Veterinary and comparative oncology最新文献

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.

Stereotactic body radiation therapy (SBRT) has become a non-invasive alternative option for canine adrenal tumours with high surgical risks; however, its clinical benefits and risks are still to be fully understood. The goal of this multi-institutional retrospective study was to describe the clinical outcome and safety of SBRT for the treatment of 21 dogs with adrenal tumours. Ten were suspected pheochromocytomas, two adenocarcinomas, and the diagnosis was unknown in nine dogs. Vascular invasion was present in 81% of cases (17/21). Thirteen dogs received 3 fractions of 6 to 11 Gy, 7 received 5 fractions of 6 to 9 Gy, and 1 received 4 fractions of 6 Gy. For the 20 patients with follow-up imaging, 9 (43%) had partial response, 10 (47%) stable disease, and 1 (5%) progressive disease. Progression-free survival was 16.8 months (95% CI: 3.4-23), and overall survival time was 16.8 months (95% CI: 3.7-23.7). Twelve patients (57%) experienced acute adverse events (AEs); of those, seven were gastrointestinal grade ≥ III, including one grade V. Late AEs were suspected in seven dogs (33%), including gastrointestinal grade V in four of them. A total of five dogs (24%) died from radiation-related toxicities. Although SBRT seems to be effective against adrenal tumours, it was associated with a high morbidity and mortality rate, suggesting that re-evaluation of radiation therapy protocols is necessary for maintaining patient safety.

Human epidermal growth factor receptor 2 (HER2) gene mutations have been reported in 5% to 38% of canine pulmonary adenocarcinomas (cPACs), most commonly as V659E mutations in exon 20. However, their prognostic and predictive significance remains unclear. This retrospective, single-centre cohort study investigated the frequency of HER2 mutations in surgically resected cPACs and their association with clinical outcomes. Between 2005 and 2021, lung masses histologically diagnosed as cPACs were collected and subjected to direct sequencing of HER2 exons 20 and 21. A total of 72 dogs were enrolled, with successful HER2 gene analysis in 69 cases. HER2 exon 20 missense mutations were identified in 20 dogs (29.0%), including 18 harbouring the previously reported V659E hotspot mutation within the transmembrane domain. Homozygous mutations were detected in 13 dogs. Univariable analysis revealed associations between progression-free interval (PFI) and clinical signs, tumour size classification, lymph node metastasis, surgical margin status, and histologic grade. Overall survival time (OST) was associated with age, clinical signs, tumour size > 7 cm, histologic subtype, lymph node metastasis, and margin status. In multivariable analysis, tumour size classification and margin status remained significantly associated with PFI, while age, tumour size > 7 cm, and histologic subtype were independently associated with OST. Notably, the presence of HER2 mutations was significantly associated with prolonged PFI in both univariable and multivariable analyses, although no significant association with OST was observed. These findings suggest that HER2 mutation status may serve as a favourable prognostic marker for disease progression in surgically resected cPACs.

Feline mammary tumours represent the third most common malignancy in cats, with limited evidence-based tools available for risk assessment and screening guidance. Traditional veterinary approaches rely on subjective clinical judgement, lacking quantitative risk stratification methods that could optimise preventive care delivery. To develop and validate the first comprehensive machine learning-based risk prediction system for feline mammary tumours, providing evidence-based clinical decision support for veterinary practice. We developed a comprehensive synthetic dataset of 4399 feline cases spanning 2002-2022, systematically calibrated against real-world epidemiological data from published literature. The synthetic data incorporated demographic, clinical, reproductive, and environmental variables that precisely replicated actual epidemiological relationships. Five machine learning algorithms (Random Forest, XGBoost, Neural Network, SVM, Logistic Regression) were trained and combined using soft voting ensemble methodology. Model performance was evaluated using area under the curve (AUC), calibration metrics, and clinical utility measures. The ensemble model achieved excellent discrimination capability (AUC = 0.888, 95% CI: 0.873-0.903) with 80.5% accuracy, 85.7% sensitivity, and 76.0% specificity. Risk stratification demonstrated clear clinical utility: low-risk cats (< 30% probability) had 12.4% tumour prevalence, while very high-risk cats (> 80% probability) showed 89.5% prevalence. The machine learning approach substantially outperformed traditional assessment methods, showing 64.8% improvement in discriminative ability and a 163% increase in net clinical benefit. This study establishes the first validated machine learning-based clinical decision support system for feline mammary tumour risk assessment. The risk stratification approach enables personalised screening recommendations while optimising resource allocation, potentially transforming preventive veterinary oncology practice.

