Cartilaginous Tumors of the Larynx and Trachea in the Dog: Literature Review and 10 Additional Cases (1995-2014).

Cartilaginous tumors of the larynx and trachea are uncommon in the dog. The authors describe 10 cases diagnosed between 1995 and 2014 and review 16 cases in the literature. Seven of our cases were tracheal and 3 were laryngeal. Two of the laryngeal tumors were chondromas, which have not been previously reported in this site. The third laryngeal tumor was a myxochondroma. Of the 7 tracheal tumors, 6 arose from the ventral tracheal wall, including 2 that were extraluminal. Tracheal tumor types included chondrosarcoma (n = 3), chondroma (n = 2), and osteochondroma (n = 2). All of the laryngeal tumors and 5 of 7 of the tracheal tumors occurred in adult dogs (aged 5-11 years). The 2 tracheal osteochondromas were in young dogs (3-4 months) and were intrathoracic, while the remaining tracheal tumors were cervical. Surgical excision had a good outcome in most cases. Combining our 10 cases with the 16 previously reported cases showed that 6 (27%) of the affected dogs were Arctic breeds (Alaskan Malamute or Siberian Husky) suggesting a predisposition in this type of dog.

N-cadherin expression in feline mammary tumors is associated with a reduced E-cadherin expression and the presence of regional metastasis.

The cadherin family of adhesion molecules regulates cell-cell interactions. N-cadherin is expressed by neural and fibroblast cells but not by normal epithelial cells. In human medicine, the role of N-cadherin in breast cancer remains controversial, but some studies have described the switch from E-cadherin to N-cadherin as a critical step in the malignant progression of neoplastic cells. The present study was carried out on 160 feline mammary tumors (21 adenomas and 139 carcinomas). The relationship between the immunohistochemical expression of N-cadherin in neoplastic epithelial cells and 2 established prognostic factors such as regional metastasis and tumor grade was examined. The results of the study showed a statistically significant relation between the expression of N-cadherin and the 2 prognostic factors, and also a reduced expression of E-cadherin in tumors that expressed N-cadherin.

Naturally acquired visceral leishmaniosis in a captive Bennett's wallaby (Macropus rufogriseus rufogriseus).

A high prevalence of leishmaniosis has been reported from an increasing number of domestic and wild mammals around the world. In Australian macropods, Leishmania spp infection has been occasionally described in its cutaneous form only. The purpose of this report is to present a case of fatal visceral leishmaniosis in a captive Bennett's wallaby in Madrid, Spain, which was investigated by detailed macroscopic, histologic, and immunohistochemical examinations.

Intraepidermal glandular carcinoma of the nipple (mammary Paget-like disease) in 2 dogs.

Mammary Paget disease, characterized by diffuse infiltration of the nipple and areolar epidermis by carcinoma cells, develops in 1% to 3% of human mammary carcinomas. The purpose of this article is to present 2 cases of intraepidermal adenocarcinoma that resembled human mammary Paget disease, histologically and immunohistochemically, in dogs with underlying mammary carcinoma.

Reduced expression of E-cadherin and ß-catenin and high expression of basal cytokeratins in feline mammary carcinomas with regional metastasis.

Feline mammary carcinomas are highly aggressive neoplasms. Several mechanisms are thought to be involved in their progression, including the loss of epithelial adhesion molecules. The present study was carried out on 21 adenomas and 139 mammary carcinomas. Of the carcinomas, 66 were not reported to have metastasized, while the remaining 73 had evidence of regional lymph node metastasis at the moment of diagnosis. The relationship was examined between the expression of the E-cadherin-ß-catenin complex and basal (CK5/6, CK14) and luminal (CK8/18) cytokeratin expression. In the medical literature, carcinomas expressing basal cytokeratins are reported as having a poor prognosis in human breast cancer. Results revealed that preservation of the expression of E-cadherin and ß-catenin is a significant feature of carcinomas without metastasis, whereas carcinomas with metastasis reveal the loss of one or both adhesion molecules. Additionally, basal cytokeratin expression was statistically associated with the presence of regional metastasis. Furthermore, the expression of E-cadherin-ß-catenin was significantly correlated with the high expression of CK18 and low expression of CK5/6.

