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We describe and illustrate herein a case of eosinophilic pulmonary granulomatosis (EPG) in a 16-mo-old, castrated male, Great Pyrenees crossbred dog. EPG appears to differ from eosinophilic pneumonias and eosinophilic bronchopneumopathy in dogs by the presence of nodules and masses in the lungs composed of eosinophils, macrophages, and various combinations of lymphocytes, plasma cells, neutrophils, and mast cells within fibrous tissue. Specific information from this dog was added to the information from the limited number of other dogs diagnosed with EPG reported in the veterinary literature, and the information analyzed. EPG appears to have no breed or sex predilection and tends to be a disease of younger dogs, often ≤ 3 y of age. Antemortem imaging of nodules and masses in the lungs, combined with cytologic evidence of eosinophils in the lesions, is highly suggestive of EPG, and the diagnosis can be confirmed postmortem. Concurrent eosinophilia and basophilia can be features of EPG, but their diagnostic value requires further investigation, as does the possible causal association with Dirofilaria immitis infection.

Chronic liver disease is an important cause of illness in horses, and treatment is mainly supportive. Research into new treatment modalities for humans has shown promising data regarding metallothionein (MT), which has been shown to possess regenerative, antifibrotic, and anti-inflammatory properties. This study aimed to examine the relationship between hepatic MT expression and the histopathologic markers of hepatic inflammation, fibrosis and bile duct proliferation, as well as cellular regeneration in 77 selected cases of chronic liver disease in horses. We hypothesized that higher MT expression would be associated with increased heptocellular proliferation and decreased fibrosis, inflammation, and bile duct proliferation. Hepatocellular MT expression was evaluated with immunohistochemistry. Additionally, cellular regeneration was evaluated with immunohistochemistry for Ki-67, a protein expressed during all active stages of the cell cycle. The severity of inflammation and fibrosis was scored, and bile duct proliferation was assessed by counting bile duct profiles. MT expression was observed in 73 of 77 (94.8%) cases of chronically diseased livers. Ki-67 expression was seen in resident Kupffer cells ( n = 42, 54.6%), lymphocytes ( n = 39, 50.7%), bile duct epithelium ( n = 10, 13.0%), and hepatocytes ( n = 8, 10.4%). MT expression was significantly associated with Ki-67 staining in bile duct epithelium and Kupffer cells. Additionally, median MT expression was higher in cases containing lymphocytic infiltrates as compared with cases with no lymphocytic infiltrate ( P < .05). These findings are the first known report of MT expression within chronic equine hepatic disease.

Background: Improved anticoagulation control with warfarin reduces adverse events and represents a target for quality improvement. No previous study has described an effort to improve anticoagulation control across a health system., Objective: To describe the results of an effort to improve anticoagulation control in the New England region of the Veterans Health Administration (VA)., Methods: Our intervention encompassed 8 VA sites managing warfarin for more than 5000 patients in New England (Veterans Integrated Service Network 1 [VISN 1]). We provided sites with a system to measure processes of care, along with targeted audit and feedback. We focused on processes of care associated with site-level anticoagulation control, including prompt follow-up after out-of-range international normalized ratio (INR) values, minimizing loss to follow-up, and use of guideline-concordant INR target ranges. We used a difference-in-differences (DID) model to examine changes in anticoagulation control, measured as percentage time in therapeutic range (TTR), as well as process measures and compared VISN 1 sites with 116 VA sites located outside VISN 1., Results: VISN 1 sites improved on TTR, our main indicator of quality, from 66.4% to 69.2%, whereas sites outside VISN 1 improved from 65.9% to 66.4% (DID 2.3%, P < 0.001). Improvement in TTR correlated strongly with the extent of improvement on process-of-care measures, which varied widely across VISN 1 sites., Conclusions: A regional quality improvement initiative, using performance measurement with audit and feedback, improved TTR by 2.3% more than control sites, which is a clinically important difference. Improving relevant processes of care can improve outcomes for patients receiving warfarin.

A diagnosis of neoplasia was noted in 125 of 357 donkeys (35%) in our review of medical records from 5 veterinary schools in the United States and Canada. Equine sarcoid was the most common tumor in our study, accounting for 72% of all tumors and 82% of cutaneous tumors. Soft-tissue sarcomas were the second most common skin tumors. All other types of neoplasia were rare. Important differences in the occurrence of neoplasia in donkeys compared to horses included the rarity or absence of squamous cell carcinoma in any organ system and gray horse melanoma. Lymphosarcoma, the most common malignant tumor in horses, appears to be very rare in donkeys. We report several tumors in donkeys including melanocytoma, peripheral nerve sheath tumor, and gastrointestinal stromal tumor. Our data demonstrate commonalities as well as differences in neoplastic diseases of donkeys and horses. Understanding differences in carcinogenesis among these 2 closely related species can inform researchers pursuing pathogenic mechanisms of equine disease and inform veterinary diagnosticians regarding tumor prevalence., (© 2016 The Author(s).)

