The liver is the largest organ in the body and has a rich blood supply. For these reasons, almost 50% of all tumours that arise in the liver of the dog are secondary tumours, with the primary tumour located elsewhere.
Primary hepatic neoplasia is most common in the geriatric patient, with the mean age of occurrence being 10 to 11 years of age. In one study, cats with malignant hepatic masses were significantly younger than those with benign masses.
What types of liver tumour are there?
Almost irrespective of their origin, a primary hepatic tumour may develop according to three morphologic sub-types: massive, nodular, and diffuse. “Massive” is defined as a large solitary mass confined to one liver lobe. “Nodular” tumours are multifocal and may involve multiple lobes. “Diffuse” disease includes multifocal or coalescing nodules affecting all lobes, often causing effacement of normal hepatic parenchyma.
An important differential for all liver masses is nodular hyperplasia that may be found in up to 15% to 60% of geriatric dogs. Lesions can be solitary or nodular with lesions ranging from 0.1 to 5 cm in diameter. They are difficult to differentiate from other hepatic tumours; therefore it is important to biopsy them at surgery.
Hepatocellular tumours include hepatocellular carcinoma (HCC), hepatocellular adenoma, and hepatoblastoma. HCC is the most common hepatic neoplasm in the dog and may account for up to 48% of all cases of primary hepatic tumours. Morphologically, over 2/3 of HCC are massive, with the remainder either diffuse or nodular. Metastasis is more common with nodular or diffuse HCC (93% and 100%, respectively), whilst solitary tumours are thought not to have such a high rate of metastatic spread (0% to 37%).
Hepatocellular adenomas (hepatoma) are typically an incidental finding found at post-mortem and only cause clinical signs rarely. However, they can be seen as multiple nodules or pedunculated masses and distinguishing them from a more generalised metastatic disease is therefore important. Some solitary adenomas can attain a considerable size, where their encroachment on other organs can result in non-specific clinical signs. Large adenomas may also be friable, with intermittent bleeding from the surface causing anaemia and haemorrhagic ascites. In cats, hepatocellular adenoma occurs more frequently than HCC.
Bile duct tumours
Carcinoma of the bile duct (biliary carcinoma or cholangiocellular carcinoma) is the most common malignant non-haemopoietic hepatic tumour in cats and the second most common in dogs. These tumours principally arise from intrahepatic bile duct epithelium, although they can occur in the extrahepatic bile ducts or gallbladder. Intrahepatic tumours are more common in dogs whereas there is an even distribution of intrahepatic and extrahepatic tumours in cats. The morphologic distribution includes massive (37% to 46%), nodular (up to 54%), and diffuse (17% to 54%) forms. Metastasis is reported to be as high as 88% in dogs and 78% in cats occurring most often in the regional lymph nodes, lungs or peritoneum.
Benign adenoma affecting the bile duct adenomas have also been called biliary or hepatobiliary cystadenomas due to their cystic appearance. Bile duct adenomas may account for more than 50% of all feline primary hepatic tumours, affecting mainly domestic short haired cats over 10 years of age. They typically do not cause clinical signs until they are large enough to compress adjacent tissues.
Neuroendocrine tumours, also known as hepatic carcinoids, are infrequently reported in dogs and cats. Arising from neuroectodermal cells, they are embryologically similar to the cells responsible for insulinomas and gastrinomas. They tend to occur at a younger age than other hepatic tumours (7 yrs vs. 10yrs). Carcinoids have an aggressive biologic behaviour and are not usually surgically resectable as the majority are morphologically diffuse.
Primary tumours of mesenchymal origin are rare in dogs and cats. The most common primary sarcomas are leiomyosarcoma, haemangiosarcoma, and fibrosarcoma. Other sarcomas include rhabdomyosarcoma, liposarcoma, osteosarcoma, and malignant mesenchymoma. Males appear predisposed, but there is no known breed association. Massive and nodular morphology have been reported in 33% and 67% of cases respectively. Diffuse disease has not been reported. Sarcomas are aggressive biologically with metastasis rates reported in 86% to 100% of cases.
How do I know if my dog or cat has a liver tumour?
Clinical signs associated with many hepatic tumours are frequently vague and non-specific. Many animals (up to 50% of cats and 25% of dogs) may be completely asymptomatic with a liver tumour identified only during an investigation for raised liver enzymes. When they occur, clinical signs may relate to the physical presence of the mass itself or may be a consequence of hepatobiliary damage or failure. Inappetence, intermittent vomiting or diarrhoea, polyuria and polydipsia, lethargy and weight loss are amongst the signs more commonly described. Ascites, jaundice and weakness may be seen less commonly.
