Atypical hepatocellular adenoma–like neoplasms with β-catenin activation show cytogenetic alterations similar to well-differentiated hepatocellular carcinomas

Abstract

Summary 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. Published by Elsevier Inc.

Diagnostic utility and limitations of glutamine synthetase and serum amyloid-associated protein immunohistochemistry in the distinction of focal nodular hyperplasia and inflammatory hepatocellular adenoma

“…Ductular reaction was seen in 40% of the inflammatory hepatocellular adenoma cases, which is similar to 21 and 29% observed in other studies. 6,23 In addition to the histological overlap, the lack of typical features also contributes to the difficulty in establishing the diagnosis. For example, both telangiectasia and inflammation are seen in less than half of needle biopsies of inflammatory hepatocellular adenoma.…”

“…In our series, coarse cytoplasmic serum amyloid-associated protein staining was seen in hepatocytes in 93% of inflammatory hepatocellular adenoma, which is similar to the 90 and 94% figures reported earlier. 17,23 There is limited data in the literature about serum amyloid-associated protein staining in focal nodular hyperplasia. In the series by BioulacSage P et al, 17 all 20 focal nodular hyperplasia cases were negative for serum amyloid-associated protein, including cases that had another serum amyloidassociated protein-positive inflammatory hepatocellular adenoma in the same liver.…”

Hepatocellular Benign Tumors—From Molecular Classification to Personalized Clinical Care

“…15,82 Importantly, ␤-catenin mutations are associated with a high risk of malignant transformation (Table 1). 15,54,55,83 ␤-cateninmutated adenomas show strong overexpression of GLUL (coding for glutamine synthase) and LGR5 (coding for leucine-rich repeat-containing G-protein coupled receptor 5), 2 ␤-catenin target genes as revealed by quantitative reverse-transcription polymerase chain reaction analysis. 18 Using immunohistochemistry, diagnosis of a ␤-cateninmutated adenoma is performed using ␤-catenin and glutamine synthase immunostaining.…”

A Triple Stain of Reticulin, Glypican-3, and Glutamine Synthetase: A Useful Aid in the Diagnosis of Liver Lesions

“…39 In HCC, approximately 80% of cases stain diffusely positive. 23,40 Furthermore, in cases of HA with activation of the Wnt/ b-catenin pathway, GS will diffusely stain hepatocytes. 22,37 In the distinction of HCC from HA, reticulin was the most useful single stain.…”