Skip to main content
SpringerLink
Log in

Hepatoblastomas: Biology of Disease and Prognostic Factors

  • Living reference work entry
  • First Online:
Tumors and Tumor-Like Lesions of the Hepatobiliary Tract

  • 68 Accesses

Abstract

Biology of disease and prognosis in hepatoblastoma (HB) strongly depend on the initial stage of disease. At primary diagnosis, 40–60 % of HB either present as large or very large tumors, or involve both liver lobes, rendering the tumors unresectable. Therefore, downstaging of tumors by chemotherapy is a crucial approach. Tumor staging in HB has been standardized in great detail. Similar to hepatocellular carcinoma, HB has a strong tendency to invade the vascular system (macrovessel and microvessel invasion). Apart from stage, which is the most powerful prognosticator in HB, other prognostic factors include serum alpha-fetoprotein (AFP) levels, tumor histology, and molecular features. HB patients with low serum AFP concentrations form a high-risk group. Among various histologic types and subtypes, the fetal pattern is a favorable histology, whereas the small cell undifferentiated phenotype with or without rhabdoid features confers a high-risk biology. An increasing number of molecular abnormalities will be used in the future as risk stratificators.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution

Institutional subscriptions

References

  • Ang JP, Heath JA, Donath S et al (2007) Treatment outcomes for hepatoblastoma: an institution’s experience over two decades. Pediatr Surg Int 23:103–109

    Google Scholar 

  • Ara T, Fukuzawa M, Oue T, Komoto Y, Kusafuka T, Imura K, Okada A (1997) Immunohistochemical assessment of the MIB-1 labeling index in human hepatoblastoma and its prognostic relevance. J Pediatr Surg 32:1690–1694

    Article  CAS  PubMed  Google Scholar 

  • Austin MT, Leys CM, Feurer ID, Lovvom HN, O’Neill JA, Pinson CW, Pietsch JB (2006) Liver transplantation for childhood hepatic malignancy: a review of the United Network for Organ Sharing (UNOS) database. J Pediatr Surg 41:182–186

    Article  PubMed  Google Scholar 

  • Baertschiger RM, Ozsahin H, Rougemont AL, Anooshiravani M, Rubbia-Brandt L et al (2010) Cure of multifocal hepatoblastoma: is liver transplantation always necessary? J Pediatr Surg 45:1030–1036

    Article  PubMed  Google Scholar 

  • Borman JB, Harbott AJ, Morris D (1961) Hepatic lobectomy in infancy for hepatoblastoma. Br J Surg 49:11–13

    Article  CAS  PubMed  Google Scholar 

  • Brown J, Perilongo G, Shafford E, Keeling J, Pritchard J, Brock P, Dicks-Mireaux C et al (2000) Pretreatment prognostic factors for children with hepatoblastoma – results from the International Society of Paediatric Oncology (SIOP) study SIOPEL 1. Eur J Cancer 36:1418–1425

    Article  CAS  PubMed  Google Scholar 

  • Browne M, Sher D, Grant D, Deluca E, Alonso E, Whitington PF, Superina RA (2008) Survival after liver transplantation for hepatoblastoma: a 2-center experience. J Pediatr Surg 43:1973–1981

    Article  PubMed  Google Scholar 

  • Cillo et al. (2003) http://www.ncbi.nlm.nih.gov/pubmed/14697956

  • Conran RM, Hitchcock CL, Waclawiw MA, Stocker JT, Ishak KG (1992) Hepatoblastoma: the prognostic significance of histologic type. Pediatr Pathol 12:167–183

    Article  CAS  PubMed  Google Scholar 

  • Cruz PV, Wakai T, Shirai Y, Yokoyama N, Hatakeyama K (2005) Loss of carcinoembryonic antigen-related cell adhesion molecule 1 expression is an adverse prognostic factor in hepatocellular carcinoma. Cancer 104:354–360

    Article  CAS  PubMed  Google Scholar 

  • Czauderna P, Otte JB, Aronson DC, Gauthier F, Mackinley G, Roebuck D, Plaschkes J et al (2005) Guidelines for surgical treatment of hepatoblastoma in the modern age – recommendations form the Childhood Liver Tumour Strategy Group of the International Society for Paediatric Oncology (SIOPEL). Eur J Cancer 41:1031–1036

