Correlation between microbubble contrast-enhanced color doppler sonography and immunostaining for Kupffer cells in assessing the histopathologic grade of hepatocellular carcinoma: preliminary results.

Purpose: The aim of this study was to determine the histopathologic grades of hepatocellular carcinomas (HCCs) on the basis of the presence of Kupffer cells, using color Doppler sonography with the liver-specific microbubble contrast agent Levovist.

Methods: Color Doppler sonograms generated by stimulated acoustic emission were obtained 7 minutes after intravenous injection of 5 ml of Levovist (300 mg/dl) in patients with histopathologically confirmed HCCs. CT scans were also obtained and evaluated, and hematoxylin and eosin staining for morphologic examination and immunostaining (anti-CD68) for detecting Kupffer cells were performed for confirmation of the sonographic findings.

Results: Eighteen tumors had a defect in the color Doppler signal (color void) that corresponded with the baseline gray-scale image of the tumor. On histopathologic examination, these 18 tumors were all found to be either poorly or moderately differentiated HCCs with either a marked reduction in the number of or the absence of Kupffer cells. The remaining 2 tumors showed color signals. Histopathologic examination of these 2 tumors disclosed well-differentiated components within the tumors, with Kupffer cells in the tumor tissue.

Conclusions: Color Doppler sonography using a liver-specific microbubble ultrasound contrast agent appears to reflect the histopathologic features of HCCs and may thus be useful for differentiating liver tumors and determining a treatment strategy.