Abstract
Simple SummaryPrimary liver cancers (PLCs) mainly comprise hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (iCCA), and combined (c)HCC-CCA. Both small duct types iCCA (a subtype pf iCCA) and cHCC-CCA are known to be tumors with histological heterogeneity. Understanding key tumor heterogeneity is crucial as it reflects tumor aggressiveness, patient outcome, treatment choice, and is predictive of treatment efficacy. In addition, PLCs often present with multiple liver tumors, which can be a combination of different types of PLCs or HCCs (intrahepatic metastasis or multicentric occurrence), and the pathological interpretation plays an important role in these cases. The aim of this review is to clarify the pathological features of HCC, iCCA, and cHCC-CCA, including their diagnostic pitfalls, molecular profiles, and the correlation between tumor subtypes and treatment choice.Primary liver cancers (PLCs) mainly comprise hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (iCCA), and cHCC-CCA. Combined HCC-CCA and small duct type iCCA show similar clinical presentations, and their histological features are more complex than seen in HCC. Therefore, while their treatment strategy differs, it is difficult to properly diagnose these tumors. Currently, HCC is the only tumor that can be treated by liver transplantation. In addition, small duct type iCCA harbors IDH1/2 mutations and FGFR2 fusions, which can be used for targeted therapy. Thus, improving diagnostic accuracy is crucial. A further point to note is that PLCs often present as multiple liver tumors, and they can be a combination of different types of PLCs or HCCs. In the case of HCCs, two different scenarios are possible, namely intrahepatic metastasis, or multicentric occurrence. Therefore, it is essential to characterize the type of multiple liver tumors. This review aims to clarify the pathological features of HCC, iCCA and cHCC-CCA, including their diagnostic pitfalls and clinical relevance. It is designed to be of use to clinicians who are dealing with PLCs, to provide a better understanding of the pathology of these tumors, and to enable a more accurate diagnosis and optimal treatment choice.
Highlights
Primary liver cancers (PLCs) mainly comprise hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma, and cHCC-CCA (Figure 1). As indicated by their names, HCC stems from hepatocytes, and iCCA originates from cholangiocytes lining the epithelia of the biliary tracts
Despite the simplicity of the names given to PLCs, their pathological diagnosis is not always straightforward, especially in the case of iCCA and cHCC-CCA, with their complex pathological features, described as “histological heterogeneity” [1,2]
This review aims to clarify the pathological features of HCC, iCCA and cHCC-CCCC, including diaaggnnoossttiiccppiittffaalllssaannddcclilniniciacal lrerleelvevanacnec,et,htuhsuesneanbalbinlignag baebtteetrteurnudnedrsetrasntadnindginogf othfetsheestue mtuomrsofrosrfomromreoraeccaucrcautreadteiadginagosneoss,easn, danbdetbterttterretartematemntecnhtocihcoeiscfeosrfporatpieantitesn. ts
Summary
Primary liver cancers (PLCs) mainly comprise hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (iCCA), and cHCC-CCA (Figure 1). As indicated by their names, HCC stems from hepatocytes, and iCCA originates from cholangiocytes lining the epithelia of the biliary tracts. Hepatocellular carcinoma originates from mature hepatocytes, which are the main components of the liver. It is, understandable that HCC is the most frequent PLC, with an incidence around 75–85% of all PLCs [7]. The HCC structure mimics this normal parenchyma, exhibiting a trabecular growth pattern composed of eosinophilic tumor cells without mucin production. These are identified as microvascular invasions, and if they grow, they are recognized as satellite lesions
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