Hepatocellular Carcinomas Arising in Adenomas: Similar Immunohistochemical and Cytogenetic Features in Adenoma and Hepatocellular Carcinoma Portions of the Tumor
S Kakar, J P Grenert, V Paradis, N Pote, S Jakate, L Ferrell. UCSF, San Francisco; Rush University, Chicago; Beaujon Hospital, Clichy, France
Background: Well-differentiated hepatocellular carcinoma (WD-HCC) in non-cirrhotic liver can show morphological features similar to hepatocellular adenoma (HCA). In rare instances, HCC can arise in the setting of HCA. This study compares the immunohistochemical and cytogenetic features of the HCA-like and HCC portions of these tumors.
Design: Immunohistochemistry for beta-catenin (bC), glutamine synthetase (GS), serum amyloid associated protein (SAA), glypican-3 (GPC) and heat shock protein 70 (HSP70) was done in 11 cases of HCC arising in HCA in non-cirrhotic liver. Tumors with nuclear bC and/or diffuse GS were considered bC-activated. Fluorescence in situ hybridization (FISH) was done in 9 cases for gains of chromosomes 1, 8 and c-myc.
Results: There were 7 men (33-75 yrs) and 4 women (30-65 years). Focal atypical morphological features like small cell change and focal pseudoacinar architecture were seen in HCA-like areas in 7 (64%) cases. HCA-like areas showed features of inflammatory HCA in 7 (64%) cases; 4 of these also showed SAA+ in the HCC portion. bC activation was present in majority of HCA-like areas, while positive HSP70 and chromosomal gains on FISH were seen in significant minority of HCA-like areas (see table). Of the 6 cases in which HCA-like area showed bC-activation, 3 (50%) showed chromosomal gains on FISH and 2 showed positive HSP70. All patients with chromosomal gains in HCA-like portions were men. For HCA-like areas that were bC-activated and HSP70 positive, 67% and 25% respectively were in men. Of the 2 women <50 years of age, bC activation was absent in the HCA-like regions, while HSP70 was positive in 1 case.
|βcatenin||GS diffuse||SAA||GPC||HSP70||Abnormal FISH|