Mucus Retention Cyst of the Soft Palate in a Dog.

A 10 yr old 6.6 kg (14.5 lb) castrated male Chihuahua was referred to the Alta Vista Animal Hospital for evaluation of a mass of the soft palate. The cystic structure was bluntly dissected from the soft palate submucosal tissue, and the dog recovered from surgery and anesthesia without complication. Histopathology revealed salivary tissue with a large multiloculated cyst lined by a single layer of cystic and dilated cuboidal epithelium. Follow up 7 mo after surgery revealed complete resolution of clinical signs with no evidence of local recurrence. To the authors' knowledge, this is the first confirmed report of a mucus retention cyst in a dog.

Genomic analysis across 53 canine cancer types reveals novel mutations and high clinical actionability potential.

A genomic understanding of the oncogenic processes and individual variability of human cancer has steadily fueled improvement in patient outcomes over the past 20 years. Mutations within tumour tissues are routinely assessed through clinical genomic diagnostic assays by academic and commercial laboratories to facilitate diagnosis, prognosis and effective treatment stratification. The application of genomics has unveiled a wealth of mutation-based biomarkers in canine cancers, suggesting that the transformative principles that have revolutionized human cancer medicine can be brought to bear in veterinary oncology. To advance clinical genomics and genomics-guided medicine in canine oncology, we have developed and validated a canine cancer next-generation sequencing gene panel for the identification of multiple mutation types in clinical specimens. With this panel, we examined the genomic landscapes of 828 tumours from 813 dogs, spanning 53 cancer types. We identified 7856 alterations, encompassing copy number variants, single nucleotide variants, indels and internal tandem duplications. Additionally, we evaluated the clinical utility of these alterations by incorporating a biomarker framework from comprehensive curation of primary canine literature and inferences from human cancer genomic biomarker literature and clinical diagnostics. Remarkably, nearly 90% of the cases exhibited mutations with diagnostic, prognostic or therapeutic implications. Our work represents a thorough assessment of genomic landscapes in a large cohort of canine cancers, the first of its kind for its comprehensive inclusion of multiple mutation types and structured annotation of biomarkers, demonstrating the clinical potential of leveraging mutation-based biomarkers in veterinary oncology.

HES1, a target of Notch signaling, is elevated in canine osteosarcoma, but reduced in the most aggressive tumors.

BACKGROUND: Hairy and enhancer of split 1 (HES1), a basic helix-loop-helix transcriptional repressor, is a downstream target of Notch signaling. Notch signaling and HES1 expression have been linked to growth and survival in a variety of human cancer types and have been associated with increased metastasis and invasiveness in human osteosarcoma cell lines. Osteosarcoma (OSA) is an aggressive cancer demonstrating both high metastatic rate and chemotherapeutic resistance. The current study examined expression of Notch signaling mediators in primary canine OSA tumors and canine and human osteosarcoma cell lines to assess their role in OSA development and progression. RESULTS: Reverse transcriptase - quantitative PCR (RT-qPCR) was utilized to quantify HES1, HEY1, NOTCH1 and NOTCH2 gene expression in matched tumor and normal metaphyseal bone samples taken from dogs treated for appendicular OSA at the Colorado State University Veterinary Teaching Hospital. Gene expression was also assessed in tumors from dogs with a disease free interval (DFI) of <100 days compared to those with a DFI > 300 days following treatment with surgical amputation followed by standard chemotherapy. Immunohistochemistry was performed to confirm expression of HES1. Data from RT-qPCR and immunohistochemical (IHC) experiments were analyzed using REST2009 software and survival analysis based on IHC expression employed the Kaplan-Meier method and log rank analysis. Unbiased clustered images were generated from gene array analysis data for Notch/HES1 associated genes. Gene array analysis of Notch/HES1 associated genes suggested alterations in the Notch signaling pathway may contribute to the development of canine OSA. HES1 mRNA expression was elevated in tumor samples relative to normal bone, but decreased in tumor samples from dogs with a DFI < 100 days relative to those with a DFI > 300 days. NOTCH2 and HEY1 mRNA expression was also elevated in tumors relative to normal bone, but was not differentially expressed between the DFI tumor groups. Survival analysis confirmed an association between decreased HES1 immunosignal and shorter DFI. CONCLUSIONS: Our findings suggest that activation of Notch signaling occurs and may contribute to the development of canine OSA. However, association of low HES1 expression and shorter DFI suggests that mechanisms that do not alter HES1 expression may drive the most aggressive tumors.

Adrenocortical carcinoma in a dog with incomplete excision managed long-term with metastasectomy alone.

