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  • Seili-Bekafigo, Irena

    2014
    Web Resource

    Provider: - Institution: University of Rijeka. Faculty of Medicine. Department of General Pathology and Pathological Anatomy. - Data provided by Europeana Collections- Cilj istraživanja: multipli mijelom (MM) je novotvorina plazma stanica, heterogena u prezentaciji, biološkom ponašanju i odgovoru na liječenje. Zato je neophodno što ranije u dijagnostičkom procesu svrstati bolesnike u prognostičke grupe i liječenje planirati individualno. Citološka punkcija koštane srži (KS) jedan je od prvih koraka u dijagnostici MM. Cilj ovog istraživanja bio je usporediti citomorfologiju i morfometrijske parametre plazma stanica (PS) sa citogenetskim, molekularnim i kliničkim prognostičkim parametrima bolesnika sa MM. Hipoteza ovog istraživanja je da bi se na temelju nekih od analiziranih morfoloških parametara mijelomskih stanica moglo u najranijoj fazi dijagnostičkog postupka izdvojiti potencijalno prognostički nepovoljnije bolesnike. Ispitanici i metode: na uzorku od 90 novo dijagnosticiranih bolesnika sa MM usporedili smo morfološke karakteristike (struktura kromatina, paranuklearno prosvjetljenje, binukleacija i multinukleacija, istaknuti nukleoli, nepravilne jezgre, centralno smještene jezgre, vakuolizacija citoplazme, «flaming» morfologija, «pupanje» citoplazme, Russellova tjelešca i načupani rub citoplazme) i morfometrijske karakteristike plazma stanica (PS) u punktatu KS (najveći promjer jezgre i citoplazme i omjer tih parametara) sa poznatim prognostičkim čimbenicima: kliničkim stadijem bolesti po Durie-Salmonu (DS) i po International Staging System-u (ISS), izražajem NF-κB i Ki-67 odredjenih imunohistokemijski te citogenetskim promjenama: del(13q14), del(13q34), del17, t(14;16) i t(4;14) odredjenih metodom fluorescentne in situ hibridizacije (FISH). Također je analizirana medjusobna povezanost citogenetike, izražaja NF-κB i Ki-67 te kliničkih stadija. Rezultati: sa kliničkim stadijima statistički značajnu povezanost su pokazali: broj PS u KS, zrela morfologija PS, načupani rub citoplazme, «flaming» morfologija, «pupanje» citoplazme, nepravilne jezgre, paranuklearni «halo». Načupani rub citoplazme i manji omjer promjera VI jezgre i citoplazme značajno su povezani sa del(13q14), a veći udio PS sa više jezgara sa del(13q34). Russelova tjelešca češće su nađena uz t(4;14). Izražaj NF-κB povezan je sa načupanim rubom citoplazme, a Ki-67 sa krupnijim jezgrama, anizocitozom i anizonukleozom, nepravilnim jezgrama, većim brojem jezgara u PS, i paranuklearnim «haloom». Izražaj NF-κB bio je značajno veći u nižim kliničkim stadijima po DS, a izražaj Ki-67 nije povezan sa kliničkim stadijima. Klinički stadij bolesti po ISS pokazao je samo trend prema povezanosti sa učestalošću del(13q14) i sa ukupnom učestalošću kromosomskih abnormalnosti, dok klinički stadij po DS nije pokazao značajnu povezanost niti sa jednom citogenetskom promjenom. Zaključak: pojedine morfološke i morfometrijske karakteristike PS koreliraju s poznatim prognostičkim čimbenicima u MM. Zbog toga, morfološka analiza punktata koštane srži prilikom postavljanja dijagnoze može doprinijeti svrstavanju bolesnika u prognostičke skupine i dati preliminarnu orjentaciju o potrebi agresivnijeg pristupa liječenju. Kao osobito značajan morfološki parametar izdvojio se načupani rub PS.- Objectives: Multiple myeloma (MM) is a plasma cell neoplasm with a very heterogeneous presentation, biologic behaviour and response to therapy. It is very important to define a risk group for every patient as soon as possible, in order to choose a personalized therapy approach. Bone marrow (BM) aspiration is one of the first steps in the diagnostic process for MM. The aim of this study is to compare cytomorphologic and morphometric features of plasma cells (PC) with cytogenetic, molecular and clinical prognostic factors in myeloma patients. The hypothesis is that, maybe, it could be possible to select potentially high risk myeloma patients at the very beginning of the diagnostic workup, based on some morphological features of PCs. Patients and methods: In a cohort of 90 myeloma patients, PCs from BM aspirates at the moment of diagnosis, were analyzed for series of morphologic and morphometric features: chromatine structure, paranuclear halo, binucleation/multinucleation, nucleoli, irregular nuclei, centrally placed nuclei, cytoplasmatic vacuolization, flaming PCs, cytoplasmatic budding, Russell bodies, ragged cytoplasm, percentage of PCs in BM, largest nuclear and cytoplasmatic diameters and the ratio of the largest nuclear and cytoplasmatic diameters of PCs. These features were then compared to known prognostic parameters: clinical stage of the disease according to Durie-Salmon (DS) and the International Staging System (ISS), expression of NF-κB and Ki-67 in PCs, and some cytogenetic alterations in PCs assessed by fluorescence in situ hybridization (FISH). The relationship among cytogenetic changes, NF- κB and Ki-67 expression and clinical stages was analyzed as well. Results: Clinical stages of MM showed correlation with a percentage of PCs, mature morphology, ragged cytoplasm, flaming PCs, cytoplasmatic budding, irregular nuclei and paranuclear halo. Ragged cytoplasm and lesser nuclear/cytoplasmatic diameter ratio were connected to del(13q14), while a higher percentage of binuclear/multinuclear PCs was connected to del(13q34) and del(13q14). Russell bodies were more frequently found in association with t(4;14). NF-κB expression was associated with ragged cytoplasm, and Ki-67 with larger nuclei, anisocytosis and anisonucleosis, irregular nuclei, bi and multinucleation of PCs and paranuclear halo. NF-κB expression was higher in lower clinical stages according to DS, and Ki-67 expression did not show any correlation to clinical stages. ISS clinical stages only showed a tendency towards significant correlation with del(13q14) and with the overall incidence of chromosomal abnormalities whereas DS clinical stages did not show significant correlation with any of the chromosomal abnormalities. Conclusion: Some of the analyzed morphologic and morphometric PC features showed correlation with known prognostic factors in MM. Thus, morphologic analysis of BM aspirates at the moment of diagnosis can help in recognising high risk myeloma patients and provide preliminary information regarding the selection of therapeutic approach. Ragged cytoplasm of PCs turned out to be quite a significant morphologic feature.- All metadata published by Europeana are available free of restriction under the Creative Commons CC0 1.0 Universal Public Domain Dedication. However, Europeana requests that you actively acknowledge and give attribution to all metadata sources including Europeana