{"title":"Postmortem pathologic findings in dogs that underwent total body irradiation and hematopoietic cell transplant: A case series of five dogs with B-cell multicentric lymphoma","authors":"William Benedict, Steven Suter, Danielle Meritet","doi":"10.1177/03009858241249114","DOIUrl":"https://doi.org/10.1177/03009858241249114","url":null,"abstract":"Alternative therapies that can help achieve complete remission in dogs with lymphoma include total body irradiation and hematopoietic cell transplant, though there are few reports describing successes and pathologic sequelae of these procedures. During a 10-year period, 94 dogs with multicentric lymphoma received a hematopoietic cell transplant following total body irradiation at North Carolina State University College of Veterinary Medicine. Seven of these 94 dogs (7%) died prior to discharge, five (5%) of which presented for postmortem examination. Of these dogs, four received an autologous hematopoietic cell transplant, while one received a haploidentical allogeneic hematopoietic cell transplant. All five dogs had bone marrow depletion with all hematopoietic lines affected. Three had systemic candidiasis, while two had bacterial infections. To the authors’ knowledge, this is the first report to document pathologic findings and development of systemic mycoses in dogs post total-body irradiation therapy and hematopoietic cell transplant.","PeriodicalId":23513,"journal":{"name":"Veterinary Pathology","volume":"87 1","pages":""},"PeriodicalIF":2.4,"publicationDate":"2024-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140826712","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Corrigendum to mitotic index is predictive for survival for canine cutaneous mast cell tumors","authors":"","doi":"10.1177/03009858241252668","DOIUrl":"https://doi.org/10.1177/03009858241252668","url":null,"abstract":"","PeriodicalId":23513,"journal":{"name":"Veterinary Pathology","volume":"96 1","pages":""},"PeriodicalIF":2.4,"publicationDate":"2024-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140826900","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Veterinary PathologyPub Date : 2024-05-01Epub Date: 2024-01-10DOI: 10.1177/03009858231222227
Arno Wünschmann, Dana Franzen-Klein, Mia Torchetti, Michele Confeld, Michelle Carstensen, Victoria Hall
{"title":"Lesions and viral antigen distribution in bald eagles, red-tailed hawks, and great horned owls naturally infected with H5N1 clade 2.3.4.4b highly pathogenic avian influenza virus.","authors":"Arno Wünschmann, Dana Franzen-Klein, Mia Torchetti, Michele Confeld, Michelle Carstensen, Victoria Hall","doi":"10.1177/03009858231222227","DOIUrl":"10.1177/03009858231222227","url":null,"abstract":"<p><p>An epidemic of highly pathogenic avian influenza (HPAI) began in North America in the winter of 2021. The introduced Eurasian H5N1 clade 2.3.4.4b virus subsequently reassorted with North American avian influenza strains. This postmortem study describes the lesions and influenza A virus antigen distribution in 3 species of raptors, including bald eagles (<i>Haliaeetus leucocephalus</i>, n = 6), red-tailed hawks (<i>Buteo jamaicensis</i>, n = 9), and great horned owls (<i>Bubo virginianus</i>, n = 8), naturally infected with this virus strain based on positive reverse transcriptase polymerase chain reaction and sequencing results from oropharyngeal swabs. The birds presented with severe neurologic signs and either died or were euthanized because of the severity of their clinical signs and suspected influenza virus infection. Gross lesions were uncommon and included forebrain hemorrhages in 2 eagles, myocarditis in 1 hawk, and multifocal pancreatic necrosis in 3 owls. Histological lesions were common and included encephalitis, myocarditis, multifocal pancreas necrosis, multifocal adrenal necrosis, histiocytic splenitis, and anterior uveitis in decreasing frequency. Influenza A viral antigen was detected in brain, heart, pancreas, adrenal gland, kidney, spleen, liver, and eye. In conclusion, bald eagles, red-tailed hawks, and great horned owls infected with the HPAI clade 2.3.4.4b virus strain and showing neurological signs of illness may develop severe or fatal disease with histologically detectable lesions in the brain that are frequently positive for viral antigen.</p>","PeriodicalId":23513,"journal":{"name":"Veterinary Pathology","volume":" ","pages":"410-420"},"PeriodicalIF":2.4,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139404570","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Veterinary PathologyPub Date : 2024-05-01Epub Date: 2023-11-29DOI: 10.1177/03009858231214024
Mason C Jager, Eunju Choi, Joy E Tomlinson, Gerlinde Van de Walle
