Hepatocellular-Cholangiocarcinomas in Non-Alcoholic Fatty Liver Disease: Evidence for Stem Cell Origin

Authors

  • Paulo Giovanni Mendoza National Kidney and Transplant Institute, East Avenue, Quezon City, Philippines
  • Wilson Tsui Caritas Medical Centre, Hong Kong
  • Lorraine Ho Caritas Medical Centre, Hong Kong
  • Michael Wayne Beth Israel Medical Center of Albert Einstein College of Medicine, New York, USA
  • Alexander Kagen Icahn School of Medicine at Mount Sinai, Mount Sinai West, Mount Sinai St. Luke’s, New York, USA
  • Neil Theise Beth Israel Medical Center of Albert Einstein College of Medicine, New York, USA http://orcid.org/0000-0002-4048-5140

DOI:

https://doi.org/10.21141/PJP.2016.008

Keywords:

hepatocellular-cholangiocarcinoma, non-alcoholic fatty liver disease (NAFLD), steatohepatitis, stem cell

Abstract

The authors present two cases of combined hepatocellular-cholangiocarcinoma in a background of non-cirrhotic, non-alcoholic fatty liver disease (NAFLD). The increasing incidence of NAFLD and the subsequent recognition of it being a pre-malignant condition even in the absence of significant fibrosis or established cirrhosis has led to the investigations of the different pathways involved in NAFLD-associated hepatocarcinogenesis, including speculations regarding the possibility that many derive from pre-malignant hepatocellular adenomas, tumors also increasingly associated with NAFLD, or reflect malignant transformation of mature hepatocytes through genetic and epigenetic alterations reflecting inflammatory changes in NAFLD. However, NAFLD, like most chronic liver diseases, leads to progressive activation of resident hepatobiliary stem/progenitor cells that are thought to give rise to malignant tumors in other settings. In particular, combined hepatocellular-cholangiocarcinomas (with and without stem cell features) are thought to reflect malignant transformation of these activated progenitors. Our two cases of combined hepatocellular-cholangiocarcinomas suggest that malignant transformation of hepatobiliary stem/progenitor cells in NAFLD are also a possible pathway to malignancy, even in the absence of established cirrhosis.

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Author Biographies

Paulo Giovanni Mendoza, National Kidney and Transplant Institute, East Avenue, Quezon City, Philippines

Department of Pathology and Laboratory Medicine

Wilson Tsui, Caritas Medical Centre, Hong Kong

Department of Pathology

Lorraine Ho, Caritas Medical Centre, Hong Kong

Department of Radiology

Michael Wayne, Beth Israel Medical Center of Albert Einstein College of Medicine, New York, USA

Department of Surgery

Alexander Kagen, Icahn School of Medicine at Mount Sinai, Mount Sinai West, Mount Sinai St. Luke’s, New York, USA

Department of Radiology

Neil Theise, Beth Israel Medical Center of Albert Einstein College of Medicine, New York, USA

Departments of Pathology and Medicine (Division of Digestive Diseases)

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Published

2016-05-05

How to Cite

Mendoza, P. G., Tsui, W., Ho, L., Wayne, M., Kagen, A., & Theise, N. (2016). Hepatocellular-Cholangiocarcinomas in Non-Alcoholic Fatty Liver Disease: Evidence for Stem Cell Origin. PJP, 1(1), 30–35. https://doi.org/10.21141/PJP.2016.008

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Section

Case Reports