Hepatic Tumors

  • Rohit Gupta
  • André A. Dick
  • Karen F. Murray


Primary hepatic neoplasms are rare in childhood and their presentation is usually as a palpable mass with few if any other symptoms. Despite the asymptomatic presentation, the majority that do present in this young age group are malignant. Serum alpha-fetoprotein, although characteristically elevated in some hepatic tumors, is not elevated in all malignant liver tumors of childhood. Radiologic and histological assessments are vital for making accurate diagnoses and for guiding appropriate therapy. This chapter will review the most common of the benign and malignant primary hepatic masses that present in childhood.


Portal Hypertension Choledochal Cyst Focal Nodular Hyperplasia Glycogen Storage Disease Fibrous Septum 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



Serum alpha-fetoprotein


Computed tomography


Epithelioid hemangioendothelioma


Embryonal (undifferentiated) sarcoma of the liver


Fibrolamellar carcinoma


Focal nodular hyperplasia


Hepatocellular adenoma




Hepatocellular carcinoma


Hepatobiliary rhabdomyosarcoma


Infantile hepatic hemangioma


Mesenchymal hamartoma


Magnetic resonance imaging


Nodular regenerative hyperplasia


Rapidly involuting congenital hemangioma




  1. 1.
    Boon LM, Burrows PE, Paltiel HJ, Lund DP, Ezekowitz RA, Folkman J, et al. Hepatic vascular anomalies in infancy: a twenty-seven-year experience. J Pediatr. 1996;129(3):346–54. S0022-3476(96)70065-3 [pii].CrossRefPubMedGoogle Scholar
  2. 2.
    Selby DM, Stocker JT, Waclawiw MA, Hitchcock CL, Ishak KG. Infantile hemangioendothelioma of the liver. Hepatology. 1994;20(1 Pt 1):39–45. S0270913994002120 [pii].PubMedGoogle Scholar
  3. 3.
    Dehner LP, Ishak KG. Vascular tumors of the liver in infants and children. A study of 30 cases and review of the literature. Arch Pathol. 1971;92(2):101–11.PubMedGoogle Scholar
  4. 4.
    Burrows PE, Dubois J, Kassarjian A. Pediatric hepatic vascular anomalies. Pediatr Radiol. 2001;31(8):533–45.CrossRefPubMedGoogle Scholar
  5. 5.
    Chung EM, Cube R, Lewis RB, Conran RM. From the archives of the AFIP: pediatric liver masses: radiologic-pathologic correlation part 1. Benign tumors. Radiographics. 2010;30(3):801–26. doi: 10.1148/rg.303095173. 30/3/801.CrossRefPubMedGoogle Scholar
  6. 6.
    Kassarjian A, Zurakowski D, Dubois J, Paltiel HJ, Fishman SJ, Burrows PE. Infantile hepatic hemangiomas: clinical and imaging findings and their correlation with therapy. AJR Am J Roentgenol. 2004;182(3):785–95.CrossRefPubMedGoogle Scholar
  7. 7.
    Christison-Lagay ER, Burrows PE, Alomari A, Dubois J, Kozakewich HP, Lane TS, et al. Hepatic hemangiomas: subtype classification and development of a clinical practice algorithm and registry. J Pediatr Surg. 2007;42(1):62–7. doi: 10.1016/j.jpedsurg.2006.09.041; S0022-3468(06)00654-3 [pii].CrossRefPubMedGoogle Scholar
  8. 8.
    Ohama K, Nagase H, Ogino K, Tsuchida K, Tanaka M, Kubo M, et al. Alpha-fetoprotein (AFP) levels in normal children. Eur J Pediatr Surg. 1997;7(5):267–9. doi: 10.1055/s-2008-1071168.CrossRefPubMedGoogle Scholar
  9. 9.
    Keslar PJ, Buck JL, Selby DM. From the archives of the AFIP. Infantile hemangioendothelioma of the liver revisited. Radiographics. 1993;13(3):657–70.CrossRefPubMedGoogle Scholar
  10. 10.
