Inflammatory responses to Opisthorchis viverrini infection in animal models: A comparison between susceptible and nonsusceptible hosts in different anatomical locations.

Background: Inflammation caused by Opisthorchis viverrini infection increases the risk of cholangitis, cholecystitis, and leads to bile duct cancer (cholangiocarcinoma or CCA). However, only certain infected individuals are susceptible to CCA, suggesting the involvement of host factors in cancer development. In addition, there are reports indicating differences in the locations of CCA. Aim: This study aims to investigate cellular inflammatory responses in the common bile duct (CB), intrahepatic bile duct (IHB), and gallbladder (GB) in susceptible and non-susceptible hosts following O. viverrini infection. Methods: Thirty Syrian golden hamsters (a susceptible host) and 30 BALB/c mice (a non-susceptible host) infected with O. viverrini were studied at six time points (five animals per group). Histopathological evaluations were conducted on samples from the IHB, CB, and GB. Inflammatory cell infiltration was quantitatively assessed and compared between groups and time points. Statistical analysis was performed using one-way ANOVA, with a significance level of p < 0.05. Results: Inflammation was significantly more pronounced in the IHB compared to the other two biliary locations. In comparison between susceptible and non-susceptible hosts, the intensity of inflammation was higher in the OV+H group than in the OV+M group (p < 0.05). Conclusion: This study highlights the association between host response to inflammation, tissue location, and host susceptibility, with the IHB showing particular susceptibility to inflammation and pathological changes. These findings contribute to our understanding of the increased risk of CCA in susceptible hosts.

Histological and immunohistochemical features of carcinomas with pulmonary involvement in cattle.

Primary pulmonary neoplasms in cattle are rare. There are few studies on the pathological findings of these neoplasms in this species. This study aimed to describe the histological and immunohistochemical findings of primary and metastatic pulmonary carcinomas in cattle. We conducted a retrospective study of 19 cases of epithelial neoplasms with pulmonary involvement. Histologically, most of the neoplasms were classified as primary pulmonary neoplasms, including different adenocarcinoma subtypes (4/19, 21%) and adenosquamous carcinomas (3/19, 16%), followed by squamous cell carcinoma (6/19, 32%), metastatic uterine adenocarcinoma (4/19, 21%), metastatic hepatocellular carcinoma (1/19, 5%), and metastatic cholangiocarcinoma (1/19, 5%). By immunohistochemistry, all neoplasms were positive for pancytokeratin, and 4/19 (21%) were positive for vimentin. Primary pulmonary neoplasms had immunoreactivity for thyroid transcription factor-1 (6/7), while only 2 of these cases were positive for napsin A. All cases with squamous differentiation (9/9) had immunoreactivity for cytokeratin (CK) 5/6, while only 7 of these cases were positive for p40. CK20, CK7, and CK8/18 showed varied immunoreactivity in the primary and metastatic pulmonary carcinomas but were important markers to confirm the diagnosis of primary mucinous adenocarcinoma and metastatic cholangiocarcinoma. HepPar-1 was only positive in the metastatic hepatocellular carcinoma. The limited number of cases of metastatic uterine adenocarcinomas in this study precluded identification of a specific immunophenotype for this tumor. Immunohistochemistry proved to be an important tool to confirm the proper classification of these neoplasms.

Cystadenocarcinoma of the intrahepatic bile duct in a dog.

A 14-year-old spayed female Shih-Tzu was referred to the Veterinary Medical Teaching Hospital of Konkuk University for evaluation of an abdominal mass. In diagnostic imaging, two large cystic masses were identified. The affected liver lobes were surgically resected, and the specimens were submitted for histopathological evaluation and immunohistochemical staining. The two cystic lesions were diagnosed as biliary cystadenocarcinoma (BCAC). Recurrence and regional invasion were identified on ultrasonography 36 days postoperatively. The patient died on postoperative day 271. To the best of our knowledge, previously reported case studies of BCAC in dogs presented limited clinical information. In this report, we present a detailed picture comprising a range of clinical information and histopathological examination of BCAC in a dog.

Clinical, diagnostic, and pathologic features and surgical outcomes of combined hepatocellular-cholangiocarcinoma in dogs: 14 cases (2009-2021).

