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Abstract Background Cytopathology is a minimally invasive and convenient diagnostic procedure, often used as a substitute for histopathology to diagnose and characterize lymphoma in dogs. Objectives Assess the diagnostic performance of cytopathology in diagnosing lymphoma and its histopathological subtypes in dogs. Animals One-hundred and sixty-one lymph node samples from 139 dogs with enlarged peripheral lymph nodes. Methods Based only on cytopathology, 6 examiners independently provided the following interpretations on each sample: (a) lymphoma vs nonlymphoma; (b) grade and phenotype; and (c) World Health Organization (WHO) histopathological subtype. Histopathology and immunohistochemistry (IHC) findings were used as reference standards to evaluate diagnostic performance of cytopathology. Clinical, clinicopathologic, and imaging data also were considered in the definitive diagnosis. Results Classification accuracy for lymphoma consistently was >80% for all examiners, whereas it was >60% for low grade T-cell lymphomas, >30% for high grade B-cell lymphomas, >20% for high grade T-cell lymphomas, and <40% for low grade B-cell lymphomas. Interobserver agreement evaluated by kappa scores was 0.55 and 0.32 for identification of lymphoma cases, and of grade plus immunophenotype, respectively. Conclusions and Clinical Importance Cytopathology may result in accurate diagnosis of lymphoma, but accuracy decreases when further characterization is needed. Cytopathology represents a fundamental aid in identifying lymphoma and can be used as a screening test to predict grade and phenotype. However, these results must be confirmed using other ancillary techniques, including flow cytometry, histopathology, and immunohistochemistry (IHC).

Background Canine babesiosis is an important tick-borne disease in endemic regions. One of the relevant subspecies in Europe is Babesia canis , and it can cause severe clinical signs such as hemolytic anemia. Apart from acute clinical symptoms dogs can also have a more chronic disease development or be asymptomatic carriers. Our objective was to identify readily available ADVIA hematology analyzer parameters suggestive of B. canis parasitemia in dogs and to formulate a predictive model. Methods A historical dataset of complete blood count data from an ADVIA hematology system with blood smear or PCR confirmed parasitemia cases was used to obtain a model by conventional statistics (CS) methods and machine learning (ML) using logistical regression and tree methods. Results Both methods identified that important parameters were platelet count, mean platelet volume and percentage large unstained cells. We were able to formulate a CS model and ML model to screen for Babesia parasitemia in dogs with a sensitivity of 84.6% (CS) and 100% (ML), a specificity of 97.7% (CS) and 95.7% (ML) and a positive likelihood ratio (LR+) of 36.78 (CS) and 23.2 (ML). Conclusions This study introduces two methods of screening for B. canis parasitemia on readily available data from ADVIA hematology systems. The algorithms can easily be introduced in laboratories that use these analyzers. When the algorithm marks a sample as ‘suggestive’ for Babesia parasitemia, the sample is approximately 37 times more likely to show Babesia merozoites on blood smear analysis. Graphical Abstract

Abstract Background Measurement of free metanephrines is recommended for screening of pheochromocytoma (PCC) but requires appropriate reference intervals (RIs). Hypothesis/Objectives To report RIs for plasma, urinary and salivary concentrations of free metanephrines and to determine the diagnostic performance of plasma free normetanephrine (pNMN) and metanephrine (pMN) concentrations in dogs with PCC, hypercortisolism (HC), and nonadrenal illness (NAI). Animals Eighty healthy dogs, 11 PCC dogs, 25 HC dogs, 6 NAI dogs. Methods Plasma, urine, and saliva were collected prospectively from healthy dogs, and free metanephrine concentrations were determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS). In addition, medical records of dogs that had plasma free metanephrine concentrations measured by LC-MS/MS between 2018-2021 were studied retrospectively. Results The RIs for free metanephrines in plasma, urine and saliva are reported. Dogs with PCC had significantly higher pNMN than dogs with HC (P < .001) and NAI (P = .002). The PCC dogs had significantly higher pMN than HC dogs (P < .001), but not higher than NAI dogs (P = .29). Using the upper reference limit, pNMN (>3.56 nmol/L) showed high sensitivity (100%, 95% confidence interval [CI]: 72-100) and specificity (94%, 95% CI: 79-99) for diagnosis of PCC, whereas pMN (>2.49 nmol/L) showed moderate sensitivity (73%, 95% CI: 39-94) and high specificity (94%, 95% CI: 79-99). Conclusions and Clinical Importance With establishment of these RIs, biochemical testing for PCC in dogs can be substantially improved. Measurement of pNMN is superior to pMN in dogs with PCC.