    Kuroda T, Kumagai M, Nosaka S, Nakazawa A, Takimoto T, Hoshino K. Critical infantile hepatic hemangioma: results of a nationwide survey by the Japanese infantile hepatic hemangioma study group. J Pediatr Surg. 2011;46(12):2239–43. doi: 10.1016/j.jpedsurg.2011.09.007; S0022-3468(11)00746-9 [pii].CrossRefPubMedGoogle Scholar
  11. 11.
    Mhanna A, Franklin WH, Mancini AJ. Hepatic infantile hemangiomas treated with oral propranolol – a case series. Pediatr Dermatol. 2011;28(1):39–45. doi: 10.1111/j.1525-1470.2010.01355.x.CrossRefPubMedGoogle Scholar
  12. 12.
    Storch CH, Hoeger PH. Propranolol for infantile haemangiomas: insights into the molecular mechanisms of action. Br J Dermatol. 2010;163(2):269–74.CrossRefPubMedGoogle Scholar
  13. 13.
    Bosemani T, Puttgen KB, Huisman TA, Tekes A. Multifocal infantile hepatic hemangiomas – imaging strategy and response to treatment after propranolol and steroids including review of the literature. Eur J Pediatr. 2012;171(7):1023–8.CrossRefPubMedGoogle Scholar
  14. 14.
    Yeh I, Bruckner AL, Sanchez R, Jeng MR, Newell BD, Frieden IJ. Diffuse infantile hepatic hemangiomas: a report of four cases successfully managed with medical therapy. Pediatr Dermatol. 2011;28(3):267–75.CrossRefPubMedGoogle Scholar
  15. 15.
    Barlow CF, Priebe CJ, Mulliken JB, Barnes PD, Mac DD, Folkman J, et al. Spastic diplegia as a complication of interferon alfa-2a treatment of hemangiomas of infancy. J Pediatr. 1998;132(3 Pt 1):527–30.CrossRefPubMedGoogle Scholar
  16. 16.
    Stringer MD, Alizai NK. Mesenchymal hamartoma of the liver: a systematic review. J Pediatr Surg. 2005;40(11):1681–90. doi: 10.1016/j.jpedsurg.2005.07.052; S0022-3468(05)00622-6 [pii].CrossRefPubMedGoogle Scholar
  17. 17.
    Koumanidou C, Vakaki M, Papadaki M, Pitsoulakis G, Savvidou D, Kakavakis K. New sonographic appearance of hepatic mesenchymal hamartoma in childhood. J Clin Ultrasound. 1999;27(3):164–7. 10.1002/(SICI)1097-0096(199903/04)27:3<164::AID-JCU12>3.0.CO;2-J [pii].CrossRefPubMedGoogle Scholar
  18. 18.
    Kitano Y, Ruchelli E, Weiner S, Adzick NS. Hepatic mesenchymal hamartoma associated with mesenchymal stem villous hyperplasia of the placenta. Fetal Diagn Ther. 2000;15(3):134–8. [pii] 20992.CrossRefPubMedGoogle Scholar
  19. 19.
    Yen JB, Kong MS, Lin JN. Hepatic mesenchymal hamartoma. J Paediatr Child Health. 2003;39(8):632–4. 250 [pii].CrossRefPubMedGoogle Scholar
  20. 20.
    Srouji MN, Chatten J, Schulman WM, Ziegler MM, Koop CE. Mesenchymal hamartoma of the liver in infants. Cancer. 1978;42(5):2483–9.CrossRefPubMedGoogle Scholar
  21. 21.
    Kamata S, Nose K, Sawai T, Hasegawa T, Kuroda S, Sasaki T, et al. Fetal mesenchymal hamartoma of the liver: report of a case. J Pediatr Surg. 2003;38(4):639–41. doi: 10.1053/jpsu.2003.50142; S0022346802631513 [pii].CrossRefPubMedGoogle Scholar
  22. 22.
    Meinders AJ, Simons MP, Heij HA, Aronson DC. Mesenchymal hamartoma of the liver: failed management by marsupialization. J Pediatr Gastroenterol Nutr. 1998;26(3):353–5.CrossRefPubMedGoogle Scholar
  23. 23.
    Luciani A, Kobeiter H, Maison P, Cherqui D, Zafrani ES, Dhumeaux D, et al. Focal nodular hyperplasia of the liver in men: is presentation the same in men and women? Gut. 2002;50(6):877–80. Pubmed PMCID:PM:PMC1773241.CrossRefPubMedCentralPubMedGoogle Scholar
  24. 24.