OBJECTIVE: To describe the clinical, diagnostic, and pathological features and postoperative prognosis of canine combined hepatocellular-cholangiocarcinoma (cHCC-CCA). ANIMALS: 14 privately owned dogs that underwent surgical treatment. PROCEDURES: The medical records, including signalment, clinical signs, blood test, urine analysis, computed tomography (CT) findings, intraoperative findings, and pathological findings, were retrospectively reviewed in the dogs with cHCC-CCA. RESULTS: Of 306 dogs that underwent surgical removal of hepatic masses, 14 dogs (4.6%) were pathologically confirmed to have cHCC-CCA. Median age and body weight were 11.3 years and 7.3 kg, respectively. There were no specific clinicopathological findings for cHCC-CCA. CT revealed a massive hepatic mass in all dogs and the inclusion of cyst-like lesions within the mass in 13 dogs. Intrahepatic metastases were found at time of surgery in 2 dogs (14.3%). Of the residual 12 dogs, 1 dog showed postoperative formation of intrahepatic nodules suggestive of metastases and another had intrahepatic and pulmonary nodules and a forelimb skin mass, suggesting postoperative metastases. The median survival time of the patients with cHCC-CCA was 700 days (range, 10 to 869 days) after surgery. CLINICAL RELEVANCE: To the authors' knowledge, this is the first study to describe the clinical, diagnostic, and pathological features and postoperative prognosis of canine cHCC-CCA. The clinical and diagnostic features of canine cHCC-CCA might be more similar to those of HCC rather than to those of CCA, but the preoperative diagnosis differentiating between HCC and cHCC-CCA was challenging. Our study suggests that the postoperative prognosis of canine patients with cHCC-CCA is similar to that of dogs with HCC.

Metastatic cholangiocarcinoma mimicking tuberculosis in a cow.

Here we describe a metastatic hepatic cholangiocarcinoma (cholangiocellular carcinoma) in a 14-y-old Beefmaster cow that was euthanized because of depression and progressive weight loss. Gross changes included coalescing, white-to-yellow, firm-to-hard nodules with central areas of necrosis and mineralization that effaced much of the hepatic parenchyma, omentum, mesentery, ruminal serosa, and diaphragm. A fresh sample of a hepatic nodule was submitted for a modified acid-fast (MAF) stain during autopsy to rule out tuberculosis. The MAF stain was inconclusive, and the sample was subsequently submitted for a PCR assay for Mycobacterium spp. Histologically, all nodules consisted of a neoplastic proliferation of epithelial cells surrounded by extensive areas of desmoplasia, consistent with a metastatic cholangiocarcinoma. PCR for Mycobacterium spp. was negative. Although the histologic diagnosis in our case was metastatic hepatic cholangiocarcinoma, gross changes were strikingly similar to those described in cases of tuberculosis, highlighting the need to remain vigilant in the identification of zoonotic and suspected foreign animal diseases during autopsy to protect human health.

Aberrant Expression of Cell Cycle Regulator 14-3-3-σ and E-Cadherin in a Metastatic Cholangiocarcinoma in a Vervet Monkey (Chlorocebus pygerythrus).

We present a unique case of metastatic cholangiocarcinoma with concurrent abdominal cestodiasis in an African green monkey (Chlorocebus pygerythrus) that presented with respiratory insufficiency and abdominal discomfort. There were multiple white-grey masses in the liver and colonic serosa alongside intra-abdominal parasitic cysts. Histopathologically, the liver masses were composed of poorly-differentiated epithelial cells that formed densely cellular solid areas and trabeculae. The neoplastic cells were strongly immunopositive for CK7 but negative for Hep-Par1 antigen, which confirmed a diagnosis of cholangiocarcinoma. Interestingly, there was strong and diffuse neoexpression in the tumour of the cell cycle regulator 14-3-3σ, which is not constitutively expressed in normal liver. There was aberrantly strong expression of E-cadherin, a key cell-cell adhesion protein, in neoplastic cells with evidence of cytoplasmic internalization. This is the first immunohistochemical analysis of 14-3-3σ and E-cadherin in a liver neoplasm in an animal species and the use of these markers requires further investigation in animal liver neoplasms.

