A morphologic and immunocytochemical study of hepatic neoplasms in cats.

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.     

Hepatobiliary neuroendocrine carcinoma in cats: a clinicopathologic, immunohistochemical, and ultrastructural study of 17 cases

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.     

Choledochotomy and primary repair of extrahepatic biliary duct rupture in seven dogs and two cats

Objective : To report clinical findings and outcome in dogs and cats undergoing choledochotomy or primary repair of extrahepatic biliary duct rupture. Methods : Retrospective study of dogs (n=7) and cats (n=2) that had choledochotomy or primary bile duct repair. Results : Extrahepatic biliary obstruction was confirmed at surgery in all cases. The underlying cause in four dogs and both cats was choledocholithiasis, two dogs had gall bladder mucocoeles with associated bile duct rupture, and one dog had inspissated bile obstructing the bile duct secondary to gall bladder carcinoid tumour. Three dogs and both cats had choledochotomies performed to relieve extrahepatic biliary obstruction, and four dogs with bile duct rupture underwent primary repair of the defect. One dog with a bile duct rupture was re‐explored four days postoperatively and had suffered dehiscence of the repair; this rupture was re‐repaired. All animals were discharged from the hospital, and did not have clinical recurrence of extrahepatic biliary obstruction. Clinical Significance : Choledochotomy and primary repair of extrahepatic biliary duct rupture were associated with low perioperative morbidity and no mortality in this small cohort of cases. These techniques are reasonable options either alone or in conjunction with other procedures when bile duct patency cannot be re‐established by catheterisation or bile duct discontinuity exists.     

Cholangiocarcinoma in a 4-month-old double yellow-cheeked Amazon parrot (Amazona autumnalis)

A cholangiocarcinoma was diagnosed in a 4-month-old double yellow-cheeked Amazon parrot (Amazona autumnalis). Histologically, neoplastic cells effaced hepatocellular architecture. Ultrastructurally, variably dilated bile ductules were lined by simple cuboidal to low columnar ciliated epithelial cells with sparse cellular organelles and prominent junctional complexes. Elongated single cilia arising from basal bodies in the apical cytoplasm were occasionally evident. The presence of such a neoplasm in a 4-month-old parrot is extremely unusual.     

Innervation of Extrahepatic Biliary Tract,With Special Reference to the Direct Bidirectional Neural Connections of the Gall Bladder,Sphincter of Oddi and Duodenum in Suncus murinus,in Whole‐Mount Immunohistochemical Study

Sphincter of Oddi dysfunction is one of the most important symptoms in post‐cholecystectomy syndrome. Using either electrical or mechanical stimulation and retrogradely transported neuronal dyes, it has been demonstrated that there are direct neural pathways connecting gall bladder and the sphincter of Oddi in the Australian opossum and the golden hamster. In the present study, we employed whole‐mount immunohistochemistry staining to observe and verify that there are two different plexuses of the extrahepatic biliary tract in Suncus murinus. One, named Pathway One, showed a fine, irregular but dense network plexus that ran adhesively and resided on/in the extrahepatic biliary tract wall, and the plexus extended into the intrahepatic area. On the other hand, named Pathway Two, exhibiting simple, thicker and straight neural bundles, ran parallel to the surface of the extrahepatic biliary tract and passed between the gall bladder and duodenum, but did not give off any branches to the liver. Pathway Two was considered to involve direct bidirectional neural connections between the duodenum and the biliary tract system. For the first time, morphologically, we demonstrated direct neural connections between gall bladder and duodenum in S. murinus. Malfunction of the sphincter of Oddi may be caused by injury of the direct neural pathways between gall bladder and duodenum by cholecystectomy. From the viewpoint of preserving the function of the major duodenal papilla and common bile duct, we emphasize the importance of avoiding kocherization of the common bile duct so as to preserve the direct neural connections between gall bladder and sphincter of Oddi.     

