Cellular alterations preceding neoplasia in Pseudopleuronectes americanus from Boston Harbor

Abstract

Dysplastic and neoplastic liver disease has been described in adult winter flounder from Boston Harbor. In this study we examined the pathogenesis of the disease. Early changes, in fish of 100–300 mm, included biliary proliferation, abnormal vacuolation of biliary pre-ductular epithelial cells and macrophage aggregation. The identification of biliary pre-ductular epithelial cells was based on nuclear morphology, numerous cellular junctions with adjacent hepatocyte apices, lack of contiguity with sinusoidal structures and central location in the hepatic tubule. Fish longer than 300 mm had progressively worsening pan-tubular changes in cholangiocytes and hepatocytes which culminated in grossly visible foci of vacuolation and associated neoplasia. Flounder from less contaminated sites showed occasional macrophage aggregations, but none of the other changes noted above. We suggest that the initial vacuolar change in Boston flounder occurs predominantly in pre-ductular cells, which may be stem cells, extending later to fill entire hepatic tubules and intrahepatic portions of the biliary system. The involvement of the vacuolation process in the development of neoplasia is a question we are currently addressing.