Primary hepatic neoplasms in cattle / Neoplasmas hepáticos primários de bovinos

Primary hepatic neoplasms are mostly detected in cattle as incidental findings in slaughterhouses or diagnosed at the necropsy, wherein it may be related to the cause of death. A proper characterization of primary hepatic neoplasms is essential to provide an accurate diagnosis, especially at the slaughter lines, in order to reduce erroneous condemnations. This work aimed to characterize the gross, histological, and immunohistochemical features of primary liver neoplasms detected in slaughtered cattle in Southern Brazil. Nineteen primary hepatic neoplasms were identified. Grossly, these lesions were classified according to their distribution, as focal, multifocal, or diffuse. Histologically, the shape and arrangement of the cells, as well as possible malignant features were evaluated. Immunohistochemistry (IHC) was also performed for biliary epithelium (anti-CK7) and hepatocytes (anti-Hep Par-1) markers. Hepatocellular carcinoma (84.2%) was the most frequently detected hepatic neoplasm, followed by cholangiocarcinoma (15.8%), and these were only identified in adult cows. Hepatocellular carcinomas occurred as solitary masses or multifocal nodules, which on the cut surface were often green. Cholangiocarcinomas occurred as multifocal nodules, occasionally showing an umbilicated appearance. Histologically, hepatocellular carcinomas had mostly trabecular and solid patterns, while cholangiocarcinomas presented mostly a solid arrangement. Upon IHC, all hepatocellular carcinomas were immunolabeled for anti-Hep Par-1, ranging from mild (25%), moderate (31.2%) to marked (43.7%), while immunolabeling for anti-CK7 was detected only in one case of cholangiocarcinoma.(AU)

Os neoplasmas hepáticos primários são detectados em bovinos principalmente como achados incidentais em matadouros ou diagnosticados na necropsia, quando podem estar relacionados à causa da morte. A caracterização adequada dos tumores hepáticos primários é essencial para obter diagnósticos precisos, especialmente nas linhas de abate, com o propósito de reduzir condenações errôneas. Este trabalho teve o objetivo de determinar as características macroscópicas, histológicas e imuno-histoquímicas dos neoplasmas primários do fígado de bovinos abatidos em um matadouro-frigorífico no Sul do Brasil. Dezenove neoplasias hepáticas primárias foram identificadas. Macroscopicamente, os tumores hepáticos foram classificados de acordo com sua distribuição, como focais, multifocais ou difusos. Histologicamente, a forma e o arranjo das células e possíveis características malignas foram avaliados. Também foi realizada imuno-histoquímica (IHQ) para marcadores de epitélio biliar (anti-CK7) e hepatócitos (anti-Hep Par-1). O carcinoma hepatocelular (84,2%) foi o neoplasma hepático mais frequentemente detectado, seguido pelo colangiocarcinoma (15,8%). Esses tumores foram identificados apenas em vacas adultas. Os carcinomas hepatocelulares eram vistos como massas solitárias ou nódulos multifocais que na superfície de corte geralmente eram esverdeados. Os colangiocarcinomas foram observados como nódulos multifocais, ocasionalmente com aspecto umbilicado. Histologicamente, os padrões mais observados nos carcinomas hepatocelulares foram trabeculares e sólidos, enquanto nos colangiocarcinomas o arranjo sólido foi o mais frequente. Na IHQ, todos os carcinomas hepatocelulares foram marcados por anti-Hep Par-1, com marcação que variou de leve (25%), moderada (31,2%) a acentuada (43,7%); imunomarcação para anti-CK7 foi detectada em apenas um caso de colangiocarcinoma.(AU)

Contrast-enhanced ultrasound features of malignant focal liver masses in dogs.

