Hyperalbuminemia associated with hepatocellular carcinoma in a dog

Abstract: A 12‐year‐old, neutered male, mixed‐breed dog was presented to The Ohio State University Veterinary Teaching Hospital with a history of weight loss and weakness. Laboratory abnormalities reported by the referring veterinarian during the past year included increased alkaline phosphatase (ALP) activity, hyperalbuminemia, and nonregenerative anemia. On referral, the dog appeared hydrated and had moderate muscle wasting and hepatomegaly. A large lobular hepatic mass was observed ultrasonographically. Laboratory results included mild to moderate nonregenerative anemia, urine‐specific gravity of 1.035, 3+ proteinuria, increased serum activities of alanine aminotransferase (229 U/L, reference interval 10–55 U/L), ALP (813 U/L, reference interval 15–120 U/L), and the steroid‐induced isoform of ALP (676 U/L, reference interval 0–6 U/L), marked hyperalbuminemia (5.3 g/dL, reference interval 2.9–4.2 g/dL), and an increased A/G ratio (1.7). Hyperalbuminemia was confirmed by reanalysis on 2 different analyzers and by agarose gel electrophoresis, and colloid osmotic pressure (COP) was markedly increased (42.5 mmHg, reference interval 20–25 mmHg). Cytologic examination of a fine‐needle aspirate of the hepatic mass indicated hepatocellular proliferation; histologic examination of an excisional biopsy confirmed hepatocellular carcinoma. Three weeks after surgery, the albumin concentration, A/G ratio, COP, and ALT activity had normalized, but ALP activities remained high. We hypothesized that hyperalbuminemia developed secondary to hepatocellular carcinoma due to increased synthesis of albumin by malignant hepatocytes or due to decreased negative feedback from impaired hepatocellular osmoreceptivity. Hepatocellular carcinoma has been associated with paraneoplastic secretion of other proteins, but hyperalbuminemia has been reported only once in a human patient and has not previously in dogs.     

Ectopic hepatocellular carcinoma in a dog

CASE HISTORY: A 14-year-old neutered male Bearded Collie was presented with a history of recurrent, intermittent urinary incontinence of 7 years duration.

CLINICAL FINDINGS: A large, firm, non-painful mass was found in the mid-abdominal region on palpation. Ultrasonography of the mass revealed a compartmentalised structure with mixed echogenicity, and which did not appear to be associated with any of the abdominal organs. Ultrasound-guided fine needle aspirates contained several clusters of epithelial cells with cytological features of hepatocytes. At exploratory laparotomy, the mass was found in the gastrosplenic ligament within the greater omentum.

PATHOLOGICAL FINDINGS AND DIAGNOSIS: Histopathologically, the mass consisted of sheets of hepatocytes, but without the characteristic hepatic architecture. The cells showed moderate variation in nuclear size and were sometimes binucle- ate. A diagnosis of hepatocellular carcinoma (HCC) in the mesentery was made.

CLINICAL RELEVANCE: The presence of ectopic hepatic tissue has been reported rarely in man and cats, but not in the dog. Neoplastic transformation of ectopic hepatic tissue is seen in man. This is the first report of the presentation, clinical findings and treatment of a dog with ectopic HCC.     

Ectopic hepatocellular carcinoma in a dog

CASE HISTORY: A 14-year-old neutered male Bearded Collie was presented with a history of recurrent, intermittent urinary incontinence of 7 years duration. CLINICAL FINDINGS: A large, firm, non-painful mass was found in the mid-abdominal region on palpation. Ultrasonography of the mass revealed a compartmentalised structure with mixed echogenicity, and which did not appear to be associated with any of the abdominal organs. Ultrasound-guided fine needle aspirates contained several clusters of epithelial cells with cytological features of hepatocytes. At exploratory laparotomy, the mass was found in the gastrosplenic ligament within the greater omentum. PATHOLOGICAL FINDINGS AND DIAGNOSIS: Histopathologically, the mass consisted of sheets of hepatocytes, but without the characteristic hepatic architecture. The cells showed moderate variation in nuclear size and were sometimes binucleate. A diagnosis of hepatocellular carcinoma (HCC) in the mesentery was made. CLINICAL RELEVANCE: The presence of ectopic hepatic tissue has been reported rarely in man and cats, but not in the dog. Neoplastic transformation of ectopic hepatic tissue is seen in man. This is the first report of the presentation, clinical findings and treatment of a dog with ectopic HCC.     

