Insulin-secreting tumor: diagnosis and medical and surgical management in 55 dogs

Insulin-secreting tumor of the pancreas was diagnosed in 55 dogs. Diagnosis was based mainly on the increase of serum insulin concentrations in the presence of hypoglycemia. The use of the amended insulin/glucose ratio to diagnose the tumor, although providing less false-negative results than did increased serum insulin concentrations alone, appeared less specific and gave false-positive results in dogs without insulin-secreting tumors. Management of the disease included surgical intervention alone (26 dogs), surgery plus medical management with diazoxide (14 dogs), and medical management with diazoxide alone (4 dogs). Eleven dogs were euthanatized at the time of diagnosis. Diazoxide therapy controlled hypoglycemia in about 70% of the dogs.     

Immunocytochemistry of normal pancreatic islets and spontaneous islet cell tumors in dogs

Immunocytochemical studies of the distribution of glucagon, gastrin, insulin, and somatostatin in normal canine pancreatic islets and 20 canine islet cell tumors were done using the peroxidase-anti-peroxidase (PAP) technique. In the normal adult canine pancreas, islets typically consisted of clusters of 20-30 cells, but smaller foci and even individual cells were identified. Alpha cells (glucagon) were often peripherally located, beta cells (insulin) were centrally located and most numerous, and delta cells (somatostatin) were the least numerous and randomly located. Both juvenile and adult canine pancreases did not stain for gastrin. Of the 20 tumors examined, 18 had positive immunoreactivity for insulin, nine for glucagon, 14 for somatostatin, and one for gastrin. Two tumors were uninterpretable due to autolysis. Three tumors were pure insulinomas, but no pure somatostatinomas, glucagonomas, or gastrinomas were identified. Most tumors and metastases had mixed positive immunoreactivity; one neoplastic cell type predominated with lesser numbers of other cell types. Metastatic sites (liver and lymph node) stained for insulin and somatostatin, only. Foci of non-neoplastic islet cell tissue (nesidioblastosis), often located at the pancreatic-mesenteric junction, stained strongly positive for insulin, glucagon, and somatostatin but not for gastrin. The tumor staining pattern did not consistently correlate with tumor function, as determined by blood glucose and serum insulin assays. The PAP technique works well on paraffin-embedded, formalin-fixed tissue using rabbit or guinea pig antisera as the primary antibody. Staining occurred on sections of paraffin blocks stored for up to 7 years.     

Retrobulbar tumors in dogs and cats: 25 cases

Twenty-five cases of retrobulbar tumors are presented and discussed. Affected animals were dogs and cats (average 10.7 years). No breed or sex predisposition was noted. The most common clinical signs were exophthalmos (84%), conjunctival hyperemia (40%), protrusion of the nictitating membrane (28%), exposure keratitis (20%) and fundus abnormalities (20%). Diagnostic tools included fine needle aspiration, radiography, ultrasonography, computed tomography and histology. Surgical treatment by orbitotomy or exenteration was combined with chemotherapy and radiotherapy in some cases. The prognosis was poor with low survival times: 1 month in cats, and 10 months in dogs, with a high rate of euthanasia (35%) at the time of diagnosis.     

Streptozocin for treatment of pancreatic islet cell tumors in dogs: 17 cases (1989-1999)

OBJECTIVE: To determine toxic effects of streptozocin given in combination with a diuresis protocol in dogs and establish whether streptozocin is efficacious in treatment of pancreatic islet cell tumors in dogs. DESIGN: Retrospective study. ANIMALS: 17 dogs. PROCEDURE: Medical records were reviewed to obtain information regarding signalment, tumor stage and staging tests performed, number of streptozocin treatments, adverse effects, results of biochemical and hematologic monitoring during streptozocin treatment, tumor dimensions, duration of normoglycemia, and date of death, when applicable. Dogs were compared with a historical control group of 15 dogs treated surgically and medically. RESULTS: 58 treatments were administered to the 17 dogs. Only 1 dog developed azotemia. Serum alanine aminotransferase activity increased in some dogs but decreased when treatment was discontinued. Hematologic toxicoses were rare. Vomiting during administration was uncommon but occasionally severe. Two dogs developed diabetes mellitus after receiving 5 doses. Median duration of normoglycemia for 14 dogs with stage-II or -III insulinoma treated with streptozocin was 163 days (95% confidence interval, 16 to 309 days), which was not significantly different from that for the control dogs (90 days; 95% confidence interval, 0 to 426 days). Two dogs had rapid resolution of paraneoplastic peripheral neuropathy, and 2 others had measurable reductions in tumor size. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that streptozocin can be administered safely to dogs at a dosage of 500 mg/m2, IV, every 3 weeks when combined with a protocol for induction of diuresis and may be efficacious in the treatment of dogs with metastatic pancreatic islet cell tumors.     