A total of 185 cases (150 retrospectively and 35 prospectively) of malignant liver masses were collected. In the retrospectively collected cases hyperenhancement during wash-in was the most common feature in HCCs but there was a high percentage of cases showing no enhancement or hypo/isoenhancement. ICCs displayed a large variety of contrast enhancement patterns and, although statically significant differences between ICCs and HCCs were evident, no clear distinction between these two pathologies was possible based only on their CEUS appearance. Sarcomas displayed all the possible degrees of wash-in enhancement with non-enhancing being the most common appearance. Metastases displayed all the possible contrast-enhancement patterns, with the most common being hyperenhancement in the wash-in phase followed by hypoenhancement in the wash-out phase. A decision tree was developed based on the features of the retrospectively selected cases. Based on the developed decision tree 27/35 prospectively collected cases were correctly classified. Even if some significant differences among groups were evident, all the histotypes displayed all the possible patterns of contrast enhancement, and, therefore, the differentiation of liver masses in dogs based only on their CEUS features is not feasible and, therefore, cytology or histopathology is required.

Pathological and immunohistochemical aspects of primary hepatobiliary neoplasms in cats / Aspectos patológicos e imuno-histoquímicos de neoplasias hepatobiliares primárias em gatos

Primary hepatobiliary neoplasms (PHN) are uncommon in cats, and originate in hepatocytes, intra- and extrahepatic bile ducts, mesenchymal cells, and cells of neuroendocrine origin. The aim of this study was to determine the frequency of PHN in cats diagnosed in the metropolitan region of Porto Alegre (RS), Brazil, for a period of 17 years, determining their epidemiological, anatomopathological and immunohistochemical aspects. Necropsy reports of 2.090 cats were analyzed, 125 were diagnosed with primary hepatobiliary diseases, of which 15 were cases of PHN, representing 12% of the specific hepatobiliary conditions and 0.7% of the necropsies. All PHN were malignant, of which 93.3% had epithelial origin and 6.7% presented mesenchymal origin. Cholangiocarcinoma was the most commonly diagnosed neoplasm, followed by hepatocellular carcinoma and hemangiosarcoma. In general, cats with no defined breed were the most affected. Concerning sex, 60% were females and 40% males. Age ranged from five to 18 years, with a mean age of 10.5 years (median of ten years). Grossly, cholangiocarcinoma and hemangiosarcoma were multinodular and hepatocellular carcinoma was massive. Microscopically, cholangiocarcinomas were arranged in acini and ducts, whereas hepatocellular carcinomas were arranged in solid sheets or trabeculae. On immunohistochemistry, cholangiocarcinomas, hepatocellular carcinomas, and hemangiosarcomas were positive for the antibodies CK 7, Hep Par-1, and vimentin and von Willebrand factor, respectively.(AU)

Neoplasias hepatobiliares primárias (NHP) são incomuns em gatos e se originam de hepatócitos, células dos ductos biliares intra e extra-hepáticos, células mesenquimais e ainda células de origem neuroendócrina. O objetivo do trabalho foi determinar a frequência das NHP em gatos diagnosticados na Região Metropolitana de Porto Alegre, no período de 17 anos, abordando seus aspectos epidemiológicos, anatomopatológicos e imuno-histoquímicos (IHQ). Foram analisados os laudos de necropsia de 2.090 gatos sendo que 125 foram diagnosticados com doenças hepatobiliares primárias, destes 15 foram casos de NHP, representando 12% das condições hepatobiliares específicas e 0,7% do total de necropsias. Todos os diagnósticos de NHP eram malignos, destes 93,3% apresentaram origem epitelial e 6,7% mesenquimal. Colangiocarcinoma foi a neoplasia mais diagnosticada, seguido do carcinoma hepatocelular e hemangiossarcoma. De uma maneira geral, os gatos sem raça definida foram os mais acometidos. Em relação ao sexo 60% eram fêmeas e 40% machos. A idade variou de cinco a 18 anos, com a idade média de 10,5 anos (mediana de 10 anos). Macroscopicamente o colangiocarcinoma e hemangiossarcoma eram multinodulares, e o carcinoma hepatocelular, maciço. À histologia, houve predomínio do arranjo acinar e ductal nos colangiocarcinomas e sólido, no carcinoma hepatocelular. Na IHQ os colangiocarcinomas foram reativos para CK 7, carcinoma hepatocelular para Hep Par-1 e hemangiossarcoma para vimentina e fator de von Willebrand.(AU)

Cholangiocarcinoma in a Free-Ranging Eurasian Brown Bear (Ursus arctos arctos) from Northern Spain.

