Canine Journal Summaries

Journal of Comparative Pathology 2008-2009 Canine Arteriovenous Haemangioma in Two Dogs and a Cat- These are rare tumors with differentiation into arterioles, venules and capillaries. All have VWF + endothelium and Smooth muscle Actin + tunica media. Primary Gastric Choriocarcinoma in a Dog – Choriocarcinomas are characterized by polygonal cells with multinucleated syncytiotrophoblastic giant cells. They are hCG positive and PAS and Alcian blue negative in contrast to gastric carcinomas. They do not invade the mucosa. There is increased β-catenin with upregulation of c-myc and Ras oncogenes Expression of Transforming Growth Factor-β1, -β2 and -β3 in Normal and Diseased Canine Mitral Valves : in chronic valvular disease (endocardiosis) there is activation and proliferation of valvular stromal cells and transdifferentiation into myofibroblasts like cells. In mild and strong valvular disease there was increased expression of TGF- β1 and β3 and smooth muscle actin Detection and Characterization of Chondroid Metaplasia in Canine Atrioventricular Valves: seen most commonly in elderly large breeds of dogs and tricuspid valve was the only valve affected (in some other study mitral valve was most commonly affected). Cartilage present in valve was fibrocartilage (type I and IV collagen) and hyaline cartilage (type III and VI collagen). Metaplasia of mesenchymal cells to chondrocytes (may be due to TGF- β1) initiated by mechanical forces. Canine Cutaneous Spindle Cell Tumours with Features of Peripheral Nerve Sheath Tumours: A Histopathological and Immunohistochemical Study -- Antoni type A (interlacing bundles, storiform, concentric) or type B (loose textured) growth pattern. Tumors were positive for NSE (81%) and Protein gene product 9.5 (93%). Expression of S-100, laminin and collagen IV may be used to define a schwannoma. Tonsillar Lymphangiomatous Polyp in an Adult Dog- Tonsilar tumors were reported in humans but none in animals so far. Histopathology- Dilated, thin-walled lymphatic channels embedded in a dense, fibrovascular stroma and lined by a single layer of flattened, discontinuous endothelium with scattered intraluminal valves. Immunopositive for CD31 (Endothelial cell marker- Platelet Endothelial Cell Adhesion Molecule-1) and von Willebrand factor (Factor VIII). Expression of the Anti-apoptotic Factors Bcl-2 and Survivin in Canine Vascular TumoursThe expression of high levels of Bcl-2 and survivin play an important role in promoting the malignant growth of canine hemangiosarcomas. Cervical Chondroid Chordoma in a Shetland Sheep Dog - Origin: Chordoma is an uncommon, slow-growing neoplasm, arising in the cerebrospinal axis from embryonic notochordal remnants. Histopath: Physaliphorous cells surrounded by connective tissue + Cartilagenous component (for chondroid chordoma). DDx: Chordoma – No cartilage component, Chondroma/chondrosarcoma – cytokeratin negative, Myxosarcoma, Liposarcoma. Leiomyosarcoma of the Pericardium, with Epicardial Metastases and Peripheral Eosinophilia in a Dog Gross findings- There was an extensive mass encircled the heart and obliterated the pericardial sac, with probable metastatic spread to the epicardium. Associated lesions - Eosinophilic infiltration of the neoplastic mass, lamina propria of the stomach and duodenum, interstitium of the kidney, and submucosa of the bladder was consistent with a possible paraneoplastic eosinophilia. Paraneoplastic syndromes are the systemic complications of neoplasia. The neoplasms sporadically associated with eosinophilia in dogs and cats include mast cell tumours (including systemic mastocytosis), lymphoma, pilomatrixoma, basal cell carcinoma, transitional carcinoma, fibrosarcoma, myxosarcoma, osteosarcoma and anaplastic mammary carcinoma. Bone Marrow Pathology in Dogs and Cats with Non-Regenerative Immune-Mediated Haemolytic Anaemia and Pure Red Cell Aplasia: Non-regenerative IMHA in dogs and cats has been associated with pure red cell aplasia, erythroid maturation arrest or bone marrow erythroid hyperplasia. PRCA and erythroid maturation arrest may result from immune-mediated destruction of erythroid precursor cells within the bone marrow. However,

IMHA due to erythroid hyperplasia could be due to variety of pathological changes in bone marrow including dysmyelopoiesis, myelonecrosis, myelofibrosis, altered vascular permeability/acute inflammation, and hemophagocytic syndrome Histopathological Features of Ocular Leishmaniosis in the Dog: Granulomatous with some lymphoplasmacytis infiltration. Ocular tissues affected, in order of frequency, were conjunctiva and limbus, ciliary body, iris, cornea, sclera and iridocorneal angle, choroid and the optic nerve sheath. The conjunctiva was the most commonly involved ocular structure. Expression of Claudin-1, -2, -3, -4, -5 and -7 Proteins in Benign and Malignant Canine Mammary Gland Epithelial Tumours. Claudin proteins are important in tight junction formation and function . Loss or reduction of expression of claudin-1, -2, -5 and -7 may lead to cellular disorientation, detachment and invasion in canine mammary neoplasia. Gastric Neuroendocrine Carcinoma Associated with Atrophic Gastritis in the Norwegian Lundehund. J. Comp. Path. 2008, Vol. 139, 194e201. The Norwegian Lundehund (puffin dog) is predisposed to the development of gastric neoplasia associated with chronic atrophic gastritis characterized by reduction in parietal cells and hyperplasia of neuroendocrine cells. Four of the tumors displayed neuroendocrine (enterochromaffin-like cell; ECL) differentiation. Pathogenesis (proposed): Atrophic gastritis Rise in gastric pH Hypergastrinemia  proliferation of ECL  neoplasia. (ECL cells produce histamine which increases production of gastric acid). Leptospirosis in dogs: a review with emphasis on clinical aspects. Gram Negative Spirochete-enters wounds bacteremic liver, spleen, brain. Kidneys,  Proximal renal tubules. Virulence factors- LPS, Sphingomyelinase, hemolysins, porins. Lesions- vasculitis, necrosis, hemorrhage, DIC, Neutrophilic to lymphoplasmacytic inflammation. Presence of Endosymbiont Wolbachia in heartworms (Dirofilaria immitis). Wolbachia is rickettsia like obligate intracellular bacteria. WSP (surface protein) released from dead adult heartworms stimulated neutrophil chemotaxis. Canine parvovirus strains identified from clinically ill dogs in the United Kingdom CPV-2a; 33% CPV-2b; 67% Mycotic Encephalitis and Nephritis in a Dog due to Infection with Cladosporium cladosporioides: the fungal agent most often identified in systemic phaeohyphomycosis is Cladophialophora bantiana . This report describes German shepherd dog with granulomatous encephalitis and nephritis due to C. cladosporioides. German shepherd breed may have an abnormality in mucosal IgA production predisposing them systemic fungal infection, particularly Aspergillus spp. An Immunohistochemical Analysis of Canine Haemangioma and Haemangiosarcoma J. Comp. Path. 2009, Vol. 140, 158e168 Forty samples of canine cutaneous and visceral haemangiosarcoma, 29 samples of cutaneous and visceral haemangioma and 10 control samples of granulation tissue were labeled with antisera specific for vimentin, smooth muscle actin, von Willebrand factor, CD117, vascular endothelial growth factor receptor-3, vascular endothelial growth factor-C and CD44. Further antisera were employed to determine the level of cellular proliferation and toluidine blue staining was used to detect populations of tumour-infiltrating mast cells. There was greater expression of CD117, VEGFR-3 and CD44 in HSA than in HA, suggesting that these proteins might be suitable targets for the future development of novel therapeutic approaches to canine HSA. Marked infiltration of MC was detected in HA, suggesting a possible role for these cells in the pathogenesis of benign vascular neoplasia in the dog. Thallium toxicosis in a Pit Bull Terrier. J Vet Diagn Invest 18:134–137 (2006- Signs- conscious proprioceptive deficits, and a hemorrhagic diarrhea before death. A severe, acute necrotizing enterocolitis was evident Liver and kidney thallium concentrations were 18 and 26 ppm, respectively. The source of the thallium was a person with the intent to harm family members.

Disseminated transmissible venereal tumor in a dog. J Vet Diagn Invest 18:130–133 (2006). Transmissible venereal tumor (TVT) -no breed or sex predilection and a low metastatic rate. Neoplastic nodules in the subcutis , lung, anterior mediastinum, liver, spleen, kidney, and superficial and deep lymph nodes in both abdominal and thoracic cavities. Immunohistochemical staining, the neoplastic cells were positive for lysozyme and Vimentin but were negative for cytokeratin, desmin, CD3, and CD79a. The diagnosis of the TVT was further supported by the identification and analysis of long interspersed nuclear elements (LINE) from paraffin-embedded tumor tissue. Genetic characterization of canine rotavirus isolated from a puppy in Korea and experimental reproduction of disease. J Vet Diagn Invest 19:78–83 (2007). Canine rotavirus - mild diarrhea, and the isolate was genetically characterized. Group A rotaviruses cause neonatal diarrhea in human and many animal species. Rotavirus is a nonenveloped and double-stranded RNA virus with 2 outer capsid-independent neutralizing antibody-inducing proteins, VP7 and VP4, which are used for classification into G and P serotypes, respectively. Both proteins are involved in protective immunity.8 Canine rotavirus most often causes mild enteritis, especially in pups younger than 2 weeks. Aflatoxicosis in nine dogs after exposure to contaminated commercial dog food. J Vet Diagn Invest 19:168– 175 (2007). Aflatoxin B1 metabolite M1 –Gross  Enlarged, pale yellow livers with subacute hepatopathy, and cirrhosis in the dog with chronic hepatopathy. Histopathologic  hepatic lipidosis, portal fibroplasia, and biliary hyperplasia, marked lobular atrophy, bridging portal fibrosis, and regenerative hepatocellular nodules characterized the dog with chronic hepatopathy. Serological prevalence of canine respiratory coronavirus in southern Italy and epidemiological relationship with canine enteric coronavirus. J Vet Diagn Invest 19:176–180 (2007). Of adult domestic dogs, 23.3% had antibodies to CRCoV, compared with 86.1% with antibodies to CECoV. Amongst a population of kenneled pups, 4.0% had antibodies to CRCoV, and 97.0% had antibodies to CECoV. A number of pathogens have been associated with CIRD, including canine adenovirus 2 (CAV-2), canine parainfluenza virus (CPIV), Bordetella bronchiseptica, canine herpesvirus (CHV), and mycoplasmas, and disease may result from one or a combination of these agents. Vertebral polyostotic lymphoma in a young dog. J Vet Diagn Invest 19:205–208 (2007). Lymphoma with vertebral involvement. Ventral fusion of the lumbar vertebrae by new bony tissue deposition and neoplastic lymphoid cells in lymph nodes and bone marrow. Histologically, vertebral bone and osteophytes, liver, bone marrow, kidney, and lymph nodes were diffusely infiltrated by neoplastic, lymphoid cells, with scant cytoplasm and round hyperchromatic nuclei. Fatal ricin toxicosis in a puppy confirmed by liquid chromatography/mass spectrometry when using ricinine as a marker. J Vet Diagn Invest 19:216–220 (2007). Ricin, a lectin from the castor bean plant (Ricinis communis). Ingestion of masticated seeds results in high morbidity, with vomiting and watery to hemorrhagic diarrhea. Histopathologic findings included superficial necrotizing enteritis of the jejunum and occasional, random foci of coagulative necrosis in the liver. The alkaloid ricinine was detected in gastric content by using a newly developed LC/MS method. This confirmation of exposure is important in the diagnosis of ricin toxicosis, because ingestion of castor beans is not always fatal, histologic lesions are nonspecific, and the degree of mastication can influence the effective dose of ricin. Diagnosis of Amanita toxicosis in a dog with acute hepatic necrosis. J Vet Diagn Invest 19:312–317 (2007). Microscopically, the liver showed panlobular coagulative necrosis of hepatocytes. A presumptive diagnosis of amanita poisoning was based on suspect history of exposure to mushrooms, clinical signs, and pathologic findings. Exposure to amanitin was confirmed through detection of a-amanitin in the liver by liquid chromatography/mass spectrometry. Evaluation of tongue as a complementary sample for the diagnosis of parvoviral infection in dogs and cats. J Vet Diagn Invest 19:409–413 (2007). Real-time polymerase chain reaction (PCR), immunohistochemistry (IHC), and direct fluorescent antibody testing (FA). Parvoviral DNA was detected by PCR in both small intestine and tongue. Nineteen of 22 animals (86%) with suspect or positive FA staining in the small intestine also had positive FA and IHC staining in the tongue. Three of 3 dogs (100%) whose carcasses had been frozen and thawed prior to necropsy had more consistently positive staining in tongue than in small intestine by FA and IHC. These data

confirm tongue as an excellent complementary sample for parvoviral testing in dogs and cats, especially in cases in which postmortem autolysis has occurred. Immunohistochemical diagnosis of canine ovarian epithelial and granulosa cell tumors. J Vet Diagn Invest 19:431–435 (2007). Granulosa cells were negative for cytokeratin 7 and displayed variable expression of vimentin, cytokeratin AE1/AE3, and inhibin-a toward follicular maturation. Granulosa cell tumors were negative for cytokeratin 7 and positive for inhibin-a. Conversely, ovarian epithelial cells tumors were positive for cytokeratin 7 and negative for inhibin-a. Both granulosa and epithelial cell tumors displayed variable expression of vimentin. Cytokeratin AE1/AE3 was expressed by all epithelial-derived tumors and 6 of 8 granulosa cell tumors. Outbreaks of renal failure associated with melamine and cyanuric acid in dogs and cats in 2004 and 2007. J Vet Diagn Invest 19:525–531 (2007). Distal tubular lesions were present in all 16 animals, and unique polarizable crystals with striations were present in distal tubules or collecting ducts in all animals. The proximal tubules were largely unaffected. A chronic pattern of histologic change, characterized by interstitial fibrosis and inflammation, was observed in some affected animals. Melamine and cyanuric acid were present in renal tissue from both outbreaks. Oxalate crystals are predominantly in proximal tubules, lighter green with a glassy appearance, often oblong in shape, and more difficult to appreciate without polarization. In contrast, melamine/ cyanuric acid crystals are predominantly within distal tubular segments, green to blue in appearance, often exhibit striations, and easily visualized histologically without polarization. Occurrence of canine parvovirus type 2c in the United States. J Vet Diagn Invest 19:535–539 (2007). Canine parvovirus (CPV) type 2 (CPV-2) emerged around 1978 as a major pathogen of dogs worldwide. In the mid-1980s, the original CPV-2 had evolved and was completely replaced by 2 variants, CPV- 2a and CPV-2b. In 2000, a new variant of CPV (named CPV-2c) was detected in Italy and now co-circulates with types 2a and 2b in that country. Arizona, California, Georgia, Oklahoma, and Texas. Membranoproliferative glomerulonephritis type III in a simultaneous infection of Leishmania infantum and Dirofilaria immitis in a dog. J Vet Diagn Invest 19:569–572 (2007). MPGN is subdivided, based on ultrastructural alterations in the glomerular basement membrane (GBM), as type I (subendothelial deposits), type II (intramembranous dense deposits), and type III (immune complex subendothelial and mesangial region, similarly to type I); in addition, numerous subepithelial deposits are present. Heavy and coarse granular complement C3 deposition and a weaker positive reaction to immunoglobulin G were present along peripheral glomerular basement membrane and in the mesangium in the immunofluorescent study. Development of a sensitive and specific indirect enzyme-linked immunosorbent assay based on a baculovirus recombinant antigen for detection of specific antibodies against Ehrlichia canis. J Vet Diagn Invest 19:635– 642 (2007). Canine monocytic ehrlichiosis (CME), caused by Ehrlichia canis, is a tick-borne disease transmitted by the brown dog tick Rhipicephalus sanguineus. 3 phases are described in the pathogenesis of CME: acute phase, subclinical phase, and chronic phase. Clinical signs of canine ehrlichiosis are often nonspecific and include fever, anorexia, lymphadenomegally, lethargy, depression, splenomegaly, and hemorrhagic tendencies. Different clinical abnormalities, such as anemia, thrombocytopenia, and hyperproteinemia due to hypergammaglobulinemia, can be found in dogs infected by E. canis. Pathological findings in dogs naturally infected with Angiostrongylus vasorum in Newfoundland and Labrador, Canada J Vet Diagn Invest 20:11–20 (2008). Pathological findings consisted of severe pyogranulomatous interstitial pneumonia with myriad eggs, larvae, and numerous intravascular pulmonary adult nematodes with extensive arterial thrombosis. Five hundred and seventy-two adult worms were removed from pulmonary arteries. Foci of granulomatous inflammation, often associated with larvae and/or eggs, were present in tracheobronchial lymph nodes, adrenal gland, brain, and kidneys. Urine sampling for real-time polymerase chain reaction–based diagnosis of canine leishmaniasis. J Vet Diagn Invest 20:64–67 (2008). This finding suggests that a real-time PCR analysis of urine from infected dogs could be a useful and noninvasive tool for monitoring the severity of leishmaniasis.

