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An 8-year-old neutered male French Bulldog was presented with a 2-day history of intermittent vomiting, reduced appetite and recent rapid development of multiple cutaneous masses over the head and neck regions. On presentation, the patient had a moderate volume of pericardial and bilateral pleural effusion. Echocardiography demonstrated irregular, heterogeneous thickening of the walls of the right ventricle and right atrium, consistent with infiltrative intramyocardial disease. Cytological examination of fine needle aspirates from one of the cutaneous masses confirmed a mast cell tumour. Pericardial fluid analysis revealed a haemorrhagic neoplastic effusion due to mast cell neoplasia. Histopathological and immunohistochemical examination of tissues obtained post mortem confirmed a high-grade cutaneous mast cell tumour with metastasis to the heart, pericardium, mediastinum and spleen. No metastatic disease was present in the submandibular lymph nodes or liver. Immunohistochemistry demonstrated KIT staining pattern 2. There was strong nuclear Ki67 labelling in an average of 65.0 cells per grid and an average of three positive AgNORs per nucleus in neoplastic cells. Polymerase chain reaction for the activating duplication mutation in exons 8 and 11 of c-Kit were negative. To the authors’ knowledge, this is the first report of a canine cutaneous mast cell tumour associated with neoplastic pericardial effusion and widespread intrathoracic metastasis.

Gene expression profiling has revealed molecular heterogeneity of diffuse large B cell lymphoma (DLBCL) in both humans and dogs. Two DLBCL subtypes based on cell of origin are generally recognized, germinal center B (GCB)-like and activated B cell (ABC)-like. A pilot study to characterize the transcriptomic phenotype of 11 dogs with multicentric BCL yielded two molecular subtypes distinguished on the basis of genes important in oxidative phosphorylation. We propose a metabolic classification of canine BCL that transcends cell of origin and shows parallels to a similar molecular phenotype in human DLBCL. We thus confirm the validity of this classification scheme across widely divergent mammalian taxa and add to the growing body of literature suggesting cellular and molecular similarities between human and canine non-Hodgkin lymphoma. Our data support a One Health approach to the study of DLBCL, including the advancement of novel therapies of relevance to both canine and human health.

Monocytes are key cells of the innate immune system. Their phenotypic and functional roles have been investigated in humans, mice and other animals, such as the rat, pig and cow. To date, detailed phenotypic analysis of monocytes has not been undertaken in dogs. Two important surface markers in human monocytes are CD14 and MHC class II (MHC II). By flow cytometry, we demonstrated that canine monocytes can be subdivided into three separate populations: CD14posMHC IIneg, CD14posMHC IIpos and CD14negMHC IIpos. Both light and transmission electron microscopy confirmed the monocytic identity of all three populations. The CD14posMHC IIneg population could be distinguished on an ultrastructural level by their smaller size, the presence of more numerous, larger granules, and more pseudopodia than both of the other populations.

The serum or plasma biochemical profile is essential in the diagnosis and monitoring of systemic disease in veterinary medicine, but current reference intervals typically take no account of breed-specific differences. Breed-specific hematological phenotypes have been documented in the domestic dog, but little has been published on serum biochemical phenotypes in this species. Serum biochemical profiles of dogs in which all measurements fell within the existing reference intervals were retrieved from a large veterinary database. Serum biochemical profiles from 3045 dogs were retrieved, of which 1495 had an accompanying normal glucose concentration. Sixty pure breeds plus a mixed breed control group were represented by at least 10 individuals. All analytes, except for sodium, chloride and glucose, showed variation with age. Total protein, globulin, potassium, chloride, creatinine, cholesterol, total bilirubin, ALT, CK, amylase, and lipase varied between sexes. Neutering status significantly impacted all analytes except albumin, sodium, calcium, urea, and glucose. Principal component analysis of serum biochemical data revealed 36 pure breeds with distinctive phenotypes. Furthermore, comparative analysis identified 23 breeds with significant differences from the mixed breed group in all biochemical analytes except urea and glucose. Eighteen breeds were identified by both principal component and comparative analysis. Tentative reference intervals were generated for breeds with a distinctive phenotype identified by comparative analysis and represented by at least 120 individuals. This is the first large-scale analysis of breed-specific serum biochemical phenotypes in the domestic dog and highlights potential genetic components of biochemical traits in this species.

