title: Invading and metastasizing cardiac hemangioendothelial neoplasms in a cohort of the fish Rivulus marmoratus: unusually high prevalence, histopathology, and possible etiologies.
abstract: An unusually high, unprecedented prevalence of cardiac hemangioendotheliomata, including hemangiomas, hemangioendotheliomas, and hemangioendotheliosarcomas, was found in a laboratory cohort of the small, teleost fish Rivulus marmoratus. The neoplasms occurred in 51 of 204 fish (25%) used in a carcinogenicity study of butylated hydroxyanisole fed in a lyophilized chicken liver diet for up to 9 months. The cardiac neoplasms occurred in approximately equal numbers of both control (fed lyophilized chicken liver but not exposed to butylated hydroxyanisole) and exposed (fed 0.8% butylated hydroxyanisole in chicken liver) fish. The neoplasms occurred in the bulbus arteriosus and ventricle (accompanied by an intense epicarditis), and in some cases, in the gills. At least one case of hemangioma was characterized by cavernous vessels in the bulbar wall. Hemangioendothelioma cases consisted of pleomorphic endothelial cells that formed continuous tracts and anastomosing, typical vascular channels of varying sizes. The hemangioendotheliosarcomas consisted of atypical, spindle, polygonal, or round endothelial cells that formed solid tumor masses that contained abnormal vessels with atypical endothelium tufting into their lumina. Some fish had neoplasm cases containing varying regions with mixtures of the above features. Incipient neoplasms occurred on/in the semilunar valves, and their cells appeared to invade the adjacent walls of the bulbus and/or the ventricle. The gill lesions represented possible metastatic neoplasms, probably formed by atypical endothelial cells that exfoliated from the edges of cardiac neoplasms into the lumina of the ventricle or bulbus and were then pumped to the arterioles of the gills via the ventral aorta. Fish examined from the original colony in the laboratory and from the wild had no neoplasms. Possible causes are discussed, and studies are under way in an attempt to determine the etiology of the neoplasm and to evaluate Rivulus marmoratus as a possible model organism for study of these types of cardiac neoplasms.
authors.affiliation: Environmental Protection Agency, Environmental Research Laboratory, Gulf Breeze, Florida 32561, USA.
authors.forename: J A
authors.initials: JA
authors.lastname: Couch
mesh_terms: D000818:Animals; D015331:Cohort Studies; D005393:Fish Diseases / Q000453:epidemiology* / Q000209:etiology / Q000473:pathology*; D005399:Fishes; D005880:Gills / Q000473:pathology; D006338:Heart Neoplasms / Q000453:epidemiology* / Q000209:etiology / Q000662:veterinary*; D006390:Hemangioendothelioma / Q000453:epidemiology* / Q000209:etiology / Q000662:veterinary*; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D015995:Prevalence