SIGNALMENT: 14-year-old, Female spayed, Whippet, canine
SOURCE/HISTORY: Left liver lobe removed, cut in half to fit in jars. Since October 3, 2017 liver enzymes have been elevated. Ultrasound on 31 October 2017 revealed mass.
Click here for the IDEXX Pathology Report on this case.
Two wedge biopsies of liver are submitted but are not labeled on the container. Two sections of each sample are evaluated. There is a multilobulated expansile and minimally invasive mass comprised of neoplastic hepatocytes arranged in trabeculae often two to three cell layers thick. Neoplastic hepatocytes are polygonal with distinct cell borders and abundant eosinophilic cytoplasm. There is minimal anisocytosis and anisokaryosis. Nuclei are round to oval with coarse clumped chromatin and prominent nucleoli. There is one mitotic figure identified within 10 400X fields. Present within the neoplastic mass,there are no visible portal triads. There is a large area of necrosis in the center of the mass that contain cellular detritus and degenerate neutrophils. This is surrounded by dense fibrous stroma. Adjacent to this there is another area of necrosis with dense fibrous stroma and osseous metaplasia. The adjacent, nonaffected liver is characterized by marked cell swelling with moderate accumulation of collagen around portal areas and moderate numbers of lipogranulomata scattered throughout the stroma. Nodular proliferation of liver is also present.
- Liver: Hepatocellular carcinoma with adjacent necrosis and osseous metaplasia
Mitotic count: 1 (number of mitotic figures observed in 10 high power fields)
Margins: Extends to margins
Vascular invasion: Not observed
- Liver: Hepatocellular vacuolar degeneration, diffuse, moderate to severe with moderate, chronic periportal fibrosis and hyperplastic nodules
Hepatocellular carcinoma (HCC) is the most common primary liver tumor in dogs, accounting for 50% of cases. Etiologic factors implicated in the development of HCC in humans include infection with hepatitis viruses B or C and cirrhosis. A viral etiology has not been demonstrated in dogs, and cirrhosis is rare in dogs with HCC. In one study, 20% of dogs with HCC were diagnosed with additional tumors although most were benign and endocrine in origin. A breed and sex predisposition has not been confirmed in dogs with HCC, but Miniature Schnauzers and male dogs are overrepresented in some studies.
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. The metastatic rate varies from 0-37% for dogs with massive HCC and 93-100% for dogs with nodular and diffuse HCC.
HCC can be massive, nodular, or diffuse. Massive HCC are usually a single neoplasm that involves one or contiguous liver lobes. Nodular HCC forms scattered nodules, often within multiple liver lobes. Diffuse HCC are characterized by minute indistinct masses spread throughout the liver parenchyma. The massive form is more common in dogs than the other forms. HCC can be found in all lobes of the liver, but the left lateral lobe is reported to be most commonly affected.
Reference: Tumors in Domestic Animals, 4th ed.
Periportal fibrosis is indicative of prior hepatic damage. There is no indication of ongoing diffuse inflammation of the liver although the tumor has probably altered blood flow and cause chronic changes in the liver. The submitted liver contained nonspecific vacuolar degeneration that could result from several underlying causes. Common causes include endogenous or exogenous hyperadrenocorticism, adrenal hyperplasia syndrome with abnormal sex hormone production, diabetes mellitus, lipid metabolic disorders, toxin exposure, and biliary disease. In relation to hyperadrenocorticism, any condition associated with chronic stress (> 4-week duration) can also result in vacuolar degeneration. Chronic infections and neoplasia fall into the latter category. Other conditions that can be associated with vacuolar degeneration include pancreatitis, gastroenteritis, and bacterial septicemias with or without endotoxemia.
Serum bile acid levels can be useful diagnostically in these cases. In animals with significantly elevated bile acid levels, vacuolar degeneration is more commonly associated with a primary hepatic problem. Animals that have only mild elevations or normal bile acid levels are more likely to have extrahepatic disease. Certain proliferative lesions of the liver can also show vacuolar degeneration. These include benign nodular hyperplasia of older dogs and hepatocellular adenomas.
Osseous metaplasia has not been reported with hepatocellular carcinoma in the Veterinary or human literature that I am aware of. I have shown this case to some of my colleagues and our impression is this area of osseous metaplasia has arisen in the focal area of necrosis which is surrounded by a fibrous capsule. There have been reports of calcification in the necrotic areas of the liver surrounded by fibrosis adjacent to untreated hepatocellular carcinomas in humans but no reports of osseous metaplasia. This is probably more of a curiosity and will not affect the prognosis.
Nicole Kraipowich, DVM, MS
Diplomate, American College of Veterinary Pathologists
Direct: 720-977-6154 1-888-433-9987, option 0, x76154