Journal of Gastrointestinal Cancer

, Volume 43, Issue 1, pp 97–102 | Cite as

A Rare Case of Metastatic Pancreatic Hepatoid Carcinoma Treated with Sorafenib

  • Fausto PetrelliEmail author
  • Maria Ghilardi
  • Silvia Colombo
  • Enrico Stringhi
  • Cecilia Barbara
  • Mary Cabiddu
  • Stefano Elia
  • Daniela Corti
  • Sandro Barni
Case Report



Hepatoid carcinoma (HC) is a rare histopathological tumor type with prominent features of hepatoid differentiation, and while most of the reported cases are of gastric origin, ten cases of pancreatic HC have been reported to date. The majority of HC cases are metastatic at presentation, mainly to the liver, lymph nodes, and lungs. They are aggressive, invading, and proliferating in the venous and lymphatic systems, with a behavior similar to that of hepatocellular carcinoma. Diagnosis is challenging: alpha-Fetoprotein, the most useful marker, is not always positive.


We present the first case of metastatic pancreatic HC treated with sorafenib, an oral multikinase inhibitor approved for advanced hepatocellular carcinoma that has antiangiogenic, pro-apoptotic, and raf-kinase inhibitory properties.


The patient, a 37-year-old male, was diagnosed with hepatoid carcinoma of the pancreas that had metastasized to liver, lungs, and lymph nodes. The cytokeratin (CK) profile was useful for the diagnosis: Both the hepatoid and adenocarcinoma components of the tumors were CK18+, CK19+, and CK20+/−, whereas normal and neoplastic hepatocytes are CK18+, CK19−, and CK20−. Amylase, lipase, and liver enzyme levels were elevated, but bilirubin was normal. Treatment with sorafenib resulted in more than 7 months of progression-free survival. Therapy was discontinued after 8 months when his bilirubin level increased dramatically. Signs of liver failure resolved temporarily with insertion of a biliary stent, but his condition deteriorated and he died 3 months later, 1 year after diagnosis.


In the absence of evidence-based experience with this rare and aggressive tumor and given its similarities with hepatocellular carcinoma, sorafenib should be considered as a possible treatment.


