Cancer in Children - Liver Tumors

Pediatric Liver Tumors

Primary liver tumors are uncommon in children comprising less than 3% of tumors seen in the pediatric population.¹ Of these tumors, about two thirds are benign and one third are malignant. (Table 1).² In general the most common presenting feature of pediatric of liver neoplasms is an asymptomatic abdominal mass. Depending on the histology other symptoms include pain, hemorrhage, vomiting, weight loss, hypertension and precocious puberty. Nearly all children that present with a large abdominal mass have an ultrasound as their first study that is excellent in differentiating solid from cystic liver lesion and in addition with the use of Doppler imaging can evaluate vascular lesions. Computed tomography (CT) and magnetic resonance (MR) imaging are the most definitive diagnostic test and can often differentiate benign and malignant tumors preoperatively. The use of (MR) angiography has essentially replaced arteriography in assessing resectability in complex cases. Laparotomy or laparoscopy is required in the majority of patients to establish the diagnosis and to allow resection or other therapy.

Vascular Tumors

Hemangioma is the most frequently observed benign liver tumor in children, however, hemangiomas are usually incidental findings in asymptomatic patients. This is in contrast to the infantile hemangioendothelioma, which presents in the neonatal period or early infancy often with a triad of hepatomegaly, cutaneous hemangiomas and cardiac failure. A consumptive coagulopathy as a result of thrombocytopenia (Kasabach-Merritt Syndrome) develops in about one half of these patients.³ Similar to hemangiomas, hemangioendotheliomas when asymptomatic require no specific treatment and will undergo spontaneous involution with in 12-18 months. In symptomatic patients with evidence of congestive heart failure and or thrombocytopenia potential management includes steroids, interferon-alpha2a, embolization, hepatic artery ligation, resection or liver transplantation.⁴ The mortality in cases of extensive hemangiomatosis remains high.

Mesenchymal Hamartoma

Mesenchymal hamartomas are uncommon benign hepatic tumors arising from the mesenchyme of the portal triad often presenting in the first year of life. The vast majority involve the right lobe of the liver, are almost always solitary lesions, but may achieve significant size. The mixed solid and cystic tumor is treated with resection in symptomatic patients but also may undergo spontaneous resolution.⁵

Malignant Tumors

Hepatoblastoma is the most common pediatric liver malignancy followed by hepatocellular carcinoma (HCC) and much rarer primary liver sarcomas. Metastatic disease is also seen primarily with neuroblastoma and Wilms tumors.

Hepatoblastoma

Hepatoblastoma presents usually within the first two years of life with greater than 90% having an elevated a-fetoprotein level. Occasionally, precocious puberty or virilization, secondary to excess androgen secretion is seen in children with hepatoblastoma. Hepatoblastoma occurs in association with Beckwith-Wiedemann syndrome and also with hemihypertrophy. Hepatoblastoma has also been associated with glycogen storage disease type 1B, familial adenomatous polyposis, maternal use of oral contraceptives, and the fetal alcohol syndrome. Improvements in outcome are directly related to improved chemotherapy and surgical techniques.⁷ Surgical resectability is the most important factor for survival of patients with hepatoblastoma, however, primary hepatic resection is only possible in a minority of patients. The rate of resectability has improved dramatically with chemotherapy. The treatment of advanced unresectable, metastatic hepatoblastoma is improving but remains unsatisfactory with survival rates for stage 3 and stage 4 disease currently 65% and 15% respectfully.^{8, 9} Chemoembolization and or liver transplantation are being evaluated to treat unresectable disease localized to the liver.^{10, 11} Although in some cases aggressive surgical resection of pulmonary metastases has lead to some cures, improved chemotherapy or other biologic therapies will be needed to impact on advanced disease.

Hepatocellular Carcinoma

Hepatocellular carcinoma occurs in school age children and has an aggressive biological behavior similar to its counter part in adults. In addition to the association with hepatitis B infection, HCC has also been associated with children with tyrosinosis, glycogen storage disease, neonatal hepatitis, and biliary atresia. The serum alpha-fetoprotein level is elevated in 50-60% of HCC carcinoma patients at diagnosis. Less than a one third of cases of HCC are amenable to complete resection. HCC is much less responsive to chemotherapy with less than 20% of patients able to undergo second-look surgery.¹² Innovative therapies are needed to impact on HCC which continues to have a dismal prognosis.

Table 1: Incidence of Primary Hepatic Tumors in Childhood

Adapted from Weinberg AG, Finegold MJ: Primary hepatic tumors of childhood. Hum Pathol 1983, 14:512.

