Tolerability and pharmacokinetic profile of a novel benzene‐poly‐carboxylic acids complex with cis‐diammineplatinum (II) dichloride in dogs with malignant mammary tumours

The pharmacokinetic profile, tolerability and efficacy of benzene‐poly‐carboxylic acids complex with cis‐diammineplatinum (II) dichloride (BP‐C1) were studied in dogs with mammary cancer. A three‐level response surface pathway designed trial was performed on seven dogs. At each level BP‐C1 was administered subcutaneously daily for 7 days followed by a 7‐day rest period in a dose escalating manner. Adverse events according to VCOG‐CTCAE, performance status and tumour progression were recorded. The pharmacokinetic profile followed a two‐compartment model with rapid absorption, short distribution, and a slow elimination phase. The overall elimination half‐life was 125 h. The maximum tolerated dose of BP‐C1 was estimated to be above 0.46 mg kg^?1. A significant reduction in VCOG‐CTCAE toxicity which correlated negatively with increasing dose was found. The dogs' general performance status remained unchanged. No decrease in total tumour burden was found, although temporary tumour reduction was seen in some target tumours.     

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.     

百日鸡J-亚群禽白血病组织病理学与超微病理学研究

利用ELISA试剂盒,对百日鸡的禽白血病抗体和抗原进行了检测。在5个百日鸡父母代鸡群中,1个鸡群的ALV-J抗体阳性率为57.14%,其余鸡群皆为阴性;所有鸡群的ALV-A、B抗体均为阴性;ALV p27抗原除1个鸡群为阴性外,其余鸡群阳性率都较高。在百日鸡的J亚群禽白血病病例中,肝脏、脾脏和肾脏显著肿大,且有弥漫性分布的肿瘤结节;在其他脏器也呈现肿瘤结节。组织病理学观察,发现其脏器等组织中,有一定比例的胞质含红色嗜酸性颗粒的髓细胞样瘤细胞与成淋巴细胞,排列致密呈局灶性生长,正常的组织细胞被挤压或破坏。超微病理观察,在脾脏和法氏囊等组织中均看到病毒颗粒,有囊膜,直径约100nm。部分淋巴细胞核膜、细胞膜水肿或溶解破裂,线粒体和内质网也水肿或池变大、细胞质中出现很多空泡状结构。肿瘤细胞的增多以及细胞内和细胞间的水肿,可能是各脏器严重肿大的主要原因。     

A case of hepatic carcinoid in a red deer hind (Cervus elaphus)

A carcinoid tumour in the liver of a red deer hind (Cervus elaphus) is described. Macroscopically, the liver was considerably enlarged with multifocal, firm, yellow and red nodular neoplastic masses, which were histopathologically diagnosed as hepatic carcinoids. The diagnosis was confirmed by modified Grimelius staining, which demonstrated numerous small argyrophilic granules in the cytoplasm of neoplastic cells, and by immunohistochemistry. The neoplastic cells gave a strong positive reaction for neuron-specific enolase (NSE) and synaptophysin and a weak positive reaction for chromogranin A. To our knowledge, this is the first report of a hepatic carcinoid in red deer.     

Influence of E‐cadherin genetic variation in canine mammary tumour risk,clinicopathological features and prognosis

E‐cadherin is a cell adhesion molecule that participates in several cellular processes that guarantee the maintenance of structural and functional integrity of epithelial tissues. E‐cadherin plays an important role in mammary carcinogenesis, and various studies have demonstrated the effect of CDH1 genetic variation in risk, progression and biological behaviour of human breast cancer. Although there are some recognized genetic variations in canine CDH1 gene, their influence in canine mammary tumour development and progression has not been previously evaluated. In this study, we aim to assess the influence of CDH1 SNPs rs850805755, rs852280880 and rs852639930 in the risk, clinicopathological features and clinical outcome of canine mammary tumours. A case‐control study was conducted involving 206 bitches with mammary tumours and 161 bitches free of mammary neoplasia. CDH1 SNPs rs850805755 and rs852280880 were associated with a decreased risk and a later onset of mammary tumour development. Furthermore, these SNPs were related to the development of small size carcinomas, of low histological grade and low nuclear pleomorphism. SNP rs852639930 was associated with the development of small size tumours with a non‐infiltrative, non‐invasive growth pattern. Data from the present investigation demonstrate that these CDH1 genetic variants could have a protective role in canine mammary tumours, by being associated with low risk of tumour development, delayed onset of the disease and less aggressive clinicopathological features.     