Correlation between the clinical course of granulomatous meningoencephalomyelitis in dogs and the extent of mast cell infiltration

The data from 20 dogs with histopathologically confirmed granulomatous meningoencephalomyelitis were reviewed in an attempt to identify clinical signs and morphological and cellular parameters, particularly the infiltration of mast cells, which might be associated with the clinical course of the disease. Thirteen of the dogs had the acute form of the disease and seven had the chronic form. Young to middle-aged, small breed female dogs were over-represented. Central vestibular signs were observed in six of the dogs with the acute disease. Analyses of cerebrospinal fluid revealed moderate to severe pleocytosis and high protein concentrations in all cases. Histopathological investigations revealed disseminated perivascular cuffs, large confluent granulomata, tissue necrosis, infiltration with neutrophils and a large number of mitotic cells in the dogs with either of the clinical forms of the disease. Tryptase-positive mast cells were observed in all the cases, but there were significantly larger numbers in the dogs with the acute form.     

The diagnosis and prognosis of synovial tumors in dogs: 35 cases

Although synovial cell sarcoma is reported to be the most common neoplasm of the canine synovium, this retrospective study of 35 canine synovial tumors found that the majority were of histiocytic origin. Five (14.3%) synovial cell sarcomas were identified by positive immunohistochemical staining with antibodies to cytokeratin. Eighteen (51.4%) histiocytic sarcomas were identified by cell morphology and immunohistochemical staining with antibodies to CD18. Six (17.1%) synovial myxomas were identified by histologic pattern. The remaining six (17.1%) synovial tumors represented a variety of sarcomas, including two malignant fibrous histiocytomas (actin positive), one fibrosarcoma, one chondrosarcoma, and two undifferentiated sarcomas. Rottweilers were overrepresented in the histiocytic sarcoma category and Doberman Pinschers were overrepresented in the synovial myxoma category. The average survival time was 31.8 months for dogs with synovial cell sarcoma, 5.3 months for dogs with histiocytic sarcoma, 30.7 months for dogs with synovial myxoma, and 3.5 months for dogs with other sarcomas. Among the dogs with follow-up information available, metastatic disease was detected in 25% of dogs with synovial cell sarcoma, in 91% of dogs with histiocytic sarcoma, in none of the dogs with synovial myxoma, and in 100% of dogs with other sarcomas. Immunohistochemical staining for cytokeratin, CD18, and smooth muscle actin is recommended to make the diagnosis and thereby predict the behavior of synovial tumors in dogs.     

A phase II clinical trial of vinorelbine in dogs with cutaneous mast cell tumors

Background: Few effective drugs are available to treat dogs with locally aggressive or metastatic mast cell disease.
Hypothesis: Vinorelbine, a semisynthetic derivative of vinblastine, is an effective drug for the treatment of canine mast cell tumors (MCT).
Animals: Twenty-four dogs with cutaneous MCT.
Methods: Dogs with at least 1 measurable, cytologically confirmed, and previously untreated cutaneous MCT received a single treatment with vinorelbine at the previously established dosage of 15 mg/m² IV. Tumor measurements and CBC were evaluated before and 7 days after treatment. Adverse events were graded according to Veterinary Cooperative Oncology Group (VCOG) guidelines.
Statistics: Data were accrued in accordance with a Simon's 2-stage design with a noninteresting response rate of .05, a target response of .25, and α and β values of .10.
Results: Three of 24 dogs (13%) had a response to treatment, including 1 measurable complete response and 1 measurable partial response. The 3rd dog had microscopic complete response to treatment with stable measurable disease. Twenty other dogs (83%) had stable disease and 1 dog (4%) had progressive disease. Neutropenia occurred in 13 dogs (54%) (grade 1, n = 4; grade 3, n = 6; grade 4, n = 3). Gastrointestinal toxicity occurred in 11 dogs (46%) (anorexia: grade 1, n = 3; grade 2, n = 1; grade 3, n = 1; diarrhea: grade 1, n = 2; grade 3, n = 1; vomiting: grade 1, n = 5; grade 3, n = 1).
Conclusions and Clinical Importance: Vinorelbine was associated with an overall response rate of 13% and a high prevalence of neutropenia. Additional studies are indicated to determine if repeated dosing of vinorelbine or combination of vinorelbine with other drugs increases the observed biologic activity against canine MCT.     

