+ Biologic Behavior

• Primary hepatic tumors are uncommon:
• Hepatic tumors account for 1.0%-2.9% of all feline tumors, but up to 6.9% of non-hematopoietic tumors
• Hepatic tumors account for 0.6%-1.5% of all canine tumors
• Metastatic tumors are more common and occur 2.5 times more frequently than primary liver tumors in dogs
• 4 categories of primary hepatic tumors: hepatocellular, bile duct, neuroendocrine (or carcinoid), and mesenchymal
• Malignant tumors are more common in dogs, while benign tumors occur more frequently in cats
• 3 morphologic types of these primary hepatic tumors: massive, nodular, and diffuse
• Massive liver tumors are defined as a large, solitary mass confined to a single liver lobe
• Nodular tumors are multifocal and involve several liver lobes
• Diffuse involvement may represent the final spectrum of neoplastic disease with multifocal or coalescing nodules in all liver lobes or diffuse effacement of the hepatic parenchyma

+ Clinical Features

• Hepatobiliary tumors are symptomatic in 50% of cats and 75% of dogs
• Clinical signs are non-specific and include inappetence, weight loss, lethargy, vomiting, polydipsia-polyuria, and ascites
• Seizures are uncommon and caused by hepatic encephalopathy, paraneoplastic hypoglycemia, or CNS metastasis
• Icterus is more commonly seen in dogs with extrahepatic bile duct carcinomas and diffuse neuroendocrine tumors
• Cranial abdominal mass is palpable in up to 75% of cats and dogs with liver tumors
• Palpation can be misleading as hepatic enlargement may either be absent in nodular and diffuse forms of liver tumors, or missed due to the protected position of the liver in the cranial abdomen deep to the caudal rib cage

+ Hematology

• Hematologic and serum biochemical abnormalities are usually non-specific
• Leukocytosis, anemia, and thrombocytosis are common in dogs with liver tumors
• Leukocytosis is probably caused by inflammation and necrosis associated with large liver masses
• Anemia is usually mild and non-regenerative
• Anemia and thrombocytopenia can be seen in dogs with primary and metastatic hepatic HSA
• Prolonged coagulation times and clotting factor abnormalities have been identified in dogs with hepatobiliary tumors, but these are rarely clinically relevant

+ Serum Biochemistry

• Liver enzymes are commonly elevated in dogs with hepatobiliary tumors
• No correlation between the degree of hepatic involvement and magnitude of liver enzyme alterations
• However, liver enzyme abnormalities may provide an indication of the type of tumor, and differentiate primary and metastatic liver tumors
• ALP and ALT are commonly increased in dogs with primary hepatic tumors
• AST and bilirubin are more consistently elevated in dogs with metastatic liver tumors
• AST-to-ALT ratio < 1 is consistent with HCC or bile duct carcinoma
• ALT-to-AST ratio > 1 is consistent with neuroendocrine tumor or sarcoma
• Other changes in serum biochemical profile in dogs with hepatic tumors include hypoglycemia, hypoalbuminemia, hyperglobulinemia, and increased pre- and post-prandial bile acids
• Azotemia is often present in cats with hepatobiliary tumors and may be the only biochemical abnormality, although liver enzyme abnormalities, especially ALT, AST and total bilirubin, are also common and are significantly higher in cats with malignant tumors

+ Imaging

• Survey radiographs, ultrasonography, and advanced imaging can be used for the diagnosis, staging, and surgical planning of cats and dogs with hepatobiliary tumors
• Cranial abdominal mass, with caudal and lateral displacement of the stomach, is common on survey abdominal radiographs ± mineralization of the biliary tree with bile duct carcinoma
• Abdominal ultrasonography is the preferred method for identifying and characterizing hepatobiliary tumors
• Sonographic examination is useful in determining the presence of a hepatic mass and defining the tumor as cystic or solid, and massive, nodular, or diffuse
• Size and location of the mass, and its relationship with adjacent anatomical structures, such as the gall bladder or caudal vena cava, should be assessed if the mass is focal
• Ultrasonographic appearance of hepatobiliary tumors varies and does not correlate with histologic tumor type
• Ultrasound-guided FNA or needle-core biopsy of hepatic masses is associated with a correct diagnosis in 62.0% of hepatic aspirates and 93.5% of needle-core biopsies
• Coagulation profile is recommended prior to hepatic biopsy as mild hemorrhage is reported in 5.6% dogs and moderate hemorrhage in 1.6%

