Noninvasive diagnostic criteria for hepatocellular carcinoma: A boat that leaks like a sieve

We read the interesting article by Vilana et al., who reported that intrahepatic cholangiocarcinoma (ICC) arising in the cirrhotic liver may display on contrast-enhanced ultrasound (CEUS) a vascular pattern indistinguishable from that of hepatocellular carcinoma (HCC). Such a typical dynamic imaging pattern after intravenous contrast administration (i.e., intense arterial uptake followed by washout in venous phases) was found in 3 of 4 ICC nodules smaller than 2 cm and in 7 of 17 ICC nodules larger than 2 cm. According to the noninvasive diagnostic guidelines proposed by the American Association for the Study of Liver Diseases (AASLD), these larger nodules would have been misdiagnosed as HCC (i.e., false-positive results) because only small nodules require a second contrast-enhanced imaging technique for confirmation of the diagnosis. In their series, the lack of concordance with magnetic resonance imaging suggested an opportunity for nodule biopsy, which resulted in a proper ICC diagnosis. However, they did not mention how large the cohort was from which these 21 patients were extracted. Therefore, we wonder how many other patients might have received a false-positive diagnosis of HCC because the criteria that the authors applied did not consider that a nodule arising in a patient with liver cirrhosis could be something other than HCC. Indeed, for the diagnosis of small HCC by two imaging techniques, such guidelines seem to be affected by low sensitivity (33%), as recently reported by the same authors. We are also especially concerned about the decision to biopsy only the largest nodule when multiple lesions were present. We report the case of a 70-year-old man with hepatitis C virus– related liver cirrhosis who was referred to us for the assessment of two hepatic nodules identified during ultrasound (US) surveillance. The nodules were located in the VII and VIII segments and had diameters of 24 and 39 mm, respectively. For characterization and staging, CEUS and contrast-enhanced computed tomography were performed. Both techniques showed intense and homogeneous arterial enhancement (Fig. 1A,B) followed by washout in the portal and delayed phases (Fig. 1D,E). In order to complete the genetic and immunochemical study protocol, biopsy was performed on both nodules. The lesion in the VIII segment was revealed to be well-differentiated ICC (Fig. 1C), whereas the other lesion showed features of well-differentiated HCC (Fig. 1F). This case clearly demonstrates the risk of accepting imaging findings as conclusive for HCC in the setting of liver cirrhosis and the risk of considering the largest of multiple nodules to be representative of all others. The AASLD guidelines should be amended with respect to the possible misdiagnosis of lesions whose imaging simulates HCC but that are due to different diseases (e.g., ICC or non-Hodgkin’s lymphoma) and with respect to synchronous nodules occurring in patients with cirrhosis. In conclusion, our case and the results of Vilana et al. confirm that aimed biopsy is the most accurate option for a confident diagnosis of liver nodules. The AASLD diagnostic criteria increasingly seem to display evidence of low sensitivity and specificity, and this suggests the need for redefinition.