beta-human chorionic gonadotropin (beta-hCG).
The alpha-fetoprotein (AFP) and beta-hCG tumor markers are very helpful in diagnosis and management of liver tumors.
Cure of hepatoblastoma or hepatocellular carcinoma requires gross tumor resection. If a hepatoblastoma is completely removed, the majority of patients survive, but less than one-third of patients have lesions amenable to complete resection at diagnosis. Thus, it is critically important that a child with probable hepatoblastoma be evaluated by a pediatric surgeon experienced in the resection of hepatoblastoma in children.
Chemotherapy can often decrease the size and extent of hepatoblastoma, allowing complete resection.[9,10,11,15,16] Orthotopic liver transplantation provides an additional treatment option for patients whose tumor remains unresectable after preoperative chemotherapy;[16,17,18] however, the presence of microscopic residual tumor at the surgical margin does not preclude a favorable outcome.[19,20] This is probably because additional courses of chemotherapy generally are administered after resection to all patients except those with stage I and pure fetal histology, whether the resection occurs before or after chemotherapy.[9,10,20]
While hepatocellular carcinoma is often extensively invasive or multicentric, hepatoblastoma is most often unifocal. Therefore, resection is possible more often in hepatoblastoma than hepatocellular carcinoma, in which less than 30% are resectable. Orthotopic liver transplantation has also been successful in selected children with hepatocellular carcinoma.
Tumor marker-related factors
Ninety percent of patients with hepatoblastoma and two-thirds of patients with hepatocellular carcinoma have a serum tumor marker, AFP, that parallels disease activity. The level of AFP at diagnosis and rate of decrease in AFP during treatment should be compared to the age-adjusted normal range. Elevation of AFP levels is not diagnostic of hepatic malignancy. Lack of a significant decrease of AFP levels with treatment may predict a poor response to therapy. Absence of elevated AFP levels at diagnosis occurs in a few percentage of children with hepatoblastoma and appears to be associated with poor prognosis, as well as with the small cell undifferentiated variant of hepatoblastoma.[19,23,24,25,26,27]