Search

Hepatobiliary neuroendocrine carcinoma was diagnosed in 17 cats in a period of 10 years. Seven tumors were of intrahepatic origin, one of which was a composite containing components of epithelial and neuroendocrine carcinoma. Nine tumors were of extrahepatic origin, and one tumor was located in the gall-bladder. The cats were adult and geriatric, and the male : female ratio varied according to tumor group. Hepatomegaly, anorexia, weight loss, and vomiting were the most common clinical signs observed in the cats with hepatic neuroendocrine carcinoma. The cats with extrahepatic neuroendocrine carcinoma showed these signs plus icterus (5/9) and high concentrations of hepatic enzymes. Histologically, the hepatic neuroendocrine carcinomas had two patterns, one with acinar structures separated by vascular stroma lined by cuboidal or columnar cells and the other solid with groups of anaplastic cells separated by vascular stroma. The composite tumor consisted of both bile duct carcinoma and neuroendocrine carcinoma. The extrahepatic neuroendocrine carcinomas and the gallbladder neuroendocrine carcinoma were characterized by solid sheets or groups of round to oval cells with vascular or fibrovascular stroma. Immunohistochemical examination of 10 of the neuroendocrine carcinomas revealed that all 10 stained with neuron-specific enolase; one bile duct carcinoma and the gallbladder carcinoma stained with chromogranin; four of five bile duct carcinomas and the gall bladder carcinoma stained with synaptophysin; and one bile duct carcinoma stained with gastrin. One cat with hepatic carcinoma had duodenal ulcer; in this cat, ultrastructural studies showed neurosecretory granules leading to the diagnosis of Zollinger-Ellison syndrome. In four cats in which necropsy was permitted, carcinomatosis (4/4), lymph nodes (4/4), lungs (2/4), and intestines (1/4) were the metastatic sites. Fourteen of the 17 cats were euthanatized during or immediately after surgery.

Ten dogs with neuroendocrine carcinoma of the liver were selected for inclusion in the study. Clinical signs were anorexia (7), vomiting (5), polydipsia/polyuria (3), icterus (2), lethargy (2), weight loss (2), paresis (1), ataxia (1), weakness (1), collapse (1), and urinary tract infection (1). Hematologic and biochemical abnormalities included anemia (2/8), leukocytosis (4/8), high liver enzyme activity (serum alkaline phosphatase, 7/9; alanine transaminase, 7/9; aspartate transaminase, 8/9), and high total bilirubin (6/9). Grossly, the tumors were diffuse, involving all liver lobes in six dogs, and two dogs had various-sized nodules in addition to diffuse involvement. Histologically, there were eight tumors with solid or trabecular pattern (group A), one tumor with cords or rows of neoplastic cells (group B), and one tumor with multiple rosette-like structures (group C). Immunohistochemical studies revealed that all 10 neoplasms were positive for at least one of the endocrine markers used: neuron-specific enolase (NSE; 8/10), synaptophysin (5/10), and chromogranin-A (3/10). A panel of NSE, chromagranin-A, and synaptophysin detected 100% of the tumors in our series. Electron microscopy confirmed the diagnosis by the presence of intracytoplasmic neurosecretory granules in the two examined cases. Our results show that neuroendocrine markers commonly used in humans can be used for the diagnosis of hepatic neuroendocrine carcinoma in dogs, preferably a panel of synaptophysin, chromagranin-A, and NSE because chromogranin-A alone is not as useful in dogs as in humans.

Nonhematopoietic hepatic neoplasms (n = 25) were diagnosed in 21 cats during a 5.5-year period. Thirteen of the neoplasms were benign bile duct adenomas and 12 were malignant, 6 of which were bile duct adenocarcinomas. All cats were greater than or equal to 10 years old, and 14 were male. Main clinical signs were anorexia and lethargy, and 15 of 21 cats had hepatomegaly. All 21 cats were feline leukemia virus-test negative. Although there was a trend toward high activities of serum alanine transaminase and aspartate transaminase, neither clinical signs nor enzyme activity were specific for diagnosis of hepatic neoplasia in the cats of this study.

During a 5-year period, leiomyosarcoma was diagnosed in 57 dogs. Forty-four dogs were included in the study on the basis of completeness of medical records. All dogs underwent exploratory laparotomy, and dogs were allotted to 4 groups according to primary site of tumor: spleen (16 dogs, median age 10.3 years), stomach/small intestine (13 dogs, median age 10.3 years), cecum (10 dogs, median age 11.8 years), and liver (5 dogs, median age 9 years). All dogs with leiomyosarcoma of the liver had visible metastasis and were euthanatized at surgery. In the other 3 groups, 79% of the dogs had no gross evidence of metastasis at surgery, and 64% survived greater than 2 weeks. Median survival in these 3 groups was 10 months (range, 1 month to 7 years); 48% died of metastasis, 32% died of unrelated causes, and 16% died of unknown causes. The prognosis in dogs with leiomyosarcoma of the spleen, stomach, small intestine, and especially the cecum is good to excellent if surgery is performed. In dogs with leiomyosarcoma of the liver, the prognosis is poor.

