JPC SYSTEMIC PATHOLOGY
DIGESTIVE SYSTEM
October 2018
D-T05

Signalment (JPC #1783194):  3-year-old female Bedlington terrier

HISTORY:  This dog presented with lethargy, anorexia, vomiting, and icterus.

HISTOPATHOLOGIC DESCRIPTION:  Liver:  Affecting approximately 30% of the section, centrilobular hepatocytes are separated and surrounded by, or lost and replaced by nodular aggregates of: macrophages, lymphocytes, fewer non-degenerate neutrophils and plasma cells, small amounts of eosinophilic cellular and karyorrhectic debris (necrosis); surrounded by: eosinophilic fibrillar material (fibrin), increased clear space (edema) and scattered reactive fibroblasts with fibrous connective tissue (fibrosis) that often bridges to other central venous areas or occasionally to portal areas. Adjacent hepatocytes are multifocally swollen with pale eosinophilic, finely vacuolated cytoplasm (degeneration) or are individualized, angular with intensely eosinophilic cytoplasm and pyknotic nuclei (necrosis).  Macrophages (within areas of inflammation), Kupffer cells (within sinusoids), and hepatocytes frequently contain either intracytoplasmic brown to gray granular pigment (ceroid or copper) or golden to dark brown granular pigment (bile or hemosiderin).  Multifocally scattered bile canaliculi contain variably-sized linear plugs of green-brown bile (cholestasis).  Multifocally, within centrilobular and portal areas, there are scattered ectatic lymphatics often associated with areas of inflammation.

D-T05B:  Rhodanine:  Primarily within inflammatory foci and scattered throughout the remainder of the section, hepatocytes, macrophages, and Kupffer cells in sinusoids are distended by intracytoplasmic red globular pigment (copper).

MORPHOLOGIC DIAGNOSIS:  Liver:  Hepatocellular degeneration, necrosis and loss, centrilobular, chronic, diffuse, marked, with lymphohistiocytic hepatitis, cholestasis, fibrosis, and hepatocellular and histiocytic copper accumulation, Bedlington terrier, canine.

CONDITION:  Inherited copper toxicosis of Bedlington terriers

GENERAL DISCUSSION:

PATHOGENESIS:

TYPICAL CLINICAL FINDINGS:

TYPICAL GROSS FINDINGS:

TYPICAL LIGHT MICROSCOPIC FINDINGS:

ULTRASTRUCTURAL FINDINGS:

ADDITIONAL DIAGNOSTIC TESTS:

DIFFERENTIAL DIAGNOSIS:

For chronic hepatotoxicity in dogs:

COMPARATIVE PATHOLOGY:

REFERENCES:

  1. Brown DL, Van Wettere AJ, Cullen JM. Hepatobiliary system and exocrine pancreas. In: McGavin MD, Zachary JF, eds. Pathologic Basis of Veterinary Disease. 6th ed. St. Louis, MO: Elsevier; 2017:440, 457.
  2. Cullen JM, Stalker MJ. Liver and biliary system. In: Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol 2. 6th ed. St. Louis, MO: Elsevier, 2016:302-305, 342-343.
  3. Hurwitz BM, Center SA, Randolph JF, McDOnough SP, Warner KL, et al. Presumed primary and secondary hepatic copper accumulation in cats. J Am Vet Med Assoc. 2014; 24(1):68-77.
  4. LaDouceur EEB, Wynne J, Garner MM, Nyaoke A, Keel MK. Lesions of copper toxicosis in captive marine invertebrates with comparisons to normal histology. Vet Pathol. 2016; 53(3):648-658.
  5. Langlois DK, Smedley RC, Schall WD, Kruger JM. Acquired proximal renal tubular dysfunction in 9 Labrador retrievers with copper-associated hepatitis. J Vet Intern Med. 2013: 27(3):491-499.
  6. Ramirez CJ, Kim DY, Hanks BC, Evan TJ. Copper toxicosis in New Zealand white rabbits (Oryctolagus cuniculus). Vet Pathol. 2013;50(6):1135-1138.
  7. van den Ingh TSGAM, Van Winkle T, Cullen JM, Charles JA, Desmet VJ. Morphological classification of parenchymal disorders of the canine and feline liver, 2. Hepatocellular death, hepatitis and cirrhosis.  In: WSAVA Standards for clinical and histological diagnosis of canine and feline liver disease. Philadelphia, PA: Saunders Elsevier; 2006:95-96. 
  8. van Winkle T, Cullen JM, van den Ingh TSGAM, Charles JA, Desmet VJ. Morphological   classification of parenchymal disorders of the canine and feline liver, 3. Hepatic abscesses and granulomas, hepatic metabolic storage disorders and miscellaneous conditions.  In: WSAVA Standards for clinical and histological diagnosis of canine and feline liver disease. Philadelphia, PA: Saunders Elsevier; 2006:106-110.
  9. Wynne J, LaDouceur EEB, Ryan H. Clinical copper toxicosis in a large mixed group of marine invertebrates. J Zoo Wildl Med. 2015; 46(3):601-604.


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