The review describes the role of cells of extracellular matrix (ECM) as a source of neoplastic outgrowths additional to the original tumour. The cells undergo a spontaneous transformation or stimulation by the original tumour through intercellular signals, e.g. through Shh protein (sonic hedgehog). Additionally, cells of an inflammatory infiltrate, which frequently accompany malignant tumours and particularly carcinomas, may regulate tumour cell behaviour. This is either by restricting tumour proliferation or, inversely, by induction and stimulation of the proliferation of another tumour cell type, e.g. mesenchymal cells. The latter type of tumour may involve formation of histologically differentiated stromal tumours (GIST), which probably originate from interstitial cells of Cajal in the alimentary tract. Occasionally, e.g. in gastric carcinoma, proliferation involves lymphoid follicles and lymphocytes of GALT (gut-associated lymphoid tissue), which gives rise to lymphoma. The process is preceded by the earlier stage of intestinal metaplasia, or is induced by gastritis alone. This is an example of primary involvement of inflammatory infiltrate cells in neoplastic progression. Despite the numerous histogenetic classifications of tumours (zygotoma benignum et zygotoma malignum, or mesenchymomata maligna et mesenchymomata benigna), currently in oncological diagnosis the view prevails that the direction of tumour differentiation and its degree of histologic malignancy (grading) are more important factors than the histogenesis of the tumour.
Janusz A. Madej, Jan P. Madej, Piotr Dzięgiel, Bartosz Puła and Marcin Nowak
The study aimed to demonstrate the expression of hypoxia-inducible factor (HIF-1α) in soft tissue mesenchymal tumours (fibroma and fibrosarcoma) in dogs. An attempt was made to correlate the obtained results with density of blood vessels (expression of von Willebrand Factor, vWF), expression of Ki-67 proliferation antigen, and with intensity of apoptosis in studied tumours. The study was performed on paraffin sections of 15 fibromas and 40 fibrosarcomas sampled from 55 female dogs aged 6 to 16 years. Immunohistochemical staining against HIF-1α, vWF, and Ki-67 was performed. Apoptosis was detected with the use of TUNEL reaction. A significantly higher HIF-1α expression was noted in fibrosarcomas in comparison to fibromas (P < 0.0001). HIF-1α expression in fibromas manifested strong positive correlation with tumour vascularity (r = 0.67, P = 0.007). Moreover, HIF-1α expression in fibrosarcomas manifested a moderate positive correlation with tumour malignancy grade (r = 0.44, P = 0.004), tumour vascularity (r = 0.52, P < 0.001), Ki-67 antigen expression (r = 0.42; P = 0.007), and TUNELpositive cells (r = 0.37, P = 0.017). Expression of HIF-1α was detected in 86.7% of fibroma type tumours and in 100% of fibrosarcomas. In all studied tumours expression of HIF-1α manifested positive correlation with the density of blood vessels, and in fibrosarcomas it correlated also with malignancy grade, intensity of Ki-67 expression, and with intensity of apoptosis in tumour cells.
Małgorzata Kandefer-Gola, Marcin Nowak, Rafał Ciaputa and Janusz A. Madej
Immunohistochemical studies have become an indispensable element of establishing the correct histopathological diagnosis of poorly differentiated lesions, proving particularly suitable, and occasionally indispensable, for diagnosis of poorly differentiated neoplastic tumours. Knowledge of the mechanism of action and normal reaction of individual proteins is required in selection of the antibody pattern for a given tissue and in evaluation of the obtained results. This paper aims to promote the application of immunohistochemical techniques in routine diagnosis, especially in cases of poorly differentiated or undifferentiated tumours.
Małgorzata Kandefer-Gola, Rafał Ciaputa, Marcin Nowak and Janusz A. Madej
The study aimed at morphological and immunohistochemical characteristics of laryngeal squamous cell carcinomas and their metastases in canine lymph nodes and lungs. Tissue sections were stained using classical technique with haematoxylin and eosin. In addition, immunohistochemical studies were performed with p16, cytokeratin, and Ki-67 antibodies. An expression of all examined antigens was detected in laryngeal tumours, while in tumour metastases only expression of p16 protein and cytokeratin was demonstrated. The results pointed to higher proliferative potential of the primary tumour than of their metastases.
Rafał Ciaputa, Małgorzata Kandefer-Gola, Marcin Nowak and Janusz A. Madej
The study aimed at the analysis of prevalence frequency and localisation of tumours in domestic animals. The research material comprised 4,212 tumours developed in dogs, cats, horses, and exotic animals, isolated during surgery, autopsy or biopsy, performed for the purpose of histopathological diagnosis. The most numerous group involved canine tumours, including 3,585 cases (85.1%), followed by tumours in cats (532 cases, 12.6%), ferrets (34 cases, 0.81%), rats (19 cases, 0.45%), horses (15 cases, 0.36%), and rabbits (14 cases, 0.33%). A significant increase in incidence of tumours was noted, as compared to studies performed in the same region of Poland in 1957-1995 and 2000-2004 or in 2005-2008. This was particularly evident in exotic animals, in which 80 cases (1.9%) were detected in 2009-2011 but only 20 cases (1.2%) in 2005-2008. The most frequent localisation of neoplasia involved the skin, subcutaneous tissue, and mammary gland.
