DIAGNOSTIC-CRITERIA FOR DEGENERATIVE, INFLAMMATORY, PROLIFERATIVE NONNEOPLASTIC AND NEOPLASTIC LIVER-LESIONS IN MEDAKA (ORYZIAS-LATIPES) - CONSENSUS OF A NATIONAL TOXICOLOGY PROGRAM PATHOLOGY WORKING GROUP

Diagnostic criteria are presented for degenerative, inflammatory, nonn coplastic proliferative, and neoplastic lesions in the liver of medaka (Oryzias latipes), a small fish species frequently used in carcinogen esis studies. The criteria are the consensus of a Pathology Working Gr oup (PWG) convened by the National Toxicology Program. The material ex amined by the PWG was from medaka exposed to N-nihosodiethylamine for 28 days, removed to clean water, and sacrificed 4, 6, or 9 mo after in itiation of exposure. Degenerative lesions included hepatocellular int racytoplasmic vacuolation, hepatocellular necrosis, spongiosis hepatis , hepatic cysts, and hepatocellular hyalinization. Inflammatory lesion s consisted of granulomas, chronic inflammation, macrophage aggregates , and focal lymphocytic infiltration. Nonneoplastic proliferative lesi ons comprised foci of cellular alteration (basophilic focus, eosinophi lic focus, vacuolated focus, and clear cell focus) and bile duct hyper plasia. Neoplastic lesions included hepatocellular adenoma, hepatocell ular carcinoma, cholangioma, and cholangiocarcinoma. Two lesions compo sed mainly of spindle cells were noted, hemangiopericytoma and spindle cell proliferation. Rather than being an exhaustive treatment of meda ka liver lesions, this report draws from the published literature on c arcinogen-induced liver lesions in medaka and other fish species and a ttempts to consolidate lesion criteria into a simplified scheme that m ight be useful to pathologists and other researchers using medaka lesi ons for risk assessment or regulatory purposes.