Receptor Tyrosine Kinase Expression Profiles in Canine Cutaneous and Subcutaneous Mast Cell Tumors.

The receptor tyrosine kinase (RTK) KIT is a major focus of current research into canine mast cell tumors (MCTs). Little is known about the role of other RTKs, such as vascular endothelial growth factor receptors (VEGFRs) and platelet-derived growth factor receptors (PDGFRs). These RTKs are dysregulated in many human and animal cancers and are key regulators of tumor angiogenesis. The aims of this study were to assess the expression and activation (phosphorylation) status of KIT, VEGFR2, and PDGFR (α and ß) in canine MCTs and to examine associations with various clinical outcomes. c-KITmutational status and KIT cellular localization pattern were also evaluated for these tumors. Twenty-seven MCTs, consisting of 5 subcutaneous and 22 cutaneous tumors, from 25 dogs were evaluated. MCT biopsies, cultured mast cells, and skin from the surgical margin were analyzed through Western blotting. MCT biopsies were also used for KIT immunohistochemical labeling and polymerase chain reaction for c-KITmutational analysis. MCT had heterogeneous expression profiles for all 3 RTKs, which varied in intensity and activation status. Statistical analyses showed phosphorylated KIT, VEGFR2, and KIT cellular localization to be predictive of decreased survival time, disease-free interval, and increased metastatic rate. Expression of VEGFR2 and KIT diffuse cytoplasmic labeling were also significantly associated with increased rate of local recurrence. The results of the study show that phosphorylated KIT, KIT, VEGFR2, and PDGFRß, in addition to KIT localization, may be valuable prognostic determinants in MCTs and should be further studied to improve diagnostic and therapeutic modalities.

Outcome After Pneumonectomy in 17 Dogs and 10 Cats: A Veterinary Society of Surgical Oncology Case Series.

OBJECTIVE: To report the signalment, presenting clinical signs, surgical complications, histologic diagnosis, postoperative complications, and outcome of dogs and cats undergoing pneumonectomy. STUDY DESIGN: Retrospective case series; multicenter study. ANIMALS: Client-owned dogs (n=17) and cats (n=10). METHODS: Signalment, clinical signs, side affected, surgical data, preoperative diagnostic tests (including complete blood count, serum biochemistry, cytologic diagnosis, chest radiographs, and computed tomography), histologic diagnosis, surgical complications, adjunctive therapy, and date and cause of death were collected from records of dogs and cats that underwent pneumonectomy. Survival estimates and complication were assessed. RESULTS: Seventeen animals had a left-sided pneumonectomy performed (12 dogs, 5 cats) and 10 animals had a right-sided pneumonectomy (5 dogs, 5 cats). Fourteen animals were diagnosed with neoplasia (52%). The overall incidence of complications for dogs and cats were 76 and 80%, respectively, with major complications in 41 and 50%, respectively. Respiratory complications (persistent pleural effusion, oxygen dependence, persistent increased respiratory rate, or coughing) were the most frequent complications. No animals died or were euthanatized intraoperative or within the first 24 hours postoperative. One dog (6%) and 2 cats (20%) died, or were euthanatized in the first 2 weeks postoperative. CONCLUSION: Based on this case series, right and left pneumonectomy can be performed with low perioperative mortality in dogs and cats, with some animals experiencing prolonged survival.

Diagnosing the etiology of hypercalcemia in a dog: a case of primary hyperparathyroidism.

A 13-year-old spayed Labrador Retriever cross dog presented for polyuria and polydipsia. Serum total calcium, free calcium, and intact parathyroid hormone concentrations were elevated. Surgical exploration of the ventral neck revealed a grossly enlarged right external parathyroid gland. The histopathological diagnosis for the excised right parathyroid gland was an incompletely resected parathyroid carcinoma. Parathyroid carcinoma in the dog is an infrequent cause of hypercalcemia and primary hyperparathyroidism.

Diagnostic accuracy of contrast-enhanced computed tomography for assessment of mandibular and medial retropharyngeal lymph node metastasis in dogs with oral and nasal cancer.

The diagnostic accuracy of contrast-enhanced CT for detection of cervical lymph node metastasis in dogs is unknown. The purpose of this retrospective, observational, diagnostic accuracy study was to assess the efficacy of CT for detection of mandibular and medial retropharyngeal lymph node metastasis in dogs. Histopathology of dogs with cancer of the head, CT and bilateral mandibular and medial retropharyngeal lymphadenectomy was reviewed. A single radiologist measured lymph nodes to derive short axis width and long-short axis ratios. Two blinded radiologists separately assessed lymph node margins, attenuation and contrast enhancement and each provided a final subjective interpretation of each node site as benign or neoplastic. Where radiologists' opinions differed, a consensus was reached. Sensitivity, specificity and accuracy were calculated for mandibular and medial retropharyngeal sites. Agreement between radiologists was assessed. Fisher's exact test and the Kruskal-Wallis H-test were used to assess associations between variables. Forty-one primary tumours were recorded in 40 dogs. Metastasis to mandibular or retropharyngeal lymph nodes occurred in 16 out of 40 dogs (43/160 nodes). Agreement between radiologists was almost perfect for margination, attenuation and enhancement, strong for interpretation of mandibular lymph node metastasis, and weak for interpretation of medial retropharyngeal lymph node metastasis. Sensitivity of CT was 12.5% and 10.5%, specificity was 91.1% and 96.7%, and accuracy was 67.5% and 76.3% for mandibular and medial retropharyngeal lymph nodes respectively. No individual CT findings were predictive of nodal metastasis. Given the low sensitivity of CT, this modality cannot be relied upon alone for assessment of cervical lymph node metastasis in dogs.