Background High-grade lymphoma in dogs is a chemotherapy-responsive neoplasia with remission rates exceeding 80% under combination chemotherapy protocols. Usually these protocols are intensive and 24 + weeks. The objective of the present study was to investigate if a shorter protocol combined with an oral lomustine maintenance treatment (3 × in 8 weeks) would present an acceptable result, both for B- and T-cell lymphomas, and for the different types of lymphomas normally encountered in private veterinary practice. Results 144 dogs entered the study. Lymphoma types included multicentric (n = 123), alimentary (n = 13), miscellaneous (n = 7), and mediastinal lymphoma (n = 1). Overall response rate was 83.3% (B-cell: 86.6%, T-cell: 79.4%). Complete remission (CR) was achieved in 72.2% (B-cell: 77.3%, T-cell: 67.6%) and partial remission (PR) in 11.1% (B-cell: 9.3%, T-cell: 11.8%) of the dogs. Median duration of first CR amounted to 242 days (B-cell: 263 d, T-cell: 161 d). Median survival in dogs with CR was 374 days (B-cell: 436 d, T-cell: 252 d), and median overall survival time was 291 days (B-cell: 357d, T-cell: 210d). Immunophenotype demonstrated an independent significant influence on duration of remission and survival in the whole group. Findings of splenic and hepatic cytology were not significant associated with patient outcome. Treatment was well tolerated; the majority of adverse events were classified as grade 1 or 2. Conclusions Short-term chemotherapy followed by lomustine consolidation leads to compara-ble remission and survival times compared to conventional protocols with cyclophosphamide, doxorubicin, vincristine and prednisolone with acceptable toxicosis in dogs with both B-cell and T-cell lymphoma.

Drug resistance (DR) is the major limiting factor in the successful treatment of systemic neoplasia with cytotoxic chemotherapy. DR can be either intrinsic or acquired, and although the development and clinical implications are different, the underlying mechanisms are likely to be similar. Most causes for DR are pharmacodynamic in nature, result from adaptations within the tumor cell and include reduced drug uptake, increased drug efflux, changes in drug metabolism or drug target, increased capacity to repair drug‐induced DNA damage or increased resistance to apoptosis. The role of active drug efflux transporters, and those of the ABC‐transporter family in particular, have been studied extensively in human oncology and to a lesser extent in veterinary medicine. Methods reported to assess ABC‐transporter status include detection of the actual protein (Western blot, immunohistochemistry), mRNA or ABC‐transporter function. The three major ABC‐transporters associated with DR in human oncology are ABCB1 or P‐gp, ABCC1 or MRP1, and ABCG2 or BCRP, and have been demonstrated in canine cell lines, healthy dogs and dogs with cancer. Although this supports a causative role for these ABC‐transporters in DR cytotoxic agents in the dog, the relative contribution to the clinical phenotype of DR in canine cancer remains an area of debate and requires further prospective studies.

Background Canine breeds may be considered good animal models for the study of genetic predisposition to cancer, as they represent genetic clusters. From epidemiologic and case collection studies it emerges that some breeds are more likely to develop lymphoma or specific subtypes of lymphoma but available data are variable and geographically inconsistent. This study was born in the context of the European Canine Lymphoma Network with the aim of investigating the breed prevalence of canine lymphoma in different European countries and of investigating possible breed risk of lymphoma overall and/or different lymphoma subtypes. Results A total of 1529 canine nodal lymphoma cases and 55,529 control cases from 8 European countries/institutions were retrospectively collected. Odds ratios for lymphoma varied among different countries but Doberman, Rottweiler, boxer and Bernese mountain dogs showed a significant predisposition to lymphoma. In particular, boxers tended to develop T-cell lymphomas (either high- or low-grade) while Rottweilers had a high prevalence of B-cell lymphomas. Labradors were not predisposed to lymphoma overall but tended to develop mainly high-grade T-cell lymphomas. In contrast with previous studies outside of Europe, the European golden retriever population did not show any possible predisposition to lymphoma overall or to specific subtypes such as T-zone lymphoma. Conclusion Further prospective studies with more precise and consistent subtype identification are needed to confirm our retrospective results and to create the basis for the investigation of possible genes involved in different predispositions.

Despite clinical successes in the treatment of some early stage cancers, it is undeniable that novel and innovative approaches are needed to aid in the fight against cancer. Targeted therapies offer the desirable feature of tumor specificity while sparing healthy tissues, thereby minimizing side effects. However, the success rate of translation of these therapies from the preclinical setting to the clinic is dramatically low, highlighting an important point of necessary improvement in the drug development process in the oncology field. The practice of a comparative oncology approach can address some of the current issues, by introducing companion animals with spontaneous tumors in the linear drug development programs. In this way, animals from the veterinary clinic get access to novel/innovative therapies, otherwise inaccessible, while generating robust data to aid therapy refinement and increase translational success. In this review, we present an overview of targetable membrane proteins expressed in the most well-characterized canine and feline solid cancers, greatly resembling the counterpart human malignancies. We identified particular areas in which a closer collaboration between the human and veterinary clinic would benefit both human and veterinary patients. Considerations and challenges to implement comparative oncology in the development of anticancer targeted therapies are also discussed.