Hypertrophic osteopathy associated with hepatocellular carcinoma in a dog

A 9-year-old spayed female dog diagnosed with hepatocellular carcinoma and hypertrophic osteopathy was negative for additional lesions on computed tomography of the thorax and abdomen. Resection of the affected liver lobe resulted in resolution of clinical signs. This is the first case of hypertrophic osteopathy secondary to hepatocellular carcinoma.     

En block resection of a large hepatocellular carcinoma involving the caudal vena cava in a dog

A 13-year-old neutered female Shih Tzu was referred for investigation of a cranial abdominal mass. Investigations including conventional radiography, abdominal ultrasonography and computed tomography confirmed the mass in the caudate lobe of the liver. As a collateral vein originating from the caudal vena cava (CVC) communicated with the azygos vein, the CVC was ligated and transected cranial to the right renal vein and cranial to the mass under temporary occlusion of the thoracic descending aorta and posthepatic CVC. The mass combined with the CVC was excised. The mass was confirmed as hepatocellular carcinoma (HCC). This report describes the first case with successful en bloc resection of a large HCC involving the CVC in a dog.     

Diabetes mellitus induced in a dog after administration of corticosteroids and methylprednisolone pulse therapy

An 8-year-old ovariohysterectomized Chow Chow was referred because of dermatologic lesions diagnosed as pemphigus foliaceus. Intolerance to orally administered corticosteroids necessitated the use of methylprednisolone pulse therapy. One week after treatment, diabetes mellitus was diagnosed on the basis of blood and urine test results. For 3 years after treatment, the dog has remained a well-regulated diabetic. Complete remission of pemphigus foliaceus is maintained by alternate-day, orally administered prednisone (0.5 mg/kg of body weight).     

Diabetes insipidus associated with metastatic pancreatic carcinoma in a dog

Diabetes insipidus was diagnosed in a dog with metastatic pancreatic carcinoma. Histologic examination of the pituitary gland revealed extensive invasion of the pars intermedia and neurohypophysis by metastatic tumor cells.     

Combined hepatocellular and cholangiocellular carcinoma in a dog

A transitional type of combined hepatocellular and cholangiocellular carcinoma developed in a 12-year-old male Yorkshire terrier dog. The tumor was histologically composed of both hepatocellular carcinoma and cholangiocellular carcinoma components, and both elements were closely intermingled. Intraluminal mucin accumulation in cytokeratin-positive tubular/glandular structures was observed within the cholangiocellular carcinoma components and this feature was useful histological marker for a differential diagnosis between combined hepatocellular and cholangiocellular carcinoma and a pseudoglandular type of hepatocellular carcinoma. This primary hepatic tumor is extremely rare in dogs.     

Temporary remission of hypoglycemia in a dog with an insulinoma after treatment with streptozotocin.

Temporary remission of hypoglycemia was achieved in a dog with an insulinoma by treatment, using streptozotocin. Nephropathy, manifested as a renal tubular defect, and hepatopathy were associated with the administration of streptozotocin.     

Paraneoplastic hypoglycemia in a diabetic dog with an insulin growth factor-2-producing mammary carcinoma

A 6-year-old intact female Labrador Retriever had diabetes mellitus, which had been difficult to control with insulin. The dog also had a solid ductal mammary carcinoma with very rapid growth, which was temporally related to onset of hypoglycemia. Eight months after initial diagnosis of diabetes, the dog had a hypoglycemic crisis. Insulin administration was stopped and serum glucose concentration returned to normal. Three months after discontinuing insulin, another hypoglycemic crisis occurred. During subsequent months, serum glucose concentrations remained at life-threatening levels (1.64-2.12 mmol/L, reference interval 4.44-6.66 mmol/L) simultaneously with an increase in the size of the mammary tumor, which reached a diameter of about 16 cm. At the time of surgery for removal of the tumor serum glucose concentration was 2.20 mmol/L and was then monitored every 3 hours after excision of the tumor. The glucose concentration continued to rise and reached 9.99 mmol/L 12 hours after the removal of the mammary tumor. Immunohistochemical staining demonstrated expression of insulin growth factor-2 by tumor cells, which apparently had caused the hypoglycemia during tumor growth even in a diabetic dog. Hyperglycemia associated with diabetes was pronounced after excision of the tumor and had been masked by the paraneoplastic effect of the tumor.     

