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Morphometry of Hepatic Neoplasms and Altered Foci in the Mummichog, Fundulus heteroclitus

University of Maryland College Park, Department of Veterinary Medicine, Aquatic Pathobiology Laboratory, College Park, Maryland, USA

David L. Smith

University of Maryland School of Medicine, Department of Epidemiology and Preventive Medicine, Baltimore, Maryland, USA

Wolfgang K. Vogelbein

Virginia Institute of Marine Science, College of William & Mary, Gloucester Point, Virginia, USA

John C. Harshbarger

Department of Pathology, George Washington University Medical Center, Washington, DC, USA

Prabhakar R. Gudla

University of Maryland College Park, Department of Biological Resources Engineering, College Park, Maryland, USA

Michael M. Lipsky

University of Maryland School of Medicine, Department of Pathology, Baltimore, Maryland, USA

Andrew S. Kane

University of Maryland College Park, Department of Veterinary Medicine, Aquatic Pathobiology Laboratory, College Park, Maryland, USA, akane{at}umaryland.edu

The goal of this study was to intensively sample a small number of livers from a population of mummichog exposed to PAH-contaminated sediments and evaluate them for lesion pathology, distribution, shape, and volume, and the number of histological sections needed to adequately describe the extent of various lesions. Volumetric data for each lesion type from each step section was derived from digitized section images. The total number of hepatic alterations ranged from 10—125 per fish. Alterations included: eosinophilic, basophilic, and clear cell foci; hepatocellular carcinomas; hemangiopericytomas; and cholangiomas. Lesion volumes ranged from 0.00012—64 mm3 and represented 0.21%—67% of total liver volume. There was a tendency for the lesions to be more dorsal-ventrally compressed than spherical or ropelike when observed from longitudinal sections. Periodic subsampling of the data indicated that, on average, 6 evenly spaced, longitudinal histological sections were required to accurately estimate lesion volume and extent in our model population. These data provide a formulation for histological sampling techniques and methodological support for piscine and other cancer study models that observe lesion volume changes over time. Further, this study fosters the development of early quantitative endpoints, rather than using a large number of animals and waiting for tumor progression or death to occur.

Key Words: Cancer • mummichog • lesion volume • liver • morphometry • neoplasia • PAH (polycyclic aromatic hydrocarbons) • stereology.

Toxicologic Pathology, Vol. 32, No. 4, 375-383 (2004)
DOI: 10.1080/01926230490440899


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