Primary nonlymphoid gastrointestinal neoplasms in dogs in Rio Grande do Sul / Neoplasmas gastrointestinais primários não linfoides em cães no Rio Grande do Sul

Gastrointestinal neoplasms (GIN) are uncommon in dogs, but they mainly show malignant behavior and poor prognosis. The types of GIN in dogs and their frequency, as well as their epidemiological and histopathological characteristics were analyzed through a retrospective study of biopsies from 24.711 dogs from 2005 to 2017. Additionally, histological sections of neoplasms were subjected to immunohistochemistry (IHC) using antibodies against pancytokeratin, vimentin, smooth muscle actin, c-Kit, S-100, CD31, CD79αcy, and neuron-specific enolase. Of the total samples from dogs analyzed, 88 corresponded to GIN. Neoplasms occurred more frequently in purebred dogs (64.8%, 57/88), males (53.4%, 47/88), with a median age of 10 years. The intestine was affected by 84.1% (74/88) of the cases. Of these, the large intestine was the most affected (67.6%, 50/74). Most of the neoplasms had malignant behavior (88.6%, 78/88). Regarding the classification of neoplasms, 46.6% (41/88) of the diagnoses corresponded to epithelial, 46.6% (41/88) were mesenchymal, 5.7% (5/88) were hematopoietic, and 1.1% (1/88) was neuroendocrine. The most frequently diagnosed neoplasms were papillary adenocarcinoma (19.3%, 17/88), leiomyosarcoma (17.0%, 15/88), gastrointestinal stromal tumors (GISTs) (12.5%, 11/88), and leiomyoma (5.0%, 8/88). Adenocarcinomas were located mainly in the rectum, whereas leiomyosarcomas and GISTs developed mainly in the cecum. Epithelial neoplasms showed a greater potential for lymphatic invasion whereas mesenchymal neoplasms appeared to be more expansive with intratumoral necrosis and hemorrhage. Immunohistochemistry was found to be an important diagnostic technique for the identification of infiltrating cells in carcinomas and an indispensable technique for the definitive diagnosis of sarcomas.(AU)

Neoplasmas gastrointestinais (NGI) são pouco comuns em cães, mas possuem principalmente comportamento maligno e prognóstico reservado. Os tipos de NGI em cães e sua frequência, bem como características epidemiológicas e histopatológicas foram analisados por meio de um estudo retrospectivo dos exames de biópsias de 24.711 cães entre os anos de 2005 a 2017. Adicionalmente, cortes histológicos de NGI foram submetidos à técnica de imuno-histoquímica (IHQ), utilizando os anticorpos anti-pancitoqueratina, vimentina, actina de músculo liso, c-Kit, S-100, CD31, CD79αcy e enolase neurônio específica. Do total de cães analisados, 88 corresponderam a NGI não linfoides. Os neoplasmas ocorreram com maior frequência em cães de raça pura (64,8%, 57/88), machos (53,4%, 47/88), com mediana de idade de 10 anos. O intestino foi acometido em 84,1% dos casos (74/88). Destes, o intestino grosso foi o segmento mais afetado (67,6%, 50/74). A maior parte dos neoplasmas tinha comportamento maligno (88,6%, 78/88). Quanto à classificação, 46,6% (41/88) dos diagnósticos corresponderam a neoplasmas epiteliais, 46,6% (41/88) mesenquimais, 5,7% (5/88) hematopoiéticos e 1,1% (1/88), neuroendócrino. Os neoplasmas mais frequentemente diagnosticados foram adenocarcinoma papilar (19,3%, 17/88), leiomiossarcoma (17,0%, 15/88), tumor estromal gastrointestinal (GIST) (12,5%, 11/88) e leiomioma (12,5%, 8/88). Adenocarcinomas localizavam-se principalmente no reto, enquanto leiomiossarcoma e GISTs desenvolveram-se principalmente no ceco. Os neoplasmas epiteliais demonstraram um potencial maior de invasão linfática enquanto que os mesenquimais aparentaram ser mais expansivos, com necrose e hemorragia intratumorais. A imuno-histoquímica mostrou ser uma técnica diagnóstica importante para a identificação de células neoplásicas infiltravas no caso dos carcinomas e uma técnica indispensável para o diagnóstico definitivo de sarcomas.(AU)

Acinar cell carcinoma of exocrine pancreas in two horses.

