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In canine cutaneous mast cell tumours (cMCTs), histologic grade and clinical stage are the most important prognostic factors, with high-grade tumours and metastatic lymph nodes (LNs) significantly influencing the evolution of disease. However, it is uncertain whether histologic grade and clinical stage should be given equal weighting value in patient prognostication and management. Dogs with low- and high-grade cMCTs and at least one overtly metastatic sentinel LN undergoing standardized treatment, consisting of surgical excision of the cMCT, lymphadenectomy and chemotherapy, were retrospectively included. The aim was to determine whether, at the same clinical stage, histologic grade retained prognostic relevance. Sixty dogs were included: 26 had a high-grade cMCT tumour and 34 had a low-grade cMCT. Median follow-up was 367 days (range, 187-748) in the high-grade group, and 1208 days (range, 180-2576) in the low-grade group. Median time to progression was significantly shorter in the high-grade group than in the low-grade group (214 days versus not reached; p .001), as well as tumour-specific survival (545 days versus not reached; p .001). On multivariable analysis, a high histologic grade and incomplete margins retained prognostic significance for both tumour progression and tumour-specific death. In dogs with cMCT and at least one overtly metastatic LN undergoing multimodal treatment, histologic grade significantly correlated with outcome. Overall prognosis was not unfavourable, even in the high-grade group, further supporting that a multimodal therapeutic approach, addressing primary tumour and sentinel LN, should be offered. Whether chemotherapy should be incorporated in the therapeutic planning of low-grade cMCTs remains to be defined.

Localized histiocytic sarcoma may occur as a primary lesion in periarticular tissues of large appendicular joints. Treatment options for the primary lesion include radical surgical excision, radiation therapy (RT), or both, in combination with chemotherapy for potential systemic metastases. In an effort to better characterize the time to progression (TTP) following surgical vs non-surgical approaches for periarticular histiocytic sarcoma (PAHS), a contemporary European population of affected dogs was retrospectively surveyed. Medical records were queried for newly-diagnosed PAHS cases undergoing surgery (predominantly limb amputation) or RT followed by systemic chemotherapy. Of 49 dogs, 34 underwent RT and 15 underwent surgery. All dogs received adjuvant chemotherapy. There was no statistically significant difference in TTP or overall survival between groups. The median TTP was 336 days for the operated dogs and 217 days for the irradiated dogs (P = .117). The median overall survival time was 398 days for the operated dogs and 240 days for the irradiated dogs (P = .142). On multi-variable analysis, the variables significantly associated with an increased risk of both tumour progression and tumour-related death were regional lymph node and distant metastasis at admission. Survival and local control rates following RT may be comparable to radical resection. These data may better inform shared decision-making processes between multi-disciplinary care providers and owners.

Objectives The aim of this study was to evaluate the relationship between the ultrasonographic (US) diffuse honeycomb pattern (HCP) of the spleen and a pathological diagnosis in cats, and to assess the influence of transducer type on HCP visualisation. Methods Abdominal ultrasounds of cats with an HCP were reviewed and splenic size, shape, margination, other parenchymal alterations and splenic hilar lymphadenopathy were recorded. When applicable, images acquired with high-frequency linear and curvilinear transducers were compared to determine if an HCP was more frequently demonstrated on high-resolution images. A retrospective review of the corresponding splenic cytohistopathological samples was also performed. Results Thirty-three cats met the inclusion criteria. Five cases were diagnosed by histology and 28 by cytology, confirmed by PCR for antigen receptor rearrangements (PARR) in uncertain cases. There were 15 cases of lymphoid hyperplasia, eight cases of lymphoma (four B cell, three T cell and one large granular lymphocytes), six cats with splenitis, three with extramedullary haematopoiesis and one with histiocytic sarcoma. The prevalence of lymphoma in cats with an HCP of the spleen was 24%. Splenomegaly was the most frequent US feature associated with an HCP and was observed in all lymphoma cases. In the images obtained from both high-frequency linear and micro-convex transducers the visualisation of an HCP was enabled in all cases (24/24) and in 62.5% (15/24), respectively. Conclusions and relevance: Based on our findings, a US HCP of the spleen in cats can be associated with benign and malignant disorders and is infrequently associated with lymphoma in comparison with dogs. Cytological or histological examination, possibly supplemented by PARR, should always be performed for diagnostic support. Use of high-frequency linear transducers is recommended to properly recognise an HCP or subtle changes in splenic parenchyma.

