Mucosal melanoma is a rare and poorly characterized subtype of human melanoma. Here we perform a cross-species analysis by sequencing tumor-germline pairs from 46 primary human muscosal, 65 primary ...canine oral and 28 primary equine melanoma cases from mucosal sites. Analysis of these data reveals recurrently mutated driver genes shared between species such as NRAS, FAT4, PTPRJ, TP53 and PTEN, and pathogenic germline alleles of BRCA1, BRCA2 and TP53. We identify a UV mutation signature in a small number of samples, including human cases from the lip and nasal mucosa. A cross-species comparative analysis of recurrent copy number alterations identifies several candidate drivers including MDM2, B2M, KNSTRN and BUB1B. Comparison of somatic mutations in recurrences and metastases to those in the primary tumor suggests pervasive intra-tumor heterogeneity. Collectively, these studies suggest a convergence of some genetic changes in mucosal melanomas between species but also distinctly different paths to tumorigenesis.
BACKGROUND—Surgery for severe mitral regurgitation is indicated if symptoms or left ventricular dilation or dysfunction occur. However, prognosis is already reduced by this stage, and earlier surgery ...on asymptomatic patients has been advocated if valve repair is likely, but identifying suitable patients for early surgery is difficult. Quantifying the regurgitation may help, but evidence for its link with outcome is limited. Cardiovascular magnetic resonance (CMR) can accurately quantify mitral regurgitation, and we examined whether this was associated with the future need for surgery.
METHODS AND RESULTS—One hundred nine asymptomatic patients with echocardiographic moderate or severe mitral regurgitation had baseline CMR scans and were followed up for up to 8 years (mean, 2.5±1.9 years). CMR quantification accurately identified patients who progressed to symptoms or other indications for surgery91% of subjects with regurgitant volume ≤55 mL survived to 5 years without surgery compared with only 21% with regurgitant volume >55 mL (P<0.0001). A similar separation was observed for regurgitant fraction ≤40% and >40%. CMR-derived end-diastolic volume index showed a weaker association with outcome (proportions surviving without surgery at 5 years, 90% for left ventricular end-diastolic volume index <100 mL/m versus 48% for ≥100 mL/m) and added little to the discriminatory power of regurgitant fraction/volume alone.
CONCLUSIONS—CMR quantification of mitral regurgitation was associated with the development of symptoms or other indications for surgery and showed better discriminatory ability than the reference-standard CMR-derived ventricular volumes. CMR may be able to identify appropriate patients for early surgery, with the potential to change clinical practice, although the clinical benefits of early surgery require confirmation in a clinical trial.
Sarcomas are malignant tumors arising from the embryonic mesodermal cell lineage. This group of cancers covers a heterogenous set of solid tumors arising from soft tissues or bone. Many features such ...as histology, biological behavior and molecular characteristics are shared between sarcomas in humans and dogs, suggesting that human sarcoma research can be informative for canine disease, and that dogs with sarcomas can serve as relevant translational cancer models, to aid in the understanding of human disease and cancer biology. In the present paper, risk factors for the development of sarcoma in dogs are reviewed, with a particular focus on recent advances in clinical genetics, and on the identification of simple and complex genetic risk factors with a comparison with what has been found in human orthologous disease.
Histiocytic sarcoma (HS) is a common tumour in flat coat retrievers (FCRs) often affecting periarticular tissues and joints. Palliative‐intent radiotherapy, seeks to achieve local tumour control, ...pain relief and improve limb function. However, the effect of palliative‐intent radiotherapy on analgesic levels of dogs with localised HS has not been studied. We hypothesised that palliative‐intent radiotherapy could improve lameness in dogs affected by localised HS. This study aimed to assess the impact of palliative‐intent radiotherapy on lameness of FCRs with localised HS. A retrospective cohort single institution study was performed. Medical records of FCR dogs with HS that received external beam radiotherapy between 2003 and 2022 were reviewed and included demographic, staging, severity of baseline lameness, therapeutic management and outcome data. Descriptive statistics, McNemar's chi‐squared test, Fisher's exact test and Kaplan–Meier analysis were used for statistical analysis. Thirty‐nine dogs were included with a median age of 7.2 years, 25 were male and 14 were female. HS was most commonly located in the forelimb (29 dogs, 74.3%), affecting the shoulder joint (19 dogs, 48.7%). Staging was performed in all 39 dogs with 22 (56.4%) dogs having localised HS, six (15.3%) dogs had localised HS with node metastasis and 11 (28.2%) dogs had localised HS with systemic metastasis. All dogs received palliative‐intent hypo‐fractionated radiation therapy, 32 (82%) dogs showed improvement in lameness. In conclusion, palliative intent radiation treatment has an analgesic effect reducing lameness or clinical signs associated with affected tumour‐bearing joints.