Testicular Neoplasms (Interstitial and Sertoli Cell Tumours) in a Domestic Ferret (Mustela putorius furo)

Unilateral testicular enlargement was detected in a 5‐years‐old domestic ferret during a routine sterilization. The right testicle showed two different types of proliferative lesions: (i) round nodules, well demarcated, showing a soft yellow tissue; (ii) white nodules, firm, with irregular‐shaped invaginations. Microscopically, the neoplastic proliferations were identified as an interstitial neoplasm and Sertoli cell tumour, respectively. The left testicle was small and showed intense testicular atrophy. Clinical evaluation of the ferret did not show any other apparent pathological processes. This study is the first case reporting the concomitant occurrence of a Sertoli cells tumour and an interstitial cell tumour in a domestic ferret.     

Endocrinological characterization of an ovarian sex cord–stromal tumor with a Sertoli cell pattern in a Japanese Black cow

A Japanese Black cow was evaluated for prolonged post‐partum anestrus and enlargement of the right ovary. Transrectal ultrasonography revealed that the right ovary was markedly enlarged and had a solid appearance, while the left ovary was small and inactive. The presumptive diagnosis was directed towards granulosa‐theca cell tumour (GTCT) which was supported by markedly elevated plasma anti‐Müllerian hormone (AMH; 332.0 ng/ml), oestradiol (E₂; 103.3 pg/ml) and immunoreactive inhibin (ir‐INH; 2.1 ng/ml) in comparison with the diagnostic cut‐off points for bovine GTCTs. Since the cow had been infertile and had swelling of the udder, slaughter was chosen. Histopathological examination revealed that the tumour was an ovarian sex cord–stromal tumour (SCST) with a Sertoli cell pattern. These findings suggest that plasma AMH, ir‐INH and E₂ could be possible biomarkers for bovine ovarian SCST with a Sertoli cell pattern, whereas this case could not be distinguished from GTCTs based on endocrinological profile.     

Intradural extramedullary granular cell tumour in a cat

A 7-year-old domestic shorthair cat was evaluated for progressive paraparesis, inability to jump, a paralysed tail and inability to void the bladder. Neurologic examination was consistent with a L4-S3 localisation. Survey radiographs of the lumbar vertebral column revealed L4-L7 vertebral body remodelling. A pre-contrast T1-weighted hyperintense, diffusely enhancing intradural lesion extending from L4 to S1 vertebral bodies was detected by MRI. Large, mesenchymal, round-to-polygonal cells arranged in nests or sheets were found on histologic examination at post mortem. These cells were characterised by abundant intracytoplasmic PAS-positive, diastase-resistant granules and positive immunoexpression of vimentin, S-100, neuron-specific enolase and desmin. This is the first report of a spinal granular cell tumour in a cat.     

Identification of occult micrometastases and isolated tumour cells within regional lymph nodes of previously diagnosed non‐metastatic (stage 0) canine carcinomas

Metastatic dissemination of carcinomas to lymph nodes impacts prognosis and treatment recommendations in human and veterinary medicine. Routine histopathologic evaluation of regional lymph nodes involves haematoxylin and eosin (H&E) staining to identify intra‐nodal neoplastic cells; however, identification of small volume metastases (micrometastases and individual tumour cells) may be missed without the aid of immunohistochemistry or additional step‐sections. The aim of this study was to identify occult carcinoma metastases in previously diagnosed non‐metastatic lymph nodes using step‐sections and pancytokeratin (panCK) immunohistochemistry. Samples from 20 regional lymph nodes diagnosed as non‐metastatic were serially sectioned and evaluated with panCK. Of these, 25% (n = 5) contained micrometastases (n = 1) or isolated tumour cells (n = 4). This study demonstrates the increased efficacy of serial step‐sections combined with panCK immunohistochemistry to identify small volume metastases in regional lymph nodes. The prognostic significance of micrometastases and isolated tumour cells in regional lymph nodes warrants further investigation in veterinary medicine.     

