How to Differentiate Borderline Hepatic Nodules in Hepatocarcinogenesis: Emphasis on Imaging Diagnosis

Abstract

Background: Rapid advances in liver imaging have improved the evaluation of hepatocarcinogenesis and early diagnosis and treatment of hepatocellular carcinoma (HCC). In this situation, detection of early-stage HCC in its development is important for the improvement of patient survival and optimal treatment strategies. Because early HCCs are considered precursors of progressed HCC, precise differentiation between a dysplastic nodule (DN), especially a high-grade DN, and early HCC is important. In clinical practice, these nodules are frequently called “borderline hepatic nodules.” Summary: This article discusses radiological and pathological characteristics of these borderline hepatic nodules and offers an understanding of multistep hepatocarcinogenesis by focusing on the descriptions of the imaging changes in the progression of DN and early HCC. Detection and accurate diagnosis of borderline hepatic nodules are still a challenge with contrast enhanced ultrasonography, CT, and MRI with extracellular contrast agents. However, gadoxetic acid-enhanced MRI may be useful for improving the diagnosis of these borderline nodules. Key Messages: Since there is a net effect of incomplete neoangiogenesis and decreased portal venous flow in the early stage of hepatocarcinogenesis, borderline hepatic nodules commonly show iso- or hypovascularity. Therefore, precise differentiation of these nodules remains a challenging issue. In MRI using hepatobiliary contrast agents, signal intensity of HCCs on hepatobiliary phase (HBP) is regarded as a potential imaging biomarker. Borderline hepatic nodules are seen as nonhypervascular and hypointense nodules on the HBP, which is important for predicting tumor behavior and determining appropriate therapeutic strategies.

The AFSUMB Consensus Statements and Recommendations for the Clinical Practice of Contrast-Enhanced Ultrasound using Sonazoid

“…In the early stages of hepatocarcinogenesis, such as DNs and early HCCs, hepatocytes show increased fat accumulation compared to that of the background liver [112]. The incidence of fat accumulation is increased in DNs and early HCC.…”

Differentiation of Small Hepatocellular Carcinoma From Dysplastic Nodules in Cirrhotic Liver: Texture Analysis Based on MRI Improved Performance in Comparison Over Gadoxetic Acid-Enhanced MR and Diffusion-Weighted Imaging

“…Early detection of HCC, differentiation from benign cirrhotic nodules, provides the greatest chance for long-term survival (4). However, a complete characterization of these nodules still remains a difficult diagnostic dilemma due to the overlap of imaging features (5,6).…”

A New Concept: Pre‐HCC Disease

“…Recent advances in liver imaging have improved the diagnosis of early stages of hepatocarcinogenesis, such as high‐grade dysplastic nodule (HGDN) and early HCC. ( ) A cirrhotic lesion showing arterial phase nonhyperintensity, hepatobiliary phase hypointensity, and diffusion‐weighted imaging nonhyperintensity on the Gd‐EOB‐DTPA (gadoxeticacid) enhanced magnetic resonance imaging is most likely an HGDN, ( ) and a patient with cirrhosis carrying such a lesion should be considered as having pre‐HCC disease and should be taken seriously, given the malignant potential of HGDN. ( )…”