Prior joint disease is associated with increased risk of periarticular histiocytic sarcoma in dogs.

Periarticular histiocytic sarcoma (PAHS) is the most common synovial tumour in dogs and is characterized by aggressive local disease with a high rate of distant metastasis. Previously, an association between PAHS and prior joint disease has been demonstrated in the Bernese Mountain Dog breed and suggested in the Rottweiler. We hypothesized that this association would be present in other breeds and investigated this via a retrospective, case-controlled analysis. Cases were dogs diagnosed with PAHS of the stifle or elbow. Controls were age, breed and sex-matched dogs without a diagnosis of histiocytic sarcoma. Diagnosis of prior joint disease was determined based on review of medical records and direct veterinarian and owner communications. Data were evaluated using logistic regression, 2-sampled t tests, and chi-squared analysis. Our study population consisted of 28 cases and 46 controls, including Flat-Coated, Golden and Labrador Retrievers, Rottweilers, English Bulldogs, Shih Tzus, Australian Shepherds, Staffordshire Terriers and mixed breed dogs. Dogs with PAHS were more likely to have prior joint disease in the tumour-affected joint compared with the control population (odds ratio [OR] = 13.42, P < .0001, 95% confidence interval [CI] = 4.33-48.63). A total of 88.2% of dogs with stifle PAHS had prior joint disease in their tumour-affected joint, most commonly cranial cruciate ligament rupture. This study confirms that the previously noted association between prior joint disease and PAHS in Bernese Mountain Dogs also applies to other breeds. Additional studies are needed to further investigate for a causal relationship.

Histiocytic sarcoma in 14 miniature schnauzers - a new breed predisposition?

OBJECTIVES: To describe a series of miniature schnauzers diagnosed with histiocytic sarcoma and assess for possible breed predisposition. MATERIALS AND METHODS: Medical records of miniature schnauzers with a diagnosis of histiocytic sarcoma between January 2008 and April 2015 were reviewed. Data collected included signalment, body weight, presenting complaint, date of diagnosis, clinicopathologic and diagnostic imaging findings, treatment, therapeutic response, date of death or last follow-up and necropsy findings. Breed predisposition was assessed with odds ratios, using breed-matched dogs without histiocytic sarcoma admitted during the study period as controls. Pedigree analysis was performed for dogs with available registration information. RESULTS: Fourteen miniature schnauzers were diagnosed with histiocytic sarcoma during the study period, making them over-represented among the hospital population (odds ratio=4·8, P=0·0009). Disease was considered localised in ten dogs and disseminated in four. Of the dogs with localised disease, nine were diagnosed with primary pulmonary histiocytic sarcoma based on the presence of a large pulmonary mass with (n=7) or without (n=2) evidence of intra-thoracic metastasis, and one had gastric histiocytic sarcoma with nodal metastasis. Treatments varied, but an aggressive clinical course was found in most patients. Pedigree analysis revealed a recent common ancestor for a subset of the dogs assessed. CLINICAL SIGNIFICANCE: Miniature schnauzers were over-represented among dogs with histiocytic sarcoma in this patient population. Pedigree analysis supports an inherited risk factor, which has not previously been suggested in the breed. Primary pulmonary involvement with or without intra-thoracic metastasis was common in this cohort.

Comparison of presumptive echocardiographic and definitive diagnoses of cardiac tumors in dogs.

