title: Hepatocellular carcinoma arising in adenoma: similar immunohistochemical and cytogenetic features in adenoma and hepatocellular carcinoma portions of the tumor.
abstract: Well-differentiated hepatocellular carcinoma in non-cirrhotic liver can show morphological features similar to hepatocellular adenoma. In rare instances, hepatocellular carcinoma can arise in the setting of hepatocellular adenoma. This study compares the immunohistochemical and cytogenetic features of the hepatocellular adenoma-like and hepatocellular carcinoma portions of these tumors. Immunohistochemistry for β-catenin, glutamine synthetase, serum amyloid A protein, glypican-3, and heat-shock protein 70 was done in 11 cases of hepatocellular carcinoma arising in hepatocellular adenoma in non-cirrhotic liver. Tumors with nuclear β-catenin and/or diffuse glutamine synthetase were considered β-catenin activated. Fluorescence in situ hybridization (FISH) was done in nine cases for gains of chromosomes 1, 8 and MYC. There were seven men (33-75 years) and four women (29-65 years). Focal atypical morphological features were seen in hepatocellular adenoma-like areas in 7 (64%) cases. Hepatocellular adenoma-like areas showed features of inflammatory hepatocellular adenoma in 7 (64%) cases; 4 of these were also serum amyloid A-positive in the hepatocellular carcinoma portion. β-Catenin activation, heat-shock protein 70 positivity, and chromosomal gains on FISH were seen in the hepatocellular adenoma portion in 55%, 40%, and 56% of cases, and 73%, 60%, and 78% of cases in the hepatocellular carcinoma portion, respectively. In conclusion, the hepatocellular adenoma-like portion of most cases of hepatocellular carcinoma arising in hepatocellular adenoma shows features typically seen in hepatocellular carcinoma such as focal morphological abnormalities, β-catenin activation, heat-shock protein 70 expression, and chromosomal gains. Hepatocellular adenoma-like areas in these tumors, especially in men and older women, may represent an extremely well-differentiated variant of hepatocellular carcinoma, whereas the morphologically recognizable hepatocellular carcinoma portion represents a relatively higher grade component of the tumor.
authors.affiliation: Department of Anatomic Pathology, University of California, San Francisco, CA, USA.|Department of Pathology, Veteran Affairs Medical Center, San Francisco, CA, USA.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Kakar
authors.affiliation: Department of Anatomic Pathology, University of California, San Francisco, CA, USA.
authors.forename: James P
authors.initials: JP
authors.lastname: Grenert
authors.affiliation: Department of Pathology, Beaujon Hospital, Clichy, France, Rush University, Chicago, IL, USA.
authors.forename: Valerie
authors.initials: V
authors.lastname: Paradis
authors.affiliation: Department of Pathology, Beaujon Hospital, Clichy, France, Rush University, Chicago, IL, USA.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Pote
authors.affiliation: Department of Pathology, Rush University, Chicago, IL, USA.
authors.forename: Shriram
authors.initials: S
authors.lastname: Jakate
authors.affiliation: Department of Anatomic Pathology, University of California, San Francisco, CA, USA.
authors.forename: Linda D
authors.initials: LD
authors.lastname: Ferrell
mesh_terms: D018248:Adenoma, Liver Cell / Q000737:chemistry / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000737:chemistry / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D002454:Cell Differentiation; D002878:Chromosomes, Human, Pair 1; D002898:Chromosomes, Human, Pair 8; D005260:Female; D005974:Glutamate-Ammonia Ligase / Q000032:analysis; D053673:Glypicans / Q000032:analysis; D018840:HSP70 Heat-Shock Proteins / Q000032:analysis; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008113:Liver Neoplasms / Q000737:chemistry / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D018193:Neoplasms, Complex and Mixed / Q000737:chemistry / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D011237:Predictive Value of Tests; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics; D000685:Serum Amyloid A Protein / Q000032:analysis; D051176:beta Catenin / Q000032:analysis
chemical_list: D014408:Biomarkers, Tumor; C495270:CTNNB1 protein, human; C105937:GPC3 protein, human; D053673:Glypicans; D018840:HSP70 Heat-Shock Proteins; C489427:MYC protein, human; D016271:Proto-Oncogene Proteins c-myc; D000685:Serum Amyloid A Protein; D051176:beta Catenin; D005974:Glutamate-Ammonia Ligase
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