Combination vinblastine and palladia for high-grade and metastatic mast cell tumors in dogs

High-grade and metastatic canine mast cell tumors carry a guarded prognosis because of their unpredictable biologic behavior. An ideal chemotherapy regime is yet to be established. The aim of this study was to review the efficacy and toxicity of combination vinblastine and toceranib for high-grade and metastatic mast cell tumors. Twenty-eight dogs were categorized with either high-grade, lymph node metastasis or Stage IV disease. Demographics, disease, and treatment variables were compared between categories (Kruskal-Wallis test for continuous data and Fisher’s Exact test for categorical data). Survival times and progression-free intervals (PFI) were calculated and compared between groups (log rank test). The PFI was 310 d [95% confidence interval (CI): 155 to 1425] and overall survival was 373 d (95% CI: 226 to 1219). There was no difference between disease categories for PFI (P = 0.9) or survival (P = 0.5). The protocol was well-tolerated with increased liver enzyme activity and gastrointestinal toxicity most frequently observed. Progression-free intervals and survival times were similar in dogs with high-grade, metastatic and Stage IV disease.     

Mast cell tumors of the gastrointestinal tract in 39 dogs

Mast cell tumors (MCTs) of gastrointestinal origin that had been surgically removed from 39 dogs were examined to evaluate their pathologic features. Miniature breeds, especially Maltese, were most frequently affected. The average age of affected dogs was 9.7 +/- 2.6 years. No sex difference was apparent. The most frequently affected sites were in the upper digestive tract, and the prognosis was very poor. Grossly, the gastrointestinal wall was prominently thickened, and the lumen of the affected gut was usually narrowed. Microscopically, there was diffuse transmural invasion of round to pleomorphic tumor cells. Tumor cells had moderate to abundant cytoplasm, round to ovoid nuclei with scattered chromatin, and mitotic figures. Fibrous stroma was observed in about half of the tumors. There was variable infiltration of eosinophils. In all tumors, cytoplasmic granules showed weak metachromasia, but the number of granules was very small. Immunohistochemical staining for c-kit and mast cell tryptase was positive in 77% and 62% of tumors, respectively. All tumors were positive for at least two of these markers. Immunohistochemical staining for p53 was positive in 13% of the tumors. Reactivity for staining markers and p53 was unrelated to cell pleomorphism, vessel invasion, or survival time. Gastrointestinal MCTs have histologic and immunohistochemical features completely different from those of other primary or metastatic gastrointestinal tumors. The combination of immunostaining for mast cell tryptase and c-kit and histochemical staining for metachromasia appears to be a powerful tool for the diagnosis of gastrointestinal MCTs.     

Pancreatic islet cell adenocarcinoma: clinical and diagnostic features of six cases.

The clinicopathologic aspects of pancreatic islet cell adenocarcinoma in 6 dogs were compared. Diagnosis was based on insulin-glucose ratios in 5 dogs. Surgical excision of the tumor resulted in absence of clinical signs for at least 1 year in 3 dogs.     