    Article  PubMed  Google Scholar 

  • D’Antiga L, Vallortigara F, Cillo U, Talenti E, Rugge M, Zancan L, Dall’Igna P, De Salvo GL, Perilongo G (2007) Features predicting unresectability in hepatoblastoma. Cancer 110:1050–1058

    Article  PubMed  Google Scholar 

  • Davies JQ, de la Hall PM, Kaschula RO, Sinclair-Smith CC, Hartley P, Rode H, Millar AJ (2004) Hepatoblastoma – evolution of management and outcome and significance of histology of the resected tumor. A 31-year experience with 40 cases. J Pediatr Surg 39:1321–1327

    Article  CAS  PubMed  Google Scholar 

  • De Ioris M, Brugières L, Zimmermann A, Keeling J, Broch P, Maibach R, Pritchard J et al (2008) Hepatoblastoma with a low serum alpha-fetoprotein level at diagnosis: the SIOPEL group experience. Eur J Cancer 44:545–550

    Article  PubMed  Google Scholar 

  • Debré R, Mozziconacci P, Habib R (1954) L’Hépatoblastoma (tumeur maligne du foie à cellules embryonnaires) (in French). Arch Fr Pédiat 11:1013–1034

    PubMed  Google Scholar 

  • Dehner LP, Manivel JC (1988) Hepatoblastoma: an analysis of the relationship between morphologic subtypes and prognosis. Am J Pediatr Hematol Oncol 10:301–307

    Article  CAS  PubMed  Google Scholar 

  • Dicken BJ, Bigam DL, Lees GM (2004) Association between surgical margins and long-term outcome in advanced hepatoblastoma. J Pediatr Surg 39:721–725

    Article  PubMed  Google Scholar 

  • Doss BJ, Vicari J, Jacques SM, Qureshi F (1998) Placental involvement in congenital hepatoblastoma. Pediatr Dev Pathol 1:538–542

    Article  CAS  PubMed  Google Scholar 

  • Douglass EC, Finegold M, Reynolds M et al (1993) Cisplatin, vincristine and fluorouracil therapy for hepatoblastoma: a Pediatric Oncology Group Study. J Clin Oncol 11:96–99

    Article  CAS  PubMed  Google Scholar 

  • Ehrlich PF, Greenberg ML, Filler RM (1997) Improved long-term survival with preoperative chemotherapy for hepatoblastoma. J Pediatr Surg 32:999–1003

    Article  CAS  PubMed  Google Scholar 

  • Exelby PR, Filler RM, Grosfeld JL (1975) Liver tumors in children in the particular reference to hepatoblastoma and hepatocellular carcinoma: American Academy of Pediatrics Surgical Section Survey – 1974. J Pediatr Surg 10:329–337

    Article  CAS  PubMed  Google Scholar 

  • Faraj W, Dar F, Marangoni G, Bartlett A, Mlenedez HV, Hadzic D, Dhawan A, Mieli-Vergani G et al (2008) Liver transplantation for hepatoblastoma. Liver Transpl 14:1614–1619

    Article  PubMed  Google Scholar 

  • Fuchs J, Rydzynski J, Von Schweinitz D, Bode U, Hecker H, Weinel P, Burger D, Harms D et al (2002) Pretreatment prognostic factors and treatment results in children with hepatoblastoma a report from the German Cooperative pediatric Liver Tumor Study HB 94. Cancer 95:172–182

    Article  PubMed  Google Scholar 

  • Giacomantonio M, Ein SH, Mancer K, Stephens CA (1984) Thirty years of experience with pediatric primary malignant liver tumors. J Pediatr Surg 19:523–526

    Article  CAS  PubMed  Google Scholar 

  • Gururangan S, O’Meara A, MacMahon C, Guiney EJ, O’Donnell B, Fitzgerald RJ, Breatnach F (1992) Primary hepatic tumours in children: a 26-year review. J Surg 50:30–36

    CAS  Google Scholar 

  • Gyugos M, Lendvai G, Kenessey I, Schlachter K, Halasz J, Nagy P, Garami M, Jakab Z et al (2014) MicroRNA expression might predict prognosis of epithelial hepatoblastoma. Virchows Arch 464:419–427

    Article  CAS  PubMed  Google Scholar 

  • Haas JE, Muczynski KA, Krailo M, Ablin A, Land V, Vietti TJ, Hammond GD (1989) Histopathology and prognosis in childhood hepatoblastoma and hepatocarcinoma. Cancer 64:1082–1095

