Pediatric Hepatocellular Carcinoma Clinical Presentation
- Author: Paulette Mehta, MD, MPH; Chief Editor: Max J Coppes, MD, PhD, MBA more...
Elements to ascertain include a prior history of hepatitis B or hepatitis C, chronic cirrhosis, or other diseases that tend to induce liver dysfunction. Co-infection with human immunodeficiency virus (HIV) may further enhance a patient's risk for developing hepatocellular carcinoma (HCC). Most patients complain of abdominal pain, weight loss, and diminished appetite. In patients with a history of chronic liver disease, a change in routine symptoms may indicate the presence of a liver tumor.
Most patients with hepatocellular carcinoma present with a slowly enlarging, right upper-quadrant mass that may be found during a routine physical examination, brought to medical attention by the patient, or discovered by the patient's parents. Many children also experience localized pain, nausea, vomiting, and weight loss. Nearly 25% of patients present with jaundice.
In adults, chronic hepatitis secondary to alcohol exposure, infection with hepatitis, and hereditary hemochromatosis are predisposing factors. Aflatoxins and other environmental factors also are likely to play a role in the pathogenesis in adults. In comparison, children are far more likely to have inherited errors of metabolism, such as tyrosinemia or urea cycle enzymopathies. Liver diseases that cause cirrhosis increase risk for developing hepatocellular carcinoma (eg, alpha-1 antitrypsin deficiency).
Children with biliary atresia, chronic cholestasis, or glycogen-storage diseases are at increased risk. Symptoms can be masked in children with preexisting hepatic diseases, and, accordingly, a change in a chronic disease pattern merits careful consideration for the possibility of a new malignancy.
The physical examination often reveals abnormalities attributable to a hepatic tumor. In advanced cases, or when the primary tumor is large, the liver may be palpable below the right costal margin. In addition, deep palpation often reveals pain, especially over the location of the liver. Scleral icterus and other signs of jaundice are frequent. The patient's history also may indicate weight loss, the extent of which may be observed during the examination. In patients in whom metastatic disease to the lungs is in question, percussion of the lungs may reveal a difference in density, suggesting a pleural effusion. Other painful sites discovered on the examination should lead to radiographic imaging to determine the extent of malignant spread. This is particularly true for bone pain at presentation.
Although no cause has been clearly elucidated, the risk factors for children and adolescents include a history of hepatitis B or C, alpha-1 antitrypsin deficiency, hereditary tyrosinemia, Gaucher disease, congenital biliary atresia, urea cycle defects, severe iron overload (as occurs with thalassemia or sickle cell disease requiring chronic blood transfusion), or other forms of chronic cirrhosis or liver dysfunction. Acquired hepatitis C from blood product transfusions is an important risk factor because the risk of hepatocellular carcinoma in patients with chronic hepatitis C and cirrhosis is highest (2-8% per year).
In areas of the world where hepatitis B or C are endemic, the incidence is likely to be proportionally increased in children and adolescents.
Czauderna P, Mackinlay G, Perilongo G, et al. Hepatocellular carcinoma in children: results of the first prospective study of the International Society of Pediatric Oncology group. J Clin Oncol. 2002 Jun 15. 20(12):2798-804. [Medline].
Chou R, Cuevas C, Fu R, Devine B, Wasson N, Ginsburg A, et al. Imaging Techniques for the Diagnosis of Hepatocellular Carcinoma: A Systematic Review and Meta-analysis. Ann Intern Med. 2015 May 19. 162 (10):697-711. [Medline].
Evans AE, Land VJ, Newton WA, Randolph JG, Sather HN, Tefft M. Combination chemotherapy (vincristine, adriamycin, cyclophosphamide, and 5-fluorouracil) in the treatment of children with malignant hepatoma. Cancer. 1982 Sep 1. 50(5):821-6. [Medline].
Llovet JM, Ricci S, Mazzaferro V, et al. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med. 2008 Jul 24. 359(4):378-90. [Medline].
Schmid I, Häberle B, Albert MH, Corbacioglu S, Fröhlich B, Graf N, et al. Sorafenib and cisplatin/doxorubicin (PLADO) in pediatric hepatocellular carcinoma. Pediatr Blood Cancer. 2012 Apr. 58(4):539-44. [Medline].
Zhang XF, Liu XM, Wei T, Liu C, Li MX, Long ZD, et al. Clinical characteristics and outcome of hepatocellular carcinoma in children and adolescents. Pediatr Surg Int. 2013 Aug. 29(8):763-70. [Medline].
