Davide Berlato

Histologic Grading of Canine Mast Cell Tumor Is 2 Better Than 3

Mast cell tumor (MCT) is a common canine cutaneous neoplasm with variable biological behavior. A 2-tier histologic grading system was recently proposed by Kiupel et al to reduce interobserver variation and eliminate prognostic uncertainty of the Patnaik system. This study compared the ability of these 2 grading systems to predict survival in a cohort of dogs with MCTs. However, surgical margins were unknown, and the risk of developing new/metastatic MCTs was not studied. Histologic grade was assessed according to both systems for 137 surgically resected cutaneous MCTs. The relationship between grade and survival was evaluated. According to the Patnaik system, 18 MCTs (13.1%) were classified as grade I, 83 (60.6%) as grade II, and 36 (26.3%) as grade III. Grade III was associated with a poorer prognosis (P < .001), but no significant difference between grades I and II was detected. Grading according to the Patnaik system was based on consensus grading among 3 pathologists, and interobserver variability was not considered. All grade I MCTs were low grade in the Kiupel system, and all grade III were high grade. Among grade II, 71 (85.6%) were low grade, and 12 (14.4%) were high grade, with a 1-year survival probability of 94% and 46%, respectively (P < .001). The 2-tier system had a high prognostic value and was able to correctly predict the negative outcomes of some grade II MCTs. Data also confirm that histologic grading cannot predict biological behavior of each MCT and should be supplemented with molecular methods for more accurate prognostication.

Initial evaluation of canine urinary cystatin C as a marker of renal tubular function

OBJECTIVES To evaluate the performance of a particle-enhanced turbidimetric assay for measuring canine urinary cystatin C and to investigate if the urinary cystatin C to creatinine ratio is higher in dogs with renal disease than in non-renal disease dogs. METHODS Urinary cystatin C was measured by particle-enhanced turbidimetric assay using an avian antihuman cystatin C antibody and the performance of this assay was evaluated. Clinical relevance was tested in 46 dogs that were divided into three groups: healthy dogs (n=14), non-renal disease dogs (n=17) and dogs with renal disease (n=15). RESULTS The assay was linear (R(2)=0·99) and precise (mean intra- and inter-assay coefficients of variation were 2·3 and 2·9%, respectively). The recovery was 111·5% and the limit of blank was 0·02 mg/L. Urinary cystatin C and urinary cystatin C to creatinine ratio differed significantly (P<0·001) between the three cohorts of dogs. CLINICAL SIGNIFICANCE Measurement of cystatin C by particle-enhanced turbidimetric assay performed with high precision and linearity. This assay can be processed on automated clinical chemistry analysers making it widely available to commercial laboratories. Urinary cystatin C to creatinine ratio can differentiate dogs with renal disease from dogs without renal disease. These preliminary results suggest that urinary cystatin C to creatinine ratio is a promising marker for evaluating renal tubular function.

Canine oral mucosal mast cell tumours

Mast cell tumours (MCTs) are the most common cutaneous tumours of dogs, however rarely they can arise from the oral mucosa. This subset of MCT is reported to demonstrate a more aggressive clinical course than those tumours on the haired skin and the authors hypothesised that dogs with oral, mucosal MCT would have a high incidence of local lymph node metastasis at presentation and that this would be a negative prognostic factor. An additional hypothesis was that mitotic index (MI) would be prognostic. This retrospective study examines 33 dogs with MCTs arising from the oral mucosa. The results suggest that oral mucosal MCTs in the dog have a high incidence of lymph node metastasis at diagnosis (55%) which results in a poor prognosis. MI and nodal metastasis is highly prognostic. Loco-regional progression is common in these patients and dogs with adequate local control of their tumour had an improved outcome. Despite a more aggressive clinical course, treatment can result in protracted survivals, even when metastasis is present.

Comparison of mitotic index and Ki67 index in the prognostication of canine cutaneous mast cell tumours.

