Issue 1, suplement 1

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1 Issue 1, suplement 1 ISSN COBISS.SR-ID Materia Medica Congress programme 16th National SPCA Congress 2nd International SPCA Congress 16. Nacionalni kongres UPCS 2. Internacionalni kongres UPCS Morphology is in the Heart of Pathology! Morfologija je u srcu patologije! 18th-21st April, 2018 Zlatibor, Serbia Final Programme 59 1 KLINIČKO BOLNIČKI CENTAR ZEMUN

2 2018. Vol. 34 Issue 1, suplement 1 MATERIA MEDICA Volumen 34 - Issue 1, suplement 1, Indexed in Biomedicina Serbica Indexed in SCIndeks beta Glavni i odgovorni urednik / Editor-in-Chief Prof. dr Sanja M. Milenković Pomoćni urednici /Associate Editors Prof. dr Milan B. Jovanović Dr Vuk Aleksić Ombudsman časopisa / Ombudsman of the Journal Prof. dr Biljana Putniković Sekretar časopisa / Secretary of the Journal Aleksandra Lukić Izdavački savet/ Publishers Advisory Board Dr Miloje Marjanović Mr sc dr Saša Drinjaković Ivana Škundrić, dipl. pravnik Andjelka Mihajlović, dipl. ecc Aleksandra Stojić, VMS Snežana Pejović, VSTS Olga Sneškov Osnivač, vlasnik i izdavač / Founder, Owner and Publisher KLINIČKO BOLNIČKI CENTAR ZEMUN-BEOGRAD (Osnovan 1784 / Founded 1784) Predsednik Izdavačkog saveta / President of the Publishers Board Dr Miloje Marjanović Adresa uredništva / Editorial Address Vukova 9, Zemun - Beograd, 011/ , KBCZemunMateriaMedica@gmail.com Priprema za štampu i grafička obrada / Prepress and layout: Uroš Cvijić Nacionalni uređivački odbor National Editorial Board Atanasijević Tatjana, ISM, Beograd Cvetković Zorica, KBC Zemun, Beograd Dejan Stevanović, KBC Zemun Beograd Dragoš Stojanović, KBC Zemun Beograd Gluvić Zoran, KBC Zemun, Beograd Isenović Esma, INN Vinca Beograd Jović Nebojša, VMA Beograd Libek Vesna, KBC Zemun Marinković Tatjana, VSZS Visan, Beograd Miodrag Vukčević, KBC Zemun Beograd Mitrović Nebojša, KBC Zemun, Beograd Neškovic Aleksandar, KBC Zemun, Beograd Panjković Milana, KC Vojvodine, Novi Sad Perović Milan, GAK Narodni front, Beograd Puškaš Laslo, MF Beograd Ratko Tomašević, KBC Zemun, Beograd Štrbac Mile, KBC Zemun Tamara Jemcov, KBC Zemun Beograd Vidaković Radoslav, KBC Zemun Beograd Međunarodni uređivački odbor International Editorial Board Priebe Stefan, London, UK Tot Tibor, Falun, Sweden Andrejević Predrag, Pieta, Malta Podvinec Mihael, Aarau, Switzerland Begum Najma, Bethesda, USA Nina Gale, Ljubljana, Slovenia Galizia Caruana Gordon, Pieta, Malta Stojanović-Susulić Vedrana, Randor, USA Attard Alex, Pieta, Malta Vujanić Gordan, Cardiff, UK Štampa / Printed by: Alta Nova, Zemun ISSN COBISS.SR-ID

3 SADRŽAJ/CONTENTS SPECIJALNA SESIJA: SESIJA SPECIJALIZANATA SPECIAL SESSION: RESIDENTS SESSION PLENARNE USMENE PREZENTACIJE PLENARY ORAL PRESENTATION SPECIJALNA SESIJA: KATEDRA ZA PATOLOGIJU MEDICINSKOG FAKULTETA, UNIVERZITETA NOVI SAD, SRBIJA SPECIAL SESSION: DEPARTMENT OF PATHOLOGY, MEDICAL FACULTY, UNIVERSITY NOVI SAD, SERBIA POSTER SESIJA POSTER SESSION APSTRAKTI ABSTRACTS UPUSTVO ZA AUTORE

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5 Specijalna sesija: Sesija specijalizanata Special Session: Residents Session Imunohistohemijska analiza angiogenog profila u T1 karcinomu mokraćne bešike sa konkomitantnim in situ karcinomom Ana Ristić Petrović, Slavica Stojnev, Miljan Krstić, Dragana Stokanović, Ljubinka Janković Veličković Medicinski fakultet Univerziteta u Nišu, Niš, Srbija Cilj: Cilj rada je da se ustanovi ekspresija i značaj angiogenih markera u T1 karcinomu mokraćne bešike sa konkomitantnim in situ karcinomom. Uvod: Ustanovljeno je da prekomerna ekspresija hipoksijom indukovanog inducibilnog faktora 1 alfa (HIF-1alfa), vaskularnog endotelnog faktora rasta (VGFR) i receptora 1 za VGFR korelira sa histološkim gradusom, progresijom bolesti i recidivom, kao i sa kraćim ukupnim preživljavanjem. Karcinom in situ (CIS) se često vida zajedno sa tumorima mokraćne bešike i predstavlja dodatnu poteškoću u lečenju T1 karcinoma mokraćne bešike. Materijal i metode: Imunohistohemijska ekspresija HIF-1alfa, VEGF, and VEGFR1 je analizirana na 295 T1 karcinoma mokraćne bešike, tehnikom tkivnih mikroereja. Aktivnost HIF-1alfa procenjivana je u jedru, dok je angiogeni profil posmatran kroz citoplazmatsku ekspresiju VEGF i VEGFR1. Mali krvni sudovi su identifikovani bojenjem endotelnih celija na CD34, a gustina malih krvnih sudova je prikazana kao srednja vrednost izbrojanih krvnih sudova. Rezultati: Nakon praćenja u trajanju od 53 meseca utvrđeno je da pacijenti sa T1 karcinomom mokraćne bešike i konkomitantnim CIS-om imaju manje ukupno preživljavanje (p<0.05), kao i manju ekspresiju HIF-1alfa (p<0.05) i VEGFR1 (p<0.05). Ekspresija VEGF, VEGFR1, HIF-1alfa, kao i MVD, nisu imale značajan uticaj na stopu preživljavanja kao i na dalji ishod bolesti. Zaključak: Utvrđeno je da tumori sa CIS-om u okolini imaju manju ekspresiju angiogenih markera, a pacijenti kraće ukupno preživljavanje. Procena HIF-1alfa i VEGFR1 ekspresije može biti dijagnostička dopuna za odabir pacijenata sa T1 urotelnim karcinomom mokraćne bešike, kojima je neophodno intenzivnije praćenje. Ključne reči: angiogeneza, HIF-1alfa, VEGFR1, karcinom mokraćne bešike, karcinom in situ. An immunohistochemical analysis of angiogenic profile in T1 bladder cancer with concomitant carcinoma in situ Ana Ristic Petrovic, Slavica Stojnev, Miljan Krstic, Dragana Stokanovic, Ljubinka Jankovic Velickovic Faculty of Medicine, University of Nis, Nis, Serbia Aim: The aim of this study was to establish the expression and the significance of angiogenic markers in T1 bladder cancer with concomitant carcinoma in situ. Introduction: It has been determined that overexpression of hypoxia-inducible factor 1-alpha (HIF-1alfa), vascular endothelial growth factor (VEGF), and vascular endothelial growth factor receptor1 (VEGFR1) correlates with tumor grade, disease progression and recurrence, as well as poor overall survival. Carcinoma in situ (CIS) is frequently seen in conjunction with bladder tumors and represents an additional obstacle for management of T1 bladder cancer patients. Material and Methods: The immunohistochemical expressions of HIF-1alfa, VEGF, and VEGFR1 were evaluated in 295 T1 bladder cancer samples, incorporated in tissue microarrays. HIF1-alpha was assessed through nuclear staining, while the angiogenic profile was estimated through cytoplasmatic positivity of the VEGF and VEGFR1. Microvessels were identified by immunostaining of endothelial cells for CD34 and microvessel density (MVD) was presented as the average number of counted microvesels. Results: After a mean followup of 53 months, we found that T1 bladder cancer patients, who had concomitant carcinoma in situ had worse overall survival (p<0.05), furthermore, those tumor samples less expressed HIF-1alfa (p<0.05), and VEGFR1 (p<0.05). Expression of VEGF, VEGFR1, HIF-1alfa, as well as MVD, did not have significant impact to survival rate and further outcome. Conclusion: Worse overall survival and decreased expression for angiogenic markers in samples with accompanying CIS were established. Estimation of HIF-1alfa and VEGFR1 expression emerged as potential diagnostic supplement, selecting the T1 bladder cancer patients that could require an intensive follow-up. Key words: angiogenesis, HIF-1alfa, VEGFR1, bladder cancer, carcinoma in situ 5

6 SPECIJALNA SESIJA: SESIJA SPECIJALIZANATA Interakcije NCAM/FGFR i TGF-beta signalnih puteva: in vitro studija i evaluacija u biopsijama bubrega Maja Životić 1, Aleksandar Rakić 1, Gerhard A. Müller 2, Claudia Müller 2, Radomir Naumović 3, Jasmina Marković- Lipkovski 1 1 Institut za patologiju, Medicinski fakultet, Univerzitet u Beogradu 2 Odeljenje nefrologije i reumatologije, Univerzitetski medicinski centar Getingen, Nemačka (Georg-August University) 3 Klinika za nefrologiju, Klinički centar Srbije, Medicinski fakultet, Univerzitet u Beogradu Cilj: Analizirali smo interakcija NCAM/FGFR1 i signalnog TGF-β1 u procesu nastanka intersticijske fibroze u bubrega. Uvod: Epitelno mezenhimna transformacija (EMT) doprinosi nastanku intersticijske fibroze u bubregu, dovodeći do progresivnog oštećenja bubrežnog parenhima. Poznato je da neuralni ćelijski adhezioni molekul (NCAM) i receptor za fibroblastni faktor rasta (FGFR) mogu biti jedni od ključnih incijatora EMT procesa. Kako doprinos interakcija ova dva molekula u procesu nastanka intersticijske fibroze u bubregu nije ispitan, odlučili smo da evaluiramo njihov značaj, kao i da ispitamo ekspresiju gena značajnih u procesu fibroze bubrega. Materijal i metode: Na modelu in vitro indukovane EMT, korišćenjem ćelija proksimalnih tubula bubrega indukovinh uz pomoć TGF-β1 (10ng/mL) liganda, ispitan je NCAM/FGFR signalni put uz pomoć metoda optičke mikroskopije, imunofluorescence, qrt-pcr i migracionog ćelijskog eseja. Modulacija NCAM/FGFR interakcija podrazumevala je primenu FGFR inhibitora (PD nM). Distribucija TGF-β1 nishodnih efektorskih protein procenjena je na ćelijskim kulturama, kao in a 50 biopsijskih uzoraka bubrega. Rezultati: EMT se morfološki počeo detektovati 48h nakon TGF-β1 stimulacije ćelijske linije proksimalnih tubula bubrega, a promene su postale jasno vidljive 72h nakon tretmana. Ove promene bile su udružene sa smanjenom ekspresijom E-kadherina i trenskripcionom indukcijom SNAIL, SLUG, TWIST1, MMP2, MMP9, N-kadherin, integrina α5, integrina β1, α-sma i FSP1. 24h nakon ekspozije TGF-β1, u najranijoj fazi EMT procesa, uočena je značajna transkripciona indukcija NCAM izofromi i FGFR1 molekula, ukazujući na potencijalnu mehanističku povezanost NCAM/FGFR1 signalne indukcije i incijacije EMT procesa. Ove pretpostvake su potvrđene kada je EMT proces uspešno suprimiran primenom FGFR inhibitora. Štaviše, pokazan je značajan in vivo uticaj TGF-β signalnog puta u biopsijama bubrega i korelacija sa markerima EMT, što je klnički koreliralo sa oštećenjem bubrežne funkcije. Zaključak: Modulacija NCAM/FGFR1 signalnog puta suprimira EMT process u ćelijskoj kulturi. NCAM/FGFR1 interakcije značajane su procesu incijacije fibroze bubrega. Ključne reči: NCAM, FGFR1, PD173074, TGF-β1, EMT process, fibroza bubregamyelofibrosisi:diagnost ic pitfalls Crosstalk between NCAM/FGFR and TGF-beta signalings: an in vitro study and evaluation of human kidney biopsies Maja Zivotic 1, Gerhard A. Müller 2, Claudia Müller 2, Radomir Naumović 3, Jasmina Marković-Lipkovski 1 1 Institute of Pathology, Faculty of Medicine, University of Belgrade, Serbia 2 Department of Nephrology and Rheumatology, University Medical Center, Georg-August University, Germany 3 Clinic of Nephrology, Clinical Center of Serbia, Faculty of Medicine, University of Belgrade, Serbia Aim: Here, we explored the role of NCAM/FGFR1 signaling and pro-fibrotic gene expression signatures as initiating or driving forces of EMT program in cultured human proximal tubular epithelial cells. Introduction: Epithelial-to-mesenchymal transition (EMT) contributes to maladaptive repair and parenchymal damage during renal fibrosis. Based on previous reports, neural cell adhesion molecule (NCAM) and fibroblast growth factor receptor 1 (FGFR1) are both considered to be mechanistically involved in the EMT process. Material and Methods: By using an established in vitro model of EMT of the human proximal tubular epithelial cells (HK-2 cells) in response to TGF-β1 (10ng/mL) exposure, NCAM/FGFR1 signaling responses were analyzed by light microscopy, immune-labelling, qrt-pcr and scratch assays. Modulation of FGFR1 was induced using PD (100nM). Distribution of TGF-β1 downstream effectors was assessed in HK-2 cells of the EMT program as well as in 50 biopsies of different human kidney diseases to explore their in vivo correlation. Results: EMT associated with morphological changes started 48h after TGF-ß1 treatment of the HK-2 cells and was clearly apparent after 72 hours, associated with loss of CDH1 (encoding E-Cadherin) and transcriptional induction of SNAI1 (encoding SNAIL), SNAI2 (encoding SLUG), TWIST1, MMP2, MMP9, CDH2 (encoding N-Cadherin), ITGA5 (encoding integrin-α5), ITGB1 (encoding integrin-β1), ACTA2 (encoding α-sma) and S100A4 (encoding FSP1). After 24 hours of TGF-β1 exposure at the early stage of 6

7 SPECIAL SESSION: RESIDENTS SESSION EMT program, transcriptional induction of several NCAM isoforms along with FGFR1 was observed, implicating a mechanistic link between NCAM/FGFR1 signaling and induction of EMT. These assumptions were further supported by the inhibition of the EMT program after specific blocking of FGFR1 signaling responses by PD Moreover, there was evidence for an in vivo TGF-β1 pathway activation with EMT response signal signatures in diseased human kidneys in correlation to impaired renal excretory functions. Conclusion: Modulation of NCAM/FGFR1 signaling blocks the EMT program in cultured human proximal tubular epithelial cells. NCAM/FGFR1 signaling appears to be involved in initial phases of TGF-ß1 initiated EMT of tubular cells and thus could contribute to maladaptive repair and parenchymal damage during renal fibrosis. Key words: NCAM, FGFR1, PD173074, TGF-β1, EMT program, renal fibrosis, HK-2 cells Primarni sinovijalni sarkom pluća - prikaz slučaja Marija Ninković 1, Jelena Sopta 1, Dušan Ristic 2, Goran Šuričić 3 1 Institut za patologiju, Medicinski fakultet, Univerzitet u Beogradu, Beograd, Srbija 2 Institut za onkologiju i radiologiju Srbije, Beograd, Srbija 3 Univerzitetska dečija klinika, Beograd, Srbija Uvod: Primarni sinovijalni sarkom (PSS) pluća je izuzetno redak tumor, mada pluća predstavljaju najčešću visceralnu lokalizaciju metastatskog sinovijalnog sarkoma. PSS je visokogradusni maligni tumor mezenhimalnog porekla koji pokazuje varijabilnu epitelnu diferencijaciju i karakterističnu translokaciju t(x, 18). Prikaz slučaja: Prikazujemo pacijenta muškog pola, starosti 67 godina koji je ispitivan zbog dugotrajnog kašlja, bolova u grudima i febrilnosti. Radiografijom i kompjuterizovanom tomografijom pluća viđena je jasno definisana tumorska masa koja infiltriše strukture hilusa, nakon čega je indikovana resekcija pluca. Histopatološkom analizom tkiva pluća utvrđeno je da se radi o vretenasto ćelijskom malignom tumoru. Imunohistohemijski profil tumora (pozitivnost na vimentin, TLE-1, Bcl-2, fokalno na cytokeratin AE1/ AE3, cytokeratin 7, cytokeratin 18, cytokeratin 19, EMA, calponin i negativnost na CK 5/6, S100, STAT6, CD34, SMA, desmin, CD99 i CD 117) pokazao je da se radi o monofazičnom sinovijalnom sarkomu. Specifična translokacija t(x,18) dokazana je metodom fluorescentne in situ hibridizacije (FISH). Zaključak: Dijagnoza primarnog sinovijalnog sarkoma u plućima može biti veliki izazov koji podrazumeva isključivanje metastaze sarkoma drugih lokalizacija kao i primarne vretenasto-ćelijske tumore pluća. Molekularne analize su se pokazale kao veoma korisne ako ne i neophodne za krajnju potvrdu dijagnoze sinovijalnog sarkoma na neuobičajenim lokalizacijama, u ovom slučaju u plućima. Ključne reči: primarni sinovijalni sarkom, pluca, FISH Primary sinovial sarcoma of the lung - a case report Marija Ninkovic 1, Jelena Sopta 1, Dusan Ristic 2, Goran Suricic 3 1 Institute of Pathology, Medical Faculty, University of Belgrade, Belgrade, Serbia 2 Institute for Oncology and Radiology, Belgrade, Serbia 3 University Children s Hospital, Belgrade, Serbia Introduction: Primary sinovial sarcoma (PSS) is a very rare malignancy in lung, although lung is the most common organ-based site for metastatic synovial sarcoma. It is a high grade malignant mesenchymal neoplasm showing variable epithelial differentation and characterized by a balanced translocation t(x, 18). Case report: We report a case of a 67- year-old male presented with long lasting cough, chest pain and fever. Chest radiography and computer tomography scan revealed a large well defined lung mass invading hilum of the lung, which was indicated for the lung resection. Histopatological examination showed high-cellulare spindle cell malignant tumor. Immunohistochemically,neoplastic cells were positive for vimentin, TLE-1, Bcl-2, focally positive for cytokeratin AE1/AE3, cytokeratin 7, cytokeratin 18, cytokeratin 19, EMA, calponin and negative for CK 5/6, S100, STAT6, CD34, SMA, Desmin, CD99 and CD 117, which determinate a diagnosis of monophasic PSS of lung. Specific translocation t(x, 18) was detected by fluorescent in situ hybridization (FISH). Conclusion: Diagnosis of PSS in lung may create various diagnostic challenges. It can be established only after exclusion of metastatic sarcoma of other localizations and spindle cell primary lung malignancies. Molecular testing proved to be very helpful or necessary when spindle cell synovial sarcoma was recognized in uncommon sites. Key words: primary synovial sarcoma, lung, FISH 7

8 SPECIJALNA SESIJA: SESIJA SPECIJALIZANATA Hyperostosis frontalis interna: prikaz slučaja Ljubica Simić 1, Savo Raičević 2, Đurđa Bracanović 3, Danijela Đonić 4, Jelena Sopta 1 1 Institut za patologiju Prof. Dr Đorđe Joannović, Medicinski fakultet, Univerzitet u Beogradu, Beograd, Srbija 2 Neurohiruška klinika Klinički centar Srbije, Beograd, Srbija 3 Stomatološki fakultet, Univerzitet u Beogradu, Beograd, Srbija 4 Institut za anatomiju, Medicinski fakultet, Univerzitet u Beogradu, Beograd, Srbija Uvod: Hyperostosis frontalis interna se definiše kao progresivno, iregularno zadebljanje unutrašnje ploče frontalne kosti.do sada je povezivana sa različitim sindromima, medjutim javlja se i kao zaseban entitet. Etiologija nije u potpunosti razjašnjena, ali ispitivanja najviše govore u prilog poremećaju ženskih polnih hormona, sa najvećom incidencijom kod žena u postmenopauzi. Najčešće je asimptomatska i akcidentalno se dijagnostikuje nakon trauma endokranijuma ili post mortem. Ipak kod uznapredovalih formi može dovesti do smanjenja intrakranijalnog prostora, kompresije cerebralnog korteksa i pojave različitih neuroloških simptoma. Prikaz slučaja: Prikazujemo pacijentkinju starosti 27 godina koja je zbog čestih i jakih glavobolja, u trajanu od 3 meseca, primljena na Neurohiruršku kliniku KCS. Na CT u je uočena masivna koštana lezija desne frontalne kosti, koja štedi gornji sagitalni sinus i ne prelazi srednju liniju lobanje. Lezija zahvata celu frontalnu kost, unutrašnju ploču i diploični prostor, ali ne i spoljašnju ploču. Patološka analiza, nakon biopsije je pokazala značajno trabekularno zadebljanje kortikalne i spongiozne kosti, sa kortikalizacijom spongioze.u kortikalnoj kosti je opisana redukcija veličine i broja Haverzovih kanala, sa lakom fibrozom.gredice spongiozne kosti su bile proširene, povećane površine, sa naglašenim međugredičnm mostovima uz redukciju međugredičnih prostora. Tkivo dure je bilo lako edematozno, delom fibrozirano. U cilju bližeg određivanja etiopatogenetskih uzroka urađena je imunohistohemijska analiza estrogenskih, progesteronskih i androgenih receptora u tkivu dure. Imunohistohemijskom analizom je dokazana nuklearna pozitiznost estrogenskih i androgenih receptora u fibroblastima dure. Ekspresija progesteronskih receptora nije uočena. Zaključak: Ovakav hormonski status bi mogao govoriti u prilog hormonskoj teoriji uzroka hyperostosis frontalis interna. Ključne reči: hiperostoza, androgenski receptori, frontalna kost, menopauza. Hyperostosis frontalis interna: case report Ljubica Simic 1, Savo Raicevic 2, Danijela Bracanovic 3, Danijela Djonic 4, Jelena Sopta 1 1 Institute of Pathology Prof. dr Djordje Joannovic, Faculty of Medicine, University of Belgrade, Belgrade, Serbia 2 Neurosurgical Clinic, Clinical Center of Serbia, Belgrade, Serbia 3 Faculty of Dental Medicine, University of Belgrade, Belgrade, Serbia 4 Institute of Anatomy, Faculty of Medicine, University of Belgrade, Belgrade, Serbia Introduction: Hyperostosis frontalis interna is progressive, irregular thickeness of the frontal bone s internal table. It has been associated with a wide range of syndromes, though we know now that it can occur as an independent entity. Etiology is still unclear, but the most probable hyphothesis is alteration of steroid sex hormons, proven in high frequency among postmenopausal women. It is mostly asympthomatic or it has been accidentally diagnosed after endocranial trauma or postmortal. Because of its progression, in some cases it can cause cerebral cortical compression and varible neurological symptoms. Case report: We present a case of 27 years-old women, hospitalized in Neurosurgical Clinic, because of severe headaches lasting for 3 month. The head CT scan showed a massive, expansive lesion in right frontal bone, with spearing of the superior sagittal sinus and skull midline. Bone bulging does not affect outer table of the frontal bone, but only diploic space and inner table. Pathological analysis of the frontal bone showed marked trabecular thickening both cortical and spongy bone, with corticalisation of spongy bone. Haversian canals showed reduction in number and size, and light fibrosis. The lamellas of the spongy bones were enlarged, with prominent interlamellar bridges and the reduction of interlamellar spaces.in purpose of closer determination of etiopathogenesis,we did immunohystochemical analysis of Estrogen, Progesteron and Androgen receptors in dural tissue. Immunohistohemical stain confirmed nuclear expression of Estrogen and Androgen receptors in dural fibroblasts.progesterone receptors were negative on immune stain. Conclusion: These results could support the hormonal theory of the cause of hyperostosis frontalis interna. Key words: hyperostosis, androgen receptors, frontal bone, menopause 8

9 SPECIAL SESSION: RESIDENTS SESSION Proliferativni marker Ki-67 u ranom karcinomu dojke Tanja Lakić 1,3, Tatjana Ivković-Kapicl 2,3 1 Klinički centar Vojvodine, Novi Sad, Srbija 2 Institut za onkologiju Vojvodine, Sremska Kamenica, Srbija 3 Medicinski fakultet, Univezitet u Novom Sadu, Srbija Uvod: Karcinom dojke je heterogena bolest koju karakterišu različita morfologija, imunohistohemijski profil, klinički tok i terapijski odgovor. Cilj: Utvrditi graničnu ( cut-off ) prognostičku vrednost Ki67 indeksa kao i povezanost vrednosti Ki67 u ranom luminalnom karcinomu dojke sa životnim dobom bolesnica, veličinom tumora, histološkim gradusom (HG) i nivoom tumorske ekspresije receptora estrogena (ER) i progesterona (PR). Ki67 proliferativni indeks je jedan od markera sa prognostičkim i prediktivnim značajem, čije metodološko određivanje i analiza još uvek nisu standardizovani. Materijal i metode: Retrospektivno je analizirano 120 patohistoloških izveštaja bolesnica kojima je u periodu godine do godine na Institutu za onkologiju Vojvodine imunohistohemijskom analizom dokazan luminalni karcinom dojke (pozitivan ER i PR, negativan HER2) bez metastaza u aksilarnim limfnim čvorovima. Rezultati: Prosečna starost pacijentkinja iznosi 57,42±10,17 godina; prosečna veličina tumora 17,98±6,97mm; recidiv je registrovan kod 8 (6,7%) pacijentkinja uz prosečan vremenski period do pojave recidiva od 49±20,23 meseca. Vrednost cut off indeksa Ki67 od prognostičkog značaja za vremenski period bez recidiva iznosi 20,75%. Za ispitivanje povezanosti korišćeni su testovi χ2 i Kendal τ-b. Dokazano je da postoji nesignifikantna veza između vrednosti Ki67 i godina starosti pacijentkinja (p=0,401, odnosno p=0,293), kao i jačine ekspresije ER (p=1,00, p=0,957) i PR (p=0,273, p=0,189). Signifikantna povezanost Ki67 postoji sa veličinom (p=0,035, p=0,20) i HG tumora (p=0,041, p=0,20). Zaključak: Zbog heterogene prirode oboljenja, korišćenjem standardnih histopatoloških faktora i biomarkera teško je predvideti tok i ishod karcinoma dojke. U prognostičko-prediktivne svrhe neophodno je uvrstiti dodatne biomarkere, među kojima se pre svega ističe proliferativni Ki67 marker, čija visoka vrednost korelira sa faktorima loše prognoze. Ključne reči: karcinom dojke, Ki-67, estrogen, progesteron Proliferation marker Ki-67 in early breast cancer Tanja Lakic 1,3, Tatjana Ivkovic-Kapicl 2,3 1 Clinical Center of Vojvodina, Novi Sad, Serbia 2 Oncology Institut of Vojvodina, Sremska Kamenica, Serbia 3 Faculty of Medicine, University of Novi Sad, Serbia Aim: Determination of cut-off value for Ki67 index, it s corelation in luminal breast carcinoma with patient s age, tumor size, histological grade (HG), and expression of estrogen (ER) and progesterone (PR). Introduction: Breast cancer is a heterogeneous disease characterized by different morphology, immunohistochemical profile, clinical course and response to applied therapy. Ki67 proliferative index is one of the prognostic and predictive factors, whose methodological determination and analysis are still unstandardized. Material and Methods: Retrospectively, we analysed 120 pathohistological reports of patients who were treated in the period until at the Oncology Institute of Vojvodina, and to whom immunohistochemistry was proven luminal breast cancer (positive ER and PR, negative HER2), without axillary lymph node metastases. Results: The average patient s age was 57.42±10.17 years; average tumor size 17.98±6.97mm; recurrence was registered in 8 (6.7%) patients with average recurrence time of 49±20.23 months. Cut off Ki67 value of prognostic significance for period without recurrence is 20.75%. For correlation testing χ 2 and Kendal τ-b tests were used. It s shown unsignificant relationship between Ki67 and patient s age (p=0.401 and p=0.293), as well as the strength of expression ER (p=1.00, p=0.957) and PR (p=0.273, p=0.189). Significant correlation is present for Ki67 with size (p=0.035, p=0.20) and tumor s HG (p=0.041, p=0.20). Conclusion: Breast carcinoma is heterogeneous disease, so it s difficult to predict its course and outcome using standard histopathological factors and biomarkers. For prognostic-predictive purposes, it s necessary to include additional biomarkers, where Ki67 stands out above all, whose high value correlates with factors of bad prognosis. Key words: breast cancer, Ki-67, estrogen, progesterone 9

10 SPECIJALNA SESIJA: SESIJA SPECIJALIZANATA Histopatološki nalaz u enteričkom nervnom sistemu kod dece sa poremećajem pražnjenja creva Jovan Jevtić 1, Milica Skender Gazibara 1, Sanja Sindjić Antunović 2, Marija Lukač 2, Dragana Vujević 2, Miloš Lazić 1, Radmila Janković 1 1 Institut za patologiju, Medicinski fakultet, Beograd, Srbija 2 Univerzitetska dečija klinika Tiršova, Beograd, Srbija, Cilj: Utvrđivanje učestalosti tipova patološkog nalaza u enteričkom nervnom sistemu u biopsijama debelog creva dece koja su imala poremećaj motiliteta creva, odnosno hroničnu opstipaciju. Uvod: Hronična opstipacija je relativno česta u dečijem uzrastu i najčešće je funkcionalni problem koji se rešava odgovarajućim higijensko-dijetetskim režimom. U retkim slučajevima je neophodna biopsija i histopatološka analiza enteričkih nervnih pleksusa. Materijal i metode: Istraživanjem su obuhvaćene biopsije debelog creva 299 pacijenata pedijatrijskog uzrasta sa poremećajem motiliteta creva, analizirane na Institutu za patologiju Medicinskog fakulteta u Beogradu u periodu od do godine. U analizi podataka primenjene su standardne metode deskriptivne i analitičke statistike. Rezultati: Ukupno je analizirano 588 biopsija. Analizirane su biopsije 184 (61,5%) dečaka i 115 (38,5%) devojčica. Najčešća uputna dijagnoza zbog koje su pacijenti bioptirani je bila Hirschsprungova bolest (HB) u 51,2% (153/299). Promene u enteričkim pleksusima su nađene kod 46,1% pacijenata (138/299). Histopatološkom analizom je potvrđena klinička sumnja na HB u 48,4% (74/153) pacijenta. Posle HB najčešći patološki nalaz u enteričkim pleksusima su imaturne ganglijske ćelije (26/299, 8,7%), ektopija ganglija u mišićnom omotaču (6/299, 2%) i neklasifikovane disganglionoze (5/299, 1,7%). Kod 6 pacijenata uzrok opstipacije je bio eozinofilni proktitis i/ili mijenterički ganglionitis. Metoda acetilholin esteraze je primenjena u dijagnostici kod 29 pacijenata. Imunohistohemijska bojenja su primenjena kod 24 pacijenata. Zaključak: HB i nezrelost ganglijskih ćelija su najčešće dijagnostikovani uzroci opstipacije u biopsijama kod dece. Eozinofilni proktitis i/ili mijenterički ganglionitis su retki uzroci opstipacije kod dece. Ključne reči: opstipacija, Hiršprungova bolest, ganglijske celije Histopathological analysis of the enteric nervous system in children with constipation Jovan Jevtic 1, Milica Skender Gazibara 1, Sanja Sindic Antunovic 2, Marija Lukac 2, Dragana Vujevic 2, Milos Lazic 1, Radmila Jankovic 1 1 Institute of Pathology, Medical faculty, Belgrade, Serbia 2 University Children s Hospital Tirsova, Belgrade, Serbia Aim: Determination of frequency of patologic findings and types of pathologic findings in enteric nerve plexus (ENP) in colon biopsies in children with impaired bowel motility, specifically chronic constipation. Introduction: Chronic constipation is relatively common in children, and is most often a functional disorder that is responsive to dietary regime treatment. Rarely, some cases require biopsy and histopathologic analysis of ENP. Materials and Methods: Research consists of 299 colon biopsies taken from children with impaired bowel motility. Biopsies were analysed in Institute of pathology, Medical faculty in Belgrade, in the period of time from the year 2008 to Data analysis included standard methods of descriptive and analytic statistics. Results: Number of analysed biopsies was 588. Biopsies were taken from 184(61,5%) boys and 115(38,5%) girls. Most common referral diagnosis for biopsy was Hirschspung s disease (HD) (153/299, 51,2%). Pathologic changes in ENP were found in 46,1% of patients (138/299). Histopathologic analysis confirmed clinical suspicion for HD in 48,4%(74/153) of patients. Most frequent pathologic finding secondary to HD were immature ganglion cells (26/299, 8,7%), ectopic position of ganglia in muscle layer of colonic wall (6/299, 2%), and unclassified dysganglioses (5/299, 1,7%). In six patients, cause of constipation was eosinophilic proctitis and/or mienteric ganglionitis. Acetilcholin esterase as diagnositic metod was applied in 29 patients. Immunohistochemical analises were used in 24 patients. Conclusion: HD and immaturity of ganglion cells are by far most frequently diagnosed causes of constipation in colon biopsies in pediatric patients. Eosinophilic proctitis and/or mienteric ganglionitis are rare causes of constipation in children. Key words: constipation, Hirschsprung s disease, ganglion cells 10

11 SPECIAL SESSION: RESIDENTS SESSION Udruženost Gošeove bolesti i sarkoma mekih tkiva: prikaz slučaja Novica Boričić 1, Tatjana Terzić 1, Jelena Sopta 1, Nada Suvajdžić-Vuković 2 1 Institut za patologiju Dr Ðorde Joannovic Medicinski Fakultet, Univerzitet u Beogradu, Beograd,Srbija 2 Klinika za hematologiju, Klinicki centar Srbije, Medicinski Fakultet, Univerzitet u Beogradu, Beograd,Srbija Uvod: GB je najčešća lizozomska bolest nakupljanjna u svetu. Tip 1 je neneuropatski oblik bolesti i ujedno je i najzastupljeniji. Postoje podaci da oboleli od GB imaju veću predispoziciju za razvoj maligniteta, prvenstveno multiplog mijeloma i drugih hematoloških maligniteta. Hepatocelularni karcinom i karcinom bubrega takođe imaju veću incidencu kod obolelih od Gošeove bolesti. Kao faktori rizika za kancerogenezu se navode: akumulacija bioaktivnih lipida, alternativni put aktivacije makrofaga, poremećena regulacija imunog sistema, promene u određenim genima, splenektomija i enzimska terapija. Ekstraosealne mekotkivne tumorske promene su opisivane kod obolelih od GB. To su mekotkivne infiltracije Gošeovim histiocitima (Gošeom). Do sada u literaturi nije opisan slučaj GB i ekstraosealnog sarkoma. Cilj rada je da se prikaže vrlo redak slučaj uduženosti Gošeove bolesti (GB) (tip 1) i ekstraosealnog mekotkivnog tumora (lejomiosarkoma). Prikaz slučaja: Žena stara 81. godinu od godine zna za leukopeniju i trombocitopeniju godine joj je dijagnostikovan nediferentovani pleomorfni sarkom sa opsežnom inflamacijom na natkolenici, koji nije uklonjen u potpunosti godine na kontrolnom pregledu pored leukopenije i trombocitopenije je uočena i splenomegalija. Urađena je biopsija koštane srži i morfološki i imunohistohemijski dijagnostikovana GB. Dijagnoza je potvrđena enzimskom metodom godine je urađena revizija tumora natkolenice i dijagnostikovan je high grade lejomiosarkom. Pacijentkinja je živa i odbija lečenje. Zaključak: GB se retko dijagnostikuje u odmaklom životnom dobu. Mekotkivne tumorske mase kod obolelih od GB bi trebalo detaljno ispitati zbog povećanog rizika od pojave malignog tumora kod ovih bolesnika. Ključne reči: Gošeova bolest, mekotkivni sarkom. Gaucher disease in association with soft tissue sarcoma: a case report Novica Boricic 1, Tatjana Terzic 1, Jelena Sopta 1, Nada Suvajzic-Vukovic 2 1 Institute of Pathology Dr Ðorde Joannovic, Faculty of Medicine, University of Belgrade, Belgrade, Serbia 2 Haematology Clinic, Clinical Center of Serbia, Faculty of Medicine, University of Belgrade, Belgrade, Serbia Introduction: GD is the commonest lysosomal storage disease worldwide. The majority of the patients have Type1 GD which is the non-neuronopathic form of disease. There are data of increased risk of cancer in GD patients, such as: multiple myeloma and other haematological malignancies, hepatocellular carcinoma and renal carcinoma. Factors of cancerogenesis in GD are accumulation of bioactive lipids, alternatively activated macrophages, immune dysregulation, genetic modifiers underlying the GD, splenectomy and enzyme replacement therapy. Extra-osseous soft tissue masses are described in GD patients, like localised deposition od Gaucher macrophages (Gaucheroma). To the best of our knowledge, no other case of extra-osseous soft tissue sarcoma in association with GD has been described in literature. To present very rare case of high grade leiomiosarcoma in association with Gaucher disease (GD). Case report: The case concerns 81 years old female with leucopenia and thrombocytopenia since year In 2014 she was diagnosed with undifferentiated pleomorphic sarcoma with prominent inflammation on her thigh, which was not completely surgically removed. She was diagnosed with leucopenia, thrombocytopenia and splenomegaly in 2014 on control examination. Bone marrow biopsy was performed and histologically and immunohistochemically was diagnosed GD. The diagnosis was confirmed by enzyme activity test. In 2018 revision of pathohistological finding of thigh tumour was performed. High grade leiomiosarcoma was diagnosed. She is alive and refuses any treatment. Conclusion: GD is rarely diagnosed in older age. All soft tissue masses in GD should be carefully examined because of increased risk of cancer in GD patients. Key words: Gaucher disease, Soft tissue sarcoma ATRX i HIF-1 alfa koekspresija u karcinomu bubrežnih ćelja: pilot studija Gorana Nikolić, Sanja Cirović, Sanja Radojevic Škodrić Institut za patologiju Medicinskog fakulteta Univerziteta u Beogradu, Srbija Cilj: Istraživanje koekspresije ATRX i HIF-1a u tumoru bubrega u odnosu na njegovo poreklo. Uvod: Tumori bubrega potiču od različitih specijalizovanih ćelija nefrona - od proksimalnih tubula (karcinom bubrežnih ćelija 11