Congenital dilatation of the bile ducts (Caroli's disease) in young dogs

We describe 8 young dogs with congenital dilatation of the intra- and extrahepatic bile ducts and diffuse cystic kidney disease, compatible with Caroli's disease in humans. The dogs were referred between 1980 and 2000 because of chronic disease at an age of 6 months to 3 years. These dogs included 3 Collies, 2 Frisian Stabyhouns, 2 Jack Russell Terriers, and 1 mixed-breed dog. The most common signs were vomiting (6/6), polyuria and polydipsia (4/6), and anorexia (4/6). Ascites was a common finding (4/6). Clinicopathologic abnormalities were available for 6 dogs. All had increased plasma alkaline phosphatase activity and fasting bile acids: increased alanine aminotransferase activity and urea and creatinine concentrations were present in 50% of dogs. Ultrasound examination of the liver showed severely dilated bile ducts without evidence of obstruction, and calcification in all cases but 1. Postmortem examination revealed severe dilatation of the larger intra- and extrahepatic bile ducts. The common bile duct and gall bladder were normal, and the bile system was patent. The ducts contained a clear viscid fluid often with calcified material. Microscopically, marked portal fibrosis was present, often with abnormally structured dilated bile ducts lined with columnar or cuboid epithelium and regularly small calcifications. The lesion was complicated by ascending cholangitis in 1 dog. The kidneys showed marked cortical and medullary fibrosis with a diffuse radial cystic pattern; only slight renal fibrosis was found in the oldest dog. Seven dogs were euthanized without treatment; the oldest dog was alive and well 5 months after diagnosis and was maintained on a protein-restricted diet.     

Deformed liver with prominent proliferation of bile ducts in a pig

A deformed liver characterized by remarkable ductular proliferation was encountered in a 6-month-old pig and examined histopathologically. The most conspicuous histopathologic change was a mild to severe ductular proliferation in the interlobular areas without any degenerative changes of cholangiolar epithelial cells or hepatocytes. Fibrotic changes and reconstruction of the lobule were not found. Morphological evidence of intrahepatic and extrahepatic cholestasis was lacking. Other characteristics were deformity with displacement of the gall bladder, irregular shape and size of lobules, and structural abnormality of large-sized vessels. The severe ductular proliferation was considered to be due to structural malformations of the excretion channel of bile.     

Multiple hepatic peribiliary cysts in a young pig

Histopathologic features of hepatic peribiliary cysts were described in a young slaughtered pig. The animal was an apparently healthy 6-month-old pig of mixed breed. Macroscopically, all lobes of the liver contained numerous cysts of varying size containing serous fluid in all lobes. Histopathologically, the cysts were located mainly around the large bile duct and in the connective tissue of the portal tracts. Within serial sections, these cysts were assumed to be solitary or multilocular, but they were separated from the bile duct. The cysts were lined by a single layer of columnar, cuboidal, and flattened epithelial cells. Occasionally, goblet cells were observed. The epithelial cells were stained with periodic acid-Schiff/alcian blue and high-iron diamine/alcian blue, indicating the presence of neutral mucin, sialomucin, and sulfomucin. Grimalius' method revealed the presence of endocrine cells in the lining epithelium. There was no bile pigment in the cysts by the Hall method.     

Extrahepatic Biliary Tract in Chinchilla (Chinchilla laniger,Molina)

The aim of the study was the macromorphological analysis of extrahepatic biliary tract in chinchilla (Chinchilla laniger Molina). Bile ducts, the gall bladder and portal vein were injected with coloured latex. Using the technique of dissection, bile ducts were isolated from the liver lobes. It was found that the cystic duct in this species is rarely single. Hepatic ducts form a system of multiple anastomosing structures running in the hepatoduodenal ligament. Many bile duct openings were observed in the duodenal papilla. The results confirm wide variations of the biliary tract in mammals and may be important for comparative analysis of the morphological differentiation of these structures in small mammals.     