A hepatic cholangiocarcinoma with metastases in the gallbladder, left elbow joint, adrenal glands, and lungs was observed in a female 21-yr-old free-ranging Eurasian brown bear (Ursus arctos arctos) found in the Principality of Asturias (northern Spain). Gross and histopathologic findings are described.

Combined hepatocellular-cholangiocarcinoma in a cow.

We examined a 10-year-old cow in which about half of the liver was displaced by malignant tissue consisting of hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC). Cytokeratin (CK) 18 and 7 were expressed in the latter. Metastasis was present in the hepatic, pancreaticoduodenal and mediastinal lymph nodes, where malignant cells had hepatocellular features, but more pleomorphic and atypical than in the primary lesion. Areas composed solely of CC cells or less-differentiated HCC cells were observed. In contrast, well-differentiated HCC cells were almost always admixed with the other two types, and may have had the ability to transform into CC cells and to dedifferentiate into less-differentiated cells. This report suggests that CK18 is an excellent marker for biliary differentiation in cattle.

Hypercalcemia of Malignancy in a Dog Diagnosed With Cholangiocellular Carcinoma.

A 4-year-old, neutered male Golden Retriever was presented with a 1-week history of weight loss, polyuria, and polydipsia. The diagnostic workup showed an increased ionized calcium concentration, mild increase in serum creatinine and urea concentration, and severe hyperlipasemia. A complete abdominal ultrasound revealed multiple hepatic nodules. A cytological diagnosis of malignant epithelial neoplasia, highly suggestive of bile duct adenocarcinoma was made. In order to confirm the presumptive diagnosis of hypercalcemia of malignancy due to the presence of a hepatic neoplasia, serum parathormone-related peptide concentration was measured, and the result revealed an increased concentration. The dog was hospitalized and received supportive treatments consisting of intravenous furosemide and fluid therapy. After ruling out lymphoma and hypoadrenocorticism, oral prednisone was initiated and ionized calcium concentration decreased gradually down to normal concentration after 7 days of hospitalization. Chemotherapy with intravenous epirubicin was initiated based on the cytological diagnosis. One month after diagnosis and due to the worsening of its clinical condition, the dog was humanely euthanized. Postmortem examination confirmed a cholangiocellular carcinoma. To our knowledge, this is the first report of malignant hypercalcemia associated with cholangiocellular carcinoma in a dog.

Neoplasmas em suínos: 37 casos / Neoplasia in swine: 37 cases

Neoplasmas em suínos são raros. Esse trabalho descreve os neoplasmas encontrados em suínos na rotina diagnóstica de um laboratório de patologia veterinária localizado na Região Central do Rio Grande do Sul. Durante um período de 49 anos, 2.266 casos de várias afecções em suínos foram encontrados, dos quais 37 (1,6%) eram neoplasmas. Em ordem decrescente de frequência, os seguintes neoplasmas foram encontrados: Linfoma (11/37), nefroblastoma (11/37), melanoma (8/37) e papiloma (2/37). Adicionalmente, um caso de cada um dos seguintes tumores foi observado: Adenoma hepatocelular, carcinoma hepatocelular, colangiocarcinoma, histiocitoma fibroso maligno e sarcoma granulocítico. O aspecto macroscópico e histológico desses tumores é descrito e a sua epidemiologia é comparada com os dados disponíveis na literatura para neoplasia suína.

Neoplasms in swine are rare. This paper describes neoplasms found in swine in the diagnostic routine of a veterinary pathology laboratory in the Central Region of Rio Grande do Sul, Brazil during a 49-year period, during which 2,266 cases of the various affections in swine were diagnosed. Of those 37 cases (1.6%) were neoplasms. In decreasing order of prevalence, the following neoplasms were found: lymphoma (11 out of 37 cases), nephroblastoma (11/37), melanoma (8/37), and papilloma (2/37). Adenoma hepatocelular, carcinoma hepatocelular, cholangiocarcinoma, malignant fibrous histiocytoma, granulocytic sarcoma were each found in one case out of the 37 cases. The gross and histological aspects of these tumors are described and their epidemiology is compared with the data available in the literature for neoplasia in swine.

Imaging diagnosis-hypoglycemia associated with cholangiocarcinoma and peritoneal carcinomatosis in a horse.

