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Background: In humans, muscle-invasive bladder cancer (MIBC) is highly aggressive and associated with a poor prognosis. With a high mutation load and large number of altered genes, strategies to delineate key driver events are necessary. Dogs and cats develop urothelial carcinoma (UC) with histological and clinical similarities to human MIBC. Cattle that graze on bracken fern also develop UC, associated with exposure to the carcinogen ptaquiloside. These species may represent relevant animal models of spontaneous and carcinogen-induced UC that can provide insight into human MIBC., Results: Whole-exome sequencing of domestic canine (n = 87) and feline (n = 23) UC, and comparative analysis with human MIBC reveals a lower mutation rate in animal cases and the absence of APOBEC mutational signatures. A convergence of driver genes (ARID1A, KDM6A, TP53, FAT1, and NRAS) is discovered, along with common focally amplified and deleted genes involved in regulation of the cell cycle and chromatin remodelling. We identify mismatch repair deficiency in a subset of canine and feline UCs with biallelic inactivation of MSH2. Bovine UC (n = 8) is distinctly different; we identify novel mutational signatures which are recapitulated in vitro in human urinary bladder UC cells treated with bracken fern extracts or purified ptaquiloside., Conclusion: Canine and feline urinary bladder UC represent relevant models of MIBC in humans, and cross-species analysis can identify evolutionarily conserved driver genes. We characterize mutational signatures in bovine UC associated with bracken fern and ptaquiloside exposure, a human-linked cancer exposure. Our work demonstrates the relevance of cross-species comparative analysis in understanding both human and animal UC., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: In Europe, feline leishmaniosis is commonly caused by Leishmania infantum. There is little knowledge regarding pathogenesis, ocular manifestations and long-term follow-ups in cats with leishmaniosis., Findings: A 6-year-old female, spayed European Shorthair cat was imported from Spain to Germany 2 years prior to its first clinical presentation. The cat showed lethargy, weight loss, ulcerative lesions on the front limbs and high-grade chronic uveitis. The diagnosis of L. infantum infection was based on the cytological finding of amastigotes in skin lesions, positive qPCR of EDTA-blood and positive PCR of a cyto-brush sample from the conjunctiva. Supportive findings included positive serology by IFAT, serum protein capillary electrophoresis with peaks in alpha2- and gamma-globulin sections and marked elevation of SAA. Enucleation had to be performed on day 288 on both eyes because of blindness, glaucoma and high-grade uveitis. Histologically, high numbers of Leishmania spp. amastigotes were found in histiocytes. IFAT and PCR were positive in the aqueous humor in both eyes, respectively. Feline leukemia virus antigen and feline immunodeficiency virus antibody testings were positive. Hematological and biochemical results revealed mild leukocytosis with lymphocytosis, monocytosis and eosinopenia as well as marked elevation of SAA and hyperglobulinemia. The cat was treated with allopurinol, responded well and was still alive at follow-up on day 288 after first presentation. However, enucleation was necessary because of refractory glaucoma and uveitis.  CONCLUSION: For the first time, ocular evidence of Leishmania IgG antibodies was demonstrated in the aqueous humor of both eyes in cats. There is limited knowledge about the pathogenesis, treatment options and outcomes in cats infected with L. infantum. This case report supports the hypothesis that immunosuppression increases the risk of clinical signs of leishmaniasis in cats. Alpha2- and gamma-globulin peaks in serum protein capillary electrophoresis are supportive criteria for the diagnosis of L. infantum infection. SAA is valuable for monitoring. Regarding ophthalmology, uveitis and glaucoma may have a poor prognosis., (© 2023. The Author(s).)