Cyclooxygenase-2 expression is related with localization, proliferation, and overall survival in canine melanocytic neoplasms.

A direct relationship has been firmly established between cyclooxygenase-2 (COX-2) expression and malignant behavior in human melanoma. This report examines the relationship between COX-2 expression and tumor location, mitotic and proliferative indices, degree of T CD3(+) lymphocyte infiltration, overall survival, and frequency of recurrence and metastasis of 57 melanocytic tumors (25 oral and 32 cutaneous). COX-2 was highly or moderately expressed in 88% of oral neoplasms (22 of 25), whereas for their cutaneous counterparts, COX-2 expression was low or insignificant in 75% of cases (24 of 32). High and moderate COX-2 expression levels were observed in 73% of melanocytic tumors with a mitotic index ≥ 3 per 10 high-power fields (26 of 36), whereas in 81% of tumors with a mitotic index < 3 (17 of 21), expression was mild or absent. There were 41 cases with known clinical outcomes; of those showing high, moderate, and mild COX-2 expression, 83.3% (10 of 12), 37.5% (3 of 8), and 25% (2 of 8) died, respectively, whereas 100% of animals showing no COX-2 expression (13 of 13) were still alive at the last follow-up. COX-2 expression was statistically correlated with tumor location, mitotic and percentage Ki-67 proliferative indices, and overall survival, frequency of neoplastic recurrence and metastasis. Regression analysis also showed disease-specific predictive value for COX-2 expression for subjects with melanocytic neoplasms. Additionally, only high COX-2 expression showed significant differences in overall survival, in comparison with moderate, mild, or absent expression. These results suggest that high COX-2 expression may be considered a prognostic biomarker and potentially as a target for therapeutic and preventive strategies in canine melanocytic neoplasms.

Ganglioneuromatosis of the Gallbladder in a Dog with Cholecystitis and Cholestasis.

A 2-year-old entire female mixed-breed dog was presented with signs of cholestasis. Abdominal ultrasonography revealed a gallbladder with a thickened and hyperechoic wall and luminal calculi. Exploratory laparotomy with cholecystectomy was performed and histopathological examination of the specimens from the cholecystectomy demonstrated extensive proliferation of large, prominent nerves containing ganglion cells with no atypia mainly located in the gallbladder mucosa. The neural nature of these components was confirmed by immunohistochemical labelling with antibodies specific for synaptophysin, glial fibrillary acidic protein, S100 protein and neurofilaments. Based on these findings, the lesion was diagnosed as ganglioneuromatosis. Reports of ganglioneuromatosis in animals have so far been restricted to the intestine. This is the first case of ganglioneuromatosis affecting the gallbladder in an animal in which no intestinal involvement was apparent.

Immunohistochemical expression of MDR1-Pgp 170 in canine cutaneous and oral melanomas: pattern of expression and association with tumour location and phenotype.

Canine melanoma (CMM) more commonly affects the oral mucosa and the cutis. CMM shares several features with human melanomas (HMM), included resistance to a broad variety of antineoplastic chemotherapy agents. P-glycoprotein 1 (Pgp) expression is a well-recognized feature of multi-drug resistance and the purpose of this study was to investigate its expression in treatment naïve CMM. We also investigated Pgp association with tumour location and histological features. Histology records of CMM were retrieved, including patients from 2012-2014. Twenty-five cases of CMM were included in this study. Results revealed that Pgp is expressed in CMM and oral tumours were more likely to have a membranous Pgp expression (100%) than cutaneous tumours (66.6%) (P = 0.010). Cytoplasmic and nuclear Pgp expression could also be identified. Results of this study bring useful data that help in understanding one of the possible mechanisms responsible of intrinsic chemotherapy resistance in canine CMM.