Molecular screening of canine GM1 gangliosidosis using blood smear specimens after prolonged storage: detection of carriers among Shiba dogs in northern Japan. J Vet Diagn Invest 20:68–71 (2008). GM1 gangliosidosis, a lysosomal storage disease that affects the brain and multiple systemic organs, is due to an autosomal recessively inherited deficiency of acid β-galactosidase coded by the GLB1 gene. GM1 gangliosidosis in Shiba dogs was initially identified in 2000. Diagnosis of anatoxin-a poisoning in dogs from North America. J Vet Diagn Invest 20:89–92 (2008). Anatoxin-a, a toxin produced by several genera of blue–green algae, is considered a potent neurotoxin. Ingestion of water contaminated with the toxin results in acute neurological signs and often death. Association of canine obesity with reduced serum levels of C-reactive protein. J Vet Diagn Invest 20:224–228 (2008). C-reactive protein (CRP) is an important tool for the detection of inflammation and/or early tissue damage and is linked to obesity in humans. C-reactive protein was negatively correlated with insulin/glucose ratio and cholesterol. Based on these results, it can be postulated that CRP production is inhibited by obesity and insulin resistance in dogs. Clinical and histopathological features of a thymolipoma in a dog. J Vet Diagn Invest 20:360–364 (2008). Thymolipoma, which is a rare, slow-growing, benign tumor of the thymus composed of mature adipose tissue and thymic tissue. Microscopically, the mass was composed of adipose tissue with numerous cords and nests of thymic tissue without corticomedullary arrangement. A case of two different tumors in the heart of a dog. J Vet Diagn Invest 20:365–368 (2008). Histological examination revealed the coexistence of tubular adenocarcinoma and an undifferentiated sarcoma in the myocardium. Immunohistochemical staining of the sarcoma cells was negative for cytokeratin, desmin, and smooth muscle myosin, thus excluding their epithelial or myoepithelial origin, as well as an origin from smooth muscles cells. These findings, together with the coexpression of vimentin and a–smooth muscle actin, suggested that the sarcoma was derived from myofibroblasts. Malignant mediastinal extra-adrenal paraganglioma with spinal cord invasion in a dog. J Vet Diagn Invest 20:372–375 (2008). A locally invasive mass involving the thoracic wall. Upon necropsy, an encapsulated, fluctuant mass was noted attached to the right dorsal body wall in the region of the fifth to seventh thoracic vertebra. Churukian-Schenk staining revealed positive granules within the neoplastic cell cytoplasm and immunohistochemistry was positive for expression for cytoplasmic neuron-specific enolase and synaptophysin. Chromogranin A and S100 expression were found to be negative. Immunohistochemistry and silver staining did not allow further differentiation of the tumor, and the diagnosis remains consistent with either a chromaffin paraganglioma or a nonchromaffin paraganglioma (chemodectoma) with some production of catecholamines. Fonsecaea pedrosoi skin infection in a dog. J Vet Diagn Invest 20:379–381 (2008). Chromoblastomycosis, phaeohyphomycosis, and eumycotic mycetoma are a group of systemic and cutaneous diseases caused by dematiaceous fungi.1 Dematiaceous fungi are characterized by a brown to black pigmentation of their hyphae and are ubiquitous in nature. Most common species encountered in disease conditions include Fonsecaea spp., Alternaria spp., Bipolaris spp., Cladophialophora spp., and Curvularia spp.3 This report describes a phaeohyphomycotic condition caused by Fonsecaea pedrosoi infection in a dog. Canine parvovirus 2c infection in central Portugal. J Vet Diagn Invest 20:488–491 (2008). Both, CPV-2b and CPV-2c were found in severe disease, and significant differences were not found in the clinical outcome of dogs infected with CPV- 2b versus CPV-2c. Further, significant associations were not found between breed, age category (,12 weeks, .14 weeks), vaccination status, or clinical outcome. The original CPV-2 isolates were replaced by new antigenic types, termed CPV-2a, and a virus type displaying a single mutation that was termed CPV-2b. CPV-2c, co-circulates with CPV-2a and CPV-2b. Since its discovery, CPV-2c has also been detected in Vietnam, Europe, the United States and South America. Pathology and toxicology findings for search-and-rescue dogs deployed to the September 11, 2001, terrorist attack sites: initial five-year surveillance. J Vet Diagn Invest 20:477–484 (2008). significant numbers of both deployed and nondeployed dogs have evidence of inhaled matter as demonstrated by the presence of anthracotic pigments or refractile particulate matter in pulmonary tissue. Although S&R activities in response to the 9/11

terrorist attacks exposed dogs to a wide variety of potentially toxic compounds, to date, these dogs do not appear to suffer from higher mortality or increased pulmonary disease compared with nondeployed dogs. Effects of T lymphocytes, interleukin-1, and interleukin-6 on renal fibrosis in canine end-stage renal disease. J Vet Diagn Invest 20:585–592 (2008). The present study shows that T lymphocytes and IL-6 play important roles in renal fibrosis. secreting IL-1 in the ESRD kidney. IL-6 is a cytokine secreted by T cells, epithelial cells, and IL1-activated fibroblasts. expression of IL-6 is increased in direct proportion to the rate of fibrous area. Moreover, IL6 expression localizes in the regions of infiltrating lymphocytes and around the glomeruli in the present study (Fig. 4C). This pattern of expression indicates that T lymphocytes in the infiltrate regions and IL-1-activated fibroblasts around the glomeruli secrete IL-6 as an immune response in the ESRD kidney. Lipid-rich pleural mesothelioma in a dog. J Vet Diagn Invest 20:665–667 (2008). hard plaque-like masses that studded the epicardial, pericardial, mediastinal, and costal pleural surfaces. Within the right thorax, the lesions coalesced into a large mass that occupied most of the cavity. Histologically, the masses were composed of solid sheets and papillary aggregates of medium-sized polygonal cells that contained abundant vacuolated to clear cytoplasm. Some of the cytoplasmic vacuoles stained positive with oil red O. The stroma contained metaplastic trabeculae of woven and lamellar bone. Immunohistochemically, the neoplastic cells expressed vimentin, pancytokeratin, and S-100 protein. Transmission electron microscopy corroborated the presence of intracytoplasmic vacuoles and demonstrated prominent intercellular junctional complexes and apically located microvilli.. Epithelioid Variant of Hemangioma and Hemangiosarcoma in the Dog, Horse, and Cow. Vet Pathol 44:15– 24 (2007). Epithelioid hemangiomas, hemangioendotheliomas, and angiosarcomas are well recognized histologic variants of endothelial tumors in humans that in the past have been confused with neoplasms of epithelial or histiocytic origin. Most often reported in the dermis or subcutis. CNS Hypomyelination in Rat Terrier Dogs with Congenital Goiter and a Mutation in the Thyroid Peroxidase Gene. Vet Pathol 44:50–56 (2007). Hyperplasia of the follicular epithelium but hypothyroid (Low T4), myelin deficiency, most evident in the corpus callosum. A homozygous nonsense mutation in the thyroid peroxidase gene. Immunohistochemical Detection of Protein Gene Product 9.5 (PGP 9.5) in Canine Epitheliotropic T-Cell Lymphoma (Mycosis Fungoides). Protein gene product 9.5 (PGP 9.5), a ubiquitin COOH-terminal hydrolase is expressed in a variety of epithelial and mesenchymal tumors (and neural/neuroendocrine). All tumors were confirmed as T-cell epitheliotropic lymphoma by histopathology and immunohistochemistry for CD3. Eight of 14 cases were positive for PGP 9.5, with reactivity mainly in the cytoplasm and less commonly in the nucleus Maxillary Ameloblastic Carcinoma in an Alaskan Malamute. Vet Pathol 44:84–87 (2007). Mass in right maxilla with palisading cells distributed irregularly in cords. Histologic and Ultrastructural Studies of Juvenile Onset Renal Disease in Four Rottweiler Dogs. Vet Pathol 44:96–100 (2007). Cystic dilatation of Bowman’s space, mesangial hypercellularity, and glomerulosclerosis. Three dogs also had glomerular crescents and moderate to severe interstitial fibrosis. Electron microscopy revealed glomerular basement membranes of variable thickness, with extensive splitting or lamellation of the lamina densa. These ultrastructural findings are similar to those found in people and in other breeds of dogs with inherited defects in type IV collagen. Fibrosing Gastrointestinal Leiomyositis as a Cause of Chronic Intestinal Pseudo-Obstruction in an 8-MonthOld Dog. Vet Pathol 44:106–109 (2007). both the small and large intestines were distended and fluid-filled.. Microscopic lesions -intestinal tunica muscularis and muscularis mucosae --extensive-to-diffuse replacement of the smooth muscle by fibrous tissue and infiltration by a moderately dense mononuclear inflammatory infiltrate. A unique finding was the presence of similar microscopic lesions in the tunica muscularis of the urinary bladder and stomach. Osseous Metaplasia in the Eye of a Dog. Vet Pathol 44:222–224 (2007). Histopathology revealed a diagnosis of bone formation within otherwise normal iris tissue. Non-neoplasitc.

Amyloid-Producing Odontogenic Tumor and Its Immunohistochemical Characterization in a Shih Tzu Dog. Vet Pathol 44:233–236 (2007). nests, islands, and strands of proliferating odontogenic and squamous epithelial cells, intermingled in close association with large numbers of irregular extracellular deposits of amyloid and amorphous calcified substance. Synovial Hemangioma in the Stifle Joint of a Dog. Vet Pathol 44:240–243 (2007). vascular channels that were lined by well-differentiated endothelial cells and separated by fibrous septa. Distension of some channels resulted in endothelial disruption, thrombosis, hemorrhage, necrosis, and focal spindle-cell proliferation Cranial Nerve Hamartoma in a Dog. firm, white nodules across the petrosal crest (part of temporal bone) of the skull. Microscopically, the nodules were composed of normal myelinated nerve fibers within a mucinous stroma. Uveal Spindle Cell Tumor of Blue-Eyed Dogs: An Immunohistochemical Study. Vet Pathol 44:276–284 (2007). anti-UVssDNA, and TERT. Electron microscopy revealed intermittent basal laminae between cells. These tumors are morphologically and immunohistochemically most consistent with schwannoma. All tumors were negative for SMA, desmin, Melan A, and MITF-1. Tumors were variably positive for PGP 9.5, laminin, gadd45, p53, PCNA, anti-UVssDNA. Cellular Proliferation in Canine Cutaneous Mast Cell Tumors: Associations with c-KIT and Its Role in Prognostication. Vet Pathol 44:298–308 (2007). In this study, increased Ki67 and AgNOR counts were both associated with significantly decreased survival. Additionally, the results of this study show that MCTs with aberrant KIT protein localization or internal tandem duplication c- KIT mutations are associated with increased cellular proliferation, further suggesting a role for c-KIT in the progression of canine MCTs. Mitotic Index Is Predictive for Survival for Canine Cutaneous Mast Cell Tumors. Vet Pathol 44:335–341 (2007). For grade II tumors with anMI #5, the median survival time (MST) was 70 months, compared with 5 months for those with an MI .5 (P , .001). Diagnoses and Clinical Outcomes Associated with Surgically Amputated Canine Digits Submitted to Multiple Veterinary Diagnostic Laboratories. Vet Pathol 44:355–361 (2007). Squamous cell carcinoma was the most commonly identified tumor (n 5 109, 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 5 52, 17.3%), soft-tissue sarcoma (n 5 29, 9.7%), and mast cell tumor (n 5 20, 6.7%). Melanomas were associated with poor prognoses, with a median survival time of 365 days Kernicterus (bilirubin toxicity) in an Adult Dog. Vet Pathol 44:383–385 (2007). 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. Immunoglobulin Crystals in Reactive Plasma Cells in a Dog. Vet Pathol 44:389–391 (2007). Intracellular crystalline deposits of immunoglobulin are occasionally seen in human B-cell lymphoproliferative disorders such as multiple myeloma, chronic lymphocytic leukemia, and various forms of lymphoma. Theses were in a chronic inflammatory lesion. Microscopically, the intracellular, non-birefringent eosinophilic crystals were square to rectangular, 2–20 mm long, and caused nuclear displacement to the periphery. The crystal-containing cells, as well as some of the crystals themselves, were positive for lambda light chain. Primary Cardiac Fibrosarcoma with Pulmonary Metastasis in a Labrador Retriever. Vet Pathol 44:403–407 (2007). Large mass inside the pericardial sac associated with the left ventricle. At necropsy, the dog had marked ascites, mild hydrothorax, marked hydropericardium, and an 11.0 3 7.0 3 6.0 cm, tan and red, firm, well-demarcated mass attached to the left ventricular free wall. The mass was diagnosed as a fibrosarcoma based on the morphologic appearance and supportive immunohistochemical staining.