Heinz bodies (HBs) are known to interfere with automated hematology in cats, particularly with the white blood cell (WBC) count. We evaluated the influence of feline HBs on the complete blood count (CBC) results obtained using a flow cytometry–based analyzer. We retrospectively selected cats with circulating HBs and reviewed the results of their CBCs, including red blood cell (RBC) indices, basophil/lobularity (Baso) WBC count (WBCB), peroxidase (Perox) WBC count (WBCP), and cytograms. Based on the presence or absence of HB-related artifacts in their Baso cytogram, cats were grouped into Baso-HBs and HBs groups, respectively, for comparison. The WBCB and WBCP were compared to manual counts of WBCs carried out on blood smears at 400× (MC-WBC). We included 32 cats in our study: 9 of 32 were in the Baso-HBs group, and 23 of 32 were in the HBs group. Baso-HBs cats had a significantly increased HB percentage ( p < 0.001), WBCB ( p < 0.001), difference between WBCB and WBCP ( p < 0.001), lymphocyte count ( p < 0.001), mean corpuscular hemoglobin concentration ( p < 0.001), and difference between calculated and measured erythrocyte hemoglobin concentrations ( p < 0.001) compared to HBs cats. In Baso-HBs cats, the WBCB was significantly higher than the WBCP ( p = 0.02); no significant difference was detected between the WBCP and the MC-WBC ( p = 0.88). Evaluation of automated CBC results raised the suspicion of HB-related interference when using a hematology analyzer in cats; hence, blood smear examination remains essential in routine practice.

Treatment options for dogs with metastatic (stage III) splenic hemangiosarcoma are limited. A doxorubicin-based chemotherapy regimen is commonly administered; however, there are no published data to support this practice. The aim of this study was to investigate the impact of maximum-tolerated-dose chemotherapy (MTD), metronomic chemotherapy (MC) and no adjuvant treatment on outcome in dogs with stage III splenic hemangiosarcoma undergoing splenectomy. Medical records of dogs with stage III splenic hemangiosarcoma that underwent splenectomy followed by MTD chemotherapy, MC or no adjuvant treatment were retrieved. Time to progression (TTP), survival time (ST) and toxicity were evaluated. One hundred three dogs were identified: 23 received adjuvant MTD, 38 MC and 42 were not medically treated. Overall median TTP and ST were 50 (95% confidence interval [CI], 39-61) and 55 days (95% CI, 43-66), respectively. Dogs treated with adjuvant MTD had a significantly longer TTP and ST compared with dogs receiving MC (median TTP, 134 vs 52 days, P = .025; median ST, 140 vs 58 days, P = .023, respectively). Dogs treated by splenectomy only had the shortest median TTP (28 days) and ST (40 days). However, treatment-related adverse events (AEs) were significantly more frequent in the MTD group (P = .017). The outcome for dogs with metastatic splenic hemangiosarcoma is poor. While MTD showed greater efficacy compared to MC, toxicity was higher in this group. Treatment-related AEs need to be carefully balanced against this modest survival prolongation when offering adjuvant MTD to dogs with advanced stage hemangiosarcoma.

Hidradenitis suppurativa/acne inversa (HS) is one of the most debilitating inflammatory chronic skin diseases and it heavily impairs the emotional and relational life of the patients. Despite its clinical and epidemiological relevance, its psychological correlates are still largely unexplored. The aim of the present study was to investigate the psychological and emotional impact of HS, with a specific focus on psychiatric symptoms, particularly depression, suicidal ideation, self-esteem, anger, and some personality traits. Thirty eight patients diagnosed with HS (HS Group) were compared with a control group of 28 outpatients diagnosed with nevi (N Group) and assessed with psychometric questionnaires (GHQ-28, STAXI-2, BDI-II, BHS, RSES, EF Questionnaire, and I-R Questionnaire). Results showed significant differences between the two groups, with more psychiatric symptoms, lower self-esteem, and higher levels of state anger and of emotional fragility in HS patients. These findings suggest the evidence of a significant psychiatric comorbidity in HS and of a strong emotional impact of the disease.

