Clinical relevance of subtyping <i>CTNNB1</i>‐mutated hepatocellular adenomas: Different risk patterns according to the mutation type

Abstract Background and Aims Beta‐catenin‐activated hepatocellular adenomas (b‐HCA) with exon 3 (ex3) non‐S45, ex3 S45 or ex7/8 mutations display different glutamine synthetase (GS)‐immunostaining patterns; the latter two show a GS‐positive/CD34‐negative rim contrasting with diffuse CD34 in the HCA core. Our objective was to determine whether discriminating the three b‐HCA mutation subtypes is clinically relevant. Methods We analysed the clinicopathological data of the three b‐HCA subtypes (37 resected cases) and compared it with the corresponding subtypes of beta‐catenin‐activated inflammatory HCA (b‐IHCA, 40 cases). Results The mean age of b‐HCA ex7/8 and ex3 S45 were 25.9 and 27.3 years respectively. Clinical bleeding occurred in 67% and 63%, including five cases of pregnant women; malignant transformation was not observed in these two subtypes. The mean age of the b‐HCA ex3 non‐S45 subtype (41 years) was significantly higher; clinical bleeding occurred in 14% while all cases contained malignancy. Such differences in age and clinical complications were not found in the b‐IHCA subtypes. Additionally, we found abnormal vessels in b‐HCA ex3 S45 and ex7/8, near the GS + /CD34 − rim, which was not seen in ex3 non‐S45. These vessels can function as an adjunct to discriminate between the b‐HCA subgroups. Conclusion In our series, b‐HCA ex7/8 and ex3 S45 patients are significantly younger and have higher clinical bleeding risk than b‐HCA ex3 non‐S45 patients who have a higher malignant risk. Hence, in b‐HCA, due to the differences in clinical complications, it is clinically relevant to identify all three subtypes individually.