Clinicopathological study of canine transmissible venereal tumour in leishmaniotic dogs

Introduction : Canine transmissible venereal tumour is occasionally observed in leishmaniotic dogs, and Leishmania amastigotes can be harboured in canine transmissible venereal tumour cells. Objectives : The aim of this paper was to investigate the clinicopathological significance of the association of both diseases. Methods : Nineteen dogs affected by canine transmissible venereal tumour and canine leishmaniasis were studied retrospectively. Results : In these dogs, the tumour manifested a large size and often aggressive behaviour (42%) and no predictive sign of spontaneous regression was observed. Sporadic Leishmania amastigotes were found within the canine transmissible venereal tumour in three cases, probably transported by infected macrophages often infiltrating the tumour. A high Leishmania parasitisation of canine transmissible venereal tumour was observed in two other cases and verified by immunohistochemistry. Clinical Significance : Canine transmissible venereal tumour is a tumour of the dog able to harbour a large number of Leishmania parasites. Alternatively, the systemic disease (canine leishmaniasis) may lower the immune defence against malignancy (canine transmissible venereal tumour).     

E-cadherin expression in canine mammary carcinomas with regional lymph node metastases

E-cadherin (E-cad) is a cell adhesion molecule known for its tumour invasion-suppressor function. This study investigated the immunohistochemical expression of E-cadherin in 19 cases of malignant mammary tumours of the dog and the relationship between E-cadherin expression in primary tumours and in regional lymph node metastases. E-cadherin expression is not always parallel in the primary tumour and in the lymph node metastasis. One year follow-up was available in 12 of 19 cases. Three different patterns of expression were revealed in the lymph node metastases compared with the primary tumour: downregulation when the protein expression was weaker in the metastasis than in the primary tumour; upregulation when E-cadherin was stronger in the lymph node than in the primary tumour, and a similarly intense expression when it was equal in the metastasis and in the tumour. The lymph node pattern revealed a prevalent upregulation or downregulation with respect to the primary tumour, whereas a similar expression of E-cadherin was encountered in less than 50% of cases.     

Metabolic correlates of tumour hypoxia in malignant canine mammary carcinoma

Given its importance in human and canine tumour biology, a profound understanding of tumour hypoxia is of paramount importance. Therefore, the aim of this work was to investigate the relationship between tumour hypoxia and the expression of a number of hypoxia-induced proteins that play a role in tumour metabolism. The hypoxia marker pimonidazole was administered to dogs affected by spontaneous mammary carcinoma and compared with immunohistochemical staining for GLUT1 and 3, HK 2 and CA IX. A statistically significant correlation was found between pimonidazole staining and GLUT1-expression (R = 0.607; p = 0.001). These results indicate a strong interaction between tumour hypoxia and tumour metabolism by the induction of proteins essential to maintain a stable tumour microenvironment.     

Feline inductive odontogenic tumour in a Burmese cat

A 7-month-old, male, Burmese cat was presented with an oral mass that had rapidly regrown following excisional biopsy 3 weeks earlier. The tumour was identified by histological examination as a feline inductive odontogenic tumour. A unilateral segmental mandibulectomy was performed. Although dental malocclusion resulted from mandibular drift to the operated side, the cat displayed minimal dysphagia post-operatively and there was no evidence of tumour regrowth 8 months after surgery. Feline inductive odontogenic tumour is a rare dental tumour described exclusively in cats under 3-years-of-age. Although histopathologically benign, feline inductive odontogenic tumour grows by expansion and can infiltrate underlying bone to cause considerable local destruction. This article is intended to increase awareness of this unusual tumour which, with complete surgical excision, carries a good prognosis. It also emphasises the importance of obtaining a histological diagnosis from oral mass lesions to direct appropriate therapy and to provide an accurate prognosis.     

Microvascular growth of 7,12-dimethylbenz(α)anthracene-induced adenocarcinomas in rats: histology and scanning electron microscopy of resin casts

Vascular changes at various stages of growth of 7,12‐dimethylbenz(α)anthracene (DMBA)‐induced mammary adenocarcinomas in 22 female Sprague‐Dawley rats were investigated using histology, immunohistochemistry and scanning electron microscopy (SEM) of corrosion casts. In the early stage of tumour growth, capillaries within the neoplasms were thin, with 8–10 μm diameter, and characterized by rows of vascular sprouts representing extensive neovascularization and formation of a high‐density capillary plexus. In the intermediate stage of tumour growth, the growing tumour was multi‐nodular and tumour cells were arranged in a tubulopapillary pattern. Capillaries formed spheroid vascular capsules and were characterized by dilation, to a diameter of 10–80 μm, and blind ends. In the late stage of tumour growth, a remarkable reduction in the number of vascular endothelial growth factor‐positive cells and Ki‐67‐stained nuclei was demonstrated. The tunica media of nutritive arteries displayed a tendency to atrophy. Many arteriovenous anastomoses between the major arteries and the veins were found in regions just before their entry into the tumour. The central regions of the tumour were degenerative and necrotic, and vasculature was confined to surface regions of the tumour, forming a basket‐like configuration around the avascular central regions. Resin leakages representing haemorrhage or oedema and distortions such as flattening, break‐off and strangulations of capillaries were frequently observed, all of which are known as late tumour signs. We concluded that these microvascular alterations might change the homogeneity of tumour perfusion and contribute to necrosis in central portions of the tumour.     