Identification of prognostic factors for perivascular wall tumours (PWTs) is desirable to accurately predict prognosis and guide treatment. 100 and two dogs with surgically excised PWTs without distant metastasis were retrospectively enrolled in this multi-institutional study, and the impact of pre-treatment leukocyte parameters, clinical and histopathological variables on local recurrence (LR) and overall-survival time (OST) were evaluated. Increasing values of white blood cell count (WBCC), neutrophil count (NC) and neutrophil-to-lymphocyte ratio (NLR) were significantly correlated with the hazard of LR in univariate analysis. WBCC and NC remained prognostic when adjusted for margins, grade, tumour size, location and skin ulceration, but lost their significance when adjusted for mitotic index and necrosis, whilst NLR remained prognostic only when close margins where categorised as infiltrated. Castrated males had a higher hazard of LR than intact males in univariate analysis, but significance was lost in multivariate models. Ulcerated PWTs and those located on the distal extremities had a higher hazard of LR both in univariate and multivariate analysis. Histological grade, necrosis, mitotic count, and infiltrated margins were all associated with LR both in univariate and multivariate analysis. Boxer breed, older age, ulceration, grade III, necrosis >50% and higher mitotic count were correlated with shorter OST, although breed and age lost their significance in multivariate analysis. Prognostication of surgically excised PWTs should be based on both clinical and histopathological variables. If validated in further studies, leukocyte counts and NLR may aid the clinician in identifying dogs at higher risk of LR before treatment.

Recent literature suggests a combination of flow cytometric determination of Ki‐67 and immunophenotype as a reliable tool to classify canine lymphomas. Immunohistochemistry (IHC) on histological samples is the gold standard technique assessing Ki‐67 index. Agreement between IHC and FCM derived Ki‐67 indices has never been investigated. The aim of this study was to investigate the agreement between IHC and FCM in the assessment of Ki‐67 expression/index, in order to evaluate whether FCM may serve as a non‐invasive alternative method for the estimation of proliferative activity in canine lymphoma. Dogs with previously untreated canine lymphoma undergoing diagnostic lymphadenectomy were prospectively enrolled. Ki‐67 expression/index was assessed by FCM and IHC and expressed as percentage of positive cells. 39 dogs classified by histopathology matched the inclusion criteria. With both methods, Ki‐67 expression/index was higher in intermediate/high‐grade lymphomas. Spearman's coefficient of correlation was ρ = 0.57; (95% CI0.33‐0.75) suggesting a moderate correlation. A Bland‐Altman plot revealed a negative constant bias of −3.55 (95% CI: −10.52 to 3.42) with limits of agreement from −45.71 to 38.61. The study confirmed agreement albeit with wide confidence intervals between the values of Ki‐67 expression/index assessed with FCM and IHC. Discrepancies were observed in a subset of cases. Possible explanation could be that Ki‐67 index in IHC is determined in the most proliferative areas of the slide, which could introduce kind of sampling bias, whereas FCM evaluates many more cells in cell suspension. Further studies are warranted to investigate this phenomenon.

Background: Sepsis is a life-threatening condition associated with an exacerbated production of both pro- and anti-inflammatory cytokines that can promote a hyperactive response to infection or induce immunoparalysis. Data regarding the immune response to sepsis in cats are scarce. Establishing the profiles of cytokines and chemokines in feline sepsis to characterize the nature of the immune responses to sepsis might enable individualized treatments to be developed and targeted. Objective: To evaluate the cytokine and chemokine network in cats with sepsis and septic shock, and to investigate the associations of these analytes with disease severity and outcome. Methods: Blood samples prospectively collected at presentation of cats with sepsis and septic shock to two veterinary teaching hospitals were analyzed. Forty healthy cats were included as controls. A 19-plex feline cytokine/chemokine magnetic bead assay system was used to measure analytes in citrated plasma samples. Cytokine concentrations were compared between groups using the Kruskal-Wallis test with Dunn's post-hoc correction for multiple comparisons. Cytokine concentrations were compared between survivors and non-survivors with the Mann-Whitney U test. Odds ratios were calculated using logistic regression. A multivariable logistic regression model for prediction of septic shock was constructed. Results: The study enrolled 35 septic cats. Many cytokines were undetectable in both sick and healthy control cats and were excluded from subsequent analyses. Comparisons of cytokine concentrations among healthy controls, cats with sepsis (n = 12) and cats with septic shock (n = 23) revealed that sick cats (sepsis or septic shock) had significantly higher plasma concentrations of IL-6, IL-8, KC-like, and RANTES compared to healthy controls. The combination of MCP-1, Flt-3L, and IL-12 was predictive of septic shock. None of the cytokines analyzed was predictive of outcome in this study population. Conclusion: Plasma concentrations of IL-6, IL-8, KC-like, and RANTES are increased in cats with sepsis and may play important roles in pathogenesis. Multivariable modeling suggested that analysis of cytokines might aid differentiation of septic shock from sepsis. None of the cytokines analyzed was predictive of outcome. Measurement of these cytokines might enable future studies to better diagnose and characterize feline sepsis and septic shock.