    Scalori A, Tavani A, Gallus S, La VC, Colombo M. Oral contraceptives and the risk of focal nodular hyperplasia of the liver: a case–control study. Am J Obstet Gynecol. 2002;186(2):195–7. S0002937802382498 [pii].CrossRefPubMedGoogle Scholar
  25. 25.
    Mathieu D, Kobeiter H, Maison P, Rahmouni A, Cherqui D, Zafrani ES, et al. Oral contraceptive use and focal nodular hyperplasia of the liver. Gastroenterology. 2000;118(3):560–4. S0016508500442605 [pii].CrossRefPubMedGoogle Scholar
  26. 26.
    Kubota T, Shimizu K, Sonoyama T, Ikeda E, Kurioka H, Ouchi T, et al. Enlarged focal nodular hyperplasia of the liver under the influence of oral contraceptives. Hepatogastroenterology. 2001;48(42):1736–9.PubMedGoogle Scholar
  27. 27.
    Wanless IR, Mawdsley C, Adams R. On the pathogenesis of focal nodular hyperplasia of the liver. Hepatology. 1985;5(6):1194–200. S0270913985001525 [pii].CrossRefPubMedGoogle Scholar
  28. 28.
    Golli M, Mathieu D, Anglade MC, Cherqui D, Vasile N, Rahmouni A. Focal nodular hyperplasia of the liver: value of color Doppler US in association with MR imaging. Radiology. 1993;187(1):113–7.PubMedGoogle Scholar
  29. 29.
    Wang LY, Wang JH, Lin ZY, Yu ML, Lu SN, Chuang WL, et al. Hepatic focal nodular hyperplasia: findings on color Doppler ultrasound. Abdom Imaging. 1997;22(2):178–81.CrossRefPubMedGoogle Scholar
  30. 30.
    Carlson SK, Johnson CD, Bender CE, Welch TJ. CT of focal nodular hyperplasia of the liver. AJR Am J Roentgenol. 2000;174(3):705–12.CrossRefPubMedGoogle Scholar
  31. 31.
    Bieze M, van den Esschert JW, Nio CY, Verheij J, Reitsma JB, Terpstra V, et al. Diagnostic accuracy of MRI in differentiating hepatocellular adenoma from focal nodular hyperplasia: prospective study of the additional value of gadoxetate disodium. AJR Am J Roentgenol. 2012;199(1):26–34.CrossRefPubMedGoogle Scholar
  32. 32.
    Meyers RL. Tumors of the liver in children. Surg Oncol. 2007;16(3):195–203. doi: 10.1016/j.suronc.2007.07.002; S0960-7404(07)00068-0 [pii].CrossRefPubMedGoogle Scholar
  33. 33.
    Resnick MB, Kozakewich HP, Perez-Atayde AR. Hepatic adenoma in the pediatric age group. Clinicopathological observations and assessment of cell proliferative activity. Am J Surg Pathol. 1995;19(10):1181–90.CrossRefPubMedGoogle Scholar
  34. 34.
    Bagia S, Hewitt PM, Morris DL. Anabolic steroid-induced hepatic adenomas with spontaneous haemorrhage in a bodybuilder. Aust N Z J Surg. 2000;70(9):686–7.CrossRefPubMedGoogle Scholar
  35. 35.
    Toso C, Rubbia-Brandt L, Negro F, Morel P, Mentha G. Hepatocellular adenoma and polycystic ovary syndrome. Liver Int. 2003;23(1):35–7.CrossRefPubMedGoogle Scholar
  36. 36.
    Marie-Cardine A, Schneider P, Greene V, Metayer J, Bachy B, Vannier JP. Erythrocytosis in a child with a hepatic adenoma. Med Pediatr Oncol. 2001;36(6):659–61. doi: 10.1002/mpo.1148.CrossRefPubMedGoogle Scholar
  37. 37.
    Musthafa CP, Chettupuzha AP, Syed AA, Ayshabi KA, Aravindan KP, Shobhana DR. Liver adenomatosis. Indian J Gastroenterol. 2003;22(1):30–1.PubMedGoogle Scholar
  38. 38.
    Rubin RA, Mitchell DG. Evaluation of the solid hepatic mass. Med Clin North Am. 1996;80(5):907–28.CrossRefPubMedGoogle Scholar
  39. 39.
    Grazioli L, Federle MP, Brancatelli G, Ichikawa T, Olivetti L, Blachar A. Hepatic adenomas: imaging and pathologic findings. Radiographics. 2001;21(4):877–92.CrossRefPubMedGoogle Scholar