Duplex gall bladder associated with choledocholithiasis, cholecystitis, gall bladder rupture and septic peritonitis in a cat

A 10-year-old cat was presented with a history of inappetence, pyrexia and weight loss. Clinical investigations showed anaemia, hyperbilirubinaemia, septic peritonitis and a double gall bladder with choleliths in an extrahepatic duct. Initial medical stabilisation was performed. At laparotomy, a duplex gall bladder with two separate cystic ducts was identified. The left gall bladder was thickened and had ruptured at the apex. Multiple choleliths were identified in the left cystic duct. The right gall bladder and cystic duct were grossly normal. The ruptured gall bladder was repaired, the gallstones were removed via a choledochotomy of the left cystic duct and a choledochoduodenostomy was created from the dilated left cystic duct. The cat remained depressed and anorexic, and it was euthanased 72 hours postoperatively at the owners' request. This is the first ante-mortem investigation of extrahepatic biliary disease associated with gall bladder duplication in the cat.     

Fibrosing cholehepatitis in broiler chickens induced by bile duct ligations or inoculation of Clostridium perfringens.

The pathogenesis of fibrosing hepatitis causing condemnations in broiler chickens was investigated. Three to four week old broilers were inoculated via the hepatoenteric bile duct with saline washed suspensions of Clostridium perfringens (10(7) and 10(8) organisms). In another group of broilers, both bile ducts were ligated. The sequential development of liver and gall bladder lesions was studied at intervals ranging from 1-28 days postsurgery. The lesions were similar in both experiments in that the liver became mottled and swollen by five to seven days. Fibrinoid necrosis, heterophil and lymphocyte infiltration, bile duct hyperplasia and fibrosis with reticulin fiber proliferation occurred. By 14-17 days, the liver was enlarged, tan colored and firm with red and white foci. By 28 days, bile duct proliferation and fibrosis were massive with only a few hepatocytes remaining. The liver capsule was not involved. Jaundice was not present but the birds with ligated bile ducts excreted intensely yellow stained droppings after six to seven days. The gall bladder in inoculated birds was edematous and distended with flocculent or inspissated material. Clostridium perfringens was reisolated from gall bladder and/or liver of inoculated birds up to 28 days postsurgery. It is suggested that this organism plays a role in the pathogenesis of fibrosing cholehepatitis by inducing septic intrahepatic cholestasis.     

Testicular atrophy after bile duct ligation in chickens

Testicular atrophy associated with biliary obstruction in chickens, produced by the ligation of both extrahepatic bile ducts, was examined grossly, histologically, immunohistochemically, and ultrastructurally. Grossly, reduction in testicular size and volume was evident in chickens that underwent bile duct ligation (BDL). Histologically, there was marked reduction in tubular diameter, peritubular fibrosis, loss of spermatogenic cells, and tubules lined only by Sertoli cells. In addition, Leydig cells, which accumulated in the interstitium of the testes, contained numerous large lipid vacuoles, as determined by electron microscopy. These features suggest that BDL in chickens causes hypogonadism and low serum testosterone.     

Equine placental teratoma

The placenta from a 300-day-gestational age, female, Arabian equine fetus was examined. Multifocal to coalescing, 0.5- to 4-cm-diameter, white, smooth nodules covered 50% of the placenta. Microscopic evaluation of the nodules revealed undifferentiated germ cells and a haphazard arrangement of immature, mesenchymal stroma, cartilage, squamous cornifying epithelium, scattered ducts and secretory acini lined by cuboidal to columnar epithelium, and mineralized foci. No umbilicus, arrangement about an axial skeleton, or organized polarity of structures was present. The lesion was diagnosed as a placental teratoma, a lesion not reported in species other than man.     