Physical examination can be equally unremarkable in many cases. Because the liver is bordered by the costal arch, palpable changes may not be possible unless the liver has become significantly enlarged.
How is a liver tumour diagnosed?
Elevation in liver enzymes are observed commonly in animals with liver tumours as a consequence of hepatocellular damage and biliary stasis. As a general rule, there is no correlation between the type and magnitude of enzyme elevation and a specific underlying hepatobiliary disease.
Clotting abnormalities are a potential consequence of all liver disease. Even though these are rarely clinically significant unless hepatic failure has occurred as a consequence of diffuse disease, assessment of clotting times should always be performed prior to performing invasive procedures on the liver. Dogs with haemangiosarcoma of the liver are at risk of developing disseminated intravascular coagulopathy.
Plain abdominal radiographs may provide little specific information on hepatic neoplasia apart from offering evidence for hepatomegaly or the presence of a soft tissue mass within the cranial abdomen. Ascites may be seen on occasion. Thoracic radiography should be considered to exclude metastatic disease.
By contrast, abdominal ultrasonography is a useful and convenient method to establish not only the presence of a hepatic mass, but also to potentially characterise its morphological extent (solitary, nodular, diffuse), its relationship to adjacent structures, the presence of metastatic disease and to detect subtle volumes of ascites. However, ultrasound is rarely effective in determining the specific pathology which is present as many benign and malignant masses share similar sonographic features. For diffuse hepatic disease, the overall accuracy of ultrasonographic diagnosis alone was <40% in dogs and <60% for cats. For nodular disease, it is generally accepted that benign and malignant disease cannot be reliably differentiated using conventional ultrasound imaging alone. Diagnosis is best achieved using the ultrasound to guide percutaneous collection of specimens for cytological or histological assessment. The development of contrast harmonic ultrasound has enabled better accuracy at distinguishing benign and malignant nodules in the dog but requires specialised ultrasound equipment and microbubble contrast agents.
The use of advanced imaging techniques such as three-phase contrast CT have surpassed ultrasound as the tool of choice for the evaluation of human patients with focal hepatic lesions. Although CT is unable to provide a precise tissue diagnosis, the value of CT is to 1) determine the extent and location of the hepatic lesion to allow a reliable assessment of the surgical resectability of a specific lesion and 2) reveal the presence of additional metastatic deposits which may influence the prognosis. The value of this improved diagnostic sensitivity and anatomical characterisation of hepatic lesions provided by CT is that may prevent unnecessary surgeries or biopsies on patients with benign or unresectable lesions.
How are liver tumours treated?
Surgical resection is the recommended treatment in all cases of solitary hepatic tumours, with a decision to operate based mainly on the potential for resectability (and the presence of metastatic lesions) rather than the underlying pathological diagnosis alone. This point emphasises the importance of advanced imaging modalities like CT in the pre-surgical investigation of liver tumours to reliably triage the surgical patient. Surgery is rarely an option for most nodular or diffuse hepatobiliary tumours as they tend to affect several lobes and complete surgical extirpation is impossible. However, localized resection of primary or metastatic nodules may be considered if such intervention can be achieved simply and is likely to provide effective palliation of clinical signs by for example 1) removal of a space occupying mass, 2) reduce the systemic burden of paraneoplastic effects (e.g. insulinoma) or 3) reducing the potential for life-threatening haemorrhage.
Liver lobectomy is most commonly performed for removal of mass lesions. Lobectomy may be partial or complete and may be performed by several different techniques. Partial lobectomy may be performed by placing overlapping rows of full thickness horizontal mattress sutures proximal to the lesion and excising the diseased tissue just distal to the sutured margin. Tumours affecting the right or central divisions of the liver present a more challenging proposition as the caudal vena cava is buried within the parenchyma of the liver and is more susceptible to injury during dissection. Surgical stapling devices may be used, but the hepatic parenchyma is generally thicker than the opening of the jaws, and haemostasis may not be optimal with double-rowed (‘non-vascular’) stapling systems. Bleeding from a liver lobe stump following lobectomy with a TA55 stapler can be very significant and potentially life-threatening.
Tumours encroaching on the hilus of the liver can sometimes be difficult to cleanly resect using stapling techniques. The parenchyma of the right lateral liver lobe and caudate process of the caudate lobe envelop the vena cava, which makes visualization of the hepatic veins to these lobes impossible until some parenchymal dissection has been completed. Liver resection using an anatomical strategy focussed on natural lobar divisions within the liver can have significant benefits. This is a highly specialised strategy that requires considerable experience to perform. However, it can allow successful removal of very large and traditionally challenging liver tumours. With this method, ligation of individual vessels and biliary ducts can be performed to help minimize the potential for life-threatening blood loss as well as improve the likelihood of obtaining clean surgical margins.
