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Diagnostic Criteria for Degenerative, Inflammatory, Proliferative Nonneoplastic and Neoplastic Liver Lesions in Medaka (Oryzias latipes): Consensus of a National Toxicology Program Pathology Working Group

Laboratory of Experimental Pathology, National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709

Suzanne Botts

Experimental Pathology Laboratories, Inc., Herndon, Virginia 22070-0474

Tracie E. Bunton

Johns Hopkins University, School of Medicine, Baltimore, Maryland 21205-2196

John W. Fournie

U.S. Environmental Protection Agency, Gulf Ecology Division, Gulf Breeze, Florida 32561

John C. Harshbarger

Registry of Tumors in Lower Animals, George Washington University Medical Center, Washington, D.C. 20037

William E. Hawkins

Gulf Coast Research Laboratory, Ocean Springs, Mississippi 39566-7000

David E. Hinton

School of Veterinary Medicine, University of California-Davis, Davis, California 95616

Michael P. Jokinen

Pathology Associates, Inc., Durham, North Carolina 27713

Mark S. Okihiro

School of Veterinary Medicine, University of California-Davis, Davis, California 95616

Marilyn J. Wolfe

Experimental Pathology Laboratories, Inc., Herndon, Virginia 22070-0474

Diagnostic criteria are presented for degenerative, inflammatory, nonneoplastic proliferative, and neoplastic lesions in the liver of medaka (Oryzias latipes), a small fish species frequently used in carcinogenesis studies. The criteria are the consensus of a Pathology Working Group (PWG) convened by the National Toxicology Program. The material examined by the PWG was from medaka exposed to N-nitrosodiethylamine for 28 days, removed to clean water, and sacrificed 4, 6, or 9 mo after initiation of exposure. Degenerative lesions included hepatocellular intracytoplasmic vacuolation, hepatocellular necrosis, spongiosis hepatis, hepatic cysts, and hepatocellular hyalinization. Inflammatory lesions consisted of granulomas, chronic inflammation, macrophage aggregates, and focal lymphocytic infiltration. Nonneoplastic proliferative lesions comprised foci of cellular alteration (basophilic focus, eosinophilic focus, vacuolated focus, and clear cell focus) and bile duct hyperplasia. Neoplastic lesions included hepatocellular adenoma, hepatocellular carcinoma, cholangioma, and cholangiocarcinoma. Two lesions composed mainly of spindle cells were noted, hemangiopericytoma and spindle cell proliferation. Rather than being an exhaustive treatment of medaka liver lesions, this report draws from the published literature on carcinogen-induced liver lesions in medaka and other fish species and attempts to consolidate lesion criteria into a simplified scheme that might be useful to pathologists and other researchers using medaka lesions for risk assessment or regulatory purposes.

Key Words: Carcinogenesis • bioassay • histopathology • fish • alternative species • diethylnitrosamine

Toxicologic Pathology, Vol. 25, No. 2, 202-210 (1997)
DOI: 10.1177/019262339702500210


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