Two horses were presented with non-specific clinical signs of several weeks' duration and were humanely destroyed due to a poor prognosis. At necropsy examination, both horses had multiple small, white nodules replacing pancreatic tissue and involving the serosal surface of the abdominal cavity, the liver and the lung. Microscopically, neoplastic cells were organized in acini and contained abundant (case 1) or sparse (horse 2) intracytoplasmic zymogen granules. Immunohistochemically, both tumours expressed amylase and pan-cytokeratin, but not insulin or neuron-specific enolase. In case 2, a low percentage of neoplastic cells expressed glucagon and synaptophysin. The presence of zymogen granules was confirmed in both cases by electron microscopy and occasional fibrillary or glucagon granules were observed in cases 1 and 2, respectively. A diagnosis of pancreatic acinar cell carcinoma was established in both horses.

Expression of claudin-4 molecule in canine exocrine pancreatic acinar cell carcinomas.

AIMS: Claudins, integral membrane proteins are components of the tight junction structures between epithelial and endothelial cells. These transmembrane proteins create a primary barrier to prevent paracellular transport of solutes, and also restrict the lateral diffusion of membrane lipids and proteins to maintain the cellular polarity. The aim of the present study was to characterise the expression pattern of claudin-4 tight junction molecule in canine normal pancreatic tissues and in the well-differentiated and poorly-differentiated pancreatic acinar cell carcinomas in canines. METHODS AND RESULTS: The necropsy samples included canine intact pancreatic tissues, and canine well-differentiated and poorly-differentiated pancreatic acinar cell carcinomas samples. Claudin-4 was detected as an intense lateral membrane labelling of acinar cells in all intact pancreatic tissues. The intact epithelial cells of the different ducts were negative for the claudin-4 molecule. All primary and secondary canine well-differentiated exocrine pancreatic acinar cell carcinoma tissues showed intense apical lateral positivity for the claudin-4 molecule. All primary and secondary poorly-differentiated pancreatic acinar cell carcinoma tissues showed diffusely the loss of claudin-4 expression. CONCLUSION: Consequently, we hypothesize that the loss of expression of claudin-4 plays a role in the progression of canine pancreatic acinar cell carcinoma and may lead to cellular detachment, disorientation and invasion of these pancreatic cancers. Furthermore, claudin-4 can be used as an immunohistochemical marker to distinguish canine well-differentiated and undifferentiated exocrine pancreatic acinar cell carcinomas.

Canine pancreatic clear acinar cell carcinoma showing an unusual mucinous differentiation.

A small solitary pancreatic nodule was identified in a 10-year-old mixed breed male dog. Microscopically, the lesion consisted of neoplastic clear acinar cells with diffuse, marked mucin production. Immunohistochemical and ultrastructural investigations confirmed the exocrine acinar origin of the tumour. The tumour was classified as a pancreatic clear acinar cell carcinoma (ACC) showing an unusual mucinous differentiation.

Expression of claudin-5 in canine pancreatic acinar cell carcinoma - An immunohistochemical study.

Claudin-5 is an endothelium-specific tight junction protein. The aim of the present study was to detect the expression pattern of this molecule in intact pancreatic tissues and in well-differentiated and poorly differentiated pancreatic acinar cell carcinomas from dogs by the use of cross-reactive humanised anticlaudin-5 antibody. The necropsy samples taken from dogs included 10 nonneoplastic pancreatic tissues, 10 well-differentiated pancreatic acinar cell carcinomas, 10 poorly differentiated pancreatic acinar cell carcinomas, 5 intrahepatic metastases of well-differentiated and 5 intrahepatic metastases of poorly differentiated acinar cell carcinomas. A strong lateral membrane claudin-5 positivity was detected in exocrine cells in all intact pancreas samples. The endocrine cells of the islets of Langerhans and the epithelial cells of the ducts were negative for claudin-5. The endothelial cells of vessels and lymphatic channels in the stroma of the intact pancreas showed strong membrane positivity for this claudin. All well-differentiated exocrine pancreas carcinomas and all poorly-differentiated pancreatic acinar cell carcinoma samples showed a diffuse loss of claudin-5 expression. The claudin-5-positive peritumoural vessels and lymphatic channels facilitated the detection of vascular invasion of the claudin-5-negative cancer cells. In liver metastasis samples, the pancreatic carcinomas were negative for claudin-5. It seems that the loss of expression of claudin-5 may lead to carcinogenesis in canine exocrine pancreatic cells.

Nasal acinic cell carcinoma in a cat.