Characterization of cytoplasmic hyaline bodies in a hepatocellular carcinoma of a dog

This report describes the morphological and immunohistochemical features of intracytoplasmic inclusion bodies found in a 13-year-old Yorkshire dog with a hepatocellular carcinoma and referred for anorexia, lethargy and mild polydipsia. Fine-needle aspirates of the large abdominal mass revealed high number of pleomorphic neoplastic hepatocytes, containing round to polygonal, well-demarcated, hyaline bodies. Same findings were histologically confirmed on multiple biopsies. Immunohistochemically, the inclusion bodies were negative for alpha-1-antitrypsin, carcinoembryonary antigen, fibrinogen, IgG, IgM, cytokeratins 7, 8, 18, 19, 20. By transmission electron microscopy, the cytoplasmic inclusions were composed of granular homogeneous or reticulated electrondense matrix, enclosed within dilated rough endoplasmic reticulum or remnants of its membranes, consistent with proteinaceous material accumulated within neoplastic hepatocytes due to aberrant protein secretion or transport. This is the first detailed characterization of hyaline cytoplasmic inclusion bodies in canine hepatocellular carcinoma.     

Canine serum thermostable alkaline phosphatase isoenzyme from a dog with hepatocellular carcinoma

A dog histopathologically diagnosed with hepatocellular carcinoma (HCC) showed very high serum alkaline phosphatase (ALP) activity. A supernatant of ascitic fluid and tumor tissue extracted from the dog also showed much higher ALP activity than normal. ALP isoenzyme analysis of samples was performed using polyacrylamide gel disk electrophoresis, and a wide, broad abnormal band was observed. By various treatments, the abnormal band showed thermostability, which is a characteristic of tumor-associated ALP that has only been reported in humans. The thermostable ALP isoenzyme was not found in sera from 39 dogs with several types of tumor that originated from the liver, except for HCC, nor was it found in 10 dogs with hepatic diseases that did not include hepatic tumors. The thermostable ALP isoenzyme seemed to be associated with canine HCC.     

Diabetes mellitus in the juvenile dog: a report of four cases.

In four cases of diabetes mellitus in juvenile dogs, clinical and clinicopathologic findings were similar to those of juvenile onset diabetes mellitus in man. However, histopathologic findings varied from the usual findings in the human disease, and lack of plasma insulin was not proved in the canine cases.     

Atherosclerosis in a dog with diabetes mellitus

A seven-year-old male Pomeranian with unstable insulin-dependent diabetes mellitus developed atherosclerosis. Hyperlipidaemia, consisting of hypertriglyceridaemia and hypercholesterolaemia, was diagnosed concurrently with the onset of lipid-laden aqueous humour. Serum lipoprotein analysis was characterised by the presence of chylomicrons, an increase in the very low density lipoprotein fraction, with a broad very low density lipoprotein-low density lipoprotein band, and a reduced high density lipoprotein fraction. The dog developed ketoacidosis one year later and died. At postmortem examination, atherosclerotic plaques were observed in the terminal aorta and in medium-sized arteries, including the coronary arteries, renal and arcuate arteries, and arteries of the brain. Mineralised plaques or complicated plaques were not observed. The absence of clinical signs of organ ischaemia was thought to be associated with the absence of thrombosis and/or complete occlusion of all vessels examined. Signs of chronic organ hypoxia, although considered likely owing to the severe vessel lumen reduction, were restricted to only a low voltage QRS complex on the electrocardiogram.     

Resolution of chylothorax after resection of rib chondroma in a dog

A six-year-old, male dobermann was presented with a history of dyspnoea and bouts of coughing. Radiography and computed tomography of the thorax showed pleural effusion and a well-circumscribed, calcified mass of 10 cm in diameter, appearing to originate from the left first rib. Thoracocentesis revealed that the pleural fluid was chylous in nature. An incisional biopsy was performed, which gave a histological diagnosis of chondroma. Resolution of the chylothorax after en-bloc surgical removal of the tumour suggested that the rib tumour was the initiating cause of the chylothorax. Seventeen months later, rib neoplasia recurred without pleural effusion, and was removed successfully. To the authors' knowledge, rib chondroma, which is an unusual tumour in dogs, has not been previously documented as a cause of chylothorax.