12 SPECIJALNA SESIJA: SESIJA SPECIJALIZANATA svetloćelijski tip, ccrcc; papilarni karcinom bubrežih ćelija, prcc) i od ćelija sabirnih kanalića (hromofobni karcinom bubrega, chrcc i onkocitom). ATP-zavisna helikaza (ATRX) je hromatin remodelirajući protein koji učestuje u genskoj regulaciji i DNK metilaciji tokom kancerogeneze. Aktivacija hipoksijom indukujućeg faktora (HIF-1a) se dešava u ranom stadijumu kod većine RCC nakon mutacije VHL tumor supresorskih gena. Materijal i metode: Imunohistohemijska analiza ATRX i HIF-1a je urađena na ukupno 46 slučaja tumora bubrega. Od ukupnog broja ispitanih tumora bilo je 33 ccrcc, jedan metastatski ccrcc, četiri prcc, pet chrcc i tri onkocitoma. Rezultati: Difuzna i fokalna imunopozitivnost na ATRX je uočena kod 51,5% ccrcc dok je 54,5% ccrcc pokazalo imunopozitivnost na HIF-1a. Nije nađena korelacija ATRX/HIF-1a sa nuklearnim gradusom niti sa stadijumom ccrcc-a. Metastatski ccrcc je pokazao izrazitu imunopozitivnost na oba markera. prcc, tip II je pokazao slabu imunopozitivnost na ATRX/HIF-1a, dok je prcc tip I bio negativan na oba markera. S druge strane, nijedan analizirani onkocitom i chrcc nisu pokazali ekspresuju ATRX/HIF-1a. Zaključak: Naši rezultati sugerišu postojanje različitih signalnih puteva koji učestvuju u aktivaciji/supresiji ATRX/HIF1-a kod onkocitoma i chrcc u poređenju sa ostalim tipovima RCC-a. Gubitak koekspresije ATRX/HIF-1a kod benignih tumora i chrcc treba dalje ispitati u cilju razumevanja mehanizama koji utiču na signalne puteve ATRX i HIF-1a u neoplazmama bubrega različitog porekla. Ključne reči: Tumori bubrega, ATRX, HIF-1alfa Detection of co-expression of ATRX and HIF-1alfa in renal tumors - pilot study Gorana Nikolic, Sanja Cirovic, Sanja Radojevic Skodric, Institute of Pathology, School of Medicine University of Belgrade, Serbia Aim: To investigate co-expression of ATRX and HIF-1α in kidney neoplasm in relation to its origin. Introduction: A heterogenous group of kidney tumors is believed to arise from a variety of specialized cells along the nephron proximal tubules [Clear cell Renal Cell carcinoma (ccrcc) and papillary RCC (prcc)] and collecting tubules [chromophobe RCC (chrcc) and oncocytoma]. ATP-dependent helicase (ATRX) is a chromatin remodeling protein involved in gene regulation and aberrant DNA methylation during cancerogenesis. Activation of hypoxia inducible factor (HIF-1α) is an early event in most RCC following inactivation of the VHL tumor suppressor gene. Material and Methods: A total of 46 kidney tumors (n=33 ccrcc, n=1 mrcc, n=4 prcc, n=5 chrcc and n=3 oncocytomas) was immunohistochemically analyzed for ATRX and HIF-1α expression. Results: Diffuse and focal positivity of ATRX expression was found in 51.5% of ccrcc, while 54.5% had HIF-1α positivity. Co-expression of ATRX/HIF-1α was not related to nuclear grade and stage of ccrcc. Metastatic ccrcc had strong expression of both markers. prcc type II showed weak ATRX/HIF-1α expression, while prcc type I was negative for both markers. Interestingly, all analyzed oncocytomas and chromophobe RCC were negative for ATRX/HIF-1α. Conclusion: Our results suggest that signaling pathways have different patterns of activation/suppression of ATRX/HIF-1α in oncocytomas and chrcc compared to other RCC types. Downregulation or loss of ATRX/HIF-1α coexpression in benign tumors should be further investigated in order to determinate mechanisms of ATRX/ HIF-1α signaling transport renal neoplasm with different origin. Key words: Kidney tumors, ATRX, HIF-1alfa Prognostički značaj detekcije mutacija KRAS onkogena u tumorskom tkivu pacijenata sa metastatskim kolorektalnim karcinomom Vasiljević Tijana 1,4, Knežević-Ušaj Slavica 1,4, Šolajić Nenad 1,4, Ivković-Kapicl Tatjana 1,4, Nikolić Ivan 2,4, Protić Mlađan 3,4, Jakimov Dimitar 1 1 Služba za patoanatomsku i laboratorijsku dijagnostiku, 2 Klinika za internu onkologiju, 3 Klinika za operativnu onkologiju, Institut za onkologiju Vojvodine, Sremska Kamenica, Srbija, 4 Medicinski fakultet, Univerzitet u Novom Sadu, Srbija Cilj: Utvrditi prognostički značaj detekcije mutacije RAS onkogena kod pacijenata sa metastatskim kolorektalnim karcinomom (mkrk). Uvod: KRK je i dalje po učestalosti treći najčešći karcinom u oba pola i drugi najčešći uzrok smrti od malignih bolesti u zapadnim zemljama. Poslednjih godina, detekcija mutacija RAS onkogena u tumorskom tkivu mkrk postala je imperativ u selekciji pacijenata za ciljanu terapiju monoklonskim antitelima na Receptor Epidermalnog Faktora Rasta (EGFR). Međutim, još uvek nema konsenzusa u pogledu prognostičkog značaja određivanja RAS statusa kod pacijenata sa mkrk. Materijal i metode: Studijom je bilo obuhvaćeno 116 pacijenata sa KRK koji su operisani na Institutu za onkologiju Vojvodine (IOV) u periodu januar-decembar godine. Detekcija KRAS mutacija vršena je u 12

13 SPECIAL SESSION: RESIDENTS SESSION tumorskom tkivu fiksiranom u formalinu i ukalupljenom u parafin metodom real-time lančane reakcije polimeraze (real-time PCR) primenom IVD Cobas KRAS Mutacionog Testa i Cobas 4800 Sistema za detekciju mutacija na kodonima 12/13 i 61 KRAS gena. Rezultati: Prosečna starost ispitivane populacije pacijenata iznosila je 65 godina sa predominacijom muškog pola (66.4%). Prisustvo KRAS mutacije utvrđeno je kod 50.9% pacijenata: na kodonima 12/13 kod 44.8% pacijenata, na kodonu 61 kod 4.3% i na kodonima 12/13 i 61 kod 1.7% pacijenata. KRAS mutirani KRK (n=59) u odnosu na KRAS nemutirane (wild type) pokazivali su statistički značajnu povezanost sa muškim polom, umerenom i lošom diferencijacijom KRK, prisustvom limfovaskularne invazije i regionalnih limfonodalnih metastaza. Zaključak: Dobijeni rezultati ukazuju da, pored prediktivnog, KRAS može imati i prognostički značaj u pogledu procene rizika od limfovaskularne invazije i prisustva lokalnih ili udaljenih metastaza. Ključne reči: kolorektalni karcinom, RAS mutacija Prognostic significance of detection KRAS oncogene mutations in tumor tissue of patients with metastatic colorectal cancer Vasiljevic Tijana 1, Knezevic-Usaj Slavica 1, Solajic Nenad 1, Ivkovic-Kapicl Tatjana 1, Nikolic Ivan 2, Protic Mladjan 3, Jakimov Dimitar 1 1 Department of pathoanatomical and laboratory diagnostics, 2 Clinic for internal oncology, 3 Clinic for oncological surgery, Oncology Insitute of Vojvodina, Sremska Kamenica, Serbia, 4 Faculty of Medicine, University of Novi Sad, Serbia Aim: To determine prognosic significance of RAS oncogene mutation detection in patients with metastatic colorectal carcinoma (mcrc). Introduction: CRC is still third most common cancer of both genders and second cause of death from malignancy in Western countries. In recent years, detecting RAS mutation in mcrc tumor tissue has became an imperative in selecting patients for monoclonal antibodies targeted therapy to Epidermal Growth Factor Receptor (EGFR). Nevertheless, there is no consensus regarding prognostic relevance of determining RAS status in patients with mcrc. Material and methods: Study included 116 patients with surgicaly resected CRC at Oncology Insitute of Vojvodina between January and December KRAS mutation detection was performed in formalin-fixed paraffin embeded tumor tissue samples processed by real-time chain polymerase reaction (real-time PCR) and applyng Cobas KRAS Mutation Test and Cobas 4800 System for detection of mutations in codons 12/13 and 61 of KRAS gene. Results: Average age in tested population was 65 years, with a male gender predominance (66.4%). Presence of KRAS mutation was found in 50.9% patients: 44.8% in codons 12/13, 4.3% in codon 61 and 1.7% in both codons 12/13 and 61. RAS mutated colorectal carcinomas (n=59) compared with RAS wildtype colorectal cancers, were significantly associated with male gender, moderately differentiated tumors, lymphovascular invasion and local nodal metastases. Conclusion: Our results show that, beside predictive, KRAS can also have prognostic significance regarding risk assesment for lymphovascular invasion and presence of local and distant metastases. Key words: colorectal cancer, RAS mutation Rani poremećaj neurogeneze u subgranularnoj zoni hipokampusa kod 5xFAD transgenog animalnog modela Alchajmerove bolesti Ivan Zaletel 1, Milka Perović 2, Mirna Jovanović 2, Marija Schwirtlich 3, Milena Stevanović 3.4.5, Selma Kanazir 2, Nela Puškaš 1 1 Institut za histologiju i embriologiju Aleksandar Đ. Kostic, Medicinski fakultet, Univerzitet u Beogradu, Beograd, Srbija 2 Odeljenje za neurobiologiju, Institut za biološka istraživanja Siniša Stanković, Univerzitet u Beogradu, Beograd, Srbija 3 Laboratorija za humanu molekularnu genetiku, Institut za molekularnu genetiku i genetičko inženjerstvo, Univerzitet u Beogradu, Beograd, Srbija 4 Univerzitet u Beogradu, Biološki fakultet, Beograd, Srbija 5 Srpska akademija nauka i umetnosti, Beograd, Srbija Cilj: Cilj ovog rada bio je da se ispita uloga Sox1 i Sox2 transkripcionih faktora u subgranularnoj zoni (SGZ) hipokampusa, regionu mozga u kome se odvija adultna neurogeneza, a kod 5xFAD miševa starosti 8 nedelja. Uvod: Transgeni 5xFAD miševi predstavljaju model Alchajmerove bolesti (AB) koji se karakteriše ranim deponovanjem amiloidnih plakova, koji remete proces adultne neurogeneze u hipokampusu. Određeni transkripcioni faktori, kao što je SoxB1 grupa proteina uključena je u proces adultne neurogeneze, ali 13

14 SPECIJALNA SESIJA: SESIJA SPECIJALIZANATA njihova uloga u neurodegenerativnim oboljenjima i dalje nije u potpunosti istražena. Materijal i metode: U ovom istraživanju korišćeni su transgeni miševi oba pola i njihove odgovarajuće netransgene kontrole (6 životinja po grupi). Proliferišuće ćelije i nezreli neuroni detektovani su imunohistohemijskom ekspresijom Ki-67 i dablkortina, dok su neuronalne stem/progenitorne ćelije detektovane ekspresijom Sox1 i Sox2 proteina. Imunohistohemijsko bojenje i brojanje imunoreaktivnih ćelija izvršeno je na parafinskim presecima hipokampusa. Rezultati: Imunohistohemijska analiza pokazala je da 5xFAD miševi oba pola u SGZ imaju statistički značajniji broj Sox1 imunoreaktivnih ćelija, dok su Sox2 imunoreaktivne ćelije bile smanjene samo kod 5xFAD ženki. Takođe, pokazali smo da kod transgenih mužjaka dolazi i do smanjenja broja novoformiranih neurona, dok je broj proliferišućih ćelija nepromenjen u odnosu na netransgene kontrole. Zaključak: Rezultati ove studije pokazuju da rane promene u neurogenezi u 5xFAD modelu nastaju uprkos očuvanom proliferativnom potencijalu u SGZ. Naši rezultati jasno ukazuju na važnost određenih SoxB1 transkripcionih faktora u ranim fazama AB, kako u patogenetskom smislu, tako i u smislu novih važnih markera za proučavanje procesa adultne neurogeneze. Ključne reči: neurogeneza, Alchajmerova bolest, 5xFAD, DCX, SoxB Early changes in the neurogenesis in the subgranular zone of the hippocampus in 5xFAD transgenic mice model of Alzheimer s disease Ivan Zaletel 1, Milka Perovic 2, Mirna Jovanovic 2, Marija Schwirtlich 3, Milena Stevanovic 3,4,5, Selma Kanazir 2, Nela Puskas 1 1 Institute of Histology and Embryology Aleksandar S. Kostic, School of Medicine, University of Belgrade, Belgrade, Serbia 2 Department of Neurobiology, Institute for Biological Research Sini a Stankovic, University of Belgrade, Belgrade, Serbia 3 Laboratory for Human Molecular Genetics, Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade, Serbia. 4 University of Belgrade, Faculty of Biology, Belgrade, Serbia 5 Serbian Academy of Sciences and Arts, Belgrade, Serbia Aim: The aim of this study was to investigate the expression of Sox1 and Sox2 transcriptional factors in the subgranular zone (SGZ) of the hippocampus in 8 weeks old 5xFAD mice. Introduction: Transgenic 5xFAD mice represent a model of Alzheimer s disease (AD) characterized by an early deposition of amyloid plaques which disrupt the process of adult neurogenesis in the hippocampus. Certain transcriptional factors such as SoxB1 transcriptional factors are involved in the process of adult neurogenesis, but their roles in neurodegenerative disorders are not fully understood. Material and Methods: Transgenic mice of both genders and their respective non-transgenic controls (n=6 per group) were used in the study. Proliferating cells and immature neurons were detected by their immunohistochemical expression of Ki- 67 and doublecortin, while neuronal stem/precursor cells were identified by the expression of Sox1 and Sox2 proteins. Immunohistochemistry and counting were performed on hippocampal paraffin sections. Results: Immunohistochemical analysis showed that 5xFAD mice in the SGZ of the hippocampus have significantly lower numbers of Sox1 immunoreactive cells, while Sox2 immunoreactive cells were lower only in female 5xFAD mice. Furthermore, we have detected a decrease in the number of newly formed neurons in male transgenic mice, while the number of proliferating cells was unchanged when compared to non-transgenic controls. Conclusion: The results of our study show that early changes in the neurogenesis in 5xFAD model occur despite the preserved proliferative potential in the SGZ. Our results clearly indicate the importance of SoxB1 transcriptional factors in the early phases of AD. Key words: neurogenesis, Alzheimer s disease, 5xFAD, DCX, SoxB Protočna citometrija: rešenje u dijagnostici životno ugrožavajućih pedijatrijskih Non-Hočkin limfoma Nemanja Mitrović 1, Gordana Samardžija 1, Slaviša Đuričić 1, Tatjana Terzić 2, Miloš Kuzmanović 1 Dragomir Šokić 1, Bojana Slavković 1 1 Institut za zdravstvenu zaštitu majke i deteta Srbije dr Vukan Čupić, Beograd, Srbija 2 Institut za patologiju, Medicinski fakultet Univerziteta u Beogradu, Beograd, Srbija Cilj: Procena korisnosti protočnocitometrijske (FCM) analize seroznih izliva u dijagnostici pedijatrijskih Non-Hockin limfoma (NHL). Uvod: Serozni izlivi su neretko prva, životno ugrožavajuća manifestacija pedijatrijskih NHL-a. Imunofenotipizacija ćelija izliva FCM metodom sa dodatnom citološkom analizom 14

15 SPECIAL SESSION: RESIDENTS SESSION mogla bi biti značajna pomoć u urgentnoj dijagnostici NHL i omogućiti brzo započinjanje citoreduktivne terapije. Materijal i metode: FCM analiza seroznih izliva 17 dece i adolescenata hospitalizovanih u Institutu za zdravstvenu zaštitu majke i deteta Srbije dr Vukan Čupić pod kliničkom sumnjom na NHL, korišćenjem standardizovanog panela monoklonskih antitela: CD19, icd79a, CD20, CD10, iigm, kappa/ lambda, icd3, scd3, CD7, CD2, CD5, CD4, CD8, CD1a. Citološka analiza izliva je izvršena na May- Grunwald-Giemsa bojenim preparatima. Učinjena je korelacija sa patohistološkim nalazom dostupnih tumorskih bioptata. Rezultati: Prekursorski T-ćelijski (T-III/T-IV) fenotip je dokazan u 5 uzoraka. U 7/9 uzoraka sa zrelim B (B-IV) fenotipom FAB L3 citomorfologija je ukazala na Burkitt-ov limfom (BL), dok je u 2/9 uzoraka sugerisala difuzni B-krupnoćelijski limfom (DLBCL). Naknadna biopsija tumora je bila dostupna kod 7/14 pacijenata sa malignim izlivima i kod svih je potvrđena preliminarna dijagnoza. Kod 3 bolesnika kod kojih nije bilo malignih ćelija u izlivu, FCM i citomorfološki su uočene samo reaktivne promene, a dijagnoza je morala biti postavljena biopsijom tumora (BL 2 pacijenta i DLBCL 1 pacijent). Od 7 pacijenata dijagnostikovanih samo FCM-om i citološkom analizom izliva, 6 je postiglo remisiju bolesti. Zaključak: FCM brzo i precizno detektuje ćelije NHL u uzorcima malignih seroznih izliva. Zajedno sa citološkom analizom, dovoljna je u većini slucajeva za njihovu konačnu dijagnozu to omogućava brzo započinjanje terapije. Ključne reči: protočna citometrija, Non-Hočkin limfomi, serozni izlivi Flow cytometry: a solution in diagnosis of life threatening pediatric Non- Hodgkin lymphomas Nemanja Mitrovic 1, Gordana Samardzija 1, Slavisa Djuricic 1, Tatjana Terzic 2, Milos Kuzmanovic 1, Dragomir Djokic 1, Bojana Slavkovic 1 1 Mother and child healthcare Institute of Serbia dr Vukan Cupic, Belgrade, Serbia 2 Institute of Pathology, Medical Faculty, University of Belgrade, Belgrade, Serbia Aim: Evaluation of the usefulness of flow cytometry (FCM) serous effusion analysis in a diagnosis of pediatric Non-Hodgkin lymphomas (NHL). Introduction: Serous effusions are often the first, life-threatening manifestation of pediatric NHL. FCM immunophenotyping of effusions with cytological analysis could help in diagnosis of NHL, and thus enable fast initiating of cytoreductive therapy. Material and Methods: FCM analysis of serous effusions obtained from 17 children and adolescents hospitalized in Mother and Child Healthcare Institute of Serbia under clinical suspicion of NHL using the standardized panel of monoclonal antibodies: CD19, icd79a, CD20, CD10, iigm, kappa/lambda, icd3, scd3, CD7, CD2, CD5, CD4, CD8, CD1a. Cytological examination was performed on May-Grunwald-Giemsa stained slides. The results were correlated with histopathological findings of available tumor biopsies. Results: Precursor T-cell (T-III/T-IV) phenotype was confirmed in 5 samples. In 7/9 samples with mature B (B-IV) phenotype, FAB L3 cytomorphology indicated Burkitt lymphoma (BL), and in 2/8 suggested diffuse large B-cell lymphoma (DLBCL). Tumor biopsy was available in 7/14 patients and in all cases preliminary diagnosis was confirmed. In 3 patients with no malignant cells in effusions, FCM and cytomorphologicaly only reactive changes were observed, and diagnosis had to be made by tumor biopsy (BL 2 patients, DLBCL 1 patient). Out of 7 patients diagnosed only by FCM and cytological analysis, 6 achieved a remission of the illness. Conclusion: FCM detects NHL cells in malignant serous effusions fast and accurate. In combination with cytological analysis, FCM is sufficient for diagnosis in most cases, allowing rapid initiation of therapy. Key words: flow cytometry, Non-Hodgkin lymphomas, serous effusions 15

16 Plenarne usmene prezentacije Plenary oral presentation Simultana pojave akutne mijeloidne leukemije i monoklonske plazmacitoze u biopsiji kostne srži: prikaz slučaja Mirjana Prvanović 1, Nataša Stanisavljević 2, Olivera Marković 2, Tatjana Terzić 1 1 Institut za Patologiju, Medicinski fakultet, Univerzitet u Beogradu, Beograd, Srbija 2 KBC Bežanijska kosa, Beograd, Srbija Cilj: Prikazujemo redak slučaj simultane pojave Istovremena pojava akutne mijeloidne leukemije (AML) i monoklonske plazmacitoze (MP). Uvod: Istovremena pojava akutne mijeloidne leukemije (AML) i monoklonske plazmacitoze (MP) u biopsiji kostne srži kod pacijenta koji nije prethodno primao hemoterapiju je vrlo retka. Prikaz slučaja: Bolesnica stara 45 godina hospitalizovana je novembra godine na Odeljenju hematologije KBC Bežanijska kosa zbog malaksalosti, febrilnosti, makulopapulozne ospe, gubitka težine i bolova u kostima. U kompletnoj krvnoj slici je viđena leukocitoza 33x109/l (leukocitarna formula: neutrofili 31%, mijeloblasti 12%, monoblasti, promonociti i monociti ukupno 53%), anemija (hemoglobin 77gr/l) i trombocitopenija (34x109/l) uz 5% blasta u razmazu periferne krvi. Imunoelektroforeza proteina seruma je pokazala prisustvo monoklonskih IgA lambda tipa (IgA 9,98, IgM 2,29, IgG 10,1), kappa/lambda 0,84, Beta2mikroglobulin 3,16. U biohemijskim analizama nađene su povišene vrednosti kreatinina (93umol/l), mokraćne kiseline (412umol/l), LDH (876U/l) uz ubrzanu sedimentaciju eritrocita (50mm/h). Imunoelektroforeza proteina urina pokazala je prisustvo monoklonskih teških i lakih lambda lanaca. Imunofenotipizacija likvora je pokazala prisustvo neuroleukemije. Na MR-u i CT-u nisu uočene ostelitične lezije. U mijelogramu je viđeno 10% zrelih plazmocita, a morfološki i imunohistohemijski nalaz u kostnoj srži ukazao je na monoklonsku plazmaćelijsku infiltraciju (20%) sa infiltracijom ćelijama monocitne diferencijacije (30%). U biopsiji kožne promene dijagnostikovan je mijeloidni sarkom. Citogenetska analiza pokazala je normalan kariotip uz mutaciju FLT3 i NPM gena. Bolesnica je dijagnostikovana kao AML-M5, primenjena je indukciona terapija (DA Cytosar) i konsolidaciona hemoterapija (HiDAC), a zatim je transplantirana (alogena od nesrodnog davaoca). Ona je još uvek u kompletnoj remisiji. Zaključak: Monoklonsku plazmocitozu kostne srži bi trebalo pažljivo analizirati zbog moguće udruženosti sa drugim hematološkim malignitetima. Ključne reči: Akutna mijeloidna leukemija, monoklonska plazmacitoza, mijeloidni sarkom. Simultaneous occurrence of acute myeloid leukaemia and monoclonal plasmacytosis in bone marrow biopsy: case report Mirjana Prvanovic 1, Natasa Stanisavljevic 2, Olivera Markovic 2, Tatjana Terzic 1 1 Institute of Pathology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia 2 University Hospital Clinical Centre Bežanijska kosa, Belgrade, Serbia Aim: We present a rare case of simultaneous occurrence Concurrent occurrence of acute myeloid leukemia (AML) and monoclonal plasmacitosis (MP): Introduction: The simultaneous occurrence of acute myeloid leukemia (AML) and monoclonal plasmacytosis (MP) in bone marrow (BM) biopsy in patient without previous exposure to chemotherapy is very rare. Case report: We reported the case of a 45-year-old woman who presented with fatigue, fever, maculopapular rush, weight loss and bone pain. She was admitted to the Haematology Department of University CHC Bezanijska Kosa in November The complete blood count showed: white blood cell count 33x109/l (neutrophils 31%, myeloblasts 12%, monoblasts, promonocytes and monocytes 53%), hemoglobin 77gr/l, platelet count 34x109/l and 5% blastic cells in the peripheral smear. Serum immunoelectrophoresis showed increased monoclonal IgA (IgA 9,98, IgM 2,29, IgG 10,1), kappa/lambda 0,84, Beta2microglobulin 3,16. Biochemistry showed elevated creatinin level 93umol/l, uric acid 412 umol/l, high LDH 876U/l and sedimentation rate (50mm/h). Urine electrophoresis showed monoclonal heavy and light chains lambda type. Liquor immunophenotyping showed neuroleukemia. Skeletal survey showed no lytic lesions. The BM aspiration revealed around 10% plasma cells and BM biopsy showed infiltration by 20% monoclonal plasma cells (kappa-/lambda ) with 30% infiltration by cells with monocytes differentiation (without excess of blasts). Biopsy of skin lesion 16

17 PLENARY ORAL PRESENTATION revealed myeloid sarcoma. Cytogenetic analysis detected normal karyiotype with FLT3 and NPM mutation. The patient was diagnosed as AML-M5, administered with induction therapy (DA Cytosar) and consolidation therapy (HiDAC) and she was successfully treated with allogenenic stem cell transplantation. She achieved and maintained complete remission. Conclusion: Monoclonal plasmacytosis of BM should be carefully examined due to possible association with other haematological malignancies. Key words: AML, MP, myeloid sarcoma. Malignant gastrointestinal stromal tumor: a case report Vanja Filipovski, Katerina Kubelka-Sabit, Dzengis Jasar KB Acibadem/Sistina, Skopje, FYROM Aim: We present an unusual case of malignant gastrointestinal stromal tumor filling the entire abdominal cavity. Introduction: Gastrointestinal stromal tumors are the most common mesenchymal neoplasms of the gastrointestinal tract. Small tumors are generally benign, but large tumors disseminate to the liver, omentum and peritoneal cavity. They rarely occur in other abdominal organs. Material and Metods: The operative material consisted of segment of ileum where a tumor mass of 8 cm was found originating from the wall and fragments of small intestinal serosa and omentum where multiple nodular tumor mases were found. Representative samples were taken, and were paraffin embedded and stained routinely with Hematoxyllin-Eosin. Additionally immunohistochemical analyses were performed using the antibodies c-kit, CD34, Vimentin, CKAE1/AE3, Ki67 and others. Results: Microscopic analysis revealed a malignant gastrointestinal stromal tumor with a high mitotic rate of 58/50 HPF mitoses. However clinical reports stated that an additional large 12 cm tumor mass was found in the liver that was not removed. Conclusion: Gastrointestinal stromal tumors are the most common gastrointestinal mesenchymal neoplasms but presence of multiple tumor masses on various organs and sites is rare. Presence of multiple tumors in various organs brings about the issues of possibility of multiple primaries or the proper detection of the original tumor mass. Key words: malignant gastrointestinal stromal tumor, metastases, multiple primaries Imunohistohemija i in situ hibridizacija kao komplementarne metode u molekularnoj subtipizaciji karcinoma dojke: desetomesečno iskustvo jedne institucije Duško Dunđerović, Svetislav Tatić, Jasmina Marković Lipkovski, Sanja Ćirović, Martina Bosić, Emilija Manojlović Gačić Institut za patologiju, Medicinski fakultet, Univerzitet u Beogradu, Beograd, Srbija Cilj: Cilj studije je klasifikacija tumora na četiri glavna molekularna podtipa koristeći imunohistohemiju i in situ hibridizacione metode, kao i određivanje učestalosti podtipova. Uvod: Mogu se identifikovati četiri molekularna podtipa karcinoma dojke: Luminal A i Luminal B (ispoljavaju hormonske receptore), HER2 obogaćene (prekomerno ispoljavaju HER2 ) i Trostruko negativne/ Basal-like (ne pokazuju amplifikaciju HER2 onkoproteina i ne ispoljavaju steroidne receptore). Materijal i metode: Studija preseka, sprovedena na Institutu za patologiju, Medicinskog fakulteta Univerziteta u Beogradu, tokom desetomesečnog perioda godine obuhvatila je 337 pacijenata sa dijagnozom karcinoma dojke. Koristeći metodu imunohistohemije, sva četiri markera (estrogen, progesteron, HER2 i Ki67) su procenjena na tkivima karcinoma dojke. Kao dodatne metode, in situ hibridizacija (FISH, SISH), su korišćene u slučejevima kada su rezultati HER2 onkoproteina na imunohistohemiji bili dvosmisleni. Rezultati: Luminal A, Luminal B, HER2 obogaćeni i trostruko negativni karcinomi bili su prisutni u 133 (39,45%), 147 (43,62%), 22 (6,5%), 34 (10,08%) slučajeva. Za 55 (16,35%) slučajeva izvršena je in situ hibridizacija kako bi se klasifikovali karcinomi u odgovarajući molekularni podtip. Zaključak: Učestalost molekularnih podtipova karcinoma dojke u na našoj studiji slična je podacima iz literature za evropske zemlje. S obzirom na to, da ova podela karcinoma dojke ima prognostičke i prediktivne vrijednosti za dalje lečenje pacijenta, to treba uraditi u ustanovama sa odgovarajućom opremom i osposobljenim osobljem, kako bi se postigli najbolji rezultati u najkraćem roku. Ključne reči: karcinom dojke, molekularni suptipovi, imunohistohemija, in situ hibridizacija 17

18 PLENARNE USMENE PREZENTACIJE Immunohistochemistry and in situ hybridisation as complementary methods in molecular subtyping of breast carcinomas: a 10 months period, single institution experience Dusko Dunderovic, Svetisla Tatic, Jasmina Markovic Lipkovski, Sanja Cirovic, Martina Bosic, Emilija Manojlovic Gacic Institute of Pathology, Faculty of medicine, University of Belgrade, Belgrade, Serbia Aim: The aim of the study is to classify tumors into four main molecular subtypes using immunohistochemistry and in situ hybridisation methods, as well as to determine frequency of different carcinoma subtypes. Introduction: Four molecular subtypes of breast carcinoma can be identified: Luminal A and Luminal B (hormone receptors positive), HER2 enriched (HER2 overexpression) and Triple Negative / Basal-like (absence of HER2 amplification and steroid receptors expression). Materials and Methods: Cross-sectional study, conducted in Institute of pathology, Medical Faculty, University in Belgrade, during the ten months period in 2017, included 337 patients with diagnosed breast carcinoma. Using the methods of immunohistochemistry, all four markers (estrogen, progesteron, HER2, and Ki67) were evaluated on breast carcinoma tissues. As additional methods, in situ hybridisation (FISH, SISH) was used in cases if HER2 oncoprotein results on immunohistochemistry were equivocal. Results: Luminal A, Luminal B, HER2 enriched, and Triple Negative carcinomas were present in 133 (39,45%), 147 (43,62%), 22 (6,5%), 34 (10,08%) cases, respectively. For 55 (16,35%) cases, in situ hybridisation had been done in order to classify carcinomas in proper molecular subtype. Conclusion: Frequency of molecular subtypes of breast carcinomas in our study are similar to literature data for European countries. Breast carcinoma subtyping has prognostic and predictive values for further patient treatment, and should be done in institutions with adequately trained personnel and equipment, in order to achive best results in the shortest time. Key words: breast carcinoma, molecular subtypes, immunohistochemistry, in situ hybridisation Promena statusa hormonskih i HER2 receptora lokalno uznapredovalih HER2 amplifikovanih karcinoma dojke posle neoadjuvantne terapije sa Trastzumabom Bojan Radovanović 1,2, Tijana Vasiljević 1,2, Nenad Šolajić 1,2, Zoran Nikin 1,2, Dragana Tegeltija 1,3, Vladimir Zečev 4, Tatjana Ivković-Kapicl 1,2 1 Univerzitet u Novom Sadu, Medicinski fakultet Novi Sad, Novi Sad, Srbija 2 Institut za onkologiju Vojvodine, Sremska Kamenica, Srbija 3 Institut za plućne bolesti Vojvodine, Sremska Kamenica, Republika Srbija 4 Opšta bolnica Sombor, Sombor, Srbija Cilj: Cilj našeg istraživanja bila je procena statusa estrogenskih i progesteronskih hormonskih receptora (ER i PR) i HER2 receptora u dijagnostickim core biopsijama, u poređenju sa hirurškim resekcionim uzorcima istih pacijentkinja nakon NAC-a protokola koji su uključivali trastuzumab. Uvod: Neoadjuvantna hemioterapija (NAC) povezana je sa fenotipskom promenom karcinoma dojke, posebno sa promenom molekularnog fenotipa kroz modulaciju ekspresije hormonskih i HER2 receptora. Materijal i metode: Istraživanje je obuhvatilo 35 pacijentkinja sa lokalno proširenim HER2-amplifikovanim karcinomom dojke koji su bili tretirani NAC režimima sa trastuzumabom i koji su imali status receptora utvrđenog na core biopsiji pre NAC-a i na hirurškom uzorku nakon završetka terapije. Rezultati: Patološki potpuni odgovor (pcr) primećen je u 4 slučaja (11,4%), dok je parcijalni odgovor na terapiju zabeležen u 31 slučaju (88,6%). U 27 slučajeva (87,1%) najčešći histološki tip je bio invazivni karcinom dojke nijednog specijalnog tipa (NST), dok je najčešći histološki stepen (HG) bio HG3 u 27 slučajeva (87,1%). Nije bilo zabeleženih promena u histološkom tipu ili gradusu karcinoma. Zastupljenost ER i PR receptorske pozitivnosti na dijagnostickoj core-biopsiji u poredenju sa uzorcima hirur kih resekata nakon NAC-a su sa 61,29% na 67,74% i sa 48,39% na 64,52%, respektivno. Status HER2 receptora promenio se sa pozitivnog na negativan u 2 slučaja (6,45%). Zaključak: Promene u statusu receptora karcinoma dojke nakon NAC-a su značajne zbog njihovih implikacija u pristupu ciljane terapiji i naknadne modifikacije žima adjuvantne terapije. Ključne reči: karcinom dojke, neoadjuvantna terapija, trastuzumab, hormonski receptori, HER2 18

19 PLENARY ORAL PRESENTATION Alterations of hormone receptors and HER2 receptors status in HER2 amplified locally advanced breast carcinomas after neoadjuvant therapy with Trastuzumab Bojan Radovanovic 1,2, Tijana Vasiljevic 1,2, Nenad Šolajic 1,2, Zoran Nikin 1,2, Dragana Tegeltija 1,3, Vladimir Zecev 4, Tatjana Ivkovic-Kapicl 1,2 1 University of Novi Sad, Faculty of Medicine Novi Sad, Novi Sad, Serbia 2 Institute for Oncology of Vojvodina, Sremska Kamenica, Serbia 3 Institute for Pulmonary Diseases of Vojvodina, Sremska Kamenica, Serbia 4 General Hospital Sombor, Sombor, Serbia Aim: The aim of our study was to evaluate status of estrogen and progesteron hormone receptors (ER and PR), and HER2 receptors in diagnostic core biopsy specimens, compared to surgical resection specimens of the same patients after NAC regimens all including trastuzumab. Introduction: Neoadjuvant chemotherapy (NAC) is associated with phenotypic alteration in breast carcinoma, especially with the change of molecular phenotype through the modulation of hormone and HER2 receptors expression. Material and Methods: The study included 35 patients with HER2-amplified locally advanced breast carcinoma that were treated with NAC regimens that included trastuzumab, and which had receptors status determined on pre-nac core biopsy, and on surgical specimen after the completion of the therapy. Results: Pathological complete response (pcr) was observed in 4 cases (11.4%), while partial response to therapy was noted in 31 cases (88.6%). Invasive breast carcinoma of no special type (NST) was the most common histological type in 27 cases (87.1%), while the most common histological grade (HG) was HG3 in 27 cases (87.1%). There were no noted changes in histological type or grade of the carcinoma. The rates of ER and PR receptors positivity on diagnostic core biopsy compared to post-nac surgical resection specimens were 61.29% to 67.74% and 48.39% to 64,52%, respectively. HER2 receptors status changed from positive to negative in 2 cases (6,45%). Conclusion: Changes in status of the receptors in breast carcinoma after NAC is significant due to implications in tailored therapy approach, and subsequent modification of adjuvant therapy regimens. Key words: breast carcinoma, neoadjuvant therapy, trastuzumab, hormone receptors, HER2 Procena ekspresije vaskularnih prostora strome kolorektalnog adenokarcinoma korišćenjem kompjutrerizovane ImageJ analize Ivana Tufegdžić 1, Miloš Zarić 1, Snežana Jančić 2 1 Institut za patologiju i sudsku medicinu VMA, Beograd 2 Fakultet medicinskih nauka, Kragujevac Cilj: Procena odnosa gustine, obima i vrednosti endotelijalne površine ( endothelial area, EA) vaskularnih prostora (VP) pomoću kompjuterizovane ImageJ analize i morfoloških karakteristika adenokarcinoma. Uvod: U kompleksnoj reakciji tumorskih ćelija i tumorske strome prilikom invazije adenokarcinoma kolona, angiogeneza je esencijalna za metastatski potencijal tumora. Materijal i metode: 70 resektata je retrospektivno pregledano. Za svaki tumor su određeni: histološki gradus i patološki stadijum tumora, prisutnost limfatičke, venske i perineuralne invazije, način rasta tumora, prisustvo metastaza u limfnim čvorovima i jetri. Za vizuelizaciju endotelnih ćelija je upotrebljeno imunohistohemijsko bojenje antitelom CD31. Iz svakog tumora je načinjeno devet fotografija: tri sa invazivnog fronta, tri sa mesta najveće gustine VP i tri fotografije sa nasumično izabranih mesta. Kompjuterska analiza je učinjena pomoću softverskog programa ImageJ. Za analizu EA ( EA predstavlja površinu CD31 pozitivnih endotelijalnih ćelija) program je iskazao rezultat u vidu procenta testiranog polja (% area). Gustina VP je iskazana brojem CD 31 pozitivnih VP na 1mm 2, dok je obim izražen u mm. Rezulatati svih analiziranih parametara su korelirani sa opisanim morfološkim karakteristikama adenokarcinoma. Rezultati: Nije bilo statistički značajne korelacije izmedđu gustine i obima VP i morfoloških karakteristika tumora. EA sa nasumično izabranih mesta (minimum 0,69%, maksimum 10,11%, p=0,016) korelira sa prisustvom venske invazije. EA sa invazivnog fronta i mesta najveće gustine nisu pokazali statističku korelaciju sa morfoloških karakteristikom tumora. Zaključak: Procena EA je jedini vaskularni parameter koji je pokazao statistički značajnu povezanost sa negativnim prognostičkim parametrima adenokarcinoma kolorektuma. Ključne reči: kolon, adenokarcinom, vaskularni prostori, kompjuterizovana analiza 19