BACKGROUND: Echocardiography is used for identification of cardiac tumors and presumptive diagnoses often are made based on the location of identified masses. OBJECTIVES: To determine the accuracy of echocardiographically based presumptive diagnoses of cardiac tumors when compared with clinicopathologic or histopathologic definitive diagnoses. ANIMALS: A total of 24 client-owned dogs having a cardiac mass on echocardiogram that was subsequently definitively diagnosed by cytology or histopathology. METHODS: Retrospective study. A Cardiac Veterinary Database search of animals seen at the University of Tennessee John and Ann Tickle Small Animal Hospital from 2006 to 2012 identified 24 dogs that fit the inclusion criteria. RESULTS: The presumptive diagnosis of chemodectoma, ectopic thyroid carcinoma, or lymphoma in cases with heart base masses was correct in 7/9 cases. The presumptive diagnosis of hemangiosarcoma in cases with right atrial masses was correct in 4/8 cases. Seven cases had an open diagnosis because of the unusual presentation on echocardiogram (ECG); various neoplasms were diagnosed in these animals, but hemangiosarcoma, chemodectoma, ectopic thyroid carcinoma, and lymphoma accounted for 6 of them. Pericardial effusion was seen in 10/24 cases. ECG abnormalities were seen in 8/24 cases. Survival ranged from <1 to >150 days. CONCLUSIONS AND CLINICAL IMPORTANCE: In this retrospective study, the presumptive diagnosis based on echocardiographic tumor location was only moderately accurate. Cardiac tumors that were considered unusual on echocardiogram were nonetheless frequently found to be the common cardiac tumor types seen in dogs.

Hepatic encephalopathy associated with hepatic lipidosis in llamas (Lama glama).

Hepatic encephalopathy has been listed as a differential for llamas displaying neurologic signs, but it has not been histopathologically described. This report details the neurologic histopathologic findings associated with 3 cases of hepatic lipidosis with concurrent neurologic signs and compares them to 3 cases of hepatic lipidosis in the absence of neurologic signs and 3 cases without hepatic lipidosis. Brain from all 3 llamas displaying neurologic signs contained Alzheimer type II cells, which were not detected in either subset of llamas without neurologic signs. Astrocytic immunohistochemical staining intensity for glial fibrillary acid protein was decreased in llamas with neurologic signs as compared to 2 of 3 llamas with hepatic lipidosis and without neurologic signs and to 2 of 3 llamas without hepatic lipidosis. Immunohistochemical staining for S100 did not vary between groups. These findings suggest that hepatic encephalopathy may be associated with hepatic lipidosis in llamas.

Age-associated cartilage degeneration of the canine humeral head.

The goal of this study was to determine if cartilage lesions of the humeral head in adult dogs are the consequence of osteochondrosis dissecans or degenerative joint disease. A gross and histologic survey was performed of humeral head cartilage lesions of 155 dogs ranging in age from 1 week to 19 years. The humeral head and cartilage lesion size were measured for each dog. Cartilage lesions were classified as fibrillation, fissures, erosion, and/or eburnation. The area of each lesion was multiplied by a severity score (fibrillation and fissures 1, erosion 2, and eburnation 3) to create a combined score for each humeral head. Correlations between this combined lesion score and age, humeral head size, body weight, and body condition score were assessed using a Bonferroni-corrected alpha of .01. Twenty-six humeral heads were also evaluated histologically. Of the 155 dogs, 80 (52%) had gross lesions of the articular cartilage. The presence and severity of the articular cartilage lesions were positively correlated with age, humeral head size, body weight, and body condition score. The average age of dogs with cartilage lesions was 8.8 years, and 77/105 (74%) of adult dogs had cartilage lesions. Fifty dogs were 3 years of age or younger; 3 of those had cartilage lesions, 1 of which was osteochondrosis. These data indicate that cartilage erosion of the caudal humeral head in dogs is a common degenerative lesion acquired in adult large breed dogs; osteochondrosis dissecans does not precede the lesion in the vast majority of cases.

The value of biomedical research training for veterinary anatomic and clinical pathologists.

Veterinary pathologists traditionally have been actively engaged in research as principal investigators and as collaborators. Pathologists frequently obtain advanced training in research; however, it appears that in the last 10 years there has been a reversal of a previous trend toward increasing numbers of pathologists obtaining PhD degrees. This has arisen despite an established shortage of veterinarians engaged in research. This article evaluates the benefits of research training for individual pathologists, including a wide spectrum of professional opportunities and additional skill development beyond that usually provided by diagnostic pathology training alone. Various training models are discussed, including combined and sequential diagnostic residency and research degree training as well as the nondegree research fellowship programs more commonly pursued in human medicine. Best-practice recommendations for program infrastructure, mentorship, time management, and a team approach to research and research training are advocated to facilitate the development of successful programs and to encourage a continued emphasis on integrated training for pathologists as both clinical diagnosticians and experimentalists. This article is intended to help prospective and active pathology trainees, their mentors, and educational administrators optimize opportunities to ensure the future vitality of veterinary pathologists, and their contributions, in basic and applied research.

