Early hepatocellular carcinoma with high‐grade atypia in small vaguely nodular lesions

摘要

Multistep hepatocarcinogenesis progresses from dysplastic nodules to early hepatocellular carcinoma (eHCC) and to advanced HCC. The aim of the present study was to investigate the detailed histopathological features of eHCC. We investigated 66 small vaguely nodular lesions resected from 40 patients. The degree of cellular and structural atypia and stromal invasion were assessed. The immunohistochemical expression of HCC‐related markers adenylate cyclase‐associated protein 2 (CAP2), heat shock protein 70 (HSP70), Bmi‐1, CD34 and h‐caldesmon were evaluated. Of the 66 nodules, 10 were diagnosed as low‐grade dysplastic nodules (LGDN), 10 as high‐grade dysplastic nodules (HGDN) and 46 as eHCC. Among the 46 eHCC, 18 nodules (39.1%) showed marked stromal invasion and/or the presence of the scirrhous component and were subclassified as high‐grade eHCC (HGeHCC). The remaining 28 eHCC, which lacked these features, were subclassified as low‐grade eHCC ( style="fixed-case">LGe style="fixed-case">HCC) and were examined further. style="fixed-case">HGe style="fixed-case">HCC showed high levels of cellular and structural atypia and large tumor size. The immunohistochemical expression of style="fixed-case">CAP2 and the area of sinusoidal vascularization showed increases from style="fixed-case">LGDN to style="fixed-case">HGe style="fixed-case">HCC. The density of arterial tumor vessels was high in style="fixed-case">HGe style="fixed-case">HCC compared with other nodule types. Cluster analysis of these parameters subclassified 65 nodules into style="fixed-case">HGe style="fixed-case">HCC‐dominant, style="fixed-case">LGe style="fixed-case">HCC and style="fixed-case">HGDN‐dominant, and style="fixed-case">LGDN‐dominant groups. These results indicate the increased malignant potential of style="fixed-case">HGe style="fixed-case">HCC and suggest that it is already a transitional stage to advanced style="fixed-case">HCC. We consider that our grading classification system may be valuable for considering treatment strategies for style="fixed-case">eHCC around 2 cm in diameter.