A 10 yr old bichon frise presented with a 3 mo history of polyuria, polydipsia, and hind limb weakness. Serum biochemistry revealed persistent hypokalemia. A left adrenal gland mass with right adrenal atrophy was detected ultrasonographically. Basal serum cortisol concentration was at the low end of normal (30 nmol/L; reference range, 30-140 nmol/L) and adrenocorticotropic hormone (ACTH)-stimulated cortisol concentration was low (199 nmol/L; reference range, 220-470 nmol/L). Basal serum 17-α-OH progesterone concentration was also low (0.03 ng/mL; reference range, 0.06-0.30 ng/mL), but the aldosterone concentration 2 hr after the ACTH stimulation was elevated (> 3,000 pmol/L; reference range, 197-2,103 pmol/L). A left adrenalectomy and nephrectomy were performed. Histopathology revealed an adrenocortical zona glomerulosa carcinoma. Surgical excision was considered incomplete; however, clinical signs resolved. Two years later, basal and ACTH-stimulated aldosterone concentrations were elevated. Computed tomography demonstrated a mass effect in the liver. The left lateral and left medial hepatic lobes were removed. Histopathology confirmed metastatic endocrine carcinoma. The patient was stable 1,353 days postsurgically (when this report was prepared). This is the first case report of a metastatic adrenal carcinoma that was successfully managed surgically for > 3 yr.

Pathology in Practice.

In collaboration with the American College of Veterinary Pathologists.

Multicystic bone disease (Gorham-Stout syndrome) in a spider monkey (Ateles geoffroyi ).

BACKGROUND: In April 2000, a 2.5-year-old pet female Geoffroyi's spider monkey presented for reduced activity, a subdued demeanor, and boney enlargement involving both radii. METHODS: On further examination, polyostotic bone cysts were identified involving many of the tubular bones and were identified radiographically. Microscopic examination of a bone biopsy revealed hemorrhage and other characteristics typical of an aneurysmal bone cyst. In addition, excessive osteoclasia was noted, in association with fibrotic areas rather than with Howship's lacunae as expected from a growing animal. RESULTS: These findings were consistent with Gorham-Stout syndrome, a rare condition reported previously in ∼175 human cases and in a dog at necropsy. The diet history and further testing suggested a negative calcium balance. Treatment included the administration of bis-phosphonates, which appeared to bring about marked improvement. Almost 8 years later (November 2008), radiographs were again taken and suggested some resolution of bone cysts, primarily those in the legs. CONCLUSIONS: This represents the first reported case and a potential therapy for this rare condition in a non-human primate.

Retention of dinoprostone vaginal insert beyond 12 hours for induction of labor.

We evaluate the likelihood of cesarean delivery and identify risks of retaining a sustained-release dinoprostone vaginal insert beyond 12 hours. In a secondary analysis of outcomes, data were collected during a large, randomized trial comparing different sustained-release prostaglandin vaginal inserts for labor induction. Outcomes were compared between cases in whom the dinoprostone insert was removed early (within 12 hours) or late (12 to 24 hours). A total of 431 subjects had the dinoprostone vaginal insert in place for 12 to 24 hours ( N = 226, 52.4%) or within 12 hours ( N = 205, 47.6%). Insert removal for labor complications was less frequent in the late group than in the early group (5.8% versus 21.5%; P ≤ 0.001). Abnormal uterine contractility patterns were less common in the late than early group (25.2% versus 37.6%; P = 0.03). Rates of cesarean delivery during the first hospitalization were similar for late and early groups (25.0% versus 29.2%; P = 0.33). Percentages of infants requiring immediate attention or intensive care were low and similar between groups. Sustained-release intravaginal dinoprostone left in place beyond 12 hours did not increase the risks of intrapartum complications, cesarean delivery, or immediate adverse neonatal events.

Use of a Dacron shape-memory intravascular coil to achieve slow, progressive occlusion of the jugular vein in dogs.

OBJECTIVE: To investigate the ability of shape memory Dacron polymer vascular coils to induce the complete, gradual occlusion of the canine jugular vein. STUDY DESIGN: Observational pilot study. ANIMALS: Nine purpose-bred dogs. METHODS: Eighteen coils were deployed in nine dogs using fluoroscopic-guided percutaneous transvenous coil implantation. Individual coil formulations varied around a Dacron polymer base. Jugular vein diameter, percent vessel occlusion, and thrombus echogenicity were monitored at weekly intervals using ultrasonography. Affected jugular veins were harvested at 6 weeks post-implantation and histopathological analysis was performed to assess adventitial fibrosis, intimal layer thickening, and inflammation. RESULTS: Ten coils migrated from the jugular veins to the pulmonary vasculature within 0-2 weeks following implantation. Three jugular veins achieved at least 90% occlusion at six weeks. Histopathology of these jugular veins revealed marked perivascular thickening and fibrovascular proliferation, increased infiltration of macrophages, neutrophils and lymphocytes, and abundant fibroplasia. CONCLUSIONS: Complete, gradual occlusion of a jugular vein was achieved in three dogs. Significant vessel wall reaction and inflammation can induce gradual vessel occlusion when a Dacron coil remains implanted within the jugular vein. Dacron polymer coils could be a feasible treatment option for the gradual occlusion of congenital portosystemic shunts in dogs using minimally invasive, percutaneous transvenous implantation.

