Pediatric Hepatoblastoma Clinical Presentation

Updated: Sep 15, 2017
  • Author: Jennifer Reikes Willert, MD; Chief Editor: Max J Coppes, MD, PhD, MBA  more...
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Presentation

History

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  • Patients with hepatoblastoma are usually asymptomatic at diagnosis. Disease is advanced at diagnosis in approximately 40% of patients, and 20% have pulmonary metastases.

  • Children with advanced disease may have anorexia.

  • Severe osteopenia is present in most patients and regresses with resection of the tumor. Symptoms associated with osteopenia are rare with the exception of pathologic fracture, which is often incidentally identified on routine imaging studies during evaluation of these children.

  • Rarely, patients in whom the tumor has ruptured present with symptoms consistent with acute abdomen. Occasionally, patients present with severe anemia resulting from tumor rupture and hemorrhage.

  • Family history of early onset intestinal polyps or adenocarcinoma may reveal familial adenomatous polyposis (FAP). A history of hemihypertrophy or Beckwith-Wiedemann syndrome (BWS) should prompt screening using α -fetoprotein (AFP) as a marker to detect hepatoblastoma in these patients. For such patients, AFP monitoring should be performed every 3 months until the child is aged at least 4 years. Children who survive hepatoblastoma should be considered for evaluation of FAP, and those patients found to carry an APC mutation need close surveillance because of their increased risk for colonic polyps and frank progression to adenocarcinoma.

  • Diagnosing primary malignant liver tumors before clinical signs and symptoms develop is important. Children with a history of chronic hepatitis B infection who have advanced liver disease should be monitored at least every 6-12 months with serum AFP levels and abdominal ultrasonography. Many children with hepatitis B infection are immunotolerant, do not have significant liver abnormalities, and are not at increased risk for liver cancer. Any child with documented cirrhosis for any reason should be periodically monitored with serum AFP level and ultrasonography because of their increased risk of developing a hepatic malignancy associated with advanced liver disease.

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Physical

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  • Hepatoblastoma is usually diagnosed as an asymptomatic abdominal mass.

  • Approximately 10% of patients have incidental findings of hemihypertrophy.

  • Hepatoblastoma can be associated with isosexual precocity. Penile and testicular enlargement without pubic hair is seen in patients with tumors that secrete the b subunit of human chorionic gonadotropin (b-hCG).

  • Late features of BWS, such as midface hypoplasia and slitlike indentations of the earlobe, may occur, but this is rare.

  • Patients with BWS and those with hemihypertrophy should be monitored with serial abdominal ultrasonography and serum AFP level every 3 months until at least age 4 years; some would argue that these patients should be monitored until age 7 years because of the risk of Wilms tumor as well.

  • Other associated syndromes and malformations include the following:

    • Talipes equinovarus

    • Persistent ductus arteriosus

    • Tetralogy of Fallot

    • Extrahepatic biliary atresia

    • Renal anomalies (dysplastic kidney, horseshoe kidney)

    • Cleft palate

    • Dysplasia of the earlobes

    • Goldenhar syndrome

    • Prader-Willi syndrome

    • Meckel diverticulum

  • Hepatoblastoma is also seen in association with Simpson-Golabi-Behmel syndrome. Routine screening with AFP level monitoring and abdominal ultrasonography is suggested in these patients, who are also at risk for developing Wilms tumor.

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Causes

As with other pediatric malignancies, the cause of hepatoblastoma is generally unknown. Cancer has been postulated to arise from unregulated cellular differentiation and proliferation. Similarities between the developing fetal liver and the fetal epithelial-type cells of hepatoblastoma are striking. Developing cells of the early fetal liver and the cells of fetal hepatoblastoma are similar in size and configuration. A developmental disturbance during liver formation in embryogenesis likely results in aberrant proliferation of these undifferentiated cells.

Increasing data support a role for aberrant transduction of the Wnt/β-catenin signaling pathway and its molecular targets in hepatoblastoma tumorigenesis. Research in this area may ultimately contribute not only toward a better understanding of this malignant neoplasm but may also lead to more specific molecular-targeted therapies.

  • Hepatoblastoma, like Wilms tumor, is associated with BWS and hemihypertrophy, suggesting gestational oncogenic events.

  • Persons with dysplastic kidney or Meckel diverticulum have a higher incidence of this tumor.

  • Hepatoblastoma has also been reported to be associated with maternal oral contraceptive exposure, fetal alcohol syndrome, and gestational exposure to gonadotropins.

  • Studies performed in Europe suggest an association between low birth weight (LBW), very low birth weight (VLBW), and prematurity and hepatoblastoma. The suspected correlation between LBW, prematurity (< 1000 g), and hepatoblastoma has now been confirmed in both the United States and Japan. [23, 24]

  • Patients with FAP have a significantly increased incidence of hepatoblastoma and should therefore be screened in early childhood with AFP measurements.

  • A child with neurofibromatosis type 1 (NF1) who developed hepatoblastoma was reported. [25] Hepatoblastoma has also been reported in association with other cancer predisposition syndromes including FAP, BWS, Li-Fraumeni syndrome, trisomy 18, and glycogen storage disorders.

  • Premature infants, particularly those with LBW or VLBW, are at significantly increased risk of developing hepatoblastoma. The presence of erythropoietin receptors in hepatoblastomas has been postulated to potentially contribute to this increased incidence because many premature infants with LBW or VLBW receive this medication during their time in neonatal intensive care.

  • Increasing evidence suggests that exposure to carcinogenic agents such as bromochloroacetic acid may be tumorigenic. [26]

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