{"title":"Naturally acquired equine parvovirus-hepatitis is associated with a wide range of hepatic lesions in horses.","authors":"Mason C Jager, Eunju Choi, Joy E Tomlinson, Gerlinde Van de Walle","doi":"10.1177/03009858231214024","DOIUrl":"10.1177/03009858231214024","url":null,"abstract":"<p><p>Equine parvovirus-hepatitis (EqPV-H) is the causative agent of Theiler's disease, or severe acute hepatic necrosis, in horses. However, it is poorly understood whether EqPV-H is associated with other histologic findings in horses with clinical liver disease. The objective of this study was to examine the prevalence and severity of EqPV-H infections in diagnostic liver samples. Archived formalin-fixed, paraffin-embedded (FFPE) liver samples (<i>n</i> = 98) from Cornell University and University of California, Davis, collected between 2007 and 2022 were evaluated for 15 individual histologic features and by EqPV-H <i>in situ</i> hybridization. EqPV-H was detected in 48% (<i>n</i> = 47) of samples. The most common histologic features of EqPV-H-positive samples included individual hepatocyte death (<i>n</i> = 40, 85%), lobular infiltrates (<i>n</i> = 38, 80%), portal infiltrates (<i>n</i> = 35, 74%), and ductular reaction (<i>n</i> = 33, 70%). Centrilobular necrosis, portal infiltrate, and individual hepatocyte death were positively associated with high viral load. Neutrophil infiltrates, bridging fibrosis, and portal edema were negatively associated with a high viral load. Only 4 of 49 tested samples were positive for equine hepacivirus by polymerase chain reaction (PCR), but the PCR assay was unreliable for FFPE tissues. In summary, this study demonstrates that EqPV-H is common in a variety of liver pathologies and should be considered as a differential diagnosis in cases of hepatitis other than Theiler's disease.</p>","PeriodicalId":23513,"journal":{"name":"Veterinary Pathology","volume":" ","pages":"442-452"},"PeriodicalIF":2.3,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11068485/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138452602","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Veterinary PathologyPub Date : 2024-05-01Epub Date: 2023-10-31DOI: 10.1177/03009858231207017
Kazuhiro Kojima, James K Chambers, Ko Nakashima, Kazuyuki Uchida
{"title":"Pro-inflammatory cytokine expression and the STAT1/3 pathway in canine chronic enteropathy and intestinal T-cell lymphoma.","authors":"Kazuhiro Kojima, James K Chambers, Ko Nakashima, Kazuyuki Uchida","doi":"10.1177/03009858231207017","DOIUrl":"10.1177/03009858231207017","url":null,"abstract":"<p><p>The accumulation of intraepithelial lymphocytes (IELs) is a histopathological feature of canine chronic enteropathy (CE), and IELs are considered the cells of origin of intestinal T-cell lymphoma (ITCL). However, the pathogenic mechanism of IEL activation in CE remains unclear. This study hypothesized that the expression of proinflammatory cytokines, associated with cytotoxic T/NK-cell activation, is upregulated in CE and ITCL, and examined the expression of <i>IFN-γ</i>, <i>IL-2</i>, <i>IL-12p35, IL-12p40</i>, <i>IL-15</i>, and <i>IL-21</i> and the downstream signal transducers and activators of transcription (STAT) pathway in the duodenal mucosa of dogs without lesions (<i>n</i> = 11; NC), with IEL<sup>-</sup>CE (<i>n</i> = 19; CE without intraepithelial lymphocytosis), IEL<sup>+</sup>CE (<i>n</i> = 29; CE with intraepithelial lymphocytosis), and with ITCL (<i>n</i> = 60). Quantitative polymerase chain reaction (PCR) revealed that <i>IFN-γ</i> and <i>IL-21</i> were higher in IEL<sup>+</sup>CE than in IEL<sup>-</sup>CE or NC. Western blot revealed upregulation of STAT1 and STAT3 in IEL<sup>+</sup>CE. Double-labeling immunohistochemistry revealed a positive correlation between the Ki67 index of CD3<sup>+</sup> T-cells and <i>IFN-γ</i> expression levels. Immunohistochemistry revealed a higher ratio of p-STAT1-positive villi in IEL<sup>+</sup>CE and ITCL than IEL<sup>-</sup>CE and NC, which positively correlated with <i>IFN-γ</i> expression levels. Among the 60 ITCL cases, neoplastic lymphocytes were immunopositive for p-STAT1 in 28 cases and p-STAT3 in 29 cases. These results suggest that <i>IFN-γ</i> and <i>IL-21</i> contribute to the pathogenesis of IEL<sup>+</sup>CE, and <i>IFN-γ</i> may be involved in T-cell activation and mucosal injury in CE. STAT1 and STAT3 activation in ITCL cells suggests a role for the upregulation of the STAT pathway in the pathogenesis of ITCL.</p>","PeriodicalId":23513,"journal":{"name":"Veterinary Pathology","volume":" ","pages":"382-392"},"PeriodicalIF":2.4,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71427261","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Veterinary PathologyPub Date : 2024-05-01Epub Date: 2023-11-01DOI: 10.1177/03009858231207025