Radiography, 99mTc-HDP, and 111In labeled vitamin B12 SPECT of canine osteosarcoma: a comparative study.

The objective of this article was to compare radiography, planar bone scintigraphy, and single-photon emission computed tomography (SPECT) to determine the size of osteosarcomas in long bones of dogs. Ten dogs with osteosarcoma in six radii, two humeri, one tibia, and one ulna were evaluated. Macroslides, mediolateral radiographs, planar scintigrams, and sagittal images from SPECT scans were used to obtain measurements. On the scintigraphic images, the edges of the tumor were established using the activity profile imaging tool. The radiographic magnification was factored. The mean percentage of tumor size overestimation was 9.29% on mediolateral radiographs, 5.35% on planar scintigrams, and 33.25% on SPECT images. The correlation coefficient adjusted for sample size was significantly higher (P<0.01) for technetium 99m ((99m)Tc) hydroxyethylene diphosphonate (HDP) (75.5%) and radiography (61.3%) compared with indium 111-vitamin B(12) (28.3%). The correlation coefficient for (99m)Tc-HDP was higher than that obtained for radiographs; however, statistical difference between the two variables was not demonstrated (P>0.05). (99m)Tc bone scan is a good estimator of intramedullary size of osteosarcoma in long bones when the activity profile tool to determine the margin of the tumor is used.

Nasal hydropulsion: a novel tumor biopsy technique.

Intranasal tumors of dogs and cats pose a diagnostic and therapeutic challenge for small animal practitioners. Multiple nasal biopsy techniques have been described in the past. This report describes a simplified flushing technique to biopsy and debulk nasal tumors, which often also results in immediate clinical relief for the patient. Based on the results of this retrospective study, the authors recommend high-pressure saline hydropulsion as a minimally invasive diagnostic, and potentially therapeutic, technique for nasal tumors in dogs and cats.

A randomised placebo-controlled multicentre trial of intravenous semapimod HCl for moderate to severe Crohn's disease.

OBJECTIVE: Semapimod, a small molecule known to inhibit proinflammatory cytokine activity, was studied to determine the optimal dose necessary to achieve a response in patients with moderate to severe Crohn's disease (CD). METHODS: A randomised, double-blind, placebo-controlled trial (CD04) was carried out followed by an open-label extension study (CD05). The trial was conducted in international multicentre outpatient clinics and included patients with moderate to severe CD (Crohn's Disease Activity Index (CDAI) 250-400). Placebo was administered for 3 days; 60 mg semapimod intravenously for 1 day with placebo for 2 days; or 60 mg semapimod intravenously for 3 days. Participants who completed CD04 could participate in the open-label extension study, CD05, to receive up to five additional semapimod HCl 60 mg daily doses three times every 6-8 weeks. The main outcome measures were CDAI, Inflammatory Bowel Disease Questionnaire (IBDQ), Crohn's Disease Endoscopic Inflammation Score (CDEIS) and serum C-reactive protein (CRP) concentration. RESULTS: 152 patients were randomised in CD04. Responses for 1 and 3 day regimens were similar to placebo for CDAI (p=0.82), IBDQ (p=0.85), CDEIS (p=0.57) and CRP (p=0.40). The only noteworthy treatment-related safety finding was infusion reaction (phlebitis): 7.3, 34.8 and 62.7% for the placebo and 1 and 3 day semapimod treatment groups, respectively (p<0.001). In the open-label CD05 study (included=119 patients) a posthoc analysis showed that the mean CDAI improved in patients receiving 6 compared with < or = 3 cumulative doses (204.1+/-83 vs 251.4+/-103.05, p=0.006). CONCLUSIONS: Single and 3 day dosing of semapimod (< or = 180 mg) was ineffective for the treatment of moderate to severe CD. However, cumulative dosing > or = 360 mg was associated with decreased CDAI in a limited number of patients.

Comparative Review of Malignant Melanoma and Histologically Well-Differentiated Melanocytic Neoplasm in the Oral Cavity of Dogs.

