Neoplastic signatures: Comparative proteomics of canine hepatobiliary neuroendocrine tumors to normal niche tissue.

Hepatobiliary neuroendocrine neoplasms are rare cancers in humans and dogs. To date, no large-scale primary hepatobiliary neoplasm omics analyses exist in any species. This limits the development of diagnostic biomarkers and targeted therapeutics. Neuroendocrine cancers are a heterogenous group of neoplasms categorized by their tissue-of-origin. Because the anatomic niche of neuroendocrine neoplasms shapes tumor phenotype, we sought to compare the proteomes of 3 canine hepatobiliary neoplasms to normal hepatobiliary tissue and adrenal glands with the objective of identifying unique protein signatures. Protein was extracted from formalin-fixed paraffin-embedded samples and submitted for tandem mass spectroscopy. Thirty-two upregulated and 126 downregulated differentially expressed proteins were identified. Remarkably, 6 (19%) of the upregulated proteins are correlated to non-hepatobiliary neuroendocrine neoplasia and 16 (50%) are functionally annotated within the exosome cellular compartment key to neuroendocrine signaling. Twenty-six (21%) downregulated proteins are enriched in metabolic pathways consistent with alterations in cancer. These results suggests that characteristic neoplastic protein signatures can be gleaned from small data sets using a comparative proteomics approach.

Hyphema and secondary glaucoma as a presenting complaint in a dog with chronic lymphocytic leukemia.

A 5-year-old Pomeranian was diagnosed with anterior uveitis, hyphema, and secondary glaucoma OD. Concurrent retinal hemorrhage, perivascular sheathing, and papilledema were identified OS. Work-up identified small cell lymphocytosis (>900 × 109/L), anemia, and thrombocytopenia. The patient was diagnosed with B-cell chronic lymphocytic leukemia as a cause of the ocular findings.

Factors associated with successful passage of the American College of Veterinary Internal Medicine general examination.

BACKGROUND: Board certification relies on passing the American College of Veterinary Internal Medicine (ACVIM) general examination. Pass rates might depend on properties of residency training programs (RTP). HYPOTHESIS: We hypothesized that <4 weeks of dedicated study time, lack of board preparation lectures, status as a re-taker, and private practice RTP would result in lower pass rates of the ACVIM general examination. SUBJECTS: Two hundred forty-eight ACVIM general examinees. METHODS: Cross-sectional study. Examinees were surveyed using a Qualtrics survey over a 3-year period. Factors included: study weeks, on-call duty, board preparation lectures, academic or private practice program, and status as a re-taker. RESULTS: First-attempt examinees were more likely to pass (P < .0001, OR 5.12, 95% CI [2.53, 10.52]). For first-attempt examinees, on-call duty during study weeks resulted in a lower pass rate (P = .002, OR 0.31, 95% CI [0.16, 0.67]). General didactic and specific board-preparation lectures resulted in higher pass rates (P = .003, OR 3.08, 95% CI [1.44, 6.61]; P = .02, OR 3.04, 95% CI [1.20, 7.68]). Diplomate-led board-preparation lectures resulted in higher pass rates than resident-led (P = .007, OR 10.67, 95% CI [1.75, 64.91]). Using a mixed effect logistic model, predicted pass rates were highest with both lack of on-call duty and presence of didactic lectures (predicted pass rate 95%, 95% CI [0.87, 0.98]). CONCLUSIONS AND CLINICAL IMPORTANCE: To optimize pass rates, RTP should provide study time without on-call duty. Provision of didactic lectures and specific board-preparation lectures by diplomates assist in candidate preparation.

Pathology in Practice.

In collaboration with the American College of Veterinary Pathologists.

Feline mesothelioma: case report and review of cytologic, immunocytochemical, histopathologic, and immunohistochemical findings.

Mesotheliomas are uncommon neoplasms that arise from mesothelial cells in either the abdominal or thoracic cavities and are rarely diagnosed in cats. A 10-y-old spayed female domestic shorthair cat was presented to the Louisiana State University oncology service for evaluation of a large amount of abdominal effusion. Abdominal ultrasound identified a large mesenteric mass with numerous ill-defined nodules. An abdominocentesis was performed with cytologic and immunocytochemical findings consistent with a neoplastic effusion, with large clusters of epithelioid cells that exhibited strong cytoplasmic expression of pancytokeratin, vimentin, and Wilms tumor 1 antigens. Further testing was declined, and meloxicam was prescribed until the cat died 23 d after initial presentation. Upon postmortem examination, the omentum was contracted into a firm mass adhered to multiple organs and accompanied by numerous small white nodules throughout the abdominal cavity. On histopathology and immunohistochemistry, neoplastic cells were found throughout the abdominal cavity; 60-95% exhibited moderate-to-strong cytoplasmic immunoreactivity for cytokeratin, vimentin, and Wilms tumor 1 protein. The final diagnosis was an epithelioid mesothelioma. Our case illustrates the utility of cytology, immunocytochemistry, and its relation to histology and immunohistochemistry. We also reviewed the reported cases of feline mesothelioma.

