Bile duct carcinoma

From Dog
Histological appearance of a canine cholangiocarcinoma, showing moderate cellular differentiation[1]

Biliary duct carcinoma (cholangiocarcinoma; biliary carcinoma) are an aggressive neoplastic carcinoma of intrahepatic and extrahepatic bile duct epithelium of older dogs.

These tumors commonly arise from intrahepatic bile ducts resulting in intrahepatic biliary obstruction. An underlying exposure to carcinogens or liver flukes can predispose to development of these tumors.

Bile duct carcinomas are commonly locally invasive and aggressive metastasize in up to 80% of dogs to the lungs, lymph nodes of the liver and peritoneum.

Some bile duct carcinomas are known as cystadenocarcinomas because they contain dilated cystic spaces with columnar to cuboidal epithelium with a mucin content.

Clinically affected dogs present with rapid-onset (usually within one to two weeks) of weight loss, anorexia, icterus (uncommon), ascites and vomiting.

Diagnosis can be difficult but can be achieved with blood tests (often shows hypoalbuminemia and elevated liver enzyme; ALP, GGT, conjugated bilirubin and cholesterol, indicative of cholestasis), ultrasonography, urinalysis and CT imaging.

A clotting function test should also be performed.

Radiographically, there is usually loss of intraperitoneal detail due to effusion or intraperitoneal seeding of the tumor. Hepatomegaly is also a common finding.

Contrast-enhanced ultrasonography offers a more precise method of detecting the site of origin of an abdominal mass and may be used as a guide to obtain fine-needle aspirates or for preoperative liver biopsy[2].

On exploratory laparotomy, some extrahepatic biliary duct carcinomas may appear as dilated mucus-filled structures rather than well-circumscribed masses.

A definitive diagnosis requires histopathological examination of biopsied tissue and differentiation from primary hepatic carcinoma[3], which can occur concurrent in some dogs[4].

Histologically, these tumors may be well differentiated or poorly differentiated. Intrahepatic bile duct proliferation (ductular reaction) is a common finding, as well as neoplastic changes to ductular epithelium[5].

Immunohistochemical staining with claudin-7[6], hepatocyte paraffin 1 and cytokeratin may help distinguish bile duct carcinoma from primary hepatocellular carcinoma[7].

A differential diagnosis would include hepatic adenoma, cholecystitis, liver flukes (especially Clonorchis sinensis)[8], hepatic adenoma and secondary metastatic lymphoma.

Treatment is restricted to chemotherapy such as doxorubicin[9] or regional cryoablation[10] as palliative tools as these tumors have a guarded to poor prognosis and have frequently metastasized by the time of diagnosis[11].

References

  1. WHO
  2. Nakamura K et al (2010) Contrast-enhanced ultrasonography for characterization of canine focal liver lesions. Vet Radiol Ultrasound 51(1):79-85
  3. Stockhaus C et al (2004) A multistep approach in the cytologic evaluation of liver biopsy samples of dogs with hepatic diseases. Vet Pathol 41(5):461-470
  4. Shiga A et al (2001) Combined hepatocellular and cholangiocellular carcinoma in a dog. J Vet Med Sci 63(4):483-486
  5. Yoshioka K et al (2004) Morphological characterization of ductular reactions in canine liver disease. J Comp Pathol 130(2-3):92-98
  6. Jakab C et al (2010) Claudin-7 protein differentiates canine cholangiocarcinoma from hepatocellular carcinoma. Histol Histopathol 25(7):857-864
  7. Ramos-Vara JA et al (2001) Immunohistochemical characterization of canine hyperplastic hepatic lesions and hepatocellular and biliary neoplasms with monoclonal antibody hepatocyte paraffin 1 and a monoclonal antibody to cytokeratin 7. Vet Pathol 38(6):636-643
  8. Rim HJ (2005) Clonorchiasis: an update. J Helminthol 79(3):269-281
  9. Spee B et al (2006) Specific down-regulation of XIAP with RNA interference enhances the sensitivity of canine tumor cell-lines to TRAIL and doxorubicin. Mol Cancer 5:34
  10. Yu HB et al (2009) Effect of targeted argon-helium cryoablation on the portal region in canine livers. Nan Fang Yi Ke Da Xue Xue Bao 29(3):538-540
  11. Balkman C (2009) Hepatobiliary neoplasia in dogs and cats. Vet Clin North Am Small Anim Pract 39(3):617-625