Prima segnalazione di un caso di tumore misto mulleriano dell’ovaio in un cane = First report of canine malignant mixed mullerian tumor of the ovary

Adenocarcinoma is the most represented histotype of primary ovarian neoplasms in aged bitch. In woman, adenocarcinomas are quite common, whereas mixed forms as carcinosarcomas, or malignant mixed mullerian tumors [MMMTs] are rarely reported. The aim of the present study is to describe light and immunohistochemical findings of canine heterologous ovarian MMMT

<i>Mycobacterium chelonae</i> associated with tumor-like skin and oral masses in farmed Russian sturgeons (<i>Acipenser gueldenstaedtii</i>)

Background: Non-tuberculous mycobacteria responsible for piscine mycobacteriosis usually produce visceral granulomas in both freshwater and marine species. In this study, the first occurrence of Mycobacterium chelonae associated with tumor-like lesions in the Russian sturgeon (Acipenser gueldenstaedtii) is reported. Fifteen sturgeons from an Italian fish farm showing skin and oral cauliflower-like masses were investigated by histopathology, bacterial culture and molecular analyses. Results: A total of 20 masses different in size located in the mouth and in pectoral and caudal fins (characterized by abundant calcium deposits and by mild to moderate granulomatous inflammation) were observed with a significant different degree of histological severity. All internal organs of the fish were negative for mycobacteria, Ziehl-Neelsen was positive in only one of the oral masses, whereas bacterial and PCR analyses detected the presence of M. chelonae for almost all the skin and oral masses. Based on these results, a calcinosis of dystrophic origin associated with a chronic granulomatous inflammation was considered as a primary diagnosis consequent to tissue injury in areas susceptible to trauma. Conclusions: We hypothesized that the occurrence of M. chelonae in farmed sturgeons was only a secondary event related to its presence in a stressful rearing environment and subsequent to a dystrophic calcinosis occurred in previously damaged tissues

Mycobacterium chelonae associated with tumor-like skin and oral masses in farmed Russian sturgeons (Acipenser gueldenstaedtii)

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Spontaneous feline mammary intraepithelial lesions as a model for human estrogen receptor- and progesterone receptor-negative breast lesions

Background. Breast cancer is the most frequently diagnosed cancer in women. Intraepithelial lesions (IELs), such as usual ductal hyperplasia (UH), atypical ductal hyperplasia (ADH), and ductal carcinoma in situ (DCIS) are risk factors that predict a woman's chance of developing invasive breast cancer. Therefore, a comparative study that establishes an animal model of pre-invasive lesions is needed for the development of preventative measures and effective treatment for both mammary IELs and tumors. The purpose of this study was to characterize the histologic and molecular features of feline mammary IELs and compare them with those in women. Methods. Formalin-fixed, paraffin-embedded specimens (n = 205) from 203 female cats with clinical mammary disease were retrieved from the archives of the Purdue University Animal Disease Diagnostic Laboratory and Veterinary Teaching Hospital (West Lafayette, IN), and the Department of Pathology and Veterinary Clinic, School of Veterinary Medicine (Sassari, Italy). Histologic sections, stained with hematoxylin and eosin (HE), were evaluated for the presence of IELs in tissue adjacent to excised mammary tumors. Lesions were compared to those of humans. Immunohistochemistry for estrogen receptor (ER-alpha), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER-2/neu) and Ki-67 was performed in IELs and adjacent tumor tissues. Results. Intraepithelial lesions were found in 57 of 203 (28%) feline mammary specimens and were categorized as UH (27%), ADH (29%), and DCIS (44%). Most IELs with atypia (ADH and DCIS) were associated with mammary cancer (91%), whereas UH was associated with benign lesions in 53% of cases. Feline IELs were remarkably similar to human IELs. No ER or PR immunoreactivity was detected in intermediate-grade or high-grade DCIS or their associated malignant tumors. HER-2 protein overexpression was found in 27% of IELs. Conclusion. The remarkable similarity of feline mammary IELs to those of humans, with the tendency to lose hormone receptor expression in atypical IELs, supports the cat as a possible model to study ER- and PR-negative breast lesions