Proliferation markers are commonly used for prognostication of mast cell tumours. The aim of the study is to compare the relative abilities of Ki67 and mitotic index to predict survival in the same cohort of dogs with cutaneous MCTs. Histological grade, mitotic index and Ki67 index were performed in all samples and clinical information was obtained by a follow-up questionnaire. Ninety-five dogs were included in the study with a median follow-up of 1145 days. Survival times varied significantly between categories of histological grade, mitotic index and Ki67 index. Multivariable analyses showed that the risk of dying due to MCT was similar in dogs with increased Ki67 index [hazard ratio, HR: 3.0 (95% CI 1.3-6.8)] or increased mitotic index [HR: 2.7 (95% CI 1.1-6.5)]. In conclusion, both mitotic index and Ki67 index were able to independently differentiate MCTs with worse prognosis. This distinction is particularly meaningful in selecting intermediate grade MCTs that may benefit from more aggressive local or systemic treatment.

Radiotherapy in the management of localized mucocutaneous oral lymphoma in dogs: 14 cases

Oral mucocutaneous lymphoma is rare in dogs. Surgery and chemotherapy do not usually provide effective long-term control. The objective of this study was to retrospectively evaluate survival of dogs with localized oral lymphoma treated with radiation therapy. The medical database of three institutions was searched for dogs with diagnosis of oral lymphoma treated with radiotherapy. Dogs with evidence of systemic disease were excluded. Survival was calculated with the Kaplan-Meier method and prognostic variables analysed with log-rank test. Fourteen dogs were included in the study. Mean survival was 1129 days [95% confidence interval (CI) 711-1546] with median survival of 770 days. The overall response of radiotherapy was 67% (five complete and three partial responses). A survival advantage was seen in dogs with no evidence of lymph node metastasis (P = 0.002) and that achieved a complete response to radiation therapy (P = 0.013). Radiation therapy was a well-tolerated and effective treatment for localized oral lymphoma.

Prognostic Significance of Canine Mammary Tumor Histologic Subtypes: An Observational Cohort Study of 229 Cases

Histopathology is considered the gold standard diagnostic method for canine mammary tumors. In 2011, a new histologic classification for canine mammary tumors was proposed. The present study was a 2-year prospective study that validated the 2011 classification as an independent prognostic indicator with multivariate analysis in a population of 229 female dogs, identifying subtype-specific median survival times (MST) and local recurrence/distant metastasis rates. Dogs with benign tumors and carcinoma arising in benign mixed tumors all had an excellent prognosis. Dogs with complex carcinoma and simple tubular carcinoma also experienced prolonged survival. Those with simple tubulopapillary carcinoma, intraductal papillary carcinoma, and carcinoma and malignant myoepithelioma had a more than 10-fold higher risk of tumor-related death. The prognosis was even worse for adenosquamous carcinoma (MST = 18 months), comedocarcinoma (MST = 14 months), and solid carcinoma (MST = 8 months). The most unfavorable outcome was for anaplastic carcinoma (MST = 3 months) and carcinosarcoma (MST = 3 months), which also had the highest metastatic rates (89% and 100%, respectively). Adenosquamous carcinoma exhibited the highest local recurrence rate (50%). In the same canine population, the tumor diameter was recognized as a strong predictor of local recurrence/distant metastasis and an independent prognosticator of survival in the multivariate analysis. Excision margins were predictive only of local recurrence, whereas lymphatic invasion and histologic grade were predictive of local recurrence/distant metastasis and survival, although only in univariate analyses. In conclusion, this study validated the 2011 classification scheme and provided information to be used in the clinical setting and as the basis for future prognostic studies.

Clinical outcome in 19 cats with clinical and magnetic resonance imaging diagnosis of ischaemic myelopathy (2000-2011)

Previous publications on ischaemic myelopathy in cats are limited to single case reports and small case series. The overall prognosis appears poor, with 42% of cats being euthanased. In this study the clinical outcome of 19 cats with a presumptive diagnosis of ischaemic myelopathy [based on clinical and magnetic resonance imaging (MRI) findings] was evaluated retrospectively. The degree of neurological dysfunction at the time of presentation was similar to previously reported cases, ranging from ambulatory paresis to plegia with intact nociception. The most common lesion localisations (based on MRI) were to the C1–C5 (30%) and C6–T2 (30%) spinal cord segments, with the T3–L3 and L4–S1 spinal cord segments accounting for 25% and 15%, respectively. Potential inciting or predisposing causes for development of spinal infarction were identified in 12 cats, including physical exertion, trauma, general anaesthesia, renal disease, hyperthyroidism, hypertension and hypertrophic cardiomyopathy. The median time to recovery of ambulation was 3.5 days (3–19 days). Four cats (21%) were euthanased within 2 months of diagnosis. The remaining 15 (79%) cats had a favourable outcome. Follow-up ranged from 6 months to 10 years and 4 months, with a median of 3 years and 1 month. Even when plegia was present at the time of presentation, all surviving cats with long-term, owner-derived follow-up were reported to return to a normal quality of life, suggesting that the long-term prognosis for recovery from presumed ischaemic myelopathy is favourable in the majority of cats.