Objectives
Serum amyloid A (SAA) concentrations are increased in cats with lymphoma vs healthy cats; however, the association between SAA concentrations and prognosis in cats with lymphoma is ...unclear. The aim of this study was to evaluate if SAA concentrations were different in cats with nasal vs non-nasal lymphoma, if SAA concentrations are prognostic in patients treated with high-dose chemotherapy and if SAA concentrations are correlated with other clinicopathological variables.
Methods
Cats diagnosed with intermediate- or large-cell lymphoma between 2012 and 2022 with SAA concentration data available were included. Associations between tumour site (nasal vs non-nasal), stage, response to treatment and SAA concentration were evaluated using non-parametric statistics. Associations between SAA concentrations and stage with survival time were evaluated using Cox regression analysis. Patients with nasal tumours and those not receiving high-dose chemotherapy were excluded from the survival analyses.
Results
Thirty-nine cats were included. Median SAA concentrations were significantly higher in non-nasal compared with nasal lymphoma (42 µg/ml range <0.3–797 vs <0.3 µg/ml range <0.3–0.9; P = 0.026). SAA concentrations did not correlate with tumour stage. Median survival time for patients with non-nasal tumour and undergoing chemotherapy was 49 days (range 2–1726). Responders had a better median survival time than non-responders (273 days range 43–1728 vs 39 days range 2–169; P <0.001), whereas SAA concentrations were not associated with survival time. Lower haematocrit at presentation was associated with a reduced median survival time (P = 0.007).
Conclusions and relevance
In the population examined, no correlation between serum concentration of SAA and prognosis in patients with lymphoma was identified, while low haematocrit and lack of response to treatment were both found to be associated with survival time. SAA concentrations were elevated in patients with non-nasal lymphoma vs patients with tumours confined to the nasal cavity.
Background
Seizures are a common presenting sign in dogs with brain tumors.
Hypothesis/Objectives
To investigate the effect of radiotherapy on freedom from brain tumor‐associated seizures and ...survival time in dogs.
Animals
Thirty‐two client‐owned dogs with brain tumor‐associated seizures; 18 received medical treatment and radiotherapy, 14 received medical treatment alone.
Methods
Multicenter retrospective study. Baseline characteristics (seizure semiology, magnetic resonance imaging MRI characteristics, and treatment) and duration of seizure freedom were recorded for the 2 treatment groups. Duration of seizure freedom between groups was compared (log‐rank test) using Cox's proportional hazard analysis, with baseline characteristics entered as covariates.
Results
The duration of seizure freedom and survival time were significantly longer in the radiotherapy group (P < .001), with a mean of 24 months (95% confidence interval CI, 14.3‐33.8) versus 1.7 months in the control group (95% CI, 0.5‐2.9) and a mean of 34.6 months (95% CI: 25.2‐44.1) versus 6.2 months in the control group (95% CI, 2.6‐9.7) respectively. Baseline characteristics were not associated with duration of seizure freedom after the start of treatment. In the radiotherapy group, 5 dogs were euthanized during the study period because of causes other than seizures. In the control group, recurrence of seizures was observed before death in all dogs.
Conclusions and Clinical Importance
A longer period of seizure freedom and longer survival time was observed in dogs with brain tumors after radiotherapy compared to medical treatment only. The pathophysiological mechanisms of epileptogenesis and the effect of radiation therapy on seizure control are unclear to date. Further prospective studies are needed.
OBJECTIVE To compare outcomes of dogs treated surgically for oral, nontonsillar, squamous cell carcinomas (SCCs) and fibrosarcomas (FSAs) with outcomes of dogs treated with a combination of surgery ...and postoperative radiotherapy; to explore whether postoperative, hypofractionated radiotherapy improved outcomes of dogs with incomplete excisions; and to identify prognostic factors associated with outcome. DESIGN Retrospective cohort study. ANIMALS 87 client-owned dogs that had undergone maxillectomy or mandibulectomy for treatment of oral SCC or FSA between 2000 and 2009. PROCEDURES Medical records were retrospectively reviewed. Survival analysis was performed with Kaplan-Meier and Cox regression analyses to evaluate potential prognostic factors associated with patient outcome. RESULTS Median survival time (MST) for all 87 dogs was 2,049 days, but was not reached for dogs with SCC, and was only 557 days for dogs with FSA; tumor type was a significant predictor of survival time. Dogs undergoing postoperative radiotherapy after incomplete excision of oral SCCs had a significantly longer MST (2,051 days) than did dogs with incompletely excised tumors and no radiotherapy (MST, 181 days). Postoperative radiotherapy of dogs with incompletely excised FSAs did not appear to offer protective value (MST, 299 days with radiotherapy and 694 days without radiotherapy). CONCLUSIONS AND CLINICAL RELEVANCE Wide-margin surgical excision should be considered the gold-standard treatment for dogs with oral SCC or FSA. For dogs with oral SCCs without clean surgical margins, survival times may be improved by providing postoperative, hypofractionated radiotherapy.