Cutaneous Heterotopic Brain Tissue (Neuroglial Choristoma) with Dysplastic Features in a Kitten.

A 3-month-old, male European shorthair kitten exhibited an ill-defined, soft mass on the skin of the frontal head, which was present since birth. The surgically resected tissue was representative of a discrete dermal and subcutaneous mass comprising islands of neurons, glial and meningothelial elements, sometimes atypical or dysplastic, separated by dense collagenous connective tissue. There was no evident connection between this tissue and the brain. Immunohistochemical examination confirmed the presence of neurons and a pleocellular glial population, supporting a diagnosis of cutaneous neuroglial choristoma believed to be secondary to sequestered (resolved) meningoencephalocoele. Ectopic brain tissue is very rare in small animals. Some atypical features displayed by this tissue may be misdiagnosed as neoplasia. Communication between surgeon and pathologist to clarify the relationship of the lesion to surrounding structures is helpful to avoid misdiagnosis.

Evidence for chronic morbillivirus infection in the Mediterranean striped dolphin (Stenella coeruleoalba).

In the summer of 1990 an epizootic infection caused by a morbillivirus (DMV) killed several thousand striped dolphins (Stenella coeruleoalba) in the Mediterranean Sea. In 1991 and 1992 the epizootic reached Italian and Greek waters. The infection by DMV in the acute period of the epizootic caused encephalitis, pneumonia and depletion of lymph nodes. After 1990, the systemic infection apparently disappeared from the Catalonian coast, giving way to cases of chronic infection of the CNS. Dolphins that died between 1991 and May 1994 were necropsied, and investigated for lesions due to DMV, and for the presence of morbillivirus antigen in tissues. Encephalitis occurred in 6 dolphins in which DMV antigen was demonstrated in the CNS and which were without lesions or antigen in other, non-nervous tissues. Inflammatory lesions, gliosis, and DMV antigen decreased in density and amount from cerebral grey matter, through the thalamic areas to the medulla oblongata. The cerebellum was usually spared. Lesions consisted of non-suppurative encephalitis, with diffuse gliosis and glial nodules and neuronophagia, and loss of neurons. Perivascular cuffing of lymphocytes and plasma cells was present in the cerebral cortex and the white matter beneath the cortex. Multinucleate syncytia were not detected in any of the dolphins. The haemagglutinin of DMV was detected mainly in neurons in the cerebral cortical areas. There was no clear relationship between the presence and amount of DMV antigen and the density or chronicity of lesions. Viral inclusions were seen in haematoxylin and eosin stained sections in 3/6 dolphins, principally in the nucleus and the cytoplasm of neurons. In the immunoperoxidase stained sections, dense granular deposits of chromogen, similar to viral inclusions, were evident in all 6 dolphins. The change in the distribution of lesions and of DMV antigen, from systemic to localized in the CNS, and the clustering of systemic DMV infections in the first four months of the epizootic, giving rise to sporadic occurrence of local CNS infection in the subsequent four years, as well as the chronic nature of the CNS lesions, which closely resembles subacute sclerosing panencephalitis, strongly support the existence of a chronic morbillivirus infection in the striped dolphin, as a delayed consequence of the 1990 epizootic.

Turkey rhinotracheitis virus and Escherichia coli experimental infection in chickens: histopathological, immunocytochemical and microbiological study.

