Clinical relevance of subtyping CTNNB1-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.