Search

The distinction of hepatocellular adenoma from well-differentiated hepatocellular carcinoma (HCC) arising in noncirrhotic liver can be challenging, particularly when tumors histologically resembling hepatocellular adenoma occur in unusual clinical settings such as in a man or an older woman or show focal atypical morphologic features. In this study, we examine the morphologic, immunohistochemical, and cytogenetic features of hepatocellular adenoma-like neoplasms occurring in men, women 50 years or older or younger than 15 years, and/or those with focal atypia (small cell change, pseudogland formation, and/or nuclear atypia), designated atypical hepatocellular neoplasms, where the distinction of hepatocellular adenoma versus HCC could not be clearly established. Immunohistochemistry was performed for β-catenin, glutamine synthetase, and serum amyloid A in 31 hepatocellular adenomas, 20 well-differentiated HCCs, and 40 atypical hepatocellular neoplasms. Chromosomal gains/losses had previously been determined in 37 cases using comparative genomic hybridization or fluorescence in situ hybridization. β-Catenin activation was observed in 35% of atypical hepatocellular neoplasms compared with 10% of typical hepatocellular adenomas (P < .05) and 55% of well-differentiated HCCs (P = .14). Cytogenetic changes typically observed in HCC were present in all atypical hepatocellular neoplasms with β-catenin activation. β-Catenin activation in atypical hepatocellular neoplasms was also associated with atypical morphologic features. Follow-up data were limited, but adverse outcome was observed in 2 atypical hepatocellular neoplasms with β-catenin activation (1 recurrence, 1 metastasis); transition to areas of HCC was observed in 1 case. The similarity in morphologic and cytogenetic features of β-catenin-activated hepatocellular adenoma-like tumors and HCC suggests that the former tumors represent an extremely well-differentiated variant of HCC.

During progression from normal liver to cirrhosis, total collagen increases nearly 10-fold with an abnormal increase in fibril-forming collagen and other extracellular matrix molecules. However, little is known regarding the changes each collagen type undergoes during fibrogenesis. We assessed the different collagen types by immunohistochemistry at various stages of hepatitis C-related liver fibrosis in core biopsies and compared changes in each with trichrome stain to better understand fibrogenesis. The possible utility in staging fibrosis was investigated. We found collagens III, IV, V, VI, vitronectin, and trichrome all showed statistically significant increases from early to late stages of fibrosis, but with temporal and quantitative differences. During the transition from early to late fibrosis, trichrome (stains primarily collagen I) and collagen IV showed the steepest increase and appear to be the most useful discriminators between early and late stages of fibrosis. Collagens V and VI have strong reactivity even in stage 1, which may be helpful in identifying early fibrosis when trichrome is weak or negative. Collagen III and vitronectin showed the most gradual increase. Interestingly, collagen V also showed increased staining in areas around inflammation/edema, which may overestimate established fibrosis as compared with trichrome. [ABSTRACT FROM AUTHOR]