20 PLENARNE USMENE PREZENTACIJE Assessment of angiogenesis expression of colorectal cancer by computer-assisted histopathological ImageJ analysis Ivana Tufegdžić 1, Miloš Zaric 1, Snezana Jancic 2 1 Istitute of Pathology and Forensic medicine, Military Academy, Belgrade, Serbia 2 Faculty of Medical Sciences, Kragujevac, Serbia Aim: Assessment of relationship between density, perimeter and endothelial surface ( endothelial area, EA) of vascular spaces (VS) using ImageJ analysis and morphological characteristics of adenocarcinoma. Introduction: Colorectal adenocarcinoma invasion involves complex reaction of tumor cells and stroma, whereas angiogenesis is essential for metastatic potential. Material and Methods: 70 resected specimens were reviewed. For each adenocarcinoma histological grade, pathological stage, lymphatic, venous and perineural invasion, growth pattern, metastases in lymph nodes and liver were determined. For visualization of vascular endothelial cells immunohistochemical staining CD31 antibody was used. From each tumor nine fields were photographed: three from invasive front, three from VS highest density and three selected randomly. Computer analysis of images was done using program ImageJ. For analysis of EA (EA representing surface area of CD31 positive endothelial cells) program recalculated them as percentage of tested fields (% area). VS density was shown as number VS per 1mm 2, while perimeter of VS was shown in Results of all parameters were compared with all above described morphological characteristics. Results: There was no significant correlation between density and perimeter of VS and any of histopathological findings. EA from randomly chosen fields (minimum 0,69%, maximum 10,11%, p=0,016) correlates with the presence of venous invasion. There was no significant correlation between EA from the invasive front and areas of the highest density and any of the histopathological findings. Conclusion: Assessment of vascular endothelial surface area is only vascular parameter which positively correlates with prognostic parameters that could indicate worse outcome. Key words: colon, adenocarcinoma, vascular spaces, Computer analysis Akrilamid-tihi ubica? Jelena Ilic Sabo, Djolai Matilda, Amidžić Jelena, Aleksandra Levakov Fejsa Medicinski fakultet Novi Sad, Klinički centar Vojvodine, Novi Sad, Srbija Cilj: Ispitati patohistološke promene tkiva želuca nakon peroralne primene akrilamida. Uvod: Akrilamid je toksična hemijska materija otkrivena u hrani bogatoj skrobom, koja nastaje nakon obrade hrane na visokim temperaturama. Materijal i metode: Istraživanje je sprovedeno na 6 grupa eksperimentalnih životinja sa po 5 jedinki u svakoj grupi (Wistar pacovi). Dvema kontrolnim grupama oralno je aplikovana voda. Dvema eksperimentalnim grupama aplikovan je oralno akrilamid u dozi od 25 mg/kg, dok je kod poslednje dve eksperimentalne grupe aplikovan akrilamid u dozi od 50 mg/kg. Tri grupe životinja žrtvovane su nakon 24 h, a druge tri nakon 72 h. Na histološkom materijalu tkiva želuca primenjene su kvalitativne i semikvantitativne histološke analize, stereološka merenja pojedinih delova zida želuca, kao i linearna merenja broja mastocita u mukozi i submukozi. Rezultati: Patohistološke promene u tkivu želuca javile su se u vidu direktnog oštećenja površnog epitela praćenog slabom inflamatornom reakcijom i degranulacijom mastocita. Obnavljanje epitela potvrđeno je prisustvom nezrelih oblika mukoprodukujucih ćelija. Ispitivani parametri inflamacije i oštecenja tkiva želuca pokazuju pozitivnu korelaciju sa primenjenom dozom i vremenom izlaganja akrilamidu. Zaključak: Razumevanje mehanizma delovanja akrilamida na tkivo želuca omogućava adekvatnu prevenciju, kao i primenu adekvatne terapije. Ključne reči: Akrilamid, Wistar pacovi, Tkivo želuca, Inflamacija, Reepitelizacija Acrylamide-silent killer? Jelena Ilic Sabo, Djolai Matilda, Amidzic Jelena, Aleksandra Levakov Fejsa Medical Faculty of Novi Sad, Clinical Center of Vojvodina, Novi Sad, Serbia Aim: The goal was to examine the effects of direct exposure of stomach tissue to acrylamide. Introduction: Acrylamide is a toxic chemical substance discovered in foods rich in starch, prepared at high temperatures. Material and Methods: The research was carried out 6 groups of 5 experimental animals (Wistar rats). Two control groups orally implicated distilled water. Two experimental groups orally administrated 20

21 PLENARY ORAL PRESENTATION acrylamide in a daily dose of 25 mg/kg, and two dose of 50 mg/kg. Three groups were sacrificed after 24h and three after 72h, On histological gastric tissue material is applied qualitative and semi-quantitative histological analysis, stereological measurements of individual compartments of the stomach wall, linear measuring the number of mast cells in the mucosa and submucosa. Results: Slight damage of the surface epithelium, accompanying mild inflammatory reaction and degranulation of mast cells are results of histological damages in the stomach tissue. Reconstruction of the epithelium follows directly toxic effect on epithelium, and it is confirmed by the presence of immature form of mucoproductive cells. Examined inflammatory and degenerative parameters show a positive correlation with respect to dose and/or a time of exposition to acrylamide. Conclusion: Understanding the mechanism of action of acrylamide allows to apply adequate prevention and make an appropriate choice of therapeutic methods. Key words: Acrylamide, Wistar rats, Stomach tissue, Inflammation, Reepithelization, Poremećaj cerebelarne folijacije uzrokovan prenatalnom primenom metroidazola kod zamorca Ivan Čapo 1, Nataša Hinić 2, Saša Vukmirović 3, Tihomir Dugandžija 4, Slobodan Sekulić 5 1 Zavod za histologiju i embriologiju, Medicinski fakultet, Univerzitet u Novom Sadu,Novi Sad,Srbija 2 Institut za Onkologiju Vojvodine,Medicinski fakultet, Univerzitet u Novom Sadu, Srbija, 3 Katedra za farmakologiju i toksikologiju, Medicinski fakultet, Univerzitet u Novom Sadu, Novi Sad, Srbija 4 Katedra za epidemiologiju, Medicinski fakultet, Univerzitet u Novom Sadu, Srbija, Katedra za neurologiju, Medicinski fakultet, Univerzitet u Novom Sadu, Srbija Cilj: Cilj rada je bio da se ispita uticaj prenatalne primene metronidazola na proces folijacije malog mozga kod zamorca. Uvod: Primena metronidazola u trudnoći još uvek zauzima veoma podeljene stavove među lekarima koji ih propisuju. Kao neželjena pojava u primeni metronidazola vrlo često se navodi njegova neurotoksičnost, međutim adekvatna animalna studija u kojoj bi se to potvrdilo do sada još uvek nije navedena. Materijal i metode: U istraživanju je ispitano 42 ploda zamorca dobijenih od 12 skotnih ženki. Ženke su bile podeljene u eksperimentalnu (6 ženki) i kontrolnu grupu (6 ženki). Eksperimentalnoj grupi je u periodu od dana gestacije na svakih 12 časova (u 8:00 i u 20:00) aplikovan subkutano rastvor metronidazola, u koncentraciji od 28mg/kg. Dok je u kontrolnoj grupi po istom protokolu aplikovan subkutano fiziološi rastvor. Po dostizanju 50-og dana gestacije sve jedinke su žrtvovane, a dobijeni plodovi (22 eksperimentalna i 20 kontrolnih) su fiksirani, mali mozak im je fotografisan i uzeti je sagitalni isečak vermalnog regiona obrađen standardnom histološkom tehnikom. Rezultati: Analizom fotografija makroskopskog prikaza dorzalne strane malog mozga kod eksperimentalne grupe jedinki uočene su malformacije kod 15 od ukupno 22 ploda (68,2%). Najčešci poremećaj je činila nepravilna pozicioniranost subfolija VII folije u vidu dijagonalne pozicioniranosti duž čitave dorzalne strane vermisa, kao i pojava parcijalne prisutnosti, mikro- makrogirije. Zaključak: Prenatalna primena metronidazola kod zamorca u periodu od dana gestacije dovodi do poremećaja u cerebelarnoj folijaciji. Ključne reči: mali mozak, metronidazol, folijacija Prenatal metronidazole treatment alternate normal cerebellar foliation in guinea pig fetuses Ivan Capo, Natasa Hinic, Sasa Vukmirovic, Tihomir Dugandzija, Slobodan Sekulic 1 Institute of Histology and Embryology, Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia 2 Oncology Institute of Vojvodina, Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia 3 Department of Pharmacology and Toxicology, Faculty of Medicine, Novi Sad, Serbia 4 Department of epidemiology, Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia,Department of 5 Neurology, Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia Aim: The aim of the study is to investigate the effect of prenatal treatment of metronidazole on the process of cerebellar foliation in the guinea pig. Introduction: The use of metronidazole in pregnancy still occupies very different attitudes among doctors who prescribe them. Neurotoxicity is a common side effect in the use of metronidazole, but there is still no clear animal study. Materials and Method: We studied 42 guinea pig fetuses obtain from 12 pregnant guinea pig dams. Dams were separated in experimental (6) and control6) group(k). Experimental group(e) received from day of gestation at every 21

22 PLENARNE USMENE PREZENTACIJE 12 hour (at 8 a.m. and 8 p.m.) subcutaneous injection od saline solution of metronidazole in concentration of 28 mg/kg. Control group received using same time protocol just saline solution. At 50th day of gestation all dams were sacrified and fetuses were used for further analysis. In each fetuses (22 in E, and 20 K group). Firstly we make gross picture of the brain and secondary we separated vermis region for further histological and immunohistochemical analysis. Results: An analysis of macroscopic images of the dorsal side of the cerebellum in the experimental group of individuals revealed malformations in 15 out of 22 fetuses (68.2%). The most affected folia was VII and characterized with aberrant diagonal positioning along the entire dorsal side of the vermis. Other folia were partial presence, with micro, and agyria changes. Conclusion: Prenatal use of metronidazole in guinea pigs during the 42-49th day of gestation cause disturbance in cerebellar foliation. Key words: cerebellum, metronidasole, folliation Hepatoprotektivna svojstva prirodne i sintetske žučne kiseline u animalnim modelima Bojana Andrejić-Višnjić 1, Matilda Djolai 2, Karmen Stankov 2, Momir Mikov 1, Sandra Trivunić-Dajko 2, Nebojša Pavlović 1, Bojan Stanimirov 1 1 Faculty of Medicine Novi Sad, Novi Sad, Serbia 2 Faculty of Medicine Novi Sad; Clinical Center of Vojvodina, Novi Sad, Serbia. Cilj: Cilj našeg ispitivanja bio je da ispitamo hepatoprotektivno delovanje prirodne ursodeoksiholne (UDK) i polusintetske 12-monoketoholne kiseline (MK) ispitivanjem vrednosti enzima jetre, određivanjem maloniladehida kao pokazatelja oksidativnog oštećenja hepatocita, određivanjem aktivnosti antioksidativnih enzima, histološkom i imunohistohemijskom analizom tkiva jetre I ekspresije nuklearnog farnesoid-x receptora (FXR) žučnih kiselina, markera apoptoze i proliferacije hepatocita. Uvod: Metabolizam hepatocita je izuzetno intenzivan, a procesi koji se odigravaju u hepatocitima raznovrsni, te su veoma podložni oksidativnom oštećenju koje leži u osnovi mnogih oboljenja. Dva popularna modela izazivanja oksidativnog stresa jesu primena etinilestradiola i model holestaze, kao i primena aloksana, odnosno model aloksanskog dijabetesa. Materijal i metode: U ogledu su korišćeni pacovi soja Wistar. Kontrolnoj grupi je aplikovan fiziološki rastvor (0,5 ml/kg). Tri grupe primale su etinilestradiol kao monoterapiju (EE, doza 0,5 mg/kg), ili u kombinaiji sa monoketoholnom (E-MK, 4mg/kg) ili ursodeoksiholnom kiselinom (E-UDK, 25 mg/kg). Da bi se pojačao nivo oksidativnog stresa oformljene su grupe koje su pored etinilestradiola primile i monodozu aloksana (AE, 150mg/kg), odnosno imale terapiju monoketoholnom (AE-MK) i ursodeoksiholnom (AE-UDK) kiselinom, u prethodno navedenim dozama. Tkivo jetre je uzorkovano za histološku obradu, imunohistohemijska bojenja (ki-67, FXR, Bax, Bcl-2, p53), biohemijske analize parametara jetrene funkcije (AST, ALT, GGT, bilirubin ukupni (BLRu) i bilirubin direktni (BLRd)), produkata lipidne peroksidacije (malonilaldehid, MDA), antioksidativnih enzima (katalaze (CAT), glutation peroksidaze (GSH-Px), glutation reduktaze (GSH-R), glutation-s-transferaze (GSH-ST)). Rezultati: U grupama EE i AE, vrednosti AST, ALT i GGT su bile statistički značajno povišene u odnosu na kontrolnu grupu. U poređenju sa EE i AE grupama, primena žučnih kiselina dovela je do statistički značajnog sniženja aktivnosti svih enzima kao i ukupnog i direktnog bilirubina. Obe žučne kiseline su najjači hepatoprotektivni efekat pokazale u pogledu aktivnosti AST i snižavanja koncentracije ukupnog bilirubina, čije su vrednosti primenom i UDK i MK spuštene na nivo vrednosti kontrolne grupe. U pogledu delovanja na aktivnost ALT i GGT, žučne kiseline su pokazale blagu selektivnost. Histološkom analizom, u grupama EE i AE uočeni su hepatociti koji pokazuju kariopiknozu i acidofiliju citoplazme što govori u prilog smrti ćelija, kao i promena u citoplazmi pojedinačnih hepatocita koji odgovaraju paperjastoj degeneraciji. Sve navedene promene se ne uočavaju u tkivu jetre jedinki koje su tretirane žučnim kiselinama. Analizom Ki-67 u tkivu jedinki kontrolne grupe, utvrđeno je da do 5% ćelija pokazuje nuklearnu ekspresiju, te je vrednost od 10% uzeta kao granica za pojačanu proliferativnu aktivnost hepatocita. Kod grupa koje su primale samo prooksidativne supstance, etinilestradiol i aloksan, nije uočena povećana proliferativna aktivnost hepatocita. Kod jedinki kojima je oštećenje hepatocita izazvano samo etinilestradiolom, pojačana je proliferacija hepatocita, i to za 50% primenom UDK, odnosno 100% primenom MK. Sličan hepatoprotektivni efekat ŽK su ispoljile i u odnosu na jedinke tretirane sa obe prooksidativne supstance (AE grupa), gde je u grupi AE-UDK 100% jedinki imalo pojačanu proliferativnu aktivnost hepatocita, a u grupi AE-MK 80%. Nakupljanje hepatotoksičnih, hidrofobnih ŽK u modelu holestaze, pojačava oksidativno oštećenje i indukuje apoptozu, ali i aktivira ekspresiju nuklearnih receptora kao što je farnesoid-x receptor. U kontrolnoj grupi 50% životinja pokazuje 22

23 PLENARY ORAL PRESENTATION slabu ekspresiju FXR, a umerenu i jaku po 25%. Primenom etinilestradiola i aloksana, statistički značajno povećana je zastupljenost jake ekspresije na 75% tj 60%, što ukazuje na akumulaciju hepatotoksičnih ŽK. Hepatoprotektivno dejstvo UDK i MK, dokazano je smanjenim intenzitetom ekspresije FXR. U grupama E-UDK i E-MK, ni jedna jedinka nije imala jaku ekspresiju FXR, a znatno se povećao broj jedinki sa slabom ekspresijom. Slično je i u grupama AE-UDK i AE-MK, po 60% jedinki pokazuje slabu ekspresiju FXR što se ne razlikuje statistički od rezultata kontrolne grupe. Grupe tretirane etinilestadiolom i aloksanom, imale su znatno veću koncentraciju malonilaldehida (MDA) koji je pokazatelj oksidativnog ošetećenja hepatocita. Primena UDK i MK je značajno snizila koncentraciju MDA. Aktivnost antioksidativnih enzima u grupi EE se nije statistički razlikovala od kontrole. U grupi AE gde je oksidativni stres pojačan, aktivnost enzima je statistički značajno niža, a primena UDK i MK statistički značajno pojačava aktivnost ispitivanih enzima. U cilju ispitivanja hepatoprotektivnih svojstava žučnih kiselina, ispitivana je ekspresija proteina Bcl-2 grupe, kao i p53 proteina. Hepatociti kontrolne grupe nisu eksprimirali proapoptotski protein Bax, dok je u grupi EE slaba ekspresija bila prisutna u 50% jedinki, a u AE grupi u 40%. Primenom UDK u oba modela (E-UDK i AE-UDK) je u potpunosti redukovana ekspresija Bax na nivo kontrole. Primena MK, u oba modela je dovela do supresije Bax, tako da je u EE-MK grupi Bax ekspresija 25%, a u grupi AE-MK nema ekspresije Bax. Antiapoptotski Bcl-2 protein je u kontrolnoj grupi detektovan je u 25% jedinki, za razliku od EE i AE grupa, gde je ekspresija u potpunosti suprimirana. Pospešivanjem ekspresije Bcl-2 (E-UDK u 25% jedinki, AE-UDK u 40% jedinki) UDK je pokazala jače hepatoprotektivno delovanje u odnosu na MK. U kontrolnoj grupi p53 ekspresija je zabeležena samo u citoplazmi, kod 50% jedinki, dok je u grupama EE i AE verifikovana nuklearna ekspresija u 25% tj 20% jedinki, što govori u prilog intenzivnijeg apoptotskog delovanja i indukcije transkripcije drugih proapoptotskih proteina. Kod grupa gde je primenjena UDK, nije prisutna ekspresija p53, dok je MK smanjila ekspresiju na nivo kontrolne grupe. Zaključak: UDK i MK ostavruju hepatoprotektivna svojstva antioksidativnim i antiapoptotskim delovanjem. Ključne reči: žučne kiseline, oksidativni stres, apoptoza, FXR 1. Schneider KM, Albers S, Trautwein C. Role of bile acids in the gut-liver axis. J Hepatol Mar 5. pii: S (17) doi: de Boer JF, Bloks VW, Verkade E, Heiner-Fokkema MR, Kuipers F. New insights in the multiple roles of bile acids and their signaling pathways in metabolic control. Curr Opin Lipidol Mar 16. doi: /MOL Zhang Y, LaCerte C, Kansra S, Jackson JP, Brouwer KR, Edwards JE. Comparative potency of obeticholic acid and natural bile acids on FXR in hepatic and intestinal in vitro cell models. Pharmacol Res Perspect Dec;5(6). doi: /prp Chiang JYL, Ferrell JM. Bile acid metabolism in liver pathobiology. Gene Expr Jan 11. doi: / X Shapiro H, Kolodziejczyk AA, Halstuch D, Elinav E. Bile acids in glucose metabolism in health and disease. J Exp Med Feb 5;215(2): doi: /jem Hepatoprotective properties of natural and synthetic bile acid in the animal models Bojana Andrejić-Višnjić 1, Matilda Djolai 2, Karmen Stankov 2, Momir Mikov 1, Sandra Trivunić-Dajko 2, Nebojša Pavlović 1, Bojan Stanimirov 1 1 Faculty of Medicine Novi Sad, Novi Sad, Serbia 2 Faculty of Medicine Novi Sad; Clinical Center of Vojvodina, Novi Sad, Serbia. Aim: The aim of our study was to investigate hepatoprotective properties of bile acids (BA), natural ursodeoxycholic (UDK) and semisynthetic 12-monoketocholic acid (MK) by testing the levels of liver enzymes, malonyldehyde (MDA) as an indicator of hepatocyte oxidative damage, activity of antioxidant enzymes, histological analysis of liver tissue and immunohistochemical analysis of hepatocyte proliferation, activation of nuclear farnesoid-x receptor (FXR), apoptosis and proliferation markers. Introduction: The hepatocyte metabolism is extremely intense, and the processes that take place in hepatocytes are diverse, which makes them highly susceptible to oxidative damage that is the basis of many diseases. Two popular models of oxidative stress induction are the use of ethinylestradiol and the cholestasis model, as well as the use of aloxan and aloxan-diabetes model. Results: Male Wistar rats were used in this study. Control group (K) received only saline (0.5 ml/kg). Three groups received ethinylestradiol (EE group, 0.5 mg/kg) as monotherapy or in combination with 12-monoketocholic (E-MK, 4 mg/kg) or ursodeoxycholic acid (E- 23

24 PLENARNE USMENE PREZENTACIJE UDK, 25 mg/kg). In order to increase the level of oxidative stress, in three groups monodose of aloxan was administered in addition to ethinyl estradiol, either alone (AE group), or treated additionally with 12-monoketocholic (AE-MK) and ursodeoxocholic (AE-UDK) acid at the above dosages. Liver tissue was sampled for histological analysis and biochemical analysis of liver enzymes and bilirubin (AST, ALT, GGT, bilirubin total (BLRu) and direct (BLRd)), oxidative damage (MDA), levels of antioxidant enzymes catalase (CAT), glutathione-peroxidase (GSH-Px), glutathione-reductase (GSH-R), glutathione-s-transferase (GSH-ST). In groups EE and AE, AST, ALT and GGT levels were significantly elevated compared to K group, while the use of bile acids led to a significant reduction in activity of all enzymes as well as total and direct bilirubin. Both acids have the strongest hepatoprotective effect in terms of AST activity and lowering the total bilirubin concentration, whose values using both UDC and MK were lowered to the level of K-group. In terms of ALT and GGT, bile acids showed slight selectivity. Histological analysis of liver in groups EE and AE showed hepatocytes with karyopycnosis and cytoplasmic acidophilia, which indicate the apoptotic cell death, as well as changes in individual hepatocytes corresponding to feathery degeneration. All of these changes weren`t observed in the liver of animals treated with UDK and MK. By analyzing Ki-67 in the tissue of the control group, it was found that up to 5% of the cells exhibited nuclear expression, and a value of 10% was taken as the limit for the enhanced proliferative activity of hepatocytes. In groups that received only hepatotoxic substances, ethinyl estradiol and aloxan, the expression of ki-67 was low as in controls. Animals whose hepatocyte damage was caused only by ethinylestradiol, reflected hepatoprotective properties of bile acids by enhancing hepatocyte proliferation (E-UDK in 50%, and E-MK in 100% of animal). Similar hepatoprotective effects of tested bile acids was seen when comparing group treated with both hepatotoxic substances (AE), and groups cotreated with UDK (all animals had an increased proliferative activity) and MK (80% of animals). Accumulation of hydrophobic acids in ethinylestadiol-induced cholestasis enhances oxidative damage and induces apoptosis, but also activates the expression of nuclear farnesoid-x-receptor. In the K-group, 50% of the animals showed low expression of FXR, and moderate and high expression was present in 25% of animals. In EE and AE groups, high FXR expression was significantly increased (75%, ie 60%) indicating the accumulation of hepatotoxic acids that raise the level of oxidative damage and induce apoptosis. The hepatoprotective effect of UDK and MK, has been demonstrated by the reduced content of hydrophobic acids, ie, the reduced expression of FXR. In groups in which hepatotoxicity and oxidative stress were induced only by ethinylstradiol and were treated with UDK and MK, not a single animal had high FXR expression, and a number with weak expression increased significantly. Similarly, in groups that received two toxic substances and analyzed acids (AE-MK, AE-UDK) 60% of animals had weak FXR expression, which is statistically not different from the control group. Groups treated with ethinylestadiol and aloxan had a significantly higher concentration of malonylaldehyde (MDA), an indicator of oxidative hepatocyte damage. The use of UDK and MK significantly reduced the concentration of MDA, but not to the control group level. The activity of antioxidant enzymes in the EE group did not differ statistically from control, and the use of UDK and MK resulted in significant changes. In the group AE where oxidative stress is enhanced, the activity of all analyzed enzymes is significantly decreased, and the application of UDK and MK significantly enhances the activity of the antioxidative enzymes. In order to examine the hepatotoxicity of oxidative stress and hepatoprotective properties of UDK and MK, the expression of the p53 and Bcl-2 family of proteins was studied. Hepatocytes of the control group did not express the proapoptotic Bax, while in the EE and AE groups, weak expression was present in 50% and 40%, respectively. Using UDK in both EE-UDK and AE-UDK models, Bax was completely reduced to the level of control group, ie no Bax expression was observed. The use of MK in both models led to suppression of Bax (EE-MK, 25%; AE-MK, 0%). The antiapoptotic Bcl-2 protein was detected in the control group in 25% of the individuals, unlike the EE and AE groups, where the expression was completely suppressed. By promoting the expression of Bcl-2 (E-UDK in 25% of individuals, AE-UDK in 40% of individuals), the UDK showed a stronger hepatoprotective activity compared to MK which in the AE-MK group only led to an increase in expression by 20%. In the control group p53, expression was recorded only in the cytoplasm, in 50% of animals, while in the EE and AE groups p53 had nuclear expression in 25%, ie 20% of the individuals, which speaks in favor of more intensive apoptotic action and induction of transcription of other proapoptotic proteins. In groups where UDK was administered, p53 was not present in either the nucleus or the cytoplasm, while MK reduced the expression to the control group level. Conclusion: Ursodeoxycholic and 12-monoketocholic acid have great antioxidative and antiapoptotic capacity, which explains their hepatoprotective effect. Key words: bile acid, oxidative stress, apoptosis, FXR 24

25 PLENARY ORAL PRESENTATION 1. Schneider KM, Albers S, Trautwein C. Role of bile acids in the gut-liver axis. J Hepatol Mar 5. pii: S (17) doi: de Boer JF, Bloks VW, Verkade E, Heiner-Fokkema MR, Kuipers F. New insights in the multiple roles of bile acids and their signaling pathways in metabolic control. Curr Opin Lipidol Mar 16. doi: /MOL Zhang Y, LaCerte C, Kansra S, Jackson JP, Brouwer KR, Edwards JE. Comparative potency of obeticholic acid and natural bile acids on FXR in hepatic and intestinal in vitro cell models. Pharmacol Res Perspect Dec;5(6). doi: /prp Chiang JYL, Ferrell JM. Bile acid metabolism in liver pathobiology. Gene Expr Jan 11. doi: / X Shapiro H, Kolodziejczyk AA, Halstuch D, Elinav E. Bile acids in glucose metabolism in health and disease. J Exp Med Feb 5;215(2): doi: /jem

26 Specijalna sesija: Katedra za patologiju Medicinskog fakulteta, Univerziteta Novi Sad, Srbija Special Session: Department of Pathology, Medical Faculty, University Novi Sad, Serbia Skoring sistemi u dijagostici najčešćih primarnih tumora nadbubrežne žlezde Sandra Trivunić Dajko Medicinski Fakultet, Univerzitet Novi Sad, Novi Sad, Srbija Četvrto izdanje Klasifikacije endokrinih tumora, Svetske Zdravstvene Organizacije iz godine, uvelo je neke novine u odnosu na prethodnu iz godine, zasnovane pre svega na genetskim istraživanjima. Najčešći primarni tumori korteksa nadbubrežne žlezde su adenomi, a medule feohromocitomi. Kao takvi, navedeni tumori imaju svoje specifičnosti u patohistološkoj dijagnostici, po kojima se izdavajaju od tumora drugih lokalizacija. U svakodnevnom radu patologa, koji se bavi dijagnostikom tumora nadbubrežne žlezde, mogu da se jave diferencijalno dijagnostički problemi, gde se na osnovu morfološkog izgleda tumora ne može predvideti njegovo biološko ponašanje, to se pre svega odnosi na kortikalne neoplazme i feohromocitome. U navedenim slučajevima koriste se skoring sistemi, Weiss i Lin-Weiss-Bisceglia kriterijumi za kortikalne neoplazme, a PASS kriterijumi za feohromocitome, gde se bodovanjem predloženih morfoloških parametara, dobijaju vrednosti, skor, koji vrši predikciju biološkog ponašanja tumora, tj. diferenciraju benigne od malignih neoplazmi. U prihvaćenom algoritmu dijagnostike adrenokortikalnih neoplazmi nalazi se i imunohistohemijsko bojenje na ki-67, koje potencijalno može razgraničiti adrenokortikalne adenome od karcinoma. I pored uvođenja ovih skoring sistema, jedini sigurni pokazatelj maligniteta su i dalje udaljene metastaze. Ključne reči: nadbubrežna žlezda; tumori; patologija. Scoring Systems in the Diagnosis of the Most Common Primary Tumors of the Adrenal Gland Sandra Trivunic Dajko Medical Faculty, University Novi Sad, Novi Sad, Serbia The fourth Edition of the World Health Organization s Classification of Tumours of Endocrine Organs from 2017 introduced some novelties based primarily on genetic research, compared to the previous edition from The most common primary tumors of the adrenal cortex are adenomas, and of the adrenal medulla are pheochromocytomas. As such, these tumors have their specificities in pathohistological diagnosis, by which they differentiate from tumors of other localizations. In the daily work of the pathologist dealing with the diagnosis of the tumor of the adrenal gland, differential diagnostic problems can occur, where biological behavior of the tumor cannot be predicted based on its morphological appearance; this primarily refers to cortical neoplasms and phaeochromocytomas. Scoring systems are used in these cases, Weiss and Lin-Weiss-Bisceglia criteria for cortical neoplasms, and PASS criteria for pheochromocytomas, where by recognizing the suggested morphological parameters, value or score is obtained which predicts the biological behavior of the tumor, i.e. differentiates benign from malignant neoplasms. The accepted algorithm of diagnostics of adrenocortical neoplasms also includes immunohistochemical staining for ki-67, which potentially can differentiate adrenocortical adenoma from carcinoma. Despite the introduction of these scoring systems, the only safe indicator of malignancy is still distant metastasis. Key words: adrenal gland; tumors; pathology. Literatura: 1. Lack EE, Wieneke J, Tumors of the Adrenal Gland. Fletcher C, Diagnostic Histopathology of Tumors. 4th edition. New York: Elsevier Inc, p Papotti M, Libè R, Duregon E, Volante M, Bertherat J, Tissier F. The Weiss score and beyond--histopathology for adrenocortical carcinoma. Horm Cancer. 2011;(6): Jain M, Kapoor S, Mishra A, Gupta S, Agarwal A. Weiss criteria in large adrenocortical tumors: a validation study. Indian J PatholMicrobiol. 2010;53(2):

27 SPECIAL SESSION: DEPARTMENT OF PATHOLOGY, MEDICAL FACULTY, UNIVERSITY NOVI SAD, SERBIA 4. Maithili MK, Siddhi GSK, Sanjay DD, Karekar RR, Vandana LG, Avinash RJ, Mrunal V K, Shelke RR. Malignant pheochromocytoma: new malignancy criteria Langenbecks Arch Surg. 2012; 397(2): Maithili MK, Siddhi GSK, Sanjay DD, Karekar RR, Vandana LG, Avinash RJ, Mrunal VK, Shelke RR.Risk stratification in paraganglioma with PASS (Pheochromocytoma of the adrenal gland scaled score).journal of Clinical and Diagnostic Research [serial online]2016 Sep[cited:2017 Feb 18] 09 EC01 - EC Alfred King-yin Lam. Update on Adrenal Tumours in 2017 World Health Organization (WHO) of Endocrine Tumours. Endocr Pathol. 2017; DOI /s Morfološke karakteristike prekanceroznih lezija pankreasa Mirjana Živojinov 1,2 1 Klinički centar Vojvodine, Novi Sad, Srbija 2 Medicinski Fakultet, Univerzitet u Novom Sadu Karcinom pankreasa je visoko agresivna maligna neoplazma sa vrlo lošom prognozom i procentom preživljavanja od oko 5% na petogodišnjem nivou. To je četvrti vodeći uzrok smrti u SAD, kao i u Srbiji. Stopa mortaliteta se nalazi na višoj poziciji iako se incidencija ove maligne bolest nalazi na sedmom mestu. Što se tiče južne Bačke, stopa smrtnosti je nešto niža, te se zauzima peto mesto, prema dostupnoj literaturi. Ovo se može objasniti nedostatkom visoko specifičnih i osetljivih dijagnostičkih testova, zbog čega se karcinom pankreasa najčešće otkriva u uzpredovalom, neoperabilnom stadijumom bolesti (>60%), iako je hirurška resekcija jedina terapijska metoda izlečenja. U poređenju sa drugim karcinomima, postoji postepena progresija epitelnih ćelija pankreasa, tako da svaki invazivni karcinom nastaje progresijom iz prethodne intraepitelijalne neoplazije. Postoje tri različite vrste prekanceroznih lezija pankreasa, čije kliničko otkrivanje i lečenje mogu zaustaviti progresiju do invazivnog karcinoma i smanjiti mortalitet. Prvu vrstu čine Pankresna intraepitelijalne neoplazme (PanIN), a druge dve vrste su cistični tipovi prekanceroznih lezija - Intraduktalne papilarne mucinozne neoplazme (IPMNs) i Mucinozne Cistične Neoplasme (MCNs). PanIN je najčešća i najvažnija prekursorska lezija invazivnog karcinoma pankreasa. To su asimptomatske, male (obično dijametra <5 mm), solidne, ravne ili papilarne lezije koje se javljaju u malim intralobularnim kanalima pankreasa. Histološki se sastoje od cilindričnih do kubičnih ćelija sa različitim sadržajem mucina. Prema stepenu citološke i arhitektonske atipije, PanIN se klasifikuju u tri kategorije lezije lakog, srednjeg i visokog stepena. PanIN-1A (ravna promena) i PanIN-1B (papilarna promena) su lezije lakog stepena sa minimalnom atipijom, dok PanIN-2 pripada lezijama srednjeg stepena i pokazuje znake blage do umerene atipiju, često formirajući papilarne strukture. PanIN-3, takođe poznat i kao,, karcinom in situ, karakteriše izražena citološka i arhitektonska atipija i može biti zaravnjenog, papilarnog ili kribriformnog izgleda. Imunohistohemijski profil PanIN-a varira zavisno od stepena displazije. Lezije sa displazijom lakog stepena pokazuju pozitivnost za želudačni foveolarni mucin MUC5AC i mucin piloričnih žlezda MUC6, dok je ekspresija MUC1 prisutna isključivo kod visoko stepenih PanIN lezija. Među cističnim prekanceroznim lezijama pankreasa, IPMN su najčešće lezije. IPMN se razlikuju na osnovu lokalizacije u pankreasu i veličine, a ove dve karakteristike utiču na prognozu. Kako se mogu vizuelizovati i radiološkim pregledima, moguće ih je otkriti pre nego što se razviju u karcinom. Najčešće se otkrivaju kod pacijenata koji su podvgnuti rutinskom pregledu usled pozitivne porodične anamneze za pankreasne neoplazme, ili slučajno kod ljudi koji su pregledani iz nekog drugog razloga. Ove lezije pripadaju grupi heterogenih cističnih lezija pankreasa jer papilarna proliferacija epitela i proizvodnja mucina dovode do cistične dilatacije zahvaćenih kanala. Češće su lokalizovane u glavi i uncinatnom produžetku pankreasa (oko 55%) u poređenju sa telom i repom pankreasa, a u oko 30% slučajeva lezije su multifokalne. IPMN su podeljene na IPMN glavnog pankreatičnog kanala (MD-IPMN) sa lokalizacijom u glavnom kanalu pankreasa i obično prečnika 5 mm, i na IPMN grana glavnog pankreatičnog kanala (BD-IPMN) koje su obično prečnika >5 mm i komuniciraju sa glavnim kanalom pankreasa, koji nije zahvaćen procesom. Mešovite IPMN predstavljaju kombinaciju prethodno opisana dva tipa. Mikroskopski, epitelnu komponentu predstavlja visoko cilindrični epitel sa produkcijom mucina, ali bez prisutne niželežeće strome izgleda strome jajnika, koja je prisutna u mucinoznim cističnim neoplazmama. Kao i PanIN, IPMN se gradiraju na osnovu stepena displazije na laku, umerenu i izraženu displaziju ili karcinom in situ i IPMN sa pridruženim invazivnim karcinomom. Mnoge studije su pokazale da otprilike jedna trećina bolesnika sa IPMN ima i udružen invazivni karcinoma, pa je detaljna mikroanaliza bazalne membrane imperativ prilikom histopatološkog pregleda. Na osnovu histoloških karakteristika, razlikuju se intestinalni, pankreatobilijarni, onkocitni i želudačni podtip IPMN sa svojim imunohistohemijskim profilima. Intestinalni tip IPMN 27

28 SPECIJALNA SESIJA: KATEDRA ZA PATOLOGIJU MEDICINSKOG FAKULTETA, UNIVERZITETA NOVI SAD, SRBIJA karakterišu visoko cilindrične ćelije, izduženih jedara, amfofilne citoplazme i MUC2, MUC5AC, MUC4 i CDX-2 pozitivnošću. Nasuprot tome, pankreatobilijarni podtip IPMN karakterišu razgranate papile sa visoko stepenom intraepitelijalnom displazijom i MUC1 i MUC5AC imuno pozitivnošću. Treći su onkocitni tipovi, koji se pretežno javljaju u glavnom pankreatičnom kanalu, a čine ih složene, razgranate papilarne strukture koje su obložene onkocitnim ćelijama pomešanim sa peharastim ćelijama i ćelijama koje sadrže mucin. Ovaj tip pokazuje difuznu pozitivnost za MUC5AC i MUC6 i fokalnu pozitivnost za MUC1 ili MUC2. Želudačni podtip je lezija sa lakostepenom displazijom koja se uglavnom javlja u granama glavnog pankreatičnog kanala, a sačinjena je od papilarnih formacija pokrivenih foveolarnim žlezdanim epitelom sa pozitivnošću MUC5AC, a ponekad i MUC6. Poslednja i najređa vrsta prekanceroznih lezija pankreasa je MCN. Glavna razlika između IPMN i MCN su histološka slika i prezentacija lezije. Ove cistične lezije su uglavnom solitarne, mogu dostići velike dimenzije, a obično se nalaze u telu i repu pankreasa. Često su prisutne pregrade i fibrozna pseudokapsula, sa prisustvom kalcifikacija. Histološki, neinvazivne MCN se sastoje od cilindričnog epitela sa različitim stepenom displazije (displazija lakog, umerenog i visokog stepena) i strome ovarijalnog tipa. Imunohistohemijski, epitelne ćelije su imuno-pozitivne na EMA, CEA, MUC5AC, MUC2, citokeratine 7, 8/18 i 19, dok stroma ( ovarian-like ) pokazuje imunoreaktivnost za ER, PR, vimentin i SMA. Prekancerozne lezije pankreasa su važne promene čija bi vizuelizacija i detekcija u znatnom broju smanjila incidenciju karcinoma pankreasa a samim tim i mortalitet od ove visoko agresivne neoplazme sa nepovoljnim terapijskim odgovorom. Ključne reči: prekancerozne lezije pankreasa, PanIN, IPMN, MCN Morphological characteristics of precancerous pancreatic lesions Mirjana Zivojinov 1, 2 1 Clinical Center of Vojvodina, Novi Sad, Serbia 2 Faculty of Medicine, University of Novi Sad, Serbia Pancreatic cancer is high aggressive malignant neoplasm with very poor prognosis and about only 5% a five-year survival. It is the fourth leading cause of cancer death in USA, as well in Serbia, although in terms of the incidence of this disease the mortality is rising and it takes seventh place. Speaking about the southern Backa, the mortality rate is slightly lower and it is the fifth place, according to the available literature. This can be explained by the lack of highly specific and sensitive diagnostic tests, which makes pancreatic cancer most often detected by an advanced, inoperable stage of the disease (>60%), although surgical resection is the only curative therapy. Analogous to other carcinomas, there is a gradual progression of the pancreatic duct epithelial cells, so every invasive carcinoma arises from the previous intraepithelial neoplasia. There are three different types of common precancerous lesions known for pancreatic cancer which clinical detection and treatment can stop the progression to invasive cancer and reduce mortality. The first one is Pancreatic Intraepithelial Neoplasia (PanIN), and the other two types of precancerous lesions are both larger fluid-filled types- Intraductal Papillary Mucinous Neoplasms (IPMNs) and Mucinous Cystic Neoplasms (MCNs). PanIN is an asymptomatic, small (usually <5 mm in diameter), nonfluid flat or papillary lesion arising in the small intralobular pancreatic ducts. It is the most common and important precursor of invasive pancreatic carcinoma. Histologically, it s consisted of columnar to cuboidal cells with varying amounts of mucin. Accordingly to different degrees of cytological and architectural atypia, PanIN is classified into three grades- low, intermediate and high grade. PanIN-1A (flat) and PanIN-1B (papillary) are low grade lesions with minimal atypia, while PanIN-2 belongs to intermediate lesion showing mild to moderate atypia with frequent papillae. PanIN-3, also referred as carcinoma in situ, is characterized by severe cytological and architectural atypia amd it can be flat, papillary or cribriform pattern. The immunohistochemical profile of PanINs vary with the grade of dysplasia. Low grade lesions show positivity for gastric foveolar mucin MUC5AC, pyloric gland mucin MUC6, while MUC1 is almost exclusively expressed by high grade PanINs lesions. Among fluid-filled types of precancerous pancreatic lesions, IPMNs are the most common lesions. IPMNs vary in their location and size within the pancreas size, and these two features correlate with how dangerous they are. Because they can be detected by imaging procedures, it is possible to detect them before they become cancer. They are most often detected in patients who are routinely monitored due to a high familial risk, or incidentally in people who were imaged for another reason. Those lesions belong to group of the heterogeneous group of cystic pancreatic lesions because papillary epithelial proliferation and mucin production lead to cystic dilatation of involved ducts. 28

