4. Hrvatski kongres kliniËke citologije 4th Croatian Congress ... - Penta

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4. Hrvatski kongres kliniËke citologije / 1. Hrvatski simpozij analitiËke citologije / 2. Hrvatski simpozij citotehnologije MORPHOMETRIC AND CELL KINETIC CHARACTERISTICS IN THE DIAGNOSIS AND PROGNOSIS OF NEOPLASMS Kardum-Skelin I Merkur University Hospital, Zagreb, Croatia The majority of cytologic and histopathologic diagnoses still rely on the basic light microscopy interpretation, based on visual perception and clearly defined diagnostic criteria for each particular disease. Yet, different interpretations and variations in reproducibility (inter- and intra-morphologist) are possible in various neoplasms as well as in inflammatory diseases and other pathologic events. The problem of reproducibility may even increase with the inclusion of prognostic criteria such as grade of differentiation, mitotic activity, etc. Nowadays, optimal treatment demands from the morphologist more than simple distinction between the malignant and the benign. Additional information is necessary to identify patients at an increased risk of recurrence or those with rapid disease progression, and to detect disease recurrence before its clinical manifestation. Furthermore, identification of precancerous lesions in a population at a high risk of malignancy may help in planning the approach of surveillance strategy. In the last years, efforts have been invested to improve diagnostic accuracy and to obtain new, more appropriate and objective information on the process through the introduction of sophisticated computer technologies. Malignant cell alteration leads to changes at the cell, cytoplasm, nucleus and nuclear structure levels, the latter being most numerous. Cell enlargement is most common, resulting in an increased nucleus/cytoplasmic (N/C) ratio and morphologic changes characteristic of particular tumor types. Pronounced pleomorphism and nuclear multinucleation or multilobulation are important nuclear characteristics of malignant growth. Chromatin structure may show hypo- or hyperchromatism as a reflection of abnormal DNA amount due to pathologic mitosis and an increased number of nuclei in the synthetic phase of preparation for mitosis. Both of these parameters, DNA amount and proliferative activity, reflect in abnormal cell function; abnormal DNA amount characterizes malignant and premalignant cells, whereas considerably increased proliferative activity is associated with neoplasia and biological tumor behavior. Within the nucleus, the number and size of nucleoli increase, along with changes that occur in the nucleolar substructure, the nucleolar organizer region (NOR). Generally, tumor cell nuclear morphology is highly relevant for two reasons. First, the substructure may provide diagnostic help in the identification of specific tumor types. Second, abnormalities of nuclear morphology play a major role in tumor staging. All these alterations can be numerically objectified by computer technologies through analysis of the morphometric characteristics of the cell as a whole, the nucleus and nuclear structures (AgNOR), and by determination of DNA amount using image DNA cytometry. ikardum@hi.t-com.hr 154 Analitička citologija - Plenarna i pozvana predavanja
Analytical Cytology - Plenary and Invited Lectures MOLECULAR PATHOGENESIS OF PHILADELPHIA-NEGATIVE CHRONIC MYLEOID NEOPLASMS Kušec R Department of Hematology and Molecular diagnostics and genetics, Dubrava University Hospital, and Zagreb School of Medicine, Zagreb, Croatia Myeloproliferative disorders or neoplasms (MPNs), as they have recently been renamed by the WHO 2008 classification, have been divided into polycythaemia vera (PV), essential thrombocythaemia (ET) and primary myelofibrosis (PMF). The discovery of the JAK2 V617F mutation in nearly all patients with PV and half those with ET and PMF has redefined the classification and will most likely influence the management of MPNs in the near future. It seems likely, however, that any attempt to reclassify the MPNs on the basis of JAK2 mutation status will need to retain the concepts of a disease with predominant erythrocytosis, a disease with predominant marrow fibrosis and a disease with isolated thrombocytosis, since both therapy and prognosis vary substantially across the three entities. Examination of the JAK/STAT signaling pathway and cytokine receptors led to the discovery of various gain-of-function mutations in the thrombopoietin receptor (MPL). They occur in patients with PMF and ET with a frequency of 1-9%. Both JAK2 and MPL mutations, as shown in animal models, clearly induce a myeloproliferative phenotype in vivo. For JAK2 it was shown that ratio of mutant JAK2-V617F to wild-type JAK2 determines the MPD phenotype in transgenic mice. Monoclonal origin of MPNs has been a pathogenetic fundamental and extensive studies at cytogenetic and molecular level are being conducted in search of invariant aberration of MPN specific (gene) defect. This has not been found so far. In cytogenetics lesions frequently seen in other myeloid neoplasms were detected: deletions (chr5q,13q,20q), numerical changes (1,8,9) and gains of 9p. For the increase in mutated allele frequency of JAK2 V617F a mechanism of uniparental disomy (UPD) of the short arm of chromsome 9 (9UPD) was found to be the most frequent mechanism. Besides JAK2 and MPL, recently other sporadic oncogenic point or other type of mutations (mostly small deletions) have been found in different oncogenes (e.g. TET2, CBL, IKZF1). However, all of them in a relatively small proportion and different MPN phenotypic subtypes. All these lesions create number of genotype classes of progenitors and when cultured progenitor colonies are genotyped complex pattern of different clones is found in which also variable acquisition order of genetic abberations is evident. Simulatanously occuring two different mutations are possible (JAK2 and MPL, or two independent JAK2 mutations) which suggests that MPN exhibits a certain form of mutator phenotype resulting in increased mutation frequency. Recently an MPN susceptibility haplotype of JAK2 was identified based on the uneven distribution of JAK2 V617F mutations between the two most frequent haplotypes. While it still remains to be seen wheter and which somatic mutation can make clone more suscetible to acquire a JAK2 mutation with subsequent development of MPN, in very recent study of MPNs transforming to acute leukemia interesting novel insights into the molecular pathogenesis of these event have been made. Acute leukemia following JAK2+MPN can be JAK2-mutant and JAK2-wild type. Patterns of second hits, however, 155 4 th Croatian Congress of Clinical Cytology / 1 st Croatian Symposium of Analytical Cytology / 2 nd Croatian Symposium of Cytotechnology
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Final programme and abstract book
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UTORAK, 13.10.2009. SRIJEDA, 14.10.
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4. Hrvatski kongres kliniËke citologije 4th Croatian Congress ... - Penta

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