The National Cancer Institute-led multidisciplinary Comparative Brain Tumor Consortium (CBTC) convened a glioma pathology board, comprising both veterinarian and physician neuropathologists, and conducted a comprehensive review of 193 cases of canine glioma. The immediate goal was to improve existing glioma classification methods through creation of a histologic atlas of features, thus yielding greater harmonization of phenotypic characterization. The long-term goal was to support future incorporation of clinical outcomes and genomic data into proposed simplified diagnostic schema, so as to further bridge the worlds of veterinary and physician neuropathology and strengthen validity of the dog as a naturally occurring, translationally relevant animal model of human glioma. All cases were morphologically reclassified according to a new schema devised by the entire board, yielding a majority opinion diagnosis of astrocytoma (43, 22.3%), 19 of which were low-grade and 24 high-grade, and oligodendroglioma (134, 69.4%), 35 of which were low-grade and 99 were high-grade. Sixteen cases (8.3%) could not be classified as oligodendroglioma or astrocytoma based on morphology alone and were designated as undefined gliomas. The simplified classification scheme proposed herein provides a tractable means for future addition of molecular data, and also serves to highlight histologic similarities and differences between human and canine glioma.

Highlights d Genomic, epigenomic, and transcriptomic characterization of sporadic glioma in dogs d Somatic alterations in canine glioma converge with human glioma drivers d Canine glioma resemble pediatric human glioma by mutation rate and DNA methylation d Microenvironment similarity between canine and human pediatric and adult glioma

On September 14-15, 2015, a meeting of clinicians and investigators in the fields of veterinary and human neuro-oncology, clinical trials, neuropathology, and drug development was convened at the National Institutes of Health campus in Bethesda, Maryland. This meeting served as the inaugural event launching a new consortium focused on improving the knowledge, development of, and access to naturally occurring canine brain cancer, specifically glioma, as a model for human disease. Within the meeting, a SWOT (strengths, weaknesses, opportunities, and threats) assessment was undertaken to critically evaluate the role that naturally occurring canine brain tumors could have in advancing this aspect of comparative oncology aimed at improving outcomes for dogs and human beings. A summary of this meeting and subsequent discussion are provided to inform the scientific and clinical community of the potential for this initiative. Canine and human comparisons represent an unprecedented opportunity to complement conventional brain tumor research paradigms, addressing a devastating disease for which innovative diagnostic and treatment strategies are clearly needed.

Melanocytic neoplasms are common in dogs and frequently occur within the oral cavity or in haired skin. The behavior of melanocytic neoplasms is variable and depends on tumor location, size, and histopathologic features. This study compared cytopathology and histopathology of 32 lymph nodes from 27 dogs diagnosed with melanocytic neoplasms. Agreement between the original cytology report, cytology slide review, original histopathology report, and histopathology slide review was determined for each lymph node. A subset of lymph nodes was subjected to immunohistochemistry (Melan-A) and additional histochemical stains/techniques (Prussian blue, bleach) to assist in differentiation of melanocytes and melanophages. Agreement ranged from slight to fair for each of the variables evaluated with weighted kappa (κ) or kappa (κ) analysis (original cytology vs cytology review κ = 0.24; original cytology vs original histopathology κ = 0.007; original cytology vs histopathology review κ = 0.23; cytology review vs original histopathology κ = 0.008; cytology review vs histopathology review κ = 0.006; and original histopathology vs histopathology review κ = 0.18). The diagnoses (metastatic, equivocal, or negative for metastasis) of the original report and slide review for both cytology and histopathology were not significantly correlated with survival in this population of patients. Overall, agreement between cytology and histopathology was poor even with a single clinical or anatomic pathologist performing slide review. Consensus between routine cytology and histopathology for staging of lymph nodes in patients with melanocytic neoplasms is poor and does not correlate with survival.

The barbed knotless suture appears to be a valid alternative to facilitate laparoscopic closure of the nephrosplenic space in normal horses; however, further work is necessary to investigate its suitability in clinically affected horses.

