Imaging differentiation of hepatocellular carcinoma, combined hepatocellular-cholangiocarcinoma, and intrahepatic cholangiocarcinoma: pitfalls and advances

Accurate non-invasive differentiation of primary liver cancers, such as hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (iCCA), and combined hepatocellular-cholangiocarcinoma (cHCC-CCA), is crucial for optimal management but challenging due to shared risk factors and overlapping imaging phenotypes. While the Liver Imaging Reporting and Data System LR-M category effectively captures the classic targetoid appearance of large duct type iCCA, the small duct type frequently exhibits HCC-mimicking non-rim arterial phase hyperenhancement and non-peripheral washout, potentially compromising diagnostic specificity. Furthermore, cHCC-CCA presents a formidable diagnostic dilemma, existing on a continuous imaging spectrum that reflects its histologic dominance. This continuous imaging spectrum not only blurs radiologic distinctions but also complicates tissue sampling, limiting the diagnostic accuracy of core needle biopsies and highlighting the risk of misclassification. To enhance diagnostic clarity, this review highlights their key imaging hallmarks: while HCC typically shows non-rim arterial phase hyperenhancement (APHE) and non-peripheral washout, large duct iCCA displays a classic targetoid appearance with rim APHE and progressive central enhancement. Conversely, small duct iCCA often mimics HCC, and cHCC-CCA exhibits a variable spectrum depending on its predominant histologic component. Ultimately, overcoming these diagnostic pitfalls requires a rigorous, multidisciplinary approach that synthesizes imaging findings, serologic tumor markers, and clinical contexts.