Reproducibility and Feasibility of Classification and National Guidelines for Histological Diagnosis of Canine Mammary Gland Tumours: A Multi-Institutional Ring Study

Histological diagnosis of Canine Mammary Tumours (CMTs) provides the basis for proper treatment and follow-up. Nowadays, its accuracy is poorly understood and variable interpretation of histological criteria leads to a lack of standardisation and impossibility to compare studies. This study aimed to quantify the reproducibility of histological diagnosis and grading in CMTs. A blinded ring test on 36 CMTs was performed by 15 veterinary pathologists with different levels of education, after discussion of critical points on the Davis-Thompson Foundation Classification and providing consensus guidelines. Kappa statistics were used to compare the interobserver variability. The overall concordance rate of diagnostic interpretations of WP on identification of hyperplasia-dysplasia/benign/malignant lesions showed a substantial agreement (average k ranging from 0.66 to 0.82, with a k-combined of 0.76). Instead, outcomes on ICD-O-3.2 morphological code /diagnosis of histotype had only a moderate agreement (average k ranging from 0.44 and 0.64, with a k-combined of 0.54). The results demonstrated that standardised classification and consensus guidelines can produce moderate to substantial agreement; however, further efforts are needed to increase this agreement in distinguishing benign versus malignant lesions and in histological grading. View Full-Tex

Immunohistochemical localisation and molecular expression of the steroidogenic enzyme cytochrome P450 17α-hydroxylase ⁄C(17,20)-lyase in the vestibular nuclei of adult male rats

Many biologically active neurosteroids, including dehydroepiandrosterone (DHEA), are synthesised in the brain. DHEA is a potent endogenous modulator of several neuronal functions, and alterations of DHEA are correlated with various neurobiological deficits. The cytochrome P450 17α-hydroxylase ⁄ C(17,20)-lyase (P450C17) plays a pivotal role in the synthesis of DHEA from pregnenolone and progesterone. We investigated the immunohistochemical localisation and molecular expression of P450C17 in the superior, lateral, medial and inferior vestibular nuclei (VCN) of adult male rats by western blotting and indirect immunofluorescence analysis. Immunoreactive P450C17 was widely distributed in all VCN and the expression of P450C17 was confirmed by western blot analysis. The present study demonstrates, for the first time, the presence and anatomical distribution of P450C17 in the VCN. Given that neurosteroids can modulate neuronal activities in the medial vestibular nucleus, DHEA synthesised in the VCN may play an important role in the control of specific activities at this level

Mammography and ultrasound imaging of preinvasive and invasive canine spontaneous mammary cancer and their similarities to human breast cancer

Understanding the evolution of proliferative breast disease such as atypical hyperplasia and carcinoma in situ is essential for clinical management of women diagnosed with these lesions. Therefore, an animal model that faithfully represents human breast disease in every aspect from spontaneity of dysplasia onset, histopathologic features, and genetics to clinical outcome is needed. Previously, we studied canine spontaneous atypical hyperplasia and ductal carcinoma in situ (low, intermediate, and high grade) and reported their similarities to human lesions in histopathologic and molecular features as well as prevalence. To further validate the resemblance of these lesions to humans, we examined their mammographic and sonographic characteristics in comparison with those of human’s as well as the potential of the human Breast Imaging Reporting and Data System (BI-RADS) to predict canine disease. Nonlesional, benign, and malignant mammary glands of dogs presented to Sassari Veterinary Hospital were imaged using mammography and ultrasonography. The images where then analyzed and statistically correlated with histopathologic findings and to their similarities to humans. Our results showed that canine mammary preinvasive lesions, benign, and malignant tumors have mammographic abnormalities, including the presence, pattern, and distribution of macrocalcification and microcalcification, similar to their human counterparts. BI-RADS categorization is an accurate predictor of mammary malignancy in canine, with 90% sensitivity and 82.8% specificity. The similarities of mammographic images and the ability of BI-RADS to predict canine mammary malignances with high specificity and sensitivity further confirm and strengthen the value of dog as a model to study human breast premalignancies for the development of prognostic biomarkers