Evaluation of minichromosome maintenance protein 7 as a prognostic marker in canine cutaneous mast cell tumours

Minichromosome maintenance proteins (MCMs) are sensitive markers of cellular proliferation and have been shown to be significant predictors of survival in several human malignancies. MCM7 was evaluated as a prognostic marker in canine cutaneous mast cell tumours (MCTs). MCM7 immunohistochemistry was performed and an index of MCM7-positive cells calculated in dogs with known outcome. The Receiver Operating Characteristics method was used to individuate the best cut-off value of MCM7 score as predictor of survival. Survival analysis and prognostic variables were analysed with statistical methods. Ninety-five dogs were included with 31 dying of MCTs. A value of 0.18 was used as cut-off value of MCM7 score as a binary variable. The median survival time for MCM7 score ≤0.18 was not reached at 3668 days, whereas for MCM7 score >0.18 was 187 days (log-rank test; P < 0.0001). In the multivariable analysis, MCM7 was significantly associated with survival after controlling for age, surgical margins and histological grade (hazard ratio 9.2; P = 0.001).

Rectal lymphoma in 11 dogs – a retrospective study

OBJECTIVES To retrospectively evaluate the clinical behaviour and immunophenotype of lymphoma of the rectum in dogs. METHODS Eleven dogs diagnosed with lymphoma of the rectum on histopathology were retrospectively reviewed. Immunohistochemistry with CD3 and CD79a antibodies was performed at diagnosis or retrospectively. RESULTS Treatment protocol varied with six dogs undergoing surgery and adjuvant chemotherapy, two received chemotherapy after only incisional biopsy, one had surgical resection only, one was treated symptomatically and one dog was not treated. Chemotherapy treatment consisted of either a -low-dose COP (cyclophosphamide - prednisolone - vincristine) protocol (four dogs) or a six-week CHOP-based (cyclophosphamide - vincristine - -prednisolone - anthracycline) protocol (four dogs). Dogs that received chemotherapy lived significantly longer than dogs that did not receive chemotherapy (2352 versus 70 days). Median survival time was not reached, and there was an overall mean survival time of 1697 days. Immunohistochemistry was performed in 10 of 11 samples, and was consistent with B-cell -lymphoma in all cases. CLINICAL SIGNIFICANCE Canine lymphoma of the rectum is associated with a favourable prognosis. Immunohistochemical evaluation of these lesions was consistent with B-cell lymphoma in all cases in which it was examined.

Use of Oncept melanoma vaccine in 69 canine oral malignant melanomas in the UK

OBJECTIVES Oral malignant melanomas carry a poor-to-guarded prognosis because of their local invasiveness and high metastatic propensity. The Oncept melanoma vaccine is licensed to treat dogs with stage II or III locally-controlled oral malignant melanoma and this retrospective study aimed to assess survival of affected dogs treated with the vaccine in the UK. MATERIAL AND METHODS Medical records of dogs with histopathologically-confirmed oral malignant melanoma that received the vaccine as part of their treatment were evaluated. Survival analyses for potential prognostic factors were performed. RESULTS Sixty-nine dogs were included; 56 dogs, staged I to III, and with previous locoregional therapy, had a median survival time of 455 days (95% CI: 324 to 586 days). Based on Kaplan-Meier survival analysis with associated log-rank testing, no significant prognostic factors were identified for this population. Of the 13 patients with macroscopic disease treated with vaccine alone or in combination therapy, eight showed clinical response. Three patients with stage IV oral malignant melanoma survived 171, 178 and 288 days from diagnosis. CLINICAL SIGNIFICANCE Patients treated with the melanoma vaccine in our study had survival times similar to their counterparts receiving the vaccine in the USA. There were observed responses in patients with macroscopic disease and so the vaccine could be considered as palliative treatment in dogs with stage IV disease.