Characterization of Dysplastic Nodules, Early Hepatocellular Carcinoma and Progressed Hepatocellular Carcinoma in Cirrhosis with Contrast-Enhanced Ultrasound

Background: During the progression from low-grade dysplastic nodule (DN) to progressed hepatocellular carcinoma (HCC), intranodular portal tracts gradually disappear, while unpaired arteries develop increasingly. Contrast-enhanced ultrasound (CEUS) is highly accurate in depicting intranodular vascularity. This study evaluates the usefulness of CEUS in the characterization of DN, early HCC and progressed HCC in cirrhotic livers. Materials and Methods: Forty consecutive patients with cirrhosis and a single hepatic nodule ≤2 cm underwent CEUS and subsequent ultrasound-guided biopsy of the nodule. Imaging and pathological findings of DN and HCC were compared. Results: The homogeneous pattern of hypervascularization during the arterial phase identified progressed HCC with a sensitivity of 90.9% and a specificity of 100%, whereas the inhomogeneous and reticular pattern identified early HCC with a sensitivity of 85.7% and a specificity of 96.1%. Conclusion: DN, early HCC and progressed HCC can be accurately differentiated with CEUS on the basis of the vascularization pattern during the arterial phase. Hepatocellular carcinoma (HCC) is the seventh most common cancer worldwide. In 2008, an estimated 748,000 new cases were diagnosed and 696,000 deaths were registered (1). Incidence and mortality are similar because most cases of HCC are diagnosed at an advanced stage, especially in developing countries where over 80% of the global cases occur. HCC development in the setting of a cirrhotic liver can occur either as de novo hepatocarcinogenesis or through a multistep pathway that starts from a dysplastic focus arising within a regenerative nodule and eventually leads to an overt cancer. In 1995, the International Working Party (IWP) of the World Congress of Gastroenterology classified nodular lesions found in chronic liver disease into large regenerative nodule, low-grade dysplastic nodule (L-DN), high-grade dysplastic nodule (H-DN) and hepatocellular carcinoma (HCC), and defined small HCC as a tumor measuring less than 2 cm (2). More recently, the International Consensus Group for Hepatocellular Neoplasia (ICGHN) has divided small HCC into two clinical-pathological groups named early HCC and progressed HCC (3). Early HCC is well differentiated and vaguely nodular, the presence of neoplastic cells in the portal tracts (stromal invasion) differentiates it from H-DN. Progressed HCC has a well-defined nodular pattern and is usually moderately differentiated (3). Patients with cirrhosis should be closely screened by conventional ultrasound (US) because the recurrence-free survival and the 5-year overall survival are considerably better for patients with early HCC compared to patients with progressed HCC (4). Unfortunately, the identification of an early HCC from the background nodularity of a cirrhotic liver by conventional US can be very challenging due to its small size and vague limits. Contrast-enhanced ultrasound (CEUS) substantially improves the accuracy of US in the characterization of focal liver lesions by showing different vascular patterns between benign and malignant lesions during the arterial, portal and sinusoidal phases (5). As the nodule evolves from dysplastic to malignant, neoangiogenic unpaired arteries progressively supplant intratumoral portal tracts. Therefore, overt HCC is mainly fed by the hepatic artery, whereas normal liver parenchyma and premalignant nodules are mostly perfused by the portal branches (3). This arterialization of the blood supply accounts for the