The aim of this paper is to discuss and update criteria that can guide the diagnosis, prognosis and treatment of canine and feline mammary neoplasms. It was elaborated during the IV Mammary Pathology Meeting: Diagnosis, Prognosis and Treatment of the Canine and Feline Mammary Neoplasia, held on April 29th and 30th, 2019 in Belo Horizonte – MG, Brazil, sponsored by the Laboratory of Comparative Pathology of the Federal University of Minas Gerais (UFMG), with the support of the Brazilian Association of Veterinary Pathology (ABPV) and Brazilian Association of Veterinary Oncology (ABROVET). Academics from several regions of Brazil were present and contributed to this work.
Mast cell tumor (MCT) is a frequent cutaneous neoplasm in dogs that is heterogeneous in clinical presentation and biological behavior, with a variable potential for recurrence and metastasis. Accurate prediction of clinical outcomes has been challenging. The study objective was to develop a system for classification of canine MCT according to the mortality risk based on individual assessment of clinical, histologic, immunohistochemical, and molecular features. The study included 149 dogs with a histologic diagnosis of cutaneous or subcutaneous MCT. By univariate analysis, MCT metastasis and related death was significantly associated with clinical stage ( P < .0001, r = -0.610), history of tumor recurrence ( P < .0001, r = -0.550), Patnaik ( P < .0001, r = -0.380) and Kiupel grades ( P < .0001, r = -0.500), predominant organization of neoplastic cells ( P < .0001, r = -0.452), mitotic count ( P < .0001, r = -0.325), Ki-67 labeling index ( P < .0001, r = -0.414), KITr pattern ( P = .02, r = 0.207), and c-KIT mutational status ( P < .0001, r = -0.356). By multivariate analysis with Cox proportional hazard model, only 2 features were independent predictors of overall survival: an amendment of the World Health Organization clinical staging system (hazard ratio [95% CI]: 1.824 [1.210-4.481]; P = .01) and a history of tumor recurrence (hazard ratio [95% CI]: 9.250 [2.158-23.268]; P < .001]. From these results, we propose an amendment of the WHO staging system, a method of risk analysis, and a suggested approach to clinical and laboratory evaluation of dogs with cutaneous MCT.
The canine transmissible venereal tumor (CTVT) is a cancer lineage that arose several millennia ago and survives by “metastasizing” between hosts through cell transfer. The somatic mutations in this cancer record its phylogeography and evolutionary history. We constructed a time-resolved phylogeny from 546 CTVT exomes and describe the lineage’s worldwide expansion. Examining variation in mutational exposure, we identify a highly context-specific mutational process that operated early in the cancer’s evolution but subsequently vanished, correlate ultraviolet-light mutagenesis with tumor latitude, and describe tumors with heritable hyperactivity of an endogenous mutational process. CTVT displays little evidence of ongoing positive selection, and negative selection is detectable only in essential genes. We illustrate how long-lived clonal organisms capture changing mutagenic environments, and reveal that neutral genetic drift is the dominant feature of long-term cancer evolution.
Objectives The aim of this study was to establish the safety and efficacy of a novel multidrug lomustine-based chemotherapeutic protocol for cats with high-grade multicentric or mediastinal lymphoma, in an area endemic for feline leukemia virus (FeLV). Methods This prospective study included owned cats, diagnosed (cytologically) with multicentric or mediastinal lymphoma and treated with the LOPH (lomustine, vincristine [Oncovin; Antibióticos do Brasil], prednisolone and hydroxydaunorubicin [doxorubicin]) protocol. A complete blood count was performed before every chemotherapy session and any significant abnormalities recorded as possible related toxicities. Median survival time (MST) and disease-free interval were estimated by Kaplan–Meier curves. Results Twenty-one cats were included in this study. Nineteen (90.5%) tested positive for FeLV and were therefore considered to have persistent viremia. Complete response was reported in 81% (n = 17/21), while three had partial remission and one had no response. Seven cats finished the induction protocol within 20–31 weeks (23.1 ± 4.5; median 20) and all seven received a maintenance protocol. The MST (lymphoma-related survival) for the 21 cats was 214 days. The MST was 214 days for cats with mediastinal lymphoma (n = 13), but it was not reached for multicentric lymphoma (n = 8; P = 0.9). The MST of cats with persistent FeLV antigenemia was 171 days. Grade I anorexia and vomiting occurred in 19% of the cats (n = 4/21). Hematologic toxicity was found in 100% of the cats at some point during their treatment, but it was mostly grade I or II. Neutropenia, thrombocytopenia and anemia occurred in 16/21, 21/21 and 15/21 cats, respectively. Conclusions and relevance The LOPH protocol was well tolerated by cats with lymphoma and persistent FeLV viremia, and resulted in a better MST than similar studies with other protocols. Novel studies and controlled trials are necessary in order to evaluate the efficacy of different protocols according to the lymphoma subtype, anatomic form and FeLV status.