Measurements of hypoxia ([18F]‐FMISO, [18F]‐EF5) with positron emission tomography (PET) and perfusion using PET ([15O]‐H2O) and power Doppler ultrasonography in feline fibrosarcomas*

The aim of this study was to evaluate if hypoxia in feline fibrosarcomas can be detected. This was done using positron emission tomography (PET), two hypoxia tracers and polarographic pO₂ measurements. Of the seven cats included, five received [¹⁸F]‐fluoromisonidazole and two 2‐(2‐nitro‐1H‐imidazol‐1‐yl)‐N‐(2,2,3,3,3‐pentafluoropropyl) acetamide. Perfusion was evaluated with [¹⁵O]‐H₂O (n = 4) and with contrast‐enhanced power Doppler ultrasonography (n = 5). Hypoxia was detected in three cats. Polarographic pO₂ measurements did not confirm PET results. In the ultrasonographic evaluation, low vascularity and low perfusion were seen with a peripheral vascular pattern and no perfusion in the centre of the tumour. This was in contrast to the [¹⁵O]‐H₂O scans, where central perfusion of the tumour was also found. In conclusion, it appears that hypoxia exists in this tumour type. The presence of tumour necrosis and heterogeneous hypoxia patterns in these tumours may explain the found discrepancies between the applied techniques.     

What is your diagnosis? Pancytopenia in a dog

Abstract: A 4‐year‐old male, castrated, mixed‐breed dog was presented to the Colorado State University Veterinary Teaching Hospital with a 1‐week history of polyuria, polydipsia, lethargy, fever, inappetence, weight loss, and soft mucoid stool. The dog was depressed and had pale, icteric mucous membranes. Results of a CBC included normocytic, normochromic, nonregenerative anemia, neutropenia, and thrombocytopenia, with 43% blast cells (200/μL), many of which contained fine azurophilic granules. Cytologic evaluation of the bone marrow aspirates revealed mild granulocytic hyperplasia that appeared to be left‐shifted in an apparent maturation arrest. A large population of blast cells comprised 35% of nucleated cells; the blasts had high nuclear to cytoplasmic ratios, deeply basophilic cytoplasm with vacuoles, and prominent nucleoli. Most cells also contained many fine azurophilic granules clustered in the paranuclear region. At necropsy, neoplastic cells were abundant in the bone marrow. Immunohistochemically the cells expressed CD3?, and an oligoclonal T‐cell rearrangement was found. The diagnosis was proliferative disorder of CD3⁺ granular lymphocytes, with associated pancytopenia. Because the blast cells were morphologically similar to myeloblasts and immunohistochemistry was required to confirm the diagnosis, T‐cell lymphoproliferative disease should be considered in dogs with pancytopenia presenting with similar clinical features.     

Further Field Experiments on the Use of Coccidiostatic Drugs in Unweaned Lambs

A small tumour was found at the periphery of the lung during routine necropsy of a 13-year-old Romney ewe. The tumour consisted of vacuolated, cuboidal cells which lined alveolar spaces without destroying them. Electron microscopy revealed numerous microvilli on the free surface of the cells and irregularly shaped osmiophilic inclusions within the vacuoles. No viral particles were found and the tumour was diagnosed as a well differentiated Type II pneumocyte adenocarcinoma of unknown aetiology.     