Thyroid storm in a dog secondary to thyroid carcinoma.

OBJECTIVE: To describe the clinical presentation, clinical course, and management of a dog with thyroid storm (TS) secondary to a functional thyroid carcinoma. CASE SUMMARY: A 12-year-old neutered female Golden Retriever was evaluated for severe weight loss, hyperthermia, and tachycardia. The dog had a ventral neck mass and markedly increased thyroxine concentration. Cervical ultrasound showed a suspected left thyroid mass with invasion into the jugular vein. Despite aggressive therapy, the patient progressed to a clinical TS. Postmortem examination was supportive of the clinical diagnosis. NEW OR UNIQUE INFORMATION PROVIDED: To the authors' knowledge, this is the first report of TS in a dog.

Biochemical, functional, and histopathologic characterization of lomustine-induced liver injury in dogs.

OBJECTIVE: To characterize the biochemical, functional, and histopathologic changes associated with lomustine-induced liver injury in dogs. ANIMALS: I0 healthy purpose-bred sexually intact female hounds. PROCEDURES: Dogs were randomly assigned to receive lomustine (approx 75 mg/m2, PO, q 21 d for 5 doses) alone (n = 5) or with prednisone (approx 1.5 mg/kg, PO, q 24 h for 12 weeks; 5). For each dog, a CBC, serum biochemical analysis, liver function testing, urinalysis, and ultrasonographic examination of the liver with acquisition of liver biopsy specimens were performed before and at predetermined times during and after lomustine administration. Results were compared between dogs that did and did not receive prednisone. RESULTS: 7 of the I0 dogs developed clinical signs of liver failure. For all dogs, serum alanine aminotransferase (ALT) and alkaline phosphatase (ALP) activities, bile acid concentrations, and liver histologic score increased and hepatic reduced glutathione content decreased over time. Peak serum ALT (r = 0.79) and ALP (r = 0.90) activities and bile acid concentration (r = 0.68) were positively correlated with the final histologic score. Prednisone did not appear to have a protective effect on histologic score. CONCLUSIONS AND CLINICAL RELEVANCE: In dogs, liver enzyme activities, particularly ALT and ALP activities, should be closely monitored during lomustine treatment and acute increases in those activities may warrant discontinuation of lomustine to mitigate liver injury. Nonspecific ultrasonographic findings and abnormal increases in liver function tests were not detected until the onset of clinical liver failure. Glutathione depletion may have a role in lomustine-induced hepatopathy and warrants further investigation.

Invasive histiocytoma in the ear canal of a dog.

BACKGROUND: Cutaneous histiocytomas (CH) are derived from epidermal Langerhans cells. Single CH are generally associated with a good prognosis in dogs because most undergo spontaneous remission. However, aggressive behaviour and lymph node metastasis have been reported in a small number of dogs with single CH. OBJECTIVE: To describe the clinical presentation, treatment and disease progression of an aggressive CH located in the ear canal of a dog. ANIMAL: An 8-year-old intact male Rottweiler dog. METHODS AND MATERIALS: A unilateral ear canal mass was identified as a CH on routine haematoxylin and eosin stained samples. The diagnosis was confirmed by the demonstration of markers associated with Langerhans cells (Iba-1, E-cadherin and CD18) and the absence of markers associated with B cells (CD79a, CD20, Pax5), T cells (CD3), plasma cells (Mum-1) and macrophages (CD11d, CD204). RESULTS: A total ear canal ablation was performed, but tumour cells extended throughout the horizontal canal and to the deep surgical margin. Due to the locally invasive nature of the mass and incomplete excision, adjunctive chemotherapy with CCNU was pursued. No measurable local disease was appreciable at the time of the last treatment. At 250 days post-surgery the dog was euthanized owing to the development of multiple abdominal masses. No evidence of local tumour recurrence was noted. CONCLUSIONS AND CLINICAL IMPORTANCE: Although single CH are typically associated with benign behaviour, the mass in this dog demonstrated locally invasive behaviour. Cutaneous histiocytomas in the ear canals of dogs may represent a particularly aggressive variant of the condition.

Treatment of Exuberant Granulation Tissue in an Umbrella Cockatoo (Cacatua alba) with Strontium Radiation.