Background Pulmonary hypertension (PH) is a known co-morbidity in West Highland white terriers (WHWTs) affected with canine idiopathic pulmonary fibrosis (CIPF). The pulmonary vein-to-right pulmonary artery ratio (PV/PA) has recently been described for the detection of pre-capillary PH in dogs. The objective of the present study was to estimate the prevalence of PH at diagnostic, in WHWTs affected with CIPF, by using PV/PA, in comparison with a group of healthy breed-matched controls (CTRLs). Additional study objective was to explore whether the presence of PH at initial diagnosis of CIPF impacted survival time in dogs treated with sildenafil. Results Twenty-five client-owned WHWTs presented with CIPF and 19 CTRLs were included in the study. PV/PA in either two-dimensional mode (2D) or time-motion mode or both were measured from cineloops in each dog. Dogs were classified according to PV/PA value into non/mild PH (PV/PA measured in 2D ≥ 0.7) or moderate/severe PH (PV/PA < 0.7). Survival data of WHWTs affected with CIPF were extracted from medical record to assess association between presence of PH at diagnosis and outcome. 60 % overall prevalence for moderate/severe PH was estimated in this cohort of WHWTs presented with CIPF vs. 5 % in CTRLS ( P  = 0.0002). The presence of moderate/severe PH at initial presentation was not associated with survival. Conclusions Results of the present study confirm a high prevalence of PH at diagnosis in WHWTs affected with CIPF and highlight the utility of PV/PA as a non-invasive surrogate for assessment of PH in this population.

Histiocytic sarcoma (HS) is an aggressive malignant tumor of histiocytes, which can affect almost any organ in the body and is characterized by a broad array of tumor locations and clinical presentations. So far, no complete overview exists of the array of clinical aspects of HS in specific dog breeds in large groups. Therefore, we investigated the clinical characteristics of HS in a population of Bernese Mountain Dogs (BMD; n = 365) and Flat-Coated Retrievers (FCR; n = 289), which are two of the most affected dog breeds. Cases were selected from databases from different pathology services, and clinical information was retrospectively collected for each case. Localized HS was reported significantly more frequently in the FCR (60.6%) than in the BMD (39.2%), and disseminated HS was recorded significantly more frequently in the BMD (60.8%) than in the FCR (39.4%). Lameness was seen more often in FCR than in BMD, and the vast majority (78.1%) of LHS leading to lameness was located in the front legs in the FCR, while in the BMD, there was a more even distribution. BMD had significantly more often leukocytosis and thrombocytopenia, even corrected for the type of HS, than FCR. No significant difference in the frequency of anemia was recorded between BMD and FCR. In those dogs in which blood examination was performed, hypercalcemia was diagnosed in 15 BMD, while none of the FCR had hypercalcemia. The new information provided in this study can aid the diagnostic process and allow for prompt treatment recommendations.

Background: Some dogs with severe mitral valve regurgitation can have chronic cough, but its cause is unclear. Many of these dogs exhibit left principal (synonym mainstem) bronchial collapse or compression. Some clinicians believe that an enlarged heart, particularly the dilated left atrium, compresses the left principal bronchus, while others argue that a healthy bronchus cannot be compressed and that the cough is due to concurrent airway disease, such as bronchomalacia. In this study, we aimed to investigate the correlation between chronic cough and radiographic signs of bronchial narrowing in dogs with cardiomegaly secondary to primary mitral valve regurgitation. Methods: Four radiologists independently evaluated 51 sets of thoracic radiographs from client-owned dogs with cardiomegaly due to severe mitral valve regurgitation, including 26 sets of radiographs belonging to dogs with chronic (>8 weeks) cough and 25 without cough. The presence or absence of bronchial narrowing was assessed while the radiologists were blinded to patient characteristics and each other’s findings. Results: Interobserver variability was high, and the radiologists could not reliably predict which dogs had a chronic cough. Dogs with left atrial enlargement and airway narrowing sometimes coughed and sometimes did not. Likewise, some dogs with left atrial enlargement but no signs of airway compression or collapse coughed, and some did not. It was impossible to distinguish the groups based on these features. Conclusions: Bronchial compression by an enlarged heart and left atrium is an unlikely cause of chronic cough in dogs with severe primary mitral valve regurgitation.