Expression of Monocarboxylate Transporter 1 in Oral and Ocular Canine Melanocytic Tumors. Vet Pathol 44:449–457 (2007). Monocarboxylate transporter 1 (MCT1) is a major proton transporter in mammalian cells that transports monocarboxylates, such as lactate and pyruvate, together with a proton across the plasma membrane. Increased MCT1 expression in oral melanomas compared with ocular melanocytic tumors may reflect the very different biology between these tumors in dogs. These results are the first to document canine MCT1 expression in canine tumors and suggest that increased MCT1 expression may provide a potential therapeutic target for oral melanoma. Inactivation of the p16 Cyclin-Dependent Kinase Inhibitor in High-Grade Canine Non-Hodgkin’s T-Cell Lymphoma. Vet Pathol 44:467–478 (2007). p16 deletion or inactivation occurs almost exclusively in high-grade T-cell NHL; however, alternative pathways can generate functional phenotypes of Rb deficiency in low-grade Tcell NHL and in high-grade B-cell NHL. Simultaneous Canine Distemper Virus, Canine Adenovirus Type 2, and Mycoplasma Cynos Infection in a Dog with Pneumonia. Vet Pathol 44:508–512 (2007). Pathologic examination revealed a fibrinous necrotizing pneumonia with large amphophilic intranuclear and acidophilic intracytoplasmatic inclusion bodies in different lung cells. Immunohistochemically, CDV antigen was present in lung and many other organs. In situ hybridization for detection of CAV nucleic acid showed positive signals in the lung only. Polymerase chain reaction of lung tissue and consecutive sequencing of the amplification product identified CAV type 2. Bacteriologic examination of lung tissue yielded large amounts of M cynos. The bacteria seem to have been responsible for a strong necrotizing component of the pneumonia, as they were predominantly localized in such areas. Genitourinary Rhabdomyosarcoma with Systemic Metastasis in a Young Dog. Vet Pathol 44:518–520 (2007). the uterine wall was thickened with poorly defined neoplastic infiltrates. The urinary bladder was markedly thickened due to botryoid nodules exhibiting exophytic growth into the lumen. Metastases to lung, liver, kidney, and abdominal and thoracic lymph nodes were also noted. Microscopically, the genital tract and retroperitoneal masses were consistent with the alveolar subtype of rhabdomysarcoma, while the urinary bladder mass had characteristics of the embryonal subtype. Immunohistochemically, the neoplastic cells in all these tissue sites were intensely positive for desmin, sacromeric actin, and vimentin, while they were uniformly negative for cytokeratin and smooth muscle actin. Phosphotungstic acid hematoxylin stain revealed cross-striations in the cytoplasm of scattered neoplastic cells. Mammary Carcinoma with Sebaceous Differentiation in a Dog. Vet Pathol 44:525–527 (2007). Microscopically, the tumors were composed of two distinctive neoplastic components, intraductal papillary adenocarcinoma and sebaceous carcinoma. The regions of sebaceous tumor were clumped separately, contained well-developed sebaceous cells and keratinized epithelial cells, and were surrounded by few to several layers of basaloid cells. The cells with abundant foamy cytoplasm that resembled sebaceous cells were also found within the intraductal papillary-like nests of mammary carcinoma, providing evidence of sebaceous metaplasia. Intramedullary Cavernous Malformation of the Spinal Cord in Two Dogs. Vet Pathol 44:528–532 (2007). Extensive intraparenchymal hemorrhage was found on gross postmortem examination in both dogs, and a distinct lobulated intramedullary mass was evident in the second dog. Microscopically, both lesions were composed of dilated, thin-walled vascular channels with little-to-no intervening neural parenchyma. Both dogs had evidence of channel thrombosis along with perilesional hemorrhage and hemosiderin accumulation. Lenticular Invasion by a Ciliary Body Adenocarcinoma in a Dog. Vet Pathol 44:540–542 (2007). Histologic evaluation of the enucleated eye revealed a ciliary body adenocarcinoma with lens invasion. Where the tumor encroached on the lens, the lens capsule was absent and there was scrolling of the broken ends of the capsule. Cholesterol Granuloma Associated with Otitis Media and Destruction of the Tympanic Bulla in a Dog. Vet Pathol 44:547–549 (2007). The necessary factors for the development of CG in the middle ear and other normally aerated bony cavities are thought to be hemorrhage, interference with drainage, and obstruction of ventilation. Possible causes of the initial hemorrhage include mucosal inflammation, trauma, and pressure changes within the air cells. Cholesterol, originating from erythrocyte membranes and possibly mucosa or transudate, precipitates forming crystals which, stimulate a granulomatous reaction and the development of CG.

Canine Hyperplastic Intraepidermal Pustular and Suprabasal Acantholytic Dermatosis with Features of Human Pemphigus Vegetans. Vet Pathol 44:550–555 (2007). Pemphigus vegetans is a rare autoimmune blistering acantholytic dermatosis of humans that combines unusually hyperplastic and verrucous pustular skin lesions and mucosal erosions. circulating autoantibodies against canine desmoglein-1 were solely identified. This antigen target is different from that of the human disease in which antidesmoglein-3 autoantibodies are detected most commonly. Pathology of Mucopolysaccharidosis IIIA in Huntaway Dogs. Vet Pathol 44:569–578 (2007). By histology, there were variably stained storage cytosomes within neurons, including many that stained for gangliosides. On ultrastructure examination, these cytosomes contained either moderately dense granular material, tentatively interpreted as precipitated glycosaminoglycan; a variety of multilaminar bodies, interpreted as being associated with secondary accumulation of gangliosides; or a mixture of both types Cellular Characterization of Multidrug Resistance P-glycoprotein, Alpha Fetoprotein, and Neovascular Endothelium-Associated Antigens in Canine Hepatocellular Carcinoma and Cirrhotic Liver. Vet Pathol 44:600–606 (2007). P-gp was expressed at higher levels in HCC than in cirrhotic livers, and was most commonly localized in biliary canaliculi and small ductuli. AFP was localized mainly in the cytoplasm in HCC and in. CD31 was expressed strongly in the portal area and parenchyma in HCC, but it was rarely observed in the parenchyma in cirrhosis. CD34 expression could not be detected in both HCC and cirrhosis. The Spectrum of Canine Cutaneous Perivascular Wall Tumors: Morphologic, Phenotypic and Clinical Characterization. Vet Pathol 44:607–620 (2007). Perivascular wall tumors (PWTs) are defined as neoplasms deriving from mural cells of blood vessels, excluding the endothelial lining. The spectrum of human cutaneous PWT includes glomus tumor, hemangiopericytoma (HEP), myopericytoma, angioleiomyoma/sarcoma, angiomyofibroblastoma, and angiofibroma. Diagnosis was established on the basis of vascular growth patterns (staghorn, placentoid, perivascular whorling, bundles from media) and immunohistology, including 7 smooth muscle markers and the cell membrane ganglioside of unknown origin recognized by the antibody 3G5 (CMG3G5). HEP is a diagnosis of exclusion. Metastatic Iridociliary Adenocarcinoma in a Labrador Retriever. Vet Pathol 44:672–676 (2007). Histopathologic evaluation of the globe revealed extensive invasion of the uvea and sclera by a pleomorphic cell population that formed disorganized cords and exhibited PAS-positive basement membrane material. Necropsy revealed a morphologically similar tumor in the ipsilateral orbit and lung. On immunohistochemical examination, the intraocular tumor stained diffusely immunopositive for vimentin, S-100, and neuron-specific enolase and multifocally, sparsely immunopositive for Cytokeratin AE1/AE3. Immunohistochemical Characterization and Evaluation of Prognostic Factors in Canine Oral Melanomas with Osteocartilaginous Differentiation. Vet Pathol 44:676–682 (2007). oral melamonas with osteocartilaginous differentiation have a clinical course similar to that of other melanomas in the oral cavity. Analysis of the mitotic index and the expression of proliferation marker Ki-67 could be useful tools for predicting the biological behavior of these neoplasms. Histopathologic Evidence of Capecitabine Corneal Toxicity in Dogs. Vet Pathol 44:700–702 (2007). Capecitabine (CPC) was administered as an oral immunosuppressive agent (renal transplant). Two dogs developed superficial keratitis, which was characterized by multifocal geographic erosions, superficial corneal epithelial pigmentation, and corneal neovascularization. These clinical signs correlated with the dose of CPC given. Ocular histopathologic abnormalities were limited to neovascularization and inflammatory infiltrate of the anterior corneal stroma and abnormal basal cell morphology, disorganization, thinning, and pigmentation of the corneal epithelium. Tenascin-C in Chronic Canine Hepatitis: Immunohistochemical Localization and Correlation with NecroInflammatory Activity, Fibrotic Stage, and Expression of Alpha-Smooth Muscle Actin, Cytokeratin 7, and CD3+ Cells. Vet Pathol 44:803–813 (2007). TN-C is strongly correlated with increased fibrotic stage, inflammatory activity, and expression of CK7 and a-SMA. TN-C, CK7, and CD3 expression did not differ between diagnostic groups. Tenascin-C (TN-C) is one of the ECM proteins that has both adhesive and antiadhesive activities. In adult tissue, TN-C expression is absent or much reduced. However, expression is enhanced during processes involving ECM remodeling and cell migration, such as in tumor growth, fibrosis, and wound healing.

Immunohistochemical Expression of Vascular Endothelial Growth Factor and Vascular Endothelial Growth Factor Receptor Associated with Tumor Cell Proliferation in Canine Cutaneous Squamous Cell Carcinomas and Trichoepitheliomas. Vet Pathol 44:823–830 (2007). It was concluded that VEGF and VEGFR-2 may promote tumor cell proliferation in TCPs and SCCs. An autocrine pathway for VEGF probably operates in canine SCCs and TCPs, as VEGF and VEGFR-2 expression was found in most tumors and was associated with evidence for tumor cell proliferation. Immunohistochemical Detection of Multiple Myeloma 1/Interferon Regulatory Factor 4 (MUM1/IRF-4) in Canine Plasmacytoma: Comparison with CD79a and CD20. Vet Pathol 44:875–884 (2007). 1) Antibody Mum1p is very specific for canine plasmacytomas, 2) antibody Mum-1p is superior in sensitivity and specificity to CD79a and CD20 for the identification of canine plasmacytomas in formalin-fixed, paraffin-embedded tissues, 3) canine lymphomas that express MUM1/IRF4 are few and usually of B-cell origin, 4) other canine leukocytic and melanocytic tumors do not express MUM1/IRF4 (required for Ig Light chain rearrangement). Expression of the Embryonic Transcription Factor Oct4 in Canine Neoplasms: A Potential Marker for Stem Cell Subpopulations in Neoplasia. Vet Pathol 44:893–900 (2007). Oct4 has been consistently associated with pluripotent or stemlike cells, and it is hypothesized that Oct4 is necessary for the maintenance of pluripotency. We hypothesize that Oct4- positive cells are present in all canine neoplasms and that these subpopulations of neoplastic cells might represent ‘‘cancer stem’’ cells. All tumors included in this study contained a subpopulation of Oct4positive cells. Pulmonary Lymphomatoid Granulomatosis in a Dog: Evidence of Immunophenotypic Diversity and Relationship to Human Pulmonary Lymphomatoid Granulomatosis and Pulmonary Hodgkin’s Disease. Vet Pathol 44:921–923 (2007). Histopathologic examination showed a mixed population of atypical lymphoid cells that had infiltrated into the pulmonary blood vessels angiocentrically. The lymphocytes were CD3 positive, consistent with a pan-T-cell phenotype. The lymphoid cells in the lesion were also positive for CD20cy and CD79a, indicative of the presence of B cells. We also observed large Reed- Sternberg–like cells (large pleomorphic and binucleated nuclei) that were positive for CD15 and CD30, similar to observations in human pulmonary Hodgkin’s disease (PHD). In conclusion, canine PLG in this Cocker Spaniel was associated with B and T cells, which is first identified in a case of canine PLG. It was histopathologically similar to human lymphomatoid granulomatosis and immunophenotypically similar to human PHD. Histologic and Immunohistochemical Characterization of a Testicular Mixed Germ Cell Sex Cord-Stromal Tumor and a Leydig Cell Tumor in a Dog. Vet Pathol 44:936–943 (2007). Histologically, MGSCT consisted of two nodules of seminiferous tubules lined by germ cells and Sertoli cells in variable proportions. Germ cells had variable size and nuclear features, with frequent giant cells. Germ cells were evenly mixed with Sertoli cells or located in the center of tubules. Markers that labeled mainly germ cells and few or no Sertoli or Leydig cells were calretinin, KIT, and PGP 9.5. E-cadherin, GATA-4, inhibin-a (INH-a), and neuron-specific enolase (NSE) were predominantly detected in Sertoli cells, whereas melan A was particularly expressed in Leydig cells and vimentin in all three cell types. Immunohistochemical Demonstration of the Putative Canine Distemper Virus Receptor CD150 in Dogs with and without Distemper. Vet Pathol 44:943–948 (2007). Signaling lymphocyte activation molecule (SLAM) or CD150 can function as a receptor for the canine distemper virus (CDV) in vitro. Additionally, virus infection is associated with up-regulation of SLAM, potentially causing an amplification of virus in the host. SLAM labeling was also found in multiple organs, including footpad lymph nodes, lung, transitional cell epithelium of the urinary tract, and in the stomachs and intestines of control dogs (Nos. 1–7) and CDV-infected dogs. Sarcocystis neurona Encephalitis in a Dog. Vet Pathol 44:956–961 (2007). Multiple foci of encephalitis were found in the cerebrum and particularly in the cerebellum. Protozoa morphologically consistent with Sarcocystis sp. were identified at sites of intense inflammation and malacia. Additionally, multiple schizonts were identified in areas without inflammation. Immunohistochemistry using both polyclonal and monoclonal antibodies specific for Sarcocystis neurona was strongly positive. No reaction to polyclonal antisera for Toxoplasma gondii or Neospora caninum was found. Polymerase chain reaction confirmed that the protozoa were S. neurona.