The study was conducted on ventricular and atrial wall preparations from 11 dogs with clinically diagnosed dilated cardiomyopathy. After fixation, the specimens were stained with haematoxylin and eosin and Masson-Goldner trichrome technique. Parenchymal changes (fibrosis and fatty infiltration), vascular changes (congestion and coronary vessel wall hypertrophy), degenerative changes (loss of striation, changes in cardiomycyte and nuclei structure), and presence of inflammatory infiltrates (mononuclear and polynuclear) were estimated. Complex histological changes in both ventricular and atrial muscles were shown. It was not determined whether the processes occurring in the myocardium have a primary character, or are a consequence of developing heart failure. Such issues will be put under further and more detailed examination.
Rafał Ciaputa, Marcin Nowak, Maciej Kiełbowicz, Agnieszka Antończyk, Karolina Błasiak and Janusz A. Madej
The study aimed at presenting the most frequent male gonadal tumours in dogs, their clinical and histopathological aspects, at outlining aetiopathogenesis and differential diagnosis of the tumours. As examples of the most frequently manifested testicular tumours, three clinical cases were presented, involving tumour of interstitial (Leydig) cells, tumour of Sertoli cells, and seminoma. Respective clinical diagnosis employed USG, X-ray patterns, and morphological and biochemical tests. The surgically sampled material was stained with H+E and an attempt was made to establish expression of E-cadherin, calretinin, and Ki-67. It was shown that histopathological diagnosis of testicular tumours in dogs is frequently very difficult and complex and requires multidirectional studies.
Rafał Ciaputa, Marcin Nowak, Janusz A. Madej, Izabela Janus, Elżbieta Górzyńska and Małgorzata Kandefer-Gola
Immunohistochemical profiles of the most common canine testicular tumours, including the Leydig cell tumours, seminomas, and Sertoli cell tumours were analysed, and the results were compared with those obtained in the corresponding types of human testicular neoplasms. The expressions of vimentin, von Willebrand factor (FVIII), chromogranin A, synaptophysin, and MCM3 were quantified. In the case of Sertoli cell tumours, only canine ones were analysed, since this type of tumour is very rarely diagnosed in men. The expression of the analysed proteins in the testicular tumours was similar. The von Willebrand factor exhibited the strongest expression in Leydig cell tumours in dogs and men, while vimentin was expressed more strongly in dogs (96.7% had an intensity at +++) than in men (62.5% had +++) in the Leydigioma. The immunoexpression of MCM3 in seminomas was high in both men and dogs – 90% +++ and 100% +++ respectively. The lack of chromogranin A and synaptophysin was observed in almost 100% of seminomas in men and dogs. This differed from the results obtained for Leydigioma, where chromogranin A was expressed in 70% of dogs at +++ and in 100% of men at ++++. The results may indicate that the antibodies were selected correctly. Their analysis and interpretation provides valuable information concerning the nature of the studied tumours.
Małgorzata Kandefer-Gola, Janusz A. Madej, Stanisław Dzimira, Izabela Janus, Marcin Nowak and Rafał Ciaputa
The aim of the study was to assess the microvessel density based on the analysis of the expression of the CD31, VEGF, and LIMS-1 proteins in canine mast cell tumours. The study was conducted on 60 mastocytomas; 16 cases were classified as the grade I, 26 as the grade II, and 18 as the grade III. Statistical analysis showed a positive correlation only between the grade of the tumour and the expression of LIMS-1. In conclusion, LIMS-1 could be successfully used as a prognostic endothelial cell marker in mast cell tumour. CD31 may be a useful marker, but further examinations are necessary. VEGF is not recommended
Anna Kycko, Agnieszka Jasik, Łukasz Bocian, Iwona Otrocka-Domagała, Mateusz Mikiewicz, Anna Śmiech, Wojciech Łopuszyński, Izabella Dolka, Marcin Nowak and Janusz A. Madej
Introduction: Apocrine sweat gland carcinomas (ASGCs) are malignant neoplasms of dogs and other animals, rarely reported worldwide. The aim of this study was to summarise the occurrence of this cancer in a population of dogs in Poland between 2009 and 2014 with regards to histological features and body location of the tumours, as well as age, sex and breed of the cancer-affected dogs.
Material and Methods: The study involved 40 canine ASGC cases diagnosed in five national veterinary pathology laboratories. The material was processed according to routine histological methods.
Results: Histological types of the tumours involved simple and complex apocrine carcinoma of cystic/papillary (62.5%), solid (15%), and tubular type (12.5%), as well as apocrine ductal carcinoma (10%). The epidemiological analysis revealed peak incidence of the cancer in dogs between 8 and 14 years of age, with the most commonly affected sites being forelimbs and thorax. The highest number of the cancer cases was diagnosed in mixed breed dogs and German Shepherds; no sex predilection was noted.
Conclusion: To the authors’ knowledge, this is the first report recounting the study on canine malignant apocrine sweat gland tumours in Poland providing detailed phenotypical and histological data, which are otherwise rarely described in veterinary literature. This type of cancer appears to be diagnosed more frequently in dogs than in humans. Being an easily accessible material for research, canine ASGCs might serve as a relevant animal model for studies related to pathogenesis of sweat gland tumours.