Veterinary and comparative oncology最新文献

Lymphoma constitutes 24% of canine neoplastic diseases and 85% of haematopoietic tumours, with B-cell subtypes accounting for 60%-80% of cases. As the most prevalent spontaneous tumour in canines, this disease model holds significant translational value for human non-Hodgkin lymphoma research. To address diagnostic limitations in canine B-cell lymphoma, we developed a canine-specific CD19 monoclonal antibody (HAC19.1) with high affinity and established a dual-platform detection system compatible with flow cytometry and immunohistochemistry. Additionally, a novel CD19-targeting chimeric antigen receptor (CAR) gene sequence (HUA-1) was engineered and successfully transduced into Jurkat cells via lentiviral vectors, confirming stable CAR membrane expression. This breakthrough provides critical technical groundwork for advancing autologous CAR-T cell therapy in canines.

Contaminants in municipal drinking water, specifically total trihalomethanes (TTHMs), are mutagenic. Exposures to TTHMs have been associated with urothelial carcinoma (UC) in both people and dogs. Mutations in the BRAF gene and other genomic copy number aberrations detected in voided urothelial cells with commercial CADET BRAF and BRAF-PLUS tests have also been associated with the presence of UC in dogs. However, it is not known whether these urothelial mutations can be linked to TTHM exposures in dogs. The objectives of this ecological study were to compare the incidence of detected urinary BRAF mutations or genomic copy number aberrations in dogs residing in a city with relatively high drinking water TTHMs (Las Vegas, NV) to a city with significantly lower TTHMs (Reno, NV), and to expand the study group to include BRAF and BRAF-PLUS test results and municipal drinking water TTHM concentrations by zip code across the United States. Dogs living in Las Vegas had a higher relative risk of urothelial mutations compared to dogs living in Reno (RR 2.52; 95% CI, 1.77-3.38; p < 0.0001). However, this risk could not be attributed to higher municipal drinking water TTHMs. Across the United States, the population-adjusted incidence of urothelial mutations in voided urine was not associated with municipal water TTHMs, but was instead associated in cross-sectional analyses with age, neutered status, higher regional test submission rates and previously reported high-risk breeds for UC (Scottish terriers, West Highland white terriers, Shetland sheepdogs, beagles and wirehaired fox terriers). The higher RR for a positive BRAF or BRAF-PLUS test in Las Vegas versus Reno could be solely due to higher test submission rates (2.97 versus 0.97 per 1000 dogs) but could also reflect other environmental exposures not considered in this study.

Hemangiosarcoma (HSA) in dogs is a malignant vascular tumour that exhibits rapid growth, frequent early metastasis, and resistance to conventional therapies, often resulting in short survival times. Building on our previous systematic review of biomarkers in human angiosarcoma, this review focuses specifically on the canine counterpart, synthesizing current evidence on diagnostic, prognostic, and therapeutic biomarkers. A comprehensive PRISMA-compliant search of PubMed and Embase was conducted for studies published from 1996 through 2024, inclusive. Fifty-one eligible studies were identified and assessed for methodological quality using the Newcastle-Ottawa Scale. This review highlights promising protein, molecular, and haematological biomarker candidates, evaluates their clinical relevance, and identifies key gaps in the literature and existing knowledge. By drawing parallels to human angiosarcoma research, this work lays the foundation for comparative oncology efforts and supports the development of novel diagnostic tools and targeted therapies for canine HSA.

Despite the high prevalence of neoplastic diseases in dogs, tumour-cell embolism is poorly documented. This study aimed to characterise the presence and pathological features of distant blood vascular tumour-cell emboli (TCE) in dogs submitted for necropsy. TCE were histologically confirmed in 31/528 dogs (5.9%) that died or were euthanized due to neoplastic disease, most frequently mammary carcinomas (17/31, 54.8%). In 15/31 dogs (48.4%), TCE were associated with secondary macroscopic lesions, such as haemorrhage, whereas in 16/31 dogs (51.6%), there was no clear association with additional pathological changes. TCE were most commonly observed in the lungs (25/31), kidneys (9/31), adrenals (5/31), brain (5/31), and myocardium (5/31). Macroscopic pulmonary changes included petechiae or suffusions (8/31), and TCE-associated haemorrhages were also observed in the myocardium (4/31), kidneys (2/31), adrenals (2/31), brain (2/31), and gastrointestinal serosae (2/31). Histological lesions associated with TCE included haemorrhage (18/31), thrombosis (11/31), oedema (8/31), infarcts (7/31), and intimal proliferation and perivascular fibrosis (4/31). Taken together, these findings suggest that blood vascular TCE may be more prevalent in dogs than currently recognised and reinforce the importance of careful pathological evaluation for their detection. The clinical, macroscopic, and microscopic features described herein provide a practical framework for recognising TCE in veterinary pathology and underscore the need for further studies addressing their pathogenesis, clinical significance, and impact on disease progression in dogs.