BackgroundSurgery is the treatment of choice for regional control of mammary neoplasms in female dogs. Various surgical techniques may be used, as long as mammary gland anatomy, lymphatic drainage, and known prognostic factors are respected. The purpose of this study was to compare surgical stress—including duration of surgery, nociception and hematological changes—and postoperative complications in dogs undergoing regional and unilateral radical mastectomy. Eighteen dogs were selected for each technique. Postoperative pain (nociception), hematological changes, and postoperative complications were compared between the two groups.ResultsThe group treated with radical mastectomy had a longer surgical duration, showed more intense physiological changes, achieved higher scores on nociception scales, and experienced more postoperative complications.ConclusionCompared to regional mastectomy, radical mastectomy was associated with longer surgical duration, greater nociceptive stimulus, greater surgical stress, and higher incidence of postoperative complications in dogs. Although evaluation of long-term results was not a goal of this study, it is suggested that postoperative recovery and patient quality of life should be considered when choosing a surgical approach for treating mammary tumors in dogs.
Infectious diseases can cause deleterious effects on bird species, leading to population decline and extinction. Haemosporidia can be recognized by their negative effects on host fitness, including reproductive success and immune responses. In captivity, outbreaks of haemosporidian infection have been observed in birds in zoos and aviaries. The endemic Brazilian Atlantic rainforest species Aburria jacutinga is one of the most endangered species in the Cracidae family, and wild populations of this species are currently found mainly in conservation areas in only two Brazilian states. In this study, we aimed to evaluate the effects of avian haemosporidia on hematological and biochemical parameters in two captive populations of A. jacutinga. Forty-two animals were assessed, and the haemosporidian prevalence was similar for males and females. The occurrence of haemosporidian infection in captive A. jacutinga observed in this study was similar to results found in other captive and wild birds in Brazil. We found three different lineages of haemosporidia. Two lineages were identified as Plasmodium sp., one of which was previously detected in Europe and Asia, and the other is a new lineage closely related to P. gallinaceum. A new third lineage was identified as Haemoproteus sp. We found no significant differences in hematological and biochemical values between infected and non-infected birds, and the haemosporidian lineage did not seem to have an impact on the clinical and physiological parameters of A. jacutinga. This is the first report on an evaluation of natural haemosporidian infections diagnosed by microscopic and molecular methods in A. jacutinga by hematology, blood biochemistry, and serum protein values. Determining physiological parameters, occurrence and an estimation of the impact of haemosporidia in endangered avian species may contribute to the management of species rehabilitation and conservation.
The aim of the present prospective-retrospective study was to evaluate the response of high-risk canine mast cell tumours (MCTs) to tyrosine kinase inhibitors (TKIs) and to correlate this with prognostic factors. A total of 24 dogs presented with macroscopic cutaneous MCTs at disease stage II or III, and therefore, at high-risk of associated mortality, were included in the study and treated with masitinib (n=20) or toceranib (n=4). A total of 12/24 dogs achieved an objective response and the overall survival (OS) for all subjects was 113 days. Dogs responding to treatment had a significant increase in OS compared to non-responders (146.5 days vs. 47 days, P=0.02). Internal tandem duplications in exon 11 of the c-kit gene were identified in 6/24 cases. Ki67, KIT immunolabelling and c-kit mutation did not provide information regarding prognosis or prediction of response to TKIs in this population. Initial response to TKIs appears to be the most reliable prognostic factor for survival duration.
Autonomous replication and segregation of mitochondrial DNA (mtDNA) creates the potential for evolutionary conflict driven by emergence of haplotypes under positive selection for 'selfish' traits, such as replicative advantage. However, few cases of this phenomenon arising within natural populations have been described. Here, we survey the frequency of mtDNA horizontal transfer within the canine transmissible venereal tumour (CTVT), a contagious cancer clone that occasionally acquires mtDNA from its hosts. Remarkably, one canine mtDNA haplotype, A1d1a, has repeatedly and recently colonised CTVT cells, recurrently replacing incumbent CTVT haplotypes. An A1d1a control region polymorphism predicted to influence transcription is fixed in the products of an A1d1a recombination event and occurs somatically on other CTVT mtDNA backgrounds. We present a model whereby 'selfish' positive selection acting on a regulatory variant drives repeated fixation of A1d1a within CTVT cells.
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