Reports of canine ependymoma are generally restricted to single case reports with tumor incidence estimated at 2% to 3% of primary central nervous system (CNS) tumors. While most commonly reported in the lateral ventricle, tumors can occur anywhere in the ventricular system and in extraventricular locations. Rosettes and pseudorosettes are a common histologic feature; however, these features can be mimicked by other CNS neoplasms. Thirty-seven potential ependymoma cases were identified in a retrospective database search of 8 institutions, and a histologic review of all cases was conducted. Of 37 cases, 22 candidate cases were further subjected to a consensus histologic and immunohistochemical review, and only 5 of 37 (13.5%) were conclusively identified as ependymoma. The neuroanatomic locations were the lateral ventricle (3/5), third ventricle (1/5), and mesencephalic aqueduct (1/5). Subtypes were papillary (4/5) and tanycytic (1/5). Histologic features included rosettes (5/5), pseudorosettes (5/5), ependymal canals (2/5), tanycytic differentiation (1/5), blepharoplasts (1/5), ciliated cells (1/5), and high nuclear to cytoplasmic ratio (5/5). Immunolabeling for GFAP (4/4) and CKAE1/3 (3/4) was found in pseudorosettes, rosettes, and scattered individual neoplastic cells. Diffuse but variably intense cytoplasmic S100 immunolabeling was detected in 3 of 4 cases. Olig2 intranuclear immunolabeling was observed in less than 1% of the neoplastic cells (3/3). Tumors that had pseudorosettes and mimicked ependymoma included oligodendroglioma, choroid plexus tumor, pituitary corticotroph adenoma, papillary meningioma, and suprasellar germ cell tumor. These findings indicate that canine ependymoma is an extremely rare neoplasm with histomorphologic features that overlap with other primary CNS neoplasms.

GM1 gangliosidosis (GM1) is a fatal neurodegenerative lysosomal storage disease that occurs most commonly in young children, with no effective treatment available. Long-term follow-up of GM1 cats treated by bilateral thalamic and deep cerebellar nuclei (DCN) injection of adeno-associated virus (AAV)-mediated gene therapy has increased lifespan to 8 years of age, compared with an untreated lifespan of~8 months. Due to risks associated with cerebellar injection in humans, the lateral ventricle was tested as a replacement route to deliver an AAVrh8 vector expressing feline b-galactosidase (b-gal), the defective enzyme in GM1. Treatment via the thalamus and lateral ventricle corrected storage, myelination, astrogliosis, and neuronal morphology in areas where b-gal was effectively delivered. Oligodendrocyte number increased, but only in areas where myelination was corrected. Reduced AAV and b-gal distribution were noted in the cerebellum with subsequent increases in storage, demyelination, astrogliosis, and neuronal degeneration. These postmortem findings were correlated with endpoint MRI and magnetic resonance spectroscopy (MRS). Compared with the moderate dose with which most cats were treated, a higher AAV dose produced superior survival, currently 6.5 years. Thus, MRI and MRS can predict therapeutic efficacy of AAV gene therapy and non-invasively monitor cellular events within the GM1 brain.

Background: Differentiating benign from canine malignant mammary tumors requires invasive surgical biopsy. Circulating microRNAs (miRNA) may represent promising minimally invasive cancer biomarkers in people and animals.Objectives: To evaluate the serum mRNA profile between dogs with and without mammary carcinoma, and to determine if any of these markers have prognostic significance.Animals: Ten healthy client-owned female dogs (5 intact, 5 spayed) and 10 dogs with histologically confirmed mammary carcinoma were included; 9 were client-owned, whereas 1 was a research colony dog.Methods: Retrospective study. Serum miRNA was evaluated by RNA deep-sequencing (RNAseq) and digital droplet PCR (dPCR).Expression of candidate biomarkers miR-18a, miR-19b, miR-29b, miR-34c, miR-122, miR-125a, and miR-181a was compared with clinical characteristics, including grade, metastasis, and survival.Results: 452 unique serum miRNAs were detected by RNAseq. Sixty-five individual miRNAs were differentially expressed (>±1.5-fold) and statistically significant between groups. Serum miR-19b (P = .003) and miR-125a (P < .001) were significantly higher in the mammary carcinoma group by dPCR. Both had high accuracy based on receiver operator characteristic area under the curve (0.930 for miR-125a; 0.880 for miR-19b). Circulating miR-18a by RNAseq was significantly higher in mammary carcinoma dogs with histologic evidence of lymphatic invasion (P = 0.03). There was no significant association with any miRNA and survival or inflammatory status. Conclusions and Clinical Importance: Circulating miRNAs are differentially expressed in dogs with mammary carcinoma. Serum miR-19b and miR-18a represent candidate biomarkers for diagnosis and prognosis, respectively. Abbreviations: AUC, area under the curve; CMT, canine mammary tumor(s); dPCR, digital droplet PCR; FAM, 6-carboxyfluorescein; miRs/miRNA, microRNA; qPCR, quantitative PCR; RNAseq, RNA deep-sequencing; ROC, receiver operator characteristic.