Comparability of differential proteomics data generated from paired archival fresh-frozen and formalin-fixed samples by GeLC–MS/MS and spectral counting

In this study, a Veterinary Department repository composed by paired formalin-fixed paraffinembedded (FFPE) and fresh-frozen (FrFr) sets of the same tissues, routinely archived in the typical conditions of a clinical setting, was exploited to perform a comparative evaluation of the results generated by GeLC–MS/MS (1-DE followed by in-gel digestion and LC–MS/MS) and spectral counting with the two types of archival samples. Therefore, two parallel differential proteomic studies were performed using 3 canine mammary carcinomas and 3 normal controls in a paired fashion (6 FrFr and 6 FFPE in total). As a result, the FrFr and FFPE differential proteomic datasets exhibited fair consistency in differential expression trends, according to protein molecular function, cellular localization, networks, and pathways. However, FFPE samples were globally slightly less informative, especially concerning the high-MW subproteome. As a further investigation, new insights into the molecular aspects of protein fixation and retrieval were obtained. In conclusion, archival FFPE samples can be reliably used for differential proteomics studies employing a spectral counting GeLC–MS/MS approach, although some typical biases need to be taken into account, and FrFr specimens (when available) should still be considered as the gold standard for clinical proteomics

Canine Mammary Tumor Histopathological Image Classification via Computer-Aided Pathology: An Available Dataset for Imaging Analysis

Histopathology, the gold-standard technique in classifying canine mammary tumors (CMTs), is a time-consuming process, affected by high inter-observer variability. Digital (DP) and Computer-aided pathology (CAD) are emergent fields that will improve overall classification accuracy. In this study, the ability of the CAD systems to distinguish benign from malignant CMTs has been explored on a dataset—namely CMTD—of 1056 hematoxylin and eosin JPEG images from 20 benign and 24 malignant CMTs, with three different CAD systems based on the combination of a convolutional neural network (VGG16, Inception v3, EfficientNet), which acts as a feature extractor, and a classifier (support vector machines (SVM) or stochastic gradient boosting (SGB)), placed on top of the neural net. Based on a human breast cancer dataset (i.e., BreakHis) (accuracy from 0.86 to 0.91), our models were applied to the CMT dataset, showing accuracy from 0.63 to 0.85 across all architectures. The EfficientNet framework coupled with SVM resulted in the best performances with an accuracy from 0.82 to 0.85. The encouraging results obtained by the use of DP and CAD systems in CMTs provide an interesting perspective on the integration of artificial intelligence and machine learning technologies in cancer-related research

A Statistical Analysis of Risk Factors and Biological Behavior in Canine Mammary Tumors: A Multicenter Study

Canine mammary tumors (CMTs) represent a serious issue in worldwide veterinary practice and several risk factors are variably implicated in the biology of CMTs. The present study examines the relationship between risk factors and histological diagnosis of a large CMT dataset from three academic institutions by classical statistical analysis and supervised machine learning methods. Epidemiological, clinical, and histopathological data of 1866 CMTs were included. Dogs with malignant tumors were significantly older than dogs with benign tumors (9.6 versus 8.7 years, p &lt; 0.001). Malignant tumors were significantly larger than benign counterparts (2.69 versus 1.7 cm, p &lt; 0.001). Interestingly, 18% of malignant tumors were smaller than 1 cm in diameter, providing compelling evidence that the size of the tumor should be reconsidered during the assessment of the TNM-WHO clinical staging. The application of the logistic regression and the machine learning model identified the age and the tumor&rsquo;s size as the best predictors with an overall diagnostic accuracy of 0.63, suggesting that these risk factors are sufficient but not exhaustive indicators of the malignancy of CMTs. This multicenter study increases the general knowledge of the main epidemiologica-clinical risk factors involved in the onset of CMTs and paves the way for further investigations of these factors in association with CMTs and in the application of machine learning technology