title: Hepatic 'stem cell' malignancies in adults: four cases.
abstract: OBJECTIVE
  Combined hepatocellular/cholangiocarcinomas have been explained by some investigators as bidirectional differentiation of neoplastic progenitor cell populations. The presence of hepatic progenitor cells has now been confirmed in humans, though whether they can give rise to malignant tumours has not been confirmed. We report four cases of small tumours identified in livers with features of chronic hepatitis which may suggest a role for malignant transformation of hepatic stem cells in hepatic malignancies.
  
  
  METHODS
  Tumour samples were studied from four patients by histochemistry and immunohistochemistry.
  
  
  RESULTS
  Two patients had chronic hepatitis B, one had chronic hepatitis C and chronic alcoholic liver injury, and one had non-B non-C chronic hepatitis. Stages of disease ranged from portal fibrosis to cirrhosis. All tumours contained undifferentiated cells with morphological and immunohistochemical features that would be expected of hepatic progenitor cells. These cells merged with both hepatocellular carcinoma and cholangiocarcinoma components as well as with mature appearing hepatocytes within the tumours.
  
  
  CONCLUSIONS
  We suggest that these tumours are of hepatic progenitor cell origin, supporting the concepts that human hepatocarcinogenesis can be based on transformation of progenitor cells and that such a process may underlie development of some mixed hepatocellular/cholangiocarcinomas and dysplastic nodules.
authors.affiliation: Department of Pathology, New York University Medical Center, New York, NY, USA. ntheise@chpnet.org
authors.forename: N D
authors.initials: ND
authors.lastname: Theise
authors.forename: J L
authors.initials: JL
authors.lastname: Yao
authors.forename: K
authors.initials: K
authors.lastname: Harada
authors.forename: P
authors.initials: P
authors.lastname: Hytiroglou
authors.forename: B
authors.initials: B
authors.lastname: Portmann
authors.forename: S N
authors.initials: SN
authors.lastname: Thung
authors.forename: W
authors.initials: W
authors.lastname: Tsui
authors.forename: H
authors.initials: H
authors.lastname: Ohta
authors.forename: Y
authors.initials: Y
authors.lastname: Nakanuma
mesh_terms: D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000473:pathology; D002471:Cell Transformation, Neoplastic / Q000473:pathology*; D018281:Cholangiocarcinoma / Q000473:pathology; D005260:Female; D006521:Hepatitis, Chronic / Q000150:complications / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000150:complications / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D013234:Stem Cells / Q000473:pathology*