Hepatic Neoplasia

Description

Primary hepatic tumours are rare, accounting for less than 1.5% of all canine tumours and 1.0-2.9% of all feline tumours. However, the liver is a common site for the establishment of metastatic tumours due to its rich blood supply from the hepatic portal vein and hepatic artery. In dogs, hepatic neoplasia are 2.5 times more likely to be metastases than primary neoplasia whereas primary hepatobillary tumours are more frequent than metastatic tumours in cats.

Malignant tumours are more common in dogs but benign neoplasia are more common in cats. Primary tumours found in the liver include:

• Hepatocellular carcinoma or adenoma (hepatoma)
• Cholangiocellular carcinoma or cystadenoma
• Gall bladder carcinoma or adenoma
• Haemangiosarcoma
• Mast cell tumour
• Hepatic carcinoids (neuroendocrine)
• Lymphoma

Care must be taken to distinguish between all hepatic tumours and benign nodular hyperplasia which is frequently observed in older dogs. The most significant primary tumours in the dog are hepatomas, hepatocellular and cholangiocellular carcinomas and hepatic carcinoids. Hepatocellular carcinomas and cholangiocellular carcinomas are the most significant tumours to occur in cats.

Signalment

Hepatocellular Tumours

Hepatocellular tumours include hepatocellular carcinomas (HCC) and hepatomas. HCC occurs more frequently in dogs but hepatomas are more common in cats. These are the most common primary liver tumour in dogs and the second most common in cats.

Male dogs over 10 years old are most frequently affected by HCC and the Miniature schnauzer breed may be predisposed to the disease. The metastatic rate of hepatocellular tumours depends on the nature of the mass, with massive tumours spreading at a rate of 0-37% and nodular or diffuse tumours metastasising in 93-100% of cases. The most common sites of metastasis are the regional lymph nodes (the hepatic and diaphragmatic nodes), the peritoneum and lungs. Hepatomas) are usually incidental findings but they may cause hypoglycaemia as a paraneoplastic syndrome.

Cholangiocellular Tumours

Cholangiocellular tumours include bile duct carcinomas and adenomas. Bile duct carcinomas are the most common malignant hepatobillary tumours in cats and the second most frequent in dogs, with female animals possibly being predisposed. Intra-hepatic carcinomas are more frequent in dogs but in cats, it is unclear whether extra-hepatic masses occur more frequently or whether intra- and extra-hepatic masses occur with equal frequency.

Bile duct carcinomas are aggressive and they often metastasise to distant sites. In dogs, these metastases are most common in the regional lymph nodes and lungs but diffuse intra-peritoneal metastasis and carcinomatosis are more common in cats. Bile duct adenomas (also known as biliary or hepatobiliary cystadenomas) are common in cats, particularly in males. These tumours are generally insignificant unless they of sufficient size to compress surrounding soft tissue structures and cause biliary tract obstruction.

Carcinoids

Carcinoids are neuroendocrine tumours that usually occur in younger animals than do the other primary hepatobiliary tumours. Primary tumours are aggressive and often affect more than one liver lobe with frequent metastasis to the regional lymph nodes, lungs and peritoneum.

Sarcomas

The most common sarcomas encountered are haemangiosarcomas (HSA), leiomyosarcomas and fibrosarcomas. HSA is the most common hepatic sarcoma in cats whereas leiomyosarcomas are more common in dogs. These tumours are aggressive and metastasis to the spleen and lungs is frequently observed.

Diagnosis

Tumours are symptomatic in approximately 75% of dogs and 50% of cats and this is more likely to be the case with malignant neoplasia.

