title: Ductal Plate Malformation in the Liver of Boxer Dogs: Clinical and Histological Features.
abstract: Ductal plate malformations (DPMs) represent developmental biliary disorders with a wide phenotypic spectrum. This study characterizes DPM in 30 Boxer dogs. Median age was 1.5 (range, 0.3-10.0) years, with 12 dogs <1 year. Clinical features included increased serum levels of liver enzymes (28), gastrointestinal signs (16), poor body condition (14), abdominal effusion (9), and hepatic encephalopathy (2). Additional malformations included gallbladder atresia (8), atrophied left liver (2), absent quadrate lobe with left-displaced gallbladder (1), portal vasculature atresia (left liver, 1), intrahepatic portosystemic shunt (1), and complex intrahepatic arteriovenous malformation (1). All dogs had portal tracts dimensionally expanded by a moderate-to-severe multiple small bile duct phenotype embedded in abundant extracellular matrix; 80% displayed variable portal-to-portal bridging. Quantitative analysis confirmed significantly increased fibrillar collagen and a 3-fold increased portal tract area relative to 6 Boxer and 10 non-Boxer controls. Biliary phenotype was dominated by tightly formed CK19-positive ductules, typically 10 to 15 μm in diameter, with 3 to >30 profiles per portal tract, reduced luminal apertures, and negative Ki-67 immunoreactivity. CK19-positive biliary epithelium intersected directly with zone 1 hepatocytes as a signature feature when considered with other DPM characteristics. Phenotypic variation included a multiple small bile duct phenotype (all dogs), predominantly thin-walled sacculated ducts (4), well-formed saccular ducts (4), and sacculated segmental, interlobular, and intralobular ducts (Caroli malformation, 2 dogs, one with bridging portal fibrosis). Histologic evidence of portal venous hypoperfusion accompanied increased biliary profiles in every case. We propose that this spectrum of disorders be referred to as DPM with appropriate modifiers to characterize the unique phenotypes.
authors.affiliation: Comparative and Genomic Pathology at Memorial Sloan Kettering Cancer Center, Laboratory of comparative pathology, New York, NY, USA.
authors.forename: S
authors.initials: S
authors.lastname: Pillai
authors.affiliation: Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY, USA sac6@cornell.edu.
authors.forename: S A
authors.initials: SA
authors.lastname: Center
authors.affiliation: Department of Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY, USA.
authors.forename: S P
authors.initials: SP
authors.lastname: McDonough
authors.affiliation: Garden State Veterinary Specialists, Tinton Falls, NJ, USA.
authors.forename: J
authors.initials: J
authors.lastname: Demarco
authors.affiliation: Garden State Veterinary Specialists, Tinton Falls, NJ, USA.
authors.forename: J
authors.initials: J
authors.lastname: Pintar
authors.affiliation: Garden State Veterinary Specialists, Tinton Falls, NJ, USA.
authors.forename: A K
authors.initials: AK
authors.lastname: Henderson
authors.affiliation: Tuft's Veterinary Emergency Treatment and Specialities, Walpole, MA, USA.
authors.forename: J
authors.initials: J
authors.lastname: Cooper
authors.affiliation: Internal Medicine Resident, Department of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX, USA.
authors.forename: T
authors.initials: T
authors.lastname: Bolton
authors.affiliation: Blue Pearl Specialty and Emergency Medicine for Pets, Grand Rapids, MI, USA.
authors.forename: K
authors.initials: K
authors.lastname: Sharpe
authors.affiliation: Veterinary Specialty Hospital, San Diego, San Diego, CA, USA.
authors.forename: S
authors.initials: S
authors.lastname: Hill
authors.affiliation: VCA Shoreline Veterinary Referral and Emergency Center, Shelton, CT, USA.
authors.forename: A G
authors.initials: AG
authors.lastname: Benedict
authors.affiliation: South Carolina Veterinary Specialists, Columbia, SC, USA.
authors.forename: R
authors.initials: R
authors.lastname: Haviland
mesh_terms: D000818:Animals; D001652:Bile Ducts / Q000196:embryology / Q000378:metabolism / Q000473:pathology*; D016767:Caroli Disease / Q000196:embryology / Q000378:metabolism / Q000473:pathology / Q000662:veterinary*; D004283:Dog Diseases / Q000196:embryology / Q000378:metabolism / Q000473:pathology*; D004285:Dogs; D005260:Female; D005704:Gallbladder / Q000473:pathology; D022781:Hepatocytes / Q000378:metabolism / Q000473:pathology; D053539:Keratin-19 / Q000378:metabolism; D008099:Liver / Q000196:embryology / Q000378:metabolism / Q000473:pathology*; D008103:Liver Cirrhosis / Q000196:embryology / Q000378:metabolism / Q000473:pathology / Q000662:veterinary*; D008297:Male; D010641:Phenotype
chemical_list: D053539:Keratin-19
keywords: Caroli malformation; congenital hepatic fibrosis; cytokeratin; dogs; ductal plate malformation; liver; portal tract; primary cilia