  40. 40.
    Micchelli ST, Vivekanandan P, Boitnott JK, Pawlik TM, Choti MA, Torbenson M. Malignant transformation of hepatic adenomas. Mod Pathol. 2008;21(4):491–7. doi: 10.1038/modpathol.2008.8; modpathol20088 [pii].CrossRefPubMedGoogle Scholar
  41. 41.
    Farges O, Dokmak S. Malignant transformation of liver adenoma: an analysis of the literature. Dig Surg. 2010;27(1):32–8. doi: 10.1159/000268405; 000268405 [pii].CrossRefPubMedGoogle Scholar
  42. 42.
    Hartleb M, Gutkowski K, Milkiewicz P. Nodular regenerative hyperplasia: evolving concepts on underdiagnosed cause of portal hypertension. World J Gastroenterol. 2011;17(11):1400–9.CrossRefPubMedCentralPubMedGoogle Scholar
  43. 43.
    Giardiello FM, Petersen GM, Brensinger JD, Luce MC, Cayouette MC, Bacon J, et al. Hepatoblastoma and APC gene mutation in familial adenomatous polyposis. Gut. 1996;39(6):867–9. Pubmed PMCID:PM:PMC1383462.CrossRefPubMedCentralPubMedGoogle Scholar
  44. 44.
    Steenman M, Westerveld A, Mannens M. Genetics of Beckwith-Wiedemann syndrome-associated tumors: common genetic pathways. Genes Chromosomes Cancer. 2000;28(1):1–13. 10.1002/(SICI)1098-2264(200005)28:1<1::AID-GCC1>3.0.CO;2-# [pii].CrossRefPubMedGoogle Scholar
  45. 45.
    Van Tornout JM, Buckley JD, Quinn JJ, Feusner JH, Krailo MD, King DR, et al. Timing and magnitude of 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. 1997;15(3):1190–7.PubMedGoogle Scholar
  46. 46.
    Chung EM, Lattin Jr GE, Cube R, Lewis RB, Marichal-Hernandez C, Shawhan R, et al. From the archives of the AFIP: pediatric liver masses: radiologic-pathologic correlation. Part 2. Malignant tumors. Radiographics. 2011;31(2):483–507. doi: 10.1148/rg.312105201. 31/2/483 [pii].CrossRefPubMedGoogle Scholar
  47. 47.
    Otte JB. Progress in the surgical treatment of malignant liver tumors in children. Cancer Treat Rev. 2010;36(4):360–71. doi: 10.1016/j.ctrv.2010.02.013; S0305-7372(10)00033-2 [pii].CrossRefPubMedGoogle Scholar
  48. 48.
    Meyers RL, Czauderna P, Otte JB. Surgical treatment of hepatoblastoma. Pediatr Blood Cancer. 2012;59(5):800–8. doi: 10.1002/pbc.24220.CrossRefPubMedGoogle Scholar
  49. 49.
    Trobaugh-Lotrario AD, Katzenstein HM. Chemotherapeutic approaches for newly diagnosed hepatoblastoma: past, present, and future strategies. Pediatr Blood Cancer. 2012;59(5):809–12. doi: 10.1002/pbc.24219.CrossRefPubMedGoogle Scholar
  50. 50.
    Herzog CE, Andrassy RJ, Eftekhari F. Childhood cancers: hepatoblastoma. Oncologist. 2000;5(6):445–53.CrossRefPubMedGoogle Scholar
  51. 51.
    Brown J, Perilongo G, Shafford E, Keeling J, Pritchard J, Brock P, et al. Pretreatment prognostic factors for children with hepatoblastoma – results from the International Society of Paediatric Oncology (SIOP) study SIOPEL 1. Eur J Cancer. 2000;36(11):1418–25. S0959-8049(00)00074-5 [pii].CrossRefPubMedGoogle Scholar
  52. 52.
    Czauderna P. Adult type vs. childhood hepatocellular carcinoma – are they the same or different lesions? Biology, natural history, prognosis, and treatment. Med Pediatr Oncol. 2002;39(5):519–23. doi: 10.1002/mpo.10178.CrossRefPubMedGoogle Scholar
  53. 53.
    Ferenci P, Fried M, Labrecque D, Bruix J, Sherman M, Omata M, et al. Hepatocellular carcinoma (HCC): a global perspective. J Clin Gastroenterol. 2010;44(4):239–45. doi: 10.1097/MCG.0b013e3181d46ef2.CrossRefPubMedGoogle Scholar
