Pathological Findings in Gastrointestinal Neoplasms and Polyps in 860 Cats and a Pilot Study on miRNA Analyses.

Background: Gastrointestinal masses in cats are of clinical relevance, but pathological studies with larger case numbers are lacking. Biomarkers such as miRNA have not yet been investigated in feline intestinal neoplasms. Methods: A retrospective analysis of pathology reports included 860 feline gastrointestinal masses. Immunohistochemistry was performed on 91 lymphomas, 10 sarcomas and 7 mast cell tumours (MCT). Analyses of miRNA-20b and miRNA-192 were performed on 11 lymphomas, 5 carcinomas and 5 control tissues by ddPCR. Results: The pathological diagnosis identified 679 lymphomas, 122 carcinomas, 28 sarcomas, 23 polyps, 7 MCT and 1 leiomyoma. Carcinomas and polyps were most commonly found in the large intestine, lymphomas were most commonly found in the stomach and small intestine and MCT only occurred in the small intestine. Besides the well-described small-cell, mitotic count <2 T-cell lymphomas and the large-cell B-cell lymphomas with a high mitotic count, several variants of lymphomas were identified. The values of miRNA-20b were found to be up-regulated in samples of all types of cancer, whereas miRNA-192 was only up-regulated in carcinomas and B-cell lymphomas. Conclusions: The histopathological and immunohistochemical (sub-)classification of feline intestinal masses confirmed the occurrence of different tumour types, with lymphoma being the most frequent neoplasm. Novel biomarkers such as miRNA-20b and miRNA-192 might have diagnostic potential in feline intestinal neoplasms and should be further investigated.

Bridging the Species Gap: Morphological and Molecular Comparison of Feline and Human Intestinal Carcinomas.

Limited availability of in vivo experimental models for invasive colorectal cancer (CRC) including metastasis and high tumor budding activity is a major problem in colorectal cancer research. In order to compare feline and human intestinal carcinomas, tumors of 49 cats were histologically subtyped, graded and further characterized according to the human WHO classification. Subsequently, feline tumors were compared to a cohort of 1004 human CRC cases. Feline intestinal tumors closely resembled the human phenotype on a histomorphological level. In both species, adenocarcinoma not otherwise specified (ANOS) was the most common WHO subtype. In cats, the second most common subtype of the colon (36.4%), serrated adenocarcinoma (SAC), was overrepresented compared to human CRC (8.7%). Mucinous adenocarcinoma (MAC) was the second most common subtype of the small intestine (12.5%). Intriguingly, feline carcinomas, particularly small intestinal, were generally of high tumor budding (Bd) status (Bd3), which is designated an independent prognostic key factor in human CRC. We also investigated the relevance of feline CTNNB1 exon 2 alterations by Sanger sequencing. In four cases of feline colonic malignancies (3 ANOS, 1 SAC), somatic missense mutations of feline CTNNB1 (p.D32G, p.D32N, p.G34R, and p.S37F) were detected, indicating that mutational alterations of the WNT/ß-catenin signaling pathway potentially play an essential role in feline intestinal tumorigenesis comparable to humans and dogs. These results indicate that spontaneous intestinal tumors of cats constitute a useful but so far underutilized model for human CRC. Our study provides a solid foundation for advanced comparative oncology studies and emphasizes the need for further (molecular) characterization of feline intestinal carcinomas.

[Nephritis in a Staffordshire Terrier puppy caused by Encephalitozoon cuniculi genotype I]. / Nephritis bei einem Staffordshire-Terrier-Welpen verursacht durch Encephalitozoon cuniculi Genotyp I.

An 8-week-old puppy was presented to the clinic because of anorexia, polyuria, polydipsia and azotemia. The urinary sediment displayed large amounts of protozoan-like organisms, which could be identified by PCR as Encephalitozoon cuniculi genotype I. In the immunofluorescence antibody test (IFAT) an antibody titer against E. cuniculi of 1  :  2560 was found. The dog was treated with fenbendazole over 3 weeks. After 3 months, an antibody titer against E. cuniculi could no longer be detected. The dog recovered completely. This rare case demonstrates that E. cuniculi genotype I can cause clinical disease in dogs with renal involvement, which can be successfully treated with fenbendazole.

[Congenital and lethal semi-hairlessness in an Angler-Holstein crossbred calf]. / Kongenitale und letale Semi-Haarlosigkeit bei einem Angler-Holstein Kreuzungskalb.