The aim of this study was to evaluate the response of chickens to a combined infection with turkey rhinotracheitis virus (TRTV) and Escherichia coli O78:K80. Groups of specific-pathogen-free chickens were inoculated by eyedrop and intranasal routes with TRTV and/or E. coli O78:K80. Presence of E. coli O78:K80, histopathological changes and tissue distribution of viral antigen in the respiratory tract of chickens were evaluated. Dual infection resulted in increased severity of clinical signs, and macroscopic and microscopic lesions compared with those groups given single infections. All 36 chickens inoculated with TRTV plus E. coli O78:K80 showed severe rhinitis. Moreover, periorbital edema and fibrinous airsacculitis and pericarditis were observed in one of the three chickens inoculated with both agents and sacrificed at day 5 p.i. In addition, purulent material in the air spaces of the cranial bones was seen in three of the six animals from the same group sacrificed at days 5 and 7 p.i. The distribution of viral antigen in tissues was similar in groups inoculated with TRTV and TRTV plus E. coli, but viral antigen was detected only in main bronchi of chickens from the latter group. The quantity of E. coli O78:K80 isolated from the nasal cavity was greater in the group given dual infection. The results obtained suggest that TRTV may act as primary agent, enhancing E. coli multiplication. The lesions observed in the group inoculated with both agents could correspond to an initial stage of swollen head syndrome (SHS) and contribute to the hypothesis that SHS could be due to a mixed infection with TRTV and E. coli.

Epidermal immunocompetence in canine leishmaniasis.

The antigen-presenting cell function of the epidermis was investigated immunocytochemically in 16 dogs with different types of skin lesions induced by Leishmania infection. The degree of epidermal immunocompetence was evaluated according to the presence of Langerhans cells (LC) and keratinocytes expressing class II major histocompatibility complex (MHC II) molecules on the one hand, and the relative numbers of macrophages, T cells, and parasites in the dermis on the other, as described for human cutaneous leishmaniasis. In alopecic dermatitis, appropriate numbers of LC and MHC II-positive keratinocytes were shown to be associated with a mild T cell infiltration without significant numbers of parasites. By contrast, when the epidermis lacked antigen-presenting cells, as occurred in nodular lesions, macrophages and parasites massively infiltrated the dermis. Ulcerative lesions showed intermediate patterns of inflammation. These results suggest that dogs with alopecic dermatitis develop an effective control of the infection, whereas those with a generalized nodular disease mount an impaired immune response against the parasite. Skin lesions in dogs infected by Leishmania might not only have a prognostic value, but also represent a suitable model to study the natural course of human cutaneous leishmaniasis.

Neural cells from dogs with spontaneous distemper encephalitis express class II major histocompatibility complex molecules.

Expression of class II major histocompatibility complex (MHC) molecules by non-immune cells (e.g., parenchymal cells) leads to the presentation of self-antigens, and may have a role in the pathogenesis of many diseases mediated by autoimmunity. Such diseases, characterized by demyelination of the central nervous system and expression of class II MHC molecules on neural cells, include multiple sclerosis, experimental allergic encephalitis and Theiler's murine encephalomyelitis virus infection. Canine distemper encephalitis probably does not have an autoimmune character, but it shares many similarities with the aforementioned diseases. For this reason, the expression of class II MHC molecules in the brains of dogs with canine distemper encephalitis was investigated immunohistochemically. The results presented here demonstrate that canine microglia and astrocytes "upregulate" class II MHC expression in cases of encephalitis associated with chronic canine distemper.

A canine nephropathy resembling minimal change nephrotic syndrome in man.

In the dog, massive proteinuria and/or the nephrotic syndrome have been commonly associated with renal amyloidosis and membranous glomerulonephritis. Primary glomerulopathies associated with the nephrotic syndrome in man also include minimal change nephrotic syndrome and focal glomerular sclerosis. A 4-year-old Collie dog is described with clinical, histological, immunohistological, and ultrastructural findings similar to those which characterize the minimal change nephrotic syndrome (MCNS) in man.

Meningioangiomatosis in the brain stem of a dog.

Meningioangiomatosis (MA) is a malformation of the vasculature of the central nervous system, characterized by the proliferation of meningothelial cells around blood vessels. MA has been reported, albeit rarely, in main, cattle and dogs. This paper records a case of MA affecting the brain stem in a 9-year-old male dog, and provides histochemical and immunohistochemical evidence for a perivascular fibroblast-like cell origin of the proliferating cells.

Immunohistochemical detection of CD31 antigen in normal and neoplastic canine endothelial cells.