  54. 54.
    Yu SB, Kim HY, Eo H, Won JK, Jung SE, Park KW, et al. Clinical characteristics and prognosis of pediatric hepatocellular carcinoma. World J Surg. 2006;30(1):43–50. 10.1007/s00268-005-7965-z.CrossRefPubMedGoogle Scholar
  55. 55.
    European Association for the Study of the Liver, European Organisation for Research and Treatment of Cancer. EASL-EORTC clinical practice guidelines: management of hepatocellular carcinoma. J Hepatol. 2012;56(4):908–43. doi: 10.1016/j.jhep.2011.12.001; S0168-8278(11)00873-7 [pii].Google Scholar
  56. 56.
    Hanish SI, Knechtle SJ. Liver transplantation for the treatment of hepatocellular carcinoma. Oncology (Williston Park). 2011;25(8):752–7.Google Scholar
  57. 57.
    Mazzaferro V, Regalia E, Doci R, Andreola S, Pulvirenti A, Bozzetti F, et al. Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis. N Engl J Med. 1996;334(11):693–9. doi: 10.1056/NEJM199603143341104.CrossRefPubMedGoogle Scholar
  58. 58.
    McLarney JK, Rucker PT, Bender GN, Goodman ZD, Kashitani N, Ros PR. Fibrolamellar carcinoma of the liver: radiologic-pathologic correlation. Radiographics. 1999;19(2):453–71.CrossRefPubMedGoogle Scholar
  59. 59.
    Mavros MN, Mayo SC, Hyder O, Pawlik TM. A systematic review: treatment and prognosis of patients with fibrolamellar hepatocellular carcinoma. J Am Coll Surg. 2012;215(6):820–30.CrossRefPubMedGoogle Scholar
  60. 60.
    Crider MH, Hoggard E, Manivel JC. Undifferentiated (embryonal) sarcoma of the liver. Radiographics. 2009;29(6):1665–8. doi: 10.1148/rg.296085237. 29/6/1665 [pii].CrossRefPubMedGoogle Scholar
  61. 61.
    Noguchi K, Yokoo H, Nakanishi K, Kakisaka T, Tsuruga Y, Kamachi H, et al. A long-term survival case of adult undifferentiated embryonal sarcoma of liver. World J Surg Oncol. 2012;10:65. doi: 10.1186/1477-7819-10-65. Pubmed PMCID:PM:PMC3407002 DOI: 1477-7819-10-65 [pii].CrossRefPubMedCentralPubMedGoogle Scholar
  62. 62.
    Makhlouf HR, Ishak KG, Goodman ZD. Epithelioid hemangioendothelioma of the liver: a clinicopathologic study of 137 cases. Cancer. 1999;85(3):562–82. 10.1002/(SICI)1097-0142(19990201)85:3<562::AID-CNCR7>3.0.CO;2-T [pii].CrossRefPubMedGoogle Scholar
  63. 63.
    Lyburn ID, Torreggiani WC, Harris AC, Zwirewich CV, Buckley AR, Davis JE, et al. Hepatic epithelioid hemangioendothelioma: sonographic, CT, and MR imaging appearances. AJR Am J Roentgenol. 2003;180(5):1359–64.CrossRefPubMedGoogle Scholar
  64. 64.
    Buetow PC, Buck JL, Ros PR, Goodman ZD. Malignant vascular tumors of the liver: radiologic-pathologic correlation. Radiographics. 1994;14(1):153–66.CrossRefPubMedGoogle Scholar
  65. 65.
    Spunt SL, Lobe TE, Pappo AS, Parham DM, Wharam Jr MD, Arndt C, et al. Aggressive surgery is unwarranted for biliary tract rhabdomyosarcoma. J Pediatr Surg. 2000;35(2):309–16. S0022-3468(00)90030-7 [pii].CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Rohit Gupta
    • 1
  • André A. Dick
    • 2
  • Karen F. Murray
    • 1
  1. 1.Division of Pediatric Gastroenterology and HepatologySeattle Children’s Hospital, University of Washington School of MedicineSeattleUSA
  2. 2.Division of Pediatric Transplantation, Department of SurgeryUniversity of Washington School of Medicine, Seattle Children’s HospitalSeattleUSA

Personalised recommendations