Patient and tumour factors influencing canine mast cell tumour histological grade and mitotic index

The aim of this study was to identify patient and tumour factors most frequently associated with high histological grades of canine mast cell tumours (MCTs). Search criteria in a shared database of multiple Animal Referral Hospital locations within Australia generated 400 canine MCTs in 286 patients. Patient and tumour data were extrapolated and the association between a tumour being histologically high grade and patient and tumour factors, including: patient breed, patient gender and neuter status, patient age at MCT excision, tumour location and tumour size was assessed using univariate analysis. The study consisted of 90 (21.9%) tumours meeting histological high‐grade criteria. Shar peis were the most likely breed to have high grade MCTs, whereas the Pug and the Golden Retriever were the least likely breeds to develop high‐grade MCTs. No significant difference in risks could be established between the age at which the tumour was excised, or the gender and neuter status of patients. MCTs of the inguinal region were the most likely single location to be high grade. Tumour size did not influence the likelihood of a tumour being high grade or low grade. The results of this study suggest that patient and tumour factors may play a role in the histological grades of canine MCTs.     

Malignant lymphoma in nasal cavity and paranasal sinuses of a dog

A case of a canine large cell type T-cell lymphoma, with features of high-grade malignancy is described. The tumour was found confined in the nasal cavity and the paranasal sinuses of a crossbred German Shepherd dog. Histological examination revealed the features of a highly malignant large cell lymphoma. Ultrastructurally, the lymphoid tumour cells bore cytoplasmic protrusions that interdigitated tightly. From a panel of tumour markers used, the neoplastic cells were stained only for vimentin. Immunophenotyping of the tumour cells by means of CD3, CD79, kappa-light chains and lambda-light chains detection was undertaken. The tumour stained only for CD3 and was classified as T-cell lymphoma.     

Deionised water as an adjunct to surgery for the treatment of canine cutaneous mast cell tumours

Medical records of 55 dogs with a diagnosis of cutaneous mast cell tumour were reviewed. Twenty-seven of the dogs were treated with surgery plus deionised water and the remaining 28 with surgery alone. A survival analysis was performed to determine whether deionised water, as an adjunct to surgery for cutaneous mast cell tumour, affected survival time or time to tumour recurrence. Dogs in which mast cell tumour recurred had a significantly shorter survival time compared with dogs with no recurrence (P=0.05), regardless of the method of treatment. A significant negative association between tumour recurrence and method of treatment (P=0.0097) and clinical stage (P=0.0223) was observed. Dogs treated with surgery and deionised water had a significantly shorter time to recurrence of their mast cell tumour (P=0.0113). Based on these results, deionised water does not appear to be beneficial in prolonging survival time or time to tumour recurrence for dogs with cutaneous mast cell tumours.     

Anti‐tumour activity of oncolytic Western Reserve vaccinia viruses in canine tumour cell lines,xenografts, and fresh tumour biopsies

Cancer is one of the most common reasons for death in dogs. One promising approach is oncolytic virotherapy. We assessed the oncolytic effect of genetically modified vaccinia viruses in canine cancer cells, in freshly excised tumour biopsies, and in mice harbouring canine tumour xenografts. Tumour transduction efficacy was assessed using virus expressing luciferase or fluorescent marker genes and oncolysis was quantified by a colorimetric cell viability assay. Oncolytic efficacy in vivo was evaluated in a nude mouse xenograft model. Vaccinia virus was shown to infect most tested canine cancer cell lines and primary surgical tumour tissues. Virus infection significantly reduced tumour growth in the xenograft model. Oncolytic vaccinia virus has antitumour effects against canine cancer cells and experimental tumours and is able to replicate in freshly excised patient tumour tissue. Our results suggest that oncolytic vaccinia virus may offer an effective treatment option for otherwise incurable canine tumours.     

