The clinicopathological characterization of small hepatocellular carcinoma with fibrous stroma

Recent studies emphasized the significance of fibrous stroma affecting tumor biology in hepatocellular carcinoma (HCC). To further clarify fibrous stroma's significance, this study investigated the clinicopathological characteristics of HCC with fibrous stroma. A total of 214 nodules of HCC smaller than 3 cm in diameter were analyzed, and 22 (10%) were regarded as HCC with fibrous stroma. Most cases of HCC with fibrous stroma were the simple nodular type without a fibrous capsule, and histologically well- or moderately-differentiated. A subset of the scirrhous variant of HCC was included in this category, and steatohepatitic features, such as Mallory-Denk body formation and lymphoid infiltrates, were also frequently found. Foci with a histological appearance corresponding to dysplastic nodules and/or early HCC were rarely observed in HCC with fibrous stroma, suggesting that some cases occurred via a de novo carcinogenic process. The immunohistochemical expression of cytokeratin 7 and the epithelial cell adhesion molecule was more significantly increased in HCC with fibrous stroma than in conventional HCC. Furthermore, the expression of C reactive protein and serum amyloid A, indicative of the activation of the IL-6/STAT pathway, was increased in HCC with fibrous stroma. Radiologically, HCC with fibrous stroma exhibited hyperdense nodules on computed tomography and did not show a nodule-in-nodule appearance. Overall survival and disease-free survival were not significantly different between cases of HCC with fibrous stroma and conventional HCC. This study elucidated the clinicopathological features of HCC with fibrous stroma, which may represent a biologically different process occurring in HCC.