Oral malignant melanoma (OMM) is the most common neoplasm of the canine oral cavity. It is characterized by its aggressive local disease as well as its high rate of lymphatic invasion and distant metastasis. OMM carries a poor prognosis, with most patients succumbing to the disease due to progression of the neoplasm. Histopathologically, OMM is characterized by significant nuclear atypia, a mitotic index of greater than 4/10 hpf, and evidence of vascular invasion or metastasis. Clinically, these lesions can become locally invasive, causing lysis of bones and severe inflammation of the surrounding soft tissue. With time, these lesions can spread to the regional lymph node and to the lungs and other organs. Prognosis can vary depending on the size of the primary tumor, regional node involvement, and distant metastatic disease; however, multiple studies report a relatively short median survival time ranging from less than 4 months to 8 months. Histologically well- differentiated melanocytic neoplasms (HWDMN) are a variant of OMM and sometimes referred to as canine oral melanocytic neoplasms of low malignant potential. Unlike OMM, patients with HWDMN have longer survival times. Histopathologically, HWDMNs have well-differentiated melanocytes with a low mitotic index of 3 or less per 10 hpf and minimal nuclear atypia. HWDMNs have better prognosis with a mean survival time of up to 34 months. This article is a comparative review of OMM and its less aggressive counterpart.

Evaluation of novel serological markers and autoantibodies in dogs with inflammatory bowel disease.

BACKGROUND: The use of serological markers to diagnose inflammatory bowel disease (IBD) in humans is well-established. Because of the frequency of IBD in dogs and resources required for its diagnosis with current methods, new approaches are desired. OBJECTIVE: The goal is to evaluate novel serologic markers to differentiate clinical cohorts in dogs with gastrointestinal (GI) disease and assess their potential to develop a serum-based IBD diagnostic test. ANIMALS: Seventy dogs diagnosed with biopsy-confirmed IBD, 23 dogs with non-IBD predominantly acute GI diseases, and 58 normal dogs. METHODS: Prospective control study. ELISA methods were developed to detect autoantibodies to polymorphonuclear leukocytes (APMNA) and calprotectin (ACNA), antibodies against gliadins (AGA), microbial outer membrane porin C (ACA), and flagellins (AFA) isolated from diseased dogs based on clinical and histopathological scoring. RESULTS: IBD dogs displayed a 39%-76% prevalence of seropositivity against selected serologic markers that markedly decreased to 0%-13% in non-IBD and normal dogs. ROC analysis showed statistical significance in differentiating the cohorts, with seropositivity against OmpC being the highest single performance marker. The combination of markers such as OmpC and APMNA reached specificities of 93%-99% and 79%-98% and sensitivities of 76%-97% and 66%-86% when comparing IBD versus normal cohorts and non-IBD cohorts, respectively. CONCLUSION AND CLINICAL IMPORTANCE: Seropositivity of canine immunoglobulins A against selected serologic markers in dogs appears promising in the detection and differentiation of IBD versus other acute GI conditions. Among them, antibody reactivity to Escherichia coli OmpC and canine autoantibodies against polymorphonuclear leukocytes displayed the highest single marker discriminating performance.

Alimentary-associated carcinomas in five Vietnamese potbellied pigs.

CASE DESCRIPTION: 5 Vietnamese potbellied pigs were evaluated for abdominal distress that had not responded to medical treatment (4 pigs) or a draining tract of the cranial abdomen of unknown duration (1 pig). CLINICAL FINDINGS: Clinical signs in the pigs included anorexia, vomiting, and constipation. Physical examination revealed a palpable abdominal mass in all pigs. Radiography revealed distended loops of small intestine in 2 pigs. TREATMENT AND OUTCOME: 3 pigs were treated successfully with wide-margin excision of the abdominal masses, and 2 were euthanized. Primary tumors were diagnosed at necropsy or through histologic evaluation of biopsy specimens obtained during surgery. Types of tumor included cholangiocellular carcinoma, transmural gastric carcinoma, small intestinal adenocarcinoma, metastatic hepatocellular carcinoma, and carcinoma. The tumors involved the stomach, small intestine, spiral colon, liver, and gall bladder. All 3 surgically treated pigs survived at least 9 months after surgery. CLINICAL RELEVANCE: Although rare, neoplasia of the alimentary system should be considered among the differential diagnoses for potbellied pigs with signs of abdominal distress. Wide-margin excision of the neoplastic tissue may result in a good outcome in affected pigs.

Prognosis for acute nontraumatic hemoperitoneum in the dog: a retrospective analysis of 60 cases (2003-2006).