Osteoclast-like giant cell tumour arising from the kidney in a dog

In this study, a case of osteoclast-like giant cell tumour arising from the kidney is reported in an eight-year-old female Anatolian Shepherd dog. Macroscopically, the tumorous mass covered the hilus of the left kidney. It was 26 x 22 x 12 cm in size and 3700 g in weight. Metastatic tumorous nodules, 0.5-2.0 cm in diameter, were found on the abdominal side of the diaphragm and in the lungs. Microscopically, numerous large osteoclast-like multinucleated giant cells and spindle-spheroidal-shaped cells were seen. Osteoblastic differentiation and osteoid matrix were noted in a few areas at the periphery of the tumour, near the connective tissue septa. The stroma of the tumour tissue was vascular, oedematous and loose. By immunoperoxidase staining, tumour cells showed immunoreactivity for vimentin but not for keratin and desmin, indicating that the tumour had mesenchymal origin. This is the first report in the literature on a malignant osteoclast-like giant cell tumour arising from a visceral organ in animals.     

Feline cutaneous neuroendocrine carcinoma (Merkel cell tumour): clinical and pathological findings

A case of a feline Merkel cell tumour is described. An 8-year-old, female cat developed a round, alopecic, reddish mass on the nose. Wide excisional surgery was performed with cartilage resection. Histologically the mass was composed of solid islands of mostly basophilic densely packed cells with a scant cytoplasm, which was suggestive of a neuroendocrine origin. Results of immunohistochemical studies using antibodies against neurone-specific enolase, chromogranin, synaptophysin and pan-cytokeratin allowed classification of the lesion as a Merkel cell tumour. Ultrastructurally, dense core granules were identified in the cytoplasm. In a 2-year follow-up no relapses or metastases were observed. The clinical course recorded is in contrast with the malignant nature of a Merkel cell tumour recently described in a cat and of the human Merkel cell tumour, but is similar to the course of the canine Merkel cell tumour which is often benign. Early diagnosis along with the use of wide surgical excision might be considered an important factor in preventing relapse of this tumour.     

Reinke's Crystals in an Interstitial Cell Tumour of a Rabbit (Oryctolagus cuniculus)

Contents One case of interstitial cell tumour in the testicle of a New Zealand White rabbit was reported. The rabbit was 9-years old and had monolateral testicular lesion. There was enlargement of left testis and the lesion were seen on the cut surface. Light microscopy revealed intracytoplasmic crystals of Reinke that resembled to the features observed for this tumour in human. Immunohistochemically, this tumour was positive for vimentin.     

Cerebral high-grade astrocytoma (glioblastoma) in a cat

A cerebral tumour was found in the right frontal lobe of a 7-year-old female mongrel cat. The mass showed infiltrative growth and caused deformation of the corpus callosum. Histopathologically, the tumour cells showed anaplasia, pleomorphism and mitotic figures. Necrosis and vascular proliferation were prominent. The neoplastic cells surrounded areas of necrosis, but as an indistinct pseudopalisade formation. Immunohistochemically, low numbers of tumour cells labelled positively for anti-glial fibrillary acidic protein and anti-S100 protein. Electron microscopically, the majority of tumour cells had no filaments and cytoplasmic processes, but the differentiated cells presented cytoplasmic filaments and glycogen granules. Based on these findings, the tumour was diagnosed as cerebral high-grade astrocytoma, glioblastoma.     

Induction of VEGF by tepoxalin does not lead to increased tumour growth in a canine osteosarcoma xenograft

The purpose of this study was to determine the impact of the non-steroidal anti-inflammatory drug tepoxalin on canine tumour cell growth and describe the changes associated with tepoxalin treatment. In vitro experiments were performed to assess tepoxalin-associated alterations in tumour cell growth. Clinically achievable tepoxalin concentrations did not significantly alter tumour cell growth in vitro. Vascular endothelial growth factor (VEGF) production and hypoxia-inducible factor-1α dose-dependently increased in vitro in the presence of tepoxalin. A canine osteosarcoma xenograft was used to determine in vivo effects of tepoxalin on tumour growth and angiogenesis. Despite increased VEGF in vitro, there was a significant growth delay associated with tepoxalin treatment. Normal dogs were administered tepoxalin to assess effects on systemic VEGF production, but not found to have significantly increased VEGF. These data suggest that tepoxalin may moderately inhibit tumour growth and may be administered as an analgesic to tumour-bearing dogs.     

Orbital multilobular tumour of bone in a dog

A multilobular tumour of bone with left orbital involvement was diagnosed at post mortem examination in an eight-year-old German shepherd cross dog. The tumour resulted in progressive exophthalmos with lateral deviation of the left eye. Radiographs revealed that the mass was mineralised and originated from the left frontal bone with invasion of the left frontal sinus and destruction of the cribriform plate. This is the third reported case of this type of tumour involving the orbit of the dog and thus multilobular tumour of bone should be considered as a differentia] diagnosis of exophthalmos.     

