Background: In the era of targeted therapeutics, histological typing of hepatobiliary carcinomas has major clinical implications. Little is known about the reproducibility of pathologic diagnosis of primary liver carcinomas. Therefore, our study aimed to evaluate the worldwide variation in the pathologic expert diagnoses of primary liver carcinomas with fibrous stroma in non-cirrhotic patients.
Methods: We selected a single set of slides from 25 tumors, which was reviewed independently by 12 pathologists with worldwide expertise in liver tumors. Reproducibility of the diagnoses was evaluated by Light's kappa, and diagnoses were clustered by multidimensional scaling. Immunohistochemistry was performed after histological review.
Results: The interobserver reproducibility for diagnosis of hepatocellular carcinoma subtypes and cholangiocarcinomas was poor (kappa [0.23 to 0.52]), even when the experts considered that the diagnosis required no additional stains or clinical information. Interestingly, multidimensional scaling revealed 3 main clusters of tumors; hepatocellular carcinoma with no other specifications (n=13), fibrolamellar hepatocellular carcinoma (n=3) and cholangiocarcinoma (n=9). Using immunohistochemistry, these histological clusters correlated with anti-hepatocyte and anti-cytokeratin 19 expression (P<0.001).
Conclusions: Our results demonstrate the poor reproducibility among experts of the pathologic diagnosis of primary liver carcinomas with fibrous stroma in non-cirrhotic patients, and highlights that the systematic use of immunohistochemistry may improve the diagnostic accuracy.