Development of a new canine osteosarcoma cell line

Establishing a canine osteosarcoma (OSA) cell line can be useful to develop in vivo and in vitro models of OSA. The goal of this study was to develop, characterize and authenticate a new canine OSA cell line and a clone. A cell line and a clone were developed with standard cell culture techniques from a naturally occurring OSA in a dog. The clonal cell line induced a tumour after injection in RAG 1‐deficient mouse. Histology was consistent with OSA. The original tumour from the dog and the tumour induced in the mouse were both reactive with vimentin and osteonectin (ON). The parent cell line and clonal cell line were reactive with ON, osteocalcin and alkaline phosphatase. Loss of heterozygosity was found in the same three microsatellite markers in the parent and clonal cell lines, and the tumour tissue grown in the mouse.     

Epidemiological,pathological and immunohistochemical aspects of 125 cases of feline lymphoma in Southern Brazil

A retrospective study compiling cases of feline lymphoma diagnosed during 12 years (2004‐2016) in Southern Brazil was performed. A total of 125 cases of lymphoma diagnosed in cats were reviewed, and information including age, breed, sex and tumour topography were collected. FeLV and FIV immunohistochemical tests were performed, as well as immunophenotyping of lymphomas. The alimentary form represented the most common presentation (42/125), followed by mediastinal lymphoma (35/125). Out of 125 cases, 79 presented positive retroviral immunostaining in tumour tissue (52 FeLV alone, 14 FIV alone and 13 presented FIV and FeLV co‐infections), 66/125 of the cases were of T‐cell origin and 59/125 of the cases were of B‐cell origin. The median age of cats with T‐cell lymphoma was 120 months (10‐240 months), and 60 months (6‐204 months) for cats with B‐cell lymphoma. The most frequent alimentary tumour presentation was the enteropathy‐associated T‐cell lymphoma (type 1), and the major type of mediastinal tumour observed was diffuse large B‐cell lymphoma. Considering only mediastinal and alimentary lymphomas (n = 77), the prevalence of mediastinal lymphoma in FeLV‐positive cats was 2.21 times higher than the prevalence of this type of tumour in FeLV‐negative cats (P = .036). Mediastinal lymphoma was more frequently observed in younger cats, and the prevalence of mediastinal tumours in these animals was 3.06 times higher than the prevalence of this tumour form in old cats (P = .0125). The present study indicates that retroviral infections still play an important role in the development of feline lymphomas in southern Brazil.     

An ovine pulmonary tumour of alveolar epithelial Type II cells

A small tumour was found at the periphery of the lung during routine necropsy of a 13-year-old Romney ewe. The tumour consisted of vacuolated, cuboidal cells which lined alveolar spaces without destroying them. Electron microscopy revealed numerous microvilli on the free surface of the cells and irregularly shaped osmiophilic inclusions within the vacuoles. No viral particles were found and the tumour was diagnosed as a well differentiated Type II pneumocyte adenocarcinoma of unknown aetiology.     

Peripheral washout phenomenon in an animal tumour model: comparison of dynamic magnetic resonance imaging using a small molecular contrast medium with histology*

The peripheral washout sign was first described in delayed dynamic contrast‐enhanced magnetic resonance imaging (DCE‐MRI) using a small molecular contrast medium in solid lesions of the human breast and liver. It was found to be 100% specific for malignant lesions and could therefore potentially be used as an additional noninvasive diagnostic tool differentiating malignant from benign lesions. The origin of this phenomenon has not yet been explained. The objective of this study was to translate the peripheral washout sign as seen in solid tumours in delayed DCE‐MRI in human onto an animal model for further assessment of DCE‐MRI characteristics and histological analysis. Small molecular contrast medium DCE‐MRI was performed over 42 min in experimental colon carcinoma grown subcutaneously in rats. Qualitative and quantitative analyses for evaluation of presence and characteristics of the peripheral washout sign were accomplished, defining four centripetally distributed tumour zones (central, intermediate, peripheral and marginal). One hundred per cent of the carcinomas demonstrated a peripheral washout sign in DCE‐MRI starting at 20 min after bolus injection. Histomorphological analysis was performed for tissue classification and evaluation of microvasculature. Quantitative analysis revealed different enhancement profiles of the four tumour zones. Histology indicated centripetally asymmetric vascularization and vascular endothelial growth factor VEGF/VEGF receptor 2 expression within the tumour tissue. Thus, peripheral washout sign can be translated to an animal model. However, comparison of small molecular contrast medium DCE‐MRI with histology revealed that histology alone does not explain the occurrence of the peripheral washout.     