Udder development, lactation and ascites in a ewe with an ovarian granulosa cell tumour

A 20-month-old sexually intact female mixed breed sheep was examined for lameness, unexpected udder development, lactation and anorexia. Tachycardia, tachypnoea, severe abdominal distension and vaginal prolapse were evident upon physical examination. A right hindlimb lameness was present at the walk. The udder was well-developed and milk, normal in appearance, was easily expressed from each teat. Ultrasonographic evaluation revealed a non-pregnant uterus, severe ascites and a large (12 cm diameter) abdominal mass. Although surgical treatment was discussed, the owners elected to euthanase the ewe. Necropsy examination confirmed the presence of severe ascites due to a ruptured ovarian tumour. The tumour was characterised as a granulosa cell tumour histologically. Unexpected udder development and lactation presumably occurred secondary to oestrogen and progesterone production by the tumour. To the authors' knowledge, this is the first report of udder development, lactation and ascites in a ewe secondary to an ovarian granulosa cell tumour.     

Intramedullary spinal cord metastasis of a primary lung tumour in a dog

A dog was presented with signs of subacute, progressive myelopathy. A tentative diagnosis of a diffuse intramedullary spinal cord mass was made using contrast radiography (myelography). At autopsy a solitary, large bronchoalveolar carcinoma was detected in a lung lobe. Histological examination of the cranial thoracic spinal cord revealed a tumour which was similar, but not identical, to the lung tumour. Immunohistochemistry helped to confirm that the spinal lesion was a metastasis of the lung tumour.     

Canine paraganglioma: a case report

An 8-year-old castrated Cocker Spaniel with tympanic paraganglioma was presented. The tumour was resected twice with an interval of 120 days. The dog presented with tetraparesis 130 days after the second operation and had radiologic evidence of metastasis to the C5 vertebra. On pathologic examination, metastasis of the tumour was found in the myocardium, lungs, kidney, and C5 vertebra. The tumour, which is being described for the first time in the dog, was highly vascular, and was characterized by various-sized groups of medium-sized cells separated by vascular stroma. The neoplastic cells were round or polyhedral with moderately hyperchromatic nuclei, scattered chromatin, indistinct nucleoli, and eosinophilic granular cytoplasm. The metastatic lesions were histologically similar to the primary tumour.     

Olfactory esthesioneuroblastoma treated with orthovoltage radiotherapy in a dog

A 13-year-old neutered female mongrel dog presented with a 1-year history of stertorous respiration. On computed tomography examination, a mass was demonstrated in the nasal cavity. Open biopsy of the mass was performed and a diagnosis of olfactory esthesioneuroblastoma was made on histological examination. The dog was treated with orthovoltage x-ray radiation (total dose; 53 Gy given in 14 fractions over an 8 week period). Computed tomography after the twelfth irradiation revealed that tumour size had decreased. Although clinical signs were absent in the 4 months after irradiation, re-growth of the tumour was detected by radiographic evaluation and histological examination. The dog was again treated with orthovoltage x-ray radiation (total dose; 30 Gy given in three fractions over a 4-week period), however, tumour regrowth was again detected 3 months later. Clinical treatment of this tumour type has not been previously reported.     

Expression of ABC-Transport Proteins in Canine Mammary Cancer: Consequences for Chemotherapy

Intrinsic or acquired drug resistance is a major barrier for chemotherapy of cancer. Importantly, the presence of ATP-binding cassette, ABC-transport proteins in tumour cells circumvents an intracellular accumulation of chemotherapeutic drugs. In this study, 103 canine mammary tumour probes were investigated for mRNA expression of seven ABC-transporters by RT-PCR. All tumour samples expressed multidrug resistance-associated protein 1 (MRP1) and breast cancer resistance protein (BCRP). MRP7 was detected in 97.1% of tumour probes, MRP3 in 96.1%, Pgp in 92.2%, MRP5 in 85.4% and MRP6 in 64.1%. More of the half of tumour samples (56.1%) expressed all of the examined ABC-transport proteins. Approximately one-third of the tumour samples (32.7%) were lacking in one transporter and only 11.2% possessed from three to five transporters. The canine transporter cBCRP was functionally analysed in stable transfected Madin-Darby canine kidney-II cells using an MTT viability test. cBCRP transfected cells showed a 5.4-fold resistance to 10 μ m doxorubicin. Cell survival in the presence of methotrexate was not affected by cBCRP. In conclusion, absence of efficiency of chemotherapy of canine mammary cancer can be caused by expression of seven various ABC-transport proteins. Because cBCRP is expressed in all examined tumour probes and induces resistance to doxorubicin, the application of doxorubicin for treatment of canine mammary is inappropriate.