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. (J Toxicol Pathol 2002; 15: 61-68)

Hepatocellular carcinoma with intracranial metastasis in a Japanese macaque (Macaca fuscata)

“…27,28 On the other hand, a long-tailed macaque with HCC was reported to show an elevation of serum PIVKA-II rather than AFP. 8 Further validation and investigation of tumor markers may facilitate the early diagnosis of neoplasms in macaques.…”

Hepatocellular carcinoma in a free‐living marmoset (Callithrix sp.) with concomitant biliary trematodiasis

“…Hepatocellular carcinoma (HCC) has been reported in seven of approximately 300 extant NHP species . The etiology in most of these cases was undetermined.…”

“…37 Hepatocellular carcinoma (HCC) has been reported in seven of approximately 300 extant NHP species. [6][7][8][9][10][11][12][13][14][15][16][17][18] The etiology in most of these cases was undetermined. In the present case, investigation of HBV, HCV, and AFB1 exposure by IHC was negative.…”

“…Experimentally induced or naturally occurring HCC has been reported in chimpanzees ( Pan troglodytes ); common squirrel monkey ( Saimiri sciureus ) and black‐capped squirrel monkey ( Saimiri boliviensis ); cynomolgous ( Macaca fascicularis ), rhesus ( Macaca mulata ), and Japanese macaques ( Macaca fuscata ); African green monkey ( Cercopithecus aethiops ); and golden‐headed lion tamarins ( Leontopithecus chrysomelas ) . Other PLNs reported in NHPs are hepatoma in sooty mangabey ( Cercocebus atys ); neuroendocrine carcinoma in baboon ( Papio sp.…”

Superparamagnetic Iron Oxide-enhanced Magnetic Resonance Imaging of Spontaneous Hepatic Neoplasia in a Cynomolgus Macaque (Macaca fascicularis)

“…Several days later, the macaque was euthanized by using sodium pentobarbital overdose because of a poor prognosis. Biochemical findings revealed that the animal had been negative for serum α-fetoprotein 27 and positive for the PIVKA-II protein, 33 both of which are hepatic tumor markers in NHP.…”