PATHOLOGY OF ROUND CELL TUMORS AND SARCOMAS: A DIAGNOSTIC AND CLINICALLY-ORIENTED APPROACH, WITH A FOCUS ON BASIC INVESTIGATION

Neoplasms represent a constantly increasing threat for companion animals, requiring fast and reliable diagnostic techniques. In this context, cytology is a diagnostic tool widely applied to preliminarly investigate the nature of lesions observed in daily veterinary practice. Nevertheless, considered the limitations of cytology as well as the key role that a cytological diagnosis might cover for the clinical approach to each patient, estimation of the reliability of this technique represents a fundamental step. With this in mind, diagnostic accuracy studies can provide a proof of reliability of cytological results, when the latter are compared to the histopathological gold standard. With these premises, the main aim of the current Thesis was to evaluate the diagnostic accuracy of cytology applied to different round cell tumors and sarcomas currently representing a serious threat for the canine and feline species. Chapter 1 describes a study investigating the diagnostic accuracy of cytology in the evaluation of canine splenic neoplasm. To the best of our knowledge, our work was the first study conjunctively reporting overall accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of cytology in the diagnosis of these lesions. Diagnostic accuracy indexes identified limitations of negative cytological results in excluding a dog to be truly free from neoplasia; however, high specificity and positive predictive value still highlighted cytology as a valuable tool in the diagnostic approach to splenic neoplasms. In Chapter 2 is described a study investigating interobserver agreement and diagnostic accuracy of cytology in the immunophenotype prediction of feline nodal lymphoma. Our results revealed a low inter-observer agreement and a low diagnostic accuracy in immunophenotype prediction, thus highlighting potential marked differences among laboratories and even among different cytologists within the same laboratory, and consequently the mandatory need of histopathology and immunohistochemistry for a correct interpretation of feline nodal lymphoma immunophenotype. Chapter 3 describes two studies focusing on the application of cytology in the evaluation of nodal metastasis of canine mast cell tumor (MCT). The preliminary investigations described in Section 1 focused on the quantification of mast cells in cytological nodal samples obtained from both non oncological dogs and MCT-bearing dogs, revealing that mast cell (MC) quantification in lymph node (LN) cytological samples obtained from the latter might be useful to determine the nodal metastatic status. Our findings further suggested that neither the sampling technique applied to collect cytological samples nor the quantification method applied to estimate the number of MCs, influence the number of nodal MCs observed. Section 2 describes a study investigating interobserver agreement and diagnostic accuracy of cytology in the evaluation of the metastatic status of lymph nodes obtained from MCT-bearing dogs. Specifically, the study investigated the diagnostic performance of the cytological interpretative system currently available in literature as well as that of 2 amendments of the latter (AM1 and AM1.2 system). Our results revealed that the AM1.2 system, which include MC quantification besides the cytological criteria reported in the previously published cytological interpretative system, could represent a valid alternative to the latter, being characterized by an almost overlapping interrater agreement, and sensibly higher accuracy and sensitivity without substantial changes of the other diagnostic accuracy indexes. Besides studies focusing on the diagnostic accuracy of cytology, the Addendum briefly describes the results of 2 research projects investigating viral oncolysis in a cell culture model of canine histiocytic sarcoma, performed by the Ph.D. candidate during his externship at the University of Veterinary Medicine of Hannover (TiHo Hannover, Germany).