29 SPECIAL SESSION: DEPARTMENT OF PATHOLOGY, MEDICAL FACULTY, UNIVERSITY NOVI SAD, SERBIA Those lesions are slightly more common in the head and uncinate process (55%) compared with the body and the tail of the pancreas and about 30% of them are multifocal. IPMNs are subdivided into main duct IPMN (MD-IPMN) which are localized in the main pancreatic duct and measured 5 mm, while the other branch duct type (BD-IPMN) is >5 mm in diameter andcommunicates with the main pancreatic duct but it is uninvolved by the process. Mixed IPMN combines both types. Microscopically, the lining epithelial component is represented by tall mucin producing columnar cells but lack the ovarian-type seen in mucinous cystic neoplasms. Like PanINs, IPMNs are graded on the basis of the greatest degree of dysplasia into low grade, moderate and high grade dysplasia or carcinoma in situ and IPMN with associated invasive carcinoma. Many studies have showed that approximately one-third of patients with IPMN are associated with invasive carcinoma, so precise basement membrane micro analysis is an imperative. Accordingly to their histological characteristics there are intestinal, pancreatobiliary, oncocytic and gastric subtype of IPMN with different immunohistochemical profiles. Intestinal-type IPMN is characterized by tall columnar cells with elongated nuclei and amphophilic cytoplasm and MUC2, MUC5AC, MUC4 and CDX-2 positivity. In contrast, pancreatobiliary subtype of IPMN is characterised by branched papillae with high grade intraepithelial neoplasms and MUC1 And MUC5AC immuno positivity. The third are oncocytic type, predominantly occurs in main duct and presented with a complex branched papillary structures covered by oncocytic cells mixed with goblet cells and mucin-containing cells. This type shows diffuse positivity for MUC5AC, MUC6 and focal positivity for MUC1 or MUC2. The gastric subtype is low grade lesions mainly found in branched ducts and characterised by papillae covered by foveolar glandular epithelium with MUC5AC and sometimes MUC6 positivity. The last and the most infrequent type of pre-cancerous pancreatic lesions are MCNs. The principle difference between IPMNs and MCNs is how they look under a microscope, and how they behave in the patient. These cystic lesions are almost solitary, typically located in the pancreatic body and tail. Grossly, this lesion can grow very large, it is usually septated and with fibrous pseudocapsule often with calcifications. Histologically, the epithelium og noninvasive MCN is consisted of columnar cells with varying degree of dysplasia (low grade, moderate and high grade dysplasia) and underlying ovarian-like stroma. Immunohistochemically, thode epithelial cells are EMA, CEA, MU- C5AC, MUC2, cytokeratins 7, 8/18 and 19 positive, while the underlying ovarian-like stroma shows ER, PR, vimentin and SMA immune reactivity. Precancerous lesions of the pancreas are important changes whose visualization and detection in a significant number would reduce the incidence of pancreatic cancer and, consequently, the mortality of this highly aggressive neoplasm with an unfavorable therapy outcome. Key words: precancerous pancreatic lesions, PanIN, IPMN, MCN Literature: 1. Koorstra JBM, Feldmann G, Habbe N, Maitra A. Morphogenesis of pancreatic cancer: role of pancreatic intraepithelial neoplasia (PanINs), Langenbeck s Archives of Surgery, vol.393, no. 4, pp , Zamboni G, Hirabayashi K, Castelli P, Lennon AM. Precancerous lesions of the pancreas-best Practice&Research. Clinical Gastroenterology 2013;(27)2: Hruban RH, Takaori K, Klimstra DS, et al. An illustrated consensus on the classification of pancreatic intraepithelial neoplasia and intraductal papillary mucinous neoplasms, American Journal of Surgical Pathology 2004;(28)8: Nagai K, Doi R, Kida A, et al. ntraductal papillarymucinous neoplasms of the pancreas: clinicopathologic characteristics and long-term follow-up after resection. World Journal of Surgery 2008;(32)2: F. T. Bosman, F. Carneiro, R. H. Hruban, and N. Theise, Classification of Tumours of the Digestive System, WHO, Lyon, France, Zamboni G, Scarpa A, Bogina A et al. Mucinous cystic tumors of the pancreas: clinicopathological features, prognosis, and relationship to other mucinous cystic tumors. American Journal of Surgical Pathology 1999;(23)4: Klöppel G, Basturk O, Schlitter AM, Konukiewitz B, Esposito I. Intraductal neoplasms of the pancreas. Semin Diagn Pathol 2014;31: Tanaka M, Fernández-del Castillo C, Adsay V, Chari S, Falconi M, Jang JY, Kimura W, Levy P, Pitman MB, Schmidt CM, Shimizu M, Wolfgang CL, Yamaguchi K, Yamao K. International Association of Pancreatology: International consensus guidelines 2012 for the management of IPMN and MCN of the pancreas. Pancreatology 2012;12:

30 SPECIJALNA SESIJA: KATEDRA ZA PATOLOGIJU MEDICINSKOG FAKULTETA, UNIVERZITETA NOVI SAD, SRBIJA Dijagnostičke dileme na bioptiranim limfnim čvorovima Zoran Nikin Medicinski fakultet, Novi Sad, Srbija Institut za onkologiju Vojvodine, Sremska Kamenica, Srbija Patolozi često nailaze na dilemu da li je bioptirani limfni čvor reaktivan ili je zahvaćen limfoproliferativnim ili drugim malignim oboljenjem. U rutinskom radu koriste se morfološki kriterijumi i imunohistohemijska bojenja. U bolje opremljenim laboratorijama koriste se i dodatne citogenetske i molekularne metode ukoliko morfologija i imunohistohemijske analize ne dovedu do konačne dijagnoze. Značajno je poznavanje kliničke slike i utiska kliničkog doktora koji vodi slučaj. U reaktivnom limfnom čvoru osnovna morfologija je uglavnom očuvana. Distribucija B i T ćelija, makrofaga, dendritičnih ćelija i proliferacije je adekvatna. Stranih ćelija nema. Načini reakcije u limfnom čvoru su: folikularna hiperplazija, parakortikalna ekspanzija, sinusna histiocitoza i formiranje granuloma. U slučaju prisustva metastatskih depozita, najčešće karcinoma i melanoma, početno zahvatanje je najčešće subkapsularno, ređe u sinusima. Treba obratiti pažnju na razlikovanje sinusnih makrofaga od metastatskih tumorskih ćelija, što imunohistohemijske analize sa lakoćom potvrđuju. Ukoliko je u pitanju limfom nameću se dileme da li je Hočkinski ili ne-hočkinski i ako je ne-hočkinski da li je sitnoćelijski ili krupnoćelijski. Kod ne-hočkinskih limfoma obično dominiraju tumorske ćelije a prateći zapaljenski infiltrat je najčešće oskudan i obično ga čine mali T limfociti i ređi makrofagi. Kod T limfoma zapaljenski infiltrat može biti šarolik. Kod Hočkinskih limfoma najčešće brojčano dominira prateći zapaljenski infiltrat i obično je šarolik. Tumorske ćelije su krupne, sa režnjevitim ili višestrukim jedrom i upadljivim jedarcima. Imunofenotip se najčešće jasno razlikuje od ne-hočkinskih limfoma. Diferencijacija sitnoćelijskih od krupnoćelijskih ne-hočkinskih limfoma se najjednostavnije sprovodi poređenjem veličine ćelija. Ako je veličina tumorskih ćelija bliža veličini makrofaga ili endotela u pitanju je krupnoćelijski limfom a ako je bliža malim limfocitima i eritrocitima odgovara sitnoćelijskom limfomu. Diferencijacija sitnoćelijskih limfoma se bazira na izgledu i distribuciji ćelija i imunofenotipu. Za diferencijaciju krupnoćelijskih limfoma su neophodne imunohistohemijske analize jer je morfologija često vrlo slična u različitim entitetima. Postavljanje tačne dijagnoze je važno radi primene optimalne terapije i postizanja najbolje prognoze za pacijenta. Ključne reči: Limfni čvor, diferencijalna dijagnoza, morfologija, imunohistohemija Diagnostic dilemmas in lymph node biopsies Zoran Nikin Medical Faculty, Novi Sad, Serbia Institut for Oncology of Vojvodina, Sremska Kamenica, Serbia Pathologists often have a dilemma is a lymph node biopsy reactive or corresponds to a lymphoproliferative or other malignant disease. In everyday routine work, we rely on morphologic criteria and immunohistochemical analyzes. In better-equipped labs additional cytogenetic and molecular methods are used if morphology and immunohistochemical analyzes are not sufficient for getting correct diagnoses. It is important to know clinical presentation and the opinion of a clinician who runs the case. In reactive lymph nodes general morphology is mostly preserved. Distribution of B and T cells, histiocytes, dendritic cells and proliferation is adequate. Foreign cells are not present. Ways of reaction in lymph nodes are follicular hyperplasia, paracortical expansion, sinus histiocytosis and granuloma formation. If metastases are present, most often from carcinomas and melanomas, the initial deposits are usually sub capsular or less often in sinuses. One should be careful to differentiate sinus histiocytes and metastatic tumor cells, what can easily be verified by immunohistochemical stains.if it is a lymphoma, one should decide is it a Hodgkin or a non-hodgkin lymphoma. In non-hodgkin lymphomas, one should decide between small cell and large cell lymphomas. In non-hodgkin lymphomas, tumor cells are dominant and background inflammation is scant and mostly consisted of small T cells and rare histiocytes. In T cell lymphomas background inflammation can be quite various. In Hodgkin lymphomas background inflammation most often is various and almost always outnumbers tumor cells. Tumor cells are large, with lobulated or multiple nuclei and conspicuous nucleoli. The immunophenotype is usually clearly different from non-hodgkin lymphomas. The differentiation of small cell and large cell non-hodgkin lymphomas is easily made by comparing cell sizes. If tumor cell size is closer to size of histiocytes or endothelium it is a large cell lymphoma, but if it 30

31 SPECIAL SESSION: DEPARTMENT OF PATHOLOGY, MEDICAL FACULTY, UNIVERSITY NOVI SAD, SERBIA is closer to small lymphocytes and red blood cells it is a small cell lymphoma. Differentiation of small cell lymphomas is based on morphology, distribution of cells and on immunophenotype. Differentiation of large cell non-hodgkin lymphomas requires immunohistochemical analyzes because morphology is often very similar among entities. Correct diagnosis is important due to application of optimal therapy and reaching the best prognosis for the patient. Key words: Lymph node, differential diagnosis, morphology, immunohistochemistry Literature: 1. Ashton-Key M, Wright DH, Wright P. Diagnostic lymph node pathology. 3rd ed. Boca Raton, FL: CRC Press; Fletcher CDM. Diagnostic histopathology of tumors. 4th ed. Vol. 2. Edinburgh: Churchill Livingstone; Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri S, Stein H, et al. WHO classification of tumours of haematopoietic and lymphoid tissues. Lyon: International Agency for Research on Cancer; Gorczyca W, Emmons F. Atlas of differential diagnosis in neoplastic hematopathology. London: Informa Healthcare; Dabbs DJ. Diagnostic immunohistochemistry. Edinburgh: Churchill Livingstone; Application of the 8 th revision of TNM classification of lung carcinoma Aleksandra Lovrenski Pathology Department, Medical Faculty Novi Sad, Institute for pulmonary diseases of Vojvodina, Sremska Kamenica, Serbia In preparation for the 8th edition of the TNM classification for lung cancer the International Association for the Study of Lung Cancer (IASLC) collected data on 94,708 cases of lung cancer diagnosed between 1999 and 2010, donated by 35 institutions in 16 countries. After exclusions, 77,156 remained for analysis: 70, 967 cases of non-small cell lung cancer (NSCLC) and 6,189 cases of small-cell lung cancer (SCLC). Analysis of the cases of NSCLC has allowed proposals for revisions to the T, N and M descriptors and TNM Stage groupings. Size remained an important determinant and a descriptor for all of the T categories. A new cut points at 1 and 4 cm have been proposed and as a result new T categories have been created: T1a 1 cm, T1b > 1 to 2 cm, T1c > 2 to 3 cm, T2a > 3 to 4 cm, T2b > 4 to 5 cm, T3 > 5 to 7 cm and T4 > 7 cm. However, measuring precise tumor size can be challenging since it is known that tumor gross size depends on whether the size measurement is performed on fresh or formalin-fixed specimen. In about 10% of cases, formalin fixation can cause down-staging of pathologic T category as a result of tumor shrinking. Tumors invading the diaphragm have been reclassified as T4, and tumors extending within 2cms of the carina without its invasion, or tumors associated with collapse or consolidation of the whole lung have been down-staged to T2. Tis and T1mi were introduced for adenocarcinoma in situ, squamous cell carcinoma in situ and minimally invasive adenocarcinoma, respectively. Visceral pleural invasion, defined as the involvement of its elastic layer, remains unchanged as T2 category, but specific analysis of visceral pleural invasion, showed that there is two types of invasion: PL1 where tumor invades beyond the elastic layer and PL2 where tumor invades pleural surface and that these two had different prognosis, PL2 being associated with the worst outcome. Elastic stains are recommended to clarify the status of visceral pleural invasion for cases in which initial hematoxylin-and-eosin-stained slides failed to show presence of invasion. Mediastinal pleura invasion disappears as a T descriptor. N categories remained the same as in 7th edition. 8th did not bring guidelines about the minimum number of lymph nodes that should be assessed for pathohistological analysis. In M descriptor category M1a retained, while M1b has been reassigned to describe a form of limited disease with a single metastatic deposit in one distant organ. A new category of M1c has been proposed and it is reserved for situations in which there are multiple metastases in one or more distant sites. Assessment of multifocal lung tumors and the distinction of synchronous primary tumors from intrapulmonary metastases represent an important problem as this decision significantly influences tumor staging, as well as treatment approach. Four different clinical presentation of lung cancer with multifocal lung involvement are described: second primary cancer, intrapulmonary metastasis, multifocal lung adenocarcinoma with ground glass/lepidic features, and pneumonic-type lung adenocarcinoma. The tumors are considered second primary tumor if it have clearly a different histology or have a different radiographic appearance, metabolic uptake growth pattern or different biomarkers. Each tumor is staged separately based on current TNM staging system. The nodules are considered to be intrapulmonary metastasis if exact matching breakpoints are identified by genetic hybridization or have similar clinical features such as radiographic appearance, growth pattern or significant nodal and systemic 31

32 SPECIJALNA SESIJA: KATEDRA ZA PATOLOGIJU MEDICINSKOG FAKULTETA, UNIVERZITETA NOVI SAD, SRBIJA metastasis. TNM staging depends on location of the nodule relative to the primary tumor site. If it is in the same lobe, the tumor is designated as T3, if it is in the same lung, but in different lobe as T4, and it it is in the contralateral lung as M1a. Tumors are considered multifocal lung adenocarcinoma if there are multiple subsolid nodules with at least one suspected or proven to be a cancer. Ground glass nodule <5 mm or lesion suspected to be AAH is excluded. T stage is based on highest T lesion with indicating the multiplicity. Tumor is categorized as a pneumonic-type adenocarcinoma if there is a diffuse pneumonic infiltrate or consolidation with regional distribution. Stage IA is divided into IA1, IA2 and IA3 to accommodate T1a, T1b and T1cN0M0 tumors. All N1 disease is staged IIB except for T3-T4N1M0 tumors which are stage IIIA. A new stage IIIC is created for T3-T4N3M0 tumors and stage IV is divided into IVA (M1a and M1b) and IVB (M1c). In conclusion, multi-disciplinary approach and the close cooperation among medical and radiation oncologists, pulmonologists, surgeons, radiologists and pathologists is important in properly staging of lung cancer as well as, in treatment plans. Literature: 1. Rami-Porta R, Bolejack V, Crowley J, Ball D, Kim J, Lyons G, et al. The IASLC Lung Cancer Staging Project: Proposals for the Revision of the T Descriptors in the Forthcoming Eight Edition of the TNM Classification for Lung Cancer. J Thorac Oncol 2015;10: Asamura H, Chansky K, Crowley J, Goldstraw P, Rusch VW, Vansteenkiste J, et al. The IASLC Lung Cancer Staging Project: Proposals for the Revision of the N Descriptors in the Forthcoming Eight Edition of the TNM Classification for Lung Cancer. J Thorac Oncol 2015;10: Eberhardt WEE, Mitchell A, Crowley J, Kondo H, Kim YT, Turrisi A, et al. The IASLC Lung Cancer Staging Project: Proposals for the Revision of the M Descriptors in the Forthcoming Eight Edition of the TNM Classification for Lung Cancer. J Thorac Oncol 2015;10: Detterbeck FC, Bolejack V, Arenberg DA, Crowley J, Donington JS, Franklin WA, et al. The IASLC Lung Cancer Staging Project: Background Data and Proposals for the Application of TNM Staging Rules to Lung Cancer Presenting with Separate Tumor Nodules in the Fourthcoming Eight Edition of the TNM Classification for Lung Cancer. J Thorac Oncol 2016;11: Detterbeck FC, Nicholson AG, Franklin WA, Marom EM, Travis WD, Girard N, et al. The IASLC Lung Cancer Staging Project: Summary of Proposals for Revisions of the Classification of Lung Cancers with Multiple Pulmonary Sites of Involvement in the Fourthcoming Eight Edition of the TNM Classification. J Thorac Oncol 2016;11: Patohistološka procena tumorske regresije kod nemikrocelularnih karcinoma pluća posle neoadjuvantne terapije Golub Samardžija Medicinski fakultet, Novi Sad, Srbija Institut za kardiovaskularne bolesti Vojvodine, Sremska Kamenica, Srbija Karcinomi pluća su najčešći uzrok oboljevanja i umiranja od malignih tumora u Svetu. Neodjuvantna terapija kod bolesnika sa lokalno uznapredovalim (IIIA-IIIB) karcinomom pluća i zahvaćenim N2 limfnim čvorovima jedan je od modusa multimodalnog lečenja bolesnika sa nemikrocelularnim karcinomima pluća (NSCLC) u cilju poboljšanja ishoda njihovog lečenja. Ovakav pristup podrazumeva prevođenje bolesnika iz višeg u niži stadijum bolesti - downstaging. Do danas nije utvrđena povezanost između pojedinih obrazaca tumorskog odgovora i vrste terapije. S obzirom na značaj kompletnog patološkog odgovora i tumorske regresije u prognozi ishoda lečenja, iznalaženje ove povezanosti je od značaja za dizajniranje budućih neoadjuvantnih trajala. Prilikom utvrđivnja histološke slike tumorske regresije veoma je važno i merenje areje rezidualnog tumora (ART). Kako je veličina tumora jedan od prognostičkih faktora za bolesnike sa NSCLC koji nisu primali neoadjuvantnu terapiju tako je i merenje ART, za razliku od makroskopske veličine tumora, jedan od prognostičkih faktora za bolesnike sa NSCLC koji su primali neoadjuvantnu terapiju. Krajnji cilj neoadjuvantne terapije trebalo bi da bude resektabilnost i downstaging koji bi mogao da obezbedi u specifičnim kliničkim situacijama i sveukupni onkološki benefit. Osnovni ciljevi ovog istraživanja su bili: da se objektivizira procena veličine ART u tumorskom tkivu pluća i limfnih čvorova; da se proceni povezanost površine ART sa veličinom tumora na postoperativnom hirurškom materijalu posle neoadjuvantne terapije; da se analizira i proceni povezanost histomorfoloških parametara kod tumorske regresije indukovane neoadjuvantnom terapijom i spontane tumorske regresije u tumorima pluća i limfnih čvorova na postoperativnom hirurškom materijalu i u zavisnosti od histološkog tipa karcinoma; 32

33 SPECIAL SESSION: DEPARTMENT OF PATHOLOGY, MEDICAL FACULTY, UNIVERSITY NOVI SAD, SERBIA da se proceni povezanost kliničkog odgovora na neoadjuvantnu terapiju prema kriterijumima Svetske Zdravstvene Organizacije i histoloških parametara u tumorima pluća i limfnim čvorovima na postoperativnom hirurškom materijalu nakon neoadjuvantne terapije; da se proceni povezanost patološkog yptn sa kliničkim yctn stadijumom bolesti i stepena tumorske regresije indukovane neoadjuvantnom terapijom i patološkog yptn i da se proceni povezanosti između kliničke i patološke zahvaćenosti N2 limfnih čvorova posle neoadjuvantne terapije. Merenje ukupne veličine očuvanih ART je najznačajniji objektivni parametar u proceni stepena tumorske regresije. Veličina rezidualnog tumora nije u korelaciji sa veličinom tumora posle neoadjuvantne terapije. Postoji signifikantna razlika u patohistološkoj slici tumorske regresije indukovane neoadjuvantnom terapijom i spontane tumorske regresije. Ne postoji signifikantna razlika između histološkog tipa tumora i histološke slike tumorske regresije. Ne postoji signifikantna povezanost između kliničkog odgovora i stepena tumorske regresije nakon neoadjuvantne terapije. Ne postoji korelacija između kliničkog i patološkog stadijuma bolesti posle neoadjuvantne terapije. Ne postoji korelacija između stepena tumorske regresije indukovane neoadjuvantnom terapijom i yptn stadijuma bolesti. Ne postoji korelacija između kliničke i patološke zahvaćenosti N2 limfnih čvorova posle neoadjuvantne terapije. Stepen regresije tumora i merenje ART posle neoadjuvantne terapije određen histopatološkom analizom reseciranog tumora je najobjektivniji kriterijum za procenu hemioterapijskog odgovora i predviđanja ishoda lečenja pacijenata. Histopathologic assessment of tumor regression in non-small cell lung cancer after neoadjuvant therapy Golub Samardzija Pathology Department, Medical Faculty Novi Sad, Institute for cardiovascular diseases of Vojvodina, Sremska Kamenica, Serbia Lung cancers are the most common cause of morbidity and mortality from malignant tumors in the World. The neodjuvant therapy in patients with locally advanced (IIIA-IIIB) lung cancer and affected N2 lymph nodes is one of the modes of multimodal treatment of patients with non-small cell lung cancer (NSCLC) in order to improve the outcome of their treatment. This involves converting patients from a higher to a lower stage of the disease - downstaging. There has been no significant connection between some forms of tumor response and types of therapy. Given the importance of complete pathological responses and tumor regression in the prediction of treatment outcomes, finding this relationship is of importance for the design of future neoadjuvant trails. In determining the histological tumor regression is very important measurement of area of residual tumor (ART). As the size of the tumor is one of the prognostic factors in patients with NSCLC who did not receive neoadjuvant therapy so the measurement of ART, as opposed to the macroscopic size of the tumor, one of the prognostic factors in patients with NSCLC, who had received neoadjuvant therapy. The ultimate goal of neoadjuvant therapy should be resectability and downstaging that could provide overall oncology benefit in specific clinical situations. The main objectives of this research were: to objectively estimate the size of ART in tumor tissue of lung and lymph nodes; to estimate the relation between the surface of ART with the size of the tumor on postoperative surgical material after neoadjuvant therapy; to analyze and estimate the relation between histomorphological parameters in tumor regression induced by neoadjuvant therapy and spontaneous tumor regression in tumors of the lung and lymph nodes in the postoperative surgical material and depending on the histological type of cancer; to estimate the relation between clinical response to neoadjuvant therapy according to criteria of the World Health Organization and histological parameters in lung tumors and lymph nodes in the postoperative surgical material after neoadjuvant therapy; to estimate the correlation of the pathological yptn with clinical yctn stage of the disease and the degree of tumor regression induced by neoadjuvant therapy and pathological yptn and estimation of the relation between clinical and pathological involvement of N2 lymph nodes after neoadjuvant therapy. Measurement of the total size of the preserved ART is the most important objective parameter in the assessment of the grade of tumor regression. Size of residual tumor did not correlate with the size of the tumor after neoadjuvant therapy. There was a significant difference in the histological picture of tumor regression induced by neoadjuvant therapy and spontaneous tumor regression. There was no significant difference between the histologic type of tumor and histological tumor regression. There is no significant correlation between clinical response and the grade of tumor regression after neoadjuvant therapy. There is no correlation between clinical and pathological staging of the disea- 33

34 SPECIJALNA SESIJA: KATEDRA ZA PATOLOGIJU MEDICINSKOG FAKULTETA, UNIVERZITETA NOVI SAD, SRBIJA se after neoadjuvant therapy. There is no correlation between the grade of tumor regression induced by neoadjuvant therapy and yptn stage of the disease. There is no correlation between the clinical and the pathological involvement of the N2 lymph nodes to neoadjuvant therapy. The grade of tumor regression and measurement ART after neoadjuvant therapy determined by histopathological analysis of the resected tumor is the most objective criterion for evaluation of chemotherapeutic response and prediction of treatment outcome in patients. Literature: 1. Depierre A, Milleron B, Moro-Sibilot D, Chevret S, Quoix E, Lebeau B, Braun D, Breton JL, Lemarie E, Gouva S, Paillot N, Brechot JM, Janicot H, Lebas FX, Terrioux P, Clavier J, Foucher P, Monchatre M, Coetmeur D, Level MC, Leclerc P, Blancho F, Rodier JM, Thiberville L, Villeneuve A, Westeel V, Chastang C, French Thoracic Cooperative Group. Preoperative chemotherapy followed by surgery compared with primary surgery in respectable stage I (except T1N0) II and IIIA non-small cell lung cancer. J Clin Oncol 2002;20: Kyungs SL, Mog Y, Chan Y. Primary Tumor and mediastinal lymph nodes after Neoadjuvant concurent chemoradiotherapy in lung cancer. Serial CT findings and Pathologic correlation. Journal of Computer Assisted Tomography 2000;24:1, Xiaolin Liu-Jarin, Mark B. Stoopler, Haralambos Raftopoulus, Mark Ginsburg, Lyall Gorenstein, Alain C. Borczuk. Histologic Assessment of Non-Small Cell Lung Carcinoma after Neoadjuvant Therapy. Modern Pathology 2003;16(11): Yamane Y, Ishii G, Goto K, Kojima M, Nakao M, Shimada Y, Nishiwaki Y, Nagai K, Kohrogi H, Ochiai A. A novel histopatological evaluation method predicting the outcome of non-small lung cancer treated by neoadjuvant therapy: the prognostic importance of the area of residual tumor. J Thorac Oncol Jan;5(1): Junker K, Thomas M,Schulmann K, Klinke F,Bose U,Muller KM. Tumour regression in non-small-cell lung cancer following neoadjuvant therapy. Histological assessment. J Cancer Res Clin Oncol 1997;123: Efikasnost bronhoskopske biopsije u detekciji mutacija receptora epidermalnog faktora rasta u adenokarcinomu pluća Dragana Tegeltija Medicinski fakultet, Novi Sad, Srbija Institut za respiratorne bolesti Vojvodine, Sremska Kamenica, Srbija Karcinom pluća je vodeći uzrok porasta morbiditeta i mortaliteta od malignih bolesti u svetu. Adenokarcinom je najčešćei histološki tip poslednjih decenija zbog: promena u duvanskoj industriji, pušačkih navika i primene imunohistohemije. Kod više od polovine obolelih adenokarcinom pluća se dijagnostikuje u proširenom stadijumu bolesti. Otkriće mutacija receptora epidermalnog faktora rasta (epidermal growth factor receptor-egfr) u adenokarcinomu pluća predstavlja veliki napredak u molekularnoj patologiji i novi pristup u lečenju ovih bolesnika. Bolesnici sa EGFR mutiranim adenokarcinomom pluća primaju ciljanu terapiju (Tyrosine Kinase Inhibitors-TKI) koja kod njih dovodi do poboljšanja prognoze bolesti i kvaliteta života. Lančana reakcija polimeraze u realnom vremenu (Polymerase Chain Reaction-PCR) je najrasprostranjenija i najpouzdanija metoda jer zahteva minimalnu količinu polaznog materijala i omogućava amplifikaciju željenog segmenta DNK do milijardu puta. Na ovaj način se u oko 90% slučajeva detektuju delecije na egzonu 19, češće kod žena, nepušača i na teritoriji Azije. Za EGFR testiranje može da se koristi: sveže tkivo, brzosmrznuto tkivo, tkivo koje je nakon fiksacije u formalinu ukalupljeno u parafinske blokove i citološki materijal dobijen struganjem sa staklenih pločica. Tkivo obrađeno procesom dekalcinacije, tkivo tretirano kiselinama ili teškim metalima treba izbegavati. Iako hirurški uzorci predstavljaju zlatni standard u određivanju EGFR mutacija dobijeni rezultati su kompatibilni su sa rezultatima koji su dobijeni bronhoskopskom biopsijom tako da se otklanja potreba za invazivnim dijagnostičkim procedurama. Bronhoskopija je invazivna dijagnostička metoda, sprovodi se sa ciljem: dijagnostikovanja tumora pluća, određivanja endoskopske proširenosti bolesti i procene operabilnosti tumora. Na prisustvo tumora može da ukaže različit bronhoskopski aspekt endobronijalne sluznice. Senzitivnost i specifičnost ove metode zavisi od: utreniranosti bronhologa, endoskopskog nalaza, broja biopsijskih uzorka, stručne osposobljenosti patologa-citologa i dobijene količine tumora. Količina tumora je uglavnom mala, zavisi od: histološkog tipa, endoskopskog nalaza, tehnike uzorkovanja i prisustva drugih ćelija. Preporuka je da se uzima tri do pet biopsijskih uzoraka, koji se koriste u dijagnostikovanju bolesti, ali i za molekularno testiranje. Na 34

35 SPECIAL SESSION: DEPARTMENT OF PATHOLOGY, MEDICAL FACULTY, UNIVERSITY NOVI SAD, SERBIA osnovu dobijenih rezultata se primenjuje ciljana terapija. S obzirom da se biopsijski uzorci ukalupljeni u parafin seku na više histoloških rezova, da se količina tumora smanjuje neophodno je potrošnju svesti na minimum. Koncentracija izolovane DNK se ne razlikuje kod bolesnika sa wt EGFR i mutiranim EGFR adenokarcinomom. Do danas ne postoji koncenzus u pogledu broja tumorskih ćelija potrebnih za određivanje mutacija EGFR uz preporuku da su to uzorci sa minimalno 200 do 400 ćelija tumora. Invalidni rezultati dobijeni PCR metodom su najčeće posledica malog broja očuvanih ćelija tumora u biopsijskom uzorku. Krv i nekroza mogu da budu limitirajući faktori za molekularno testiranju, ali ne i faktori isključivanja za molekularno testiranje. Bronhoskopski biopsijski uzorak je adekvatan za određivanje EGFR mutacija zato što: većina biopsijskih uzoraka ima više od 100 ćelija tumora, razlika između koncentracije izolovane DNK u EGFR mutiranim i wt EGFR adenokarcinomima nije statistički značajna, EGFR mutacije se detektuju i u uzorcima sa manjim brojem ćelija tumora ukolliko se koriste visoko senzitivni testovi. The efficiency of bronhoscopic biopsy in detecting the mutations in epidermal growth factor receptor in lung adenocarcinoma Dragana Tegeltija Pathology Department, Medical Faculty Novi Sad, Institute for pulmonary diseases of Vojvodina, Sremska Kamenica, Serbia Lung carcinoma is the leading cause of increases in the morbidity and mortality rates of malignant diseases worldwide. Adenocarcinoma has been the most common histological type in the last decades due to: changes in the tobacco industry, smoking habits and the use of immunohistochemistry. Among more than half of patients, lung adenocarcinoma is diagnosed in an advanced stage of the disease. The discovery of mutations in epidermal growth factor receptor (EGFR) in lung adenocarcinoma is a major advancement in molecular pathology and a new approach to the treatment of these patients. Patients with EGFR mutated lung adenocarcinoma receive a targeted therapy (Tyrosine Kinase Inhibitors-TKI) which leads to improvements in disease prognosis and quality of life. Real-time polymerase chain reaction (PCR) is the most widely used and most reliable method since it requires a minimum amount of starting material and allows the amplification of the desired DNA segment up to a billion times. In this way, deletions in exon 19 are detected in approximately 90% of cases, more often in women, non-smokers and in the territory of Asia. The following may be used for EGFR testing: fresh tissue, fast-frozen tissue, tissue molded into paraffin blocks after fixation in formalin and cytological material obtained by scraping from glass tiles. Tissue processed by decalcination, acid treated or heavy metal treated tissue should be avoided. Although surgical samples represent the golden standard in determining EGFR mutations, the results obtained are compatible with the results obtained by bronchoscopic biopsy and thus eliminate the need for invasive diagnostic procedures. Bronchoscopy is an invasive diagnostic method, whose objectives are to diagnose lung tumors, determine the endoscopic spread of the disease and assess tumor operability. The presence of a tumor may be indicated by a different bronchoscopic aspect of the endobronial mucosa. The sensitivity and specificity of this method depends on: bronchologist s skills, endoscopic findings, the number of biopsy samples, the professional competence of pathologist-cytologist and the obtained tumor amount. The tumor amount is generally small and depends on the histological type, endoscopic findings, sampling technique and the presence of other cells. It is recommended to take three to five biopsy samples, used for diagnosing but also for molecular testing. Targeted therapy is applied based on the obtained results. Given that biopsy samples molded in paraffin are cut into multiple histological sections, and that the tumor amount decreases, it is necessary to minimize the consumption. The concentration of isolated DNA does not differ among patients with wt EGFR and mutated EGFR adenocarcinoma. To date, there has been no consensus regarding the number of tumor cells necessary to determine EGFR mutations, and it is recommended to take samples with a minimum of 200 to 400 tumor cells. Invalid results obtained by using the PCR method are most commonly the result of a small number of preserved tumor cells in a biopsy sample. Blood and necrosis may be limiting factors for molecular testing, but not exclusion factors for the same. Bronchoscopic biopsy sample is adequate for the determination of EGFR mutations because the majority of biopsy samples have more than 100 tumor cells, the difference between the concentration of isolated DNA in EGFR mutated and wt EGFR adenocarcinomas is not statistically significant, EGFR mutations are also detected in samples with a small number of tumor cells when using highly sensitive tests. Literature: 35

36 SPECIJALNA SESIJA: KATEDRA ZA PATOLOGIJU MEDICINSKOG FAKULTETA, UNIVERZITETA NOVI SAD, SRBIJA 1. Midha A, Dearden S, McCormack R. EGFR mutation incidence in non-small-cell lung cancer of adenocarcinoma histology: a systematic review and global map by ethnicity (mutmapii). Am J Cancer Res Aug 15;5(9): Swati I, Zhang S, Tull J, Khurana KK. Accuracy of cytology specimen and needle core biopsies for detection of mutation in non-small cell carcinoma: comparison with resection specimen. World J Oncol Jun;2(6): Scarpino S, Pulcini F, Di Napoli A, Giubettini M, Ruco L. EGFR mutation testing in pulmonary adenocarcinoma: evaluation of tumor cell number and tumor percent in paraffin sections of 120 small biopsies. Lung Cancer Jan;87(1): Wang S, Yu B, Chiu Chin Ng, Mercorella B, Selinger CI, O Toole SA, et al. The suitability of small biopsy and cytology specimens for EGFR and other mutation testing in non-small cell lung cancer. Trans Lung Cancer Res April; 4(2): Coghlin CL, Smith LJ, Bakar S, Stewart KN, Devereux GS, Nicolson MC, et al. Quantitative analysis of tumor in bronchial biopsy specimens. J Thorac Oncol Apr;5(4):

37 P1 Četvrtak 19. April 2018 godine Poster sesija Značaj lokalne i sistemske ekspresije Survivina kod pacijenata sa melanomom Milena Jović 1, Snežana Cerovic 1, Lidija Zolotarevska 1, Milomir Gačević 2, Danilo Vojvodić 3 1 Institut za patologiju i sudsku medicinu, Vojnomedicinska akademija, Beograd, Srbija, 2 Klinika za plastičnu hirurgiju i opekotine, Vojnomedicinska akademija, Beograd, Srbija, 3 Institut za medicinska istraživanja, Vojnomedicinska akademija, Beograd, Srbija, Cilj: Cilj rada bio je da se ispita udruženost lokalne ekspresije survivina u tumoru i serumske koncentracije sa kliničkim i histopatološkim parametrima kod bolesnika sa melanomom. Uvod: Survivin je multifunkcionalni protein bogato ispoljen u tumorima različite vrste, uključujući i melanom. Retki su radovi koji opisuju odnos ispoljavanja survivina u melanomskim ćelijama sa njegovom serumskom koncentracijom kao i sa histopatološkim karakteristikama melanoma. Materijal i metode: Nivo ekspresije survivina određivan je imunohistohistohemijski u tumorskom tkivu i ELISA testom u serumu 84 bolesnika sa melanomom. Rezultati: Intezitet ekspresije survivina bio je značajno veći kod bolesnika čiji su tumori bili ulcerisani, sa visokim mitotskim indeksom, visokim Clark i Breslow indeksom, sa prisutnom vaskularnom i limfnom invazijom, kao i kod onih sa metastatskom bolesti. Bolesnici sa visokim skorom ekspresije survivina imali su skoro dvostruko kraći interval bez bolesti-dfi u odnosu na one sa slabom lokalnom ekspresijom survivina i malim brojem survivin pozitivnih ćelija (9-7 vs meseci). Stepen prisustva tumor infiltrišućih limfocita u tumorskom tkivu bio je značajno inverzno udružen sa koncetracijom survivina u serumu. Zaključak: Ekspresija survivina u tumorskom tkivu i njegova serumska koncentracija značajno koreliraju sa kliničkim i histopatološkim parametrima melanoma. Serumski nivo može biti važan kao inicijalni indikator kod onih bolesnika koji bi mogli imati agresivan lokalni tumorski rast i širenje. Ključne reči: melanom, survivin, imunohistohemija, ELISA Significance of local and systemic expression of Survivin in patients with melanoma Milena Jovic 1, Snezana Cerovic 1, Lidija Zolotarevska 1, Milomir Gacevic 2, Danilo Vojvodic 3 1 Institute for Pathology and Forensic Medicine, Military Medical Academy, Belgrade, Serbia 2 Clinic for Plastic Surgery and Burns, Military Medical Academy, Belgrade, Serbia 3 Institute for Medical Research, Military Medical Academy, Belgrade, Serbia Aim: The aim of this study was to investigate the association of local tumor survivin expression and serum concentration with clinical and histopathological parameters in melanoma patients. Introduction: Survivin is a multifunctional protein abundantly expressed in tumors of various types, including melanoma. There are still sparse data regarding relationship of melanoma cell survivin expression with accepted histopathological characteristics as well as serum concentration. Material and Methods: The level of survivin expression was determined immunohistochemically in tumor tissue and with ELISA test in the serum of 84 melanoma patients with melanoma. Results: Survivin expression was significantly higher in the patients whose tumor had ulceration, higher mitotic index, higher Clark and Breslow stage, that made vascular invasion or spread through lymphatic vessels in primary tumor, and in the patients with metastatic disease. The patients with high survivin expression score had almost double shorter disease free interval DFI comparing to those with weak local survivin expression and a small number of survivin cells (9-7 vs months, respectively). The degree of tumor infiltrating lymphocytes presence in tumor tissue was significantly inversely associated with serum survivin concentration. Conclusion: Conclusion Survivin expression in tumor tissue and its serum concetration significantly correlate with clinical and histopathological parameters. Serum levels could be important in initial follow-up as indicators of those patients that would have aggressive local tumor growth and spreading. Key words: melanoma, survivin, immunohistochemistry, ELISA. 37

