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.

Figure 1

Adenoma-like (right) and hepatocellular carcinoma (left) portions in a 52-year-old man (a, H&E, × 10). The adenoma-like portion showed inflammatory features and was positive for SAA (b, × 10). Both adenoma-like (c, × 10) and hepatocellular carcinoma portions (d, × 20) showed β-catenin activation as evidenced by diffuse glutamine synthetase staining; nuclear β-catenin was observed only in the HCC portion (e, × 20). FISH showed chromosome 1 gains in both adenoma-like (f, × 100) and hepatocellular carcinoma portions (g, × 100).

Figure 2

Adenoma-like (a, H&E, × 20) and hepatocellular carcinoma portion (b, H&E, × 20) in a tumor in a 33-year-old male. There was β-catenin activation evidenced by diffuse glutamine synthetase staining in both adenoma-like (c, × 20) and hepatocellular carcinoma portions (d, × 20). The glutamine synthetase staining was stronger in the hepatocellular carcinoma portion. There were no chromosomal gains.

Figure 3

Adenoma-like (a, H&E, × 20) and hepatocellular carcinoma (b, H&E, × 20) portions of a tumor in a 61-year-old male. Both portions showed β-catenin activation evidenced by diffuse glutamine synthetase staining (c, HCC, × 10) and patchy nuclear β-catenin staining (d, adenoma-like, × 20). Patchy heat-shock protein 70 staining (e, adenoma-like, × 20) and chromosome 8 gain (f, HCC, × 100) were observed in both portions.

Figure 4

Adenoma-like (a, H&E, × 20) and HCC portions (b, H&E, × 20) of a tumor in a 63-year-old male. Both portions were serum amyloid A-positive (c, adenoma-like, × 20) and showed chromosome 8 gain (d, hepatocellular carcinoma, × 100). There was no β-catenin activation.