Pancreatic hepatoid carcinoma Sorafenib Liver metastasis Antiangiogenic therapy 


  1. 1.
    Ishikura H, Fukasawa Y, Ogasawara K, et al. An AFP-producing gastric carcinoma with features of hepatic differentiation. A case report. Cancer. 1985;56:840–8.PubMedCrossRefGoogle Scholar
  2. 2.
    Liu CZ, Hu SY, Wang L, et al. Hepatoid carcinoma of the pancreas: a case report. Chin Med J (Engl). 2007;120:1850–2.Google Scholar
  3. 3.
    Hameed O, Xu H, Saddeghi S, et al. Hepatoid carcinoma of the pancreas: a case report and literature review of a heterogeneous group of tumors. Am J Surg Pathol. 2007;31:146–52.PubMedCrossRefGoogle Scholar
  4. 4.
    Matsueda K, Yamamoto H, Yoshida Y, et al. Hepatoid carcinoma of the pancreas producing protein induced by vitamin K absence or antagonist II (PIVKA-II) and alpha-fetoprotein (AFP). J Gastroenterol. 2006;41:1011–9.PubMedCrossRefGoogle Scholar
  5. 5.
    Oh HJ, Cheung DY, Kim TH, et al. A case of hepatoid carcinoma of the pancreas. Korean J Gastroenterol. 2006;47:389–93.PubMedGoogle Scholar
  6. 6.
    Shih NN, Tsung JS, Yang AH, et al. A unique pancreatic tumor with exclusive hepatocytic differentiation. Ann Clin Lab Sci. 2006;36:216–21.PubMedGoogle Scholar
  7. 7.
    Hughes K, Kelty S, Martin R. Hepatoid carcinoma of the pancreas. Am Surg. 2004;70:1030–3.PubMedGoogle Scholar
  8. 8.
    Paner GP, Thompson KS, Reyes CV. Hepatoid carcinoma of the pancreas. Cancer. 2000;88:1582–9.PubMedCrossRefGoogle Scholar
  9. 9.
    Yano T, Ishikura H, Wada T, et al. Hepatoid adenocarcinoma of the pancreas. Histopathology. 1999;35:90–2.PubMedCrossRefGoogle Scholar
  10. 10.
    Hruban RH, Molina JM, Reddy MN, et al. A neoplasm with pancreatic and hepatocellular differentiation presenting with subcutaneous fat necrosis. Am J Clin Pathol. 1987;88:639–45.PubMedGoogle Scholar
  11. 11.
    Tanno S, Obara T, Fujii T, et al. alpha-Fetoprotein-producing adenocarcinoma of the pancreas presenting focal hepatoid differentiation. Int J Pancreatol. 1999;26:43–7.PubMedCrossRefGoogle Scholar
  12. 12.
    Ishikura H, Kishimoto T, Andachi H, et al. Gastrointestinal hepatoid adenocarcinoma: venous permeation and mimicry of hepatocellular carcinoma, a report of four cases. Histopathology. 1997;31:47–54.PubMedCrossRefGoogle Scholar
  13. 13.
    Liu L, Cao Y, Chen C, et al. Sorafenib blocks the RAF/MEK/ERK pathway, inhibits tumor angiogenesis, and induces tumor cell apoptosis in hepatocellular carcinoma model PLC/PRF/5. Cancer Res. 2006;66:11851–8.PubMedCrossRefGoogle Scholar
  14. 14.
    Kawamoto S, Hiraoka T, Kanemitsu K, et al. Alpha-fetoprotein-producing pancreatic cancer—a case report and review of 28 cases. Hepatogastroenterology. 1992;39:282–6.PubMedGoogle Scholar
  15. 15.
    Tochigi N, Kishimoto T, Supriatna Y, et al. Hepatoid carcinoma of the ovary: a report of three cases admixed with a common surface epithelial carcinoma. Int J Gynecol Pathol. 2003;22:266–71.PubMedCrossRefGoogle Scholar
  16. 16.
    Foschini MP, Baccarini P, Dal Monte PR, et al. Albumin gene expression in adenocarcinomas with hepatoid differentiation. Virchows Arch. 1998;433:537–41.PubMedCrossRefGoogle Scholar
  17. 17.
    Ishikura H, Kanda M, Ito M, et al. Hepatoid adenocarcinoma: a distinctive histological subtype of alpha-fetoprotein-producing lung carcinoma. Virchows Arch A Pathol Anat Histopathol. 1990;417:73–80.PubMedCrossRefGoogle Scholar
  18. 18.
    Motoyama T, Aizawa K, Watanabe H, et al. alpha-Fetoprotein producing gastric carcinomas: a comparative study of three different subtypes. Acta Pathol Jpn. 1993;43:654–61.PubMedGoogle Scholar
  19. 19.
    Shintaku M, Kariya M, Shime H, et al. Adenocarcinoma of the uterine cervix with choriocarcinomatous and hepatoid differentiation: report of a case. Int J Gynecol Pathol. 2000;19:174–8.PubMedCrossRefGoogle Scholar
  20. 20.
    deLorimier A, Park F, Aranha GV, et al. Hepatoid carcinoma of the stomach. Cancer. 1993;71:293–6.PubMedCrossRefGoogle Scholar
  21. 21.
    Texler ML, Pierides J, Maddern GJ. Case report: a hepatocellular carcinoma metastasis in the distal pancreas. J Gastroenterol Hepatol. 1998;13:467–70.PubMedCrossRefGoogle Scholar
  22. 22.
    Dabeva MD, Hwang SG, Vasa SR, et al. Differentiation of pancreatic epithelial progenitor cells into hepatocytes following transplantation into rat liver. Proc Natl Acad Sci USA. 1997;94:7356–61.PubMedCrossRefGoogle Scholar
  23. 23.
    Krakowski ML, Kritzik MR, Jones EM, et al. Pancreatic expression of keratinocyte growth factor leads to differentiation of islet hepatocytes and proliferation of duct cells. Am J Pathol. 1999;154:683–91.PubMedCrossRefGoogle Scholar
  24. 24.
    Wang X, Al-Dhalimy M, Lagasse E, et al. Liver repopulation and correction of metabolic liver disease by transplanted adult mouse pancreatic cells. Am J Pathol. 2001;158:571–9.PubMedCrossRefGoogle Scholar
  25. 25.
    Yang L, Li S, Hatch H, et al. In vitro trans-differentiation of adult hepatic stem cells into pancreatic endocrine hormone-producing cells. Proc Natl Acad Sci USA. 2002;99:8078–83.PubMedCrossRefGoogle Scholar
  26. 26.
    Zalzman M, Gupta S, Giri RK, et al. Reversal of hyperglycemia in mice by using human expandable insulin-producing cells differentiated from fetal liver progenitor cells. Proc Natl Acad Sci USA. 2003;100:7253–8.PubMedCrossRefGoogle Scholar
  27. 27.
    Suzuki A, Zheng YW, Kaneko S, et al. Clonal identification and characterization of self-renewing pluripotent stem cells in the developing liver. J Cell Biol. 2002;156:173–84.PubMedCrossRefGoogle Scholar
  28. 28.
    Yamada S, Terada K, Ueno Y, et al. Differentiation of adult hepatic stem-like cells into pancreatic endocrine cells. Cell Transplant. 2005;14:647–53.PubMedCrossRefGoogle Scholar
  29. 29.
    Burris 3rd HA, Moore MJ, Andersen J, et al. Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial. J Clin Oncol. 1997;15:2403–13.PubMedGoogle Scholar
  30. 30.
    Llovet JM, Ricci S, Mazzaferro V, et al. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med. 2008;359:378–90.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Fausto Petrelli
    • 1
    Email author
  • Maria Ghilardi
    • 1
  • Silvia Colombo
    • 2
  • Enrico Stringhi
    • 3
  • Cecilia Barbara
    • 4
  • Mary Cabiddu
    • 1
  • Stefano Elia
    • 5
  • Daniela Corti
    • 6
  • Sandro Barni
    • 1
  1. 1.Medical Oncology UnitTreviglio-Caravaggio HospitalTreviglioItaly
  2. 2.Hepatology ServiceTreviglio-Caravaggio HospitalTreviglioItaly
  3. 3.Department of SurgeryTreviglio-Caravaggio HospitalTreviglioItaly
  4. 4.Medical Oncology Unit, Spedali Riuniti AUSL 6Istituto Toscano TumoriLivornoItaly
  5. 5.Radiology UnitTreviglio-Caravaggio HospitalTreviglioItaly
  6. 6.Pathology UnitTreviglio-Caravaggio HospitalTreviglioItaly

Personalised recommendations