The cancer microenvironment plays a pivotal role in oncogenesis, containing a number of regulatory cells that attenuate the anti-neoplastic immune response. While the negative prognostic impact of regulatory T cells (Tregs) in the context of most solid tissue tumors is well established, their role in lymphoid malignancies remains unclear. T cells expressing FOXP3 and Helios were documented in the fine needle aspirates of affected lymph nodes of dogs with spontaneous multicentric B cell lymphoma (BCL), proposed to be a model for human non-Hodgkin lymphoma. Multivariable analysis revealed that the frequency of lymph node FOXP3+ T cells was an independent negative prognostic factor, impacting both progression-free survival (hazard ratio 1.10; p = 0.01) and overall survival (hazard ratio 1.61; p = 0.01) when comparing dogs showing higher than the median FOXP3 expression with those showing the median value of FOXP3 expression or less. Taken together, these data suggest the existence of a population of Tregs operational in canine multicentric BCL that resembles thymic Tregs, which we speculate are co-opted by the tumor from the periphery. We suggest that canine multicentric BCL represents a robust large animal model of human diffuse large BCL, showing clinical, cytological and immunophenotypic similarities with the disease in man, allowing comparative studies of immunoregulatory mechanisms.

Remarkably little has been published on hematological phenotypes of the domestic dog, the most polymorphic species on the planet. Information on the signalment and complete blood cell count of all dogs with normal red and white blood cell parameters judged by existing reference intervals was extracted from a veterinary database. Normal hematological profiles were available for 6046 dogs, 5447 of which also had machine platelet concentrations within the reference interval. Seventy-five pure breeds plus a mixed breed control group were represented by 10 or more dogs. All measured parameters except mean corpuscular hemoglobin concentration (MCHC) varied with age. Concentrations of white blood cells (WBCs), neutrophils, monocytes, lymphocytes, eosinophils and platelets, but not red blood cell parameters, all varied with sex. Neutering status had an impact on hemoglobin concentration, mean corpuscular hemoglobin (MCH), MCHC, and concentrations of WBCs, neutrophils, monocytes, lymphocytes and platelets. Principal component analysis of hematological data revealed 37 pure breeds with distinctive phenotypes. Furthermore, all hematological parameters except MCHC showed significant differences between specific individual breeds and the mixed breed group. Twenty-nine breeds had distinctive phenotypes when assessed in this way, of which 19 had already been identified by principal component analysis. Tentative breed-specific reference intervals were generated for breeds with a distinctive phenotype identified by comparative analysis. This study represents the first large-scale analysis of hematological phenotypes in the dog and underlines the important potential of this species in the elucidation of genetic determinants of hematological traits, triangulating phenotype, breed and genetic predisposition.

Immune-mediated hemolytic anemia (IMHA) is an important cause of morbidity and mortality in dogs. IMHA also occurs in cats, although less commonly. IMHA is considered secondary when it can be attributed to an underlying disease, and as primary (idiopathic) if no cause is found. Eliminating diseases that cause IMHA may attenuate or stop immune-mediated erythrocyte destruction, and adverse consequences of long-term immunosuppressive treatment can be avoided. Infections, cancer, drugs, vaccines, and inflammatory processes may be underlying causes of IMHA. Evidence for these comorbidities has not been systematically evaluated, rendering evidence-based decisions difficult. We identified and extracted data from studies published in the veterinary literature and developed a novel tool for evaluation of evidence quality, using it to assess study design, diagnostic criteria for IMHA, comorbidities, and causality. Succinct evidence summary statements were\ud written, along with screening recommendations. Statements were refined by conducting 3 iterations of Delphi review with panel and task force members. Commentary was solicited from several professional bodies to maximize clinical applicability\ud before the recommendations were submitted. The resulting document is intended to provide clinical guidelines for diagnosis of, and underlying disease screening for, IMHA in dogs and cats. These should be implemented with consideration of animal, owner, and geographical factors.