Federico Armando, Ilaria Porcellato, Livia de Paolis, Samanta Mecocci, Benedetta Passeri, Małgorzata Ciurkiewicz, Luca Mechelli, Chiara Grazia De Ciucis, Marzia Pezzolato, Floriana Fruscione, Chiara Brachelente, Vittoria Montemurro, Katia Cappelli, Christina Puff, Wolfgang Baumgärtner, Alessandro Ghelardi, Elisabetta Razzuoli
{"title":"Vulvo-vaginal epithelial tumors in mares: A preliminary investigation on epithelial-mesenchymal transition and tumor-immune microenvironment.","authors":"Federico Armando, Ilaria Porcellato, Livia de Paolis, Samanta Mecocci, Benedetta Passeri, Małgorzata Ciurkiewicz, Luca Mechelli, Chiara Grazia De Ciucis, Marzia Pezzolato, Floriana Fruscione, Chiara Brachelente, Vittoria Montemurro, Katia Cappelli, Christina Puff, Wolfgang Baumgärtner, Alessandro Ghelardi, Elisabetta Razzuoli","doi":"10.1177/03009858231207025","DOIUrl":"10.1177/03009858231207025","url":null,"abstract":"<p><p>Vulvo-vaginal epithelial tumors are uncommon in mares, and data on the epithelial-to-mesenchymal transition (EMT) and the tumor-immune microenvironment (TIME) are still lacking. This is a study investigating the equus caballus papillomavirus type 2 (EcPV2) infection state as well as the EMT process and the tumor microenvironment in vulvo-vaginal preneoplastic/ benign (8/22) or malignant (14/22) epithelial lesions in mares. To do this, histopathological, immunohistochemical, transcriptomic, <i>in situ</i> hybridization, and correlation analyses were carried out. Immunohistochemistry quantification showed that cytoplasmic E-cadherin and β-catenin expression as well as nuclear β-catenin expression were features of malignant lesions, while benign/preneoplastic lesions were mainly characterized by membranous E-cadherin and β-catenin expression. Despite this, there were no differences between benign and malignant equine vulvo-vaginal lesions in the expression of downstream genes involved in the canonical and noncanonical wnt/β-catenin pathways. In addition, malignant lesions were characterized by a lower number of cells with cytoplasmic cytokeratin expression as well as a slightly higher cytoplasmic vimentin immunolabeling. The TIME of malignant lesions was characterized by more numerous CD204<sup>+</sup> M2-polarized macrophages. Altogether, our results support the hypothesis that some actors in TIME such as CD204<sup>+</sup> M2-polarized macrophages may favor the EMT process in equine vulvo-vaginal malignant lesions providing new insights for future investigations in the field of equine EcPV2-induced genital neoplastic lesions.</p>","PeriodicalId":23513,"journal":{"name":"Veterinary Pathology","volume":" ","pages":"366-381"},"PeriodicalIF":2.4,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71427262","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Veterinary PathologyPub Date : 2024-05-01Epub Date: 2023-11-08DOI: 10.1177/03009858231209408
Wilson Karalus, Supatsak Subharat, Geoff Orbell, Bernie Vaatstra, John S Munday
{"title":"Equine sarcoids: A clinicopathologic study of 49 cases, with mitotic count and clinical type predictive of recurrence.","authors":"Wilson Karalus, Supatsak Subharat, Geoff Orbell, Bernie Vaatstra, John S Munday","doi":"10.1177/03009858231209408","DOIUrl":"10.1177/03009858231209408","url":null,"abstract":"<p><p>Sarcoids are common mesenchymal neoplasms of horses. Although there are few studies in which sarcoids have been followed over a long period of time, sarcoids are considered locally invasive and have been reported to frequently recur following surgical excision. Currently, no histological features have been identified to predict which sarcoids will recur after excision. The present study comprised 49 sarcoids for which histology sections were available and in which the recurrence status of the case was known. Each sarcoid was excised from a different horse. Overall, 12 of the 49 (24%) sarcoids recurred after surgical excision. Mitotic count (MC), cellularity, necrosis, nuclear pleomorphism, and inflammation of the sarcoids were evaluated histologically. Of these, MC correlated with recurrence. Four of 5 (80%) sarcoids with an MC ≥ 20 in 2.37 mm<sup>2</sup> recurred, which was a significantly higher recurrence rate than that of sarcoids with an MC < 20, 8 of 44 cases recurred (18%), <i>P</i> = .0051. Clinical type was also found to correlate with recurrence. Three of 4 (75%) fibroblastic types recurred, which was a significantly higher recurrence rate than that of sarcoids with other clinical types, 9 of 45 cases (18%), <i>P</i> < .001. In addition, univariate Cox regression analysis confirmed fibroblastic type and MC ≥ 20 as significant predictors for recurrence (<i>P</i> = .016 and <i>P</i> = .005, respectively). To the authors' knowledge, this is the first large study examining recurrence rates in sarcoids, and the first time that histological features have been correlated with recurrence.</p>","PeriodicalId":23513,"journal":{"name":"Veterinary Pathology","volume":" ","pages":"357-365"},"PeriodicalIF":2.4,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11067406/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71486617","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Veterinary PathologyPub Date : 2024-05-01Epub Date: 2023-11-12DOI: 10.1177/03009858231209691