Lymph node (LN) metastasis is a negative prognostic factor in dogs with cutaneous mast cell tumours (cMCTs). While elective lymphadenectomy of metastatic LNs improves outcome, the benefit of adjuvant medical therapy in dogs with early metastatic (HN2) LNs is debated. The aim of this retrospective multicentre study was to evaluate the therapeutic benefit of adjuvant medical therapy following surgical removal of the primary low-grade cMCT (Patnaik grade 1-2 and Kiupel low-grade) and lymphadenectomy of HN2 LNs by analysing survival rates and patterns of recurrence. Seventy-three dogs were included: 42 received adjuvant medical treatment (chemotherapy and/or kinase inhibitors), and 31 did not. The median follow-up time for medically treated dogs was 619 days: two experienced local recurrence, three nodal relapse and four distant relapse. For dogs undergoing surgery only, the median follow-up time was 545 days. None of them experienced local recurrence, nodal, or distant relapse. Time to progression was significantly shorter in dogs receiving adjuvant medical treatment (P = .021). A similar tendency was observed for overall survival (P = .056). The current study shows that dogs with low-grade cMCTs, that undergo surgical excision of the primary tumour and elective lymphadenectomy of the HN2 regional LN harbour a good prognosis. The use of adjuvant medical treatment in these dogs does not seem to provide any benefit in terms of progression and survival.

Mast cell tumours (MCTs) are often diagnosed by cytology based on the identification of purple intracytoplasmic granules with methanolic Romanowsky stains, including May-Grünwald-Giemsa (MGG). In clinical practice, aqueous rapid stains (RS) are commonly used, but mast cell granules may not stain properly. Aim of this prospective study was to investigate the frequency of MCT hypogranularity with RS and its potential implications in tumour identification, cytological grading assessment and recognition of nodal metastatic disease. Cytological preparations of canine primary MCTs and metastatic lymph nodes with subsequent histopathological confirmation were included. For each case, good-quality smears were stained with both MGG and RS and comparatively assessed. Eleven of 60 (18.3%) primary MCTs were hypogranular with RS; 9 of them were histologically high-grade tumours and in 3 cases (5%) a definitive MCT diagnosis could not be made. Accuracy in cytological grading assessment (85%) did not differ between RS and MGG. Thirteen of 28 (46.4%) metastatic lymph nodes were hypogranular with RS and 3 independent observers failed to identify nodal MCT metastases in 7% to 18% of RS-stained smears. This study confirms that, in limited cases, RS can be ineffective in staining MCT granules, particularly in high-grade tumours, thus making diagnosis more dependent on experience and quality of preparations. In dubious cases, methanolic stains should be applied. The use of RS is discouraged for the search of nodal metastases, as the identification of isolated mast cells can be more challenging.

