THE MERCK VETERINARY MANUAL
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Hepatic Neoplasia in Small Animals

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Primary hepatic neoplasms are less common than metastatic neoplasms in the liver and are either carcinomas, carcinoids, sarcomas, or of hemolymphatic origin. Metastatic neoplasia of the liver can originate from multiple visceral organs and can include lymphosarcoma.

Primary tumors are most often found in older animals (<9 yr) and can be either malignant or benign. The most common include hepatocellular adenomas and carcinomas in dogs, and biliary adenomas and carcinomas in cats. Additional tumor types include hemangiosarcomas, carcinoids, and sarcomas in dogs; cystadenomas, lymphomas, and myeloproliferative disease in cats, and less frequently, leiomyosarcomas and myelolipomas.

Diagnosis may be initially pursued because of palpation of an abdominal mass or recognition of serially increasing ALT, AP, or GGT activities. Radiography may disclose a large mass lesion or emphysematous abscess within a necrotic tumor core. Ultrasonography is more sensitive for detection of mass lesions and can discriminate multiple lobe involvement. Small hepatocellular carcinomas may appear hypoechoic, hyperechoic, or heteroechoic. However, the large size of some masses precludes clear differentiation of tumor impingement on or invasion into adjacent viscera and vasculature. Hepatocellular carcinomas can occur as a single large mass in one liver lobe with or without smaller masses in other lobes (massive), as discrete nodules located in multiple lobes (nodular), or as infiltrative disease throughout the liver without obvious discrete nodularity (diffuse). Nodular and diffuse hepatocellular carcinomas, which account for 29% and 10% of all hepatocellular carcinomas, respectively, involve multiple liver lobes and are not usually amenable to surgical removal. Single massive hepatocellular carcinomas represent 61% of all canine hepatocellular carcinomas and are potentially resectable with good outcome. Tumors involving the left liver lobes carry the best prognosis.

Common clinical signs in dogs include weight loss, inappetence, and lethargy; less common signs include vomiting, PU/PD, and seizures (hypoglycemic). However, dogs may be asymptomatic until the tumor reaches massive size or develops a necrotic core. On abdominal palpation a mass may be detected, and pain notable. Abdominal effusion is uncommon. Laboratory tests may indicate nonregenerative anemia, RBC microcytosis, thrombocytosis, and increased serum activity of AP, AST, and hypercholesterolemia. High ALT and AST concentrations may reflect invasion of adjacent normal tissue or central tumor necrosis and may indicate a poor prognosis. Hypoglycemia may develop either due to large tumor mass or a paraneoplastic effect. Pulmonary metastases are uncommon. Tumor margins should be demarcated for the pathologist on submitted specimens to judge adequacy of mass resection (tumor free margin).

These tumors are more common than hepatocellular carcinomas in dogs and are uncommon in cats. They may be associated with increased liver enzyme activity, particularly AP. Dogs with atypical adrenal hyperplasia associated with high androgens or progesterone may be predisposed to hepatocellular adenomas. Rather than single mass lesions, some dogs develop multiple adenomas in different liver lobes. Hepatocellular adenomas may achieve massive size and encroach on normal structures by outgrowing their central blood supply and developing a necrotic core that may serve as a nidus for abscess formation. They may rupture, causing critical abdominal hemorrhage. Differentiating adenoma from hepatic adenocarcinoma in a patient may be controversial; this may be pedantic because wide resection is curable in either case. Tumor margins should be demarcated for the pathologist on submitted specimens to judge adequacy of mass resection (tumor free margin).

Variably classified as cholangiocellular adenocarcinomas and hepatocellular adenocarcinomas, these tumors are the most common primary malignant hepatic neoplasm in cats and may derive from intrahepatic or extrahepatic bile ducts or gallbladder. Pancreatic adenocarcinomas, invasive into hepatic structures, are also common in cats. Biliary cysts can be mistaken on gross inspection for primary biliary adenocarcinomas.

Clinical signs usually include anorexia, lethargy, and vomiting and some cats are jaundiced. Many cats have a history of antecedent liver disease based on historical biochemical profiles; histologically the chronic liver disease is nonsuppurative cholangiohepatitis. A mass or large liver may be palpable. Increased ALT, AST, and AP activity, and increased cholesterol and bilirubin concentrations are common. However, some cats with biliary adenocarcinomas have no clinical signs or laboratory abnormalities. Biliary tree obstruction is identified in some but not all cats with neoplasia associated with the common bile duct and gallbladder. Abdominal radiographs may disclose mass lesions associated with the hepatic silhouette. Ultrasonography usually delineates mass lesions, their dimensions, and lobe location. Some cats develop abdominal effusion and carcinomatosis.

Surgical resection of lesions associated with the intrahepatic biliary system distal to the porta-hepatis and associated with the gallbladder is possible. Neoplasia involving the common duct may be palliated with stent placement through the sphincter of Oddi into the duodenum or creation of a biliary diversion. Some cats survive for months with palliative supportive care (without surgery) despite developing total bile duct obstruction. However, the longterm prognosis is poor. Metastatic lesions are found in the local lymph nodes, peritoneum, and lungs.

The most common hemolymphatic tumor found in the liver in both dogs and cats, lymphoma may be primary or metastatic (from primary enteric or multifocal disease). Other myeloproliferative diseases and mast cell neoplasia also can involve the liver, especially in cats.

These benign tumors are composed of adipose cells and hematopoietic elements. The cellular composite closely resembles cellular elements found in bone marrow. These tumors are usually serendipitously discovered during abdominal ultrasonography and appear densely hyperechoic. Aspiration cytology can easily characterize the cellular features. Unless large vessels and biliary structures are compressed, these lesions do not require surgical removal.

The most common tumors that metastasize to the liver in dogs include lymphoma, pancreatic carcinoma, mammary carcinoma, pheochromocytoma, intestinal carcinoma, thyroid carcinoma, fibrosarcoma, osteosarcoma, and transitional cell carcinoma. Metastatic tumors of the liver are less common in cats, but include pancreatic, intestinal, and renal cell carcinomas. Metastatic tumors are usually multifocal.

Clinical signs can be nonspecific or specific to the liver and resemble features associated with primary hepatobiliary neoplasia: anorexia, weight loss, vomiting, PU/PD, and variable hyperbilirubinemia. Metastatic hepatic neoplasia is more likely to be associated with a malignant abdominal effusion. Neurologic signs may indicate metastatic lesions within the brain, with associated clinical signs mistaken for HE. Abnormalities on baseline hematologic or chemistry profiles may be minimal. A nonregenerative anemia may occur, but there is no consistent change in leukocyte count or distribution. Schistocytes may be observed in animals with neoplasia invading hepatic sinusoids. Eosinophilia can be seen with mast cell tumors and with lymphoma, especially in cats. Liver enzymes may be normal or variably increased. Hypoglycemia either due to large tumor mass or a paraneoplastic effect is sometimes identified. Hyperbilirubinemia and increased AST are seen more frequently in canine metastatic disease than with primary hepatic tumors. While radiographic findings are variable, ultrasonographic findings can confirm single lobe involvement, multiple nodular changes, or diffuse disease. Biopsy is needed for definitive diagnosis.

If one liver lobe is involved, surgical removal is recommended. If lymphoma or mastocytosis are diagnosed, appropriate chemotherapy may prolong life.

Last full review/revision March 2012 by Sharon A. Center, DVM, DACVIM

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