+ Other Diagnostic Tests

• Serum tumor markers, particularly α-fetoprotein, are used for the diagnosis, treatment monitoring, and prognostication of humans with HCC
• Serum levels of α-fetoprotein are increased in 75% of HCC in dogs, α-fetoprotein is also increased in other types of liver tumors, such as LSA and bile duct carcinoma, and non-neoplastic hepatic disease

+ General Considerations

• Hepatocellular tumors include HCC, hepatocellular adenoma, and hepatoblastoma
• HCC is the most common primary liver tumor in dogs, accounting for 50% of cases, and 2nd most common in cats
• Hepatoblastoma is a rare tumor of primordial hepatic stem cells and has only been reported in 1 dog
• Hepatocellular adenoma is usually an incidental finding and rarely causes clinical signs
• Hepatocellular adenoma occurs more frequently than HCC in cats
• HCC is more common than adenoma in dogs

+ General Considerations

• Breed predisposition: ± Miniature Schnauzers
• Sex predisposition: ± males
• 53%-83% of HCC are massive, 16%-25% are nodular, and up to 19% are diffuse
• Left liver lobes are involved in > 67% of dogs with massive HCC
• Metastatic rate varies from 0%-37% for dogs with massive HCC and 93%-100% with nodular and diffuse HCC
• Metastasis to regional lymph nodes, peritoneum, and lungs is more common in dogs with nodular and diffuse HCC
• Other metastatic sites include the heart, kidneys, adrenal gland, pancreas, intestines, spleen, and urinary bladder

+ Treatment

• Treatment: liver lobectomy for massive HCC
• Complications following liver lobectomy include hemorrhage, vascular compromise to adjacent liver lobes, and transient hypoglycemia and reduced hepatic function
• No effective treatment for nodular and diffuse HCC
• Role of radiation and chemotherapy in the management of HCC is unknown
• HCC is considered chemoresistant in humans as response rates are usually < 20%
• Regional ablative techniques are used in humans with nodular or diffuse HCC and include percutaneous injection of ethanol or acetic acid, cryotherapy, microwave coagulation therapy, laser therapy, and radiofrequency ablation
• Bland embolization and chemoembolization have been reported with moderate success in the palliation of 4 dogs with HCC

+ Prognosis

• Prognosis is good for dogs with massive HCC with MST > 1,460 days, 0%-6% local tumor recurrence rate, and 0%-37% distant metastatic rate
• Prognosis is poor for dogs with nodular and diffuse HCC is poor

+ Bile Duct Adenoma

• 2 types of bile duct tumors in cats and dogs: bile duct adenoma and carcinoma
• Bile duct adenomas are common in cats, accounting for > 50% of all feline hepatobiliary tumors
• Bile duct adenomas are also termed biliary or hepatobiliary cystadenomas due to their frequent cystic appearance
• Bile duct adenomas usually do not cause clinical signs until they reach a large size and compress adjacent organs
• Even distribution between single and multiple lesions
• Liver lobectomy is recommended for resectable cases
• Malignant transformation occurs in humans and anaplastic changes have been noted in some feline adenomas
• Prognosis is very good following surgical resection with resolution of clinical signs and no reports of local tumor recurrence or malignant transformation