Lymph node (LN) metastasis has been associated with shorter survival times in dogs with mast cell tumour (MCT), and treatment of metastatic LN with lymphadenectomy or irradiation has been demonstrated to improve outcomes. Identification of metastatic LN in dogs with MCT is therefore of both prognostic and therapeutic significance. The aim of this prospective, exploratory study was to investigate whether fluorine-18 fluorodeoxyglucose-positron emission tomography/computed tomography (¹⁸F-FDG-PET/CT) is a useful staging tool for the detection of metastatic LN in dogs with cutaneous or subcutaneous MCT, using histopathology as the gold standard. Sixteen client-owned dogs with cytologically or histologically confirmed cutaneous or subcutaneous MCTs underwent full-body ¹⁸F-FDG-PET/CT followed by surgical removal and histopathology of the primary tumour and regional LN(s). The maximum standard uptake value (SUV_max) of the tumour and LN(s) was measured. Primary tumours were graded using both the Patnaik and Kiupel grading systems, and mitotic count was tabulated. LNs were categorised based on Weishaar's histologic criteria for nodal metastasis. Eighteen primary tumours were excised: six subcutaneous and 12 cutaneous MCTs. Of 33 excised regional LNs, 18 (55%) were categorised as metastatic (≥ HN2). There was no difference between the median SUV_max of metastatic (3.88) and nonmetastatic LNs (3.16) (p = 0.41). SUV_max was positively correlated with the mitotic count of the primary tumour (p = 0.02). The results of this exploratory study suggest that ¹⁸F-FDG-PET/CT may not be useful for identifying metastatic LNs in canine MCT.

Canine oral malignant melanoma (OMM) has a high potential for lymph node (LN) metastasis. Standard care involves surgical excision of the OMM with sentinel and draining LNs regardless of metastatic status but carries the risk of complications. Optical coherence tomography (OCT) is a rapid, noninvasive imaging modality that has been evaluated for LN metastasis detection in human breast cancer but not yet translated to canines. The purpose of this study was to (1) compare OCT imaging features from nonmetastatic and metastatic LNs with corresponding histopathology and (2) evaluate the diagnostic accuracy of OCT imaging in identifying metastatic LNs. Thirteen dogs with OMM were prospectively enrolled and sentinel LNs were identified by indirect computed tomography lymphography. OMM and draining LNs were surgically removed. Excised LNs (n = 50) from thirteen dogs were imaged with OCT and submitted for histopathology. OCT images of 18 LNs from the first five enrolled dogs were compared to histopathology to identify image features of metastatic and nonmetastatic LNs and identify images for observer training. The subsequent OCT images of 32 LNs of eight dogs were used to generate a test set for six observers with varying OCT experience for assessment of diagnostic accuracy. The sensitivity, specificity, and correct classification rate of OCT imaging for OMM LN metastasis in dogs was 75% (95% CI: 61.2%-85.1%), 76.6% (95% CI: 70.1%-82.0%), and 76.3% (95% CI: 70.5%-81.2%), respectively. OCT image features of nonmetastatic and metastatic LNs show diagnostic potential for intraoperative detection of OMM LN metastasis.