Although atrial dilation is a common finding in feline cardiac disease, detailed investigations of atrial pathology are rare in cats. The aim of the study was to investigate the correlation between pathohistological findings, morphometric data and the degree of dilation of the left atrial appendage (LAA) in 53 cats. Based on the LAA volume, the samples were grouped into normal/control (group 0, ≤1 ml [n = 9]), mildly dilated (group 1, >1 to ≤2 ml [n = 16]), moderately dilated (group 2, >2 to ≤3 ml [n = 14]) and markedly dilated (group 3, >3 ml [n = 14]) groups, independent of the underlying disease. Samples from the LAA and the left atrium (LA) were histologically evaluated using haematoxylin and eosin- and Picrosirius red-stained sections, and morphometrically analysed using an image analysis system. The degree of endo-, myo- and epicardial fibrosis was directly correlated with increased LAA dilation. Due to cardiomyocyte hyperplasia and hypertrophy, the mean thickness of the atrial wall was significantly greater in groups 1 and 2 than in group 0. Conversely, group 3 had a lower mean atrial wall thickness than groups 1 and 2, which was attributed to increased transmural fibrosis and cardiomyocyte atrophy. These findings reflect intensive dynamic remodelling processes during LA and LAA dilation, indicating that reversibility appears to be limited in cases of severe left atrial dilation., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Simple Summary: In cats, gastrointestinal masses appear in relevant numbers. Histopathology and immunohistochemistry are needed for a detailed diagnosis but require invasive sampling. Therefore, the improvement of presurgical diagnostics (e.g., biomarkers in serum) is of interest in feline medicine. The present analysis of pathology reports included 679 alimentary lymphomas, 122 carcinomas, 29 spindle cell tumours, 23 polyps and 7 mast cell tumours (MCT). Immunohistochemical characterisation was available from 91 lymphomas, 10 sarcomas and 7 MCTs. Carcinomas and polyps were most commonly found in the large intestine, lymphomas were most commonly found in the stomach and small intestine and MCTs only occurred in the small intestine. In 68%, the submitted lymph nodes were infiltrated by neoplasms, and surgical margins were often not free of tumour cells. The prognostic and therapeutic value of cell size, mitotic count and immunophenotype in lymphomas must be interpreted carefully. A pilot study on miRNA-20b and miRNA-192 concentration in 11 lymphomas, 5 carcinomas and 5 controls was performed. The values of miRNA-20b were found to be up-regulated in samples of all types of cancer, whereas miRNA-192 was up-regulated in carcinomas and B-cell lymphomas only. The diagnostic purpose of miRNAs as potential biomarkers used for the non-invasive diagnosis of intestinal cancer in cats should be further evaluated. 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. [ABSTRACT FROM AUTHOR]

Tumors of mesenchymal origin are rarely reported in the pancreas. Therefore, this study characterized 17 feline non-epithelial pancreatic tumors, including clinical data, histopathology, and immunohistochemistry. Seventeen feline pancreatic tissue samples were investigated histopathologically and immunohistochemically. Selected pancreatic and inflammatory serum parameters, e.g., feline pancreatic lipase immunoreactivity (fPLI), 1,2-o-dilauryl-rac-glycero-3-glutaric acid-(60-methylresorufin) ester (DGGR) lipase and serum amyloid A (SAA), were recorded, when available. The neoplasms were characterized as round (n = 13) or spindle (n = 4) cell tumors. Round cell tumors included 12 lymphomas and one mast cell tumor in ectopic splenic tissue within the pancreas. Lymphomas were of T-cell (n = 9) or B-cell (n = 3) origin. These cats showed leukocytosis (3/3) and increased fPLI (5/5), DGGR lipase (3/5) and SAA(4/5) values. Spindle cell tumors included two hemangiosarcomas, one pleomorphic sarcoma and one fibrosarcoma. The cat with pleomorphic sarcoma showed increased SAA value. Overall survival time was two weeks to seven months. These are the first descriptions of a pancreatic pleomorphic sarcoma and a mast cell tumor in accessory spleens within feline pancreas. Although rare, pancreatic tumors should be considered in cats presenting with clinical signs and clinical pathology changes of pancreatitis. Only histopathology can certainly distinguish solitary pancreatitis from a neoplasm with inflammation. [ABSTRACT FROM AUTHOR]