In situ complex adenocarcinoma on the femoral part of the hindlimb in an Asian Leaf Turtle (Cyclemys dentata)

A heterotopic in situ complex adenocarcinoma developing on the hindlimb is reported for the first time from an Asian Leaf Turtle (Cyclemys dentata). The tumour mechanically hampered the movement of the animal. The turtle refused to eat and consequently developed a poor condition. Histopathology of the tumour revealed all characteristics of a well-differentiated adenocarcinoma originating from apocrine gland-like tissue: the irregular, tubular structures varying in size were generally lined by two to four layers of cuboidal to columnar neoplastic epithelial cells. Claudin-5, pancytokeratin, cytokeratin, vimentin, α-SMA and Ki-67 immunohistochemical antibodies were employed for characterising the tumour. The diagnosis was a complex adenocarcinoma originating from apocrine gland-like tissue in a turtle.     

Extrahepatic biliary tract obstruction in two ferrets (Mustela putorius furo)

This report describes extrahepatic bile duct obstruction in two ferrets, which were presented with anorexia, chronic weight loss and general weakness. Physical examination revealed lethargy, cachexia, dehydration, abdominal pain and icterus. Marked haematological, serum chemistry and urinalysis abnormalities included hyperbilirubinaemia (65·5 and 114·2 μmol/L), high concentrations of alanine transaminase (1327·53 and 2578·88 IU/L) and biluribinuria. Abdominal ultrasonography revealed thickening of the bile duct together with the gall bladder wall. The common bile duct was obviously distended. Choledochotomy revealed inspissated bile with fragile green gelatinous plugs that was removed to allow the bile to flow into the duodenum. Cytology and culture of the biliary tract contents were negative for bacteria. Laboratory analyses of biliary plugs showed presence of only protein substances, without detectable mineral composition. Histopathological examination of the liver showed diffuse steatosis and non-specific cholangiohepatitis in both cases.     

Gall bladder rupture associated with cholecystitis in a domestic ferret (Mustela putorius)

A six‐year‐old neutered female albino ferret was presented with an acute episode of lethargy and anorexia. Clinical examination revealed marked cranial abdominal pain. A severe neutrophilic leukocytosis was present. Abdominal ultrasound was consistent with a diffuse peritonitis and severe bile duct inflammation. Cytology of the abdominal effusion revealed bile peritonitis. An exploratory laparotomy was performed and the gall bladder appeared inflamed with multiple perforations. A cholecystectomy was performed. The ferret recovered without complication. Bacteriological culture of the bile and gall bladder yielded a pure growth of Pseudomonas aeruginosa. Histopathological analysis of the gall bladder and liver was consistent with a marked cholecystitis and cholangiohepatitis. On the basis of sensitivity testing, the ferret was treated with marbofloxacin for one month. No complications or reoccurrence were seen up to 1 year after the diagnosis. To the author's knowledge, this is the first report of bile peritonitis secondary to gall bladder rupture in a ferret.     

Light and electron microscopic study of the thoracic respiratory air sacs of the fowl

There are conflicting reports in the existing literature on the nature of the epithelial lining and the content of the supporting connective tissue of the respiratory air sacs of birds. The present study describes the light and electron microscopic structure of the thoracic air sacs of the fowl. A simple squamous epithelium lined the greater part of the thoracic air sacs. The squamous cells characteristically contained vesicles filled with lamellar or myelinoid material. Localized areas of cuboidal to columnar ciliated epithelium were randomly distributed and often associated with underlying blood vessels. Isolated ciliated cells first appeared on squamous or low cuboidal cells and increased in frequency as the cells became taller. Occasional basal and goblet cells were seen between the ciliated columnar cells. A fibrous connective tissue stroma supported the epithelium. Fine elastic fibres were particularly prevalent immediately below the epithelium. Isolated smooth muscle myocytes were present in the connective tissue stroma. A sheet of smooth muscle extended some distance into the membrane from the attachment of the latter to the body wall. Numerous small blood vessels, lymphatics and occasional nerve bundles were observed in the stroma.     

