Immunohistochemical Characterization of Immune Cell Infiltration in Feline Glioma.

The relationship between inflammatory cells and tumour biology has been defined in many human intracranial neoplasms, but it is relatively poorly characterized in veterinary medicine. The aim of this study was to define the immune cell infiltration in cases of feline glioma and its possible association with tumour morphology and type. A retrospective search identified 18 gliomas that met inclusion criteria. Tumours were subjected to immunohistochemistry (IHC) for CD3, CD20, Iba1, MAC387 and factor VIII-related antigen. For each antibody, the number of labelled cells was counted in 10 high-power (×400) fields and a cumulative score for each antibody was generated. Intratumoural and peritumoural CD3+ T lymphocytes were observed in all cases and occurred primarily within perivascular spaces and rarely around areas of necrosis or leptomeningeal spread. Perivascular CD20+ B lymphocytes were detected in 12/18 (67%) cases and occurred within and around tumours and near areas of leptomeningeal spread. MAC387 immunoreactivity highlighted intravascular monocytes in 9/18 (50%) cases, but failed to highlight tumour-associated macrophages. Intratumoural and peritumoural Iba1 immunoreactivity was observed in all cases, with increased overall intensity around areas of necrosis and leptomeningeal spread. Intratumoural and peritumoural factor VIII-related antigen immunoreactivity was also detected in all cases and was concentrated in areas of microvascular proliferation and necrosis. No significant associations were found between IHC scores for immune cells (i.e. lymphocytes and macrophages) and tumour morphology and type. Average factor VIII reactivity was higher in astrocytomas than oligodendrogliomas (P = 0.003).

Glial Changes and Evidence for Apoptosis in the Brain of Cats Infected by Cytauxzoon felis.

Ischaemic neuropathological changes associated with Cytauxzoon felis infection in cats have been reported recently. This paper describes the associated glial changes and the evidence for apoptosis in the brain of cats infected naturally by C. felis. Sections of brain from eight affected cats and eight age- and sex-matched control cats were evaluated by immunohistochemistry for expression of glial fibrillary acidic protein, CD18 and cleaved caspase-3. Vascular changes in the leptomeninges and parenchyma, the number of positive astrocytes and phagocytic cells (microglia or macrophages) and the average astrocytic cytoplasmic area and number and length of astrocytic processes were quantified, and a mean value for the grey and white matter in both groups was generated. Astrocytic hyperplasia (astrogliosis) and phagocytic cell hyperplasia were detected in all affected cats. Immunoexpression of cleaved caspase-3 was detected in intravascular and perivascular macrophages in the leptomeninges and, less often, in the grey and white matter in all affected cats. Four cats with encephalomalacia had additional cytoplasmic immunolabelling of phagocytic cells around the necrotic foci and macrophages and cell debris within the areas of necrosis. These results support the role of an extensive reaction of the brain tissue to hypoxia-ischaemia and a potential role of apoptosis in the neuropathogenesis of C. felis infection in cats.

Cytologic Criteria for Mast Cell Tumor Grading in Dogs With Evaluation of Clinical Outcome.

A 2-tiered histologic grading scheme for canine cutaneous mast cell tumors (MCTs) is based on morphologic characteristics of neoplastic cells, including karyomegaly, multinucleation, nuclear pleomorphism, and mitotic figures. Aspirates from MCTs may provide the same information more quickly, inexpensively, and less invasively. This study used these criteria to develop a cytologic grading scheme for canine MCTs to predict outcome. Three anatomic pathologists graded histologic samples from 152 canine MCTs. Three clinical pathologists evaluated aspirates from these masses using similar criteria. A cytologic grading scheme was created based on correlation with histologic grade and evaluated with a kappa statistic. Survival was evaluated with Kaplan-Meier survival curves. Cox proportional hazards regression was used to estimate hazard ratios for tumor grades and individual grading components. Simple logistic regression tested for relationships between risk factors and mortality. The cytologic grading scheme that best correlated with histology (kappa = 0.725 ± 0.085) classified a tumor as high grade if it was poorly granulated or had at least 2 of 4 findings: mitotic figures, binucleated or multinucleated cells, nuclear pleomorphism, or >50% anisokaryosis. The cytologic grading scheme had 88% sensitivity and 94% specificity relative to histologic grading. Dogs with histologic and cytologic high grade MCTs were 39 times and 25 times more likely to die within the 2-year follow-up period, respectively, than dogs with low grade MCTs. High tumor grade was associated with increased probability of additional tumors or tumor regrowth. This study concluded that cytologic grade is a useful predictor for treatment planning and prognostication.

