Liver tumors represent approximately
1% of all childhood cancers. There are approximately 100
to 150 new cases of liver cancer diagnosed in children each year
in the United States.1 Hepatoblastoma is the most common
malignant tumor of the liver and accounts for two thirds of all
liver cancer in children.2 Hepatoblastoma occurs almost
always in the very young child, with a mean age of onset of approximately
18 to 20 months and 95% of cases occurring before 5 years
of age. The incidence of hepatoblastoma has approximately doubled
over the past few decades.3 Hepatoblastoma is considered
an embryonal tumor because histologically, tumor cells resemble
cells seen in the developing liver.
Hepatocellular carcinoma is the primary liver malignancy in older
children and adolescents. The male-to-female ratio is approximately
1.5:1 for hepatoblastoma and hepatocellular carcinoma. Other less
common liver tumors include undifferentiated embryonal sarcoma,
rhabdoid tumor, angiosarcoma, rhabdomyosarcoma of the biliary tract,
cholangiocarcinoma, and other germ cell tumors. One third of all
tumors of the liver in children turn out to be benign entities that
include vascular tumors (hemangioendotheliomas), mesenchymal hamartomas,
As with most types of pediatric cancers, the underlying causes
are largely unknown; however, several genetic syndromes are associated
with hepatoblastoma, and epidemiologic studies have provided some
clues to their etiology.
Beckwith-Wiedemann syndrome (BWS) is an overgrowth syndrome characterized
by large birth weight, macroglossia, omphalocoele, and visceromegaly.
Children with BWS are at risk of developing embryonal tumors including
Wilms tumors, hepatoblastoma, neuroblastoma, and adrenocorticocarcinoma.
A national registry of children with BWS reports that the risk of
children with BWS developing hepatoblastoma is 2280-fold higher
than the general population and that the risk for hepatoblastoma
was significantly higher than for Wilms or any other type of cancer
in children with BWS. Screening children with BWS with periodic
abdominal ultrasounds and serum alpha-fetoprotein levels every 3
months during the first decade of life may be associated with detection
at an early stage and is therefore recommended.5
Familial adenomatous polyposis (FAP), an autosomal dominant syndrome
characterized primarily by polyp growth in the colon which begins
in adolescence and without intervention progresses to colon cancer, is
also associated with a high risk of hepatoblastoma.6 Mutation
in the causative adenomatous polyposis coli (APC) gene can be readily
detected in children with hepatoblastoma who have a family history
of early onset colon cancer. These children are clearly at risk
for polyps and colon cancer and need follow-up with lifelong surveillance.
It is less clear how great the risk of carrying such a cancer predisposition
is in other children with hepatoblastoma without a clear history
of FAP, but it has been suggested that children with hepatoblastoma
be screened for APC mutations and also that asymptomatic children
from FAP families be screened for mutation carrier status and for
hepatoblastoma if APC mutations are detected.
In addition to BWS and FAP, several other syndromes ...