Metastatic, disseminated, and locally infiltrative cancers, including metastatic carcinoma, melanoma, lymphoma, hemangiosarcoma, and histiocytic sarcoma, can often affect the hepatic parenchyma.1,2 Compared with metastatic or secondary cancerous processes involving the liver, primary hepatobiliary tumors are uncommon in companion animals, representing only about 2.6% of canine tumors and about 5.5% of feline tumors.1,3-9 Of these, epithelial tumors of hepatic, biliary, and neuroendocrine origin as well as primary sarcomas are the most commonly diagnosed (Table 1). Other rarely documented primary hepatobiliary tumors include hepatoblastoma, plasmacytoma, and osteosarcoma in dogs and sarcomas, plasmacytoma, and myelolipoma in cats.2,4,8,10-15
Table 1 Types of Hepatobiliary Neoplasia
This article focuses on diagnosing and treating hepatobiliary epithelial tumors and primary sarcomas in dogs and cats. Because of the nonspecific clinical signs of these tumors, dogs and cats may have advanced disease at the time of diagnosis. However, given the infrequency of primary hepatobiliary tumors in both dogs and cats, differential diagnoses to consider upon identifying a hepatobiliary mass include focal hepatic nodular regeneration, a hepatic cyst (parasitic or other), a hepatic abscess (Figure 1), granuloma, hematoma, and a biliary pseudocyst.
CANINE HEPATOBILIARY TUMORS
Primary hepatobiliary tumors most commonly affect older dogs (average age = 10 to 11.1 years).1,16,17 In general, no sex or breed predisposition has been identified.1 In dogs with primary hepatobiliary tumors, hematologic and biochemical changes tend to be variable and nonspecific; however, some biochemical abnormalities may increase the index of suspicion for specific tumor types (e.g. marked hyperlipasemia is supportive of a diagnosis of pancreatic or hepatic neoplasia) or may hint at overall disease extent.18 Serum alpha-fetoprotein may help you differentiate between neoplastic and nonneoplastic hepatic disorders, and higher concentrations of serum alpha-fetoprotein may differentiate hepatocellular carcinomas from cholangiocarcinomas.19,20 Compared with metastatic hepatic tumors, primary hepatic tumors are more likely to cause hypoglycemia, hypoproteinemia, and elevations in alkaline phosphatase (ALP) and alanine transaminase (ALT) activities and are less likely to cause hyperbilirubinemia.16
Figure 1. The liver from a 5-year-old mixed-breed dog that had an acute onset of lethargy, vomiting, and elevated liver enzyme activities. A large, yet confined area of necrosis affects one liver lobe, with gross morphologic abnormalities consistent with a focal hepatic abscess.
Perform a thorough clinical evaluation, including a complete blood count, serum chemistry profile, and urinalysis, in all dogs suspected of having neoplastic hepatobiliary disease. The results of additional diagnostic tests such as coagulation profiles, hepatic function tests (bile acids, ammonia concentrations), diagnostic imaging (ultrasonography, computed tomography [CT], or magnetic resonance imaging [MRI]), cytology, and tissue biopsy may be crucial in guiding therapeutic decisions (see text titled "Definitively diagnosing hepatobiliary tumors in dogs and cats" at the end of the article).
Although most canine hepatobiliary tumors are histologically malignant, surgical excision remains the recommended treatment if anatomically feasible.1 Up to 75% of a normal liver can be resected without impairing hepatic function, and complete parenchymal regeneration can be achieved within eight weeks after surgical resection.21 For dogs with hepatobiliary tumors treated with surgery alone, the prognosis can be influenced by the histologic type, the degree of hepatic dysfunction, and evidence of locoregional or distant metastasis. However, for massive hepatocellular carcinoma, residual disease does not appear to negatively affect postoperative survival times.22
Despite anecdotal reports of responses to mitoxantrone and gemcitabine in veterinary medicine, systemic chemotherapy is considered relatively ineffective for treating hepatobiliary tumors.23-25 The preliminary results of chemoembolization in veterinary medicine for improved therapeutic delivery are encouraging.26 In studies in people, overexpression of the MDR1 gene (multidrug resistance gene) and its product P-glycoprotein has been demonstrated in hepatocellular carcinoma and is associated with chemoresistance.27,28 Because P-glycoprotein is normally expressed in hepatocytes as a drug efflux pump, the limited efficacy of systemic chemotherapy may be a result of altered detoxification functions of hepatocytes and biliary epithelium, allowing hepatobiliary-derived tumor cells to resist the cytotoxic effects of antineoplastic agents.