Randomised comparison of uterine artery embolisation (UAE) with surgical treatment in patients with symptomatic uterine fibroids (REST trial): 5-year results.

OBJECTIVE: To compare the long-term results of uterine artery embolisation (UAE) with surgery for women with symptomatic uterine fibroids. DESIGN: Pragmatic, open, multicentre, randomised trial. SETTING: Twenty-seven participating UK secondary care centres. SAMPLE: Women aged ≥18 years with symptomatic fibroids who were considered to justify surgical treatment. METHODS: In total, 157 women were randomised (in a 2:1 ratio): 106 to UAE and 51 to surgery (hysterectomy 42; myomectomy nine). MAIN OUTCOME MEASURES: Quality of life at 5 years, as assessed by the Short Form General Health Survey (SF-36). Secondary measures included complications, adverse events and the need for further intervention. RESULTS: There were no significant differences between groups in any of the eight components of the SF-36 scores at 5 years (minimum P = 0.45). Symptom score reduction and patient satisfaction with either treatment was very high, with no group difference. Rates of adverse events were similar in both groups (19% embolization and 25% surgery; P = 0.40). The 5-year intervention rate for treatment failure or complications was 32% (UAE arm) and 4% (surgery arm), respectively. The initial cost benefit of UAE over surgery at 12 months was substantially reduced because of subsequent interventions, with treatments being cost neutral at 5 years. CONCLUSIONS: We have found that UAE is a satisfactory alternative to surgery for fibroids. The less invasive nature of UAE needs to be balanced against the need for re-intervention in almost a third of patients. The choice should lie with the informed patient.

Developing and validating a predictive model for stroke progression.

BACKGROUND: Progression is believed to be a common and important complication in acute stroke, and has been associated with increased mortality and morbidity. Reliable identification of predictors of early neurological deterioration could potentially benefit routine clinical care. The aim of this study was to identify predictors of early stroke progression using two independent patient cohorts. METHODS: Two patient cohorts were used for this study - the first cohort formed the training data set, which included consecutive patients admitted to an urban teaching hospital between 2000 and 2002, and the second cohort formed the test data set, which included patients admitted to the same hospital between 2003 and 2004. A standard definition of stroke progression was used. The first cohort (n = 863) was used to develop the model. Variables that were statistically significant (p < 0.1) on univariate analysis were included in the multivariate model. Logistic regression was the technique employed using backward stepwise regression to drop the least significant variables (p > 0.1) in turn. The second cohort (n = 216) was used to test the performance of the model. The performance of the predictive model was assessed in terms of both calibration and discrimination. Multiple imputation methods were used for dealing with the missing values. RESULTS: Variables shown to be significant predictors of stroke progression were conscious level, history of coronary heart disease, presence of hyperosmolarity, CT lesion, living alone on admission, Oxfordshire Community Stroke Project classification, presence of pyrexia and smoking status. The model appears to have reasonable discriminative properties [the median receiver-operating characteristic curve value was 0.72 (range 0.72-0.73)] and to fit well with the observed data, which is indicated by the high goodness-of-fit p value [the median p value from the Hosmer-Lemeshow test was 0.90 (range 0.50-0.92)]. CONCLUSION: The predictive model developed in this study contains variables that can be easily collected in practice therefore increasing its usability in clinical practice. Using this analysis approach, the discrimination and calibration of the predictive model appear sufficiently high to provide accurate predictions. This study also offers some discussion around the validation of predictive models for wider use in clinical practice.

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.

Feline gastrointestinal eosinophilic sclerosing fibroplasia.

