A subset of well-differentiated hepatocellular carcinomas are Arginase-1 negative

Hepatocellular carcinoma (HCC) is a common malignancy both in the United States of America and worldwide. Despite the refinement of imaging techniques in at-risk populations, a needle biopsy diagnosis remains an important diagnostic tool for HCC in many cases. Various immunohistochemical markers have been developed to facilitate this diagnosis, such as HepPar-1, glypican-3 and, most recently, arginase-1. Amongst them, arginase-1 has been shown to have superior sensitivity and specificity than the others. Performance of arginase-1 has been reported to be excellent for diagnosis of well-differentiated HCCs, with some tail-off in sensitivity for poorly differentiated tumors. Our experience has suggested that a subset of well-differentiated HCCs can be negative for arginase-1. We examined 68 consecutive confirmed cases of well-differentiated HCC diagnosed on needle biopsy, and found 7 (10%) to be completely negative for arginase-1. This finding is of fundamental clinical importance in view of previous studies that have shown arginase-1 to be always positive in well-differentiated HCC.