The chronic form of primary hepatitis occurs commonly in dogs, and the etiology is rarely found. Metallothionein (MT) is a heavy metal-binding protein found in many organs, including the liver. MT was recently shown to enhance liver regeneration and decrease hepatic fibrosis in human beings. This study examined the expression of MT in 24 cases of chronic hepatitis in dogs using immunohistochemistry. To understand the role of MT as a determinant of hepatic inflammation, fibrosis, bile duct proliferation, and regeneration, we correlated its expression with histologic lesions of chronic hepatitis, such as hepatic inflammation, fibrosis, and bile duct proliferation, as well as hepatocellular growth fraction as measured by Ki67 immunolabeling. Hepatocellular growth fraction was used as a measure of hepatic regeneration. Regression analysis revealed a significant positive correlation between MT labeling intensity and growth fraction (r(2) = 0.29, P < .05). The percentage of MT-positive cells and the overall MT expression were both positively correlated with growth fraction (r(2) = 0.25 and 0.26, respectively; P < .05). A negative correlation was found between the overall MT labeling and fibrosis (r(2) = 0.18, P < .05). A similar trend of negative correlation was also found between the percentage of MT-positive cells and fibrosis, but the P value was not statistically significant (r(2) = 0.14, P = .0684). These findings suggest a protective role of MT in dogs affected by chronic hepatitis, similar to its role in human beings. These dogs may respond to treatment modules focusing on enhancing the expression of MT., (© The Author(s) 2015.)

A retrospective study of brain lesions in goats was conducted to identify the range of lesions and diseases recognized and to make recommendations regarding the best tissues to examine and tests to conduct in order to maximize the likelihood of making a definitive diagnosis in goats that may have had clinical signs referable to the brain. One hundred thirty-nine goats with a brain lesion were identified. The most common lesion, in 52.5% of the goats, was suppurative inflammation. Approximately two-thirds of these goats had encephalitic listeriosis. Other goats were found to have suppurative inflammation in association with septicemia, pituitary abscesses, dehorning injury, and otitis. Thirty goats (21.6%) were diagnosed with polioencephalomalacia. Twenty-one goats (15.1%) were diagnosed with nonsuppurative inflammation. In more than half of these goats, no definitive diagnosis was made, while 8 were infected with Caprine arthritis encephalitis virus and 1 with Rabies virus. However, few goats were tested for rabies. Based on these findings, it is recommended that, in addition to appropriate handling of the brain, the head should be examined with attention paid to the sella turcica and the temporal bones for evidence of a pituitary abscess and otitis, respectively. Histologic examination should include multiple areas of the brain, including the brainstem, for lesions of encephalic listeriosis; the cerebral cortex, for lesions of polioencephalomalacia; and the hippocampus, for Negri bodies associated with Rabies virus infection. Consideration should be given to collecting samples of other tissues including, but not limited to, the spinal cord and liver for ancillary testing if warranted.

Equine sarcoids are the most common tumor of horses. Bovine papillomavirus (BPV) has been suggested as the cause of sarcoids. Studies have shown that BPV is present in swabs or biopsies from nonsarcoid-bearing equine skin. Skin biopsies from a variety of different conditions and normal skin from horses with no reported history of sarcoids were examined by polymerase chain reaction (PCR) for the presence of BPV, which was found in all different types of skin conditions as well as normal skin. Forty-one out of 86 skin biopsies from horses without sarcoids were found to contain BPV DNA. Laser microdissection, followed by DNA amplification through both PCR and isothermal loop-mediated amplification, was performed on these 41 biopsies and on 70 additional BPV-positive sarcoid biopsies to localize the virus. Location of BPV DNA was different between sarcoid and nonsarcoid groups. Nonsarcoid skin biopsies were more likely to have BPV within intact or inflamed epidermis than sarcoids (P = 0.016 and P = 0.007, respectively). Areas of inflammation within the dermis and epidermis were more likely to contain BPV than in noninflamed areas (P = 0.008 and P = 0.009, respectively). Bovine papillomavirus was also found in the epidermis of all types of sarcoids examined, more frequently in occult sarcoids than in fibroblastic and nodular types (P = 0.03 and P = 0.01, respectively). Results suggest that BPV is commonly found in normal and inflamed equine skin, and it is likely an important predisposing factor in the development of sarcoids.

The long-term administration of low doses of rotenone has been used to produce a model of Parkinson disease (PD) in rats. However, only about 50% of similarly treated rats develop the PD-like syndrome, with many dying during the first few days of treatment. The lesions in male Lewis rats that became moribund or died after short-term, low-dose rotenone administration are described. Dosed rats had fibrinoid change and acute hemorrhage involving small arteries and arterioles of the brain and lungs. The thalamus, hypothalamus, and medulla oblongata were most frequently and severely affected. Blood vessels in the brain of some male Lewis rats appeared acutely susceptible to the effects of rotenone. Understanding the selective nature of the fibrinoid change and hemorrhage might explain how rotenone produces PD-like signs and lesions in rats, and it might also provide the basis for a model of intraparenchymal hemorrhagic cerebrovascular disease (i.e., hemorrhagic strokes) in humans.