A retrospective study was done of 47 neoplasms of the hepatic and biliary systems from 47 cats brought to The Animal Medical Center over a period of 10 years (1980 to 1989). Histologic examination of specimens taken at necropsy revealed that 87% (41/47) of the hepatic neoplasms were epithelial and 13% (6/47) were nonepithelial. Of the epithelial tumors, 25/47 (53%) were of intrahepatic bile duct origin, 9/47 (19%) were of hepatocellular origin, 5/47 (11%) involved the extrahepatic bile ducts, and 2/47 (4%) were adenocarcinomas of the gall bladder. Of the nonepithelial neoplasms, hemangiosarcomas were more common, 5/47 (11%), than leiomyosarcomas, 1/47 (2%). Multiple liver lobes were involved in 21/34 (62%) of the epithelial and all six of the nonepithelial intrahepatic neoplasms. Most of the bile duct adenocarcinomas (6/9) were predominantly characterized by acinar structures with mucin production, diffuse necrosis, and little desmoplasia. The hepatocellular carcinomas were characterized by three patterns-trabecular (five tumors), pseudoglandular pattern (two tumors), and anaplastic (one tumor). The hepatic carcinoid was characterized by various-sized groups of acinar and rosettelike structures, some with lumens, separated by thin fibrovascular stroma. The extrahepatic bile duct adenocarcinomas (4/4) were acinopapillary with moderate desmosplasia, whereas the adenocarcinomas of the gall bladder had elongated tubular structures lined by anaplastic cells and a severe desmoplastic reaction. The neuroendocrine carcinoma of the extrahepatic bile duct, the hemangiosarcomas, and the leiomyosarcoma had morphologic features characteristic of these neoplasms. Two of the 16 (13%) bile duct adenomas had anaplastic and precancerous changes. Residual benign components were seen in 10/15 (67%) of the biliary adenocarcinomas, 4/9 (44%) of the intrahepatic bile duct adenocarcinomas, and all of the extrahepatic bile duct adenocarcinomas and gall bladder adenocarcinomas. Results of immunohistochemical studies of the biliary neoplasms were similar to those described in studies of biliary neoplasms in human beings. Results of this study revealed that the frequency of different types of hepatic neoplasms in cats varied from that seen in dogs and human beings, but the morphologic features were comparable.

One hundred ten primary hepatic neoplasms, excluding hematopoietic and vascular tumors, were diagnosed in 12,245 canine necropsies. Included were 55 hepatocellular carcinomas, 24 bile duct carcinomas, 2 combined hepatocellular and cholangiocarcinomas, 15 carcinoids and 14 sarcomas. A majority of the dogs with hepatocellular carcinoma (80%), bile duct carcinoma (65%) and sarcoma (61%) were 10 years old or older; 71% of the dogs with carcinoid were under 10 years old. Hepatocellular carcinoma and sarcoma occurred more often in males, bile duct carcinoma in females, and no sex predisposition was found in dogs with carcinoid. All dogs had hematologic and biochemical abnormalities relating to liver function. The aspartate amino transferase/alanine amino transferase ratio was less than one in cases of hepatocellular carcinoma and bile duct carcinoma, and more than one in cases of carcinoid and sarcoma. A massive lesion in one of the liver lobes was the most common gross morphologic feature in cases of hepatocellular carcinomoa and bile duct carcinoma, with the left lateral lobe affected most often. In cases of carcinoid, most of the lesions were diffuse. The most common sites of metastases were lymph nodes and lungs for hepatocellular carcinoma and bile duct carcinoma, lymph nodes and peritoneum for carcinoid, and spleen for sarcoma.

Hypoglycemia associated with nonislet cell tumor was found in 13 dogs. In each dog, clinical signs were related directly to adrenergic and neuroglucopenic effects of hypoglycemia and included collapsing episodes, tremors, restlessness, weakness, and grand mal seizures that were responsive to glucose administration. Eight of the dogs had hepatocellular carcinoma; surgical resection of the tumor achieved remission of clinical signs in 3 of these dogs. Other hepatic tumors associated with hypoglycemia included leiomyosarcoma and hemangiosarcoma involving solitary lobes of the liver. Nonhepatic tumors included splenic hemangiosarcoma, diffuse metastatic melanoma, and salivary gland adenocarcinoma.

In 110 primary hepatic neoplasms in the dog, 15 carcinoids were diagnosed. Diffuse involvement of all liver lobes with severe hemorrhage and necrosis was seen in all cases. The neoplasms had three distinct histologic patterns: solid nests, cords or ribbons; and an alveolar pattern with rosettes. In all three groups there was fibrovascular stroma that was hyalinized, mineralized, and thick in some places. The neoplastic cells were relatively uniform, polygonal to spindle-shaped, with eosinophilic, granular cytoplasm and vesiculated nuclei. Mitotic activity varied among the three groups. Argyrophilia was seen in all specimens stained with modified Grimelius stain. Metastasis occurred in 14 of 15 dogs (93.3%); the peritoneal wall and adjoining lymph nodes were the most common sites.

In a study of 110 primary hepatic neoplasms in dogs, 55 hepatocellular carcinomas and two combined hepatocellular and cholangiocarcinomas were diagnosed. These neoplasms were classified into the following 11 groups based on histo-architectural pattern: trabecular, peliod, cobblestone, peritheliomatous, anaplastic, pseudoglandular, pleomorphic, scirrhous, clear cell, solid, and combined hepatocellular and cholangiocarcinoma. The neoplastic hepatocytes varied from almost normal to highly anaplastic spindle cells. Pleomorphic and giant cells were common in some groups, rare or absent in others. Metastasis was found in 61% (35 of 57), in contrast to a much higher percent in man, indicating the possibility of a different pathogenesis in the dog.