A retrospective study of cases of a unique intramural inflammatory mass within the feline gastrointestinal tract was performed in order to describe and characterize the lesion. Twenty-five cases were identified from archival surgical and postmortem tissues. The lesion most often occurred as an ulcerated intramural mass at the pyloric sphincter (n = 12) or the ileocecocolic junction or colon (n = 9); the remaining cases were in the small intestine. Seven cases also had lymph node involvement. The lesions were characterized by eosinophilic inflammation, large reactive fibroblasts, and trabeculae of dense collagen. Intralesional bacteria were identified in 56% of the cases overall and all of the ileocecocolic junction and colon lesions. Fifty-eight percent of cats tested had peripheral eosinophilia. Cats treated with prednisone had a significantly longer survival time than those receiving other treatments. We propose that this is a unique fibroblastic response of the feline gastrointestinal tract to eosinophilic inflammation that in some cases is associated with bacteria. The lesion is often grossly and sometimes histologically mistaken for neoplasia.

Multicentric physeal dysplasia in two cats.

Feline physeal dysplasia typically presents as unilateral or bilateral, atraumatic, slipped capital femoral epiphysis. The femoral physeal lesion consists of retention of a cartilaginous physis beyond the expected age of closure, with disorganization of the chondrocytes and subsequent slippage. In this article, we describe two cats with feline physeal dysplasia and slipped capital femoral epiphysis that died of unrelated causes (cardiomyopathy and lymphosarcoma). At necropsy, additional sites were found to have retained physes with similar abnormal arrangement of chondrocytes. This confirms that physeal dysplasia in cats is a widespread multicentric disorder of chondrocytes that precedes the development of slipped capital femoral epiphysis.

The diagnosis and prognosis of synovial tumors in dogs: 35 cases.

Although synovial cell sarcoma is reported to be the most common neoplasm of the canine synovium, this retrospective study of 35 canine synovial tumors found that the majority were of histiocytic origin. Five (14.3%) synovial cell sarcomas were identified by positive immunohistochemical staining with antibodies to cytokeratin. Eighteen (51.4%) histiocytic sarcomas were identified by cell morphology and immunohistochemical staining with antibodies to CD18. Six (17.1%) synovial myxomas were identified by histologic pattern. The remaining six (17.1%) synovial tumors represented a variety of sarcomas, including two malignant fibrous histiocytomas (actin positive), one fibrosarcoma, one chondrosarcoma, and two undifferentiated sarcomas. Rottweilers were overrepresented in the histiocytic sarcoma category and Doberman Pinschers were overrepresented in the synovial myxoma category. The average survival time was 31.8 months for dogs with synovial cell sarcoma, 5.3 months for dogs with histiocytic sarcoma, 30.7 months for dogs with synovial myxoma, and 3.5 months for dogs with other sarcomas. Among the dogs with follow-up information available, metastatic disease was detected in 25% of dogs with synovial cell sarcoma, in 91% of dogs with histiocytic sarcoma, in none of the dogs with synovial myxoma, and in 100% of dogs with other sarcomas. Immunohistochemical staining for cytokeratin, CD18, and smooth muscle actin is recommended to make the diagnosis and thereby predict the behavior of synovial tumors in dogs.

Piloleiomyosarcoma in seven ferrets.

In each of seven ferrets (Mustela putorius furo) with leiomyosarcoma, a single dermal mass was identified and biopsied. Each mass consisted of a well-demarcated but nonencapsulated proliferation of large spindle- to strap-shaped cells arranged in interwoven bundles. The cells resembled the smooth muscle cells of the adjacent arrector pili muscles, but with marked nuclear pleomorphism. Immunohistochemical staining for smooth muscle actin, desmin, and vimentin was positive and staining for myoglobin and cytokeratin was negative. Follow-up on three of the ferrets indicates that the prognosis is good following complete surgical excision.

Cause of death in dogs according to breed: a necropsy survey of five breeds.