Introduction Mast cell tumors (MCTs) are often diagnosed by cytology based on the identification of their characteristic purple intracytoplasmic granules with methanolic Romanowsky stains, including May Grünwald-Giemsa (MGG). In clinical practice, aqueous Romanowsky stains are commonly used because of their rapidity, but the risk exists that mast cell granules may not stain properly. The purpose of this study was to investigate the phenomenon of hypogranularity of MCT with rapid staining (RS) in terms of frequency and correlations with tumor characteristics, along with diagnostic and prognostic implications. Materials and Methods A prospective study was carried out on cytologic preparations of histologically-confirmed canine primary MCTs and metastatic lymph nodes. For each case, good-quality smears were stained with both MGG and RS and comparatively assessed. Results Fifteen out of 60 (25%) primary canine MCTs were hypogranular with RS (P=0.002). These were predominantly cutaneous high-grade tumors and in 7 of them (11.7%) a certain diagnosis could not be made with RS. Accuracy in grading assessment was not significantly different compared with MGG (79% vs 83%). Ten of 25 (40%) metastatic lymph nodes were hypogranular with RS (P=0.002); the negative predictive value in the detection of nodal metastases, assessed with three independent observers, was significantly lower (100% vs 73%; P=0.010). Discussion This study confirms that RS can be ineffective in staining MCT granules, especially in biologically aggressive tumors, and can occasionally prevent the achievement of a correct diagnosis. The use of RS is discouraged for the search of nodal metastases, as the identification of isolated mast cells can be particularly challenging.

Feline large granular lymphocyte (LGL) lymphoma is an uncommon subtype of lymphoma characterized by a grave prognosis and scarce response to chemotherapy. There are limited reports on clinico-pathological and prognostic factors. One-hundred and 9 cats with newly diagnosed LGL lymphoma that underwent initial staging (including hematology, serum biochemistry, thoracic radiographs and abdominal ultrasound), and followed-up were retrospectively evaluated. LGL lymphoma was localized within the gastrointestinal tract with or without extra-intestinal involvement in 91.7% of the cases, and at extra-gastrointestinal sites in 8.3%. Symptoms were frequent. Anemia (31.2%) and neutrophilia (26.6%) were commonly observed, and 14 (12.8%) cats had neoplastic circulating cells. Frequent biochemistry abnormalities included elevated ALT (39.4%) and hypoalbuminemia (28.4%). Twenty (54.1%) of 37 cats had elevated serum LDH. Treatment varied among cats, and included surgery (11%), chemotherapy (23%), corticosteroids (38.5%) and no treatment (27.5%). Median time to progression (MTTP) was 5 days, and median survival time (MST) 21 days. MST was significantly shorter in the case of substage b, circulating neoplastic cells, lack of chemotherapy administration, and lack of treatment response. A small subset of cats (7.3%) survived more than 6 months, suggesting that a more favorable clinical course can be found among LGL lymphoma patients.

There is little information on sequence variation of canine adenovirus type 1 (CAdV-1), the aetiological agent of infectious canine hepatitis (ICH). This study reports hexon and fibre gene sequence variants of CAdV-1 in a dog with systemic ICH and a dog with the ocular form of the disease (‘blue eye’) in Northern Italy in 2013. One of the sequence variants matched a CAdV-1 fox sequence previously detected in Italy.

Immature granulocytes (IG) are a marker of severe inflammatory states in human beings and animals, and have been linked to a diagnosis of sepsis and poor prognosis. The delta neutrophil index (DNI), automatically calculated by a haematological analyser, provides an estimate of circulating IG. In particular, an increased DNI value has been associated with the severity of sepsis, and mortality, in critically ill human beings. The aims of this study were to determine the DNI reference interval (RI) in healthy dogs, and to evaluate its diagnostic and prognostic significance in dogs with sepsis. A total of 118 dogs with sepsis undergoing a complete blood cell count (CBC) at the time of hospital admission were included retrospectively. Dogs with sepsis were compared to 20 dogs with primary immune-mediated haemolytic anaemia (IMHA) and 99 healthy controls. The DNI RI was set from 0 to 9.2%. The DNI was significantly higher in dogs with sepsis compared to dogs with IMHA and healthy dogs (P < 0.001), and significantly higher in dogs with septic shock compared to septic dogs without circulatory failure (P < 0.03). No differences were detected between survivors (78/118) and non-survivors (40/118). Septic dogs with a DNI above the RI had significantly higher frequencies of IG and toxic neutrophil changes on manual blood smear evaluation (P = 0.03 and P < 0.001, respectively). The DNI had a fair performance in identifying dogs with sepsis in this population and predicted septic shock. Larger prospective studies are needed to validate DNI measurement in dogs and to test its clinical utility.