Characterization of a Population of Unique Granular Lymphocytes in a Bitch Deciduoma, Using a Panel of Histo- and Immunohistochemical Markers. Vet Pathol 44:521–524 (2007). Discrete swellings were found in the uterine horns, with the macroscopic appearance of normal early pregnancy. At histologic examination, the endometrium, devoid of any conceptus and chorion, showed a marked proliferation, on the basis of which a diagnosis of deciduoma was made. Our data indicate that the peculiar lymphocyte population observed in the bitch deciduoma shows similarities with the granulated decidual cells, until now described only in primates and rodents (uNK cells). S-100 IHC- S-100 is normally present in cells derived from the neural crest (Schwann cells, melanocytes, and glial cells), chondrocytes, adipocytes, myoepithelial cells, macrophages, Langerhans cells, dendritic cells, and keratinocytes. S100 proteins are involved in regulation of protein phosphorylation, transcription factors, Ca++ homeostasis, the dynamics of cytoskeleton constituents, enzyme activities, cell growth and differentiation, and the inflammatory response. It can be found in melanomas, 50% of malignant peripheral nerve sheath tumors, and clear cell sarcomas. Expression of Genes Encoding Matrix Metalloproteinases (MMPs) and their Tissue Inhibitors (TIMPs) in Normal and Diseased Canine Mitral Valves. J. Comp. Path. 2009, Vol. 140, 271e277. MMPs are Ca2+ and Zn2+ dependent proteases secreted as inactive zymogens and are activated by other MMPs, plasmin, interleukin-1b (IL1b), tumour necrosis factor- a (TNF-a) and other mediators. They are inhibited by specific tissue inhibitors (TIMPs). In the valves from dogs with CVD there was significantly increased transcription of mRNA encoding MMP-1 and -14 and TIMP-2, -3 and -4, but no elevation in mRNA encoding MMP-2 and -9. MMPs and TIMPs. This suggests that reduced catabolism contributes to the structural alteration of canine Mitral valves. Hypospadias in six dogs. Veterinary Record (2009) 164, 331-333. Hypospadias is a congenital abnormality in which the urethral opening is in an abnormal position. In dogs there are five forms of hypospadias; the urethral opening can be located on the ventral penile glans (glandular form), on the penile shaft (penile form), on the scrotum (scrotal form), on the perineum (perineal form), or in the anal area (anal form). The etiology of the abnormality is unknown. In human beings it is postulated to result from the exposure of the fetus to high levels of progesterone, and vitamin A deficiency during pregnancy. No involvement of teratogenic factors has been described in dogs with hypospadias. It has been found more frequently in hermaphrodites but it can also occur as a single abnormality. Hypospadias is frequently accompanied by other anatomical abnormalities, such as, most frequently, cryptorchidism, underdeveloped testicles, shortening of the penis, lack or cleft of the scrotum and the remains of the Müller’s duct. Metastasising liposarcoma of bone in a young dog. Veterinary Record (2009) 164, 372-373. Arises from adipocyte precursors in the marrow cavity and has been observed in the long bones or lumbar vertebrae of dogs. Extensive lysis of cortical bone was noted. In the sacral lymph nodes, pericardium, liver, spleen and kidneys, expansive non-encapsulated tumour nodules were found. The cytoplasmic vacuoles stained positive for fat using Sudan III staining, and for S100 protein by immunohistochemistry. Expression of vimentin was confined to well differentiated tumour cells. Immunohistochemistry was negative for α-smooth muscle actin, desmin, cytokeratin and CD3. Pathological Findings in Dogs with Fatal Heatstroke: Journal of Comparative Pathology Volume 140, Issues 2-3, February-April 2009, Pages 97-104: The most commonly observed lesions in this study of natural cases of canine heatstroke were hyperaemia, oedema, haemorrhages (skin, lung, brain) and necrosis (SI, renal tubular epithelium, periacinar hepatocyte necrosis and neurons) in various organs. Pathogenesis: Strenuous exerciseshunting of blood to skin, muscles intestinal ischemia, hypoxia and hypoperfusionintestinal mucosal necrosis endotoxemia, endothelial injurytissue thromboplastin and factor XII coagulation and complement cascasde systemic inflammatory response syndrome DIC (plays major role) COX-2 Expression in Canine Normal and Neoplastic Mammary Gland COX-2 was constitutively expressed in normal mammary tissue with membranous apical labelling of glandular epithelium. In neoplastic lesions and in adjacent non-neoplastic mammary tissue COX-2 was expressed in the cytoplasm of epithelial cells. Marked expression of COX-2 was observed in 8.3% of benign neoplasms and in 42.2% of malignant neoplasms, mainly in poorly differentiated areas. The majority of metastatic lesions exhibited strong COX-2 labelling.

An Immunohistochemical Analysis of Canine Haemangioma and Haemangiosarcoma J. Comp. Path. 2009, Vol. 140, 158e168 Haemangiosarcomas express high levels of CD117 (c-kit gene), VEGFR-3, CD44 compared to hemangiomas. CD117: is a tyrosine kinase growth factor receptor for stem cell factor on stem cells. VEGFR-3: Angiogenesis CD44: Cell surface adhesion molecule involved in cell-to-cell and cell-to-matrix interactions which helps in metastasis. A Clonal Outbreak of Acute Fatal Hemorrhagic Pneumonia in Intensively Housed (Shelter) Dogs Caused by Streptococcus equi subsp. Zooepidemicus Vet Path 2008 Jan: All dogs had hemothorax and an acute, fibrinosuppurative pneumonia with large numbers of colonies of bacterial cocci. Vascular thrombosis was seen in spleen and kidney. Extensive Bilateral Odontogenic Cysts in the Mandible of a Dog Vet Path 2008 Jan: cystic cavities lined by stratified squamous epithelium overlying a fibrous layer infiltrated by mononuclear cells. Reported odontogenic cysts include radicular cysts, dentigerous cysts, and keratocysts.

Esophageal Duplication Cyst in a Dog Vet Path 2008 Jan: 3 criteria for esophageal duplication cyst 1)present within the esophageal wall; 2)contains 2 muscle layers; 3) must contain squamous, columnar, cuboidal, pseudostratified, or ciliated epithelium

Extraventricular Neurocytoma of the Spinal Cord in a Dog Vet Path 2008 Jan: Neurocytomas are welldifferentiated tumors, benign tumors with various architectural patterns (honeycomb arrangement of oligodendroglioma and large fibrillary areas that resemble the irregular rosettes of pineocytoma) Estrogens Metabolism Associated with Polymorphisms: Influence of COMT G482a Genotype on Age at Onset of Canine Mammary Tumors Vet Path 2008 Mar: Catechol-O-methyltransferase (COMT) is an important enzyme participating in inactivation of carcinogenic oestrogen metabolites. In humans there is a single nucleotide polymorphism in COMT gene has been associated with an increased risk for developing breast cancer. In this study dogs carrying the variant allele have a threefold likelihood of developing mammary tumors after 9 years of age in comparison with noncarriers. Vascular Endothelial Growth Factor mRNA Expression and Peritumoral Edema in Canine Primary Central Nervous System Tumors Vet Path 2008 Mar: Vascular endothelial growth factor (VEGF) is an important regulator of tumor angiogenesis and vascular permeability, and has been implicated both in progression of central nervous system (CNS) tumors and development of vasogenic peritumoral edema. Increased expression of VEGF relative to normal cerebral cortex tissue was seen predominantly in high grade astrocytic (grade IV) and oligodendroglial (grade III) tumors. The Clinical and Morphologic Features of Nonepidermolytic Ichthyosis in the Golden Retriever Vet Path 2008 Mar: 46 cases of ichthyosis were diagnosed histologically in Golden Retriever. A total of 22 < 1 year; 3 dogs between 1 and 2 years; 13 dogs developed lesions at older than 2 years. Histo: Mild to moderate laminar orthokeratotic hyperkeratosis with an absence of epidermal hyperplasia and dermal inflammation. Ultrastructurally, all affected dogs had retained and convoluted membranes with crystalline structures in the stratum corneum. This unique hyperkeratotic/scaling disorder in Golden Retrievers has distinctive clinical, histologic, and ultrastructural features, which are consistent with a primary cornification defect.

Nasal and Paranasal Adenocarcinomas with Neuroendocrine Differentiation in Dogs Vet Path 2008 Mar: Tumors of the nasal cavity or paranasal sinuses of 18 dogs were examined and classified as adenocarcinomas (13), transitional carcinomas (3), SCC (1), and 1 adenosquamous carcinoma. 5 of the 13 adenocarcinomas were argyrophilic and positive for synaptophysin and chromogranin A, indicating that neuroendocrine markers may be detected despite the lack of typical histologic features of neuroendocrine differentiation.

Bone Dysplasia in the Radial and Ulnar Metaphysis of a Newfoundland Dog Vet Path 2008 Mar: The lesions in the distal radius and ulna were characterized by focal, longitudinal striations of sclerosis of the bone marrow cavity, surrounding thin trabeculae of primary spongiosa of the distal metaphysis. The most likely pathogenesis is focal failure of conversion of primary to secondary spongiosa. The condition was termed as Sclerosing bone dysplasia. DDx. 1) Metaphyseal osteopathy (hypertrophic osteodystrophy) is characterized by alternate radiodense and radiolucent zones parallel to growth plate and histologically neutrophilic infiltration and necrosis of trabecular bone. 2) Enostosis (panosteitis), focally increased radiodensity in the medulla around nutrient foramen.

Mandibular Ossifying Fibroma in a Dog Vet Path 2008 Mar: Benign fibro-osseous proliferations of bone in veterinary species include ossifying fibroma, osteoma, and fibrous dysplasia; Osteomas are typically solitary osteosclerotic lesions arise from the surface of bones of the jaw or skull; trabeculae of woven bone constitute the bulk of the tumor, are rimmed by 1 layer of well-differentiated osteoblast; Fibrous dysplasia is a tumorlike lesion, involve 1 or multiple bones, often in young animals. It arises within the bone, rather than from the periosteal surface, and its ample fibrous stroma contains only thin, curved trabeculae of woven bone. The bony trabeculae are generally not rimmed by osteoblasts; Ossifying fibroma has histologic features intermediate between those of osteoma and fibrous dysplasia. This is an expansile, lytic, and invasive mass develops within the bone, particularly the mandible. Its bony trabeculae are rimmed by osteoblasts but are arranged haphazardly.

Xanthogranulomatous Inflammation of the Small Bowel in a Dog Vet Path 2008 Mar: Disseminated yellowwhite 2-3 mm nodules on the serosal surface of the small bowel. Histo: nodular collection of foamy cells (with lipid droplets), in serosa and muscularis with necrotic areas, hemorrhages, neovascularization, variable numbers of reactive spindle cells, neutrophils, lymphocytes and rare multinucleated giant cells. Transmural lymphangectasia and mucosal lymphoplasmacytic inflammation were also observed Necrotizing Meningoencephalitis in Five Chihuahua Dogs Vet Path 2008 May: Multifocal asymmetrical areas of necrosis or collapse in both gray and white matter of the cerebral hemispheres was seen grossly in 4 brains. Microscopically in all dogs, there was a severe, asymmetrical, intensely cellular, nonsuppurative meningoencephalitis usually with cystic necrosis in subcortical white matter. There were no lesions in the mesencephalon or metencephalon. Cells: CD3, CD11d, CD18, CD20, CD45, CD45 RA, and CD79a. In fresh frozen lesions, both CD1b,c and CD11c Primary Intimal Aortic Angiosarcoma in a Dog Vet Path 2008 May: Aneurysmal dilatation of the aorta was associated with a friable, necrotic mass attached to the endothelial surface, which partially occluded the aortic lumen. On histologic examination, plump neoplastic spindle cells formed a plaque-like mass arising from the intima that merged with a large accumulation of fibrin and necrotic debris, and projected into the lumen. Neoplastic cells invaded periaortic vessels and were seen in some infarct-associated thromboemboli. Tumor cells expressed vimentin and CD31, with infrequent, patchy staining with factor VIII-related antigen; tumor cells were negative for cytokeratin and smooth-muscle actin. Characterization of Melamine-containing and Calcium Oxalate Crystals in Three Dogs with Suspected Pet Food–induced Nephrotoxicosis Vet Path 2008 May: Histomorphologic findings in each case included acute, marked tubular degeneration and necrosis with many intratubular birefringent crystals, and

lymphoplasmacytic interstitial nephritis. most of the crystals were rough, pale brown, and stained with ORO 72h but did not stain with Alizarin Red S (pH 4.1–4.3) or Von Kossa stains; these features were consistent with a plastic or lipid. A second crystal type identified in each case was smooth and platelike with staining characteristics and IR spectroscopy and SEM/EDXA results consistent with calcium oxalate crystals. Melamine-containing crystals have distinct light microscopic, histochemical, and SEM/ EDXA characteristics that facilitate their identification in tissue. Complementary Distributions of Amyloid-b and Neprilysin in the Brains of Dogs and Cats. Vet Pathol 45:455–466 (2008). Neprilysin is an amyloid-b-degrading enzyme. The distribution of neprilysin was almost identical in dogs and cats, being high in the striatum, globus pallidus, and substantia nigra, but very low in the cerebral cortex. The white matter and hippocampus were negative. In both species, amyloid-b deposition appeared in the cerebral cortex and the hippocampus. End-Stage Kidney Disease Probably due to Reflux Nephropathy with Segmental Hypoplasia (Ask-Upmark Kidney) in Young Boxer Dogs in Norway. A Retrospective Study. Vet Pathol 45:467–474 (2008). Morphologic signs of abnormal metanephric differentiation (renal dysplasia) were observed in all cases in the form of atypical tubules or asynchronous nephronic development (immature glomeruli) or both. However, other morphologic primary dysplastic features were absent. Based on the morphologic features, it is concluded that the end-stage kidney disease in these young Boxer dogs was the result of chronic atrophic nonobstructive pyelonephritis, most probably caused by vesico-ureteral reflux, compatible with reflux nephropathy causing segmental hypoplasia (Ask-Upmark kidney) in man. It is proposed that atypical tubular epithelium in the form of adenomatoid proliferation of collecting ductepithelial cells should be considered an acquired compensatory lesion, rather than the result of disorganized metanephric development. Hyalinizing Pancreatic Adenocarcinoma in Six Dogs. Vet Pathol 45:475–483 (2008). On microscopic examination, neoplasms were composed of tubules and acini of epithelial cells, with bright eosinophilic granular apical cytoplasm. Tubular lumina and tumor stroma contained abundant hyaline material that resembled amyloid. The hyaline material was not congophilic, and tumor cells and hyaline material were immunohistochemically negative for amyloid A, immunoglobulin light chains (k and l), amylin (islet amyloid polypeptide), laminin, and a1-antitrypsin. Immunohistochemical Characterization of a Pulmonary Large-Cell Carcinoma in a Dog. Vet Pathol 45:484– 488 (2008). Histologically, pulmonary alveolar spaces contained clusters of large round anaplastic cells with ample eosinophilic cytoplasm and large irregularly shaped nuclei with prominent nucleoli. Immunohistochemistry was used to distinguish large-cell carcinoma from malignant pulmonary histiocytosis. Tumor cells had strong immunoreactivity for cytokeratin, consistent with epithelial origin. The type II alveolar epithelial cell was considered the cell of origin of the neoplasm based on the presence of lamellar bodies in some neoplastic cells and immunoreactivity for surfactant protein A and thyroid transcription factor-1. Renal Collecting Duct Carcinoma in a Dog. Vet Pathol 45:489–494 (2008). Histologically, the renal mass and the other nodules were mainly composed of papillotubular structures lined by oval-to-polygonal pleomorphic cells. The cells were reactive with DBA, PNA, and UEA-1 lectins and positive for vimentin but negative for CD10 and high molecular weight cytokeratin.. Human RCCs are classified as clear cell, papillary, chromophobe, and collecting duct carcinoma (CDC) based on histopathologic and molecular biologic properties. Oncocytoma, a benign neoplasm derived from the collecting duct, is also described. Among renal tumors, CDC is the most aggressive.