Spontaneous cholangiofibrosis adjacent to a dilated common bile duct with intestinal metaplasia in a Royal College of Surgeons rat

A 130-week-old male Royal College of Surgeons rat kept as a non-treated animal in a long-term animal study presented with a mass in the hepatic portal region that adhered to a dilated common bile duct and the duodenum. Histopathologically, the solitary mass showed expansive growth with no apparent compression and continued to dilate the common bile duct, which had a hyperplastic epithelium with intestinal metaplasia. The mass mainly consisted of small to large dilated and/or tortuous ducts with abundant dense connective tissue and many inflammatory cells. The single-layer lining epithelium of the duct changed from cuboidal to columnar. Immunohistochemically, the lining cells were positive for cytokeratin 7, cytokeratin 19, and OV-6, which are bile duct markers. Based on the pathological characteristics, the rat was diagnosed as spontaneous cholangiofibrosis adjacent to a dilated common bile duct with intestinal metaplasia.     

Canine ovarian neoplasms: a clinicopathologic study of 71 cases, including histology of 12 granulosa cell tumors

In a retrospective study of 71 primary ovarian tumors in the dog, epithelial tumors (46%) were more common than sex cord stromal (34%) and germ cell tumors (20%). There were more adenocarcinomas (64%) than adenomas. Sex cord stromal tumors were equally divided into Sertoli-Leydig (12/24) and granulosa cell tumors (12/24). There were equal numbers (7/14) of dysgerminomas and teratomas among the germ cell tumors. Most teratomas (6/7) were malignant. Most granulosa cell tumors were solid; two were mostly cystic. Patterns included sheets of round and ovoid to spindle-shaped cells separated by thin, fibrovascular stroma; neoplastic cells formed rosettes or Call-Exner bodies. In some areas, neoplastic cells were in cords or columns and formed cyst-like structures. Four granulosa cell tumors were macrofollicular, having cysts lined with granulosa cells. Median ages of dogs with different ovarian neoplasms were similar; all were more than 10 years old, except the dogs with teratoma (mean age, 4 years). Most neoplasms were unilateral (84%), except the Sertoli-Leydig cell tumors, many of which were bilateral (36%). Size of ovarian neoplasms varied (2 cm3 to 15,000 cm3). Twenty-nine percent of neoplasms metastasized; adenocarcinomas (48%) and malignant teratomas (50%) had the highest rates, and distant metastasis was more common in malignant teratoma. Endometrial hyperplasia was in 67% of the dogs; it was most common in dogs with sex cord stromal tumors (95%). Uterine malignancy was not seen in dogs with granulosa cell tumors, although hyperplasia endometrium was in all dogs with this tumor. Cysts in the contralateral ovaries were most common in dogs with sex cord stromal tumors.     

Treatment and long-term follow-up of extrahepatic biliary obstruction with bilirubin cholelithiasis in a Somali cat with pyruvate kinase deficiency

A 2-year-old female neutered Somali cat was presented with vomiting and acute onset jaundice 1 year after diagnosis of pyruvate kinase (PK) deficiency. Diagnostic investigations revealed a moderate regenerative haemolytic anaemia, severe hyperbilirubinaemia and elevated liver enzymes. Ultrasonography revealed marked distension of the gall bladder and common bile duct (CBD), consistent with extrahepatic biliary obstruction (EHBO). At cholecystotomy, the gall bladder contained purulent material, and two obstructive choleliths were removed from the CBD by choledochotomy. The cat recovered from surgery uneventfully, and serum liver enzymes and bilirubin normalised within 10 days. Postoperative treatment consisted of cephalexin, metronidazole and ursodeoxycholic acid (UDCA). Bacterial culture of the gall bladder contents yielded a pure growth of an Actinomyces species. Cholelith analysis revealed that they consisted of 100% bilirubin. Antibiotic treatment was stopped 4 weeks after surgery but UDCA was continued indefinitely. The cat remains clinically well with no recurrence of cholelithiasis 20 months after initial presentation. This is the first report of successful treatment and long-term follow-up of a cat with EHBO due to bilirubin cholelithiasis in association with PK deficiency-induced chronic haemolysis.