    Article  CAS  PubMed  Google Scholar 

  • Honda et al. 2013. http://www.ncbi.nlm.nih.gov/pubmed/23989600

  • Horton JD, Lee S, Brown SR, Bader J, Meier DE (2009) Survival trends in children with hepatoblastoma. Pediatr Surg Int 25:407–412

    Article  PubMed  Google Scholar 

  • Jung SE, Kim KH, Kim MY, Kim DY, Lee SC, Park KW, Kim WK (2001) Clinical characteristics and prognosis of patients with hepatoblastoma. World J Surg 25:126–130

    Article  CAS  PubMed  Google Scholar 

  • Katzenstein HM, London WB, Douglass EC, Reynolds M, Plaschkes J, Finegold MJ, Bowman LC (2002) Treatment of unresectable and metastatic hepatoblastoma: a pediatric oncology group phase II study. J Clin Oncol 20:3438–3444

    Article  PubMed  Google Scholar 

  • Keeling JW (1971) Liver tumours in infancy and childhood. J Path 103:69–85

    Article  CAS  PubMed  Google Scholar 

  • Koneru B, Flye MW, Busuttil RW, Shaw BW, Lorber MI, Emond JC, Kalayoglu M et al (1991) Liver transplantation for hepatoblastoma. The American experience. Ann Surg 213:118–121

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mahour GH, Wogu GU, Siegel SE, Isaacs H (1983) Improved survival in infants and children with primary malignant liver tumors. Am J Surg 146:236–240

    Article  CAS  PubMed  Google Scholar 

  • Maibach R, Roebuck D, Brugieres L, Capra M, Brock P, Dall’Igna P, Otte JB, De Camargo B et al (2012) Prognostic stratification for children with hepatoblastoma: the SIOPEL experience. Eur J Cancer 48:1543–1549

    Article  PubMed  Google Scholar 

  • Malogolowkin MH, Katzenstein HM, Meyers RL, Krailo MD, Rowland JM, Haas J, Finegold MJ (2011) Complete surgical resection is curative for children with hepatoblastoma with pure fetal histology: a report from the Children’s Oncology Group. J Clin Oncol 29:3301–3306

    Article  PubMed  PubMed Central  Google Scholar 

  • Malogolowkin MH, Katzenstein HM, Krailo M, Meyers RL (2012) Treatment of hepatoblastoma: the North American cooperative group experience. Front Biosci (Elite Ed) 4:1717–1723

    Article  Google Scholar 

  • Matsunaga T, Sasaki F, Ohira M, Hashizume K, Hayashi K, Hayashi A, Hayashi Y et al (2003) Analysis of treatment outcome for children with recurrent or metastatic hepatoblastoma. Pediatr Surg Int 19:142–146

    PubMed  Google Scholar 

  • Mejia A, Langnas AN, Shaw BW, Torres C, Sudan DL (2005) Living and deceased donor liver transplantation for unresectable hepatoblastoma at a single center. Clin Transpl 19:721–725

    Article  Google Scholar 

  • Meyers RL (2007) Tumors of the liver in children. Surg Oncol 16:195–203

    Article  PubMed  Google Scholar 

  • Milman DH, Grayzel DM (1951) Mixed tumor of the liver; report of case with review of literature. Am J Dis Child 81:408–420

    CAS  Google Scholar 

  • Ortega JA, Douglass EC, Feusner JH, Reynolds M, Quinn JJ, Finegold MJ, Haas JE et al (2000) Randomized comparison of cisplatin/vincristine/fluorouracil and cisplatin/continuous infusion doxorubicin for treatment of pediatric hepatoblastoma: a report from the Children’s Cancer Group and the pediatric Oncology Group. J Clin Oncol 18:2665–2675

    Article  CAS  PubMed  Google Scholar 

  • Otte JB (2010) Progress in the surgical treatment of malignant liver tumors in children. Cancer Treat Rev 36:360–371

    Article  PubMed  Google Scholar 

  • Otte JB, Pritchard J, Aronson DC, Brown J, Czauderna P, Maibach R, Perilongo G, Shafford E, Plaschkes J, International Society of Pediatric Oncology (SIOP) (2004) Liver transplantation for hepatoblastoma: results from the International Society of Pediatric Oncology (SIOP) study SIOPEL-1 and review of the world experience. Pediatr Blood Cancer 42:74–83

    Article  CAS  PubMed  Google Scholar 

  • Otte JB, de Ville de Goyet J, Reding R (2005) Liver transplantation for hepatoblastoma: indications and contraindications in the modern era. Pediatr Transplant 9:557–565