A 26-year-old female umbrella cockatoo (Cacatua alba) was presented for reoccurrence of a soft tissue mass extending from a fractured area of the rhinotheca. The mass was originally observed 12 years before, after unknown trauma. Histopathology after initial removal was consistent with inflammatory granulation tissue. The mass reoccurred 3 additional times in the same location despite surgical removal and cryogenic therapy. On the fourth surgical resection, strontium-90 radiotherapy was applied to the site immediately after the surgical procedure. No recurrence of the tissue mass from this location has been observed for almost 2 years. This case demonstrates the novel use of strontium radiotherapy to treat exuberant granulation tissue in a bird.

Myxosarcoma Associated with the Kidney in a Cat: Case Report.

A 12 yr old spayed female domestic shorthair with a history of lethargy, anorexia, and a pendulous abdomen was referred after a cranial abdominal mass was palpated on physical examination. Thoracic radiographs and an abdominal ultrasound revealed a mass associated with the kidney and moderate hemoperitoneum. Exploratory laparotomy revealed abdominal hemorrhage originating from a right renal mass that was adhered to the caudal vena cava. Following a right nephrectomy, histopathology diagnosed the mass as a perirenal/renal myxosarcoma. Based upon thoracic radiographs and abdominal ultrasound, the patient remains disease free at 14 mo postoperatively.

Treatment of leiomyosarcoma in a tiger (Panthera tigris) with stereotactic radiotherapy.

A 10-year-old male captive tiger (Panthera tigris) developed right-sided facial asymmetry and enlargement. Computed tomography revealed a destructive mass of the right maxillary bone with right nasal cavity involvement. Histopathology indicated a spindle cell sarcoma. A single fraction of 22 Gy using stereotactic radiotherapy was prescribed. After treatment, the facial conformation returned to normal and the tiger resumed normal behavior. Diagnostics 4 months later indicated severe metastatic disease. Humane euthanasia and necropsy were performed. This is the first case utilizing stereotactic radiotherapy for the treatment of cancer in a tiger.

Long-Term Survival and Glycemic Control with Toceranib Phosphate and Prednisone for a Metastatic Canine Insulinoma.

Canine insulinoma is a highly metastatic neoplasm that is associated with a guarded to poor prognosis in dogs with distant metastases. A median survival of 6 mo has been reported for dogs with metastatic insulinoma. The dog in this report, diagnosed with stage III pancreatic insulinoma, had long-term glycemic control with survival of over 24 mo while receiving prednisone and toceranib phosphate after partial pancreatectomy. Toceranib phosphate has been shown to be an efficacious therapy for canine mast cell tumors with increasing evidence that it may be beneficial in the medical management of neuroendocrine tumors.

Long-term clinical control of feline pancreatic carcinoma with toceranib phosphate.

An 11-year-old, spayed female, domestic shorthair cat was presented with a non-resectable abdominal mass diagnosed as carcinomatosis of pancreatic origin. Treatment with toceranib phosphate was started. Abdominal ultrasound approximately 1 year after diagnosis revealed progressive disease. The cat was humanely euthanized approximately 792 days after initial presentation due to progressive clinical signs.

Contrôle clinique à long terme du carcinome pancréatique félin avec le tocéranib phosphate. Un chatte commune domestique stérilisée âgée de 11 ans a été présentée avec une masse abdominale non résécable diagnostiquée comme une carcinomatose d'origine pancréatique. Le tocéranib phosphate a été administré. L'échographie abdominale environ 1 an après le diagnostic a révélé une maladie progressive. La chatte a été euthanasiée sans cruauté environ 792 jours après la présentation initiale en raison de signes cliniques progressifs.(Traduit par Isabelle Vallières).

Concurrent 5-fluorouracil and carboplatin for the treatment of canine carcinomas.

5-Fluorouracil (5-FU) is used in combination chemotherapy protocols for human head and neck cancer and other epithelial neoplasms. However, a paucity of literature describing use of this drug in veterinary oncology exists, likely due to previous reports of fatal neurotoxicity in both dogs and cats, mainly due to ingestion of human creams. The primary aim of this retrospective study was to report the safety of concurrent 5-FU and carboplatin in canine carcinomas. Secondarily, we aimed to look at the efficacy of the combination using overall response rate in treated dogs. Medical records were searched from 2007 to 2017 for dogs treated with both agents; 24 dogs met inclusion criteria. Carboplatin dosages ranged from 180 to 250 mg/m2 (median 200 mg/m2 ); 5-FU dosage was 150 mg/m2 . Fourteen dogs had myelosuppression, ranging from Grade I to asymptomatic Grade IV; thrombocytopenia was more common than neutropenia. Gastrointestinal upset was uncommon, with only seven dogs having Grade I or II nausea, vomiting or diarrhoea. No cases were hospitalized for any of the above toxicities. One dog had an episode of ataxia, which could not be differentiated between otitis and 5-FU neurotoxicity. This protocol is well tolerated. Response rate in the gross disease setting was 43% (three complete responses, three partial responses). Prospective analysis of this combination protocol, and potentially 5-FU with other platinum agents, is warranted in the treatment of canine carcinomas.