An 8-year-old Thoroughbred mare presented for decreased appetite, ataxia, and weakness. Abdominal ultrasound revealed a large volume of anechoic fluid along with multiple masses involving the spleen, liver, and diaphragm. Pleural fluid was identified via ultrasonography and thoracic radiography. Thoracic radiographs also identified pulmonary interstitial nodules, an undulant dorsal diaphragmatic margin and enlargement of tracheobronchial lymph nodes. Clinical signs of weakness and mild seizures were concurrent with hypoglycemic episodes. The final diagnosis was cholangiocarcinoma with extensive metastasis. Clinical signs of weakness, ataxia, and seizures were attributed to a paraneoplastic syndrome of tumor-associated hypoglycemia that has been infrequently reported in horses.

[Sonographic findings in two miniature goats with metastatic bile duct carcinoma]. / Sonographische Befunde bei zwei Zwergziegen mit metastasierendem Gallengangskarzinom.

This case study describes 2 miniature goats with metastatic bile duct carcinoma. The main clinical sign was a pear-shaped abdomen due to abdominal distension in case 1 and stranguria and pollakiuria in case 2. Liver enzyme activity was markedly elevated in both goats, and ultrasonographic examination showed multiple round echoic structures that were partly surrounded by a hypoechoic zone. A tentative diagnosis of liver tumour was made based on the sonographic findings, and a final diagnosis of intrahepatic bile duct carcinoma was made post mortem.

Intrahepatic cholangiocarcinoma in a captive meerkat (Suricata suricatta).

A 9-yr-old male meerkat (Suricata suricatta) living in captivity, with a history of anorexia, lethargy, and weight loss, was examined postmortem. Physical examination revealed poor body condition, dehydration, and icteric mucous membranes. Macroscopically, white to yellowish, multinodulated masses were found protruding from the liver. These multinodular masses were also observed in all lobes of the lungs and the mediastinal lymph nodes. Microscopic examination revealed tumors with well-circumscribed, atypical proliferating cuboidal to columnar bile duct epithelial layers arranged in solid sheets and papillary patterns. The neoplastic masses were separated by dense fibrous connective tissues and invaded the normal parenchyma. Periodic acid-Schiff-positive material was occasionally found within the lumen of tubuloacinar structures. Immunohistochemical labeling revealed that neoplastic cells were intensely positive for pan-cytokeratin, but negative for vimentin. Based on the macroscopic and microscopic findings, intrahepatic cholangiocarcinoma was diagnosed. This is the first report describing cholangiocarcinoma in a meerkat.

Cholangiocarcinoma of intrahepatic bile ducts with disseminated metastases in an African lion (Panthera leo).

A cholangiocarcinoma is reported in an 18-yr-old, female African lion (Panthera leo). The primary tumor consisted of multifocal to coalescing, hepatic, white-yellow masses distributed throughout the liver lobes. Metastases were present in regional lymph nodes, peritoneal surface, and lungs. Histologically, the tumor was characterized by a tubular pattern with alcian- and periodic acid-Schiff-positive secretory material in cystic spaces. The neoplastic cells were positive to broad-spectrum cytokeratins. Histochemical and immunohistochemical stains were consistent with bile duct carcinoma. Biliary tumors arising from the gallbladder have been reported in lions. However, to the authors' knowledge, this is the first case of intrahepatic bile duct carcinoma reported in an African lion.

Combined hepatocellular-cholangiocarcinoma in a Yellow-headed Amazon (Amazona oratrix).

A 9-year-old male Yellow-headed Amazon (Amazona oratrix) with a history of anorexia and vomiting died of a liver tumor. The tumor consisted of neoplastic cells with hepatocellular and cholangiocellular differentiations and their intermingled areas. Neoplastic hepatocytes showed islands or trabecular growth with vacuolated eosinophilic cytoplasm. Cells showing biliary differentiation formed ducts or tubules lined by cytokeratin AE1/AE3-positive epithelia, accompanied by desmoplasia consisting of myofibroblasts reacting to α-smooth muscle actin and desmin. The tumor was diagnosed as a combined hepatocellular-cholangiocarcinoma, which is very rare in the avian.