New malignant grading system for hepatocellular carcinoma using the Sonazoid contrast agent for ultrasonography

Background The ultrasonography contrast agent Sonazoid provides parenchyma-specific contrast imaging (Kupffer imaging) based on its accumulation in Kupffer cells. This agent also facilitates imaging of the fine vascular architecture in tumors through maximum intensity projection (MIP). We examined the clinical utility of the malignancy grading system for hepatocellular carcinoma (HCC) using a combination of 2 different contrast-enhanced ultrasonography images. Methods We studied 121 histologically confirmed cases of HCC (well-differentiated, 45; moderately differentiated, 70; poorly differentiated, 6). The results of Kupffer imaging were classified as (1) iso-echoic pattern or (2) hypo-echoic pattern. The MIP patterns produced were classified into one of the following categories: fine, tumor vessels were not clearly visualized and only fine vessels were visualized; vascular, tumor vessels were visualized clearly; irregular, tumor vessels were thick and irregular. Based on the combined assessment of Kupffer imaging and the MIP pattern, the samples were classified into 4 grades: Grade 1 (iso-fine/vascular), Grade 2 (hypo-fine), Grade 3 (hypo-vascular), and Grade 4 (hypo-irregular). Results The distribution of moderately and poorly differentiated HCCs was as follows: Grade 1, 4 % (1/24); Grade 2, 52 % (15/29); Grade 3, 85 % (44/52); and Grade 4, 100 % (16/16). The grading system also predicted portal vein invasion in 72 resected HCCs: Grade 1, 0 % (0/4); Grade 2, 13 % (1/8); Grade 3, 23 % (11/48); and Grade 4, 67 % (8/12). Conclusions This new malignant grading system is useful for estimation of histological differentiation and portal vein invasion of HCC.