Systemic inflammatory response syndrome (SIRS) and sepsis can be challenging to diagnose in cats. Retrospectively, we investigated the diagnostic and prognostic potential of serum amyloid A (SAA), a major feline acute-phase protein (APP), in a population of critically ill cats with SIRS related to trauma or sepsis. A total of 56 SIRS cats (trauma n = 27; sepsis n = 29) were included and compared with healthy controls ( n = 18). SAA concentration was significantly increased in SIRS cats compared to controls, confirming its potential for the detection of systemic inflammation in this species. Significantly higher values of SAA were detected in cats belonging to the sepsis group; however, according to the results of the receiver operating characteristic curve analysis, the value of using SAA (>81 mg/L) to discriminate septic cats was only moderate (AUC = 0.76). Additionally, cats with sepsis had significantly higher serum bilirubin concentrations and toxic neutrophil changes compared to the trauma group. Overall, 38 of 56 cats were survivors; 18 of 56 were non-survivors, with 83% of the non-survivors (15 of 18) belonging to the sepsis group. Serum bilirubin concentration, but not SAA, was able to predict outcome. Prospective studies are needed to assess the potential of SAA in the diagnosis of feline sepsis and outcome prediction.

Background and Hypothesis: We retrospectively evaluated the Clinicopathologic findings and outcome predictors in dogs with Leptospira interrogans Australis serogroup infections. Animals and Methods: The medical records of 159 dogs that had a leptospiral microscopic agglutination test (MAT) performed between 2001 and 2004 were reviewed. Results: Twenty dogs met serologic criteria for either symptomatic (16 dogs) or asymptomatic (4 dogs) infection caused by Leptospira interrogans Australis serogroup. Seven of 16 symptomatic dogs died or were euthanized and 9/16 recovered. Systemic inflammatory response syndrome (SIRS) was observed in 9/16 dogs. The presence of SIRS did not affect prognosis (P= .357). C-reactive protein (CRP) and haptoglobin (Hpt) concentrations were altered in all symptomatic dogs, but results did not differ significantly between survivors and nonsurvivors (P= .08 and P= .055, respectively). Conversely, the CRP to Hpt ratio (CRP/Hpt) was significantly increased in nonsurvivors. Disseminated intravascular coagulation (DIC) was diagnosed in 7/16 dogs. DIC did not significantly affect outcome (P= .126). Multiple organ involvement was present with renal failure in 16/16, liver damage in 12/16, cardiac damage in 11/16, and muscular damage in 8/16 dogs. Conclusions and Clinical Importance: Among the evaluated Clinicopathologic biomarkers, serum albumin, cardiac troponin I, CRP/Hpt, urinary albumin, and urinary total protein to creatinine ratio were found to predict outcome and warrant evaluation in larger prospective studies.

In recent years, the evaluation of lymphoproliferative malignancies by molecular assays has become increasingly popular in human medicine. Since microscopic techniques are often unable to recognise a residual neoplastic population whenever they account for less than 1% of the total cells, molecular tools are mainly used for the assessment of the MRD ( Campana et al., 1995; Rezuke et al., 1997). Many different molecular markers have been evaluated in order to increase the sensitivity of the diagnostic tools; among these, the clonal rearrangements of immunoglobulin (VDJ segments) and TCR receptor (TRCγ V and J segments) genes, have been investigated. A PCR assay for the identification of BCR and TCR clonal rearrangements has also recently validated in veterinary medicine; this assay was used in association with cytology and/or histology for diagnosing lymphoproliferative diseases in dogs (Burnett et al., 2003; Dreitz et al., 1999; Vernau et al., 1999). The aim of this work was to evaluate the usefulness of this PCR assay in identification of MRD in lymphoma-affected dogs, in order to modulate therapeutic protocols to obtain longer remission times.

Canine non-Hodgkin's lymphoma (NHL) is considered to be a good animal model for its human counterpart; nevertheless, comparative data on neoangiogenesis are completely lacking. The aim of this study is to investigate the levels of serum vascular endothelial growth factor (VEGF) and matrix metalloproteinases (MMPs) 2 and 9 in lymphoma-affected dogs. Circulating levels of VEGF and both MMP 2 and 9 activities significantly correlate with the WHO substage b prognostic factor; moreover, VEGF at admission have an independent influence on the length of the disease free interval. As in humans, serum VEGF concentration and most likely also MMPs plasma activity have prognostic value in canine NHL spontaneous model.