The final necropsy diagnoses, obtained between 1985 and 1999, were compared among 1,206 golden retrievers, boxers, German shepherd dogs, Labrador retrievers, and rottweilers. A significantly larger proportion of boxers and golden retrievers died of neoplastic disease than the other three breeds. The ages at death were not significantly different among golden retrievers, German shepherd dogs, and Labrador retrievers. However, rottweilers and boxers died at a younger age from both neoplastic and nonneoplastic diseases. Although boxers were already known to be at a higher risk for neoplasia, a similar index of suspicion for neoplasia should now be used for golden retrievers.

Clinical, clinicopathologic, radiographic, and ultrasonographic characteristics of intestinal lymphangiectasia in dogs: 17 cases (1996-1998).

OBJECTIVE: To characterize the clinical, clinicopathologic, and imaging findings in dogs with intestinal lymphangiectasia and to compare the histologic grade of lymphangiectasia with clinicopathologic and imaging abnormalities. DESIGN: Retrospective study. ANIMALS: 17 dogs with a histologic diagnosis of intestinal lymphangiectasia. PROCEDURE: Medical records of dogs with a histologic diagnosis of intestinal lymphangiectasia were reviewed for signalment, history, clinical signs, results of exploratory laparotomy, and clinicopathologic, radiographic, ultrasonographic, and histologic findings. RESULTS: Mean age of dogs was 8.3 years; the most common clinical signs were diarrhea, anorexia, lethargy, vomiting, and weight loss. Abnormal physical examination findings included dehydration, ascites, and signs of pain on palpation of the abdomen. The most notable clinicopathologic findings were low serum ionized calcium concentration and hypoalbuminemia. Abdominal ultrasonography was performed in 12 dogs and revealed intestinal abnormalities in 8 dogs and peritoneal effusion in 7 dogs. Exploratory laparotomy revealed abnormalities in 9 of 16 dogs including thickened small intestine, dilated lacteals, lymphadenopathy, and adhesions. On histologic examination of the small intestine, concurrent inflammation was observed in 15 of 17 dogs, crypt ectasia in 5 of 17, and lipogranulomas in 2 of 17. CONCLUSIONS AND CLINICAL RELEVANCE: Intestinal lymphangiectasia in dogs appears to be a heterogeneous disorder characterized by various degrees of panhypoproteinemia, hypocholesterolemia, lymphocytopenia, and imaging abnormalities. In most dogs, the severity of hypoalbuminemia appears to offer the best correlation with severity of histologic lesions of lymphangiectasia. Imaging abnormalities are common in dogs with intestinal lymphangiectasia but are not specific enough to differentiate this disorder from other gastrointestinal disorders, nor are they predictive of histologic severity.

Correlation between leukocytosis and necropsy findings in dogs with immune-mediated hemolytic anemia: 34 cases (1994-1999).

OBJECTIVE: To determine whether severity of leukocytosis correlates with severity of postmortem lesions in dogs with immune-mediated hemolytic anemia (IMHA). DESIGN: Retrospective study. ANIMALS: 34 dogs with IMHA that had CBC performed within 48 hours prior to death and complete necropsy examinations. PROCEDURE: Dogs were independently assigned to 4 leukocytosis groups (within reference range; mild leukocytosis, moderate leukocytosis, marked leukocytosis) and 3 lesion severity groups (mild lesions, moderate lesions, severe lesions). RESULTS: Moderate to marked leukocytosis correlated with moderate to severe postmortem lesions. Ischemic necrosis within liver, kidney, heart, lung, and spleen attributable to thromboembolic disease or anemic hypoxia were the most common important lesions found at necropsy. None of the dogs with mild lesions had moderate or marked leukocytosis. Four of 14 severely affected dogs had WBC counts within reference range, but all 4 had neutrophilic left shifts. Three of these 4 dogs had toxic change in neutrophils. CONCLUSION AND CLINICAL RELEVANCE: Moderate to marked leukocytosis, neutrophilic left shift, and toxic change in neutrophils in dogs with IMHA should alert clinicians to the potential for moderate to severe tissue injury, which could complicate treatment and worsen prognosis. Lesions appear to be secondary to anemic hypoxia, thromboembolic disease, or both; therefore, treatment objectives should focus on improving blood oxygen-carrying capacity and monitoring for thromboembolic disease.