Agreement among pathologists interpreting histologic specimens is an area of interest within human pathology, but little work in this area has been reported in the veterinary literature. Agreement among pathologists evaluating routine histologic sections of amputated digits from cats and dogs submitted to multiple diagnostic centers was examined. Histologic sections from surgical specimens were reviewed in a blinded fashion by two pathologists, and a comparison to the original diagnosis, as stated in the diagnostic report, was recorded. A total of 513 cases were reviewed, and complete agreement was reached in 409 (79.7%). Of the 104 instances of disagreement, 77 (74.0%) were considered to be of clinical significance. The diagnosis of keratoacanthoma was disagreed with in 19 of 21 diagnoses (90.4%). No other individual diagnosis was similarly disputed. The overall level of disagreement is large and is similar to that reported in human pathology and suggests that further study of this issue would be useful in veterinary pathology.

Amputation is commonly performed to both treat and diagnose conditions affecting the digits of dogs. Although histopathologic evaluation of these digits is routinely done, data on the prevalence and prognosis of neoplasms of the digit are scarce. The records of multiple veterinary diagnostic laboratories were searched to identify submissions of amputated digits from dogs. Four hundred twenty-eight separate submissions were reviewed for diagnosis, age, sex, limb of origin, and digits affected, and the original submitting clinics were surveyed to determine clinical outcome of the animal. No diagnosis could be agreed upon in 24 animals, and these were excluded from the study. Kaplan-Meier product-limit method was used to determine the disease-free interval and survival time. Neoplastic disease was identified in 296 of 404 submissions, with exclusively inflammatory lesions composing 108 cases. A total of 30 different neoplastic processes were identified. In 233 (77.7%) of the neoplastic cases, a malignant tumor was identified. Squamous cell carcinoma was the most commonly identified tumor (n = 109, 36.3%), and 11 of 42 dogs for which clinical follow-up information was available developed metastatic disease. Squamous cell carcinoma of the digit appears to have a greater metastatic potential than that occurring elsewhere in the body. Other common diagnoses included melanoma (n = 52, 17.3%), soft-tissue sarcoma (n = 29, 9.7%), and mast cell tumor (n = 20, 6.7%). Melanomas were associated with poor prognoses, with a median survival time of 365 days.

A 7-year-old, spayed female, Wheaton terrier dog was icteric, lethargic, and anorexic with increased activity of hepatocellular and cholestatic liver enzymes and an extreme hyperbilirubinemia level of 609 micromol/L (reference interval: 1.0-4.0 micromol/L). Necropsy findings included profound icterus and red and yellow mottling of the liver. Yellow discoloration of the thalamic and subthalamic nuclei was detected on subgross examination of the formalin-fixed brain. Histologic examination of the brain revealed neuronal necrosis within the discolored nuclei, necrosis of Purkinje cells, and Alzheimer type II astrocytes in the cerebrocortical gray matter and in the nuclei, with gross discoloration. Histologic examination of the liver revealed extensive necrosis in a periacinar-to-bridging pattern and often extending to portal triads. A case of naturally occurring kernicterus in an adult dog secondary to extreme hyperbilirubinemia resulting from fulminant hepatic failure is reported. The few reports of this disease in domestic species involved neonates, namely 1 foal and 1 kitten.

Amputation is commonly performed in an attempt to both treat and diagnose conditions affecting the digits of cats. The records of multiple veterinary diagnostic laboratories were searched to identify submissions of amputated digits from cats. Eighty-five separate submissions were reviewed for diagnosis, age, sex, limb of origin, and digits affected; and the original submitting clinics were surveyed to determine clinical outcome. The Kaplan-Meier product-limit method was used to determine the disease-free interval and survival time. Neoplastic disease was identified in 63 of 85 submissions, with exclusively inflammatory lesions composing the other 22 cases. In 60 (95.2%) of the neoplastic cases, a malignant tumor was identified. Squamous cell carcinoma was the most commonly identified malignant tumor (n = 15; 23.8%) and was associated with a median survival time of 73 days. Other diagnoses included fibrosarcoma (n = 14; 22.2%); adenocarcinoma, likely metastases of a primary pulmonary neoplasm (n = 13; 20.6%); osteosarcoma (n = 5; 7.9%); mast cell tumor (n = 4; 6.3%); hemangiosarcoma (n = 5; 7.9%); malignant fibrous histiocytoma (n = 2; 3.2%); giant cell tumor of bone (n = 2; 3.2%); and hemangioma (n = 2; 3.2%). Giant cell tumor of bone has not been previously described in the digits of cats. Various neoplasms can occur in the digits of cats, and submission of the amputated digit for histopathologic diagnosis is essential to determine the histogenesis and predict the clinical outcome.