    Article  PubMed  Google Scholar 

  • Perilongo G, Shafford E, Maibach R, Aronson D, Brugières L, Brock P, Childs M, Czauderna P et al (2004) Risk-adapted treatment for childhood hepatoblastoma, final report of the second study of the International Society of Paediatric Oncology – SIOPEL-2. Eur J Cancer 40:411–421

    Article  CAS  PubMed  Google Scholar 

  • Perilongo G, Maibach R, Shafford E, Brugières L, Brock P, Morland B, de Camargo B et al (2009) Cisplatin versus cisplatin plus doxorubicin for standard-risk hepatoblastoma. N Engl J Med 361:1662–1670

    Article  CAS  PubMed  Google Scholar 

  • Pritchard J, Brown J, Shafford E et al (2000) Cisplatin, doxorubicin and delayed surgery for childhood hepatoblastoma: a successful approach. Results of the first prospective study of the International Society for Pediatric Oncology. J Clin Oncol 15:3819–3828

    Article  Google Scholar 

  • Purcell R, Childs M, Maibach R, Miles C, Turner C, Zimmermann A, Czauderna P, Sullivan M (2012) Potential biomarkers for hepatoblastoma: results from the SIOPEL-3 study. Eur J Cancer 48:1853–1859

    Article  CAS  PubMed  Google Scholar 

  • Reyes JD, Carr B, Dvorchik I, Kocoshis S, Jaffe R, Gerber D, Mazariegos GV, Bueno J, Selby R (2000) Liver transplantation and chemotherapy for hepatoblastoma and hepatocellular cancer in childhood and adolescence. J Pediatr 136:795–804

    Article  CAS  PubMed  Google Scholar 

  • Reynolds M (1995) Conversion of unresectable to resectable hepatoblastoma and long-term follow-up study. World J Surg 19:814–816

    Article  CAS  PubMed  Google Scholar 

  • Reynolds M, Douglass EC, Finegold M, Cantor A, Glicksman A (1992) Chemotherapy can convert unresectable hepatoblastoma. J Pediatr Surg 27:1080–1083

    Article  CAS  PubMed  Google Scholar 

  • Robinson HB, Bolande RP (1985) Case 3. Fetal hepatoblastoma with placental metastases. Pediatr Pathol 4:163–167

    Article  PubMed  Google Scholar 

  • Rugge M, Sonego F, Pollice L, Perilongo G, Guido M, Basso G, Ninfo V, Pennelli N, Gambini C, Guglielmi M et al (1998) Hepatoblastoma: DNA nuclear content, proliferative indices, and pathology. Liver 18:128–133

    Article  CAS  PubMed  Google Scholar 

  • Sasaki F, Matsunaga T, Iwafuchi M, Hayashi Y, Ohkawa H, Ohira M, Okamatsu T et al (2002) Outcome of hepatoblastoma treated with the JPLT-1 (Japanese Study Group for Pediatric Liver Tumor) Protocol-1: a report from the Japanese Study Group for Pediatric Liver Tumor. J Pediatr Surg 37:851–856

    Article  CAS  PubMed  Google Scholar 

  • Schlachter K, Gyugos M, Halasz J, Lendvai G, Baghy K, Garami M, Gyöngyösi B, Schaff Z et al (2014) High tricellulin expression is associated with better survival in human hepatoblastoma. Histopathology 65:631–641

    Article  PubMed  Google Scholar 

  • Schnater JM, Aronson DC, Plaschkes J, Perilongo G, Brown J, Otte JB, Brugieres L et al (2002) Surgical view of the treatment of patients with hepatoblastoma: results from the first prospective trial of the International Society of Pediatric Oncology Liver Tumor Study Group. Cancer 94:1111–1120

    Article  PubMed  Google Scholar 

  • Semeraro M, Branchereau S, Maibach R, Zsiros J, Casanova M, Brock P, Domerg C et al (2013) Relapses in hepatoblastoma patients: clinical characteristics and outcome – experience of the International Childhood Liver Tumour Strategy Group (SIOPEL). Eur J Cancer 49:915–922

    Article  CAS  PubMed  Google Scholar 

  • Seo T, Ando H, Watanabe Y, Harada T, Ito F, Kaneko K, Horibe K, Sugito T, Ito T (1998) Treatment of hepatoblastoma: less extensive hepatectomy after effective preoperative chemotherapy with cisplatin and adriamycin. Surgery 123:407–414

