Pathological diagnosis at early stage: reaching international consensus

Distinguishing small well-differentiated hepatocellular carcinoma (HCC) from dysplastic nodules (DN) is frequently difficult, and the precise pathological diagnosis is a key issue in clinical management of the patients. However, the morphologic criteria for confident diagnosis of early HCC are still controversial. To improve the consistency of pathological diagnosis of early HCC, the International Consensus Group for Hepatocellular Neoplasia comprising 34 pathologists and 2 clinicians from 13 countries was convened in 2002, and the group met on several occasions until 2007. The members discussed the diagnosis of resected nodules <2 cm in diameter at the first meeting and additional sets of small nodules at the second meeting. The overwhelming diagnostic challenge was the differentiation of high-grade DN from well-differentiated small HCC (early HCC). It has been recognized that the presence or absence of 'invasion' is of key importance in deciding if a tumor is malignant or benign. In early HCC, varying degrees of tumor cell invasion (i.e. stromal invasion) into the portal tracts within the tumor is the most helpful morphologic clue to distinguish early HCC from high-grade DN. After the first meeting, the kappa value for HCC rose from 0.30 to 0.49. In addition, it has been well understood that most early HCCs are hypovascular lesions and unlikely classical HCC which is a hypervascular lesion.