Bile Duct Dysplasia and Congenital Hepatic Fibrosis Associated with Polycystic Kidney (Caroli Syndrome) in a Rat

Abstract

Abstract. Hepatic fibrosis with bile duct ectasia and hyperplasia associated with polycystic kidney disease, analogous to Caroli syndrome in humans, was observed in a rat used as a control in a subchronic toxicity study. Light microscopy of liver sections showed multiple cystic and segmental saccular dilatations and hyperplasia of the intrahepatic bile ducts associated with overgrowth of portal connective tissue; the kidneys had diffuse cystic dilatation of cortical renal tubules. The lesions resembled those of human cases of the fibropolycystic disease termed as Caroli syndrome, which is thought to be the result of a pathologic developmental process known as ductal plate malformation. Recently, an animal model of Caroli syndrome has been described in mutant rats from a colony that constantly showed renal and hepatic cysts and an autosomal recessive mode of inheritance. The finding in our case of identical hepatorenal lesions suggests that the same mutation has occurred incidentally in a standard colony.Key words: Caroli disease; congenital hepatic fibrosis; polycystic kidney; rats. A 5-month-old male Sprague-Dawley rat, included as a control case in a subchronic toxicity study to test plastic material for vascular prosthesis, was euthanatized with CO 2 at the end of the study. At necropsy, moderate enlargement of the liver in association with an irregularly lobular, gray pattern and increased firmness of the hepatic parenchyma was noted (Fig. 1); furthermore, both kidneys were moderately enlarged and bilaterally presented multiple cortical cysts ranging in size from 3 to 5 mm in diameter (Fig. 2). Tissue samples were fixed in 10% neutral buffered formalin, embedded in paraffin, sectioned at 4 m, and stained with hematoxylin-eosin and Masson trichrome. In histologic sections of the liver the connective tissue in portal tracts was widened and formed thick bands that surrounded bile ducts and ductules (portal fibrosis); bile ducts were increased in number (bile duct hyperplasia) and markedly dilated (bile duct ectasia) (Fig. 3). The irregularly shaped bile ducts were lined by normal cuboidal epithelium, but there were bulbar protrusions of the duct wall into the lumen and occasional bridge formation of the duct wall across the lumen (bile duct dysplasia suggestive of ductal plate malformation) in more dilated bile ducts. The lumen of dilated bile ducts occasionally contained amorphous or globular weakly eosinophilic material. In some portal tracts, there was hypoplasia of portal vein branches in association with supernumerary hepatic artery branches. Occasionally, portal tracts showed mild lymphocytic infiltration. The hepatic parenchyma lacked regenerative features, and the lobular pattern was maintained. The kidneys showed multiple cystic dilatations of renal tubules, particularly marked at the cortical-medullary junction, that tended to spread to the cortex; glomeruli were spared, and there were no glomerulocystic lesions (Fig. 4). Some dilated tubules contained amorphous eosinophilic proteinaceous material; mu...

Factors contributing to diagnostic delay of Caroli syndrome: a single-center, retrospective study

“…Caroli syndrome (CS) is a rare congenital disorder associated with ductal plate malformation and hepatic brosis [9]. CS is usually diagnosed during childhood or adolescence but may be diagnosed in adulthood [10,11], consistent with our ndings.…”

Polycystic liver in farmed turbot, Scopthalmus maximus (L.)

“…According to Woo et al (2002), multiple kidney and hepatic cysts in fish and mammals may have their origins in failure of component cells such as biliary duct cells and renal tubular epithelium. In these cases, cysts were surrounded by cuboidal to cylindrical epithelial cells, and ectasia or segmental dilation of the intrahepatic ducts was observed (McKenna & Carpenter 1980;Picone et al 1981;Bettini et al 2003). In the present report, as in those of Bruno & Ellis (1986) and Bruno & Poppe (1996), cysts were surrounded by a connective tissue capsule but epithelial tissue was not observed.…”

“…Non‐parasitic hepatic cysts have occasionally been observed in several animals including, humans, dogs, rats, goats, deer and chamois (McKenna & Carpenter 1980; Picone, Williams, Leid & Fay 1981; Krotec, Meyer, Freeman & Hamir 1996; Bettini, Mandrioli & Morini 2003; Glawischnig & Bago 2010). In humans, polycystic liver disease is genetically determined and characterized by the growth of fluid‐filled cysts of biliary epithelial origin (Glawischnig & Bago 2010).…”

“…In these cases, cysts were surrounded by cuboidal to cylindrical epithelial cells, and ectasia or segmental dilation of the intrahepatic ducts was observed (McKenna & Carpenter 1980; Picone et al. 1981; Bettini et al. 2003).…”

Clinical classification of Caroli's disease: an analysis of 30 patients

“…Caroli's disease is a rare, autosomally recessive inherited congenital disorder associated with an incomplete and faulty remodelling of the embryonic ductal plate . It is usually diagnosed during childhood or adolescence, but may be diagnosed in adulthood .…”