38 POSTER SESIJA P2 Metastaza malignog melanoma u leiomiom tela materice Jelena Amidžic 1, Nada Vučković 1, Aleksandra Fejsa Levakov 1, Nenad Šolajić 2, Matilda Đolaji 1 Jelena Ilić Sabo 1, Milan Popović 3 1 Klinicki centar Vojvodine, Medicinski fakultet Univerziteta u Novom Sadu, Novi Sad, Srbija 2 Institut za onkologiju Vojvodine, Medicinski fakultet Univerziteta u Novom Sadu, Novi Sad, Srbija 3 Medicinski fakultet Univerziteta u Novom Sadu, Novi Sad, Srbija Cilj: Prikazom ovog slučaja naglašavamo visok potencijal malignog melanoma ka diseminaciji bolesti, kao i njegovu sklonost da daje metastaze u neuobičajenim lokalizacijama.uvod: Maligni melanom je zloćudna bolest porekla melanocita sa visokim malignim potencijalom. Incidenca javljanja malignog melanoma je u statistički značajnom porastu. Melanom ima visoku sklonost ka metastaziranju. Nakon primarne ekscizije tumora oko 30 % svih pacijenata će razviti metastaze u udaljene organe unutar prvih 5 godina nakon dijagnoze. Prikaz slučaja: Pacijentkinji starosti 48 godina je urađena histerektomija zbog miomatozno izmenjene materice. Nakon patohistološke analize dijagnostikovana je metastaza malignog melanoma u jednom od multiplih lejomioma tela materice. Dijagnoza je potvrdena imunohistohemijsim bojenjem na MART1 i S100 protein. Naknadnim uvidom u medicinsku dokumentaciju utvrdeno je da je pacijentkinji, 2 godine pre ove histerektomije, postavljena dijagnoza superficijalno širećeg malignog melanoma (Clark IV, Breslow III) na koži iznad leve dojke, kao i metastaze malignog melanoma u 2 od 13 pregledanih limfnih čvorova aksilarnog regiona levo (pt3an2bm0). Postavljena je dijagnoza stadijuma IV malignog melanoma (metastaze u lejomiom tela materice). Zaključak: Za razliku od drugih malignih tumora kože, melanom je izrazito agresivna bolest nepredvidive evolucije i s obzirom na činjenicu da ima visoki metastatski potencijal, pojave metastaza u neuobičajenim i neočekivanim lokalizacijama, kao što je u prikazanom slučaju u benigni tumor udaljenog organa. Ključne reči: melanom, lejomiom, metastaza, tumor-u-tumor Metastasis of Melanoma to Uterine Leiomyoma Jelena Amidzic 1, Nada Vuckovic 1, Aleksandra Fejsa Levakov 1, Nenad Solajic 2, Matilda Djolai 1, Jelena Ilic Sabo 1, Milan Popovic 3 1 Clinical Centre of Vojvodina, Faculty of Medicine Novi Sad, Novi Sad, Serbia 2 Oncology Institute of Vojvodina, Faculty of Medicine Novi Sad, Novi Sad, Serbia 3 Faculty of Medicine Novi Sad, Novi Sad, Serbia Aim: To highlight the widespread metastatic potential of the cutaneous melanoma, as well as its tendency for unusual presentation of metastatic disease. Introduction: Melanoma is an aggressive, highly malignant disease that is derived from melanocytes. The incidence of melanoma is significantly increasing. Melanoma has a strong tendency for metastasis. After primary excision of tumour, about 30% of all patients shall develop distant metastasis within first 5 years after tumour diagnosis. Case report: A 48-year-old female patient had undergone a hysterectomy because of myomatous uterus. After pathohistological examination metastasis of melanoma was diagnosed in one of multiple leimyoma. Diagnosis was confirmed with positive immunohistochemical staining with MART1 and S100 protein. Insight into the medical records, revealed that patient was diagnosed with superficially spreading melanoma (Clark IV, Breslow III) on skin above her left breast, as well as 2 regional tumour-involved lymph nodes (pt3a- N2bM0), 2 years prior to this hysterectomy. Uterine leiomyoma was the first diagnosed distant metastasis of cutaneous melanoma. Diagnosis of stadium IV melanoma was established. Conclusion: Melanoma is a particularly aggressive disease with unpredictable evolution, so the occurrence of metastases in unusual and unexpected localizations, as is the distant benign tumour in the presented case, shall probably happen more often in the future. Key words: melanoma, leiomyoma, metastasis, tumour-to-tumour 38

39 POSTER SESIJA P3 Rearanžman gena kinaze anaplastičnog limfoma u benignim tumorima kože: prikaz dva slučaja Milena Jovanovic 1, Sanja Ćirović 2, Martina Bosić 2 1 Medicinski fakultet, Univerzitet u Beogradu, Beograd, Srbija 2 Laboratorija za molekularnu patologiju, Institut za patologiju, Medicinski fakultet, Univerzitet u Beogradu, Beograd, Srbija. Cilj: Prikaz dva slučaja benignih tumora kože različite histogeneze sa rearanžmanom gena kinaze anaplastičnog limfoma (engl. Anaplastic lymphoma kinase, ALK). Uvod: Tumori sa rearanžmanom ili mutacijom ALK gena (ALKomi) su heterogena grupa u kojoj takav genetski nalaz ima dijagnostički ili prediktivni značaj. Fuzije ALK gena se dovode u vezu sa tumorigenezom pojedinih benignih tumora kože, kao to su pleksiformni Spitz nevus (PSN) i epiteloidni fibrozni histiocitom (EFH). Prikazi slučajeva: Analizirane su histološke, imunohistohemijske (IHH) i genetske karakteristike dva tumora kože sa rearanžmanom ALK gena dokazanim metodom fluorescentne in situ hibridizacije (FISH). Prvi slučaj predstavlja PSN kože lica kod dečaka starosti osam godina. Tumor je bio sačinjen od epidermalnih i dermalnih gnezda vretenastih ćelija, pleksiformnog rasporeda, sa sledećim IHH fenotipom: HMB45 fokalno, p16, Ki67 u 1% ćelija. Delecija CDKN2A gena nije uočena u značajnom broju, dok je ALK rearanžman bio pozitivan u 37/50 (74,2%) ćelija. Drugi slučaj predstavlja EFH kože ramena kod devojčice starosti 16 godina. Tumor su činile gusto raspoređene krupne epiteloidne ćelija, koje su bile CD68, p16, S100-, HMB45-, SOX10-, CD1a-, Ki67 (<5% ćelija). ALK rearanžman bio pozitivan u 24/100 (24%) ćelija, uz fokalnu polizomiju hromozoma 2. Nišu jednom tumoru nisu uočene mitoze i nekroza. Zaključak: ALKomi kože su tumori sa heterogenim histološkim i imunohistohemijskim karakteristikama, ali i varijabilnim obimom ALK rearanžmana. Ključne reči: Spitz nevus, Fibrozni histiocitom, Tumori kože, ALK, FISH Anaplastic lymphoma kinase gene rearrangement in benign skin tumors: Report of two cases Milena Jovanovic 1, Sanja Cirovic 2, Martina Bosic 2, 1 School of Medicine, University of Belgrade, Belgrade, Serbia 2 Laboratory for Molecular Pathology, Institute of Pathology, School of Medicine, University of Belgrade, Belgrade, Serbia. Aim: Report of two cases of benign skin tumors of different histogenesis with anaplastic lymphoma kinase (ALK) gene rearrangement. Introduction: ALK gene mutation or rearrangement positive tumors (ALKomas) are heterogeneous group in which such genetic finding has diagnostic or predictive value. ALK gene fusions are associated with tumorigenesis of some cutaneous tumors, e.g. plexiform Spitz nevus (PSN) and epithelioid fibrous histiocytoma (EFH). Cases reports: Histological, immunohistochemical (IHC) and genetic characteristics were analyzed in two skin tumors with ALK gene rearrangement proved by fluorescent in situ hybridization (FISH). First case is PSN localized on face in a 8-year-old boy. Tumor was consisted of spindle cells arranged in plexiform growth pattern throughout epidermis and dermis, with following IHC characteristics: HMB45 focally, p16, Ki67 in 1% of cells. Deletion of CDKN2A gene was not detected in significant number, while ALK gene rearrangement was positive in 37/50 (74,2%) of cells. Second case is EFH localized on shoulder in a 16-year-old girl. This dermal based tumor was consisted of tightly packed large epithelioid cells, which were CD68, p16, S100-, HMB45-, SOX10-, CD1a-, Ki67 (<5% of cells). ALK gene rearrangement was positive in 24/100 (24%) of cells, and focal chromosome 2 polysomy was noted. Neither mitoses nor necrosis were present in any of presented cases. Conclusion: Skin ALKomas are tumors with heterogeneous histological and immunohistochemical characteristics, and also with variable extent of ALK rearrangement. Key words: Spitz nevus, Fibrous histiocytoma, Skin tumors, ALK, FISH 39

40 POSTER SESIJA P4 Klinički značaj ekspresije CD34 u endometroidnom karcinomu tela materice Tomislav Jocić 1, Milena Rakočević 2 1 Opšta bolnica, Pirot, Srbija, 2 Fakultet medicinskih nauka, Kragujevac, Srbija Cilj: Naš cilj je ispitivanje ekspresije CD34 u endometroidnom karcinomu (EC) tela materice i povezanosti neoangiogeneze sa klasičnim kliničko-prognostičkim parametrima.uvod: Stopa incidence EC raste sa starošću tako da se u oko 75% slučajeva javlja u postmenopauzalnih žena. Materijal i metode: Na biopsijskim uzorcima dobijenim nakon histerektomije 36 bolesnica, operisanih od EC tela materice u Opštoj bolnici u Pirotu, su primenjene rutinska HE i imunohistohemijska ABC metoda sa anti-cd34 antitelima. Na osnovu ekspresije CD34 stereometrijski je izračunata mikrovaskularna gustina (mvd) po mm2 tkiva. Za statističku obradu korišćen je programski paket SPSS(verzija 19.0). Rezultati: Značajno izražena ekspresija CD34 je prisutna u svim slučajevima tumora u pt2a-pt3a i svim slučajevima tumora u IIA-IIIA FIGO stadijuma. Signifikantno visok indeks neoangiogeneze je prisutan u 72.2% umereno diferentovanih tumora, u oko 70% tumora sa umerenom/izraženom nuklearnom atipijom, u 92% slučajeva sa mikrovaskularnom invazijom i u 76.5% tumora koji su zahvatili preko 50% miometrijuma. Ekspresija CD34 je u umerenoj, pozitivnoj i signifikantnoj korelaciji sa invazijom limfnih sudova, patološkim stadijumom tumora i invazijom krvnih sudova i miometrijuma (kk= ). Slabija je korelativna zavisnost ovog markera i histološkog i nuklearnog gradusa tumora (kk=0.444 i 0.410). Zaključak: Signifikantna povezanost CD34 sa agresivnim fenotipom EC tela materice ima značajne prognostičke implikacije. Ključne reči: Endometroidni karcinom, telo materice, neoangiogeneza, imunohistohemija Clinical significance of cd34 expression in endometrioid carcinoma of the uterine body Tomislav Jocic 1, Milena Rakocevic 2 1 General Hospital, Pirot, Sebia, 2 Faculty of Medical sciences, Kragujevac, Serbia Aim: Our aim is to examine the expression of CD34 in the endometrioid carcinoma (EC) of the uterine body and association of neoangiogenesis with classical clinical and prognostic parameters. Introduction: The incidence rate increases with age, so in about 75% of cases it occurs in postmenopausal women.material and Methods: On the biopsy samples obtained after the hysterectomy of 36 patients operated from EC of the uterine body, operated in the General hospital Pirot, where applied routine H E and the imunohistochemical ABC method with anti-cd34 antibodies. Based on the expression of CD 34, the microvascular density per mm2 of the tissue was calculated stereometrically. For statistical analysis SPSS software package were used (version 19.0). Results: The significantly pronounced expression of CD34 is present in all cases of tumors in pt2a to pt3a, and in all cases of the IIA-IIIA FIGO stage. A significantly high neoangiogenesis index is present in 72% of moderately differentiated tumors, in about 70% of tumors with moderate/expressed nuclear atypies, in 92% of cases with microvascular invasion and in 76,5% of tumors affecting over 50% of myomterium. CD34 expression is in positive, moderate and significant correlation with invasion of lymph vessels, pathological stage of the tumor and invasion of blood vessels and myometrium (kk=0,636-0,587). The correlation between this marker and the histological and nuclear tumor grade is weaker (kk=0,444 and 0,410). Conclusion: Significant association of CD34 with the aggressive phenotype of the EC of uterine body has significant prognostic implications. Key words: Endometrioid carcinoma, uterine body, neoangiogenesis, imunohistochemistry 40

41 POSTER SESIJA P5 Lobularna endocervikalna glandularna hiperplazija vs. Adenokarcinom minimalne diferencijacije: prikaz slučaja Ljubiša Jovanović, Simić Ljubica, Stefanović Radomir, Vrtikapa Jelena, Pajević Mila, Atanacković Jasmina, Milenković Svetlana Služba za patohistologiju, Klinika za ginekologiju i akušerstvo, Klinički centar Srbije, Beograd, Srbija Cilj: Lobularna endocervikalna glandularna hiperplazija je vrlo redak, diferencijano dijagnostički zahtevan entitet, koji cesto uspešno oponaša agresivnije endocervikalne lezije, sa lošijom prognozom. Uvod: Lobularna glandularna endocervikalna hiperplazija(legh) je benigna lezija koja podrazumeva lobularnu proliferaciju endocervikalnih žlezdi koje su obložene endocervikalnim epitelom bez ili sa minimalnom nuklearnom atipijom. Lobularna struktura se može širiti duboko u tkivo cerviksa, bez stromalne invazije, to je bitna razlika u odnosu na adenokarcinom minimalne devijacije(mda) koji se definiše kao dobro diferentovani endocervikalni tip adenokarcinoma, koji vrlo podseća na LEGH leziju. Prikaz slučaja: Pacijentkinja 50 godina, sa jasno ograničenim istmičnocervikalnim nodoznim, multicističnim tumorom koji zahvata čitavu debljinu cerviksa. Mikroskopskom analizom tkivo cerviksa pokazuje brojne izrazito cistično dilatirane endocervikalne žlezde, lobularnog rasporeda, okružene umnoženom fibroznom stromom. Lobulusi žezdanih acinusa su difuzno lokalizovani, sa centralno dilatiranim acinusom i perifernije manjim tubularnim strukturama. Žlezde su bez prisustva arhitektualnih promena, obložene uniformnim, endocervikalnim epitelom, bazalno postavljenih jedara, bez prisustva citonuklearne atipije.imunohistohemijska analiza je pokazala:cea-/ca125fokalno /p16 fokalno/er i Pr fokalno epitel,difuzno u stromi. Obzirom da su opisane strukture prisutne duboko u tkivu cerviksa, diferencijalno dijagnostički se razmatra MDA. Međutim, žlezde ne pokazuju znake distorzije(arhitektualne atipije) koja je bitna karakteristika ovog entiteta, kao ni izraženu okolnu dezmoplastičnu stromalnu reakciju. Makroskopski je tumor jasno ograničen, CEA marker je negativan, to takođe dodatno sugeriše LEGH. Zaključak: LEGH i MDA pokazuju priličnu kliničku i histološku sličnost. Dokazana je udruženost LEGH(50%) sa MDA i 40% sa cervikalnim adenokarcinomom, to sugeriše mogući prekancerozni potencijal LEGH. U tom smislu istraživanje mikrokruženja lezije bi moglo biti interesantan predmet daljeg istraživanja. Ključne reči: LEGH, MDA, cerviks. Lobular endocervical glandular hyperplasia vs. Minimal deviation adenocarcinoma: case report Ljubiša Jovanović, Simić Ljubica, Stefanović Radomir, Vrtikapa Jelena, Pajević Mila, Atanacković Jasmina, Milenković Svetlana Department of Pathology, Clinic for Gynecology and Obstetric, Clinical Centre of Serbia, Belgrade, Serbia Aim: Lobular endocervical glandular hyperplasia is very rare, differential diagnostic difficult entity, which often mimics more aggressive endocervical lesions, with worse prognosis. Introduction: Lobular glandular endocervical hyperplasia(legh) is benign lesion with lobular proliferation of endocervical glands and endocervical epithelium without or with minimal nuclear atypia. Lobular structure can be deep into the cervical tissue without stromal invasion, which is important difference between adenocarcinoma of minimal deviation(mda), well-differentiated endocervical type of adenocarcinoma, similar to LEGH. Case report: The patient is 50 years, with demarcated, nodular, multicystic tumor, localized deep in cervical tissue. Microscopic analysis shows numerous cystically dilated endocervical glands with lobular presentation, surrounded by hyperplastic fibrous stroma. Glandular acini are diffusely localized, with centrally dilated acinus and peripheral smaller tubular structures. Glands are without the presence of architectural changes and cytonuclear atypia, with uniform, endocervical epithelium.immunochemical analysis showed:cea- /CA125focal /p16 focal /Er and Pr focal epithelium, diffusely in stroma. Because structures were described deep in the cervical tissue, MDA is considered diagnostically differential. However, glands do not show signs of distortion(architectural atypia), which is important feature of this entity, as well as no pronounced surrounding desmoplastic stromal reaction. Macroscopic tumor is well demarcated, and the CEA marker is negative, which also suggested LEGH. Conclusion: LEGH and MDA show a quiet clinical and histological similarity. Association of LEGH(50%) with MDA and 40% with cervical adenocarcinoma has been demonstrated, suggesting the possible precancerous potential of LEGH. Research of the lesion microenvironment could be an interesting subject for further research. Key words: LEGH, MDA, cervix. 41

42 POSTER SESIJA P6 Patohistološka procena tumorske regresije kod karcinoma dojke nakon neoadjuvantne terapije Tatjana Ćulafić 1, Mirjana Miladinović 1, Ljiljana Vučković 1, Mileta Golubović 1, Filip Vukmirović 1, Ivana Jeličić 2, Tanja Lakić 1, Janja Raonić 1 1 Klinički centar Crne Gore, Podgorica, Crna Gora 2 Opšta bolnica Vrbas, Vrbas, Srbija Cilj: Evaluacija rezultata patohistološke procene terapijskog odgovora primarnog karcinoma dojke na primenjenu neoadjuvantnu terapiju.uvod: Karcinom dojke je heterogena bolest i moe se klasifikovati u nekoliko molekularnih podtipova, koristeći imunohistohemijsku analizu i in situ hibridizaciju. Neoadjuvantna terapija se primenjuje u slučajevima lokalno uznapredovalih karcinoma dojke i za procenu hemiosenzitivnosti tumora, to je veoma važno za prognozu bolesti.materijal i metode: U istra ivanje je ukljuceno 35 pacijentkinja koje su godine lecene radikalnom mastektomijom, nakon IV ciklusa neoadjuvantne terapije, u Klinickom centru Crne Gore. Svim pacijentkinjama je prije lecenja radena core biopsija (potvrden invazivni karcinom dojke, odreden molikularni podtip). Patohistolo ki odgovor primarnog tumora na primenjenu terapiju procenjivan je kao kompletan odgovor (pcr), parcijalni odgovor (ppr) i bez odgovora (pnr). Rezultati: Prosečna starost u ispitivanoj grupi pacijentkinja je bila 59,25 godina. U 68,58% slučajeva radilo se o invazivnom duktalnom, 17,14% invazivnom lobularnom i u 14,28% mešovitom invazivnom karcinomu. Zastupljenost molekularnih podtipova je bila sledeća bez promene u odnosu na core biospiju : 34,28% Luminalni A, 42,85% Luminalni B Her2 negativni, 5,71% Luminalni B Her2 pozitivni, 8,58% Her2 pozitivni i 8,58% trostruko negativni. Kod 6 pacijentkinja (17,15%) dobijen je pcr, kod 21 (71,42%) ppr, a kod 4 (11,43%) nije bilo odgovora. U grupi pacijentkinja kod kojih je dobijen pcr radilo se o Her2 pozitivnom i trostruko negativnom karcinomu. Zaključak: Patolo ka procena rezidualne bolesti je najva nija komponenta procene karcinoma dojke nakon neoadjuvantne terapije. Najčešće se radi o parcijalnom odgovoru, dok se kompletni odgovor najčešće dobije kod Her2 pozitivnih ili trostruko negativnih karcinoma. Ključne reči: karcinom dojke, neoadjuvantna terapija Pathohistological evaluation of tumor regression at breast cancer after neoadjuvant therapy Tatjana Culafic 1, Mirjana Miladinovic 1, Ljiljana Vuckovic 1, Mileta Golubovic 1, Filip Vukmirovic 1, Ivana Jelicic 2, Tanja Lakic 1, Janja Raonic 1 1 Clinical Center of Montenegro, Podgorica, Montenegro 2 General hospital Vrbas, Vrbas, Serbia Aim: Evaluation of pathological estimation results of therapeutic response of primary breast carcinoma to applied neoadjuvant therapy. Introduction: Breast carcinoma is heterogeneous disease, that could be classified into several molecular subtypes by using immunohistochemical analysis and in situ hybridization. Neoadjuvant therapy is applied in cases of locally advanced breast carcinoma and for tumor chemosensitivity evaluation, which is very significant for disease prognosis. Material and Methods: The research was conducted on 35 female patients, that were treated with radical mastectomy in 2017, after IV cycle of neoadjuvant therapy, in Clinical Centre of Montenegro. Before treatment, all patients underwent core biopsy (confirmed invasive breast carcinoma, molecular subtype determined).pathohistological response of primary tumor to applied therapy was estimated as complete response (pcr), partial response (ppr) and no response (pnr). Results: Average age in examined group of patients was 59,25 years.in 68,58% of cases it was invasive ductal, in 17,14% invasive lobular and in 14,28% mixed invasive carcinoma. Representation of molecular subtypes was (without change in respect to the core biopsy): 34,28% Luminal A, 42,85% Luminal B Her2 negative, 5,71% Luminal B Her2 positive, 8,58% Her2 positive and 8,58% triple negative. In 6 patients (17,15%) pcr was obtained, in 21 (71,42%) ppr, and in 4 (11,43%) no response. In group of patients confirmed for pcr, it was Her2 positive or triple negative carcinoma. Conclusion: Applying of neoadjuvant therapy leads to tumor response to applied therapy. Most commonly it is partial response, while complete response most commonly occurs in Her2 positive or triple negative carcinomas. Key words: breast, carcinoma 42

43 POSTER SESIJA P7 Pouzdanost odredivanja ekspresije steroidnih receptora, receptora humanog epidermalnog faktora rasta 2 i molekularnog podtipa tumora u core biopsiji dojke Janja Raonić, Ljiljana Vučković, Jelena Vučinić, Filip Vukmirović, Mileta Golubović, Tanja Nenezić, Tatjana Ćulafić, Mirjana Miladinović Centar za patologiju, Klinicki centar Crne Gore, Podgorica, Crna Gora Cilj: Ispitati stepen slaganja rezultata ekspresije steroidnih receptora, receptora humanog epidermalnog faktora rasta 2 (Her2) i određenih molekularnih podtipova tumora u operativnom materijalu (OM) i uzorcima dobijenim core biopsijom (CB). Uvod: CB predstavlja iroko prihvacenu metodu u inicijalnoj dijagnostici karcinoma dojke. Pouzdanost metode u odredivanju statusa steroidnih i Her2 receptora, Ki67 indeksa i molekularnog podtipa tumora i dalje je predmet razmatranja. Materijal i metode: Analizirana su 54 slučaja invazivnog karcinoma dojke, kod kojih je određena ekspresija estrogenskih (ER), progesteronskih (PR) i Her2 receptora i Ki67 indeks, najprije na CB, a potom i na OM. Stepen slaganja rezultata ekspresije ER, PR i Her2 receptora i određenih molekularnih podtipova, izmedu CB i OM, izračunat je korišćenjem k-testa (p<0,001). Rezultati: Prosječna starost pacijentkinja iznosila je 62 godine. U OM, najčešće je dijagnostikovan Luminal A podtip (48%). Sledeći po ucestalosti bili su: Luminal B Her2- (31%) i TNBC (13%), dok su LuminalB Her2 i Her2-enriched bili zastupljeni sa po 4%. U CB, učestalost molekularnih podtipova bila je: Luminal A (41 %), Luminal B Her2- (33%), TNBC (15%), Luminal B Her2 (7%), Her2-enriched (4%). Stepen slaganja rezultata ekspresije za ER receptore iznosio je 93.8% (Kappa=0.936), za PR 77.5% (Kappa=0.773), za Her2 80.0% (Kappa=0.78), a za odredene molekularne podtipove 80.9% (Kappa=0.753). Zaključak: Statisticka analiza pokazala je veoma dobro slaganje rezultata određenih molekularnih podtipova i ekspresije ER receptora, kao i dobro slaganje rezultata ekspresije PR i Her2 receptora u CB i OM. CB predstavlja pouzdanu metodu za određivanje statusa steroidnih i Her2 receptora, kao i molekularnog podtipa tumora. Ključne reči: karcinom dojke, core biopsija, ekspresija receptora Reliability of determination of steroid and human epidermal growth factor 2 receptors expression and tumor molecular subtypes in breast core biopsy Janja Raonic, Ljiljana Vuckovic, Jelena Vucinic, Filip Vukmirovic, Mileta Golubovic, Tanja Nenezic, Tatjana Culafic, Mirjana Miladinovic Center for pathology, Clinical center of Montenegro, Podgorica, Montenegro Aim: To investigate concordance rate between the results of expression of steroid receptors, human epidermal growth factor 2 receptors (Her2) and determined molecular subtypes in surgical specimens (SS) and samples obtained by core biopsy (CB). Introduction: CB is widely accepted method in the initial diagnosis of breast cancer, but its reliability in determining the status of steroid and Her2 receptors, Ki67 index and molecular subtypes is still a matter of debate. Material and Methods: We analyzed 54 cases of invasive breast cancer, in which the expression of estrogen (ER), progesterone (PR) and Her2 receptors and Ki67 index were determined both in CB and SS. Concordance rate for ER, PR and Her2 receptors expression and molecular subtypes, between CB and SS, was calculated using k-test (p<0.001). Results: The average age of patients was 62. In SS, Luminal A subtype was most commonly diagnosed (48%), followed by: Luminal B Her2-(31%) and TNBC (13%), while Luminal B Her2 and Her2-enriched subtypes were represented by 4% each. Frequencies of molecular subtypes in CB were: Luminal A (41%), LuminalB Her2- (33%), TNBC (15%), Luminal B Her2 (7%), Her2-enriched (4%). Concordance rate for ER receptors was 93.8%(Kappa=0.936), for PR 77.5%(Kappa=0.773), for Her2 80.0%(Kappa=0.78) and for molecular subtypes 80.9%(Kappa=0.753). Conclusion: Statistical analysis showed very good agreement in terms of determined molecular subtypes and ER receptors expression and good agreement for the expression of PR and Her2 receptors. CB represents reliable method for determining the status of expression of steroid and Her2 receptors, as well as tumor molecular subtypes. Key words: breast cancer, core biopsy, receptor expression 43

44 POSTER SESIJA P8 Komparacija citoloških metoda četkaste biopsije i transbronhijalne iglene biopsije u dijagnostici karcinoma pluća Jelena Džambas, Vesna Škuletić, Željka Tatomirović, Ivan Aleksić, Ljiljana Tomić, Snežana Cerović Institut za patologiju i sudsku medicinu, Vojnomedicinska akademija, Beograd, Srbija Cilj: Poredenje specifičnosti, senzitivnosti i tačnosti četkaste- brush biopsije (BB) i transbronhijalne iglene biopsije (transbronchial needle aspiration-tbna) u dijagnostici karcinoma pluća, kao i korelacija i komparacija sa patohistološkom dijagnozom. Uvod: Karcinom pluća je vodeci uzrok smrti širom sveta kod oba pola. U ranoj dijagnostici karcinoma pluća koriste se brojne citološke tehnike- BB, aspirat bronha, TBNA, brohoalveolarna lavaža, transtorakalna i pleuralna punkcija. Materijal i metode: U jednogodišnjoj retrospektivnu studiju bilo je uključeno 359 pacijenata sa sumnjom na karcinom pluća upućenih na bronhoskopiju prilikom koje su uzimani citološki uzorci za razmaze metodama BB i TBNA kao i biopsije za patohistološku dijagnostiku koja je bila zlatni standard. Uzorci su mikroskopski analizirani i podaci su statistićki obrađivani korišćenjem deskriptivne statistike i neparamterijskog Kendal-tau koeficijenta korelacije (nivo statisticke značajnosti p<0,05). Rezultati: Senzitivnost BB i TBNA bila je 97,17%, odnosno 98,32%, dok je specificčnost bila 97,26% to jest 97,75 %. Pozitivni prognostički značaj bio je 97,14% kod BB i 99,66% kod TBNA, a negativni 93,23% kod BB i 98,77% kod TBNA. Tačnost BB bila je 96,51%, a TBNA 99,14%. Neslaganje citološke i patohistološke dijagnoze bilo je u 3,21% BB i 2,03% TBNA. Nije bilo statistički značajne razlike između citološke i patohistološke dijagnoze kod BB (p=0,550) niti kod TBNA metode (p=0,602) citološkog uzorkovanja. Zaključak: Bez obzira na metod uzorkovanja materijala citologija je značajna i korisna metoda u dijagnostici karcinoma pluća jer pruža skoro iste informacije kao patohistologija. Ključne reči: karcinom pluća, citologija, patohistologija, korelacija Comparative study of bronchial brushing and transbronchial needle aspiration cytology in diagnosing lung cancer Jelena Dzambas, Vesna Skuletic, Zeljka Tatomirovic, Ivan Aleksic, Ljiljana Tomic, Snezana Cerovic Institute of Pathology and Forensic Medicine, Military Medical Academy, Belgrade, Serbia Aim: To compare sensitivity, specificity and accuracy of bronchial brushing (BB) and transbronchial needle aspiration (TBNA) cytology in diagnosing lung cancer and to correlate and compare them with corresponding histopathology. Introduction: Lung cancer is a leading cause of death worldwide in both genders. Various cytological techniques such as BB and aspirate, TBNA, bronchoalveolar lavage, transthoracic and pleural puncture can aid in early diagnosis of lung malignancies. Material and Methods: One-year retrospective study included 359 patients with suspected lung cancer who underwent bronchoscopy. During bronchoscopy, cytopathological samples were obtained for smears using BB and TBNA as well as biopsy for histopathological examination that was considered the gold standard. All the samples were microscopically examined and statistically analyzed using descriptive methods and non-parametric Kendal-tau correlation coefficient (the level of significance p<0.05). Results: Sensitivity of BB and TBNA cytology comparing to histopathology was 97.17% and 98.32% respectively whereas specificity was 97.26% and % respectively. Positive predictive value was 97.14% in BB and 99.66% in TBNA and negative predictive value was 93.23% in BB and 98.77% in TBNA. The accuracy of BB was 96.51% and 99.14% of TBNA cytology. Discordance of BB cytological and histopathological diagnosis was in 3.21%, whereas discordance of TBNA was in 2.03% cases. There was no statistically significant difference neither between BB (p=0.550) nor between TBNA (p=0.602) cytology and histopathological diagnosis. Conclusion: Cytology is valuable and useful in establishing lung cancer diagnosis, which yields almost the same information as histopathology no matter which method of cytological sampling is used. Key words: lung cancer, cytology, histopathology, correlation 44

45 POSTER SESIJA P9 Odnos izmedu ekspresije tiroidnog transkripcionog faktora 1 i mutacija receptora epidermalnog faktora rasta u adenokarcinomu pluća Dragana Tegeltija 1, Aleksandra Lovrenski 1, Golub Samardžija 2, Tijana Vasiljević 3, Vladimir Zečev 4, Živka Eri 1, Dejan Vučković 1 1 Institut za plućne bolesti Vojvodine, Univerzitet u Novom Sadu, Medicinski fakultet,novi Sad, Srbija 2 Institut za kardiovaskularne bolesti Vojvodine, Univerzitet u Novom Sadu, Medicinski fakultet, Novi Sad, Srbija 3 Institut za onkologiju Vojvodine, Univerzitet u Novom Sadu, Medicinski fakultet, Novi Sad, Srbija 4 Vladimir Zečev, Opšta bolnica Sombor, Sombor, Srbija Cilj: Da se utvrdi stepen korelacije izmedu TTF-1 (+) ekspresije i EGFR mutacionog statusa u adenokarcinomu pluća. Uvod: Adenokarcinom pluća se uglavnom dijagnostikuje na osnovu standardnih morfoloških kriterijuma. Thyroid Transcription Factor (TTF-1) je trenutno najčešće korišćen imunohistohemijski marker u diferencijaciji invazivnog adenokarcinoma pluća od drugih primarnih i metastatskih karcinoma, ima prognosticki značaj i predstavlja prediktor EGFR mutacionog statusa. Materijal i metode: U ovu retrospektivnu studiju je bilo uključeno 60 bolesnika kod kojih je histološka dijagnoza primarnog adenokarcinoma pluća potvrđena u hirurškom uzorku na Institutu za plućne bolesti Vojvodine od do U uzorcima ovih pacijenata analizirana je TTF-1 ekspresija i EGFR mutacije koristeći imunohistohemijsku i PCR analizu. Statistička analiza je u statističkom softvru Statistica 12. Rezultati: U istraživanje je bilo uključeno 35 muškaraca i 25 žena, prosečne starosti od 61,8ą8,08 god. Od 60 slučajeva TTF-1 (+) ekspresija je evidentirana u 52 (87%) (p<0.001), statistička razlika nije značajna kada se porede pušačke navike, prema polu i veličina tumora među njima. EGFR ( ) mutacioni status je naden u 3/60 (5%) slučajeva [egzon 21 (2) i egzon 20 (1)] od kojih je TTF-1 (+ ) ekspresija je bila u dva slučaja. Zaključak: Postoji statistički znacajna razlika izmedu TTF-1 (-) i TTF-1 (+) adenokarcinoma i visok stepen korelacije izmedu EGFR mutacionog statusa i TTF-1 (+) ekspresije. Ključne reči: adenokarcinom pluća, TTF-1, EGFR mutacije. The relationship between thyroid gland transcriptiom factor expression and epidermal growth factor receptor mutation in the lung adenocarcinoma Dragana Tegeltija 1, Aleksandra Lovrenski 1, Golub Samardzija 2, Tijana Vasiljevic 3, Vladimir Zecev 4, Zivka Eri 1, Dejan Vuckovic 1 1 Institute for Pulmonary Diseases of Vojvodina, University of Novi Sad, Faculty of Medicine, Novi Sad, Serbia 2 Institute for Cardiovascular Diseases of Vojvodina, University of Novi Sad, Faculty of Medicine, Novi Sad, Serbia 3 Oncology Institute of Vojvodina, University of Novi Sad, Faculty of Medicine, Novi Sad, Serbia 4 General Hospital Sombor, Sombor, Serbia Aim: To determine the degree of correlation between TTF-1 (+) expression and EGFR mutation status in lung adenocarcinoma. Introduction: Adenocarcinoma of the lung is mainly diagnosed based on standard morphological criteria. The thyroid gland transcription factor (TTF-1) is currently the most commonly used immunohistochemical marker in the differentiation of invasive adenocarcinoma of the lung from another primary and metastatic carcinoma, has a prognostic significance and is a predictor of the EGFR mutation status. Material and Methods: This retrospective study enrolled 60 patients with histologically confirmed primary lung adenocarcinoma who underwent lung cancer surgery at Institute for lung disease Vojvodina between 2010 and Tumor specimens of these patients were investigated for TTF-1 expression and mutations in EGFR using immunohistochemistry and PCR analysis. Statistical analysis is in statistic software Statistica 12. Results: The study included 35 men and 25 women, with an average age of 61.8 ą 8.08 years. Of the 60 cases, TTF-1 ( ) expression was recorded in 52 (87%) (p <0.001), the statistical difference is not significant when comparing smoking habitsby gender, and tumor size among them. EGFR ( ) mutation status was found in 3/60 (5%) cases [egzon 21 (2) and exon 20 (1)], of which TTF-1 (+) expression was in two cases. Conclusion: There is a statistically significant difference between the TTF-1 (-) and TTF-1 (+) adenocarcinoma and a high degree of correlation between EGFR mutation status and TTF-1 (+) expression. Key words: lung adenocarcinoma, TTF-1, EGFR mutations. 45