Treatment of unresectable hepatocellular adenoma in dogs with transarterial iodized oil and chemotherapy with and without an embolic agent: A report of two cases

Transarterial iodized oil with chemotherapy was evaluated in two dogs with large, surgically unresectable hepatocellular adenoma. A single cycle of therapy was used in each dog. Chemoembolic mixtures varied: doxorubicin emulsified with iodized oil radiographic contrast (case 1), doxorubicin and mitomycin C emulsified with iodized oil radiographic contrast (case 2). In addition, dog 2 underwent arterial embolization with polyvinyl alcohol granules. Response was assessed by computed tomography at 1 and 3 months after treatment. Superselective catheterization of the hepatic arterial branch supplying the tumour was not achieved in either case. In the immediate post‐operative period, both dogs developed mild clinical signs that may have been consistent with post‐embolization syndrome, but neutropenia and reduced liver function were not observed. Tumour response was minimal: stable disease at 1 month and progressive disease at 3 months was observed in both cases.     

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.     

Fasting reduces the incidence of vincristine‐associated adverse events in dogs

Fasting has been shown to decrease chemotherapy‐associated adverse events (AEs), in part through insulin‐like growth factor (IGF‐1) reduction, and may induce a protective effect on normal cells during chemotherapy treatment in mice and people. The purpose of this study was to evaluate the effect of fasting on constitutional, bone marrow and gastrointestinal (GI) AEs, and serum glucose, IGF‐1 and insulin levels in dogs receiving vincristine. The study was a prospective, crossover clinical trial in tumour‐bearing dogs. Dogs were randomized to be fasted for 24 to 28 hours prior to and 6 hours following their first or second vincristine treatment, and fed normally for the alternate dose. A significant reduction in nausea, anorexia, lethargy and serum insulin was observed when dogs were fasted; however, no significant differences were found in other GI symptoms, neutrophil count, serum glucose or IGF‐1. Fasting prior to vincristine therapy is a safe and effective treatment modality that helped mitigate constitutional and GI AEs in tumour‐bearing dogs.     

What is your diagnosis? Perifemoral mass in a cow

Abstract: A 15‐year‐old female Simmental cross‐breed cow was presented to the Purdue University Veterinary Teaching Hospital for evaluation of a perifemoral soft tissue mass. Impression smears made from an excisional biopsy contained a population of pleomorphic mesenchymal cells with abundant, periodic acid–Schiff‐positive (PAS), intracytoplasmic granular material, and rare elongated multinucleated cells consistent with strap‐like cells. A second population of small round cells suggestive of lymphocytes or progenitor cells was also noted. A cytologic diagnosis of sarcoma was made, with rhabdomyosarcoma considered most likely based on the large amount of PAS‐positive material (presumed to be glycogen) and the rare strap‐like cells. Histopathologic sections contained an unencapsulated, densely cellular neoplasm composed of haphazardly arranged highly pleomorphic mesenchymal cells and a few small round cells. The mesenchymal cells were positive for vimentin, non‐specific muscle actin, and myoglobin, and negative for phosphotungstic acid‐hematoxylin, smooth muscle actin, and desmin. Glycogen granules were confirmed by transmission electron microscopy. A diagnosis of pleomorphic rhabdomyosarcoma was made. While cytologic findings may suggest rhabdomyosarcoma, cytologic features can be highly variable, and a definitive diagnosis usually requires cytochemical and immunohistochemical staining.