References

1. Gurarangan S, O'Meara A, MacMahon C, Guiney EF, O'Donnell B, Fitzgerald RJ, Breatnach F: Primary hepatic tumors in children: a 26 year review. J Surg Oncol 1992, 50:30-36.
2. Weinberg AG, Finegold MJ: Primary hepatic tumors of childhood. Hum Pathol 1983, 14:512.
3. Kasabach HH, Merritt KK: Capillary hemangioma with extensive purpura. Am J Dis Child 1940, 59:1063.
4. Daller JA, Bueno J, Gutierrez J, Dvorchik I, Towbin RB, Dickman PS, Mazariegos G, Eyes J: Hepatic hemangioendothelioma: clinical experience and management strategy. J Pediatr Surg 1999, 34(1):98-105; Discussion 105-6.
5. Barnhart DC, Hirschl RB, Garver KA, Geiger, JD, Harmon, CM, Coran, AG: Conservative management of mesenchymal hamartoma of the liver. J Pediatr Surg 1997, 32(10)1495-1498.
6. Van Tornout JM, Buckly JD, Quinn JJ, Feusner JH, Krailo MD, King DR, Hammond GD, Ortega JA: Timing and magnitude decline in alpha-fetoprotein levels in treated children with unresectable or metastatic hepatoblastoma are predictors of outcome: a report from the Children's Cancer Group. J Clin Oncol 197, 15(3):1190-1197.
7. Ortega JA, Krailo MD, Haas JE, King DR, Ablin AR, Quinn JJ, Feusner J, Campbell JR, Lloyd DA, Cherlow J: Effective treatment of unresectable or metastatic hepatoblastoma with cisplatin and continuous infusion doxrubicin chemotherapy: a report form the Children's Cancer Study Group. J Clin Oncol 1991, 9:2167-2176.
8. Van Schweinitz D, Hecker H, Harms D, Bode U, Weinel P, Burger D, Erttmann R, Mildenberger H: Complete resection before development of drug resistance is essential for survival from the advanced hepatoblastoma: a report from the German Cooperative Pediatric Liver Tumor Study HB-89. J Pediatr Surg 1995, 30:845-852.
9. Plaschkes J, Perilongo G, Shafford EA, Brock P, Brown J, Dicks-Mireaux C, Habrand JL, Keeling J, Philips A, Pritchard J, Vos A: SIOP trial report: overall preliminary results of SIOPEL-I for the treatment of hepatoblastoma (HB) with preoperative chemotherapy. Continuous infusion cisplatin and doxrubicin (PLAO). Med Pediatr Oncol 1994, 23:170.
10. Koneru B, Flye MW, Busuttil RW, Shaw BW, Lorber MI, Emond JC, Kalayogulu M, Freese DK, Starzl TE: Liver transplantation for hepatoblastoma: the American experience. Ann Surg 1991, 213:118-121.
11. Oue T, Fukuzama M, Kusafuka T, Kohmoto Y, Okada A, Imura K: Transcatheter arterial chemoembolization in the treatment of hepatoblastoma. J Pediatr Surg 1998, 33(12):1771-1775.
12. Chen JC, Chen CC, Chen WJ, Lai HS, Hung WT, Lee PH: Hepatocellular carcinoma in children: a clinical review and comparison with adult cases. J Pediatr Surg 1998, 33(9):1350-1354.

Information on Neuroblastoma

Suggested readings authored by the University of Michigan, Section of Pediatric Surgery

1. Partrick, D, Bensar, D, Geiger, JD, Teitelbaum, DH: Successful throacoscopic lung biopsy in children utilizing preoperative CT-guided localization. J Pediatr Surg 37(7): 970-973, 2002.
2. Geiger JD, Hutchinson RJ, Hohenkirk LF, McKenna EA, Yanik GA, Levine JE, Chang A, Braun TM, Mul, J: Vaccination of Pediatric Solid Tumor Patients with Tumor Lysate-Pulsed Dendritic Cells Can Expand Specific T Cells and Mediate Tumor Regression. Cancer Research 61, 8513-8519, December 1, 2001.
3. Hemmila MR, Foley DS, Castle VP, Hirschl RB. The response to splenectomy in pediatric patients with ideopathic thrombocytopenic purpura who fail high-dose intravenous immune globulin. J Ped Surg 35(6):967-72, 2000.
4. Azizkhan RG, Rescorla FJ, Haase GM, Applebaum H, Dillon PW, Coran AG, Sawin RS, King PA, Ding DR, Hodge DS: Diagnosis, Management and Outcome of Teratomas in Neonates and Infants: A Multi-Institutional Study: Paediatr Croat 43: 163-171, 1999.
5. Barnhart DC, Hirschl RB, Garver KA, Geiger JD, Harmon CM, Coran AG. Conservative management of mesenchymal hamartoma of the liver. J Ped Surg 32:1495-1498, 1997.
6. Geiger JD: Surgery for Hepatoblastoma in Children, Current Opinion in Pediatrics, 8(3)282-290, 1996.
7. Dillion P, Whalen T, Azizkhan R, Haase G, Coran AG, King D and Smith M: Neonatal soft tissue sarcomas: The influence of pathology on treatment and survival. J Ped Surg 30: 1038-1041, 1995.
8. Geiger JD, Hutchinson RJ, Hohenkirk LF, McKenna E, Chang A, Mul, J: Treatment of Solid Tumours in Children with Tumour Lysate-Pulsed Dendritic Cells. The Lancet, 356(9236) 1163-1164, September, 2000.
9. Schmeling DJ and Coran AG: Wilms' Tumor (Nephroblastoma). Pediatric Rounds 8:3-5, 1988.

This information is provided by the University of Michigan Department of Surgery, Section of Pediatric Surgery and is not intended to replace the medical advice of your doctor or health care provider. Please consult your health care provider for advice about a specific medical condition. For additional health information, please contact your health care provider or our offices.