A male Angler-Red Holstein crossbred calf was almost completely hairless since its birth. Hair growth was not observed within the course of its life, but with increasing age the hair structure changed from a thin and soft hair to a wiry to coarse hair fibre. Growth rate of the animal was reduced, body condition was poor but appetite was good. In addition, accompanying malformations were found including brachygnathia superior and a reduction or a particularly pronounced fine countenance skull ("shrew head"). The calf died unexpectedly at the age of five months. In the subsequent gross pathological and histopathological examination, a pronounced hyperkeratosis, degeneration of follicular epithelial cells, a reduced number of hair follicles, an increased number of telogen hair follicles, sclerosis of the corium, dilated apocrine glands and inflammatory changes of the gastrointestinal tract were seen. Based on the course of the disease, the phenotypic appearance of hypotrichosis and hair fibre as well as the histopathological changes the present case resembles a lethal semi-hairless form of hypotrichosis. This congenital anomaly in the present case is likely genetically determined.

Multicentric T-cell lymphoma accompa- nied by infiltration of the peripheral and central nervous system in a fattening pig.

Multicentric lymphomas, usually of B-cell origin, are rather common neoplasms in pigs, which usually affect lymph nodes and different organ systems. An uncommon manifestation of malignant lymphoma represents neoplastic peripheral nerve involvement, which has been reported in human medicine. So far, only single cases of lymphoma with manifestation in peripheral nerves (known as neurolymphomatosis) without leukemic conversion have been mentioned in different animal species others than swine. The present case report describes the occurrence of a multicentric T-cell lymphoma in a fattening pig with marked leukocytosis. The pig was presented with symptoms of lethargy, weight loss, and fever. Bone marrow aspirate contained all stages of granulocytic and erythrocytic precursors, and a remarkable large number of eosinophiles and undifferentiated blasts. At necropsy, the carcass showed generalized lymphadenopathy and severe hepatosplenomegaly. Histological findings included neoplastic round cell infiltrations in lymph nodes, bone marrow, tonsils, lung, spleen, liver, kidneys, urinary bladder, small and large intestine, and meninges. Additionally, neoplastic cells were present in the sciatic and medial plantar nerve of the left hind leg. The diagnosis T-cell lymphoma was confirmed immunohistochemically. To the author's knowledge, this work represents the first report of peripheral nerve involvement in a pig with multicentric T-cell lymphoma accompanied by CNS involvement and leukemia.

Canine gut dendritic cells in the steady state and in inflammatory bowel disease.

Alongside the intestinal border, dendritic cells (DCs) sample large amounts of endogenous and potentially pathogenic antigens followed by initiation of protective immune responses or induction of tolerance. Breakdown of oral tolerance towards commensal bacteria is suggested to be crucial for the development of both human and canine inflammatory bowel disease (IBD). The aim of this study was to investigate canine intestinal DCs in the steady state and in dogs with IBD using multicolour immunofluorescence. In the healthy gut, DC-like cells expressed MHC II, CD1a8.2 and CD11c, and, in lower amounts, CD11b, within lamina propria, Peyer's patches (PPs) and mesenteric lymph nodes (MLNs), whereas those expressing CD80 and CD86 were only present in PPs and MLNs. Occasionally, DC-like cells were in contact with the intestinal lumen through transepithelial projections. In canine IBD, CD1a8.2+, CD11b+ and CD11c+ DC-like cells were decreased within the stomach, duodenum and colon, whereas the colonic mucosa revealed elevation of CD86+ DC-like cells. The complex network of DC-like cells in the gut indicates their important role in canine mucosal immunity, including active sampling of luminal antigens. Furthermore, their shift in diseased dogs suggests a pathogenetic significance for canine IBD.

Immunohistochemical investigation of Foxp3 expression in the intestine in healthy and diseased dogs.

Intestinal immune regulation including development of oral tolerance is of great importance for the maintenance of intestinal homeostasis. Concerning this, regulatory T cells (Tregs) occupy a pivotal role in cell-mediated immunosuppression. Dysregulation of mucosal immunology leading to an abnormal interaction with commensal bacteria is suggested to play a key role in the pathogenesis of Inflammatory Bowel Disease (IBD) in men and dogs. The aim of this study was to characterise the expression of Foxp3 in the normal canine gut of 18 dogs (mean age: 6.03 years), in 16 dogs suffering from IBD (mean age: 5.05 years), and of 6 dogs with intestinal nematode infection (mean age: 0.87 years) using immunohistochemistry. In the duodenum, Tregs in healthy dogs declined from villi (median: 10.67/62 500 µm2) to crypts (median: 1.89/62 500 µm2). Tregs were further increased in the villi of middle-aged dogs (median: 18.92/62 500 µm2) in contrast to juvenile (median: 3.50/62 500 µm2) and old (median: 9.56/62 500 µm2) individuals. Compared to healthy controls, animals suffering from IBD revealed reduced numbers of Tregs in duodenal villi (median: 4.13/62 500 µm2). Dogs with intestinal nematode infection displayed increased numbers of Tregs (median: 21.06/62 500 µm2) compared to healthy animals.Age-related changes indicate a progressive establishment of oral tolerance and immunosenescence in the canine elderly. The results further suggest that a defect in Treg homeostasis may be involved in the pathogenesis of canine IBD. In contrast, increased numbers of Tregs in the duodenum may be due to nematode infection.