OBJECTIVE To describe cytologic characteristics of renal fine-needle aspirate (FNA) samples from dogs, evaluate proportions of cytologic specimens deemed adequate for interpretation (diagnostic yield), assess diagnostic utility of cytologic examination for neoplastic and nonneoplastic diseases, and characterize ultrasonographic features of evaluated kidneys to determine whether the imaging characteristics could be used to inform cytologic interpretations. DESIGN Retrospective, observational study. SAMPLE 102 cytologic specimens and 97 ultrasonographic studies from 100 dogs. PROCEDURES Medical records were reviewed to identify dogs that underwent ultrasound-guided renal FNA. Slides were categorized as adequate or inadequate for interpretation; adequate slides were used for retrospective cytologic diagnosis. Sensitivity, specificity, and predictive values of cytologic examination for detection of neoplastic and nonneoplastic conditions were calculated by comparison with histologic or lymphoid cell clonality assay results. Ultrasonographic characteristics of neoplastic and nonneoplastic renal lesions were described. RESULTS 74 of 102 (72%) specimens had slides adequate for interpretation; 26 were included in the diagnostic accuracy analysis. Sensitivity of cytologic examination was 78% and 50% for detection of neoplastic and nonneoplastic conditions, respectively, with specificities of 50% and 77%, respectively; sensitivity for detection of lymphoma was 100%. Ultrasonographic appearance of kidneys with confirmed neoplasia varied; masses were most commonly found in kidneys with carcinoma (5/5), lymphoma (5/7), or other neoplasia (3/4) and absent in kidneys with nonneoplastic conditions (n = 5). CONCLUSIONS AND CLINICAL RELEVANCE Renal FNA specimens were adequate for interpretation at rates comparable with those reported for other organs and were considered clinically useful for diagnosis of neoplasia. Imaging characteristics may potentially aid differentiation between neoplastic and nonneoplastic lesions; however, further investigation is needed.

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Background Tumors are complex tissues containing collections of phenotypically diverse malignant and nonmalignant cells. We know little of the mechanisms that govern heterogeneity of tumor cells nor of the role heterogeneity plays in overcoming stresses, such as adaptation to different microenvironments. Osteosarcoma is an ideal model for studying these mechanisms—it exhibits widespread inter- and intra-tumoral heterogeneity, predictable patterns of metastasis, and a lack of clear targetable driver mutations. Understanding the processes that facilitate adaptation to primary and metastatic microenvironments could inform the development of therapeutic targeting strategies. Results We investigated single-cell RNA-sequencing profiles of 47,977 cells obtained from cell line and patient-derived xenograft models as cells adapted to growth within primary bone and metastatic lung environments. Tumor cells maintained phenotypic heterogeneity as they responded to the selective pressures imposed during bone and lung colonization. Heterogenous subsets of cells defined by distinct transcriptional profiles were maintained within bone- and lung-colonizing tumors, despite high-level selection. One prominent heterogenous feature involving glucose metabolism was clearly validated using immunofluorescence staining. Finally, using concurrent lineage tracing and single-cell transcriptomics, we found that lung colonization enriches for multiple clones with distinct transcriptional profiles that are preserved across cellular generations. Conclusions Response to environmental stressors occurs through complex and dynamic phenotypic adaptations. Heterogeneity is maintained, even in conditions that enforce clonal selection. These findings likely reflect the influences of developmental processes promoting diversification of tumor cell subpopulations, which are retained, even in the face of selective pressures.

BackgroundEnzymatic activity of Telomerase Reverse Transcriptase (TERT) is important in maintaining the telomere length and has been implicated in cancer and aging related pathology. Since cancer susceptibility as well as longevity of dogs vary between breeds, this study involved sequencing the entire TERT gene of Canis familiaris from DNA samples obtained from forty dogs, with ten dogs each of four breeds: Shih Tzu, Dachshund, Irish Wolfhound, and Newfoundland, each with different life expectancies and susceptibility to cancer.ResultsWe compared the sequences of all forty individuals amongst one another and with the published sequence of canine TERT, and analyzed relationships between members of the same or different breeds. Two separate phylogenetic trees were generated and analyzed from these individuals. Polymorphisms were found most frequently in intronic regions of the gene, although exonic polymorphisms also were observed. In many locations genotypes were observed that were either homozygous for the reference sequence or heterozygous, but the variant homozygous genotype was not observed.ConclusionsWe propose that these homozygous variants are likely to have adverse effects in dogs. It was also found that the polymorphisms did not segregate by breed. Because the four breeds chosen come from geographically and physiologically distinct backgrounds, it can be inferred that the polymorphic diversification of TERT preceded breed derivation.