Cholestasis associated microtrabecular and pseudoacinar morphologies in hepatocellular carcinoma: Predicting...

Over the last two decades, there has been gradual shift in the approach to management of hepatocellular carcinoma (HCC). More emphasis on obtaining pretreatment biopsies for morphomolecular characterization and developing targeted therapies is becoming increasingly crucial. Gain-of-function mutations of CTNNB1, which encodes beta-catenin, occur in 27% of HCC patients. Although molecular analysis for beta-catenin mutation is considered gold standard, immunohistochemical (IHC) analysis is a routinely practiced method. In this study, we aim to address different histomorphological patterns of HCC and their correlation with immunohistochemical expression patterns of beta-catenin, glutamine synthetase expression, clinicoradiological and serological parameters.

A retrospective, single-center study was conducted on 18 selected HCC cases from 73 diagnosed in core needle biopsies at our institute between 2020 and 2023. Four histological groups were identified: microtrabecular, pseudoacinar, mixed pattern, and any of the aforementioned groups with cholestasis. Beta-catenin expression was classified into membranocytoplasmic, nucleocytoplasmic, and pure membranous patterns. A semiquantitative scoring system for glutamine synthetase (GS) expression was used (nil, low, medium, and high). Clinicopathological and radiological data were analyzed statistically and radiological data were correlated with appropriate statistical analysis.

The morphological group with cholestasis was found to have a statistically significant correlation with nucleocytoplasmic beta-catenin ( P = 0.009), high GS expression ( P = 0.003), nil portal vein involvement ( P = 0.018) and better survival ( P = 0.017).

We propose that HCCs showing strong GS expression and cholestasis irrespective of microtrabecular, pseudoacinar, or mixed pattern should be subjected to further beta-catenin analysis by IHC and molecular testing to categorize them as CTNNB1-mutated tumors as they have prognostic and predictive values.