The complete medical records of 60 dogs with hemoabdomen were reviewed. All dogs underwent exploratory laparotomy and had a diagnosis established by a veterinary pathologist. Final diagnoses were hemangiosarcoma in 38 (63.3%) dogs, splenic hematoma in 16 (26.6%) dogs, splenic torsion in three (5%) dogs, hepatocellular carcinoma in two (3.3%) dogs, and carcinomatosis in one (1.6%) dog. Twenty-four (63.1%) dogs with hemangiosarcoma, 14 (87.5%) dogs with splenic hematoma, three (100%) dogs with splenic torsion, and two (100%) dogs with hepatocellular carcinoma were discharged from the hospital. Dogs with hemangiosarcoma were given a poor prognosis, while dogs with splenic hematoma, splenic torsion, and hepatocellular carcinoma were given a fair to good prognosis.

Use of single-agent carboplatin as adjuvant or neoadjuvant therapy in conjunction with amputation for appendicular osteosarcoma in dogs.

Survival following amputation and administration of single-agent carboplatin for treatment of appendicular osteosarcoma (OSA) in dogs was retrospectively examined. Records of 155 dogs with appendicular OSA treated with amputation and single-agent carboplatin were included from 14 centers. Any carboplatin dosage, number of doses, and protocol schedule were eligible for inclusion. The median disease-free interval (DFI) was 256 days. The median overall survival time was 307 days. Similar prognostic survival factors were identified in this study as reported in prior studies of canine appendicular OSA. Median DFI and survival were comparable to those reported in the original Bergman et al publication. Carboplatin treatment improves the survival probability in dogs with appendicular OSA compared to amputation alone and remains an acceptable alternative to adjuvant treatment with cisplatin.

Clinicopathological Correlation and Prevalence of Increased Copper in Canine Hepatic Cytology.

Special staining and grading of canine liver cytology samples aids in detection of increased copper content. The prevalence of copper in routine diagnostic liver cytology samples, clinical findings associated with high cytologic copper (cCu) grade, and the correlation between cCu grade and histologic findings, including histologic copper (hCu) grade, are unknown. This data may be helpful in ascertaining when to determine a cCu grade and when interpreting cCu grade. Clinical data and available archived hepatic histologic and cytologic samples from 198 dogs were collected, evaluated, rhodanine stained, and graded for copper. Prevalence of increased cCu >5 in a randomly collected group of 163 individuals, and the correlation between cCu and clinical data (n = 198), hCu grade (n = 37), or findings on hematoxylin and eosin-stained hepatic sections (n = 32) were evaluated. The observed prevalence was 1.23%. Dogs with elevated alanine transaminase >180 IU/L or aspartate transaminase >90 IU/L and patients who subsequently had hepatic copper quantification were statistically more likely to have pathologic levels of copper detected by cytology. There was significant and modest correlation between cCu and hCu, interface hepatitis, portal inflammation, and fibrosis. Evidence of hepatocellular leakage may be indications for determination of cCu.

Apocrine gland anal sac adenocarcinoma in cats: 30 cases (1994-2015).

OBJECTIVE To describe the signalment, clinical signs, biological behavior, and outcome for cats with apocrine gland anal sac adenocarcinoma (AGASACA) that underwent surgical excision. DESIGN Retrospective case series. ANIMALS 30 client-owned cats. PROCEDURES Databases of 13 Veterinary Society of Surgical Oncology member-affiliated institutions were searched for records of cats with a histologic diagnosis of AGASACA that underwent tumor excision. For each cat, information regarding signalment, clinical signs, diagnostic test results, treatment, and outcome was extracted from the medical record. The Kaplan-Meier method was used to determine median time to local recurrence (TLR), disease-free interval (DFI), and survival time. Cox regression was used to identify factors associated with TLR, DFI, and survival time. RESULTS Perineal ulceration or discharge was the most common clinical sign in affected cats. Eleven cats developed local recurrence at a median of 96 days after AGASACA excision. Incomplete tumor margins and a high nuclear pleomorphic score were risk factors for local recurrence. Nuclear pleomorphic score was negatively associated with DFI. Local recurrence and a high nuclear pleomorphic score were risk factors for death. Median DFI and survival time were 234 and 260 days, respectively. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that, in cats, perineal ulceration or discharge should raise suspicion of AGASACA and prompt rectal and anal sac examinations. Local recurrence was the most common life-limiting event in cats that underwent surgery for treatment of AGASACA, suggesting that wide margins should be obtained whenever possible during AGASACA excision. Efficacy of chemotherapy and radiation therapy for treatment of cats with AGASACA requires further investigation. (J Am Vet Med Assoc 2019;254:716-722).