A clear understanding of human and canine osteosarcoma (hOS and cOS) immunobiology is needed to develop effective immunotherapeutic strategies, a promising option to improve outcomes. Previous studies in humans and dogs have underscored the importance of the macrophagic infiltrate. Notably, high M2-like macrophage infiltration has been associated with increased metastatic progression-free survival in hOS treated with surgery and chemotherapy. Given the strong similarities between hOS and cOS, we hypothesized that tumour infiltration by M2-like macrophages would also be associated with an improved prognosis in dogs. Eighty-four dogs with a histological diagnosis of cOS were retrospectively selected from the database of five veterinary institutions and one pathology laboratory. Medical data and associated cOS samples were retrieved from electronic records and original pathology laboratories. Macrophage populations were identified by immunohistochemistry using anti-CD204 and anti-CD206 antibodies. Univariate and multivariate Cox proportional hazard models were performed to identify factors associated with overall survival time (OST) in dogs treated with surgery with (SOC) or without (SxOnly) adjuvant chemotherapy. In dogs treated surgically (SOC + SxOnly), only high CD206+ infiltrate was associated with longer OST in both univariate (p = 0.019) and multivariate analysis (p = 0.014). Within the SOC group, high CD206+ infiltrate (p = 0.006) and lower body weight (p = 0.029) were associated with better outcome in the univariate analysis while high CD206+ infiltrate (p = 0.003) and female sex (p = 0.044) were associated with a longer survival in the multivariate analysis. This observation underscores the role of M2-like macrophages in OS and strengthens the relevance of cOS as a model for hOS in the immunological field.

Alkaline phosphatase (ALP) enzymatic activity has been proposed as a marker for distinguishing canine acute leukaemia (AL) subtypes (i.e., myeloid vs. lymphoid). However, ALP enzymatic activity has not been fully evaluated in CD34+ AL. Determine whether ALP enzymatic activity can differentiate CD34+ AL subtypes in dogs and distinguish CD34+ AL from CD34- haematopoietic tumours in tissue/effusion samples. Peripheral blood from 64 dogs with CD34+ AL, 10 with B cell chronic lymphocytic leukaemia (CLL), and 10 healthy controls were prospectively evaluated for ALP enzymatic activity via cytochemical staining; a subset also underwent ALP detection by flow cytometry (FC). Archived cytology slides from 67 tissue/effusion specimens, including 27 CD34+ AL, 22 T cell lymphomas, and 18 B cell lymphomas, were retrospectively assessed. CD34+ AL cases were categorised as acute myeloid leukaemia (AML), acute lymphoid leukaemia (ALL) or acute unclassifiable leukaemia (AUL) by established FC criteria. ALP positivity was defined as > 3% ALP+ neoplastic cells, which was selected based on receiver operating characteristic (ROC) curve analysis. Cytochemical ALP activity was detected in 61/64 (95.3%) CD34+ AL cases, with no significant differences between AML, ALL, and AUL subtypes (p > 0.05). All lymphoma and B cell CLL cases were ALP-negative. FC-based ALP analysis showed poor concordance with cytochemistry, and the correlation between %CD34 + ALP+ cells and %ALP+ neoplastic cells was weak (Spearman's ρ = 0.25). While ALP enzymatic activity is present in most CD34+ AL cases, it does not reliably differentiate CD34+ AL subtypes via cytochemistry. However, ALP may help distinguish CD34+ AL from B and T cell lymphomas. FC-based ALP analysis is not a reliable marker for CD34+ AL classification.