What if surgery isn’t possible?
Chemotherapy has shown limited efficacy in the management of non-surgically resectable primary and metastatic liver tumours. Adjuvant chemotherapy may be a consideration for haemangiosarcoma of the liver if complete resection of the primary mass has been accomplished.
In humans, a variety of regional techniques (such as radiofrequency ablation, microwave ablation, laser thermal ablation, cryoablation, percutaneous ethanol injection) and transcatheter arterial chemoembolisation are being used to improve local control and tumour response rates for a variety of tumour (primary and metastatic) types. Chemoembolisation involves the selective intra-arterial delivery of chemotherapy to the vascular bed containing the tumour, with subsequent particle embolisation. This results in a 10-50- fold increase in intratumoural drug concentration, with no increase in systemic toxicity. In addition, the vascular embolisation results in tumour necrosis as tumour cells are less able to tolerate reductions in oxygenation. Although still in its infancy, chemoembolisation has been successfully performed in a limited number of veterinary patients.
Lymphoma of the liver may be managed with systemic chemotherapy, as described elsewhere.
In patients where the liver tumour is considered non-resectable, or is diffusely infiltrating the liver or when owners decline surgery, there is the option of transarterial chemoembolization (TACE). This technique has been performed for several years and offers an option in cases which surgery is not appropriate or declined. As HCC receive almost their entire blood supply from the hepatic artery whereas the normal liver receives most of its supply from the portal vein it makes them particularly susceptible to arterial chemoembolization. Access is gained via the femoral artery and using fluoroscopic guidance this is followed by selection of the celiac and common hepatic artery. After this super-selection of the specific arterial branches supplying the tumour is achieved to ensure minimal non-target embolization occurs (care in particular must be taken to avoid embolisation of the gastroduodenal artery as this may result in significant morbidity, in particular pancreatitis). The combined chemotherapy and embolization agent (generally either cyanoacrylate glue mixed with lipiodol or polyvinyl alcohol particles) is administered into the feeding arteries and a repeat contrast fluoroscopy study performed to confirm vascular stasis within the tumour. Following chemoembolization an HCC does not generally significantly reduce in volume (10-30%) however repeat CT angiogram 6-8 weeks post embolisation will often show marked changes in the attenuation of the mass indicating significant tumour necrosis. The aim should be “stable disease” rather than cure. The procedure may need to be repeated every 3-6 months to limit tumour growth.
What is the prognosis for liver tumours?
The prognosis for all primary or metastatic liver tumours where surgical resection is not possible is generally poor, with survival times following presentation influenced by the clinical status of the patient and the success of any palliative interventions directed at improving appetite, hydration or general comfort. In cats with biliary carcinoma, diffuse intraperitoneal carcinomatosis is often present at the time of diagnosis in 67-80% of cases.
When surgical resection of a solitary hepatobiliary mass is possible, the prognosis for virtually all histopathological variants of hepatic cancer is significantly enhanced.
Surgical management is the recommended strategy for all patients with solitary massive HCC. In one study evaluating outcome for dogs with massive HCC, dogs treated conservatively were 15.4 times more likely to die from tumour related causes than those treated surgically and had a significantly reduced median survival time (270 days vs. >1460 days). Whilst tumour location may increase the risks associated with surgery (e.g. right sided lesions), tumour location had no influence on outcome for patients who survived the surgery. Local recurrence following surgery for HCC is uncommon (0-13%) and although metastatic disease has been reported to occur in up to a third of patients, clinical results suggests that metastasis is uncommon in surgically-managed patients and most deaths are unrelated to HCC.
For bile duct adenoma (biliary cystadenoma) in the cat, liver lobectomy is recommended for cats if the lesion is solitary or if a multifocal lesion is confined to one or two lobes only. If complete resection is achieved, the prognosis is good with no local recurrence or malignant transformation reported.
For solitary biliary carcinoma lesions in the dog and cat, liver lobectomy is recommended to palliate clinical signs. However, survival times remain poor with development of locally recurrent or metastatic disease within 6 months of surgery.
Most carcinoids have an aggressive biological behaviour and rarely, if ever, present as a solitary lesion. The prognosis is poor, and metastasis to regional lymph nodes, peritoneum and lungs has usually occurred at the time of diagnosis.
Liver lobectomy may be attempted for solitary lesions where pre-operative planning has deemed such intervention to be prudent. This strategy may provide palliation of space-occupying effects of the lesion or prevent catastrophic haemorrhage from occurring. However, development of metastatic disease remains a concern and consideration of adjuvant chemotherapy is appropriate.