46 POSTER SESIJA P10 Primarni endobronhijalni sinovijalni sarkom Dragana Tegeltija 1, Aleksandra Lovrenski 1, Golub Samardžija 2, Tijana Vasiljevic 3, Mišel Milošević 1, Živka Eri 1, Dejan Vucković 1 1 Institut za plućcne bolesti Vojvodine, Univerzitet u Novom Sadu, Medicinski fakultet, Novi Sad, Srbija 2 Institut za kardiovaskularne bolesti Vojvodine, Univerzitet u Novom Sadu, Medicinski fakultet, Novi Sad, Srbija 3 Institut za onkologiju Vojvodine, Univerzitet u Novom Sadu, Medicinski fakultet, Novi Sad, Srbija Cilj: Prikazujemo slučaj žene sa endobronhijalnim pulmonalnim sinovijalnim sarkomom. Uvod: Primarni pulmonalni sinovijalni sarkom je izuzetno redak tumor koji ima iste histomorfološke karakteristike i hromozmske translokacije kao i sinovijalni sarkom porekla mekih tkiva. Materijal i metode: Žena stara 58 godina, pušač, bez aktuelnih simptoma bolesti javila se u na u ustanovu zbog nodusa koji je videnog na CT grudnog koša. Polip (26 mm) se nalazio u donjem desnom lobarnom bronhu. Medijastinalni i hilusni limfni čvorovi nisu bili uvećani. Radiološki pregled je urađen u sklopu rutinske kontrole nakon operacije meningeoma pre tri godine. Urađena je desna donja lobektomija i resekcija regionalnih limfnih čvorova. Rezultati: Makroskopskim pregledom, u lumenu bronha za donji desni režanj, nađen je jasno ograničen, neinkapsulisan, sivkasto-beličast čvor dimenzija 2,6 x 2,6 x 1 cm. Histološki, tumor su gradili isprepleteni fascikulusi uniformnih vretenastih cćelija ovalnih svetlih jedra, neupadljivih nukleolusa, oskudne citoplazme i nejasnih ćelijskih granica. Imunohistohemijski tumorske ćelije su bile pozitivne na CD99, bcl2 i vimentin. Hirurške margine i regionalni limfni čvorovi nisu bili zahvaćeni. Detaljnim kliničkim i radiološkim pregledom potvrđeno je primarno plućno poreklo dijagnostikovanog sinovijalnog sarkoma. Godinu dana nakon operacije bolesnica se oseća dobro. Zaključak: Morfološka i imunohistohemijska analiza uz detaljan klinički i radiološki pregleda potvrđuje primarno plućno poreklo sinovijalnog sarkoma Ključne reči: primarni pulmonalni sarkom, imunohistohemija. Primary endobronchial synovial sarcoma Dragana Tegeltija 1, Aleksandra Lovrenski 1, Golub Samardzija 2, Tijana Vasiljevic 3, Misel Milosevic 1, Zivka Eri 1, Dejan Vuckovic 1 1 Institute for Pulmonary Diseases of Vojvodina, University of Novi Sad, Faculty of Medicine, Novi Sad, Serbia 2 Institute for Cardiovascular Diseases of Vojvodina, University of Novi Sad, Faculty of Medicine, Novi Sad, Serbia 3 Oncology Institute of Vojvodina, University of Novi Sad, Faculty of Medicine, Novi Sad, Serbia Aim: We present the case of a woman with endobronchial pulmonary synovial sarcoma. Introduction: Primary pulmonary synovial sarcoma is an extremely rare tumor that has the same histomorphological characteristics and chromosomal translocations as the synovial sarcoma of soft tissue origin. Material and Methods: A woman aged 58 years, the smoker, without the current symptoms of the disease, came to our institution because of the nodus that was seen on the CT chest. The polip (26 mm) was located in the lumen of the lower right lobar bronchus. The mediastinal and hilar lymph nodes were not increased. The radiological examination was done as part of a routine control after the meningeoma surgery three years ago. Right lower lobectomy and resection of regional lymph nodes were performed. Results: By a macroscopic examination, in the lumen of the bronchus for the lower right lobes, a clearly limited, nonencapsulated, grayish-white node of 2.6 x 2.6 x 1 cm was found. Histologically, the tumor was showed interweaving fascicular uniform spindle cell with ovoid, pale staining nuclei, and inconspicuous nucleoli, scant cytoplasm and the cell borders indistinct. Immunohistochemical tumor cells were positive for CD99, bcl2 and vimentin. Surgical margins and regional lymph nodes were not affected. A detailed clinical and radiological examination confirmed the primary lung origin of the diagnosed synovial sarcoma. A year after surgery the patient feels good. Conclusion: Morphological and immunohistochemical analysis with detailed clinical and radiological examination confirms the primary lung origin of synovial sarcoma Key words: primary pulmonary sarcoma, immunohistochemistry. 46

47 POSTER SESIJA P11 Intersticijalne bolesti pluća u hirurškim biopsijama Aleksandra Lovrenski 1, Dragana Tegeltija 1, Golub Samardžija 2, Milana Panjkovic 3, Dejan Vuckovic 1, Živka Eri 1 1 Institut za plućne bolesti Vojvodine, Sremska Kamenica, Srbija 2 Institut za kardiovaskularne bolesti Vojvodine, Sremska Kamenica, Srbija 3 Klinicki centar Vojvodine, Novi Sad, Srbija Cilj: Analiza materijala dobijenog hirurškombiopsijom pluća kod pacijenata sa klinički i radiološki postavljenom dijagnozom intersticijalne plućne bolesti. Uvod: Intersticijalne bolesti pluća (IBP) su grupa bolesti koje zahvataju plućni intersticijum. Brojni entiteti unutar ove grupe dele slične kliničke i radiološke osobine, te se definitivna dijagnoza prvenstveno postavlja histopatološkim pregledom materijala dobijenog hirurškom biopsijom. Materijal i metode: Studija je obuhvatila 30 pacijenata kod kojih je u desetogodišnjem periodu na Institutu za plućne bolesti Vojvodine u Sremskoj Kamenici izvršena hirurška biopsija pluća. Za patohistološku analizu korišćeno je standardno HE bojenje, a u nekim slučajevima specijalna bojenja za vezivno tkivo i glatki mišić, kao i imunohistohemijska analiza. Analizirani su starost, pol, klinički simptomi, hirurški tip biopsije i histološke promene u bioptičkom uzorku. Rezultati: Od 30 pacijenata koji su bili podvrgnuti hiruškoj biopsiji pluća, otvorena biopsija pluća prema Claassenu bila je izvedena kod 14 pacijenata, u 12 pacijenata materijal je dobijen biopsijom prema Maassenu, dok je kod 4 pacijenta materijal za histopatološku analizu uzet videoasistiranom torakoskopijom. Najčešće mesto biopsije bio je gornji režanj u 16 slučajeva, zatim lingula u 10, srednji režanj u 2, i donji režanj i baza pluća u po 1 pacijenta. Histopatološkom analizom, postavljene su sledeće dijagnoze: UIP u 8 pacijenata, PLCH u 7, sarkoidoza u 6, hipersenzitivni pneumonitis u 3, NSIP u 2, LAM, LIP, DIP i ACIF u po jednog pacijenta. Zaključak: Dijagnoza IBP zasniva se na istoriji bolesti, fizikalnom pregledu, HRCT-u, testovima plučnih funkcija i biopsiji pluča koja predstavlja zlatni standard u dijagnostičkom pristupu ovim oboljenjima. Ključne reči: Intersticijalne plucne bolesti, dijagnoza, patohistologija Interstitial lung diseases in surgical biopsies Aleksandra Lovrenski 1, Dragana Tegeltija 1, Golub Samardžija 2, Milana Panjkovic 3, Dejan Vuckovic 1, Zivka Eri 1 1 Institute for pulmonary diseases of Vojvodina, Sremska Kamenica, Serbia 2 Institute for cardiovascular diseases of Vojvodina, Sremska Kamenica, Serbia 3 Clinical center of Vojvodina, Novi Sad, Serbia Aim: To evaluate surgical lung biopsies in patients with a clinically and radiologically set diagnosis of ILD. Introduction: Interstitial lung diseases (ILDs) are a group of lung diseases affecting the lung interstitium. These entities share similar clinical and radiological features and are distinguished primarily by the histopathologic patterns on surgical lung biopsy. Material and Methods: The study included 30 patients with a surgical lung biopsy performed in 10-year period at the Institute for Pulmonary Diseases of Vojvodina in Sremska Kamenica. Standard H E stain, special stains for conective tissue and smooth muscle, as well as immunohistochemistry in some cases were used. The patient s age, sex, clinical symptoms, surgical biopsy type and histological findings were analyzed. Results: Of the 30 patients who underwent surgical lung biopsy, an open lung biopsy according to Claassen was performed in 14 patients, in 12 biopsies biopsy according to Maassen was obtained, while in 4 patients material for histopathological analysis was taken by VATS (Video - Assisted Thoracoscopic Surgery). The most common biopsy site was upper lobe in 16 cases, then lingula in 10, middle lobe in 2, and lower lobe and lung base in 1 patient. By histopathological analysis, diagnosis of UIP in 8, PLCH in 7, sarcoidosis in 6, hypersensitivity pneumonitis in 3, NSIP in 2, LAM, LIP, DIP and ACIF in 1 patient. Conclusion: Diagnosis of ILD is based on history, physical examination, high-resolution CT imaging, pulmonary function tests, and lung biopsy which presents golden standard in diagnostic approach. Key words: ILD, diagnosis, pathohistology 47

48 POSTER SESIJA P12 Invazivna plućna aspergiloza Aleksandra Lovrenski 1, Anika Trudić 1, Dragana Tegeltija 1, Golub Samardžija 2, Dejan Vuckovic 1, Živka Eri 1 1 Institut za plućne bolesti Vojvodine, Sremska Kamenica, Srbija 2 Institut za kardiovaskularne bolesti Vojvodine, Sremska Kamenica, Srbija Cilj: Analiza dva slučaja IPA sa naglaskom na radiološki i patohistološki nalaz ovog entiteta. Uvod: Gljvice iz roda Aspergillus mogu da izazovu čitav spektar plućnih bolesti u zavisnosti od stanja imuniteta i postojećih plućnih oboljenja. Invazivna plućna aspergiloza (IPA) je retka, teška forma ć mikoze gde dolazi do pojave granulomatozne upale sa razvojem nekroze i fokusa supuracije, kao i invazijom hifa u plućni parenhim i u krvne sudove i proširenja bolesti van pluća. Materijal i metode: U petogodišnjem periodu na Institutu za plućne bolesti Vojvodine dijagnostikovana su dva slučaja IPA. Materijal za patohistološku analizu, dobijen u jednog pacijenta hirurškim putem, a u drugog postmortem na autopsiji, obojen je standardnim HE bojenjem, kao i specijalnim metodama za dokazivanje gljivica: PAS i Grocott. Rezultati: Pacijenti su bili starosti 67 i 48 godina i oboje su lečeni zbog akutne limfoblastne leukemije. Na IPBV su primljenišu respiratornoj insuficijenciji i teškoj neutropeniji sa ški postavljenom dijagnozom IPA na osnovu nalaza HRCT-a na kome se opisivao halo sign. Ovaj znak histološki odgovara fokusima nekroze parenhima pluća koji su okruženi zonom krvarenja. Pored ovih fokusa nekroze, u zidu i lumenima krvnih sudova nađene su i brojne septirane hife gljivica koje su se dihotomno granale pod uglom od 45. Zaključak: Iako patohistološka dijagnostika predstavlja jedini način za postavljanje definitivne dijagnoze IPA, s obzirom na invazivnost tehnika dobijanja materijala za analizu, dijagnoza se sa velikom sigurnošću može postaviti HRCT-om na osnovu nalaza halo sign. Ključne reči: IPA, halo-sign, HRCT Invasive pulmonary aspergillosis Aleksandra Lovrenski 1, Anika Trudic 1,Dragana Tegeltija 1, Golub Samardžija 2, Dejan Vuckovic 1, Zivka Eri 1 1 Institute for Pulmonary Diseases of Vojvodina, Sremska Kamenica, Serbia 2 Institute for Cardiovascular Diseases of Vojvodina, Sremska Kamenica, Serbia Aim: Analysis of two cases of IPA with an emphasis on the radiological and pathohistological findings of this entity. Introduction: Aspergillus spp. can cause a wide range of lung diseases, depending on the current state of immunity and the existing pulmonary diseases. Invasive pulmonary aspergillosis (IPA) is severe form of pulmonary mycosis, with the appearance of granulomatous inflammation with the development of necrosis and suppuration, as well as the invasion of hyphae into pulmonary parenchyma and the blood vessels and spreading the disease out of the lungs. Material and Methods: In the five-year period, two cases of IPA were diagnosed at the Institute of Pulmonary Diseases of Vojvodina. Material for pathohistological analysis, obtained by surgical method and on autopsy, was stained with standard H E staining, as well as with special staining methods: PAS and Grocott. Results: Patients were 67 and 48 years old and both were treated for acute lymphoblastic leukemia. They were admitted to our hospital in respiratory insufficiency and severe neutropenia with a radiologically diagnosed IPA based on HRCT finding of halo sign. This sign pathohistologically corresponds to foci of necrosis of lung parenchyma surrounded with the zone of hemorrhage. In addition to these foci of necrosis, in the wall and lumen of blood vessels, numerous septate hyphae with dichotomous branching at 45 were found. Conclusion: Although the pathohistological diagnosis is golden standard for diagnosis of IPA, given the invasiveness of the techniques for obtaining material for analysis, diagnosis can be made based on HRCT finding of halo sign. Key words: IPA, halo-sign, HRCT 48

49 POSTER SESIJA P13 Karcinosarkom pluća: prikaz slučaja Tanja Nenezić, Filip Vukmirović, Ljiljana Vučković, Tatjana Ćulafić, Mileta Golobović, Janja Raonić, Jelena Vučinić, Centar za patologiju,klinicki centar Crne Gore, Podgorica, Crna Gora Cilj: Značaj patohistološke analize operativnog materijala i imunofenotipa tumora u diferencijalnoj dijagnostici sarkomatoidnih karcinoma i karcinosarkoma rijetkih malignih neoplazmi pluća. Uvod: Karcinosarkom pluća, bifazični tumor, građen od nesitnoćelijskog karcinoma i sarkomatoidne heterogene komponente je rijetka neoplazma i čini manje od 1% svih malignih tumora pluća. Prikaz slučaja: Muškarac starosti 64 godine, javio se ljekaru zbog povišene temerature u trajanju od dva mjeseca. CT toraksa je pokazao znake infiltracije pluća, desno uz hilus i medijastinalnu limfadenopatiju, te su urađjene bronhoskopija i biopsija suspektne promjene patohistolški nalaz je bio Carcinoma squamosum invasivum. Usledila je lobektomija gornjeg režnja desnog plućnog krila i medijastinalna limfadenektomija. Makroskopskim pregledom reseciranog režnja, na 5 mm od resekcionog ruba bronha, nađeno je tumorsko tkivo promjera 22x7x5 mm, bjeličaste boje koje infiltrije zid lobarnog bronha. Histološkom analizom utvrđeno je da je tumorsko tkivo dijelom građeno od atipičnih pločastih epitelnih ćelija, krupnijih, mitotski aktivnih jedara, sa fokusima orožavanja (karcinomska komponenta), a dijelom od atipičnih ovalnih i vretenastih ćelija, hiperhromatičnih, umjereno pleomorfnih jedara, višeg mitotskog indeksa (sarkomska komponenta). Limfni čvorovi bili su bez elemenata tumorskog tkiva. Rezultati imunohistohemijske analize tumorskog tkiva: Cytokeratin - pozitivan u karcinomskoj komponenti, Vimentin - pozitivan u sarkomskoj komponenti, Actin, Desmin i S100 - negativni. Na osnovu morfoloških osobina i rezultata imunohistohemijske analize tumorskog tkiva postavljena je definitivna patohistološka dijagnoza karcinosarkom pluća. Zaključak: Za postavljenje decidirane patohistološke dijagnoze u slučajevima bifazičnih tumora, neophodan je patohistološki pregled operativnog materijala, a morfološku procjenu potrebno je dopuniti imunohistohemijom analizom. Ključne reči: karcinosarkom, pluća, rijetke neoplazme Lung carcinosarcoma: a case report Tanja Nenezic, Filip Vukmirovic, Ljiljana Vuckovic, Tatjana Culafic, Mileta Golubovic, Janja Raonic, Jelena Vucinic Department of Pathology, Clinical Center of Montenegro,Podgorica, Montenegro Aim: The significance of pathohistological analysis of operative material and tumor immunophenotype in differential diagnosis of sarcomatoid carcinoma and carcinosarcoma rare malignant lung neoplasms. Introduction: Lung carcinosarcoma, biphasic tumor, composed of non-small caracinomatous and sarcomatous heterogeneous components, is a rare neoplasm and represents less than 1% of all malignant lung tumors. Case report: A 64-year old man reported to physician complainig of fever that lasted for two months. Chest CT showed signs of right lung infiltration, close to the hilus and mediastinal lymphadenopathy. After bronchoscopy and biopsy of the suspected changes pathohistological finding was: carcinoma squamosum invasivum. Lobectomy of upper right lobe and mediastinal lymphadenectomy were performed. On gross examination, distanced 5 mm from the resection margin, withish tumor (22x7x5mm) infiltrating the wall of the lobar bronch was found. Histological analysis found that tumor tissue was partly consisted of atypical epithelial cells, with larger, mitotically active nuclei with focuses of keratinization and partialy of atypical oval and spindle cells,with hyperchromatic, pleomorphic nuclei, with high mitotic index. Lymph nodes were negative for tumor tissue. Results of immunohistochemical tumor tissue analysis: Cytokeratin - positive in carcinomatous component, Vimentin - positive in sarcomatous component, Actin, Desmin and S100 - negative. According to the results of morphological and immunohistochemical analysis of the tumor tissue lung carcinomsarcoma was diagnosed. Conclusion: For establishing definitive pathohistological diagnosis in biphasic tumor cases, a pathohistological examination of operative material is necessary, and morphological assessment should be suported by immunohistochemical analysis. Key words: carcinosarcoma, lung, rare neoplasm 49

50 POSTER SESIJA P14 Analiza imunoekspresije koneksina-43 kod karcinoma pluća Ivana Savić 1, Petar Milovanović 2 1 Institut za patologiju, Medicinski fakultet Univerzitet u Beogradu, Srbija 2 Institut za anatomiju, Medicinski fakultet Univerzitet u Beogradu, Srbija Cilj: Ispitati imunohistohemijsku ekspresiju i lokalizaciju koneksina-43 kod primarnog karcinoma pluća i njegovih metastaza. Uvod: Koneksini su transmembranski proteini koji učestvuju u izgradnji poroznih veza koje omogucavaju meducelijsku komunikaciju. Znacaj ovih veza i koneksina u karcinomima pluća nisu dovoljno jasni. Materijal i metode: Analizirali smo uzorke obdukovanih sa primarnim i metastatskim karcinomima pluća na Institutu za patologiju Medicinskog fakulteta u Beogradu. Ukupno je bilo 11 primarnih karcinoma pluća, 7 metastaza karcinoma pluća u limfnim nodusima i 12 hematogenih metastaza. Prosečna starost obdukovanih bila je 68 ±10 godina. Uradili smo imunohistohemijsko bojenje na koneksin-43 (Cx43). Mereni su stepen ekspresije (procenat pozitivnih ćelija i intenzitet bojenja) i lokalizacija koneksina-43 u primarnom tumoru i u limfogenim i hematogenim metastazama. Rezultati: Rezultati ove studije su pokazali da limfogene i hematogene metastaze karcinoma pluća jače eksprimiraju koneksin-43 nego sam primarni tumor. Za razliku od 9% primarnih karcinoma, 28% limfogenih metastaza i 50% hematogenih metastaza su imali ekspresiju koneksina u više od 50% tumorskih ćelija (p=0.11). Intenzitet ekspresije koneksina-43 je bio statistički manji kod primarnog karcinoma pluća nego kod svih metastaza zajedno (p=0.04). Ekspresija ovog markera se razlikovala medu histološkim tipovima, gde je sitnoćelijski karcinom retko ispoljavao koneksin, dok je skvamoznišuglavnom bio pozitivan na Cx43. Dominantna lokalizacija ekspresije bila je kombinovana citoplazmatsko-membranska. Zaključak: Rezultati studije pokazaju da karcinomi pluća ispoljavaju koneksin-43, uglavnom i u citoplazmi i na ćelijskoj membrani. Potrebna su dalja istraživanja na većem uzorku da bi se ustanovilo da li se koneksin-43 mo e koristiti kao prognostički biomarker u karcinomima pluća. Ključne reči: koneksin-43, karcinom pluća, metastaze, imunohistohemija Analysis of immunohistochemical expression of Connexin-43 in lung carcinoma Ivana Savic 1, Petar Milovanovic 2 1 Institute of Pathology, Medical Faculty University of Belgrade, Serbia 2 Institute of Anatomy, Medical Faculty University of Belgrade Serbia Aim: To investigate immunohistochemical expression and the localization of connexin-43 (Cx-43) in primary lung cancer and its metastases. Introduction: Connexins are transmembrane proteins forming gap junctions that allow intercellular communication. Significance of gap junctions and connexins in lung cancer are not clear enough. Material and Methods: We analyzed autopsy samples of primary and metastatic lung carcinoma from Institute of Pathology in Belgrade. There were 11 primary lung carcinomas, 7 lung cancer metastases in lymph nodes, and 12 haematogenic metastases. We performed immunohistochemical staining for connexin-43 (Cx43) and measured expression (percentage of positive cells and intensity of staining) and localization of Cx43 in primary tumor and its metastases. Results: Lymphatic and hematogenous metastases of lung cancer showed a stronger expression of connexin-43 than primary tumor itself. Unlike 9% of primary carcinoma, 28% of lymphatic metastases and 50% of hematogenous metastases had expression of connexins in more than 50% of tumor cells (p=0.11). The intensity of connexin-43 expression was statistically significantly less in primary lung cancer than in all the metastases together(p=0.04). The expression of this marker was different in different histological types, where small cell carcinoma rarely expressed connexin, while the squamous carcinoma was mostly positive to immunohistochemical staining on Cx43. Dominant localization of expression was the combined cytoplasmic-membranous. Conclusion: Our results showed that lung cancer expresses connexin-43 mostly in cytoplasm as well as on the cell membrane. Further research on a larger sample is required to establish whether Cx-43 could be used as a prognostic biomarker in lung cancer. Key words: connexin-43,lung cancer, metastases, immunohistochemistry 50

51 POSTER SESIJA P15 Pneumotoraks i potkožni emfizem kao prva manifestacija milijarne tuberkuloze Vladimir Zečev 1, Dragana Tegeltija 2, Tijana Vasiljević 3, Bojan Radovanović 3, Živka Eri 2 1 Opšta bolnica Sombor, Sombor, Srbija 2 Univerzitet u Novom Sadu, Medicinski fakultet Novi Sad, Novi Sad, Srbija, Institut za plucne bolesti Vojvodine, Sremska Kamenica, Srbija 3 Univerzitet u Novom Sadu, Medicinski fakultet Novi Sad, Novi Sad, Srbija, Institut za onkologiju Vojvodine, Sremska Kamenica, Srbija Cilj: Prikazujemo slučaj bolesnice sa pneumotoraksom i potkožnim emfizemom kao prvom manifestacijom milijarne tuberkuloze. Uvod: Milijarna tuberkuloza nastaje kao posledica hematogene diseminacije Mycobacterium tuberculosis kod bolesnika koji imaju slab odbrambeni mehanizam. Pneumotoraks i potkožni emfizem su moguće komplikacije milijarne tuberkuloze. Prikaz slučaja: Žena stara 64 godine javila se u regionalnu ustanovu zbog otežanog disanja. Na radiogramu grudnog koša je uočen pneumotoraks levo i postavljen levi torakalni dren. Potkožni emfizem i globalna respiratorna insuficijencija su se javili sat vremena kasnije nakon čega je bolesnica premeštena u našu ustanovu. Na prijemu je bila u lošem opštem stanju, intubirana, hemodinamski nestabilna, markeri inflamacije su bili povišenišuz prisutan elektrolitski disbalans i tešku anemiju. Na radiogramu grudnog koša evidentiran je: pneumotoraks levo, pneumonija desno i generalizovani subkutani emfizem te je plasiran i toraklani dren. Na intenzivnu terapiju došlo je do poboljšanja te je bolensica ekstubirana. Progresija respiratorne insuficijencije i letalni ishod su nastupili drugog dana od prijema. Uradena je obdukcija. Makroskopskim pregledom i patohistološkom analizom uzoraka uzetih sa tela pokojnice nađen je: masivni potkožni emfizem u grudnom košu, dobro plasiran torakalni dren, obostrani pleuralni izliv, obostrane akutne tuberkulozne kaverne u plućima i nekrotizirajuci granulomi u: plucima, jetri, slezini i laringsu koji su doveli do asfiksije i letalnog ishoda. Zaključak: Kod loše uhranjenih bolesnika sa razvojem pneumotoraksa, potkožnog emfizema i teškim respiratornim poremećajem treba posumnjati na tuberkulozu. Ključne reči: milijarna tuberkuloza, pneumotoraks Pneumotorax and subcutaneus emphysema as the first manifestation of miliary tuberculosis Vladimir Zecev 1, Dragana Tegeltija 2, Tijana Vasiljevic 3, Bojan Radovanovic 3, Zivka Eri 2 1 General Hospital Sombor, Sombor, Serbia 2 University of Novi Sad, Faculty of Medicine Novi Sad, Novi Sad, Serbia, Institute for Pulmonary Diseases of Vojvodina, Sremska Kamenica, Serbia 3 University of Novi Sad, Faculty of Medicine Novi Sad, Novi Sad, Serbia, Institute for Oncology of Vojvodina, Sremska Kamenica, Serbia Aim: We present a case of a patient with pneumothorax and subcutaneous emphysema as the first manifestation of miliary tuberculosis. Introduction: Miliary tuberculosis is the result of hematogenous dissemination of Mycobacterium tuberculosis in patients with weak immuno-defensive mechanisms. Pneumothorax and subcutaneous emphysema are possible complications of miliary tuberculosis. Case report: A woman aged 64 years old reported to the regional institution because of breathing difficulties. On the radiograph of the chest, pneumothorax was observed left, and the left thoracic drain was placed. Subcutaneous emphysema and global respiratory insufficiency were reported an hour later after which the patient was transferred to our facility. At the admission the patient was in poor general condition, intubated, hemodynamically unstable, markers of inflammation were elevated with the presence of electrolyte imbalance and severe anemia. On the chest radiogram, there was recorded: pneumothorax left, pneumonia right and generalized subcutaneous emphysema, and thoracal drain that was placed. Intensive therapy had improved the condition of the patient, after which she was extubated. Progression of respiratory insufficiency and lethal outcome occurred on the second day of admission. An autopsy was performed. A macroscopic examination and pathohistological analysis found: massive subcutaneous emphysema in the chest, well-placed thoracal drain, bilateral pleural effusion, bilateral acute tuberculous caverns in the lungs and necrotizing granulomas in: the lungs, liver, spleen and larynx which have led to asphyxiation and aviation outcome. Conclusion: In poorly-fed patients with the development of pneumothorax, subcutaneous emphysema and severe respiratory disorders, it is necessary to suspect tuberculosis. Key words: miliary tbureculosis, pneumothorax 51

52 POSTER SESIJA P16 Prisustvo mutacija EGFR gena i kvalitet uzoraka karcinoma pluća testiranih u Institut za patologiju Medicinskog fakulteta u Beogradu Sanja Ćirović 1, Sofija Glumac 2, Nevena Pandrc 1, Zorica Tojaga 1, Ivan Zaletel 3, Jovan Jevtić 2, Violeta Mihailović Vučinić 4, Natalija Samardžić 4, Sanja Radojevic Škodric 2, Martina Bosić 1 1 Laboratorija za molekularnu patologiju, Institut za patologiju Prof. Dr Đorde Joannovic, Medicinski fakultet, Univerzitet u Beogradu, Beograd, Srbija 2 Institut za patologiju Prof. Dr Đorde Joannovic, Medicinski fakultet, Univerzitet u Beogradu, Beograd, Srbija 3 Institut za histologiju i embriologiju Aleksandar Đ. Kostic, Medicinski fakultet, Univerzitet u Beogradu, Beograd, Srbija 4 Klinika za pulmologiju, Klinicki centar Srbije, Beograd, Srbija, Medicinski fakultet, Univerzitet u Beogradu, Beograd, Srbija Cilj: Ispitati adekvatnost poslatih uzoraka karcinoma pluća, zastupljenost i tip mutacija EGFR gena i njihovu korelaciju sa kliničkim karakteristikama pacijenata (pol, starost, pušački status i staž, klinički stadijum). Uvod: Mutacije receptora za epidermalni faktor rasta (engl. Epidermal Growth Factor Receptor, EGFR) imaju ulogu u nastanku karcinoma pluća i češće su kod žena i nepušaća. Terapija karcinoma pluća ciljanom terapijom tirozin kinaznim inhibitorima zahteva prvobitno ispitivanje mutacija EGFR gena. Uspešnost testiranja zavisi od kvaliteta ispitivanih uzoraka, kao i vrste primenjene metode. Materijal i metode: Pregledani su izveštaji real-time PCR analiza mutacija EGFR gena u karcinomima pluća izvršenih u Laboratoriji za molekularnu patologiju, Instituta za patologiju Medicinskog fakulteta u Beogradu od juna do februara Prisustvo mutacija je korelirano sa kliničkim karakteristikama pacijenata. Rezultati: Na testiranje je upućen 341 uzorak, a 40 (11,7%) je bilo neadekvatno usled niskog procenta tumorskih ćelija (<5%). Detektovana su tri tipa mutacija u ukupno 24 (8%) slučaja: L858R u 12 (50%) uzoraka, delecije egzona 19 u 10 (41,7%) uzoraka i G719A/C/S u dva slučaja (8,3%). Mutacije su bile češće kod žena (13,7%), nego kod muškaraca (4,3%) (p=0,004). Pacijenti sa mutacijama su bili stariji (67,6ą9,4 godina), nego pacijenti bez mutacija (62,3ą8,8 godina) (p=0,003). Pozitivna anamneza o pušenju, dužina pušačkog staža i stadijum bolesti nisu bili povezani sa prisustvom mutacija. Mutacije su detektovane samo u adenokarcinomima. Zaključak: Naši rezultati ukazuju da su mutacije EGFR relativno retke kod testiranih pacijenata, ali su češće kod žena i starijih pacijenata sa adenokarcinomom pluća. Ključne reči: Adenokarcinom pluća, Skvamocelularni karcinom, EGFR, mutacije, Tirozin kinaza EGFR mutations in lung carcinomas and quality of samples tested at Institute of Pathology, School of Medicine in Belgrade Sanja Cirovic 1, Sofija Glumac 2, Nevena Pandrc 1, Zorica Tojaga 1, Ivan Zaletel 3, Jovan Jevtic 2, Violeta Mihailovic Vucinic 4, Natalija Samardzic 4, Sanja Radojevic Skodric 2, Martina Bosic 1 1 Laboratory for Molecular Pathology, Institute of Pathology Prof. Dr Djordje Joannovic, School of Medicine, University of Belgrade, Belgrade, Serbia 2 Institute of Pathology Prof. Dr Djordje Joannovic, School of Medicine, University of Belgrade, Belgrade, Serbia 3 3 Institute of Histology and Embriology Aleksandar Dj. Kostic, School of Medicine, University of Belgrade, Belgrade, Serbia 4 Klinika za pulmologiju, Klinicki centar Srbije, Beograd, Srbija, Medicinski fakultet, Univerzitet u Beogradu, Beograd, Srbija Aim: To examine the quality of tested lung carcinoma samples, frequency and type of EGFR mutations, and their correlation with patients clinical characteristics (gender, age, smoking habits, clinical stage). Introduction: Mutations in Epidermal Growth Factor Receptor (EGFR) have a role in lung carcinoma development and they are more prevalent in women and non-smokers. Evaluation of EGFR mutations in lung carcinomas in mandatory for targeted therapy with tyrosine kinase inhibitors. Test performance depends on the quality of tested samples and a test type. Material and Methods: We evaluated reports of EGFR mutation real-time PCR analyses in lung carcinoma samples performed from June 2017 till February Presence of mutations was correlated with clinical characteristics of lung carcinoma patients. Results: A total of 341 samples was received for testing, among which 40 (11.7%) was unsuitable for analysis due to a low tumor cell content (<5%). Three types of mutations were detected in a total of 24 (8%) cases: L858R in 12 (50%) cases, exon 19 deletion in 10 (41.7%) cases, and G719A/C/S in two cases (8.3%). Mutations were more prevalent in women (13.7%) then in men (4.3%) (p=0.004). Patients with EGFR mutated tumors were older (67,6ą9,4 years), compared to those with non-mutated tumors (62,3ą8,8 years) (p=0,003). Smoking habits and clinical stage were not associated with mutation status in lung carcinomas. Mutations were detected only in adenocarcinomas. Conclusion: Our results suggest the low frequency of EGFR mutations in tested patients, but they are more prevalent in women and older patients. Key words: Lung adenocarcinoma, Squamous cell carcinoma, EGFR, mutation, Tyrosine kinase 52

53 POSTER SESIJA P17 Prognostički značaj ekspresije Ezh2 u superficijalnom urotelnom karcinomu mokraćne bešike Slavica Stojnev 1, Miljan Krstić 1,2, Ana Risticć-Petrović 1, Irena Conić 3, Ana Ristić 1, Ljubinka Janković Veličković 1,2 1 Medicinski fakultet, Univerzitet u Nišu, Niš, Srbija, 2 Centar za patologiju i patološku anatomiju, Klinički centar Niš, Niš, Srbija 3 Klinika za onkologiju, Klinicki centar Niš, Niš, Srbija 4 Elbe-Elster Klinikum, Hercberg, Nemačka Cilj: Cilj ovog istraživanja je analiza profila ekspresije Ezh2 u superficijalnom urotelnom karcinomu mokraćne bešike, ispitivanje korelacije Ezh2 sa klinicko-patološkim parametrima i određivanje značaja ekspresije Ezh2 za prognozu bolesti. Uvod: Superficijalni urotelni karcinom mokraćne bešike, bez invazije mišićnog sloja zida, odlikuje se čestom pojavom recidiva i predstavljaja značajno opterećenje za zdravstveni sistem. Ezh2 je epigenetski regulator koji igra važnu ulogu u urotelnoj onkogenezi. Klinička ispitivanja lekova koji blokiraju aktivnost Ezh2 u lecenju solidnih neoplazmi već daju ohrabrujuće rezultate. Materijali i metode: Uzorci tumora 410 pacijenata sa superficijalnim karcinomom mokraćne bešike (172 patološkog stadijuma pta i 238 pt1 tumora), dobijenih transuretralnom resekcijom, inkorporirani su u tkivne mikroareje i analizirani imunohistohemijski na ekspresiju Ezh2. Ispitivanje korelacije sa kliničko-patološkim parametrima urađeno je u programu za statisticku obradu podataka SPSS Rezultati: Visoka nuklearna ekspresija Ezh2 zabeležena je u 33.4% tumora, sa značajno većom učestalošću kod pt1 (46.6%) u odnosu na pta tumore (15.1%) (p<0.001). Ezh2 ekspresija bila je udružena sa visokim histološkim gradusom (p<0.001), prisustvom carcinoma in situ (p<0.001) i kancer-specifičnim mortalitetom (p<0.001). U Kaplan-Majerovoj analizi preživljavanja visoka ekspresija Ezh2 bila je značajno povezana sa lošijom prognozom i kraćim preživljavanjem pacijenata (p<0.001). Nije nađena značajna korelacija sa pojavom rekurentne bolesti niti vremenom do pojave recidiva (p<0.05). Zaključak: Imunohistohemijska ekspresija transkripcionog represora Ezh2 u superficijalnom urotelnom karcinomu mokraćne bešike ukazuje na agresivno ponašanje tumora i lošiju prognozu. Ezh2 bi se mogao koristiti kao prognosticki marker u selekciji pacijenata koji zahtevaju intenzivnije kliničko sagledavanje i kao potencijalna meta antikancerske terapije. Ključne reči: urotelni karcinom, Ezh2, imunohistohemija, prognoza Prognostic significance of Ezh2 expression in superficial urothelial bladder cancer Slavica Stojnev 1, Miljan Krstic 1,2, Ana Ristic-Petrovic 1, Irena Conic 2, Ana Ristic 3, Ljubinka Jankovic Velickovic 1,2 1 Faculty of Medicine, University of Nis, Nis, Serbia 2 Center for Pathology, Clinical Center Nis, Nis, Serbia 1 Faculty of Medicine, University of Nis, Nis, Serbia 2 Center for Pathology, Clinical Center Nis, Nis, Serbia 3 Elbe-Elster Klinikum, Herzberg, Germany Aim: The aim of this research is to analyze the profile of Ezh2 expression in superficial urothelial bladder cancer, to investigate its correlation with clinicopathological parameters, as well as to determine the prognostic significance of Ezh2. Introduction: Superficial urothelial bladder cancer, without invasion of muscle layer, is associated with frequent recurrence, and represents significant burden for health care system. Ezh2 is epigenetic regulator with a major role in urothelial oncogenesis. Clinical investigations of Ezh2 inhibitors in treatment of solid cancers have already given encouraging results. Materials and Methods: Tumor samples from 410 patients with superficial bladder cancer (172 pta, 238 pt1), obtained by transurethral resection, were incorporated in tissue microarrays, and analyzed immunohistochemically to Ezh2 expression. Correlation analysis with clinicopathological parameters was performed using SPSS Results: High nuclear expression was found in 33.4% tumors, and it was significantly more frequent in pt1 (46.6%), compared to pta tumors (15.1%) (p<0.001). Ezh2 expression was associated with high histologic grade, presence of carcinoma in situ, and cancer specific death (p<0.001, respectively). In Kaplan-Mayer survival analysis high Ezh2 expression was significantly associated with poor prognosis and shorter patients survival (p<0.001). There was no significant correlation between Ezh2 and recurrence of the disease, and recurrence free interval (p<0.05). Conclusion: Immunohistochemical expression of transcription repressor Ezh2 in superficial urothelial bladder cancer indicates aggressive behavior of the tumor, and poor prognosis. Ezh2 could be used as pronostic marker in selection of the patients that might require more intense clinical treatment, and as potential target of anticancer therapy. Key words: urothelial carcinoma, Ezh2, immunohistochemistry, prognosis 53

54 POSTER SESIJA P18 Lipom rektuma inkarceriran u anusu kao uzrok obilne rektoragije Katarina Erić 1, Marko Miladinov 1, Milena Ćosić Micev 1, Zoran Krivokapić 2 1 Klinički centar Srbije, Beograd, Srbija 2 Klinički Centar Srbije, Beograd, Medcinski fakultet, Univerzitet u Beogradu Cilj: Prikaz slučaja za retku komplikaciju rektoragije izazvanu lipomom distalnog rektuma inkarceriranim u anusu. Uvod: Kolorektalni lipomi su retki tumori koji se najčešće dijagnostikuju u desnom kolonu slučajno tokom kolonoskopije. Kada su lipomi veći od 2 cm, tada prouzrokuju bolove, krvarenje,opstrukciju, inkaceraciju, torziju. Prikaz slučaja: Prikazujemo slučaj muškarca od 50 godina koji dolazi u hitnu prijemnu ambulantu sa obilnom rektoragijom i krvlju prisutnu na vešu i butinama. Inspekcijom perianalne regije se konstatuje prolaps mekane strukture kroz anus koja se reponira u anus. Zatim je uradena anoproktoskopija, kojom se utvrduje da se radi o polipu rektuma, iako je izgledalo da se radi o inkarceriranom hemoroidu, naročito zbog činjenice da pacijent više godina boluje od hemoroidalne bolesti sa čestim krvarenjem, koju leči konzervativno. Utvrđeno je da nije bilo prolapsa hemoroida, ni krvarenja iz njih. Zatim je učinjena fleksibilna rektoskopija na nepripremljenom crevu i tom prilikom verifikovana polipoidna promena, na peteljci u distalnom rektumu na 3,5 cm od zupčaste linije. Promena je elektroresekovana i poslata na patohistološki pregled. Pacijent je dobro podneo intervenciju. Resekcioni materijal čini sesilni pseudopolipoidni tumor, erodirane mukoze promera 28x25x24 mm. Histopatologija je pokazala submukozni lipom rektuma.mukoza je erodirana i praćena fokusima mikrokrvarenja. Unutar lipoma se uočavaju retki mikrofokusi masne nekroze. Zaključak: Lipom rektuma je veoma redak entitiet i dijagnostikuje se najčešće, slučajno kolonoskopski. Izuzetno retko prouzrokuje krvarenje, što mi prikazujemo u ovom radu. Ključne reči: lipom, rektoragija, rektum Rectal lipoma incarcerated in the anus as the cause of abudant rectorrhagia Katarina Eric 1, Marko Miladinov 1, Milena Cosic Micev 1, Zoran Krivokapic 2 1 Clinical Center of Serbia, Belgrade, Serbia 2 Clinical Centar of Serbia,Faculty of Medicine, University of Belgrade, Serbia Aim: Case report for rare complication rectorrhagia induced by rectal lipoma incarcerated in the anus. Introduction: Colorectal lipomas are rare tumors that are commonly diagnosed in the right colon, accidentaly during colonoscopy. When the lipomas are larger then 2 cm, they cause pain, bleeding, obstruction, incarceration and torsion. Material and Methods: We present the case of 50-year old man who comes to emergency ambulance with abundant rectorrhagia and blood presented on underwear and thighs. It is noted prolapse of the soft structure through the anus which is reponated into the anus. Anoproctoscopy was performed, which determines that it is polyp of rectum, although it seemed to be incarcerated hemorrhoids, due to the fact that the patient has been suffering from hemorrhoids with bleeding for several years,which is treated conservatively. It was found that it was not hemorrhoids prolaps or bleeding from them. Flexibile rectoscopy was performed on the untreated gut. The polypoid structure on peduncle,was verified in the distal rectum,3,5 cm from the pectinate line. Polypoid formation was electroresected and sent for pathohistological examination. Results: The patient was well tolerated intervention. Resected specimen revealed sessile pseudopolypoid tumor,eroded mucosa, diameter 28x25x24 mm.histopathology revealed submucosal lipoma. Eroded mucosa is accompanied by focuses microbloods. Microcircuits of fatty necrosis are visible inside the lipoma. Conclusion: Lipom of the rectum is rare entity which is accidentaly diagnosed during colonoscopy. Extremly rare, lipom causes bleeding, which we present here. Key words: lipom, rectorrhagia, rectum 54

