Tais Meziara Wilson

Discrepancy between Clinical and Postmortem Diagnosis of Dogs in a Veterinary Medical Teaching Hospital

Background: The postmortem examination offers the opportunity to study the processes involved in disease. Although a portion of veterinary medical professionals and students consider the necropsy as a diagnostic tool of purely academic interest, it can provide valuable assistance in formulating health strategies in order to prevent and control animal diseases. The number of necropsies performed in general is higher in universities where the cost is subsidized. In veterinary medicine, studies intended to assess the frequency of necropsy and the discrepancy between clinical and postmortem diagnosis of dogs are rare. The main purpose of the necropsy is to discover the cause of death of dogs, by defining a possible etiology and pathogenesis in order to reach a diagnosis. Material, Methods & Results: We used medical records and necropsy records to define the clinical and postmortem diagnosis, respectively. Data relating to deaths was recorded as the number of euthanized dogs and natural deaths in 2014. From the information cause of death, these were categorized as infectious disease, cardiac, gastrointestinal, renal, pulmonary, neurological, metabolic or endocrine disease, neoplastic disease, trauma, or systemic disease. We used the Binomial discrepancy in the comparison of the rates between different years and also to verify the association between discrepancy and the correlation between clinical and postmortem diagnosis of dogs with euthanasia and natural death, with statistical significance (P < 0.05). In 2009, 56.81% (25/44) of cases included in the study had a concordance between the clinical and postmortem diagnosis, while 43.19% (19/44) were discordant. In 2014, it was observed that 71.70% (76/106) of the diagnosis was confirmed with the necropsy, while 28.30% (30/106) were discordant. The disagreement rate was higher in 2009 (P < 0.05) and there was a reduction of 14.89% in the disagreement rate between 2009 and 2014. Regarding the cause of death, infectious diseases, gastrointestinal disease, and heart disease were the categories in which the discrepancy was higher. It was found that in the group of dogs euthanized, the discrepancy rate was lower compared with the group of dogs that had anatural death (P < 0.05). Discussion: The disagreement rate can be considered high when compared with a veterinary study and similar to those observed in a human study. Decrease in the discrepancy rate in the years, as observed by other authors, that can be attributed to improvements and expansion of diagnostic services of the hospital and better training of veterinarians. The difficulty in determining the etiology of infectious diseases is associated with lack of specific diagnostic tests and the high cost of available tests, which often is not bank rolled by the tutor. Dogs in this study were rarely submitted to diagnostics tests such as electrocardiogram or echocardiogram which explains the high discordance in the diagnosis of heart disease. Distemper is an infectious disease of great importance regarding euthanized animals, especially in cases that progress to central nervous system injuries with extremely poor prognosis and wind up having euthanasia indication. Another common cause of domestic animals euthanasia indication is the occurrence malignant neoplasms, which depends on the progression of the disease and psychological and social conditions of the owner. The results generated herein suggests that infectious, gastrointestinal and cardiac diseases origin tend to have a greater discordance between clinical and postmortem diagnosis, however this rate is decreasing due to improved infrastructure of veterinary centers with better professionals qualification.

Prognostic Factors in Canine Mammary Carcinomas and HER2 Expression Relationship

Background: The human epidermal growth factor type 2 (HER2) receptor is a membrane glycoprotein tyrosine kinase. In woman, HER2 expression is diagnosed in 30% of breast carcinomas and it is associated with a worse prognosis, higher rate of recurrence and mortality. In the bitch, the HER2 overexpression in canine mammary tumors is still controversial and the prognostic value remains uncertain. Thus, we aimed to verify the HER2 expression in canine mammary carcinomas and relate it to the type and histological grade, lymph node metastasis and clinical staging. Materials, Methods & Results: Ninety bitches diagnosed with mammary carcinoma were included in this study. The inclusion criteria were bitches with complete clinical examination, thoracic radiographic examination and submitted unilateral or bilateral mastectomy. Ninety-nine samples of mammary carcinoma were used and the fragments of tumor and regional lymph nodes were fixed in 10% neutral formalin for histopathological and immunohistochemistry analysis. The lesions were evaluated by two pathologists and classified according to the type and histological grade. HER2 expression was performed by semi-quantitative analysis of the slides according to the HerceptTestTM (Dako) recommended score. Simple carcinomas were the most frequent (51.51%) followed by complex carcinomas (46.47%) and in situ carcinoma (2.02%). The histological grade of 97 carcinoma samples was attributed, except in situ carcinoma, 37 (38.14%) of the neoplasms were grade I, 50 (51.55%) grade II and only 10 (10.31%) tumors were classified as grade III. Forty bitches were submitted to clinical staging (TNM) and 42.50% of the bitches received staging in grade I and, 25% of the bitches staged in grade IV and V, with metastases. The HER2 expression, 13/99 samples (13.13%) received score +2, 19/99 (19.19%) score +1 and absence of marking (score 0) was identified in 67 samples (67.80 %). Immunostaining in hyperplastic or normal epithelial cells was evidenced, often in association with weak or moderate cytoplasmic labeling. Of the samples expressing +2 score for HER2 (n = 13), eight samples (17.39%) were complex carcinoma and five (9.80%) simple carcinomas. There was no relationship between HER2 immunostaining with age, tumor size, TNM, histological type, histological gradation, lymph node metastasis and distance. Animals with lymph node metastasis, as well as those diagnosed with distant metastasis, did not present HER2 expression in the tumors. Discussion: The simple carcinoma seems to be the most frequent type histological diagnosed in canine mammary carcinomas, followed by carcinoma in mixed tumor and complex carcinoma. Tubulopapillary carcinomas are more invasive in the female dogs as well as in the woman. Carcinomas grade I and II are more frequent and present a better prognosis for the dog. However, bitches with grade III carcinoma survived for a shorter time when compared to dogs with grade I or II tumors. A factor that may have contributed to the lower number of bitches at worst prognostic stage (EC IV and V) is the current owners’ awareness that they have sought veterinary help earlier, as soon as they detect small nodules in mammary gland. Overexpression of HER2 in women breast cancer is diagnosed in 20-30% of cases, whereas in bitches, this expression is variable. Also the different percentages of canine HER2 immunostaining are due to the lack of standardization for the analysis of the immunostaining, the immunohistochemical techniques employed and the non-specificity of the HER2 antibody. In canine mammary carcinomas the HER2 expression in low and this immunostaining is not related to other established prognostic factors. This study reinforces the hypothesis put forward by other authors that in the bitch the expression of HER2 may not be related to malignancy and tumor progression.