This case report describes the clinical, magnetic resonance imaging (MRI)-related, and pathologic features of a nasal acinic cell carcinoma in a cat. A 16-year-old, castrated male, oriental shorthaired cat, weighing 3.8 kg, was presented with history of sneezing, coughing, and nasal discharge persisting several months. Evaluation by MRI revealed an heterogeneous, space-occupying lesion that filled the left nasal cavity and was diagnosed by histopathologic examination as an acinic cell carcinoma arising from a minor salivary gland of the nasal cavity. Acinic cell carcinoma is a rare tumor in veterinary medicine. The tumor is composed mainly of cells resembling serous cells of salivary glands and originates from major or minor salivary glands. Clinicians and pathologists should be aware of the occurrence of acinic cell carcinoma in the sinonasal tract and include the tumor in the differential diagnosis of feline nasal diseases.

Pancreatic acinar cell carcinoma with intracranial metastasis in a dog.

This report concerns a case of pancreatic carcinoma with widespread metastases to many organs including intracranial metastasis. An eleven-year-old, male, mixed-breed dog showed emaciation, ataxia, and multiple visible tumors within the neck. A MRI examination of the patient was conducted because of ataxia, and it was found that the intracranial invasive growth had resulted in compression of the brain stem. Necropsy was performed after the patient died. Based on gross and microscopic examination, the primary tumor cells were located in the left lobe of the pancreas and widespread metastasis was found into various organs, including the brain, lungs, liver, kidneys, tonsils, serosal surface of the esophagus, and submandibular, pulmonary hilar, mediastinal, and mesenteric lymph nodes. This case indicates that pancreatic adenocarcinoma should be included in the differential diagnosis list when cervical neck masses are detected.

Carcinoma of the submandibular salivary glands with multiple metastases in a cat.

A 9-year-old neutered male domestic shorthair cat was presented because of coughing, dysphagia, and prostration. Examination revealed firm bilateral anterocervical swellings extensively adhered to the surrounding tissues. Anisocoria with left-side miosis was also evident. X-ray and ultrasound examinations along with a fine-needle aspiration biopsy were performed. Slides were stained with May-Grünwald Giemsa, and a diagnosis of salivary gland carcinoma was made. At surgery, the tumor was found to involve both submandibular salivary glands as well as adjacent lymph nodes and surrounding tissues. The cat was euthanized and necropsy was performed. The majority of tissues and organs examined histologically, including mandibular and retropharyngeal lymph nodes, soft palate, laryngopharynx and lungs, contained neoplastic cells whose appearance was consistent with adenocarcinoma. Bilateral salivary adenocarcinoma has not previously been reported in cats, and extensive metastases are rare.

Acinic cell carcinoma in an African pygmy hedgehog (Atelerix albiventris).

A male African pygmy hedgehog (Atelerix albiventris), estimated to be 3 years old, presented with exophthalmos and fixed abduction of the right eye. Radiographic examination revealed a retrobulbar tumor in the right orbital cavity. The mass was surgically resected but recurred 3 months later and the hedgehog died. There was no gross or microscopic evidence of salivary or lacrimal gland involvement of the tumor at surgery or at necropsy. The histopathologic, immunohistochemical, and ultrastructural findings were those of acinic cell carcinoma, the origin of which was unknown. This is the first known case of acinic cell carcinoma in an African hedgehog.

Exocrine pancreatic carcinogenesis in the guppy Poecilia reticulata.

Exocrine pancreatic neoplasms developed in the guppy Poecilia reticulata following exposure to the direct-acting carcinogen methylazoxymethanol acetate (MAM-Ac). Fish 6 to 10 d old were exposed to nominal, non-toxic concentrations of 4 and 10 mg MAM-Ac l(-1) for 2 h and then transferred to carcinogen-free water for grow-out. Whole specimens were sampled monthly up to 9 mo post-exposure to follow the histologic progression of the lesions. No neoplasms occurred in 119 control specimens examined. Pancreatic acinar cell adenomas and carcinomas occurred in 42 of 243 (17%) of the specimens exposed to MAM-Ac. As in earlier studies, specimens exposed to the low MAM-Ac concentration exhibited a higher pancreatic neoplasm incidence (27.8%) than those exposed to the high concentration (7.8%). Acinar cell adenomas accounted for 27 of the 42 neoplasms. Adenomas exhibited a high degree of acinar cell differentiation and some contained foci of atypical acinar cells that were less differentiated and more basophilic than were surrounding adenoma cells. Carcinomas occurred in 15 specimens and exhibited a range of cellular patterns. Although no distant metastases were found, carcinomas tended to invade neighboring tissues and organs. The occurrence of carcinogen-induced pancreatic neoplasms in guppies strengthens the usefulness of small fish species in carcinogen testing and provides an additional model for studying pancreatic neoplasia.