    Article  CAS  PubMed  Google Scholar 

  • Stiller CA, Pritchard J, Steliarova-Foucher E (2006) Liver cancer in European children: incidence and survival, 1978–1997. Report from the Automated Childhood Cancer Information System project. Eur J Cancer 42:2115–2123

    Article  CAS  PubMed  Google Scholar 

  • Trobaugh-Lotrario AD, Chaiyachati BH, Meyers RL, Häberle B, Tomlinson GE, Katzenstein HM et al (2013) Outcomes for patients with congenital hepatoblastoma. Pediatr Blood Cancer 60:1817–1825

    Article  PubMed  Google Scholar 

  • Tsai HW, Tsai HH, Kuo FY, Chang KC (2009) Computerized analysis of morphology and proliferative activity differentiated hepatoblastoma from paediatric hepatocellular carcinoma. Histopathology 54:328–336

    Article  PubMed  Google Scholar 

  • Tsukada M, Wakai T, Matsuda Y, Korita PV, Shirai Y, Ajioka Y, Hatakeyama K, Kubota M (2009) Loss of carcinoembryonic antigen-related cell adhesion molecule 1 expression predicts metachronous pulmonary metastasis and poor survival in patients with hepatoblastoma. J Pediatr Surg 44:1522–1528

    Article  PubMed  Google Scholar 

  • Venkatramani R, Wang L, Malvar J, Dias D, Sposto R, Malogolowkin MH, Mascarenhas L (2012) Tumor necrosis predicts survival following neo-adjuvant chemotherapy for hepatoblastoma. Pediatr Blood Cancer 59:493–498

    Article  PubMed  Google Scholar 

  • Von Schweinitz D, Wischmeyer P, leuschner I et al (1994) Clinicopathological criteria with prognostic relevance in hepatoblastoma. Eur J Cancer 30A:1052–1058

    Article  Google Scholar 

  • Von Schweinitz D, Hecker H, Harms D et al (1995) Complete resection before development of drug resistance is essential for survival from advanced hepatoblastoma. A report from the German Cooperative Pediatric Liver tumour Study HB-89. J Pediatr Surg 30:845–852

    Article  Google Scholar 

  • Wang JN, Chen JS, Chuang HY, Yang YJ, Chang KC, Wu JM (2002) Invasion of the cardiovascular system in childhood malignant hepatic tumors. J Pediatr Hematol Oncol 24:436–439

    Article  CAS  PubMed  Google Scholar 

  • Zsiros J, Maibach R, Shafford E, Brugières L, Brock P, Czauderna P, Roebuck D, Childs M et al (2010) Successful treatment of childhood high-risk hepatoblastoma with dose-intensive multiagent chemotherapy and surgery: final results of the SIOPEL-3HR study. J Clin Oncol 28:2584–2590

    Article  CAS  PubMed  Google Scholar 

  • Zsiros J, Brugières L, Brock P, Roebuck D, Maibach R, Childs M, Morland B, Casanova M et al (2012) Efficacy of irinotecan single drug treatment in children with refractory or recurrent hepatoblastoma – a phase II trial of the childhood liver tumour strategy group (SIOPEL). Eur J Cancer 48:3456–3464

    Article  CAS  PubMed  Google Scholar 

  • Zsiros J, Brugieres L, Brock P, Roebuck D, Maibach R, Zimmermann A, Childs M et al (2013) Dose-dense cisplatin-based chemotherapy and surgery for children with high-risk hepatoblastoma (SIOPEL-4): a prospective, single-arm, feasibility study. Lancet Oncol 14:834–842

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. University of Bern, Bern, Switzerland

    Arthur Zimmermann

Authors
  1. Arthur Zimmermann
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Arthur Zimmermann .

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer International Publishing Switzerland

About this entry

Cite this entry

Zimmermann, A. (2016). Hepatoblastomas: Biology of Disease and Prognostic Factors. In: Tumors and Tumor-Like Lesions of the Hepatobiliary Tract. Springer, Cham. https://doi.org/10.1007/978-3-319-26587-2_21-1

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-26587-2_21-1

  • Received:

  • Accepted:

  • Published:

  • Publisher Name: Springer, Cham

  • Online ISBN: 978-3-319-26587-2

  • eBook Packages: Springer Reference MedicineReference Module Medicine

Publish with us

Policies and ethics

Search

Navigation