Romano F, Stroppa P, Bravi M, et al. Favorable outcome of primary liver transplantation in children with cirrhosis and hepatocellular carcinoma. Pediatr Transplant. 2011 Sep. 15(6):573-9. [Medline].
Koniaris LG, Levi DM, Pedroso FE, et al. Is surgical resection superior to transplantation in the treatment of hepatocellular carcinoma?. Ann Surg. 2011 Sep. 254(3):527-38. [Medline].
Alagille D, Odievre M. Liver and Biliary Tract Disease in Children. New York, NY: John Wiley & Sons; 1979. 331.
Berman MM, Libbey NP, Foster JH. Hepatocellular carcinoma. Polygonal cell type with fibrous stroma--an atypical variant with a favorable prognosis. Cancer. 1980 Sep 15. 46(6):1448-55. [Medline].
Bruix J, Sherman M. Management of hepatocellular carcinoma. Hepatology. 2005 Nov. 42(5):1208-36. [Medline].
Chlebowski RT, Tong M, Weissman J, et al. Hepatocellular carcinoma. Diagnostic and prognostic features in North American patients. Cancer. 1984 Jun 15. 53(12):2701-6. [Medline].
Evans AE, Land VJ, Newton WA, et al. Combination chemotherapy (vincristine, adriamycin, cyclophosphamide, and 5-fluorouracil) in the treatment of children with malignant hepatoma. Cancer. 1982 Sep 1. 50(5):821-6. [Medline].
Farmer DG, Rosove MH, Shaked A, Busuttil RW. Current treatment modalities for hepatocellular carcinoma. Ann Intern Med. 1994. 219:236-47. [Medline].
Giacomantonio M, Ein SH, Mancer K, Stephens CA. Thirty years of experience with pediatric primary malignant liver tumors. J Pediatr Surg. 1984 Oct. 19(5):523-6. [Medline].
Greensberg M, Filler RM. Hepatic tumors. Pizzo PA, Poplack DG, eds. Principles and Practices of Pediatric Oncology. Philadelphia, PA: JB Lippincott Co; 1993.
Jeffers LJ, Dubow RA, Zieve L, et al. Hepatic encephalopathy and orotic aciduria associated with hepatocellular carcinoma in a noncirrhotic liver. Hepatology. 1988 Jan-Feb. 8(1):78-81. [Medline].
Kew MC, Fisher JW. Serum erythropoietin concentrations in patients with hepatocellular carcinoma. Cancer. 1986 Dec 1. 58(11):2485-8. [Medline].
Levy LJ, Swinburne LM, Boulton RP, Losowsky MS. Primary hepatocellular carcinoma presenting as fulminant hepatic failure in a young woman. Postgrad Med J. 1986 Dec. 62(734):1135-7. [Medline].
Mitchell RB, Wagner JE, Karp JE, et al. Syndrome of idiopathic hyperammonemia after high-dose chemotherapy: review of nine cases. Am J Med. 1988 Nov. 85(5):662-7. [Medline].
Morita K, Okabe I, Uchino J, et al. The proposed Japanese TNM classification of primary liver carcinoma in infants and children. Jpn J Clin Oncol. 1983 Jun. 13(2):361-9. [Medline].
Noda T, Sasaki Y, Yamada T, et al. Adult capillary hemangioma of the liver: report of a case. Surg Today. 2005. 35(9):796-9. [Medline].
Paradinas FJ, Melia WM, Wilkinson ML, et al. High serum vitamin B12 binding capacity as a marker of the fibrolamellar variant of hepatocellular carcinoma. Br Med J (Clin Res Ed). 1982 Sep 25. 285(6345):840-2. [Medline].
Ringe B, Wittekind C, Bechstein WO, et al. The role of liver transplantation in hepatobiliary malignancy. A retrospective analysis of 95 patients with particular regard to tumor stage and recurrence. Ann Surg. 1989 Jan. 209(1):88-98. [Medline].
Schafer DF, Sorrell MF. Hepatocellular carcinoma. Lancet. 1999 Apr 10. 353(9160):1253-7. [Medline].
Vaillo A, Rodriguez-Recio FJ, Gutierrez-Martin A, et al. Fine needle aspiration cytology of clear cell carcinoma of the gallbladder with hepatic infiltration: a case report. Acta Cytol. 2004 Jul-Aug. 48(4):560-4. [Medline].
Winter SS, Rose E, Katz R. Hyperammonemia after chemotherapy in an adolescent with hepatocellular carcinoma. J Pediatr Gastroenterol Nutr. 1997 Nov. 25(5):537-40. [Medline].
Young JL Jr, Miller RW. Incidence of malignant tumors in U. S. children. J Pediatr. 1975 Feb. 86(2):254-8. [Medline].