Hepatocellular Carcinoma with PIVKA-II Production in a Young Laboratory Monkey.

Abstract

Hepatocellular carcinoma which occurred in one male laboratory cynomolgus monkey at 5 years of age was investigated extensively by immunological, histopathological and electron-microscopic examinations. The animal exhibited no abnormalities in clinical laboratory tests including blood-chemistry, except for elevation of protein induced by vitamin K absence or antagonist II (PIVKA-II) in serum, which is one of the hepatic tumor markers. In virus antibody tests, the serum was positive for hepatitis A virus. On necropsy, a mass measuring 60 × 60 × 65 mm was seen in the hepatic left lobe. The tumor mass had a lobulated structure with hemorrhagic and necrotic areas, and was demarcated by thin fibrous capsules. Histopathologically, the tumor was composed of hepatocyte-like cells, having irregular trabecular structure with various thickness, lined by vascular endothelial cells. Cellular atypia such as polynucleated cells, mitotic figures, and invasion into the vascular cavity were also observed. Immunohistochemically, the tumor cells showed positive reaction for anti-PIVKA-II, anti-epithelial membrane antigen (EMA), anti-carcinoembryonic antigen (CEA), and anti-cytokeratin 18, as well as for proliferating cell nuclear antigen (PCNA). On electron-microscopic examination, the tumor cells had a number of tight junctions and formations of bile canaliculi between adjacent cells, basically resembling hepatocytes. This is the first case of hepatocellular carcinoma with PIVKA-II production in monkeys. Serological and immunohistochemical analyses for PIVKA-II are, therefore, practicable for diagnose as hepatocellular carcinoma in nonhuman primates.