Brucella suis in three dogs: presentation,diagnosis and clinical management

Brucella suis is an emerging, zoonotic disease predominantly affecting dogs and humans that engage in feral pig hunting in Australia and other countries. Although B. suis infection in dogs shares some clinical similarities to the host-adapted species (B. canis), B. suis remains an incompletely understood pathogen in dogs with limited published data on its pathogenesis and clinical features. This case series describes the presentations, diagnosis, and clinical management of B. suis infection in three dogs: (1) a bitch with dystocia, abortion and mastitis; (2) an entire male dog with septic arthritis and presumptive osteomyelitis; and (3) a castrated male dog with lymphadenitis. Unique features of these cases are reported including the first documented detection of B. suis from milk and isolation from lymph nodes of canine patients, as well as the follow-up of pups born to a B. suis-infected bitch. Consistent with previous reports, all three dogs showed a favourable clinical response to combination antibiotic therapy with rifampicin and doxycycline. Individually tailored drug regimens were required based on the clinical presentation and other factors, including owner expectations and compliance with therapy as well as a zoonotic risk assessment (generally considered low, except around time of whelping). The authors include their recommendations for the clinical management of dogs that are at-risk or seropositive for B. suis with or without clinical signs or laboratory-confirmed infection.     

Canine meibometry: establishing baseline values for meibomian gland secretions in dogs

Meibomian lipid secretions are essential in preventing tear evaporation. Disorders of the meibomian glands may therefore play an important role in the pathogenesis of some forms of keratoconjunctivitis sicca (KCS). Until now, meibomian lipid secretions have never been quantitatively evaluated in dogs. With the aim of establishing baseline values of canine meibomian lipid secretions, meibometry was conducted in 42 healthy dogs, 16 of which were Miniature Schnauzers. The mean meibomium level in 84 eyes of the 42 dogs was 179+/-60 Meibometer units. Age, gender and side did not affect the results. However, meibomium levels were significantly lower in the Miniature Schnauzers, a breed that is susceptible to KCS, compared to other breeds. This report demonstrates that meibometry is a simple and minimally invasive technique that may be readily used in conscious dogs to quantify meibomian gland secretions and explicate tear film dynamics in normal and dry canine eyes.     

Angiolipomatous tumors in dogs and a cat

Variants of lipoma are uncommon, although fibrolipoma and infiltrative lipoma have been well documented. This report describes two cases of rare angiolipoma in dogs and the first documentation of angiofibrolipoma and infiltrating angiolipoma in a cat and a dog, respectively. Tumors were solitary, and most were located on the thorax of middle-aged patients. Angiolipomas were composed of mature adipose tissue mixed with variable numbers of blood vessels. In addition to the adipose and vascular components, the angiofibrolipoma contained bundles of collagenous connective tissue. The infiltrative angiolipoma had a primary mass external to the muscle and was histologically similar to a mixed intramuscular hemangioma that was confined to the muscle. Both disrupted bundles of striated muscle and were associated with segmental degeneration and loss of myofibers.     

Clinicopathological features and outcome for dogs with mast cell tumors and bone marrow involvement

BACKGROUND: Mast cell tumors (MCTs) with bone marrow (BM) involvement are poorly documented in dogs and are associated with a poor prognosis. Successful treatment strategies have not been described. HYPOTHESIS: Clinicopathologic findings of affected dogs are not specific. Administration of lomustine or imatinib is beneficial. ANIMALS: Fourteen dogs with MCT and BM involvement. METHODS: Clinical and laboratory evaluations were performed in each dog on admission and during follow-up. All dogs received prednisone. Additionally, 8 dogs received lomustine and 3 dogs received imatinib. Imatinib was administered if tumor-associated tyrosine kinase KIT was aberrant. RESULTS: On admission, 11 dogs had a single cutaneous nodule and 3 dogs had multiple nodules. Involvement of regional lymph nodes, liver, or spleen was observed in each dog. BM infiltration with mast cells (MCs) was observed in all dogs. On CBC, nonregenerative anemia, leukopenia, or thrombocytopenia was common. Four dogs had circulating MCs. Increased alkaline phosphatase or alanine transferase activity was observed in 12 and 10 dogs, respectively. Treatment with lomustine induced partial remission in 1 of 8 dogs. Median survival time was 43 days (range, 14-57). Dogs on imatinib experienced complete remission. Two dogs survived for 117 and 159 days, and the third was alive after 75 days. Dogs treated symptomatically did not improve and were euthanized after 1, 14, and 32 days. CONCLUSIONS AND CLINICAL IMPORTANCE: A combination of clinical and laboratory evaluation helps in identifying dogs with MCT and BM infiltration. Administration of lomustine is not helpful in affected dogs. The beneficial effect of imatinib warrants further investigation.