This report describes the immunohistochemical detection of von Willebrand's factor (vWf) and CD31 antigen in paraffin wax-embedded, formalin-fixed tissue sections of canine normal organs and vascular neoplasms. CD31 antigen and vWf were detected in endothelial cells of all organs examined, except for the endothelia of the renal glomeruli, which were negative for vWf. All haemangiomas examined (15) were positive for both markers. Eleven of 15 haemangiosarcomas were positive for vWf and all 15 expressed the CD31 antigen. All other neoplasms investigated (fibrosarcomas, schwannomas, haemangiopericytomas) were negative for both markers. It is concluded that immunohistochemical detection of CD31 antigen is of value for studying vascular disorders of the dog in routinely processed tissue.

Muscle fibre expression of transforming growth factor-beta 1 and latent transforming growth factor-beta binding protein in canine masticatory muscle myositis.

Masticatory muscle myositis (MMM) is presumed to be an immunologically mediated canine myopathy but is of unknown origin. Severe atrophy and degeneration of masticatory muscle fibres, infiltration of eosinophilic granulocytes, and proliferation of the fibrous interstitial tissue are the hallmarks of MMM. Transforming growth factor-beta (TGF-beta) is a multifunctional regulatory peptide controlling myogenesis, inflammation and tissue repair. We investigated immunocytochemically the expression of TGF-beta 1 and latent transforming growth factor-beta binding protein (LTBP), a TGF-beta modulator protein, in cases of MMM. The study demonstrated the presence of TGF-beta and LTBP in muscle fibres. infiltrating leucocytes and extracellular matrix in MMM, and suggested that TGF-beta and LTBP play a role in muscle tissue repair, inflammation and fibrogenesis in MMM.

Evidence of cytokeratin expression in canine visceral glomerular epithelial cells in vivo.

Visceral glomerular epithelial cells (vGECs) originate from a mesenchymal blastema and transiently express cytokeratin during embryogenesis. There are no reports of cytokeratin expression in vGECs of mature, normal or damaged, human or other mammalian kidneys in vivo, but in vitro studies have provided evidence of the synthesis of cytokeratin in cultured vGECs. Cytokeratin expression was observed in vGECs in the damaged kidneys of four dogs with spontaneous renal diseases and, by using monoclonal antibodies, type 18 cytokeratin was identified. vGECs are apparently able to (re-) activate in vivo a mechanism for switching on the synthesis of cytokeratin in damaged glomeruli.

Tubular vimentin metaplasia in canine nephropathies.

The expression of the intermediate filament vimentin was examined immunocytochemically in 17 cases of histologically confirmed primary canine nephropathy, and compared with its expression in normal canine kidney. In normal renal tissue, the expression of vimentin was restricted to glomerular elements, but in all cases of chronic interstitial nephritis it extended to the cortical tubular epithelia, and was correlated with the degree of tubulo-interstitial damage. Three of four cases of renal cell carcinoma had vimentin reactivity in neoplastic cells. In only one case of familial renal disease was vimentin expressed in scattered epithelial cells of the cortical tubules.

Expression of class II major histocompatibility complex molecules in renal tubular epithelial cells of canine kidneys affected with tubulointerstitial nephritis.

Class II major histocompatibility complex (MHC) products are important molecules on various antigen-presenting cells and induce a T cell-specific immune response. The distribution of class II MHC molecules in the normal canine kidneys of dogs with tubulointerstitial nephritis was investigated by using a sensitive immunocytochemical method. In the normal canine kidney, class II MHC molecules were detected in interstitial 'dendritic' cells. In cases of tubulointerstitial nephritis, however, the expression of class II MHC molecules extended to other renal elements such as the epithelial cells of cortical and medullary tubules and, in some cases, the endothelial cells of peritubular capillaries. The tubular expression of class II MHC molecules was enhanced in dogs with higher levels of proteinuria. The results suggest that heavy proteinuria may be one triggering factor in canine tubulointerstitial damage, probably mediated by the reabsorption of filtered cytokines and immunogenic peptides which induce tubular epithelial cells to behave as immune accessory cells.