Intracardiac Ectopic Thyroid Carcinosarcoma in a Dog. Vet Pathol 45:500–504 (2008). Histopathologic diagnosis was an ectopic thyroid carcinosarcoma based on the presence of 3 distinct neoplastic tissue types. Intermixed within the tumor were neoplastic thyroid follicles containing colloid and solid nests of thyroid follicular epithelial cells, vascular channels and clefts filled with blood and lined by neoplastic endothelium, and osteoid surrounded by spindle cells and often rimmed by large multinucleated cells. Immunohistochemical reaction for thyroglobulin was positive in the tumor cells forming the colloid-filled follicles and solid nests of epithelial cells. Neoplastic endothelium was positive for factor VIII–related antigen. Cervical, Mandibular, and Parotid Lymph Nodes of Dogs Naturally Infected with Leishmania infantum: A Histopathologic and Immunohistochemistry Study and Its Correlation with Facial Skin Lesions. Vet Pathol 45:613–616 (2008). Dogs with facial skin lesions showed a higher parasite load in parotid lymph nodes than dogs without lesions of the facial skin. parasite load in parotid and cervical nodes was correlated with that of skin of the nose and pinna, as was the parasite load in mandibular lymph nodes and skin of the external nose. We demonstrated a logical involvement of the lymphatic vessels and their specific anatomic draining sites. Cervical Spinal Chordoma with Chondromatous Component in a Dog. Vet Pathol 45:650–653 (2008). A necropsy revealed a semitranslucent solid mass infiltrating dorsal and ventral dura mater and the spinal cord. Histologic examination revealed a lobulated pleomorphic mass, mainly resembling undifferentiated cartilage interspersed by spindle-shaped and polygonal cells with highly vacuolated cytoplasm (physaliphorous cells). Immunohistochemistry of the tumor cells demonstrated dual expression of vimentin and cytokeratin. Based on the histologic and immunohistochemical results, the diagnosis of a chordoma with chondromatous component was made. Survival of Dogs Following Surgical Excision of Histologically Well-differentiated Melanocytic Neoplasms of the Mucous Membranes of the Lips and Oral Cavity. Vet Pathol 45:889–896 (2008). Results of this study indicate that a favorable clinical course and prolonged survival can be expected in most dogs with histologically well-differentiated melanocytic neoplasms of the mucous membranes of the lips and oral cavity, with only local excision of the lesions and no adjunct therapy. Generalized Nodular Dermatofibrosis in the Absence of Renal Neoplasia in an Australian Cattle Dog. Vet Pathol 45:901–904 (2008). At gross necropsy, innumerable, firm, round to oval, white, 0.25 to 2 cm masses were detected throughout the subcutaneous tissues of the axial and appendicular skeleton, epimysium of numerous muscles, and parietal peritoneum of the lateral abdominal body wall. The left kidney was approximately half the size of the right, and there was severe bilateral renal medullary (papillary) necrosis. Histologically, the subcutaneous nodules were well-demarcated masses of mature, hypocellular collagen that were consistent with previous reports of nodular dermatofibrosis and renal cystadenomas or cystadenocarcinomas. In addition to diffuse acute medullary necrosis, both kidneys were affected by severe chronic lymphoplasmacytic interstitial nephritis. Cerebellar Ependymal Cyst in a Dog. Vet Pathol 45:910–913 (2008). Histologically, the lesion was characterized by extensive loss of cerebellar tissue in both hemispheres and vermis. Toward the surface of the cerebellar defect, the cavity was confined by ruptured and folded membranes consisting of a layer of glial fibrillary acidic (GFAP)-positive glial cells covered multifocally by epithelial cells. Some of these cells bore apical cilia and were cytokeratin and GFAP negative, supporting their ependymal origin. The histopathologic features of our case are consistent with the diagnosis of an ependymal cyst. Its glial and ependymal nature as demonstrated by histopathologic and immunohistochemical examination differs from arachnoid cysts, which have also been reported in dogs. Tracheal hypoplasia with a discrete subaortic septal ridge in a Rottweiler puppy. J Vet Diagn Invest 21:117–119 (2009). Concurrent tracheal hypoplasia and discrete subaortic stenosis are described in a 12-week-old Rottweiler puppy that presumably died of pulmonary edema. Osteomyelitis and discospondylitis due to Scedosporium apiospermum in a dog. J Vet Diagn Invest 21:120–123 (2009). At necropsy, T13-L1 vertebrae had large areas of necrosis within the vertebral bodies. Histopathological

findings - fungal osteomyelitis and discospondylitis. Polymerase chain reaction identified Scedosporium apiospermum, a eutrophic filamentous fungus now recognized as an emerging agent of severe infections in immunosuppressed human patients. Multiple atypical mucosal xanthomas in a dog similar to human verruciform xanthoma. J Vet Diagn Invest 21:124–128 (2009). 1–6- mm granular plaques or slightly elevated papillary nodules were found in the oral cavity (dorsal and ventral sides of the tongue, inner upper lip) and in the upper digestive tract (esophagus, stomach). Microscopically, subepithelial aggregates of large foamy cells were found in strong association with papillary epithelial hyperplasia. By immunohistochemistry, the majority of these cells tested positive for lysozyme and ACM1. The cells had cytoplasmic lipid content that stained positively with oil red O. Malignant acoustic schwannoma in a dog. J Vet Diagn Invest 21:129–132 (2009). tumor had infiltrative growth, and the spindle-shaped neoplastic cells were arranged in sheets and concentric whorls. Immunohistochemical staining of the neoplastic spindle cells was positive for S-100 antigen, neuronspecific enolase, and glial fibrillary acidic protein. Cryptococcus gattii with bimorphic colony types in a dog in western Oregon: additional evidence for expansion of the Vancouver Island outbreak. J Vet Diagn Invest 21:133–136 (2009). bimorphic morphology, melaninpigmented and unpigmented. Pigmented colonies were encapsulated budding spherical yeast, whereas unpigmented colonies were of unencapsulated ovoid budding yeast. In addition to defective melanin production, the unpigmented colony type exhibited defective mating. Verminous myelitis in a pit bull puppy. J Vet Diagn Invest 21:400–402 (2009). A 10-week-old, male pit bull dog presented to the referring veterinarian with hind limb paresis and epaxial muscle atrophy. No spinal lesions were identified at gross necropsy; however, histologically there was marked granulomatous myelitis in the spinal cord between T13 and L2 with occasional, intralesional nematode larvae. Based on morphologic characteristics, the nematode larvae were identified as Strongyloides spp., possibly Strongyloides stercoralis. Aberrant parasite migration to the spinal cord in dogs is rare. Literature searches reveal that most reports are of Spirocerca lupi and Angiostrongylus spp. migration but also include Baylisascaris procyonis8 or Dirofilaria immitis. In the current case, the larvae appear to be from the superfamily Rhabditoidae based on histomorphology. Genera of the superfamily Rhabditoidae have been reported to infect the central nervous system of horses and humans. Parasite genera found in this geographic location include Strongyloides and Halicephalobus (syn. Micronema). Dogs in the southeast United States are commonly infected with Strongyloides stercoralis. Detection of Canine Oral Papillomavirus DNA in Conjunctival Epithelial Hyperplastic Lesions of Three Dogs: presence of canine papillomavirus in ocular conjunctival plaques and papillomas suggests these benign lesions may have the potential for malignant transformation. Lambda papillomavirus COPV was detected for the first time in ocular epithelial hyperplastic lesions.

Disseminated Melanoma in a Dog with Involvement of Leptomeninges and Bone Marrow: resemble leptomeningeal melanomatosis with diffuse infiltration of neoplastic melanocytes in leptomeninges and brain.

Degenerative Myelopathy in 18 Pembroke Welsh Corgi Dogs: Degenerative myelopathy (DM) is a late onset, slowly progressive degeneration of spinal cord white matter that is reported primarily in large breed dogs. The German Shepherd Dog is the most commonly affected breed. dorsolateral portion of the lateral funiculus was the most severely

affected region in all cord segments. Spinal cord segment T12 exhibited the most severe axonal loss. Spinal nerve roots, peripheral nerves, and brain sections were within normal limits.

Inflammatory Myofibroblastic Tumors (IMT) in Two Dogs: IMT are discrete masses composed of a mixture of bland fusiform myofibroblastic cells and an inflammatory infiltrate composed of varying proportions of lymphocytes, plasma cells, and histiocytes. IMTs are regarded as pseudoneoplasms.

Identification of Cancer Stem Cells in Dog Glioblastoma: small fraction of cells in the tumor, termed cancer stem cells (CSC) possess the ability to proliferate and self-renew extensively. These cells are characterized by the expression of CD133 and nestin and ability to grow as nonadherent spheres termed "neurospheres" when cultured in the presence of EGF and FGF under serum-free conditions. CSC population from a Boxer dog with glioblastoma multiforme (GBM) was cloned, this cell line is aneuploid, forms neurospheres in culture, possesses CSC markers, and reproduces the original dog GBM when inoculated into the nude mouse brain.

Disseminated Chlorellosis in a Dog: lingual mass, lungs, liver, mesenteric and sublumbar lymph nodes, and spinal meninges had pronounced green discoloration. Histologically, pyogranulomatous inflammation and algal organisms were found. The algae had cell walls and cytolasmic granules PAS positive. Ultrastructurally, the algae had a welldefined cell wall, stacks of grana and thylakoid membrane, and dense bodies, typical of starch granules. Chlorella is a chlorophyll-containing green alga closely related to Prototheca, which is thought to be its achlorophyllous mutant. Unlike Prototheca, Chlorella spp. contains numerous starch granules that are strongly PAS-positive and diastase sensitive, birefringent under polarized light. Only the cell wall of Prototheca is PAS-positive. The life cycles of Chlorella and Prototheca are similar. Both produce hyaline cells (sporangia) that mature to produce 2–20 sporangiospores (endospores) asexually. After endosporulation, the outer sporangial wall ruptures, releasing the sporangiospores to repeat the cycle.

Bilateral Ovarian Malignant Mixed Müllerian Tumor in a Dog: Histologically, both ovaries had intermingled carcinomatous and sarcomatous components (cartilage, bone). The peritoneal metastases were carcinomatous; pulmonary metastases were sarcomatous. Epithelial component was formation of tubules and papillary structures. The carcinomatous components expressed estrogen receptor which favored MMMT diagnosis over teratoma (the ectodermal component in teratoma of hair filled follicle cyst was not present).

Tumor-associated Carbohydrate Antigens: Sialyl Lea and T/Tn Antigens in Canine Mammary Tumors: 85.70% of the tubulopapillary carcinomas expressed T and Tn antigens. Tumor-associated carbohydrate antigens divided in 2 major groups: 1) modified lacto-series type 1 or type 2 chains, represented by sialyl Le and 2) core carbohydrate structures of O-linked mucin type, represented by T and Tn antigens. Expression of T and Tn antigens seem to be associated with malignant transformation of mammary gland cells

Widespread Mismatch Repair Protein Expression in Canine Cutaneous Mast Cell Tumors: Results do not support the hypothesis that inherited MMR defects predispose some dogs to MCT development

Retrospective Study of Melamine/Cyanuric Acid–Induced Renal Failure in Dogs in Korea between 2003 and 2004: Grossly, the kidneys were greenish in color with greenish uroliths in the renal pelvis or bladder. Histologically, characteristic crystals with pinwheel radiating striations were present in distal tubular segments. Toxicologic analysis identified melamine, cyanuric acid, and ammelide. Mycotoxin (Ochratoxin A and citrinin) were initially suspected as the cause but both these toxins causes lesions in proximal convoluted tubules.

Immunohistochemical Expression of p63 and {Delta}Np63 in Mixed Tumors of Canine Mammary Glands and Its Relation with p53 Expression;

Increased Expression of BRCA2 and RAD51 in Lymph Node Metastases of Canine Mammary Adenocarcinomas: In human breast cancer, overexpression of BRCA2 and RAD51 is associated with a poor prognosis, whereas BRCA1 expression is often decreased during progression of sporadic breast cancer. BRCA2 and RAD51 were overexpressed in 50% and 60% of adenocarcinomas, respectively. An overexpression of RAD51 and BRCA2 was found in 80% and 50% of the lymph node metastases.

Thymic Cystic Degeneration, Pseudoepitheliomatous Hyperplasia, and Hemorrhage in a Dog with Brodifacoum Toxicosis: Thymic lobules were expanded and distorted by irregular cysts, lined by single to multiple layers of plump to slightly attenuated polygonal squamous epithelial cells supported by a basement membrane. Pseudoepitheliomatous hyperplasia was means epithelial proliferations that may resemble a malignant neoplastic process. The cause of death was coagulapathy due to brodifacoum poisoning, a second generation anticoagulant poison.

Massive Visceral Pentastomiasis Caused by Porocephalus crotali in a Dog: Numerous encysted parasites within the testes, mesenteric LN, omentum, liver, sub-serosa of the small and large intestines, mesentery, and lungs. The nymphs had a pseudosegmented body, containing large eosinophilic glands and a chitinous cuticle with characteristic pores. Their hook configuration was consistent with that of Porocephalus. Genera Linguatula and Armillifer are most commonly implicated in zoonosis. Adults of Linguatula serrata have been reported to infect nasal passages in dogs.

Canine Duplication of Descemet's Membrane: The thickness of the first DM, referred to as the corneal layer (CL) and the second or anterior chamber layer (ACL), were nearly the same. A fibrous collagenous matrix component was present between the CL and ACL in some cases. Activation and migration of endothelial cells, in association with Glaucoma, trauma or lens contact, play a role in the pathogenesis of this phenomenon. DM is composed of collagen components, such as I, III, IV, V, VI, and VIII, and noncollagenous components, including laminin, fibronectin, nidogen, heparin sulphate, dermatan sulphate, tenascin, and P component. Wound healing response of altered corneal endothelial cells

can lead to retrocorneal fibrous membrane formation posterior to the preexisting DM. overgrowth of basement membranes and endothelial cells over iris surface, iridocorneal angle is called as descemetization and endothelialization. Duplication is seen commonly in dogs, rarely in cats but not in horses and birds.

Immunohistochemical Features of Dystrophic Axons in Papillon Dogs with Neuroaxonal Dystrophy: IHC features of dystrophic axons in brain tissues of Papillon dogs with neuroaxonal dystrophy (NAD) were compared with cerebellar cortical abiotrophy (CCA). Axonal degeneration characterized by abundant spheroids is a pathologic hallmark of canine NAD. Dystrophic axons were positive for neurofilaments (NF), tau, /β-synuclein, HSP70, ubiquitin, synaptophysin, syntaxin-1, and synaptosomal-associated protein-25 (SNAP-25. Dystrophic axons in the nucleus gracilis, cuneatus, olivaris, and spinal tract of the trigeminal nerve, were intensely immunopositive for calcium-binding proteins calretinin, calbindin, and parvalbumin. Ultrastructually, spheroids are mixture of NFs, tubulovesicular structures, mitochondria, lysosomes, and membranous bodies

Copper-Associated Hepatitis in Labrador Retrievers: 3 causes of hepatic copper accumulation. 1) a hereditary metabolic defect that inhibits biliary excretion of copper, resulting in hepatocellular lysosomal copper accumulation(primary form of copper storage disease) human beings (Wilson's disease), Bedlington Terrier dog 2) altered biliary excretion of copper due to hepatic inflammation, fibrosis, and/or cholestasis (secondary copper storage disease, 3) excessive dietary intake. Bedlington terrier is the only breed for which primary copper-associated hepatitis has been definitively proven. In 2O cu storage disease, cu accumulation is mainly restricted to periportal areas and hepatic cu conc are usually less than 2,000 ppm, whereas in 1o hereditary copper storage disorders, copper accumulation is always centrilobular, and hepatic copper concentrations are usually greater than 2,000 ppm. Labrador retrievers in this study had centrilobular hepatitis with necrosis and in 10 out of 12 dogs had hepatic cu conc. more than 2000 ppm, so the author suggest that this is primary cu storage disease.