Melanocytic tumours (MT) occur in both humans and companion animals, presenting an opportunity for comparative oncology research. Thus, this study provides a comprehensive epidemiological analysis comparing MT in Portuguese dogs, cats and humans. Data were obtained from the Portuguese National Cancer Registry (RON) (2011-2021) and Vet-OncoNet (2020-2023), utilising standardised oncological classification systems (ICD-O-3.2 and Vet-ICD-O-canine-1). The results indicate that Melanoma was the most frequently diagnosed MT across all three species, while melanocytomas were common in dogs but rare in cats and humans. A higher incidence rate (IR) for MT was observed in dogs (IR = 16.1) compared to humans (IR = 8.1) and cats (IR = 6.3), and neutered dogs (10.8 years) were diagnosed at significantly older ages than intact ones (9.9 years). Shar-Peis (RR = 14.2, p < 0.001) had the highest RR compared to mixed-breed dogs, followed closely by Rhodesian Ridgebacks (RR = 12.2, p < 0.001) and Golden Retrievers (RR = 6.4, p < 0.001). Spatial analysis revealed significant clustering of MT cases in humans and dogs, with a strong geographical overlap (BLISA = 0.345, p < 0.001) in urban regions. This study provides the first epidemiological comparison of MT in these three species in Portugal, underscoring the sentinel role of companion animals in human oncology and the relevance of comparative oncology in translational cancer research.

Canine phaeochromocytomas (PCCs) are neuroendocrine tumours with malignant potential. Metastatic disease remains the sole definitive evidence of malignancy. Histopathological criteria to predict long-term survival have not been established in dogs. This study evaluated the reproducibility and prognostic value of histopathological parameters derived from human scoring systems, along with the Ki67 proliferation index (PI), in dogs after adrenalectomy for PCC. Tumour samples from 41 dogs were assessed by a veterinary pathologist and pathology resident. Of 10 histopathological parameters examined, only necrosis, tumour cell spindling, and extension into adipose tissue achieved sufficient inter- and intra-observer agreement (≥ 0.40) for inclusion in survival analyses, while Ki67 PI demonstrated excellent reproducibility (≥ 0.95). A composite histopathological score was generated by summing these three parameters and a dichotomised Ki67 PI (optimal cutoff 18%), as determined by ROC analysis. Among the 41 dogs, eight died within 2 weeks postoperatively, leaving 33 long-term survivors with four tumour-related events. Kaplan-Meier analysis showed significantly poorer survival (p < 0.001) in dogs with a high Ki67 PI (≥ 18%), whereas the composite score showed a borderline significant association with outcome in Cox regression (p = 0.056; hazard ratio 2.80). Overall, dogs surviving the immediate postoperative period demonstrated a favourable prognosis (mean overall survival of 2456 days). These findings suggest that, in this cohort with few tumour-related events, the dichotomised Ki67 PI alone may serve as a clinically applicable prognosticator for canine PCC. However, further research in larger populations is needed to determine whether a composite score adds prognostic value and guides postoperative management.

Canine lymphoma is a common haematopoietic neoplasm. Immunophenotype is a major prognostic factor and may influence treatment recommendations. This study assessed the diagnostic performance of the Sysmex XN-1000V white blood cell differential (WDF) scattergram to differentiate canine nodal large B-cell and T-cell lymphoma, using the percentage of highly fluorescent cells (%HFC) and visual WDF scattergram evaluation. A retrospective study was conducted on data from cases of cytologically diagnosed canine large cell lymphoma. Cases had concurrent lymph node aspirate cell suspensions in saline that were analysed using the Sysmex XN-1000V and multiparametric flow cytometry (FC) for lymphoma classification as B or T-cell. Large B-cell lymphomas (n = 86) showed significantly higher %HFC compared to large T-cell lymphomas (n = 17), with a median (IQR) of 50% (36-84) and 9.7% (3.9-19), respectively. The ROC analysis showed an AUC of 0.93, with an optimal cutoff of < 24.15 %HFC for identifying T-cell lymphoma, achieving 88.24% sensitivity, 87.21% specificity, 57.69% PPV and 97.40% NPV. The following data is expressed as 'overall-percentage-agreement (kappa value)'. Using the previous cutoff, the agreement between the %HFC classification and FC was 88.24% (κ = 0.76). Regarding the WDF scattergram evaluation, the intra- and inter-observer agreement were 86.27% (κ = 0.71) and 67.65% (κ = 0.55), respectively. Agreement between the WDF scattergram evaluation and FC was 77.45% (κ = 0.55), and improved to 90.63% (κ = 0.74) when just the confident cases were used. In conclusion, a preliminary assessment of the phenotype of canine nodal large cell lymphoma can be made using either the visual inspection of the WDF scattergram or the %HFC. This could serve as a cost-effective, fast screening tool while awaiting definitive flow cytometry results.