Physeal dysplasia with slipped capital femoral epiphysis in 13 cats.

Separation of the femoral capital epiphysis is associated with severe trauma in most species. This report describes 13 cats with slipped capital femoral epiphysis characterized by a distinctive lesion in the physeal cartilage. The lesion consists of irregular clusters of chondrocytes separated by abundant matrix on both the epiphyseal and metaphyseal side of the cleavage site. The affected population in this study is 85% male, 90% overweight, 23% Siamese, and 4.5-24 months old. The histopathology and demographics are similar to slipped capital femoral epiphysis in humans, which most often affects overweight adolescent boys.

Gongylonema macrogubernaculum in captive African squirrels (Funisciurus substriatus and Xerus erythropus) and lion-tailed macaques (Macaca silenus).

Necropsies performed between 1989 and 1995 on 15 African rope squirrels (Funisciurus substriatus) and 20 African ground squirrels (Xerus erythropus) from the Baltimore Zoo revealed 13 cases of gongylonemiasis. Nematodes were embedded in the epithelium of the esophagus, pharynx, buccal mucosa, and tongue, resulting in varying degrees of esophagitis, pharyngitis, stomatitis, and glossitis, respectively. Routine fecal examinations were negative, and the nematodes appeared to be unaffected by repeated treatments with ivermectin. Most of the affected animals had shown clinical signs of dyspnea and/or inanition and emaciation. Suppurative rhinitis was also a frequent finding at necropsy and was associated with the presence of the nematodes in eight animals. Dissection of whole nematodes from formalin-fixed specimens revealed morphologic features consistent with Gongylonema macrogubernaculum, a species previously only reported in nonhuman primates. The squirrels were housed in the same building with numerous primate species, and a review of pathology records revealed esophageal gongylonemiasis in three lion-tailed macaques (Macaca silenus), lingual gongylonemiasis in a spotnose monkey (Cercopithecus buettikoferi), and buccal gongylonemiasis in a brown-headed tamarin (Saguinus fuscicollis). Examination of whole nematodes dissected from one of the lion-tailed macaques also demonstrated the unique morphology of G. macrogubernaculum. Nematodes belonging to the species Gongylonema are acquired by ingestion of the intermediate host, the cockroach. This is the first report of G. macrogubernaculum in a nonprimate species and suggests that captive African squirrels can serve as reservoir hosts for this parasite in a zoo environment.

Endothelial cells from diverse tissues exhibit differences in growth and morphology.

An increased recognition of the role of endothelial cells in disease and the development of methods for endothelial cell culture has led to an upsurge in in vitro studies of endothelial cell function. However, the cells most often used for these studies do not reflect the in vivo heterogeneity of endothelial cells. To assess intrinsic differences between large and small vessel endothelial cells from different tissues, primary cultures of endothelial cells from capillaries (brain, lung, and adipose tissue) and a large vessel (aorta) of sheep were isolated, purified by fluorescence-activated cell sorting of acetylated low density lipoprotein (DiI-Ac-LDL) labeled cells, and characterized by phase contrast and ultrastructural morphology, expression of von Willebrand factor, and lack of expression of cytokeratin, smooth muscle actin, and glial fibrillary acidic protein (GFAP). Although all endothelial cells were cultured in the same media, only the brain microvascular endothelial cells demonstrated tight junctions by electron microscopy. Only the large vessel (aortic) endothelial cells contained Weibel-Palade bodies. Expression of von Willebrand factor decreased with passage of cells, but uptake of DiI-Ac-LDL was consistently positive regardless of culture conditions or passage number. These studies demonstrate that the unique ultrastructural characteristics of microvascular and macrovascular endothelial cells are intrinsic to the cells themselves and are not determined by differential culture conditions. This system allows the study of pathologic processes that affect endothelial cells of certain target organs selectively and should more accurately represent the response of tissue-specific endothelial cells in inflammatory processes.