Diagnostic Exercise: Epithelioid Hemangiosarcoma Mimicking Metastatic Prostatic Neoplasia in a Dog. Vet Pathol 46:548–552 (2009). A firm mass in an enlarged right testicle; a mass in the irregularly enlarged prostate; and nodules in the left kidney, liver, and spleen. Necropsy examination revealed an irregularly enlarged prostate with dark tan to red zones and multiple, discrete, beige to dark red nodules. On histologic examination, discrete nests of anaplastic carcinoma-like tumor cells were found in sections of all affected organs. Results of immunohistochemical examination revealed widespread expression of von Willebrand factor and the absence of cytokeratin in neoplastic cells. Meningioangiomatosis associated with fibrous meningioma in a dog. Veterinary Record (2009) 164, 756-758. MENINGIOANGIOMATOSIS is a rare benign hamartomatous mal formation, characterised by the proliferation of meningoendothelial cells surrounding small blood vessels, which leads to the formation of cortical fibrotic plaques. The proliferation grows along perivascular spaces and may compress adjacent nervous tissue. Thymofibrolipoma in Two Dogs. J. Comp. Path. 2009, Vol. 141, 74e77. Thymofibrolipoma is a histological variant of thymolipoma that is characterized by the presence of abundant pseudolobulated collagenous tissue interspersed with thin strands of epithelial cells, lymphoid aggregates and focal areas of fatty tissue. DDx: Lymphoma, thymoma, thymic hyperplasia, thymic cyst formation and germ cell tumour

Expression of Transforming Growth Factor-β1, -β2 and -β3 in Normal and Diseased Canine Mitral Valves : in chronic valvular disease (endocardiosis) there is activation and proliferation of valvular stromal cells and transdifferentiation into myofibroblasts like cells. In mild and strong valvular disease there was increased expression of TGF- β1 and β3 and smooth muscle actin. Detection and Characterization of Chondroid Metaplasia in Canine Atrioventricular Valves: seen most commonly in elderly large breeds of dogs and tricuspid valve was the only valve affected (in some other study mitral valve was most commonly affected). Cartilage present in valve was fibrocartilage (type I and IV collagen) and hyaline cartilage (type III and VI collagen).Metaplasia of mesenchymal cells to chondrocytes (may be due to TGF- β1) initiated by mechanical forces. Degenerative Myelopathy in Two Boxer Dogs. Vet Pathol 46:684–687 (2009). Thoracic and cranial lumbar segments. Lesions consisted of myelin vacuolation and degeneration, myelophagocytosis, reactive astrocytosis, and ellipsoid formation most prominent in the lateral and ventral funiculi. Breeds: German Shepherd Dog and Pembroke Welsh Corgi, Now Boxers. Collagenofibrotic Glomerulonephropathy with Fibronectin Deposition in a Dog. Vet Pathol 46:688–692 (2009). Histologically, renal glomeruli were enlarged with massive deposition of a homogeneous eosinophilic substance within the mesangium and capillary walls. The deposits reacted weakly with periodic acid– Schiff, stained deep blue with Masson’s trichrome, and were positive by immunofluorescence for type III collagen and fibronectin. Ultrastructurally, the deposits consisted of fibrils and amorphous material in the mesangial matrix and beneath the glomerular capillary endothelium. The fibrils had transverse bands analogous to those of collagen fibrils. Electron microscopy also revealed focal detachment of podocytes and foot process effacement in glomerular tufts, which suggested that podocyte injury had contributed to the development of proteinuria in this dog. Systemic granulomatous disease & sialometaplasia in a dog w/Bartonella infection. pp391-92. May 2006 JTP - Bartonella spp: Gm neg, intracellular bacterial rods; transmitted thru fleas & ticks; can be found in healthy animals (act as carriers) - B. vinsonii subsp. berkhoffii & B. clarridgeiae are species most often isolated from dogs; cause of uveitis, endocarditis, rhinitis, granulomatous dz in liver, LN, heart, spleen - Sialometaplasia: rare dz, unknown cause, dog & cat; in dog, usu. hits 1 submandibular salivary gland (SMG), induces infarction/necrosis, inflammation, squamous metaplasia of glandular epithelium & ducts - Systemic granulomatous dz; sialometaplasia of both SMG; Bartonella vinsonii subsp. berkhoffii & B. henselae DNA amplified - Bartonellae should be considered potential causes of sialometaplasia. K9 intraneural perineuroma. pp50-54. Jan 2006 AR • Histo: distended hypercellular fascicles; widely separated axons surrounded by concentric lamellations formed by neoplastic perineural cells and their processes; pseudo-onion bulbs separated by basophilic myxoid stroma • Immuno: cell processes laminin +; central axons NF-200 & S-100 +; MIB-1 index ~3% • EM: widely separated interdigitating perineurioma cell processes connected by desmosomal-like junctional complexes to form continuous circles; discontinuous basal lamina; axon variably myelinated & surrounded by Schwann cell

The histologic & epidemiologic basis for prognostic considerations in K9 melanocytic neoplasia. pp13649. March 2006 MT - Mitotic index (MI), nuclear atypia, tumor score, presence of metastasis or recurrence helpful to predict outcome - Oral cavity highest mortality rate & worst survival time (gingival, tongue, palate, pharynx), then feet/mucosa of lip; cutaneous least - deep inflammation, increasing size/volume, intralesional necrosis varied but significant - for feet & lip mucosa, increasing age & jxnal activity significant; increasing age significant for cutaneous - Nuclear atypia gave best overall results for all 3 locations (plus MI for feet/lips) - Epithelioid most common type in all 3 sites, followed by mixed (epithelioid + spindle); spindle uncommon (<10%), dendritic & signet ring very rare - Malignancy consistently overstated by ~30% K9 indolent nodular lymphoma. pp241-56. May 2006 AR • B-cell lymphomas (CD79a+) predominated • Marginal zone lymphoma (MZL): Largest group; Involved lymph node (33 cases); spleen (13 cases); both lymph node and spleen (5 cases) • Follicular lymphoma (FL): Lymph nodes (5 cases) • Mantle cell lymphoma (MCL): Solitary splenic masses (3 cases) • Nodal CD3+ T-zone lymphoma (TZL) (10 cases): Resembled late-stage MZL • Marginal zone hyperplasia (2 cases) • Clonal rearrangement of Ig heavy chain (IGH) in 80% MZL, 100% FL, & 100% MCL • Concurrent rearrangement of T-cell Ag receptor gamma (TCRG) in 6 MZL & 2 FL • Clonal rearrangement of TCRG in 63% TZL • B cell lymphomas (MZL, MCL, & FL) and the T-cell lymphoma (TZL) were associated with indolent behavior and long term survival T-cell lymphoma w/eosinophilic infiltration involving the intestinal tract in 11 dogs. pp339-44. May 2006 NW - Canine T-cell lymphomas characterized by small to large cell types and eosinophil infiltration developed in small intestine - Epitheliotropism is not a consistent feature of T cell lymphoma. - Be aware of T-cell lymphoma as a differential diagnosis for intestinal round cell tumors with eosinophilic infiltrate!!! - T-cell lymphomas can be very similar to mast cell tumors of gastrointestinal origin, so do IHC for mast cell markers (e.g. mast cell tryptase and c-kit) and lymphocyte markers (e.g. CD3 and CD79) for definitive diagnosis. - EM features indicating the neoplastic cells are not mast cells: o Tumor cells have smooth cell membranes, and cytoplasmic processes are not conspicuous. Ribosomal rosettes, small rough endoplasmic reticulum and lysosomes were present, but there were no granules in the cytoplasm. Intestinal choristoma in the subcutis of a dog. pp356-57. May 2006 JTP - choristoma = mass of normal tissue in an abnormal location - SQ mass, circumscribed, unencapsulated, cystic, w/bilayer wall

- inner layer like intestinal mucosa: tall columnar lining epithelium, crypt-like glands w/scattered synaptophysin + neuroendocrine cells, supporting lamina propria-like fibrovascular tissue containing lymphocytes & plasma cells - outer layer 1-2mm thick, w/intersecting & blending bundles of smooth muscle & collagen (fibromuscular layer) - 1st report of this in any nonhuman animal - hamartoma = benign tumor-like nodule of overgrowth of mature cells & tissues normally found in the affected part, but often with 1 element predominating Carcinoma ex pleomorphic adenoma with sebaceous differentiation in the mandibular salivary gland of a dog. pp374-77. May 2006 JTP - ex pleomorphic adenoma = carcinoma arising in a mixed tumor - CASE described: Salivary gland tumor with sebaceous differentiation K9 cardiac mesothelioma with granular cell morphology. pp384-87. May 2006 AR • 10 y Golden retr. w/pericardial/abdominal effus: Cardiac mesothelioma w/granular cell features • Immuno: Pancytokeratin +, Vimentin +, S-100 neg • Histo: Fibrovascular papillary projections supporting globoid cells which extended from atrial and aortic root samples; Clusters of cells with subepicardial connective tissue; Abundant eosinophilic cytoplasm; More compact peripherally; Mitoses rare • EM: Abundant lysosomes with variably electron-dense content; peripherally displaced nuclei; rare cytoplasmic organelles; abundant intercellular junctions (some desmosomes); numerous long tortuous surface microvilli without rootlets or glycocalyx Oligodendroglial dysplasia in 2 bullmastiff dogs. pp29-35. Jan 2006 COVER JTP - leukodystrophy: inherited neuro disorders, involve CNS white matter - young-adult Bullmastiffs w/moderate to severe ataxia of all limbs; whole-body tremor; no gross lesions - Numerous, MF pallid eosinophilic plaques (sharply demarcated, small, ovoid to angular areas of myelin pallor) throughout white matter tracts of brainstem & spinal cord; plaques often transversed by axons, often associated w/minimal astrocytosis; LFB (myelin stain) negative - No Gitter cells or spheroids; plaques lacked normal myelin sheaths - EM: focal proliferation of tubule-containing voluminous cytoplasmic glial cell processes (oligodendroglia) - expanded nodes of Ranvier, which disrupts saltatory conduction along nerve - Findings similar to Charolais ataxia (aka oligodendroglial dysplasia or progressive ataxia) - 1st report of oligodendroglial dysplasia in animals other than Charolais cattle Oleic acid-associated bronchiolitis obliterans-organizing pneumonia in beagle dogs. pp183-85. March 2006 AR • accidental intra-airway exposure of dogs w/pure oleic acid bronchiolitis obliterans & bronchopneumonia • necrosis of bronchioles & adjacent alveoli; hemorrhage, inflammation, fibrin exudation • hyperplasia of bronchiolar & alveolar epithelial cells • proliferation of loose fibrovascular connective tissue forming polyps or plugs

• • •

polyps in airways: fibroblasts w/loose or myxoid stroma, covered by attenuated epithelium polyps/plugs variably effaced bronchioles and adjacent alveoli changes resembled human bronchiolitis obliterans-organizing pneumonia (BOOP)

Vaginal Rhabdomyosarcoma in a Dog. Vet Pathol 43:186-188 (2006 Mar) Botryoid rhabdomyosarcoma endoscopy, multipapillary mass around urethral opening. Deciduoid Peritoneal Mesothelioma in a Dog. Vet Pathol 43:198-201 (2006 Mar) 1: Deciduoid mesothelioma - coalescent whitish-gray nodules on the serosa 5a. TEM; Tumor cell, with regular, oval nucleus (arrows) and few cytoplasmic organelles (arrowheads), and numerous elongated slender microvilli on the cell surface (short arrows and inset). 5b. Mesothelial-type microvilli line an intracytoplasmic lumen. Bar = (a) 1 µm; (b) 1.5 µm; (inset) 0.5 µm. Cutaneous viral papilloma with local extension and subungual cyst formation in a dog. J Vet Diagn Invest 21:551–554 (2009). A viral-induced digital cutaneous exophytic papilloma. The inverted cutaneous papilloma, located at the junction of the digital paw pad and ventral nail, extended focally through the nail into the subungual space, where an expansile cyst was formed. Cellular changes suggestive of papillomavirus infection were present in the epithelium of the original exophytic papilloma, as well as the endophytic mass and subungual cyst. Primary Splenic Peripheral Nerve Sheath Tumour in a Dog; J Comp Path 141 vol 2-3: splenic mass that infiltrated the mesentery and composed of spindle-shaped cells arranged in interlacing bundles, streams, whorls and storiform patterns (Antoni A pattern) and less cellular areas with more loosely arranged spindle to oval cells (Antoni B pattern). Cells expressed vimentin, S-100 and GFAP, but did not express desmin, a-smooth muscle actin or factor VIII. Derlin-1 and Stanniocalcin-1 are Differentially Regulated in Metastasizing Canine Mammary Adenocarcinomas: J Comp Path 141 vol 2-3: Derlin-1, stanniocalcin-1, epithelial glycoprotein-2 (EGP-2) and maspin are overexpressed in metastatic human breast cancer cells and are suitable markers for detection of occult metastases and circulating tumour cells. Results of this study suggest that malignant behaviour of canine mammary adenocarcinoma is associated with reduced transcription of the stanniocalcin-1 gene and overexpression of the derlin-1 gene. EGP-2 gene expression did not differ between normal, benign and malignant neoplastictissues. Maspin gene expression varied markedly among the tumors.

Expression of Serotonin and its 5-HT1A Receptor in Canine Cutaneous Mast Cell Tumours. J. Comp. Path. 2009, Vol. 141, 89e97. Both 5-HT and the 5-HT1A receptor were expressed by non-neoplastic dermal mast cells and neoplastic mast cells. More neoplastic mast cells expressed 5-HT than the 5-HT1AR. Poorly differentiated tumours expressed fewer of both molecules. 5-HT1AR functions as an autoreceptor on mast cells, gradual loss of both 5-HT and 5-HT1AR expression with decreasing levels of differentiation of canine MCTs. The 5-HT1A receptor may have a differentiating effect, pharmacological activation of the 5-HT1A receptor may be one way to alter the level of differentiation of the tumour. Serotonin receptor antagonists may help the skin irritation. Extreme monocytosis in a dog with chronic monocytic leukaemia. VETERINARY RECORD | 164, 2009 54-56 Anemia; Leukocytosis (Monocytosis) with immature forms. CD18

(leukocyte), CD45 (leukocyte), CD14(monocyte/macrophage) and CD11b(Monocyte/granulocyte) positive on flow cytometry.