Histiocytic sarcoma (HS) is an aggressive malignant tumor of histiocytes, which can affect almost any organ in the body and is characterized by a broad array of tumor locations and clinical ...presentations. So far, no complete overview exists of the array of clinical aspects of HS in specific dog breeds in large groups. Therefore, we investigated the clinical characteristics of HS in a population of Bernese Mountain Dogs (BMD; n = 365) and Flat-Coated Retrievers (FCR; n = 289), which are two of the most affected dog breeds. Cases were selected from databases from different pathology services, and clinical information was retrospectively collected for each case. Localized HS was reported significantly more frequently in the FCR (60.6%) than in the BMD (39.2%), and disseminated HS was recorded significantly more frequently in the BMD (60.8%) than in the FCR (39.4%). Lameness was seen more often in FCR than in BMD, and the vast majority (78.1%) of LHS leading to lameness was located in the front legs in the FCR, while in the BMD, there was a more even distribution. BMD had significantly more often leukocytosis and thrombocytopenia, even corrected for the type of HS, than FCR. No significant difference in the frequency of anemia was recorded between BMD and FCR. In those dogs in which blood examination was performed, hypercalcemia was diagnosed in 15 BMD, while none of the FCR had hypercalcemia. The new information provided in this study can aid the diagnostic process and allow for prompt treatment recommendations.
Colour polymorphisms have evolutionary significance for the generation and maintenance of species diversity. Demonstrating heritability of polymorphic traits can be challenging for wild populations ...of long-lived species because accurate information is required on trait expression and familial relationships. The Australian magpie Cracticus tibicen has a continent-wide distribution featuring several distinct plumage morphs, differing primarily in colour of back feathers. Black or white-backed morphs occur in eastern Australia, with intermediate morphs common in a narrow hybrid zone where the two morphs meet. This study investigated heritability of back colour phenotypes in a hybrid zone population (Seymour, Victoria) based on long-term observational data and DNA samples collected over an 18 year period (1993-2010). High extra-pair paternity (~ 36% offspring), necessitated verification of parent-offspring relationships by parentage analysis. A total of 538 birds (221 parents and 317 offspring) from 36 territories were analysed. Back colour was a continuous trait scored on a five-morph scale in the field (0-4). High and consistent estimates of back colour heritability (h
) were obtained via weighted mid-parent regression (h
= 0.94) and by animal models (h
= 0.92, C.I. 0.80-0.99). Single-parent heritability estimates indicated neither maternal nor paternal non-genetic effects (e.g., parent body condition) played a large role in determining offspring back colour, and environmental effects of territory group and cohort contributed little to trait heritability. Distinctive back colouration of the Australian magpie behaves as a quantitative trait that is likely polygenic, although mechanisms responsible for maintaining these geographically structured morphs and the hybrid zone where they meet are unknown.
Histiocytic sarcoma (HS) represents a group of malignant canine tumors to which Bernese Mountain Dogs (BMD) and Flatcoated Retrievers (FCR) are predisposed. The differential diagnosis for HS is ...broad, encompassing round cell tumors, sarcomas and other histiocytic diseases. The aim of this study was to establish morphological and immunohistochemical criteria for routine use on formalin-fixed, paraffin-embedded samples and cytological smears for the recognition and differentiation of canine HS and its subtypes.
Retrospectively, tumor sections were reviewed from 449 BMD and 380 FCR with confirmed or suspected HS, other histiocytic conditions, or a disease of the differential diagnosis of HS.
In a large proportion of cases, 47.5% for histology and for 46.3% cytology, the initial diagnosis was changed after the revision process. A large variation in morphological features of HS was observed in this study, making the existence of several subtypes in dogs also very likely. Furthermore, the different percentage of morphological features between BMD and FCR indicates the different mixture of cell type origins resulting possibly from genetic or environmental differences at the onset of HS in those breeds.
This study stresses the value of a strictly applied and standardized scoring system for microscopic evaluation of tumor sections and smears, and the implementation of review and revision of pathological diagnoses.
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