+ Bile Duct Carcinoma

• Bile duct carcinoma is the most common malignant hepatobiliary tumor in cats and the 2nd most common in dogs
• Trematode infestation, cholelithiasis, and sclerosing cholangitis are risk factors for bile duct carcinoma in humans
• Trematode infestation may also be involved in the etiology of bile duct carcinoma in cats and dogs
• Breed predisposition: Labrador Retrievers
• Sex predisposition: female dogs
• 37%-46% of bile duct carcinomas are massive, up to 54% nodular, and 17%-54% diffuse
• Bile duct carcinoma can be intrahepatic, extrahepatic, or within the gall bladder
• Equal distribution of intra- and extrahepatic tumors or extrahepatic predominance has been reported in cats with bile duct carcinoma
• Intrahepatic carcinomas are more common in dogs
• Bile duct carcinoma of the gall bladder is rare in both cats and dogs, accounting for < 5% of cases
• Bile duct carcinomas have an aggressive biologic behavior
• Diffuse intraperitoneal metastasis and carcinomatosis occurs in 67%-80% of cats
• Metastasis is also common in dogs with up to 88% metastasizing to the regional lymph nodes and lungs
• Other metastatic sites include the heart, spleen, adrenal glands, pancreas, kidneys, and spinal cord
• Surgical resection is recommended for cats and dogs with massive bile duct carcinoma
• Survival time is poor in cats and dogs treated with liver lobectomy as the majority have died within 6 months due to local tumor recurrence and metastatic disease
• Bile duct carcinomas are histologically classified as solid or cystic in cats and dogs, but this is not prognostic and other prognostic factors have not been identified

+ NEUROENDOCRINE TUMORS

• Neuroendocrine tumors (i.e., carcinoids) are rare primary tumors in cats and dogs
• Neuroendocrine tumors arise from neuroectodermal cells and are histologically differentiated from carcinomas with the use of silver stains
• Neuroendocrine hepatobiliary tumors are usually intrahepatic although extrahepatic tumors have been reported in the gall bladder
• Carcinoids tend to occur at a younger age than other primary hepatobiliary tumors
• 33% of hepatic carcinoids are nodular and 67% diffuse, with no reports of massive carcinoid morphology
• Surgical resection is usually not possible because of the frequency of nodular and diffuse morphology
• Efficacy of radiation therapy and chemotherapy is unknown
• Carcinoids have an aggressive biologic behavior with metastasis to the regional lymph nodes, peritoneum, and lungs in 93% of dogs and usually early in the course of disease
• Other metastatic sites include heart, spleen, kidneys, adrenal glands, and pancreas
• Prognosis is poor

+ SARCOMAS

• Primary and non-hematopoietic hepatic sarcomas are rare in cats and dogs
• Common primary hepatic sarcomas are leiomyosarcoma, HSA, and FSA
• Liver is a common site for metastatic HSA while only 4%-6% HSA are of primary hepatic origin in dogs
• Other sarcomas include rhabdomyosarcoma, liposarcoma, OSA, and malignant mesenchymoma.
• Benign mesenchymal tumors, such as hemangioma, are rare
• No known breed predispositions although a male predilection has been reported
• 36% of hepatic sarcomas are massive and 64% nodular, with no reports of diffuse sarcomas
• Hepatic sarcomas have an aggressive biologic behavior
• Metastasis to the spleen and lungs is reported in 86%-100% cases
• Liver lobectomy can be attempted for solitary and massive sarcomas
• However, prognosis is poor as metastatic disease is often present at the time of surgery
• Chemotherapy has not been investigated in the treatment of primary hepatic sarcomas although, similar to other solid sarcomas, response rates are likely to be poor

+ Myelolipoma

• Myelolipoma is a benign hepatobiliary tumor described in cats
• Myelolipoma is composed of well-differentiated adipose tissue intermixed with normal hematopoietic elements
• Chronic hypoxia has been proposed an etiologic factor as myelolipomas have been reported in liver lobes entrapped in diaphragmatic herniae
• Myelolipomas can either be single or multifocal
• Treatment: liver lobectomy
• Prognosis is excellent with prolonged survival time and no reports of local tumor recurrence