Matrix Metalloproteinase-2 and Matrix Metalloproteinase-9 Expression in Canine and Feline Meningioma. Vet Pathol 46:836–845 (2009). The most common histotype was malignant in dogs (12/28) and transitional in cats. MMPs showed a diffuse cytoplasmic pattern. highest values of MMP-2 and MMP-9 were observed in a psammomatous and meningothelial tumor. It has been reported that a high proliferative index in the tumor is associated with low progesterone receptor (PR) concentration, suggesting that PR expression in canine and feline meningiomas is a reliable prognostic factor in the evaluation of this tumor, as well as in humans respectively. Expression of Connexins in Normal and Neoplastic Canine Bone Tissue. Vet Pathol 46:846–859 (2009). Connexins are phylogenetically preserved proteins that compose gap junctions in different tissues, sharing a basic structure in which 6 subunits form a hemi-channel called the connexon. The main connexin involved in the development, differentiation, and regulation of bone tissue is connexin (Cx) 43. In normal bone tissue, the Cx43 protein was found mainly in the intercellular membranes. However, in all bone tumors studied here, the Cx43 was present in both cell membranes and also aberrantly in the cytoplasm. Cx46 had lower levels of expression in neoplastic bone tissues. Many physiological roles have been proposed for gap junctional intercellular communication (GJIC), and some are briefly cited: 1) Maintenance of homeostasis. 2) Gap junctions serve as electrical synapses in electrically excitable cells such as cardiac myocytes, smooth muscle cells, and neurons.3,29 In these tissues, electrical coupling permits more rapid cellto-cell transmission of action potentials than chemical synapses. In myocytes, this enables their synchronous contraction. 3) Tissue response to hormones. GJIC may enhance the responsiveness of tissue on external stimuli.24,36 4) Regulation of embryonic development.27 In bone tissue, cellular communication by gap junctions is associated with physiological processes such as formation, remodelling, and ossification as well as proliferation of osteogenic cells. Reduced PTEN Protein Expression and Its Prognostic Implications in Canine and Feline Mammary Tumors. Vet Pathol 46:860–868 (2009). Phosphatase and tensin homolog (PTEN) belongs to the group of gatekeeper tumor suppressor genes. Significant loss of PTEN protein expression found in simple carcinoma histotype, lymphatic vessel invasion, lymph node metastases, distant organ metastases, tumor dedifferentiation, tumor recurrence, and shorter overall survival. In feline mammary tumors, a significant correlation between loss of PTEN protein expression and lymphatic vessel invasion was found. Loss of PTEN expression could be a useful prognostic marker in canine mammary carcinomas. Expression of Hepatocyte Growth Factor and the Proto-oncogenic Receptor c-Met in Canine Osteosarcoma. Vet Pathol 46:869–877 (2009). Hepatocyte growth factor (HGF) and the proto-oncogenic receptor c-Met are implicated in growth, invasion, and metastasis in human cancer. Coexpression of HGF and c-Met mRNA in all canine osteosarcoma samples suggested autocrine or paracrine receptor activation. Expression of c-Met was significantly associated with metastasis via the lymphogenic route. Immunolabeling with c-Met revealed a cytoplasmic staining pattern in all osteosarcoma cell types. Polioencephalomyelopathy in Shih Tzu: JAVMA. Neuroanatomic diagnosis  C6-T2. Swelling of C5-C7 with malacia with gitter cells astrocytes, neurons not affected. Brain: spongiosis in caudal colliculi, interposital nuclei, and lateral vestibular nucleus. DDX: thiamine deficiency, hyponatremia. The pattern suggests mitochondrial defect.

Calcium reuptake genes in dogs with Chronic Mitral Valveular Insufficiency: JVIM 2009: PLN and HAX-1(PLN and HAX-1 ↑ Ca+2 in myocytes) Reduced :/: SERCA2a is transmembrane protein controlling the rate of cytosolic calcium removal via SR. PLN SERCA2a. Idiopathic Eosinophilic Masses of the Gastrointestinal Tract in Dogs: JVIM 2009: Mucosal to transmural eosinophilis, fibrosis, fibroplasia. Changes in Regulatory T cells in Dogs with Cancer and Associations with Tumor Type. JVIM 2009: Tregs was increased in cancer (carcinoma). Tregs  anergy/peripheral. Multisystem Axonopathy and Neuropathy in Golden Retrievers: JVIM: Tetraparesis, decreased reflexes. Diffuse spinal cord axonal degeneration with secondary demyelination, gitter cells. CEV stain  neuronal cell bodies loss, and vacuolation of motor nuclei of trigeminal nerve. Lymphoplasmacytic synovitis in dogs with CCLR: JAVMA: LPS is correlated with CCLR. Type I, and II collagens, Bacterial DNA, high TNF levels. Derlin-1 and Stanniocalcin-1 are Differentially Regulated in Metastasizing Canine Mammary Adenocarcinoma: Malignant behavior Stanniocalcin-1/ ↑ Derlin-1 Primary Splenic Peripheral Nerve Sheath Tumor in a dog: Interlacing bundles and streams, Antoni A (storiform), and B (loose). Vimentin, S-100, GFAP.

Expression of the Tumor Suppressor Genes NF2, 4.1B, and TSLC1 in Canine Meningiomas. Vet Pathol 46:884–892 (2009). These results suggest that loss of these tumor suppressor genes is a frequent occurrence in canine meningiomas and may be an early event in tumorigenesis in some cases. In addition, it is likely that other, as yet unidentified, genes play an important role in canine meningioma formation and growth. neurofibromatosis 2 (NF2), protein 4.1B (4.1 B), and tumor suppressor in lung cancer-1 (TSLC1) genes. Immunohistochemical Evaluation of GATA-4 in Canine Testicular Tumors. Vet Pathol 46:893–896 (2009). GATA-4 is a transcription factor expressed in Sertoli cells and less commonly in Leydig (interstitial) cells but not germ cells in adult human beings, cattle, pigs, and mice. Sex cord–stromal cells of MGSCT were also positive. Localized, Plexiform, Diffuse, and Other Variants of Neurofibroma in 12 Dogs, 2 Horses, and a Chicken. Vet Pathol 46:904–915 (2009). Neurofibromas of this study had localized, plexiform, diffuse and combined plexiform and diffuse growth patterns, and microscopic features similar to those in classic, collagenous, cellular, myxoid, and pigmented neurofibromas of humans. One diffuse neurofibroma contained areas of schwannian differentiation (hybrid neurofibroma-schwannoma). Benign peripheral nerve sheath tumors (PNST) in humans include schwannomas (neurilemmomas) and neurofibromas, as well as perineurial cell tumors, nerve sheath myxomas (neurothekeomas). Important features of schwannomas include the concurrent presence of highly and poorly cellular areas of fusiform neoplastic Schwann cells in a stroma that is either collagenous and scant, or is myxoid and abundant (designated Antoni A areas and Antoni B areas, respectively). Other features are nuclear palisading, the formation of Verocay bodies, and hyalinized microvessels, S-100 positive. Neurofibromas are a mixture of Schwann cells, perineurial cells, and fibroblasts. neurofibromas are composed of very slender, elongated cells with characteristic buckled

and/or wavy nuclei in a fibromyxoid stroma with thin, wire-like collagen fibers. Within the mass, nerve fibers can be identified; S100 immunoreactivity is restricted to a subpopulation of the tumor cells. Patients with NF1 develop multiple neurofibromas, which often undergo malignant transformation and additional neoplastic and non-neoplastic lesions in multiple organs. In contrast, NF2 is characterized by bilateral vestibular schwannoma and possible additional tumors of the central nervous system and/ or cutaneous schwannomas. Histologic Grade Predicts Recurrence for Marginally Excised Canine Subcutaneous Soft Tissue Sarcomas. Vet Pathol 46:928–933 (2009). Histologic grade is a strong predictor for recurrence of marginally excised subcutaneous soft tissue sarcomas. Clean margins predict nonrecurrence. Tumor recurrence did not significantly reduce survival time. Histologic Characterization of Canine Dilated Cardiomyopathy: Dilated cardiomyopathy (DCM), characterized by all 4 chamber dilatation (predominately left chambers) and myocardial systolic and diastolic dysfunction, is one of the most common heart diseases in dogs. clinically diagnosed DCM reveals two histologically distinct forms of DCM: 1) cardiomyopathy of Boxers and Doberman Pinschers, corresponding to the "fatty infiltration–degenerative" type and 2) the form seen in many giant, large-, and medium-sized breeds, including some Boxers and Doberman Pinschers, classified as the "attenuated wavy fiber" type of DCM. Canine X-linked muscular dystrophy may cause severe cardiac involvement, and deletion of the entire dystrophin gene has been demonstrated in German Shorthaired Pointers with skeletal myopathy and DCM. Metabolic disorders associated with DCM include hypothyroidism, diabetes mellitus, and pheochromocytoma. The attenuated wavy fiber type of DCM: myocardial cells <6 µm in diameter (normal myofiber diameter ranges from 10 to 20 µm) with a wavy appearance, myocytes separated by clear space, subendocardial fibrosis, finding wavy fibers is highly sensitive (98%) and specific (100%): Fatty infiltrationdegenerative type: myocytolysis, myofiber degeneration, vacuolization, myocyte atropy with excessive fibrosis and fatty infiltration. Interstitial Lung Disease in West Highland White Terriers: Progressive respiratory failure and pulmonary fibrosis in West Highland White Terriers (WHWT) is an apparently genetic disorder of unknown pathogenesis. Lesions in WHWT were confined to the expansion of the interstitial space of alveolar septa by extracellular matrix determined to be mixtures of type-I and -III collagens. Features of interstitial pneumonia of humans such as intra-alveolar fibroblastic foci, subpleural distribution, and honeycombing were not observed in six WHWT. Chronic pulmonary disease of WHWT is a result of aberrant collagen regulation. Invasive Epithelial Mesothelioma in a Dog: Invasive epithelial mesothelioma in an 11-year-old Golden Retriever involved the pericardium, pleura, mediastinum, and peritoneum and invaded into submesothelial tissues. Histo: the tumor consisted of nests of epithelioid cells with frequent mitotic figures and multinucleation that infiltrated submesothelial tissues. Neoplastic cells strongly coexpressed vimentin and cytokeratin. Thyroid Carcinosarcoma in a Dog: S/C mass in the cervical area and metastatic nodules in the lung. Histo: 2 types of cell, spindle cells occasionally forming osteoid (Vimentin positive), and second type was forming follicular structures (cytokeratin positive). IHC for thyroglobulin proved that the tissue of origin was the thyroid gland. Canine thyroid carcinomas occur more frequently than adenomas. Other reported sites where primary carcinosarcomas may arise in dogs are mammary gland, lung, salivary gland, ceruminous gland and eyelid.

Paraneoplastic Pemphigus in a Dog with Splenic Sarcoma: Paraneoplastic pemphigus (PNP) is a rare and severe autoimmune mucosal and cutaneous blistering disease associated with hematopoietic or solid neoplasia. PNP exhibits histologic characteristics of both pemphigus vulgaris (suprabasal clefting with acantholysis) and erythema multiforme (cell-rich interface dermatitis with lymphocyte-mediated keratinocyte apoptosis). Grossly: facial lesions were bilaterally

symmetrical with alopecia and deep erosions on the rostral, dorsal, and lateral muzzle, the dorsomedial ocular canthi, and the oral commissures. Histo: two distinct histologic patterns of PV and EM. Histo of splenic mass was diagnosed as sarcoma. PNP in dogs also associated with thymic lymphoma. Estrogen-dependent Induction of Cyclooxygenase-2 in the Canine Prostate In Vivo: COX-2 staining was observed in prostates of untreated or androgen-treated castrated or intact dogs. However, treatment of intact and castrated dogs with estrogen resulted in squamous metaplasia with intense COX-2 expression observed in both squamous epithelial cells and in cells of acini without metaplasia. Canine Hepatic Neuroendocrine Carcinoma: An Immunohistochemical and Electron Microscopic Study: 10 dogs with neuroendocrine carcinoma of the liver were selected; high liver enzyme activity (serum alkaline phosphatase, 7/9; ALT 7/9; AST, 8/9), and high total bilirubin (6/9). All 10 neoplasms were positive for at least one of the endocrine markers used: (NSE; 8/10), synaptophysin (5/10), and chromogranin-A (3/10). Use of Alkaline Phosphatase Staining to Differentiate Canine Osteosarcoma from Other Vimentin-positive Tumors: cytologically, it can be difficult to differentiate osteosarcoma (OSA) from other bone neoplasms, including fibrosarcoma, chondrosarcoma, synovial cell sarcoma, and plasma cell myeloma. ALP is a hydrolytic enzyme present in multiple tissues including liver, kidney, intestine, placenta, and bone. Tumors that expressed vimentin and were positive for ALP included 33 OSAs, one multi-lobular tumor of bone, one amelanotic melanoma, and one chondrosarcoma. Tumors that expressed vimentin and were negative for ALP included chondrosarcomas (three of four), multiple fibrosarcomas, and multiple synovial cell sarcomas. The sensitivity is 100%, and the specificity is 89%. In conclusion, ALP appears to be a highly sensitive and fairly specific marker in the diagnosis of OSA. Cutaneous Leishmaniasis in Naturally Infected Dogs is Associated with a T Helper-2–biased Immune Response: In Leishmania-infected dogs, IL-4, TNF- and IFN- mRNA production was significantly higher than controls. Dogs with a high Leishmania burden had a significantly higher IL-4 expression. Expression of IL-4, IL-13, and TNF- was slightly increased in biopsies where plasma cells prevailed on lymphocytes, whereas expression of IFN- was moderately higher when lymphocytes were predominating. Study demonstrates that the local immune response in naturally occurring leishmaniasis includes TH1 as well as TH2 cytokine subsets. Increased expression of the TH2-type cytokine IL-4 is associated with high parasite burden in the skin lesions. A Prospective Analysis of Immunohistochemically Determined Estrogen Receptor {alpha} and Progesterone Receptor Expression and Host and Tumor Factors as Predictors of Disease-free Period in Mammary Tumors of the Dog: In the malignant tumors, the presence of one or both receptors was more frequent in tumors smaller than 3 cm, without lymph node metastasis, with tubulopapillary rather than solid patterns of growth, of histologic grades I and II, without both intravascular growth and necrosis, and with lymphocyte cell infiltrates: Benign=ER -positive and PRpositive; Malignant= ER -negative and PR-positive. Only tumor size and histologic grading proved to be independent prognosticators. West Nile Virus Encephalitis in a Dog: Cl. Signs: generalized tremors, ataxia, and intermittent hyperthermia. Histo: nonsuppurative meningo encephalitis, with focal necrosis in the medulla. PCR positive for WNV. Target tissues for WNV are brain, heart and kidney. Adrenal Myelolipoma in a Dog Expression of Maspin in Mammary Gland Tumors of the Dog: Maspin is a serine protease inhibitor that inhibits tumor invasion and metastasis in human breast cancer and is expressed by mammary myoepithelial cells. Periacinar and periductal MECs of normal mammary glands were stained by the maspin and immunoreactivity was observed in the nucleus and cytoplasm of these cells. Maspin was present in MECs of benign tumors (100 %) and malignant tumors (93%); and epithelial cells of benign (16%) and malignant tumors (73%). Maspin is a sensitive marker of the normal

