Occurrence of Multinucleated Hepatocytes in Cynomolgus Monkeys (Macaca fascicularis) From Different Geographical Regions

Abstract

Multinucleated hepatocytes (MNHs) have been occasionally reported in macaques, as well as chimpanzees and gorillas, as an incidental finding. However, information is sparse on variations in incidence in the cynomolgus macaque ( Macaca fascicularis). A survey was conducted to assess the occurrence of MNHs in the liver of stock (nonstudy) animals from SNBL SRC (Alice, TX) and SNBL USA (Everett, WA) submitted for diagnostic purposes. A total of 215 cynomolgus monkeys originally from Cambodia (61), China (5), Indonesia (125), and Mauritius (24) were used for this investigation. From each animal, usually 2 liver samples were processed for histopathology with 2 sections in each slide. An MNH was defined as a hepatocyte with 3 or more nuclei. A threshold of 3 MNHs was selected for the Multinucleated Hepatocyte Grading System: 0 = not remarkable (≤3 MNHs counted from 2–4 liver sections), minimal = 4 to 15 MNHs, mild = 16 to 30 MNHs, moderate = 31 to 59 MNHs, and severe ≥60 MNHs. The incidence of MNHs was 60 of 86 (70%) in males and 72 of 129 (56%) in females for a total overall incidence of 132 of 215 animals (61%). Affected hepatocytes were frequently observed close to the capsule and generally had 3 to 8 nuclei per hepatocyte but as many as 15 occurred in a single cell. Awareness of the incidence of MNHs in cynomolgus monkeys is important for potential use as background data in preclinical safety and toxicity evaluation studies.