Clinical signs

Signs are usually non-specific or they may indicate a disease of the liver:

• Weight loss, inappetance and lethargy.
• Polyuria and polydipsia.
• Vomiting
• Ascites due to the development of portal hypertension.
• Neurological signs, including seizures, ataxia and weakness are not as common as the signs described above. They may be due to metastasis to the central nervous system, hepatic encephalopathy or hypoglycaemia which can occur as a paraneoplastic syndrome.
• Icterus occurs particularly in dogs with extrahepatic cholangiocellular carcinomas and diffuse carcinoids.
• A cranial abdominal mass will be palpable in up to 75% of cats and dogs

Laboratory Tests

The results of blood samples are usually unremarkable but the following findings may be documented in affected animals:

• Mild non-regenerative anaemia of unknown cause. The anaemia may be caused by anaemia of chronic disease, inflammation, red blood cell sequestration and iron deficiency may play roles
• Leucocytosis resulting from the associated inflammation and necrosis that can occur with large liver masses.
• Thrombocytosis, of which potential causes include production of thrombopoietin as a paraneoplastic syndrome, iron deficiency, production of inflammatory cytokines and presence of concurrent anaemia.
• Elevation in the blood levels of hepatic enzymes probably occurs due to hepatocellular damage or biliary stasis. The extent of the elevation is not proportional to severity of liver damage.
• Hypoalbuminaemia due to reduced hepatic synthesis of albumin.
• Hyperglobulinaemia due to a chronic inflammatory process.
• Hypoglycaemia can occur as a paraneoplastic syndrome where there is increased utilisation of glucose or increased production of hormones with insulin-like activity (such as the somatomedins or insulin-like growth factors).
• Elevated pre- and post-prandial bile acids
• Hyperbilirubinaemia which may be sufficiently severe to cause icterus.

Diagnostic Imaging

Radiography

Plain radiographs of the abdomen may show hepatomegaly and rounding of the margins of the liver. With massive hepatic neoplasia, a cranial abdominal mass may be visible with displacement of the stomach caudally and laterally. Mineralisation of the biliary tree is occasionally observed in dogs with cholangiocellular carcinoma. Ideally, all three thoracic views should also be taken to assess for the presence of pulmonary metastases, although this finding is uncommon at the time of diagnosis.

Ultrasonography

An abdominal ultrasound scan is advised to evaluate the condition of structures surrounding the liver. It also allows classification of the mass as massive, nodular or diffuse. Doppler techniques can be utilised to assess the vascular structure of tumours and guided fine-needle aspirates or core biopsies can be taken at this time, although it is desirable to await the results of a coagulation profile before undertaking this procedure. It is traditionally stated that hepatic lymphoma produces a hyperechoic texture on an ultrasound scan.

Advanced Imaging

CT and MRI are more sensitive in detecting small lesions and confirming the relationship of the mass with surrounding tissues and vasculature. They may also be used to detect early metastases.

Other Tests

Cytological examination of ascitic fluid may reveal the presence of neoplastic cells. Effusions are usually modified transudates but haemorrhage may indicate that the tumour has ruptured.

Treatment

Surgery

Surgical excision is advised for hepatic adenomas, bile duct adenomas and massive hepatocellular carcinomas. Nodulectomy or lobectomy can be used for focal tumours involving only one or a small number of lobes. Diffuse tumours and widespread nodular disease carry a poorer prognosis and they have frequently metastasised by the time they are diagnosed.

Chemotherapy

This treatment modality is not recommended for primary hepatic neoplasia. Some metastatic sarcomas, such as haemangiosarcomas, may show some response.

Radiotherapy

This procedure is not undertaken as it involves irradiating the entire abdomen and some surrounding organs may show poor tolerance.

Prognosis

The median survival time for massive hepatocellular carcinomas following surgery is approximately 1 year. Otherwise the prognosis is poor for other types of malignant and metastatic tumours. If successfully excised the prognosis for benign tumours is good.

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References

• Morris J, Dobson J (2001) Gastrointestinal Tract, in Small Animal Oncology, Blackwell Science, pp 137-140

• Liptak J. M, Withrow S.J, (2007), Cancer of the Gastrointestinal Tract, in Withrow and MacEwen's Small Animal Clinical Oncology, fourth edition, Eds Withrow S.J, Vail D.M, Missouri, Saunders Elsevier, pp 483-489