Cytologic comparison of the percentage of mast cells in lymph node aspirate samples from clinically normal dogs versus dogs with allergic dermatologic disease and dogs with cutaneous mast cell tumors.

OBJECTIVE To compare percentages of mast cells in lymph node (LN) aspirate samples from clinically normal dogs, dogs with allergic dermatologic disease (ADD), and dogs with cutaneous mast cell tumors (MCTs). DESIGN Prospective cross-sectional study. ANIMALS 20 healthy dogs (group 1), 20 dogs with ADD (group 2), and 20 dogs with an MCT on the head or limbs (group 3). PROCEDURES LN aspirate samples were obtained from easily accessible LNs in group 1, affected skin regions in group 2, and the likely draining LN or LNs of the MCT in group 3; the percentage of mast cells was manually determined for each LN. For group 3, LNs were cytologically categorized with a modified version of a published metastasis categorization scheme. RESULTS Median (range) percentage of mast cells in aspirate samples was 0% (0% to 0.1%) for group 1, 0.05% (0% to 0.55%) for group 2, and 0.4% (0% to 77.4%) for group 3. In group 3, 16 LNs (13 dogs) were palpably normal in size; 6 of these had evidence of possible or certain metastasis. Seven LNs (7 dogs) in group 3 were palpably enlarged, and 5 of these had evidence of certain metastasis. CONCLUSIONS AND CLINICAL RELEVANCE This study provided evidence to support the use of a uniform cytologic grading system to further define nodal metastasis in dogs with MCTs as well as estimates of the percentage of mast cells in LN aspirate samples for healthy dogs and dogs with ADD. Palpably normal LNs in dogs with cutaneous MCT may contain metastasis.

Primary frontal sinus squamous cell carcinoma in a dog treated with surgical excision.

An 8-year-old castrated male mixed breed dog was presented for a squamous cell carcinoma of the left frontal sinus. A partial craniectomy was performed and polytetrafluoroethylene mesh was placed over the craniectomy site. The dog recovered well with a good cosmetic outcome. Histopathology confirmed primary frontal sinus squamous cell carcinoma.

Carcinome squameux primaire du sinus frontal chez un chien traité par excision chirurgicale. Un chien castré de race croisée âgé de 8 ans a été présenté pour un carcinome squameux du sinus frontal gauche. Une craniectomie partielle a été réalisée et un tamis de polytétrafluoroéthylène a été placé sur le site de la craniectomie. Le chien s'est rétabli avec un bon résultat esthétique. L'histopathologie a confirmé un carcinome squameux primaire du sinus frontal.(Traduit par Isabelle Vallières).

SAFETY AND TOXICITY OF AN ACCELERATED COARSELY FRACTIONATED RADIATION PROTOCOL FOR TREATMENT OF APPENDICULAR OSTEOSARCOMA IN 14 DOGS: 10 GY × 2 FRACTIONS.

Coarsely fractionated radiation is commonly used as a method for pain control in dogs with appendicular osteosarcoma, however there is little published information on optimal protocols. The aim of this retrospective, descriptive study was to report safety and toxicity findings in a sample of dogs with appendicular osteosarcoma that had been treated with a radiation scheme of 10 Gy delivered over two consecutive days for a total of 20 Gy. Dogs were included in the study if they had osteosarcoma that was treated with the aforementioned protocol. Dogs were excluded if treated with the same protocol for any other bone tumor besides osteosarcoma or inadequate follow-up. Thirteen of the 14 patients received adjuvant therapy with pamidronate and a nonsteroidal anti-inflammatory. Nine dogs received adjuvant chemotherapy with carboplatin after radiation was complete. Within a median of 14 days, 92.8% of dogs subjectively had improved pain control. Median duration of response (DOR) was 80 days (range 20-365). The majority of patients developed VRTOG grade one toxicity, primarily alopecia. Five dogs (35.7%) developed pathologic fracture postradiation treatment. Timing of fracture was variable ranging from 24 to 250 days. This radiation protocol was well tolerated, with minimal toxicity, subjectively improved survival time, and had the benefit of being completed in two consecutive days.