Bilateral removal of the mandibular and medial retropharyngeal lymph nodes through a single ventral midline incision for staging of head and neck cancers in dogs: a description of surgical technique.

Currently, there is no standard protocol for removal of regional lymph nodes for the staging of head and neck cancers in dogs. Palpation and fine needle aspiration of mandibular lymph nodes are most commonly performed for staging of head and neck cancers. Although cytology is commonly performed for staging of head and neck, cancers histopathology is required for definitive lymph node staging. When regional lymph node biopsy is performed, mandibular lymph nodes are most commonly sampled due to their accessibility. The medial retropharyngeal lymph nodes may be the most relevant draining lymph node of the head and neck, but they are not routinely sampled due to their anatomic location medial to the salivary glands. The technique described here will allow for a standardized surgical approach for the efficient removal of both mandibular and medial retropharyngeal lymph nodes for staging of head and neck tumours via a single ventral midline approach.

Evaluation of Weight Change During Carboplatin Therapy in Dogs With Appendicular Osteosarcoma.

BACKGROUND: The prevalence of cancer cachexia in veterinary medicine has not been studied widely, and as of yet, no definitive diagnostic criteria effectively assess this syndrome in veterinary patients. OBJECTIVES: (1) To determine the patterns of weight change in dogs with appendicular osteosarcoma treated with amputation and single-agent carboplatin during the course of adjuvant chemotherapy; and (2) to determine whether postoperative weight change is a negative prognostic indicator for survival time in dogs with osteosarcoma. ANIMALS: Eighty-eight dogs diagnosed with appendicular osteosarcoma. Animals were accrued from 3 veterinary teaching hospitals. METHODS: Retrospective, multi-institutional study. Dogs diagnosed with appendicular osteosarcoma and treated with limb amputation followed by a minimum of 4 doses of single-agent carboplatin were included. Data analyzed in each patient included signalment, tumor site, preoperative serum alkaline phosphatase activity (ALP), and body weight (kg) at each carboplatin treatment. RESULTS: A slight increase in weight occurred over the course of chemotherapy, but this change was not statistically significant. Weight change did not have a significant effect on survival. Institution, patient sex, and serum ALP activity did not have a significant effect on survival. CONCLUSIONS AND CLINICAL IMPORTANCE: Weight change was not a prognostic factor in these dogs, and weight loss alone may not be a suitable method of determining cancer cachexia in dogs with appendicular osteosarcoma.

Outcome of definitive fractionated radiation followed by exenteration of the nasal cavity in dogs with sinonasal neoplasia: 16 cases.

Local control is a major challenge in treating canine nasal tumours. Surgical cytoreduction prior to radiation therapy has not been shown to offer a survival advantage. Only one study has previously evaluated the outcome when surgery is performed after radiation, which demonstrated an improved survival time compared with radiation alone. The purpose of this study was to investigate the outcome of surgery after definitive radiation on survival times in dogs with sinonasal tumours. Medical records were retrospectively reviewed for dogs with nasal tumours that received definitive radiation followed by surgery. Information obtained from medical record review included signalment, diagnosis, treatment and outcome. The median survival time was 457 days. No long-term side effects were observed. These findings suggest that exenteration of the nasal cavity following definitive radiation for treatment of dogs with nasal tumours is well-tolerated and provides a similar survival duration to previous reports of radiation alone.

Comparison of concurrent imaging modalities for staging of dogs with appendicular primary bone tumours.

This study assessed the use of whole body computed tomography (CT) for the evaluation of metastasis in dogs with primary appendicular bone tumours compared to long bone survey radiography, bone scintigraphy and thoracic radiographs. Fifteen dogs were included in this pilot study. A construct reference standard was used for detection of bone metastasis, and negative thoracic radiographs were compared against CT. Definitive lesions were only identified on bone scintigraphy. Not all lesions agreed with the construct reference standard. No definitive lesions were identified on survey radiographs or CT. Lesions were identified on thoracic CT that were not visible radiographically. Equivocal ground glass pulmonary lesions progressed in three of four cases. Whole body CT was not a suitable alternative to bone scintigraphy; however, it was useful as an adjunctive diagnostic modality. Pulmonary lesions were visible on CT that were not seen radiographically and ground glass pulmonary lesions in dogs should be considered suspicious for metastasis.

Lameness in a dog caused by thoracic wall invasion by a pulmonary neoplasm.

A 12-year-old fox-terrier dog presented with forelimb lameness of 3-weeks duration. Ultrasonography revealed a mass within the thoracic wall and osteolysis of the left third rib. A squamous cell carcinoma was diagnosed by cytological examination of an ultrasound-guided fine needle aspirate of this mass. As a result of the diagnosis of neoplasia, the dog was euthanatized. Necropsy revealed a solitary expansile mass within the left cranial lung lobe, and a mass within the adjacent thoracic wall. Thickening of the pleura between the two masses was visible, although adhesions were not present. Histology of both masses revealed a well-differentiated squamous cell carcinoma. To the authors' knowledge, this is the first detailed description of direct invasion of the thoracic wall by a canine lung tumour.