Lars Mecklenburg, Rebecca Ducore, Molly Boyle, Andrew Newell, Laura Boone, Joerg Luft, Annette Romeike, Ann-Kathrin Haverkamp, Keith Mansfield, Kelley A Penraat, J J Baczenas, Nick Minor, Shelby L O'Connor, David H O'Connor
{"title":"A new genotype of hepatitis A virus causing transient liver enzyme elevations in Mauritius-origin laboratory-housed <i>Macaca fascicularis</i>.","authors":"Lars Mecklenburg, Rebecca Ducore, Molly Boyle, Andrew Newell, Laura Boone, Joerg Luft, Annette Romeike, Ann-Kathrin Haverkamp, Keith Mansfield, Kelley A Penraat, J J Baczenas, Nick Minor, Shelby L O'Connor, David H O'Connor","doi":"10.1177/03009858231209691","DOIUrl":"10.1177/03009858231209691","url":null,"abstract":"<p><p>Hepatitis A virus (HAV) infects humans and nonhuman primates, typically causing an acute self-limited illness. Three HAV genotypes have been described so far for humans, and three genotypes have been described for nonhuman primates. We observed transiently elevated liver enzymes in Mauritius-origin laboratory-housed macaques in Germany and were not able to demonstrate an etiology including HAV by serology and polymerase chain reaction (PCR). HAV is a rare pathogen in cynomolgus macaques, and since all employees were routinely vaccinated against HAV, it was not a part of the routine vaccination and screening program. A deep sequencing approach identified a new HAV genotype (referred to as Simian_HAV_Macaca/Germany/Mue-1/2022) in blood samples from affected animals. This HAV was demonstrated by reverse transcription PCR in blood and liver and by <i>in situ</i> hybridization in liver, gall bladder, and septal ducts. A commercial vaccine was used to protect animals from liver enzyme elevation. The newly identified simian HAV genotype demonstrates 80% nucleotide sequence identity to other simian and human HAV genotypes. There was deeper divergence between Simian_HAV_Macaca/Germany/Mue-1/2022 and other previously described HAVs, including both human and simian viruses. <i>In situ</i> hybridization indicated persistence in the biliary epithelium up to 3 months after liver enzymes were elevated. Vaccination using a commercial vaccine against human HAV prevented reoccurrence of liver enzyme elevations. Because available assays for HAV did not detect this new HAV genotype, knowledge of its existence may ameliorate potential significant epidemiological and research implications in laboratories globally.</p>","PeriodicalId":23513,"journal":{"name":"Veterinary Pathology","volume":" ","pages":"488-496"},"PeriodicalIF":2.4,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89719723","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Veterinary PathologyPub Date : 2024-05-01Epub Date: 2023-10-31DOI: 10.1177/03009858231207021
Travis K Meuten, Gregg A Dean, Douglas H Thamm
{"title":"Review: The PI3K-AKT-mTOR signal transduction pathway in canine cancer.","authors":"Travis K Meuten, Gregg A Dean, Douglas H Thamm","doi":"10.1177/03009858231207021","DOIUrl":"10.1177/03009858231207021","url":null,"abstract":"<p><p>Tumors in dogs and humans share many similar molecular and genetic features, incentivizing a better understanding of canine neoplasms not only for the purpose of treating companion animals, but also to facilitate research of spontaneously developing tumors with similar biologic behavior and treatment approaches in an immunologically competent animal model. Multiple tumor types of both species have similar dysregulation of signal transduction through phosphatidylinositol 3-kinase (PI3K), protein kinase B (PKB; AKT), and mechanistic target of rapamycin (mTOR), collectively known as the PI3K-AKT-mTOR pathway. This review aims to delineate the pertinent aspects of the PI3K-AKT-mTOR signaling pathway in health and in tumor development. It will then present a synopsis of current understanding of PI3K-AKT-mTOR signaling in important canine cancers and advancements in targeted inhibitors of this pathway.</p>","PeriodicalId":23513,"journal":{"name":"Veterinary Pathology","volume":" ","pages":"339-356"},"PeriodicalIF":2.4,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71413989","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}