Hepatic carcinoma

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A large hepatic carcinoma (arrow) originated from the caudate process of the caudate lobe of the liver and adhered to the mesentery of the descending duodenum[1]

Hepatic carcinoma (hepatocellular carcinoma; HCC) is an aggressive neoplastic carcinoma of the canine liver.

Although the cause of this disease is unknown, there is an age-related incidence of hepatocellular carcinoma in older dogs, and dysregulation of the tumor suppressor gene TGFbeta-r[2], suggesting a role of exposure to environmental or dietary carcinogens in the pathogenesis of this condition.

Hepatocellular carcinoma is the most common primary hepatic tumor in dogs[3]. Canine HCC is classified into three morphologic types; massive, nodular and diffuse, and the most common pattern is a massive lesion that involves a single liver lobe[4].

Hepatocellular carcinoma frequently occur as focal intrahepatic masses, or as disseminated tumors. Synchronous (concurrent) neoplasias are common, such as bile duct carcinoma[5] and chemodectoma[6].

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

Hematological analysis often shows mild to moderate nonregenerative anemia, elevated ALT, ALP, hyperalbuminemia and increased albumin/globulin ratio[7]. Prothrombin and activated prothrombin times should also be evaluated to asses clotting function.

Abdominal cystocentesis may reveal hemoperitoneum[8] and urinalysis usually shows hematuria.

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[9] and computed tomography (CT)[10] offer a more precise method of detecting the site of origin of an abdominal mass.

A definitive diagnosis requires histopathological examination of biopsied tissue[11]. Cytological diagnosis is relatively easy when hepatocytes have prominent criteria of malignancy, but is problematic when hepatocytes have a relatively normal morphologic appearance. Common features of hepatocellular carcinomas that assist in a differentiation from hepatocellular hyperplasia or hepatic adenoma is the dissociation of hepatocytes, acinar or palisading arrangements of neoplastic cells, and the presence of naked nuclei and capillaries, together with mild anisocytosis, anisokaryosis and multinuclearity[12].

A differential diagnosis would include hepatic adenoma, cholecystitis, hepatitis, hepatic neuroendocrine tumor, bile duct carcinoma, liver flukes (especially Clonorchis sinensis)[13], hepatic adenoma and secondary metastatic lymphoma.

Liver lobectomy is the recommended treatment, and the prognosis after surgical resection is good in dogs[14]. However, the major complication following hepatic resection is hemorrhage in dogs with a massive HCC. Surgical resection of right-divisional hepatic tumors involving the caudal vena cava, in particular, have a risk of large hemorrhage as a result of injury to this vein. Generally speaking, dogs with left-sided tumors live significantly longer than dogs with right-sided tumors[15].

Adjunct therapy is recommended in metastatic cases, with use of drugs such as doxorubicin[16] or regional cryoablation[17]. With these tumors, a guarded to poor prognosis is expected[18].

References

  1. Seki M et al (2011) En block resection of a large hepatocellular carcinoma involving the caudal vena cava in a dog. J Vet Med Sci 73(5):693-696
  2. Grabarević Z et al (2009) Comparative analysis of hepatocellular carcinoma in men and dogs. Coll Antropol 33(3):811-814
  3. Hammer, AS & Sikkema, DA (1995) Hepatic neoplasia in the dog and cat. Vet Clin North Am Small Anim Pract 25:419–435
  4. Patnaik, AK et al (1980) Canine hepatic neoplasma: A clinicopathologic study. Vet Pathol 17:553–564
  5. Shiga A et al (2001) Combined hepatocellular and cholangiocellular carcinoma in a dog. J Vet Med Sci 63(4):483-486
  6. Sterczer A et al (2012) A case of synchronous hepatocellular carcinoma and aortic body chemodectoma in a dog - pathological case report. Acta Vet Hung 59(1):113-121
  7. Cooper ES et al (2009) Hyperalbuminemia associated with hepatocellular carcinoma in a dog. Vet Clin Pathol 38(4):516-520
  8. Aronsohn MG et al (2009) Prognosis for acute nontraumatic hemoperitoneum in the dog: a retrospective analysis of 60 cases (2003-2006). J Am Anim Hosp Assoc 45(2):72-77
  9. Nakamura K et al (2010) Contrast-enhanced ultrasonography for characterization of canine focal liver lesions. Vet Radiol Ultrasound 51(1):79-85
  10. Fukushima K et al (2012) CT characteristics of primary hepatic mass lesions in dogs. Vet Radiol Ultrasound 53(3):252-257
  11. 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
  12. Masserdotti C & Drigo M (2012) Retrospective study of cytologic features of well-differentiated hepatocellular carcinoma in dogs. Vet Clin Pathol 41(3):382-390
  13. Rim HJ (2005) Clonorchiasis: an update. J Helminthol 79(3):269-281
  14. Kosovsky, JE et al (1989) Results of partial hepatectomy in 18 dogs with hepatocelllar carcinoma. J Am Anim Hosp Assoc 25:203–206
  15. Liptak, JM et al (2004) Massive hapetocellular carcinoma in dogs: 48 cases (1992–2002). J Am Vet Med Assoc 225:1225–1230
  16. 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
  17. 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
  18. Balkman C (2009) Hepatobiliary neoplasia in dogs and cats. Vet Clin North Am Small Anim Pract 39(3):617-625