55 POSTER SESIJA P19 Retka lokalizacija alveolar soft part sarkoma: prikaz slučaja Radmila Janković, Jelena Sopta, Sanja Ćirovic, Martina Bosić, Jovan Jevtić, Ljubica Simić Institut za patologiju, Medicinski fakultet, Univerzitet u Beogradu, Beograd, Srbija Cilj: Prikazujemo slučaj retke lokalizacije alveolar soft part sarkoma u visceralnom organu. Uvod: Alveolar soft part sarkom (ASPS) je redak mezenhimalni tumor koji se javlja češće kod mladih pacijenata, sa predominacijom ženskog pola. Najčešće je lokalizovan u skeletnim mišićima donjih ekstremiteta. ASPS se retko može naći u viseralnim organima, obično javlja kao metastaza primarnog tumora skeletnih mišića. ASPS odlikuje tumor-specificna translokacija koja dovodi do fuzije TFE3 sa ASPL genom (poznatim i kao ASPSCR1). Prikaz slučaja: Žena starosti 47 godina je hospitalizovana zbog abdominalnog bola. Hitno je operisana zbog ileusa. Nađen je tumor ileuma zbog čega je crevo resecirano. Tumor je infiltrovao čitavu cirkumferenciju creva, dimenzija 70mm x 40mm, sa perforacijom. Histološki, tumor je bio građen do gnezda pleomorfnih ćelija odvojenih tankim fibrovaskularnim septama. Unutar gnezda je bio izražen gubitak ćelijske kohezije, što je karakterističan pseudoalveolarni obrazac. Imunohistohemijsko bojenje je bilo difuzno pozitivno za TFE3, fokalno pozitivno za CD34 i alfa-sma, dok su su bojenja za panck, DOG-1, CD117, S-100, HMB45 i Desmin bila negativna. Imunopozitivnost za Ki67 je bila prisutna u 20% tumorskih ćelija. Za FISH analizu je korišćena lokus specificna dual color break-apart TFE3 (3 and 5 ) proba kojom je dokazan rearanžman na TFE3 genu. Zaključak: Uprkos činjenici da je ASPS redak mezenhimalni tumor u visceralnim organima, mora se razmotriti kao moguća dijagnoza, posebno u slučajevima sa karakterističnom histološkom slikom i imunohistohemijskim profilom. Definitivna dijagnoza ASPS mora biti potvrdena FISH analizom. Ključne reči: alveolar soft part sarkom, FISH analiza, tumor ileuma A rare localization of alveolar soft part sarcoma: a case report Radmila Jankovic, Jelena Sopta, Sanja Cirovic, Martina Bosic, Jovan Jevtic, Ljubica Simic Institute of Pathology, Medical Faculty, University of Belgrade, Belgrade, Serbia Aim: We present the case of a rare localization of the alveolar soft part of the sarcoma in the visceral organ. Introduction: Alveolar soft part sarcoma (ASPS) is a rare mesenchymal tumor typically occurring in young patients, more frequently in females. Common localization of ASPS is skeletal musculature of lower extremities. ASPS in visceral organs usually represents a metastasis from the more common primary location in skeletal muscles. ASPS is characterized by a tumor-specific translocation which causes the fusion of the TEF3 with a ASPL gene (also known as ASPSCR1). Case report: Female 47 years old was admitted to hospital due to abdominal pain. Urgent surgery was performed due to ileus. Ileal tumor was detected intraoperatively as a cause of ileus. Tumor was infiltrated whole intestinal circumference, with dimension 70mm x 47cm and evident perforation. Histology showed well-defined nests of pleomorphic cells separated by delicate fibrovascular septae. Within described nests there is a prominent lack of cellular cohesion, representing for the distinctive pseudoalveolar pattern. Immunohistochemical stadies were diffusely positive for TFE3 and focally positive for CD34 and alpha-sma and negative for panck, DOG-1, CD117, S-100, HMB45, Desmin. Immunopositivity for Ki67 was present in 20% of tumor cells. FISH analysis was done using locus specific dual color break-apart TFE3 (3 and 5 ) probe and rearrangement in the TFE3 gene was confirmed. Conclusion: Despite the fact that ASPS is rare mesenchymal tumor in visceral organs it have to be considered as possible diagnosis especially in cases with typical histological features and immunohistochemical profile. Definitive diagnosis of ASPS must be confirmed by FISH analysis. Key words: alveolar soft part sarcoma, FISH analysis, ileal tumor P20 Collision Adenocarcinoma et small cell neuroendocrine carcinoma of the gallbladder: a case report Svetlana Kochmanovska Petreska 1, Liljana Spasevska 1, Boro Ilievski 1, Vladimir Stojkovski 2 1 Institute of Pathology, Faculty of medicine, University St. Cyril and Methodius, Skopje, Republic of Macedonia 2 Department of Pathology, General Hospital 8. September, Skopje, Republic of Macedonia 55

56 POSTER SESIJA Aim: To reported extremely rare case of collision adenocarcinomma et small cell neuroendocrine carcinomma of the gallbladder (SCNEC). Introduction: Collision cancers are malignancies in the same organ or anatomical site that comprises et least two different tumor components, with no mixed or transitional area between two component. Case report: 76 year old woman with abdominal pain, underwent ultrasonography evaluation which demonstrated cholelithiasis and gallbladder wall thickening. Cholecystectomy due to cholelithiasis was performed.the macroscopic analysis revealed 2,5cm sized round nodular lesions in the fundus of the gallbladder.formalin fixed, paraffin embedded tissues were stained with H.E. Selected samples were stained immunochistochemically with chromogranin, synaptophysin et CK7. Microscopicaly, the tumor was composed of two components. Dominant component is adenocarcinomma, composed of tubular glands lined predominantly by columnar cells with pseudostratified et ovoid or elongated nuclei.in the area close to this component there was neuroendocrine carcinomma that came in touch with the previous one, but didnt infiltrate it. Neuroendocrine carcinomma was composed of round or fusiform cells, arranged in sheets, nests and cords.tumor cells have round hyperchromatic nuclei with inconspicuous nucleoli. Neuroendocrine tumor cells were immunoreactive for chromogranin, synaptophysin. Epithelial cells were positive for CH7.The final pathologycal diagnosis was SCNEC. The tumor stage was II, T2, Nx, Mx. Conclusion: Prognosis for patient is poor.about percent of patients have disseminated disease at the time of the diagnoses.scnec appear to be highly responsive to chemotherapy as well as radiotherapy and survival time more than one year have been reported. Key words: Collision adenocarcinoma, neuroendocrine carcinoma, gallbladder P21 Retka lokalizacija gastrointestinalnog tumora dečijeg doba: prikaz slučaja Jovana Radaković, Jelena Sopta, Radmila Janković, Jovan Jevtić Institut za patologiju, Medicinski fakultet u Beogradu, Srbija Cilj: Prikazujemo redak slučaj gastrointestinalnog tumora kod dečaka. Uvod: Gastrointestinalni stromalni tumori (GIST) su mezenhimalni tumori koji se retko javljaju u pedijatrijskoj populaciji. Ovi tumori se najčešće javljaju u želucu, dok se veoma retko javljaju u jednjaku. U pedijatrijskoj populaciji se javljaju češće kod devojčica. Za razliku od adultnih, GIST-i u dečijem dobu češće pokazuju mutacije u PDGFRA receptorima ili tzv. wild-type mutacije. Prikaz slučaja: Dečak starosti 15 godina i 2 meseca sa simptomima otežanog gutanja i stenokardije u poslednjih šest meseci. Endoskopskim pregledom otkrivena je nodularna solidna lezija u distalnom delu torakalnog jednjaka, kasnije uklonjena hirurškim putem. Promena je bila dimenzija 35x25x20mm. Površina preseka je bila vrtložaste gradđe, beličasto žućkaste boje, sa sitnim poljima krvarenja. Histološ ka građa je bila dominanto vretenastoćelijska sa malom epiteloidnom komponentom, izraženog ćelijskog i nuklearnog pleomorfizma, retkim poljima nekroze i krvarenja, sa preko 18 mitoza na 50 polja velikog uveličanja i brojnim atipičnim mitotskim figurama. Imunohistohemijskom analizom je pokazan izostanak ekspresije CD117 i DOG-1, a pozitivnu ekspresiju PDGFRA. Tumor je pokazivao fokalnu ekspresiju alpha-sma i CD34. Zaključak: O gastrointestinalnim stromalnim tumorima dečijeg doba još uvek ne postoji dovoljno podataka. Iako su oni retki u dece, pri analizi mezenhimalnih neoplazmi uvek treba razmišljati i o mogućem GIST. Ključne reči: GIST, dečiji tumori, jednjak A rare localization of pediatric gastrointestinal stromal tumor - a case report Jovana Radakovic, Jelena Sopta, Radmila Jankovic, Jovan Jevtic Institute of Pathology, Faculty of Medicine, Belgrade, Serbia Aim: We present a rare case of gastrointestinal tumor in a boy. Introduction: Gastrointestinal stromal tumors (GISTs) represent rare mesenchymal tumors in pediatric population. Most of these tumors originate in the stomach and very rarely in the oesophagus. They are more frequent in young girls. As opposed to adult GISTs, those that occur in childhood show mutations in PDGFRA receptors or so called Wild type mutations. Case report: A fifteen years and 2 months old boy with symptoms of dysphagia and stenocardia for the last six months. Endoscopy showed nodular solid lesion at the distal part of the thoracal oesophagus, later surgically removed. Dimensions of the lession were 35x25x20mm with whitish- 56

57 POSTER SESIJA yellow cut surface and areas of hemorrhage. Histology showed predominant spindle cell pattern with minor epithelioid component, with pronounced cellular and nuclear pleomorphism, rare areas of necrosis and hemorrhage, with the mitotic count more than 18 per 50 high power fields and numerous atypical mitotic figures. Immunohistochemical studies were CD117 and DOG-1 negative, but positive for PDGFRA. Tumor expressed focal alpha-sma and CD34 positivity. Conclusion: Informations regarding pediatric gastrointestinal stromal tumors are still insufficient. Even though these tumors are rare in childhood, when analysing mesenchymal neoplasms potential GISTs should be considered. Key words: GIST, childhood tumors, oesophagus P22 Horistom želuca: Prikaz slučaja Aleksandra Ilić, Tanja Lakić, Mirjana Živojinov, Matilda Djolai Klinicki centar Vojvodine, Novi Sad, Srbija Univerzitet u Novom Sadu, Medicinski fakultet Cilj: Prikaz slučaja horistoma želuca. Uvod: Ektopični pankreas predstavlja prisustvo pankreatičnog tkiva van normalne lokalizacije i bez anatomske ili vaskularne povezanosti sa pankreasom. Najčešće se javlja u gornjem gastrointestinalnom traktu, pretežno u želucu. Češće se javlja kod muškaraca, u starosnoj grupi 30 do 50 godina. Prikaz slučaja: Pacijent muškog pola, starosti 30 godina, javlja se u bolnicu zbog epigastrične simptomatologije. Nakon kliničkih pretraga, urađena je ezofago-gastroduodenoskopija kojom je registrovan intramuralni čvor u predelu velike krivine želuca. Biopsijom je dobijena normalna želudacna sluznica te se posumnjalo na gastrointestinalni stromalni tumor (GIST). Nakon laparoskopske parcijalne gastrektomije materijal je poslat na patohistološku analizu. Makroskopskim pregledom identifikovano je nekoliko fragmenata sivo-ružičaste boje, obloženih svetlo ružičastom sluznicom. U najvećem opisanom fragmentu je uočen sivo-beličast čvor, iregularnog, ovalnog oblika, dimenzija 4x2,5x0,5cm, a na serijskim rezovima čvor žućkaste boje. Histološkim pregledom svi opisani fragmenti su bili sačinjeni od zida želuca sa sluznicom korpusnog tipa, dok je iregularni čvor bio sagraden od pankreatičnog tkiva smeštenog u podsluznici i mišićnom sloju želuca. Pankreatično tkivo se sastojalo od pravilnih acinusa i Langerhansovih ostrvaca sa fokalno dilatiranim izvodnim kanalima i mešovitim zapaljenskim infiltratom. U tkivu pankreasa nisu nađeni elementi displazije. Postavljena je dijagnoza ektopičnog tkiva pankreasa u zidu želuca Horistom želuca. Zaključak: Horistom je generalno retka pojava i najčešće slučajan nalaz. Bitno je da bude dijagnostikovan zbog ozbiljnih komplikacija koje se mogu javiti u zavisnosti koje je tkivo zastupljeno u organu, kao što su zapaljenje, krvarenje i maligna transformacija. Ključne reči: želudac, pankreatično tkivo, horistom Choristoma of the stomach: A case report Aleksandra Ilic, Tanja Lakic, Mirjana Zivojinov, Matilda Djolai Clinical Center of Vojvodina, Novi Sad, Serbia University of Novi Sad, Faculty of Medicine Aim: To present a case report of choristoma of the stomach. Introduction: Ectopic pancreas is defined as the presence of pancreatic tissue outside its normal location without anatomic or vascular connections with the pancreas. It mostly occurs in upper gastrointestinal tract, predominantly in the stomach. It s likely to occur in men, at the age of years. Case report: A thirty-year old male patient presented to the hospital for evaluation of epigastric symptoms. After clinical examinations, he underwent an esophago-gastroduodenoscopy which showed intramural tumor located along the greater curvature. The biopsy was taken which revealed normal gastric mucosa so it was suspected for gastrointestinal stromal tumor. The patient was submitted to laparoscopic partial gastrectomy and the material was received for pathohistological analysis. Macroscopically, there were several fragments, gray-pink coloured and lined with pink mucosa. In the largest fragment it was noticed irregular, oval gray-white node, measured 4x2.5x0.5cm. On serial cutting it was yellow. Histologically, described fragments revealed normal fundic mucosa and irregular node was consisted of pancreatic tissue localized in submucosa and lamina muscularis. It was formed of normal acini and Langerhans islets, with focally dilated pancreatic ducts and presence of mixed inflammatory infiltrate. Dysplasia wasn t found in the pancreatic tissue. The 57

58 POSTER SESIJA established diagnosis was Ectopic pancreatic tissue in stomach Choristoma of the stomach. Conclusion: Choristoma is rare condition and usually incidental finding important to be diagnosed because of the serious complications depending on which tissue is present in the organ, such as inflammation, bleeding and mailignant transformation. Key words: stomach, pancretic tissue, choristoma P23 Ektopično tkivo pankreasa u žučnoj kesi: prikaz slučaja Marija Milić Perović, Aleksandra PaunovićMarković, Nataša Šurdević, Marija Čubrilo, Jelena Kuzmanović, Jovan Juloski, Lidija Vučkovic Hardi KBC Zvezdara, Beograd, Srbija Cilj: Prikazujemo interesantan slučaja ektopičnog tkiva pankreasa u žučnoj kesi. Uvod: Ektopični ili heterotopični pankreas predstavlja tkivo pankreasa bez anatomskih i vaskularnih veza sa telom pankreasa. Prikaz slučaja: Prikaz retkog slučaja ektopicnog pankreasa u žucnoj kesi kod 38-godišnjeg pacijenta. Pacijent, je primljen na odeljenje hirurgije KBC Zvezdara, zbog prethodno zakazane laparaskopske operacije žucne kese. Godinu dana pre operacije, tokom rutinskog pregleda je urađen ultrazvuk abdomena koji je bio bez osobitosti sem prisustva kalkulusa u žucnoj kesi. Urađena je laparaskopska operacija žucne kese. Makroskopskim pregledom je utvrđeno da je žucna kesa dužine 9 cm, obima 3,5 cm, zid je debljine od 0,2 do 0,4 cm. Pri otvaranju žucne kese, u fundusu je primećen okrugli kalkulus, žuckaste boje, promera 0,6 cm. Sluznica je bila baršunasto zaravnjena. U regionu vrata žucne kese je uočen nodus promera 1, 5 cm koji je mikroskopski odgovarao dobro ograničenom heterotopičnom tkivu pankreasa, građenom od lobulusa egzokrinih acinusa i pojedinih duktusa. Langerhansova ostrvca su takode bila prisutna. Ostali isečci su pokazivali znake hroničnog holecistitisa. Zaključak: Ektopično tkivo pankreasa u žucnoj kesi je veoma redak entitet koji se uglavnom slučajno dijagnostikuje. Do sada je prijavljeno svega 30 slučajeva. Klinicki značaj ektopičnog pankreasa ostaje nerazjanjen i zahteva dalje istraživanje. Ključne reči: ektopija pankreasa, žučna kesa, holecistitis. Ectopic pancreatic tissue in a gallbladder: case report Marija Milic Perovic, Aleksandra Paunovic Markovic, Natasa Djurdjevic, Marija Cubrilo, Jelena Kuzmanovic, Jovan Juloski, Lidija Vuckovic Hardi KBC Zvezdara, Belgrade, Serbia Aim: We present an interesting case of pancreatic ectopic tissue in the gallbladder. Introduction: Ectopic or heterotopic pancreas is defined as the presence of pancreatic tissue outside the boundaries of the pancreas that show no anatomical or vascular connection with the main body of the pancreas. Case report: We present a rare case of ectopic pancreas found in a 38 year-old man s gallbladder. Male patient was admitted to the Surgical Department Clinical Hospital Center Zvezdara, as scheduled for an elective laparoscopic cholecystectomy. One year prior to the surgery he had had abdominal ultrasonography done during a routine hospital check up. Ultrasonographic examination of the whole abdomen had showed no abnormality, except for cholelithiasis. Laparoscopic cholecystectomy was done. On gross examination, the gallbladder measured 9 cm in length and 3.5 cm in circumference, with a wall thickness ranging from 0.2 to 0.4 cm. On cutting open, one yellowish round stone, measuring 0.6 cm in diameter, was noted in the fundus. The mucosa was velvety flattened. A nodule of 1,5 cm in diameter was seen in the neck region, which on microscopic examination, showed a well circumscribed rest of heterotopic pancreatic tissue, composed of lobules of exocrine pancreatic acini and an occasional duct. Islets of Langerhans were also present. Conclusion: Ectopic pancreatic tissue in a gallbladder is a very rare condition which is usually diagnosed incidentally. Up to the presents, only about 30 cases have been reported. The clinical significance of the ectopic pancreas remains unclear and it requires further exploration. Key words: ectopic pancreas, gallbladder, cholecystitis. 58

59 POSTER SESIJA P24 Ekspresija divergentnih endodermalnih linijskih markera u Yolk Sac tumoru primarne medijastinalne lokalizacije: prikaz slučaja Saša Ristić 1, Božidar Kovačević 1, Nataša Vesović 2,Dragan Živojinović 1, Vladimir Vasiljević 1, Jelena Džambas 1 1 Vojnomedicinska akademija, Institut za patologiju i sudsku medicinu, Beograd, Srbija 2 Vojnomedicinska akademija, Klinika za grudnu i kardijalnu hirurgiju,beograd,srbija Cilj: Patohistološka dijagnostika Yolc Sac tumora retke primarne medijastinalne lokalizacije. Uvod: Yolk sac tumori su maligni tumori germinativnih ćelija primitivne endodermalne diferencijacije gonada. U 1%-5% slučajeva lokalizovani su ekstragonadalno, pri čemu je medijastinalna najčešća i čini 50%-70% publikovanih kazuistika. Prikaz slučaja: Muškarac, star 30 godina, primljen je u Kliniku za grudnu hirurgiju u cilju dijagnostike i lečenja tumorske promene u medijastinumu, sa metastazama u plućima i jetri. U laboratorijskim analizama nađene su visoke vrednosti serumskog alfa-feto-proteina (AFP), kao i umerena elevacija beta-horionskog gonadotropina (ß-HCG). Nisu nađene patološke promene u testisima i retroperitoneumu. U cilju patohistološke analize učinjena je otvorena biopsija medijastinalne promene. Histološki, tumorsko tkivo pokazivalo je značajan stepen nekroze. Postojale su retikularne, mikrocistične i pseudopapilarne forme rasta neoplastičnih ćelija, okružene miksomatoznom stromom. U tumorskim ćelijama citoplazma je bila oskudna i vakuolizovana, uz naznačen polimorfizam i hiperhromaziju nukleusa. Imunohistohemijski (IMH), dobijena je pozitivna reakcija za panck, AFP, PLAP, ali i imunoreaktivnost za TTF-1 u oko 50% tumorskih ćelija, kao i fokalna reakcija za ß-HCG u retkim ćelijama multinuklearnog izgleda. Reakcije za D2-40, CD5, CK-7, CK-20, p63, CD117, CD30, napsin A i calretinin bile su negativne. Zaključak: Rezultati naše analize pokazali su ekspresiju divergentnih endodermalnih linijskih markera u Yolk Sac tumoru medijastinalne lokalizacije, posebno ispoljenu kroz TTF1 ekspresiju. Dijagnostika ovog tumora u malim biopsijama može biti teška i zahteva primenu široke paleta IMH markera u cilju bliže diferencijacije primarne lokalizacije tumora kao i primene odgovarajuće hemoterapije. Ključne reči: yolk-sac tumor, neoplazme medijastinuma, imunohistohemija. Expression of divergent endodermal linear markers in the yolk sac tumor of primary mediastinal localization: Case report Sasa Ristic 1, Bozidar Kovacevic 1, Natasa Vesovic 2, Dragan Zivojinovic 1, Vladimir Vasiljevic 1, Jelena Dzambas 1 1 Institute of Pathology and Forensic medicine, Military Medical Academy, Belgrade, Serbia 2 Clinic for Thoracic and Cardiac surgery, Military Medical Academy, Belgrade, Serbia Aim: Pathohistological diagnostics (PD) of the Yolc Sac tumor (YST) of primary mediastinal localization. Introduction: YST are malignant germ cell tumors of primitive endodermal gonadal differentiation. In 1% -5% of cases their localization is extragonadal, including mediastinal in 50% -70% published cases. Case report: A 30-year-old man was admitted to the Thoracic Surgery Clinic for diagnosis and treatment of mediastinal tumor with lungs and liver metastases. Laboratory analyzes revealed high elevations in serum alpha-fetoprotein (AFP), in addition moderate elevation of beta-chorionic gonadotropin (ß-HCG). No pathological changes in testis and retroperitoneum have been found. An open biopsy of the mediastinal change was made for PD. Histologically, tumor tissue showed a significant degree of necrosis. There were reticular, microcystic and pseudopapillary forms of neoplastic cell growth, surrounded by myxomatosis stroma. Tumor cells cytoplasm was scarce and vacuolated with high nuclear polymorphism and hyperchromasia. Positive immunohistochemical (IMH) reaction was obtained for panck, AFP, PLAP. Immunoreactivity for TTF-1 was found in about 50% of tumor cells, as well as the focal reaction for ß-HCG in rare multinuclear cells. Reactions for D2-40, CD5, CK-7, CK-20, p63, CD117, CD30, napsin A and calretinin were negative. Conclusion: The results of our analysis showed the expression of divergent endodermal linear markers in the mediastinal YST, especially TTF-1 expression. The diagnosis of YST in small biopsies can be difficult and requires using of a wide range of IMH markers in order to closer the differentiation of primary tumor localization and the application of appropriate chemotherapy Key words: yolk-sac tumor, neoplasm of mediastinum, immunohistochemistry 59

60 POSTER SESIJA P25 Zadesno smrtno trovanje kolhicinom iz biljke mrazovac (Colchicum autumnale): prikaz autopsijskog slučaja Ivan Aleksić 1, Milo Danilović 2, Jelena Džambas 1, Nadica Marinković 1 1 Vojnomedicinska akademija, Institut za patologiju i sudsku medicinu, Beograd, Srbija 2 Medicinski fakultet Vojnomedicinske akademije, Beograd, Srbija Cilj: Prikaz autopsijskog slučaja zadesnog smrtnog trovanja kolhicinom iz biljke mrazovac. Uvod: Mrazovac (Colchicum autumnale) je višegodišnja zeljasta biljka slična jestivoj biljci sremušu (Alium ursinum). Toksična supstanca u mrazovcu je alkaloid kolhicin. Trovanje kolhicinom je veoma opasno stanje, koje se može završiti smrtnim ishodom. Prikaz slučaja: Muškarac starosti 50 godina primljen je u bolnicu zbog sumnje na zadesno trovanje biljkom mrazovac. Pacijent je dan pre pojeo dve biljke misleći da su sremuš. Sedam sati nakon ingestije počele su tegobe-malaksalost, bolovi u abdomenu, mučnina, povraćanje i prolivaste stolice bez krvi sa kliničkom slikom gastroenterokolitisa, akutnom bubrežnom insuficijencijom, lezijom jetre i kardiorespiratornom insuficijencijom. Pacijent je zadesno intoksiciran alkaloidom kolhicinom sa smrtnim ishodom. Obdukcijom je makroskopski ustanovljeno: edem mozga, edem i kongestija pluća, srce mase 700 grama sa hipertrofijom leve i desne komore, fibroza miokarda, kongestija i steatoza jetre, kongestija slezine, fibroza pankreasa. Uzeti su isečci organa za patohistološku analizu i telesne tečnosti i delovi organa za toksikološko-hemijsku analizu.patohistološki nalaz:edem mozga, difuzna perivaskularna i intersticijalna fibroza miokarda, intersticijalno krvarenje u miokardu, kongestija i edem pluća, mikrovezikularna i makrovezikularna steatoza jetre i centrilobularna nekroza jetre, limfocitni zapaljenski infiltrat u portnim prostorima jetre, kongestija crvene pulpe slezine, kongestija i intersticijalno krvarenje u bubregu, koagulaciona nekroza proksimalnih tubula bubrega. Toksikološka analiza-kolhicin: krv-0,011 mg/l, urin-0,051 mg/l, jetra sa žučnom kesom-0,007 mg/kg, bubreg-0,008 mg/kg. Zaključak: Ingestija biljke mrazovac zbog toksičnog alkaloida kolhicina može dovesti do trovanja sa smrtnim ishodom. Na intoksikaciju kolhicinom treba posumnjati kod pacijenata s gastrointestinalnim simptomima posle konzumiranja divljih biljaka. Ključne reči: mrazovac, kolhicin, zadesno trovanje, autopsija Fatal colchicine poisoning by accidental ingestion of meadow saffron (Colchicum autumnale): report of autopsy case Ivan Aleksic 1, Milos Danilovic 2, Jelena Dzambas 1, Nadica Marinkovic 1 1 Military Medical Academy, Institute of Pathology and Forensic Medicine, Belgrade, Serbia 2 Faculty of Medicine Military Medical Academy, Belgrade, Serbia Aim: Reporting of autopsy case of fatal accidental poisoning by colchicine from meadow saffron. Introduction: Meadow saffron (Colchicum autumnale) is a perennial herbaceous plant similar to the edible wild garlic (Allium ursinum). Toxic substance in meadow saffron is alcaloid colchicine. Colchicine poisoning is a very dangerous condition, which can lead to fatal outcome. Case report: A 50-years-old male was admitted to the hospital complaining of weakness, abdominal pain, nausea, vomiting and diarrhea without blood. Day before he ate two plants thinking they re wild garlic and seven hours after ingestion he felt first symptoms. During the course of the hospital stay, he had gastroenterocolitis, acute renal failure, hepatic lesion and cardiorespiratory insufficiency with fatal outcome. Post-mortem examination reveled:brain oedema, lung oedema and congestion, heart weighing 700 grams, ventricular hypertrophy, myocardial fibrosis, liver congestion and steatosis, spleen congestion, pancreatic fibrosis. Organs sections were taken for pathohistological analysis. Body fluids and parts of organs were toxicologically analyzed. Pathohistological findings:brain oedema, diffuse perivascular and interstitial myocardial fibrosis, myocardial haemorrhage, lungs congestion and edema, micro- and macrovesicular liver steatosis, centrilobular liver necrosis, lymphocytic inflammatory infiltrate in liver portions, spleen s red pulp congestion, kidney congestion and interstitial bleeding, coagulation necrosis of the proximal tubules of the kidney. Toxicological analysis showed colchicine in blood mg/l, urine mg/l, liver with gallbladder mg/ kg, kidney mg/kg. Conclusion: Ingestion of the meadow saffron can lead to poisoning with fatal outcome due to colchicine. Colchicine intoxication should be suspected in patients with gastrointestinal symptoms after consuming wild plants. Key words: Meadow saffron, colchicine, accidental poisoning, autopsy 60

61 POSTER SESIJA P26 Maligni melanoma horoide: prikaz slučaja Darko Mikić, Snežana Cerović, Vojnomedicinska akademija,beograd, Srbija Cilj: Prikazati redak slučaj primarnog intraokularnog malignog melanoma sudovnjače. Uvod: Melanoma choroideae je najćešći intraokularni primarni tumor odraslih. Incidenca je 7 slučajeva na 1 miliona ljudi godišnje, dok se incidenca ovog tumora se povećava sa godinama. Prikaz slučaja: Prikazujemo slučaj 76-godišnje žene koja je imala progresivne defekte vidnog polja u levom oku najmanje dve godine. Dijagnostičkim pregledom, na levom oku je uočena sivo-smeđa promena locirana na zadnjem polu chorodeae to je predstavljalo indikaciju za enukleaciju. Makroskopski bulbus oculi je dimenzija 28x25x25mm, sa optičkim nervom dužine 5mm. Na preseku na zadnjem polu u blizini papile optičkog nerva uočava se ovalna mrko prebojena promena čija baza je pomera 8mm, a visina promene je do 3mm. Histopatološki pregled tumorske promene je pokazao jasno razgraničena solidna tumorska ostrva koja se sastoje od epitelioidnih tumorskih ćelija sa pleomorfnim, atipičnim jedrima, uočljivim nukleolusima. Takođe se uočavaju vretenaste ćelije koje formiraju fascikularne oblike. Tumorska promena je bila oskudne pigmentacije kao i vaskularizacije. Sklera je površno infiltrirana tumorskim ćelijama. Mitotska aktivnost nije bila prisutna (0 / 40HPHF). Imunohistohemijsko bojenje je pokazalo pozitvnost melanomskih ćelija: S-100, MelanA, HMB-45 /-Zaključak: Melanom u ovom regionu je retka, indolentna lezija, sa lošom prognozom. Rana detekcija može sprečiti dalje širenje bolesti i mnoge komplikacije. Metastatski horoidni melanom je visoko maligna bolest sa ograničenim trajanjem života. Ključne reči: melanom, intraokularni, melana Melanoma malignum chorioideae: case report Darko Mikic, Snezana Cerovic Military Medical Academy, Belgrade,Serbia Aim: The present a rare case intraocular primary malignant choroidal melanoma. Introduction: Melanoma choroideae is most common intraocular primary tumor of adults. Incidence is 7 cases per 1 million people per year and incidence of this tumor increases with age. Case report: We report 76 years old women who had progressive visual field defects at left eye at least two years. Diagnostic examination of eye was detected a greyish-brown mass of the posterior choroidal pole which was indication for enucleation. Macroscopically bulbus oculi was dimension 28x25x25mm, with optic nerve 5mm length. At the intersection on posterior pole nearby papila of optical nerve was detected ovoid dark lesion diameters 8x3mm. Histopathology examination was showed sharply demarcated solid tumor islands which consists of epithelioid tumor cells with pleomorphic, atypical nuclei, conspicuous nucleoli. Other type of cells were spindle look which formed fascicular shapes. Pigmentation was absent also. There was no significant vascularisation in tumor mass. Sclera was superficially infiltrated by tumor cells. Mitotic activity was absent (0/40HPHF). Immunohistochemistry staining was confirmed melanoma cells: S-100, MelanA, HMB-45 /-. Conclusion: Melanoma in this region is rare, indolent lesion, with bad prognosis. Early detection could prevent further dissemination of disease and many complications. Metastatic choroid melanoma is a highly malignant disease with a limited life expectancy. Key words: melanoma, intraocular, melana P27 Medijastinalna metastaza ekstraneuralnog ependimoma: prikaz slučaja Bojana Andrejić Višnjić 1, Živka Eri 2, Dejan Vučković 2, Lovrenski Aleksandra 2, Tegeltija Dragana 2, Samardžija Golub 3 1 Medicinski Fakultet Novi Sad, Novi Sad, Srbija 2 Medicinski Fakultet Novi Sad, Institut za plućne bolesti Vojvodine, Sremska Kamenica, Srbija 3 Medicinski Fakultet Novi Sad, Institut za kardiovaskularne bolesti Vojvodine, Sremska Kamenica, Srbija Cilj: Cilj je prikaz slučaja dijagnostikovanja medijastinalnog tumora kod pacijentkinje stare 41 godinu.uvod: Niska incidenca ekstraneuralnih ependimoma, velike varijacije u histomorfološkim odlikama i retka pojava 61

62 POSTER SESIJA metastaza, osnovni su razlog čestih grešaka u dijagnostikovanju. Prikaz slučaja: Izvršen je makroskopski pregled operativnog materijala, a potom uzorkovanje tkiva za dalju histološku i imunohistohemijsku obradu i analizu. U ovom slučaju, početak bolesti bio je pre 14 godina, kada je nakon desne adneksetomije dijagnostikovan maligni mezoteliom. Narednih godina, pacijentkinja je podvrgnuta nizu operativnih zahvata u matičnoj državi, kao i bolnicama u regionu, a na osnovu pregledanog materijala postavljeno je nekoliko različitih patohistoloških dijagnoza. Dijagnoza ekstraneuralnog ependimoma prvi put je postavljena pre 7 godina, a od tada do danas, postavljeno je još nekoliko patohistoloških dijagnoza. Po prijemu u našu ustanovu, pacijentkinji je konstatovano prisustvo lobulirane promene u medijastinumu, koja je makroskopski sivkasto-mrke boje, multicistična. Ciste su ispunjene bistrim seroznim do hemoragičnim tečnim sadržajem. Unutrašnjost cisti je glatka i delom papilarnog izgleda. Histološki, tumorske ćelije su aranžirane u solidne, papilarne i pseudopapilarne formacije, i fokalno u vidu rozeta. Imunofenotip tumorskih ćelija odgovara karakteristikama ekstraneuralnih ependimoma: GFAP, ER, PR pozitivne, kalretinin, WT-1, S100, sinaptofizin, hromogranin, CK7 i pan-ck negativne. Zaključak: Ovaj slučaj ilustruje važnu činjenicu u tumorskoj patologiji. Tumori se mogu primarno javiti i metastazirati na neuobičajenim i neočekivanim lokalizacijama, a patolozi moraju imati u vidu histološke odlike što većeg broja različitih tumora, a ne samo onih iz svog užeg polja rada. Ključne reči: ependimom, ekstraneuralni, metastaza, GFAP Mediastinal metastasis of extraneural ependymoma: case report Bojana Andrejic Visnjic 1, Zivka Eri 2, Dejan Vuckovic 2, Aleksandra Lovrenski 2, Dragana Tegeltija 2, Golub Samardzija 3 1 Faculty of Medicine Novi Sad, Novi Sad, Serbia 2 Faculty of Medicine Novi Sad, Institute for pulmonary diseases of Vojvodina, Sremska Kamenica, Serbia 3 Faculty of Medicine Novi Sad, Institute for cardiovascular diseases of Vojvodina, Sremska Kamenica, Serbia Aim: The aim of this case was a correct diagnosis of mediastinal tumor in a 41-years old female patient. Introduction: The rarity of primary extraneural ependymomas, its great variations in morphology and rare occurrence of metastasis, increase chances of misdiagnosis. Case report: Macroscopic examination of received specimen was performed, followed by histological and immunohistochemical analysis of the tissue samples. In presented case, onset of the disease was 14 years ago, when after right salpingo-oophorectomy, patient was diagnosed with malignant mesothelioma. In following years patient had multiple and extensive surgical procedures, resulting in different patohistological diagnosis, and after seven years, a diagnosis of extraneural ependymoma was established. Later on, patient was surgically treated in several medical centers across the region, again with different patohistological diagnosis. At present, tumor metastasized to mediastinum, presenting as grey to brown, multicystic formation, with cysts filed with clear serous fluid or red-brown hemorrhagic fluid. Inner surface of the cysts had smooth to partly papillary appearance. Tumor cells exhibited several architectural paterns (solid, pseudorosette or rosette formations, papillary and pseudopapilary structures), and immunophenotype specific for extraneural ependymoma (GFAP, ER, PR positive, calretinin, WT-1, S100, synaptophysin, chromogranin, CK7 and pan-cytokeratin negative). Conclusion: This case demonstrates an important principle in tumor pathology. Neoplasms may occur in unusual and unexpected primary and metastatic sites. Pathologists need to be familiar with histologic features of a wide range of neoplasms and not just the appearance of neoplasms within their own limited subspecialty area. Key words: ependymoma, extraneural, metastasis, GFAP P28 Importance and benefits of autopsies: An illustrative case Daniela Bajdevska 1, Daniel Milkovski 2, Verdi Stanojevic 3, Boro Ilievski 4, Gordana Petrushevska 4, Snezana Zaharieva 5 1 Department of Pathology, General Hospital-Kumanovo, Republc of Macedonia 2 University Clinic of Obstetrics and Gynecology, Skopje, Republc of Macedonia 3 Department of Gynecological Cytology, University Clinic of Gynecology and Obstetrics, Skopje, Republc of Macedonia 4 Institute of Pathology, Faculty of Medicine, University Ss. Cyril and Methodius, Skopje, Republic of Macedonia 5 Department of anesthesiology and reanimation, General Hospital-Kumanovo, Republc of Macedonia Aim: We present a case wherein the information obtained from autopsy examination was of critical importance to a doctor and a family. Introduction: A 24-year-old,multipara,delivered a term born male baby with a birth weight 3100gr and body length 46cm.Soon after birth the neonate developed signs of 62