A retrospective study of pancreatic tumors in slaughter cattle.

Sixteen primary pancreatic tumors were found in a retrospective study of bovine pancreatic lesions detected in slaughtered cattle. Eleven islet cell tumors and three pancreatic exocrine carcinomas were identified based on light microscopy and immunohistochemistry. Nine of 11 islet cell tumors were classified as malignant. Metastatic sites included iliac, mediastinal, hepatic, and mesenteric lymph nodes, peritoneum, mesentery, and liver. Six cows with multiple islet cell tumors also had pheochromocytomas. All 11 islet cell tumors had positive immunoreactivity to insulin and somatostatin. Three tumors also contained cells immunoreactive for glucagon and two tumors contained pancreatic polypeptide immunoreactive cells. Immunoreactivity of tumor cells in metastatic sites was similar to their respective primary tumors. All exocrine pancreatic carcinomas metastasized widely and were immunonegative for insulin, somatostatin, glucagon, and pancreatic polypeptide. No mixed endocrine-exocrine tumors were identified. None of the endocrine or exocrine tumors contained amyloid. Additional primary tumors of the bovine pancreas included one neurofibroma and one neurofibrosarcoma. Additional cases with lesions of the bovine pancreas included nodular hyperplasia in 15 cows, exocrine acinar atrophy and fibrosis in four cows (two of which also had pancreatic lithiasis), pancreatitis in one cow, peripancreatic fibrosis in two cows, pancreatic steatosis in one animal, and pancreatic hemorrhages in one cow.

Exocrine pancreatic neoplasms in the mummichog (Fundulus heteroclitus) from a creosote-contaminated site.

A high prevalence of exocrine pancreatic neoplasms occurred in mummichog, Fundulus heteroclitus, from a creosote-contaminated site in the Elizabeth River, Virginia. A total of 20 neoplasms were found in a group of about 1,300 fish obtained at this site over a 2-yr period. Of 240 fish collected during October 1991, 3.3% had pancreatic neoplasms. Adjusted total lesion prevalence for large adult fish (Size Class III: total length = 75-85 mm; Size Class IV: total length > 85 mm) was 6.7%. Pancreatic neoplasms were not observed in 234 fish collected at this site during May 1991, nor were they found in 420 fish obtained during fall 1991 from 1 uncontaminated and 6 moderately contaminated localities. Lesions involved both mesenteric and intrahepatic exocrine pancreas and ranged from well-differentiated acinar cell adenomas to poorly differentiated acinar cell carcinomas. One fish had an atypical acinar cell focus. All specimens with pancreatic neoplasms also had hepatocellular lesions. This epizootic of exocrine pancreatic neoplasia is the first to be reported in a wild fish population. Based on chemical characterization of the site and limited experimental data on chemically induced pancreatic carcinogenesis in other small fish species, the neoplasms were probably caused by exposure of the mummichog to chemical carcinogens in their environment.

Ultrastructure of normal and neoplastic exocrine pancreas in the mummichog, Fundulus heteroclitus.

The ultrastructure of exocrine pancreatic neoplasms occurring in the mummichog, Fundulus heteroclitus, from a creosote-contaminated site in the Elizabeth River, Virginia, is described and related to nonneoplastic exocrine pancreas. Normal mummichog pancreas was an anastomosing tubular gland, with parenchymal cells organized as branched, anastomosing tubules around a central ductular system. The pancreatic ductular system consisted sequentially of terminal canalicular lumens lined by acinar cells, pancreatic preductules formed by an acinar and a centroductular cell, pancreatic ductules lined by 2 centroductular cells, and pancreatic ducts lined by cuboidal or columnar epithelial cells resting on a basal lamina and stromal sheath. Acinar cell adenomas retained the normal tubular organization and relationship between acinar and centroductular cells. Tumor cells exhibited nuclear pleomorphism but contained a full complement of normal zymogen granules and rough endoplasmic reticulum (RER). Some adenomas exhibited necrosis and cellular degeneration. Acinar cell carcinomas ranged from well to poorly differentiated. They exhibited loss of cell polarity, moderate to severe nuclear pleomorphism, extensive variation in size, shape, and number of zymogen granules, variability in RER content, and cellular degeneration. Acinar cell neoplasms in the mummichog were similar to those induced chemically in other fishes and certain mammals, suggesting that this fish population has been exposed to potent chemical carcinogens and that the species may be an effective indicator of polluted estuarine environments.