and neoplastic myoepithelium that, contrary to smooth muscle differentiation markers, does not stain stromal myofibroblasts. A subset of neoplastic epithelial cells also reacted with the maspin antibody. Usefulness of Thyroid Transcription Factor-1 Immunohistochemical Staining in the Differential Diagnosis of Primary Pulmonary Tumors of Dogs: Nuclear staining for TTF-1 was detected in 64.2% of primary pulmonary epithelial tumors. The most common TTF-1–reactive tumor types were bronchioloalveolar carcinomas and bronchogenic carcinomas. Staining was diffuse, heterogeneous, or patchy. Nonpulmonary, metastatic epithelial tumors, except two of two thyroid carcinomas, did not react. Mesotheliomas and other mesenchymal tumors were also negative for this marker. A reduction or loss of reactivity was apparent in pulmonary epithelial tumors archived in paraffin blocks for 7–8 years. TTF-1 is a highly specific (with the exception of thyroid tumors) and moderately sensitive marker for canine pulmonary epithelial tumors. Assessment of Cyclooxygenase-2 Expression in Canine Hemangiosarcoma, Histiocytic Sarcoma, and Mast Cell Tumor: COX-2 has been shown to be overexpressed in selected human sarcomas and hematopoeitic tumors, the results of this study indicate that canine hemangiosarcoma, histiocytic sarcoma, and grade-II mast cell tumor do not express COX-2 in any appreciable fashion. Pathology of Bartonella Endocarditis in Six Dogs: 6 out 31 cases had Bartonella organisms identified by PCR (B. vinsonii berkhoffi was present in four dogs). 5 out 6 were in the aortic valve. Features of Bartonella endocarditis included a combination of fibrosis, mineralization, endothelial proliferation, and neovascularization with variable inflammation. Ultrastructural analyses revealed both extracellular and intraendothelial bacteria. Bartonella species are intra- and extracellular, pleomorphic, gram-negative alpha proteobacteria that are the causative agents of Orroya fever, Trench fever, and Cat Scratch disease. Bartonella organisms in dogs have subsequently been associated with granulomatous lymphadenitis, rhinitis, and hepatitis. Immunohistochemical and Histochemical Stains for Differentiating Canine Cutaneous Round Cell Tumors: Of 21 tumors with a histologic diagnosis of mast cell tumor, 100% grade I, 85.7% grade II, and 42.9% grade III tumors were diagnosed as MCT tumors based on positive staining for tryptase antigen and chymase activity. Mast cells were positive for tryptase antigen and chymase activity, indicating equal efficacy of tryptase IHC and chymase histochemistry. CD18 and MHC class II was equally effective in staining histiocytomas, although lymphosarcoma must be ruled out as lymphomas are positive for CD18, MHC-II, CD3/CD79a. Some mast cells were also positive of CD18. Langerhans' cells in canine cutaneous histiocytomas express leukocyte antigens characteristic of dendritic cell differentiation, including CD1a, CD1b, CD1c, and CD11c. Expression of CD1 molecules distinguishes Langerhans' cells from macrophages. CD20 Expression in Normal Canine B Cells and in Canine non-Hodgkin Lymphoma: CD20 is a transmembrane phosphoprotein that is expressed predominantly in pre-B cells and in mature peripheral B cells. The function of CD20 remains incompletely understood, although it appears to be important for receptor-induced calcium signals. In dogs, this antibody showed restricted membrane binding in a subset of lymphocytes in peripheral blood, in the B-cell regions (normal canine spleen and LN), and in malignant cells from 19 dogs with B-cell NHL, but not from 15 dogs with T-cell NHL. Our results show that the antibody that recognizes the intracellular domains binds a canine CD20 homolog and is suitable for use as part of a panel to identify normal and malignant canine B cells in routine diagnostic, however, it did not recognize the extracellular domain therefore it cannot be used to treat lymphomas in dogs. Melanocytic Matricoma in a Dog: Tumor at the root of the tail in a male, 2-year-old Shih Tzu dog, consisted of basaloid epithelial cells, with shadow cells and neoplastic melanocyte proliferation. Immunohistochemically, epithelial components were positive for keratin/cytokeratin but basaloid cells were negative. Mononuclear or multinuclear melanocytes were positive for vimentin, S-100 protein, and HMB-45. Mutations of Phosphatase and Tensin Homolog (PTEN) Deleted from Chromosome 10 in Canine Hemangiosarcoma: The results document somatic point mutations or deletions encompassing the PTEN C-terminal domain in canine hemangiosarcoma that

might provide cells a survival advantage within their microenvironment. PTEN is a tumor-suppressor gene and inhibits cell proliferation and activates the cell suicide program; however, the tumor-suppressive activity of PTEN appears to be largely dependent on its lipid phosphatase activity. Normally, PTEN antagonizes the activity of phosphatidylinositol 3-kinase (PI3K), which is responsible for the generation of PIP-3. Reduced levels of PIP-3 prevent activation of the survival factor Akt as well as inactivation/degradation of BAD, caspase 9, and p27 protein. Loss of PTEN  increased levels of PIP-3 and Akt hyperactivation that lead to protection from various apoptotic stimuli cell survival. Expression of Connexins 26 and 43 in Canine Hyperplastic and Neoplastic Mammary Glands: Normal, hyperplastic, and benign neoplastic mammary glands showed a punctate pattern for connexin 26 and 43 staining and an intercellular E-cadherin staining. Malignant neoplasms, especially the most aggressive cases with high cell proliferation rates, presented either fewer gap junction spots on the cell membranes or increased cytoplasmic immunostaining. Malignant tumors also expressed a less intense staining of E-cadherin; the expression of this adhesion molecule is important for the transportation of connexins to cell membranes and in forming gap junctions. Deficient expression of E-cadherin could be related to the aberrant connexin localization and may contribute to the malignant phenotype. In conclusion, the expression and distribution of connexins and E-cadherin are inversely correlated to cell proliferation in malignant mammary neoplasms of dogs. Genital Lesions Associated with Visceral Leishmaniasis and Shedding of Leishmania sp. in the Semen of Naturally Infected Dogs: A significantly higher frequency of inflammation was observed in the epididymes, glans penis, and prepuce of dogs with visceral leishmaniasis, which was associated with a high frequency of IHC positive tissues. These findings indicate that genital lesions and shedding of Leishmania sp. (donovani complex) in the semen are associated with visceral leishmaniasis. Cyclooxygenase-2 Expression is Associated with Histologic Tumor Type in Canine Mammary Carcinoma: COX-2 expression was detected in 56% samples evaluated. Anaplastic carcinomas had a significantly higher COX-2 staining distribution, intensity and index, compared with those for adenocarcinomas. COX-2 has been documented to be overexpressed in canine SCC, transitional cell carcinoma, renal carcinoma, intestinal neoplasia, mammary neoplasia, and prostatic carcinoma. E-Cadherin and ß-catenin Reduction Influence Invasion but not Proliferation and Survival in Canine Malignant Mammary Tumors: E-Cadherin and ß-catenin are known for their role in tumor invasion, but they also exert an influence on tumor proliferation. Exp. of the two proteins in the same tumors was significantly correlated. In conclusion, reduced expression of E-cad, ß-cat, or E-cad/ß-cat was significantly associated with the progression from noninfiltrating to highly infiltrating tumors but not with proliferation or survival. Characterization of Stages of Hepatozoon americanum and of Parasitized Canine Host Cells: American canine hepatozoonosis is caused by Hepatozoon americanum, a protozoan parasite, the definitive host of which is the tick, Amblyomma maculatum. Following penetration of the intestinal mucosa, sporozoites are disseminated systemically and give rise to extensive asexual multiplication in cells located predominantly in striated muscle. The most frequently recognized histologic lesion is the socalled "onion skin cyst," which is composed of a multilamellar acid mucopolysaccharide deposit that surrounds a centrally located host cell, the latter containing the trophozoite. The parasitized canine cells in "onion skin" cysts (where merogony occurs) and in granulomas (gametogony commences) situated within skeletal muscle, as well as those in peripheral blood leukocytes (PBL, gametogony continues), were identified as macrophages. Two basic morphologic forms of the parasite observed in macrophages of granulomas and PBLs were identified as merozoites and gamonts. Canine Carcinosarcomas in the Head: carcinomatous cells resembled squamous cell carcinoma The sarcomatous component had typical feature of osteosarcomas. Erythropoietin Receptor Expression in Canine Mammary Tumor: An Immunohistochemical Study: Erythropoietin (EPO) is a cytokine involved in the regulation of the erythropoiesis. It is demonstrated that EPO and its receptor (EPOR) are expressed in several neoplastic cell lines and solid tumors. A weak to moderate EPOR expression in dysplastic mammary glands, and immunoreactivity increased in malignant pattern

Bacterial Meningoencephalitis and Ventriculitis Due to Migrating Plant Foreign Bodies in Three Dogs: Regional suppurative meningoencephalitis and ventriculitis of variable chronicity was diagnosed in three young dogs residing in Colorado. Grass awns were grossly identified in the right occipital cortex of one dog and in the right lateral ventricle of another. Intralesional plant material was microscopically evident in the dura mater overlying the right occipital cortex of the third dog. Encephalitis due to bacteria introduced from migrating plant foreign material is a potential sequela of intranasal, periocular, or pharyngeal foreign bodies. Peripheral Nerve Pathology in Two Rottweilers with Neuronal Vacuolation and Spinocerebellar Degeneration: and degeneration of the spinal cord white matter. Lesions were chr neurogenic Neuronal vacuolation and spinocerebellar degeneration in young Rottweiler dogs is a neurodegenerative condition characterized by neuronal vacuolation of several nuclei in the central nervous system muscle atrophy of the intrinsic laryngeal muscles, and a loss of large myelinated fibers in the recurrent laryngeal nerve (RLN), accompanied by demyelinating/remyelinating features affecting small myelinated fibers. No significant changes were detected in cranial laryngeal, vagus, phrenic, ulnar, or peroneal nerves. These findings were indicative of a selective distal neuropathy of the RLN with early severe axonal degeneration, mainly of large myelinated fibers.

MISCELLANEOUS INFO: • Sequences in expression of the markers during muscle development: Vimentin desmin myoglobin • Neoplasms expressing both vimentin and cytokeratin include: - Synovial sarcoma, Mesothelioma, Melanoma, Chordoma - Sertoli cell tumor, Thyroid tumors, - Renal carcinoma, Highly anaplastic carcinoma • Natural infection of cowpox virus is most common in: Rodents Ectopic (Subcutaneous) Paragonimus miyazakii Infection in a Dog. Vet Pathol 46:945–948 (2009). subcutaneous inguinal mass, granulomatous panniculitis, intralesional adult trematodes and eggs, and lymphadenitis. Extrapulmonary paragonimosis in animals is rare. Solitary Intracerebral Plasmacytoma in a Dog: Microscopic, Immunohistochemical, and Molecular Features. Vet Pathol 46:949–951 (2009). The neoplasm was composed of sheets of round cells with distinct plasmacytoid features and marked anisocytosis and anisokaryosis. Cells were positive for vimentin, CD18, CD79a, and lambda light-chain, and negative for kappa light chain, cytokeratin, lysozyme, glial fibrillary acidic protein, and S100 protein. Clonally rearranged B-cell antigen receptor genes were detected by PARR (polymerase chain reaction for antigen receptor rearrangements), confirming clonal proliferation of B lymphocytes. Quadrigeminal arachnoid cysts in a kitten and a dog. J Vet Diagn Invest 21:707–710 (2009). KittenCongenital- mild internal hydrocephalus, caudal cerebellar coning, and cerebellar herniation through the foramen magnum were associated with a congenital quadrigeminal arachnoid cyst compressing the rostral cerebellum and shifting the entire cerebellum caudally Dog- In contrast, a possibly acquired quadrigeminal cyst was observed in a 2-year-old male neutered Yorkshire Terrier in association with necrotizing encephalitis. Gastric B-cell lymphoma with Mott cell differentiation in a dog. J Vet Diagn Invest 21:715–719 (2009). white, solid, nodular, infiltrative masses were observed in the stomach, duodenum, spleen, liver, and lungs

in association with generalized lymph node enlargement. variable amounts of round periodic acid–Schiffpositive cytoplasmic globules consistent with Russell bodies. The tumor most likely represented a variant of B-cell neoplasia with extensive Mott cell differentiation. Mycotic osteomyelitis caused by Schizophyllum commune in a dog Veterinary Record (2009) 165, 350-351 Schizophyllum commune is a basidiomycetous fungus found all over the world, often on various trees and decaying wood. Rare cause of human disease: onychomycosis, sinusitis, brain abscess, meningitis, ulcerative lesions of the hard palate, lung abscess and several lung disorders. Only one case of S commune infection in dogs with disseminated nodules. RADIOGRAPHY: Multiple sites of bone lysis in the proximal shaft of the left femur and the middle of the right tibia. FNA: Neutrophils, macrophages, and many branching hyaline hyphae Microscopic examination of the isolate revealed hyaline hyphae 2.5 to 3.0 μm in diameter, and confirmed the presence of clamp connections and tubercles, indicating the presence of a basidiomycete. No history of wounds to the feet or limbs, and no lesions were found in tissues other than the bone and surrounding soft tissue. Postulated that the organism gained entry via either the respiratory or gastrointestinal tracts and spread haematogenously via circulating basidiospores. Naturally Occurring and Melengestrol Acetate-associated Reproductive Tract Lesions in Zoo Canids. Vet Pathol 46:1117–1128 (2009). endometrial hyperplasia (predominantly cystic) (53%), hydrometra (33%), and adenomyosis (25%). Spontaneous Idiopathic Arteritis of the Testicular Artery in Raccoons (Procyon lotor). Vet Pathol 46:1129–1132 (2009). Segmental arteritis confined to the extratesticular portions of the testicular artery was present in raccoons of all ages. The lesions consisted of proliferative endarteritis with presence of inflammatory cells within the intima, media, and the adventitia. Cardiac Valvular and Vascular Disease in Bull Terriers. Vet Pathol 46:1149–1155 (2009). Bull Terriers (93%) had myxomatous degeneration of the mitral valve or abnormalities of the left ventricular outflow tract. Small vessel arteriosclerosis in the myocardium and fibrosis of cardiac conduction tissue were common histologic findings. Vascular injury due to any insult produces a stereotypical response that results in intimal thickening. This response includes the migration of smooth muscle cells or their precursors into the intima, where they proliferate and produce extracellular matrix.17 Bull Terriers in this study not only had coronary arteriosclerosis, but it was remarkably severe in young animals. including myxomatous degeneration of mitral and aortic valves, LVOTO, left ventricular hypertrophy, interstitial myocarditis and fibrosis associated with cardiac conduction tissue, and an unusual form of coronary arterial degeneration. Encephalomyelopathy and Polyneuropathy Associated with Neuronal Vacuolation in Two Boxer Littermates. Vet Pathol 46:1160–1165 (2009). Laryngeal muscle atrophy, neuronal vacuolation, and a combined central and peripheral axonopathy. Gross lesions were limited to atrophy of the intrinsic laryngeal muscles. Histopathologically, there was diffuse loss of axons and myelin in the dorsolateral and ventral funiculi throughout the spinal cord and extending into the caudal aspect of the brain stem. Vacuolation of scattered neuronal cell bodies was present in the spinal cord and selected brain stem nuclei. Multifocal axonal degeneration and demyelination was observed in the recurrent laryngeal nerve, sciatic nerve, and brachial plexus and was most severe in the recurrent laryngeal nerve. Ocular abnormalities included

microphthalmia, cataracts, and retinal dysplasia. The findings in these Boxer dogs, unrelated to the Rottweiler breed, are analogous to the syndrome of neuronal vacuolation and spinocerebellar degeneration reported in Rottweilers. Rectal Plasmacytoma with Intracellular Hemosiderin in a Dog. Vet Pathol 46:1181–1184 (2009). rectal mass that protruded through the anus. Cytologically, the mass was composed of neoplastic round cells consistent with an extramedullary plasmacytoma. Histiocytic sarcoma, carcinoid tumor, and melanoma were also considered because of the presence of golden-brown cytoplasmic granules. Histopathologic findings and immunohistochemical reactivity for lambda light chains confirmed the cytologic diagnosis of plasmacytoma. Prussian blue staining identified the cytoplasmic granules as hemosiderin. The granules were negative by Fontana Masson and Grimelius histochemistry. To our knowledge, this is the first report of an extramedullary plasmacytoma containing hemosiderin in a dog. Ultrastructural studies revealed that the iron granules were present within the mitochondria of the plasma cells. Based on these observations, Cook and colleagues proposed that excessive iron accumulation takes place in the mitochondria of marrow plasma cells in alcoholic patients.3 The mechanism is similar to that observed in ring sideroblast formation in alcohol induced sideroblastic disease. The presence of chronic bleeding within the mass could predispose to iron uptake by creating an iron-rich environment around the neoplastic plasma cells. The other possibility is that the neoplastic plasma cells acquired the possibility to phagocytize erythrocytes.