Fatal Canid Herpesvirus 1 Respiratory Infections in 4 Clinically Healthy Adult Dogs.

Four healthy adult dogs (Golden Retrievers aged 6 years and 9 years, Dalmatian aged 13 years, and Mastiff aged 5 years) developed clinical signs of acute respiratory disease and died within 2 to 7 days of onset of clinical signs. The lungs of the 3 dogs submitted for necropsy were diffusely and severely reddened due to hyperemia and hemorrhage. Microscopic lesions in all dogs were suggestive of acute viral or toxic respiratory damage and varied from acute severe fibrinonecrotic or hemorrhagic bronchopneumonia to fibrinous or necrotizing bronchointerstitial pneumonia. Necropsied dogs also had hemorrhagic rhinitis and tracheitis with necrosis. Virus isolation, transmission electron microscopy, and polymerase chain reaction were used to confirm the presence of canid herpesvirus 1 (CaHV-1) in the lung samples of these dogs. Lung tissues were negative for influenza A virus, canine distemper virus, canine parainfluenza virus, canine respiratory coronavirus, and canine adenovirus 2. Canid herpesvirus 1 has been isolated from cases of acute infectious respiratory disease in dogs but has only rarely been associated with fatal primary viral pneumonia in adult dogs. The cases in the current report document lesions observed in association with CaHV-1 in 4 cases of fatal canine herpesvirus pneumonia in adult dogs.

Assessment of coagulation and potential biochemical markers for hypercoagulability in canine hyperadrenocorticism.

BACKGROUND: Anecdotal accounts and limited research suggest that dogs with spontaneous hyperadrenocorticism (HAC) are at risk of developing thromboembolic complications. Detailed description of coagulation status and identification of subsets of dogs at greatest risk would impact therapeutic recommendations for these patients. HYPOTHESIS: A subset of dogs with HAC will have a hypercoagulable tendency as identified by increased procoagulant activity, decreased fibrinolysis, or both. Objective 1: To document the existence of this hypercoagulable tendency in HAC dogs using assays of individual coagulation factors, fibrinolytic activity, and systemic coagulation. Objective 2: To evaluate clinical and biochemical markers in HAC dogs to identify a subset of HAC patients at increased risk of this hypercoagulable tendency. ANIMALS: Seventeen dogs newly diagnosed with HAC. METHODS: Prospective study. Medical history, physical examination findings, routine diagnostic tests, and comprehensive coagulation testing were performed at the time of HAC diagnosis. Coagulation parameters were assessed individually and as panels for each dog. Historical and clinical variables were correlated with coagulation parameters to identify risk factors. RESULTS: The majority (88.2%) of HAC dogs exhibited a hypercoagulable tendency. Abnormalities in 1 coagulation assay did not predict abnormalities in others. Duration of clinical signs of HAC did not predict hypercoagulability. Comorbid conditions or abnormal clinicopathologic parameters that predicted hypercoagulability were not identified. CONCLUSIONS AND CLINICAL IMPORTANCE: Although HAC dogs may demonstrate a hypercoagulable tendency individually and as a group, comorbid conditions or biochemical variables that would predict more severe coagulation abnormalities were not identified.

Synovial lesions in experimental canine Lyme borreliosis.

Borrelia burgdorferi is the causative agent of Lyme disease, which is mainly characterized by lameness in dogs. More than 95% of naturally infected dogs are asymptomatic or subclinical; however, in experimental studies, histologic synovial lesions are consistently observed in asymptomatic dogs inoculated with B. burdgorferi. This study investigates the ability of a synovial histopathologic scoring system, clinicopathologic data, and polymerase chain reaction (PCR) testing to differentiate between B. burgdorferi-infected and uninfected dogs. Eighteen 18-week-old beagles were subject to challenge with B. burgdorferi-infected wild-caught ticks (Ixodes scapularis), and 4 uninfected dogs served as controls. Infection was confirmed by serology (ELISA) and PCR amplification of B. burgdorferi-specific DNA of skin biopsies taken at the tick attachment site. A synovial scoring system from human medicine was adapted and implemented on postmortem synovial samples to discriminate infected and noninfected animals. Application of this system to elbows and stifles with a cumulative joint score cutoff  > 4 showed a sensitivity of 88.2% and a specificity of 100%, with a positive likelihood ratio of infinity and a negative likelihood ratio of 0.12. Complete blood count, serum biochemistry, urinalysis, urine protein:creatinine, urine PCR, synovial and lymph node cytology, and synovial PCR were evaluated but were not reliable indicators of clinical disease.

Evaluation of the positive predictive value of serum protein electrophoresis beta-gamma bridging for hepatic disease in three domestic animal species.

Beta-gamma bridging (ß-γ bridging) on serum protein electrophoresis is touted as being virtually pathognomonic for hepatic disease. However, the criteria for ß-γ bridging are not defined, and few publications support a relationship between ß-γ bridging and liver disease. The goal of this retrospective study was to evaluate the prevalence of hepatic pathology in animals with ß-γ bridging. All serum protein electrophoretograms from clinical patients generated at the University of Georgia between 1994 and 2008 were evaluated for the presence of ß-γ bridging, defined as (1) an albumin:globulin ratio below the reference interval; (2) indistinct separation between all ß and γ globulin fractions or between the ß(2) and γ fractions, with a negative shoulder slope of < 5%; and (3) predominance of γ proteins versus ß proteins. Of the 237 electrophoretograms examined, 25 (11 dogs, 11 cats, 3 horses) met the inclusion criteria for ß-γ bridging. Patients were classified into disease categories on the basis of biochemical, cytologic, and/or histologic findings. Positive predictive values of ß-γ bridging for hepatic and infectious diseases were determined with a one-sided exact binomial test. Of 25 animals, 8 had evidence for hepatic disease, whereas 9 had infectious diseases. As such, the positive predictive value of ß-γ bridging for hepatic disease was 32.0%, with a 95% confidence interval of 15.0% to 53.5% (P < .001), whereas for infectious disease, the positive predictive value was 36.0%, with a similar confidence interval. Beta-gamma bridging is not pathognomonic for liver diseases and is as frequently found with infectious diseases.

Canine synovial myxoma: 39 cases.

This report describes the signalment, clinical findings, gross appearance, histological and immunohistochemical characteristics, and behavior of 39 cases of canine synovial myxoma. Large-breed middle-aged dogs-especially, Doberman Pinschers and Labrador Retrievers-were most commonly affected. The stifle and digit were the most common sites. Grossly, the tumors were composed of gelatinous nodules that often filled the joint cavity and exuded viscous fluid on cut section. In 12 cases (31%), radiographic bony lysis or grossly invasive growth was noted clinically. Histologically, the nodules were sparsely cellular and composed of stellate to spindle cells suspended in an abundant myxomatous matrix. By immunohistochemistry, the cells were positive for vimentin, heat shock protein 25, and cadherin 11 and negative for cytokeratin and S100 protein; some cells (20-40%) were positive for CD18. Affected dogs had long survival times (average, 2.5 years), even with incomplete excision of the tumor. Three cases had local recurrence, but none metastasized or directly resulted in death. Canine synovial myxoma is a histologically distinctive tumor with a good prognosis.

Reversible fibroadenomatous mammary hyperplasia in male and female New Zealand white rabbits associated with cyclosporine A administration.

All male and female New Zealand white rabbits in a limbal cell graft study developed marked generalized mammary gland hypertrophy. Postprocedural medications included ophthalmic 0.1% dexamethasone, ophthalmic 0.5% cyclosporine, and subcutaneous cyclosporine A. Cytologic examination revealed epithelial clusters with minimal malignant criteria. On histologic evaluation, there was diffuse glandular hyperplasia with mild cellular atypia and ductal ectasia separated by abundant hypercellular fibrous stroma, consistent with fibroadenomatous mammary gland hyperplasia. The hyperplasia resolved within 2 weeks of cessation of cyclosporine, and at necropsy identifiable mammary masses were not found. Very little has been reported about the use of cyclosporine in laboratory rabbits and its association with development of mammary gland hyperplasia. This is the first report in which administration of cyclosporine to male and female rabbits at a dose as low as 5 mg/kg/day induced benign fibroadenomatous mammary gland hyperplasia. This change regressed after cessation of the drug.

Fibrotic myopathy of the iliopsoas muscle in a dog.

Fibrosis of the iliopsoas muscle can result in pelvic limb lameness in dogs. In this case report we describe fibrosis after an initial injury of the iliopsoas muscle in a dog. A seven-year-old hunting dog developed an acute onset of lameness and pain of the left pelvic limb after an intense period of exercise. Two months later, the dog was referred for evaluation of a non-weight-bearing left pelvic limb lameness. Orthopaedic examination revealed pain on hyperextension and internal rotation of the left coxofemoral joint. Neurological examination revealed a decreased patellar reflex in the left pelvic limb. Computed tomographic images showed non-uniform, contrast enhancement of the left iliopsoas muscle. The animal was treated with an iliopsoas tenomyectomy. Histopathological examination of the affected iliopsoas muscle revealed endomysial and perimysial mature fibrous replacement tissue. Sixteen weeks after surgery, the dog had returned to pre-injury levels of exercise.