63 POSTER SESIJA a respiratory insufficiency and died within 2 hours.anamnestic data from the mother revealed uncontrolled pregnancy. Material and Methods: Standard autopsy technic and standard procedure of paraffin embedded section routinely stained with H E was performed. Results: At autopsy,the external examination revealed characteristic facial features suggestive of Potter s face including posterior rotated low-set ears,flat nose,widely separated eyes,micrognatia and short neck. Autopsy revealed presence of bilateral hypoplastic lungs with total weigh of 28g,less than the expected range (normal 49g).On dissection lungs were airless, non-crepitant and sank in the water. Histologically findings were consistent with a diagnosis of pulmonary hypoplasia.the abdominal cavity was completely filled with markedly symmetrical enlarged kidneys.total weight of both kidneys was 156g (normal 25g).On the dissection section showed multiple small cysts measuring 1-3 mm in size,completely replacing the cortex and medulla giving it a spongy like appearance and typical honeycomb structure.on microscopical examination we found cysts uniformly lined by cuboidal to flattened epithelium. Zaključak: We consider that this is a Potter Syndrome Type I due to Autosomal Recessive Polycystic Kidney Disease and is linked to a mutation in the gene PKHD1.2. Through this case,we are aware of the importance and benefit of autopsy,although the trend of autopsies in the world is decreasing. Key words: Autopsy, Neonate, Potter Syndrome P29 Proliferativna aktivnost u paratireoidnim žlezdama bolesnika sa hiperparatireoidizmom: imunohistohemijska analiza Snežana Cerovic, Božidar Kovačevic, Sanja Dugonjić, Milena Jović, Jelena Džambas Institut za patologiju i sudsku medicinu Vojnomedicinska akademija Beograd, Srbija Cilj: Utvrđjivanje imunohistohemijskih karakteristika proliferativne aktivnosti u paratireoidnim žlezdama (P ) bolesnika sa primarnim i sekundarnim hiperparatireoidizmom (HPT) primenom imunohistohemijskih markera ćelijskog ciklusa i proliferacije Ki-67 i PCNA. Uvod: Rezultati malog broja studija pokazali su značajnu detekciju Ki-67 proteina u hiperplaziji u okviru sekundarnog hiperparatireoidizma (shpt), dok je u primarnom HPT (phpt) dokazana isključivo kod adenoma. Naijizrazitija ekspresija PCNA detektuje se u hiperplastičnom tkivu P u shpt, zatim u adenomu kod phtp, dok je izrazito niska u hiperplaziji u okviru phtp. Materijal i metode: Analiziran je materijal iz hirurški odstranjenih P kod 96 bolesnika sa HPT. Uz standardne patohistološke parametre, analizirani su rezultati imunohistohemijskih reakcija za Ki-67 i PCNA u uzorcima 23 normalne P, 73 hiperplastične P i 23 adenoma. Rezultati: Kod 41 (42,7%) bolesnika postojao je phpt, a kod 55 (57,3%) shpt. U okviru phpt adenom je dijagnostikovan kod 23 (56,1%) bolesnika, a kod 18(43,9%) hiperplazija. Detekcija PCNA iznosila je 94,4% kod hiperplazije P u phpt, 91% kod hiperplazije P u shpt i kod adenoma 83%. U 22 (98%) normalnih P nije bilo PCNA ekspresije. Ekspresija Ki-67 utvrđjena je kod 13(56.5%) adenoma i 11(18,3%) nodularnih hiperplazija. Visoka statistička značajnost za Ki-67(p<0.0001) nađjena je izmeđju adenoma i phpt i shpt. Zaključak: Rezultati naše analize pokazali su visoku Ki-67 i PCNA ekspresiju u paratireoidnim adenomima. Povećana ekspresija Ki-67 odgovara porastu proliferacije ćelija i značajna je u tumorigenezi u mnogim organima, ali ne ukazuje na pravu razliku izmedju benignih i malignih tumora P. Ključne reči: hiperparatireoidizam, proliferativna aktivnost, imunohistohemija. Activity of the Parathyroid Glands in Patients with Hyperparathyroidism: An immunohistochemical analysis Snezana Cerovic, Bozidar Kovacevic, Sanja Dugonjic, Milena Jovic, Jelena Dzambas Institute of Pathology and Forensic medicine, Military Medical Academy, Belgrade, Serbia Aim: Determining the immunohistochemical characteristic of parathyroid glands (PG) proliferative activity in patients with primary and secondary hyperparathyroidism (HPT) using cell cycle and proliferation immunohistochemical markers, Ki -67 and PCNA. Introduction: A few studies results have shown A few studies results have shown significant detection of Ki-67 in hyperplasia due to secondary hyperparathyroidism (shpt), whereas it s demonstrated only in adenomas in primary HPT (phpt). The highest PCNA expression is detected in hyperplastic PG in shpt and in adenoma in phtp, but in phtp hyperplasia it s extremely low. Material and Methods: We analyzed the surgically removed PG of 96 patients with HPT. In 63

64 POSTER SESIJA addition to standard histopathological parameters the results of immunohistochemical reaction of Ki-67 and PCNA in 23 normal, 73 hyperplastic PG and 23 adenoma were analyzed. Results: 41 (42.7%) patients had phpt, and 55 (57.3%) shpt. Within phpt adenoma was diagnosed in 23 (56.1%) patients and hyperplasia in 18 (43.9%). Detection of PCNA was 94.4% in phpt hyperplasia, 91% in shpt hyperplasia, and 83% in adenoma. 22 (98%) of the normal PG didn t have PCNA expression. The expression of Ki-67 was found in 13 (56.5%) adenomas and in 11 (18.3%) nodular hyperplasia. The high statistical significance for Ki-67 (p <0.0001) was found between adenoma and phpt and shpt. Conclusion: The results of our analysis showed high Ki-67 and PCNA expression in parathyroid adenomas. Increased Ki-67 expression corresponds with increased cellular proliferation and contributes to tumorigenesis in many organs, but doesn t distinguish accurately benign from malignant PG tumors. Key words: hyperparathyroidism, proliferative activity, immunohistochemistry. P30 Metastaza signet ring cell karcinoma želuca u ureter Marija Milić Perović, Aleksandra Paunović Marković, Nataša Šurdević, Marija Čubrilo, Jelena Kuzmanović, Jovan Juloški, Lidija Vučković Hardi KBC Zvezdara, Beograd, Srbija Cilj: Prikazujemo interesantan slučaja neočekivanog metastatskog depozita signet ring cell karcinoma želuca u ureter. Uvod: Obstrukcija uretera karcinomom želuca može nastati jednim od sledećih mehanizama: direktnom ekstenzijom primarnog tumora, depozitima sa peritoneuma ili limfogenom metastazom. Materijal i metode: Prikaz slučaja metastaze karcinoma želuca u ureter kao jedina manifestacija diseminacije bolesti, dve godine nakon postavljanja dijagnoze primarnog tumora želuca. Rezultati: Pacijent, starosti 52 godine, je primljen na odeljenje urologije KBC Zvezdare, sa simptomima bola u levoj slabini i visokom temperaturom, koji su trajali 5 dana. Pre dve godine je imao operaciju parcijalne gastrektomije zbog karcinoma želuca i primio je 8 ciklusa hemoterapije. Analize krvi su bile normalne, sem povišenih vrednosti kreatinina i C-reaktivnog proteina. Ultrazvukom abdomena i kompijuterizovanom tomografijom je otkrivena hidronefroza levog bubrega i uretera, trećeg stepena. Cistoskopija je ukazala na tumor bešike promera 2 cm, koji je zahvatao orificijum levog uretera. Urađena je leva nefrektomija sa totalnom ureterektomijom i transuretralna resekcija tumora mokraćne bešike. Patohistološki nalaz hirurškog materijala je ukazao na signet ring cell karcinom koji infiltriše laminu propriju i mišićni sloj levog uretera. Patohistološki nalaz resekovanog materijala mokraćne bešike je odgovarao signet ring cell karcinomu identičnog izgleda kao u želucu. Zaključak: Metastaze karcinoma želuca u ureter su veoma retke. Shimoyama je prikazao 27 slučaja ureteralnih metastaza. Prognoza je veoma loša i u literaturi nije prijavljeno preživljavanje duže od dve godine. Ključne reči: Signet ring cell karcinoma, ureteralne metastaze, hidronefroza Metastasis of gastric signet ring cell carcinoma to the ureter Marija Milic Perovic, Aleksandra Paunovic Markovic, Nata a Djurdjevic, Marija Cubrilo, Jelena Kuzmanovic, Jovan Juloski, Lidija Vuckovic Hardi Clinical hospital centre Zvezdara, Belgrade, Serbia Aim: We present an interesting case of unexpected metastatic deposit signet ring cell of the gastric cancer in the ureter. Introduction: Ureteral obstruction caused by gastric cancer may occur by any of the following three mechanisms: direct extension from the primary site, peritoneal deposit or lymph node metastasis. Material and Methods: We report the case of a patient with ureteral metastasis as the first and sole manifestation of gastric cancer dissemination two years after he was first diagnosed with gastric cancer. Results: A 52-year old male patient was admitted to the Department of Urology, Clinical Hospital Centre Zvezdara in Belgrade, with a 5-day history of right colic flank pain and high temperature. He had a partial gastrectomy for gastric cancer two years ago and received 8 cycles of chemotherapy. Routine blood test results were normal except elevated creatinine and C-reactive protein levels. An abdominal ultrasound examination and computed tomography revealed grade 3 hydronephrosis and hydroureter. Cystoscopy indicated a tumor measuring 2 cm in size which involved left ureteral orifice. A left nephroureterectomy and transurethral resection of bladder tumor were performed. Histopathological examination of surgical 64

65 POSTER SESIJA specimen revealed signet ring cell carcinoma infiltrating lamina propria and tunica muscularis of the left lower ureter. Histopathological examination of the bladder specimen revealed signet ring cell carcinoma identical to those of the ureteral tumor. Conclusion: Ureteral metastases from gastric cancer are extremely rare. Shimoyama reviewed 27 cases of the true ureteral metastasis from gastric cancer. The prognosis is generally poor and the survival for more than 2 years has not been reported in literature. Key words: Signet ring cell carcinoma, ureteral metastasis, hydronephrosis P31 Metastaza u gornjem urinarnom traktu kao inicijalna prezentacija invazivnog lobuarnog karcinoma dojke Jelena Vučinić 1, Janja Raonić 1, Ljiljana Vučković 1, Filip Vukmirović 1, Mileta Golubović 1, Tanja Nenezić 1, Petar Kavarić 2 1 Centar za patologiju, Klinički centar Crne Gore, Podgorica, Crna Gora 2 Klinika za urologiju, Klinički centar Crne Gore, Podgorica, Crna Gora Cilj: Prikaz pacijentkinje sa rijetkom lokalizacijom metastaze lobularnog karcinoma dojke (ILC) kao inicijalne prezentacije bolesti. Uvod: Zbog specifičnog načina rasta, ILC rijetko formira tumorski čvor, što otežava njegovo otkrivanje u ranom stadijumu. Ovaj tumor karakteriše nekonvencionalan put metastaziranja, a u 3-10% slučajeva depoziti se dijagnostikuju prije primarnog tumora. Prikaz slučaja: Kod pedeset-jednogodišnje pacijentkinje, hospitalizovane u Klinici za urologiju Kliničkog centra Crne Gore zbog evaluacije bubrežne funkcije, statičkom scintigrafijom ustanovljen je funkcionalni kapacitet lijevog bubrega od 7-8%. Doneđena odluka o nefrektomiji. Centru za patologiju je dostavljen bubreg veličine 11x6x4cm, lako redukovanog, bljede prebojenog parenhima, čvrsto srasle masne kapsule, sa ureterom i pijelokaliksnim sistemom odgovarajućeg makroskopskog izgleda. Analizom hematoksilin-eozin isječaka, u bubregu je dominirala slika hroničnog pijelonefritisa, dok su u nekoliko isječaka uretera, pijelona i bubrežnog parenhima (subkapsularno) uočeni infiltrati sitnih, kockastih, atipičnih ćelija, dominantno aranžiranih u tračke debljine jedne ćelije. Imunohistohemijskom analizom utvrđena je jaka pozitivnost na EMA, CK(ae1/ae3), CK7, estrogen i mammaglobin. Malobrojne ćelije su bile pozitivne na progesteron, dok su vimentin, CK20 i neuroendokrini markeri bili negativni, a Ki67<10%. Postavljena je sumnja da se radi o depozitima ILC. Kasnije je potvrđena dijagnoza primarnog ILC, bez jasno formiranog tumorskog čvora u dojci, sa depozitima u limfnim čvorovima aksile. Tumorske ćelije su bile estrogen i progesteron pozitivne, HER2 negativne, sa Ki67 indeksom od 3%. Zaključak: Nalaz metastaza na nekonvencionalnim lokalizacijama, kod ena, mo e ukazati na postojanje primarnog tumora dojke tipa ILC. Za efikasnije inicijalno otkrivanje primarnog tumora neophodan je poseban dijagnosticki algoritam. Ključne reči: ILC, metastaza, urinarni trakt Metastasis in the upper urinary tract as initial presentation of invasive lobular breast cancer Jelena Vucinic 1, Janja Raonic 1, Ljiljana Vuckovic 1, Filip Vukmirovic 1, Mileta Golubovic 1, Tanja Nenezic 1, Petar Kavaric 2 1 Centre for Pathology, Clinical centre of Montenegro, Podgorica, Montenegro 2 Urology Clinic, Clinical centre of Montenegro, Podgorica, Montenegro Aim: Reporting a patient with unusual metastatic site of invasive lobular breast cancer (ILC) as initial presentation of the disease. Introduction: Due to specific growth pattern, ILC rarely forms an apparent tumor, which makes diagnosis very challenging at early stage. ILC is also known for unconventional metastatic spread, with deposits being discovered prior to the primary tumor in 3-10% of cases. Case report: While evaluating renal function in 51-year old female patient hospitalised at the Urology Clinic (Clinical centre of Montenegro), static scintigraphy revealed left kidney functional capacity of 7-8%. Nephrectomy was indicated. Kidney, 11x6x4cm in size, with slightly reduced, paler parenchyma, firmly attached fatty capsule and pyelocaliceal system and ureter of regular gross appearence, was delivered to the Centre for Pathology. Analysis of H E sections revealed chronic pyelonephritis. In a few sections taken from urether, pyelon and subcapsular parts of parenchyma, infiltrates of small, cuboid, atipical cells, mostly arranged in one-cell-thick files, were noted. Immunohistochemistry reveiled strong pozitivity for EMA, CK(ae1/ae3), CK7, estrogen and mammaglobin, with Ki67<10%. A few cells were progesteron positive, while vimentin, CK20 and neuroendocrine markers were negative. ILC metastasis was suspected. ILC, with axillary lymph 65

66 POSTER SESIJA node involvement, was confirmed later, although there was no macroscopically apparent tumor in the breast. Tumor cells were estrogen and progesterone positive, HER2 negative, with Ki67 of 3%. Conclusion: While assessing metastatic deposits in unconventional sites in women, primary ILC should be considered. Special diagnostic algorhytm is required for efficient initial detection of the primary tumor. Key words: ILC, metastasis, urinary tract P32 Extrapleural solitary fibrous tumor of the neck: A Case Report Blagjica Lazarova 1, Slobodan Rogach 1, Gjorgi Velkov 2, Elena Aleksoska 1, Gordana Petrusevska 3, Liljana Spasevska 3 1 Department of Pathology, Clinical Hospital, Shtip, Republic of Macedonia 2 Department of Surgery, Clinical Hospithal, Shtip, Republic of Macedonia 3 Institute of Pathology, Faculty of Medicine, Skopje, Republic of Macedonia Aim: Immunohistochemistry findings along with clinical features, are significantly important in differentiating the Extrapleural SFT in the neck, from other well-circumscribed mesenchymal neoplasms at this locations. Introduction: We present a rare case of a Extrapleural SFT in a 57 years old man in the neck, without significant past medical history. Material and Methods: The patient had a painless slow growing tumor, in right sight of the neck, diagnosed with physical examination. Total excision with local anesthesia was done, without previously biopsy of the tumor and other clinical investigations. Standard procedures for histology and immunohistochemical stains were done. Results: Tumor was well circumscribed, encapsulated measuring 5,5x4x4 cm. On section, the cut surface had a multinodular, whitish and firm appearance. On microscopic examination tumor was composed of alternating hypocellular and hypercellular areas separated from each other by thick bands of collagen and branching haemangiopericitoma like vessels. The tumor cells were round to spindle-shaped with little cytoplasm, indistinct borders, dispersed chromatin within vesicular nuclei. Area of myxoid change and subcapsular focus of hemorrhage was present, and 2 mitoses/10 HPF were found. Immunohistochemistry revealed diffuse positivity for CD34, Vimentin and BCL2, focal positivity for CD99, S100, SMA, and negativity for CKWS and EMA. Ki67 showed low proliferating index 3-5%. Conclusion: Although most cases of SFT are benign, there is no strict correlation between morphology and behavior, so patients with extrapleural solitary fibrous tumor have need of long-term post-resection follow-up. Further studies are needed to determine the optimal management of these neoplasms. Key words: extrapleural, solitary fibrous tumor, neck P33 Mioidni angioendoteliom slezine Milena Ćosić Micev, Marjan Micev, Marko Andrejević, Maja Dimić Čumić, Aleksandra Dikić Rom, Slavko Matić, Nikica Grubor Klinički centar Srbije, Beograd, Srbija Cilj: Prezentacija tri slučaja i pregled literature spleničnog mioidnog angioendotelioma (SMA) sa fokusom na imunohistohemijske karakteristike. Uvod: SMAi su veoma retki, uglavnom kod sredovečnih i starijih osoba oba pola i karakterišu se mešovitom proliferacijom kordalnih kapilara i mioidnih ćelija, izdvojeni od drugih angioendotelioma slezine usled dodatne miogene/miofibroblastne diferencijacije. Materijal i metode: Tri slučaja SMA iz Registra Službe za patohistologiju Kliničkog centra Srbije detektovana su u poslednjih 12 godina ( ) kod jednog pacijenta i dve pacijentkinje (prosečna starost 42,5 godina). Histomorfološki nalazi su revidirani pregledom svih serijskih HE preseka uzoraka histohemijskih trihromnih bojenja i imunohistohemijskih bojenja za CD8, CD31, CD34, CD68, SMA, desmin i Ki-67. Rezultati: Svi slučajevi su pokazali jasno ograničene, neinkapsulirane solitarne tumore promera 42, 55 i 20 mm, a histološki povećanu gustinu kapilarnih krvnih sudova izmešanih sa poligonalnim mioidnim stromalnim ćelijama, kao i bar fokalno ispoljenu nehomogenu hipercelularnost stromalnih i limfoidnih ćelija i fokalnu sklerozu. Neokapilari se odlikuju CD8-/CD31 /CD34 imunofenotipom, to ih razdvaja od spleničnih hamartoma i karakteritičnom izmešanošću sa miogenim elementima to ih razdvaja od kordalnih kapilarnih hemangioma: intenzivna SMA (3/3), retka fokalna desmin (2/3) i fokalna CD68 (1/3) imunoekspresija. Zaključak: SMA je nedovoljno prepoznati tip vaskularne neoplazije, koji ima kliničko-patološki diferenci- 66

67 POSTER SESIJA jalno dijagnosticki značaj jer radiološki imitira metastaze. Celularne forme SMA se moraju razlikovati od hamartoma, ali i od hemangiopericitoma i dobro diferentovanih angiosarkoma slezine. Ključne reči: slezina, mioidni angioendoteliom Splenic myoid angioendothelioma Milena Cosic Micev Marjan Micev, Marko Andrejevic, Maja Dimic Cumic, Aleksandra Šikic Rom, Slavko Matic, Nikica Grubor Clinical Centre of Serbia, Belgrade, Serbia Aim: To present three cases and review literature of splenic myoid angioendothelioma (SMA) focusing on immunohistochemical features. Introduction: SMAs are very rare, mainly in middle-aged and elderly patients of both sexes and are characterized by a mixed proliferation of cord capillaries and myoid cells, distinguished from other splenic angioendotheliomas by additional myogenic/myofibroblast differentiation. Material and Methods: Three cases of SMA from the Department of Histopathology Registry of Clinical Centre of Serbia were detected during last 12 years ( ) in one male and two female patients (42,5 ys average age). Histomorphological findings were revised by reviewing all serial HE sections, histochemical trichrome stains and immunohistochemical stainings for CD8, CD31, CD34, CD68, SMA, desmin and Ki-67. Results: All cases showed sharply demarcated non-encapsulated solitary tumors with diameters 42, 55 and 20 mm. Histologically there are dense network of capillary blood vessels intermingled with polygonal myoid stromal cells and at least focally expressed non-homogeneous cellularity of stromal and lymphoid cells with focal sclerosis. Neocapillaries show distinctive CD8- / CD31 / CD34 immunophenotype (differing them from splenic hamartomas) and characteristic mixture with myogenic elements (differing them from cord capillary hemangiomas): intense SMA (3/3), rare focal desmin (2/3) and focal CD68 (1/3) immunoexpression. Conclusion: SMA is underrecognized type of vascular neoplasia, which has a clinico-pathological differential diagnostic significance because it radiologically imitates splenic metastase. Cellular form of SMA must be distinguished from hamartoma, but also from hemangiopericytoma and well-differentiated angiosarcoma of the spleen. Key words: spleen, myoid angioendothelioma P34 Metastaza melanoma u limfnim čvorovima sa hroničnom limfocitnom leukemijom/sitnoćelijskim limfocitnim limfomom: Prikaz slučaja Dragan Živojinović, Olga Radić-Tasić, Saša Ristić, Olivera Tarabar, Zoran Mirković, Milica Rajović Institut za patologiju i sudsku medicinu, Vojnomedicinska Akademija, Beograd, Srbija Cilj: Prikaz metastaze melanoma u limfne čvorove sa hroničnom limfocitnom leukemijom/sitnoćelijskim limfocitnim limfomom (CLL/SLL) kao primer kolizionog tumora neuobičajnog sinhronog javljanja u limfnom čvoru. Uvod: Sinhroni kompozitni tumori su retki, a njihovio simultano javljanje u istom tkivu/organu je još ređe. CLL/SLL je indolentna, klonalna bolest zrelih B-limfocita koja se uglavnom javlja kod starijih osoba. Nakon primene hemioterapeutskih agenasa u cilju lečenja moguće je javljanje sekundarnih maligniteta (melanom, skvamozni karcinom). Materijal i metode: Prikazujemo slučaj 77-godišnjeg muškarca kod koga je posle desnostrane nefrektomije zbog svetloćelijskog karcinoma, dijagnostifikovana CLL/SLL sa infiltracijom kostne srži i limfnih čvorova. Nakon tri godine i primenjene hemioterapije ekscidirana je kožna promena koja histomorfološki odgovara melanomu. Posle primenjene imunoterapije za melanom, sa vrata se ekstripiraju uvećani limfni nodusi koji su obradeni histomorfološki i imunohistohemijski. Rezultati: Histomorfološki, nađena je dufuzna infiltracija limfnog čvora malim B-limfocitima, okruglih jedara, kondenzovanog hromatina, neupadljivih nukleolusa, oskudne citoplazme, jedinstvenog imunofenotipa: CD20,PAX-5,CD5,CD23,Cyclin D1-,CD3-. Deo limfnog nodusa je infiltrovan epiteloidnim ćelijama imunofenotipa: S-100, Melan A, HMB-45. Histomorfološki i imunohistohemijski je dokazana CLL/SLL uz infiltraciju melanomom kao primer kolizionih tumora. Zaključak: Limpoproliferativne neoplazme uključujući CLL/ SLL predstavljaju povecan rizik sinhronog i metahronog razvoja sekundarnih maligniteta izmedu ostalih i melanoma, koji mogu neuobičajno da se prezentuju kao sinhroni, kolizioni tumori u istom organu. Ključne reči: CLL/SLL, melanom, limfni čvor, imunohistohemija. 67

68 POSTER SESIJA Metastasis of lymph nodes melanoma with chronic lymphocytic leukemia/ small lymphocytic lymphoma: case report Dragan Zivojinovic, Olga Radic-Tasic, Sasa Ristic, Olivera Tarabar, Zoran Mirkovic, Milica Rajovic Institute of Pathology and Foresnic Medicine, Military Academy, Belgrade, Serbia Aim: Purpose of this report is to present metastasis of lymph nodes melanoma with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) as an example of collision tumor of an uncommon synchronic occurrence in the lymph node. Introduction: Synchronic, composite tumors are rare and their simultaneous and synchronic occurence within the same tissue/organ is even more rare. CLL/SLL is an indolent, clonal disease of mature B-lymphocytes which occurs mostly with adults. After the treatment with chemotherapeutic agents the occurence of the secondary malignancies (melanoma,squamous-cell carcinoma). Material and Methods: We present a 77 year old male who, after right sided nephrectomy caused by clear-cell carcinoma was diagnosed with CLL/SLL with bone marrow and lymph node infiltration. After three years and chemotherapy, skin changes were excised which histomorphologically resembles melanoma. After the immunotherapy for melanoma, the enlarged lymph nodes were extripated from the neck and histomorphologically and immunohistochemically treated. Results: Histomorphologically, a diffused infiltration of small B-lymphocytes was found in the lymph node, with round nuclei, condensed chromatin, inconspicuous nucleoli, scant cytoplasm unique immunophenotype: CD20,PAX-5,CD5,CD23,Cyclin D1-,CD3-. A part of lymph node was infiltrated by epitheloid cells with immunohistochemic profile: S-100,Melan A,HMB-45. Histomorphological and immunohistochemical CLL/SLL with melanoma infiltration as an example of a collision tumor was proved. Conclusion: Lymphoproliferative neoplasms including CLL/SLL represent an risk of synchronous, metachronous development of secondary malignancies including melanoma itself and they can uncommonly present themselves as synchronic collision tumors within the same organ. Key words: CLL/SLL, melanoma, lymph node, immunohistochemistry. P35 Sarkoidoza srca: prikaz slučaja Golub Samardžija 1, Snežana Tadić 1, Marija Bjelobrk 1, Dragana Tegeltija 2, Aleksandra Lovrenski 2, Bojana Višnjic Andrejić 3 1 Institut za kardiovaskularne bolesti Vojvodine, Univerzitet u Novom Sadu, Medicinski fakultet, Novi Sad, Srbija 2 Institut za plućne bolesti Vojvodine, Univerzitet u Novom Sadu, Medicinski fakultet, Novi Sad, Srbija 3 Univerzitet u Novom Sadu, Medicinski fakultet, Novi Sad, Srbija. Cilj: Prikaz slučaja pacijenta starosti 68 godina koji je umro od hronične srčane insuficijencije uzrokovane sarkoidozom srca (SS). Uvod: Sarkoidoza je multisistemsko oboljenje nepoznate etiologgije, koji se karakteriše granulomatoznom infiltracijom i razvojem nekazeozni granuloma u mnogim organima. Iako su pluća, oči i koža najčešce pogođeni, praktično bilo koji organ može biti zahvaćen. Klinički dokazi o SS se vide samo kod 5% pacijenata, a bolest može biti praćena sa tahiaritmijama, poremećajima provodljivosti, srčanom insuficijencijom ili iznenadnom srčanom smrću. Prikaz slučaja: Pacijent je primljen u bolnicu zbog simptoma i znakova globalne kardijalne dekompenzacije sa tegobama u vidu gušenja, nemogućnosti ležanja na ravnom i oticanja nogu. Ehokardiografskim pregledom se nađu uvećane srčane šupljine sa globalno sniženom sistolnom funkcijom, mitralnom regurgitacijom teškog stepena i EF oko 20%. Vrlo brzo nakon prijema pacijent je umro. Na obdukciji, srce je bilo dilatirano, prevashodno leva komora. Histološki, miokard je bio infiltrovan brojnim granulomima sagrađenim od limfocita, epiteloidnih ćelija i džinovskih višejedarnih ćelija Langhans tipa. Kao posledica izražene srčane insuficijencije pluća su bila edematozna sa obostranim masivnim pluralnim izlivima. Koronarne arterije su bile bez signifikantnih suženja. Zaključak: Rana dijagnoza i lečenje mogu sprečiti značajan morbiditet i mortalitet kod pacijenata sa SS. Veoma je važno da pacijenti sa SS u ranoj fazi bolesti budu lečeni sa kortikosteroidima. Ključne reči: sarkoidoza, nekazeozni granulomi, sarkoidoza srca Cardiac sarcoidosis: Case report Golub Samardzija 1, Snežana Tadic 1, Marija Bjelobrk 1, Dragana Tegeltija 2, Aleksandra Lovrenski 2, Bojana Visnjic Andrejic 3 68

69 POSTER SESIJA 1 Institute for Cardiovascular Diseases of Vojvodina, University of Novi Sad, Faculty of Medicine, Novi Sad, Serbia 2 Institute of Lung Diseases of Vojvodina, University of Novi Sad, Faculty of Medicine,Novi Sad, Serbia. 3 University of Novi Sad, Faculty of Medicine, Novi sad, Serbia Aim: We present the case of a patient aged 68 years who died of chronic heart failure caused by untreated cardiac sarcoidosis (CS). Introduction: Sarcoidosis is a multisystem disorder of unknown etiology, characterized by granulomatous infiltration and the development of noncaseating granulomas in many organ systems. Although the lungs, eyes, and skin are most commonly affected, virtually any body organ can be involved. Clinical evidence of CS is seen only in 5% of patients and the disease may present with tachyarrhythmias, conduction disturbance, heart failure, or sudden cardiac death. Case report: The patient was received in the hospital due to symptoms and signs of global cardiac decompensation with difficulties in the form of dyspnea, orthopnea, and edematous legs. Echocardiographic, cardiac cavities are very dilated with globally reduced systolic function, severe mitral regurgitation and ejection fraction about 20%. Very soon after receiving the patient is died. At autopsy, the heart was dilated, primarily the left ventricle. Histologically, the myocardium was infiltrated by numerous granulomas built of lymphocytes, epitheloid cells, and giant multicellular cells of the Langhans type. As a consequence of severe chronic heart failure, the lungs were edematous with both sides of massive plural effusions. The coronary arteries were non-significantly stenosed. Conclusion: Early diagnosis and treatment can prevent significant morbidity and mortality in patients with CS. It is very important that patients with CS in the early stage of the disease be treated with corticosteroids. Key words: sarcoidosis, noncaseating granulomas, cardiac sarcoidosis, autopsy P36 Kliničke i morfološke karakteristike tumora srca Golub Samardžija 1, Iva Bosić 1, Lazar Velicki 1, Milenko Rosić 1, Dragana Tegeltija 2, Aleksandra Lovrenski 2, Bojana Višnjic Andrejić 3 1 Institut za kardiovaskularne bolesti Vojvodine, Univerzitet u Novom Sadu, Medicinski fakultet,novi Sad, Srbija. 2 Institut za plućne bolesti Vojvodine, Univerzitet u Novom Sadu, Medicinski fakultet,novi Sad, Srbija. 3 Univerzitet u Novom Sadu, Medicinski fakultet, Novi Sad, Srbija Cilj: Analizirati starosnu i polnu distribuciju tumora srca, najčešće kliničke simptome, najčešće patohistološke tipove, najčešću lokalizaciju tumora i uporediti ehokardiografsku sa patohistološkom veličinom tumora. Uvod: Incidenca primarnih tumora srca veoma je retka i iznosi oko 0,02%. Učestalost sekundarnih tumora srca značajno veća. Primarni maligni tumori srca veoma su retki i predstavljaju najređe tumore u ljudskom organizmu. Materijal i metode: Ispitivanje je obuhvatilo 49 bolesnika operisanih u Institutu za kardiovaskularne bolesti Vojvodine u periodu od 2008 do 2017 godine. Podaci o bolesnicima su dobijeni iz istorija bolesti, informacionog sistema i patohistoloških nalaza. Rezultati: Prosečna starost celokupnog uzorka je 53,9 godina. Najčešći simptomi su bili lako zamaranje, lupanje srca, vrtoglavica, nesvestica, otežano disanje, malaksalost, kašalj i bol u gudima. Najčešći su dijagnostikovani miksomi 67,3%, papilarni fibroelastomi 28,6%, kavernozni hemangiomi 4,1%, metastatski tumor 2,04%. Najčešća lokalizacija tumora je u levoj pretkomori 63,3%, aortnim kuspisima 16,3%, desnoj pretkomori 8,2%, mitralnom zalistku 8,2%, levoj komori 2,04% i međupretkomorskoj pregradi 2,04%. Razlika srednjih vrednosti ehokardiogrfske veličine tumora i veličine tumora nakon hirurške ekstirpacije nije statistički značajna (p = 0.706). Zaključak: Iako retki, tumori srca imaju veliki klinički zanačaj pre svega zbog mogućnosti pojave ozbiljnih komplikacija kao što je embolizacija arterija mozga sa razvojem infarkta pa čak i pojava iznenadne smrti. Međutim pravovremena dijagnoza i hirurško odstranjenje tumora u najvećem broju slučajeva dovode do izlečenja pacijenata. Ključne reči: patologija, hirurgija, tumori srca Clinical and morphological characteristics of the cardiac tumors Golub Samardzija 1, Iva Bosic 1, Lazar Velicki 1, Milenko Rosic 1, Dragana Tegeltija 2, Aleksandra Lovrenski 2, Bojana Visnjic Andrejic 3 1 Institute for Cardiovascular Diseases of Vojvodina, University of Novi Sad, Faculty of Medicine, Novi Sad, Serbia 2 Institute of Lung Diseases of Vojvodina, University of Novi Sad, Faculty of Medicine,Novi Sad, Serbia. 3 University of Novi Sad, Faculty of Medicine, Novi Sad, Serbia Aim: To analyze age and sex distribution of the cardiac tumors, the most common clinical symptoms, 69

70 POSTER SESIJA pathohistological types, tumor localization and compare the echocardiographic with the pathohistological size of the tumor. Introduction: The incidence of primary cardiac tumors are very rare and amounts to about 0.02%. Incidence of secondary cardiac tumors are significantly higher. Primary malignant cardiac tumors are very rare and represent to the rarest tumors in the human organism. Materials and Methods: The study covered 49 patients who were operated in the period from 2008 to Patients data are obtained from the history of the disease, the information system and pathohistological findings. Results: The average age of the patients is 53.9 years. The most common symptoms were light fatigue, heart palpitations, vertigo, dizziness, dyspnea, exhaustion, cough and stenocardia. The most commonly diagnosed are myxomas (67.3%), papillary fibroelastomas 28.6%, cavernous hemangiomas 4.1%, and metastatic tumors 2.04%. The most common tumor localization is in the left atrium 63.3%, aortic cusps 16.3%, right atrium 8.2%, mitral valve 8.2%, left ventricle 2.04% and interventricular septum 2.04%. The difference in mean echocardiographic tumor size and tumor size after surgical extirpation was not statistically significant (p = 0.706). Conclusion: Although, cardiac tumors are rare, they have a large clinical importance, primarily because of the potential for severe complications such as embolization of the arteries of the brain with the development of cerebral infarction and even the appearance of sudden death. However, timely diagnosis and surgical removal of tumors lead to patient curing in most cases. Key words: pathology, surgery, cardiac tumors P37 Giant bilateral vertebral artery aneurysms: a case report Boro Ilievski, Ivan Domazetovski, Gordana Petrushevska Institute of Pathology, Faculty of Medicine, University Ss. Cyril and Methodius, Skopje, Republic of Macedonia Aim: We present an illustrative autopsy case of thrombosed giant bilateral vertebral artery aneurysms. Introduction: A 61-year-old male died at Department of Infective disease with a clinical diagnosis for bilateral bronchopneumonia, cerebral aneurism, fibro muscular dysplasia, CVI, HTA, chronic CMP, cardiac arrest. Material and Methods: Standard autopsy technic with neuropathology brain dissection and standard procedure of paraffin embedded section routinely stained with HE was performed. Results: Gross examination of the brain at the autopsy showed saccular giant bilateral vertebral artery aneurysms that measured 58 mm on the right and 40 mm on the left artery. They were tumor-like and compressed the medulla and pons. Both were thrombosed. The right was ruptured with subacute subarachnoid bleeding. Sections of the cerebral vessels exhibited minimal atherosclerotic plaques, with mild stenosis (focally up to 10%) of the left internal carotid artery. We found mild dilatation on ventricles and minimal cortical atrophy of the brain. During the microscopic examination angiodysplasia with abnormally dilated blood vessels on visceral organs, predominantly on brain and heart was detected. The cause of death was central type of cardiopulmonary insufficiency with pulmonary edema. Conclusion: We presented an extremely rare case with bilateral giant vertebral aneurysms. Giant cerebral aneurysms are ones that measure >25 mm in greatest dimension and account for ~5% of all intracranial aneurysms. They occur in the 5th-7th decades and are more common in females. Vertebral artery aneurysms constitute 0.5 to 3% of intracranial aneurysms and 20% of posterior circulation aneurysms. Key words: Autopsy, Giant aneurysm, vertebral artery 70

71 Apstrakti/Abstracts Granulomatozna zapaljenja u štitastoj žlezdi Božidar Kovačević Institut za patologiju i sudsku medicinu, VMA, Beograd, Srbija Cilj rada je prikaz patoloških procesa ŠŽ sa histološkom detekcijom granuloma, analiza morfoloških formi granuloma i njihovog dijagnostičkog značaja. Rad prikazuje najznačajnije granulomatozne lezije u ŠŽ na osnovu pregleda literature i uvida u arhivski materijal Instituta za patologiju i sudsku medicinu Vojnomedicinske akademije. Prisustvo granuloma u štitastoj žlezdi (ŠŽ) obuhvata specifične patološke procese kao što su subakutni tireoiditis (SAT) i palpacioni tireoiditis (PT). Klinička manifestacija granuloma može da bude praćena simetričnim ili asimetričnim uvećanjem i palpatornim bolom žlezde zbog čega su neophodna dodatna ispitivanja. Granulomi u ŠŽ mogu da budu udruženi sa raznim benignim i malignim stanjima. Postoje dve velike grupe granuloma: granulomi tipa oko stranog tela (GOST) i imunološki granulomi (IGR). Granulomi tipa oko stranog tela su histiocitne reakcije na hemijski inertne, egzogene ili endogene materijale. Etiološki, IGR nastaju u okviru infektivnih, autoimunih, toksičnih, lekovima indukovanim ili patološkim procesima nepoznate etiologije. Mikroskopska podela IGR odnosi se na granulome sa nekrozom i granulome bez nekroze. Granulomi ŠŽ infektivne, autoimune ili inflamatorne prirode nepoznate etiologiju su izuzetno retki. 1.Granulomi u specifičnim patološkim procesima ŠŽ 1.1 Subakutni (de Quervainov) tireoiditis ili granulomatozni tireoiditis je inflamatorni proces koji se klinički prezentuje uvećanom i bolnom ŠŽ. U najvećem broju slučajeva dolazi do potpunog oporavka funkcije ŠŽ, a permanentni hipotireoidizam se nalazi u oko 5% bolesnika. Pojavi SAT često prethode infekcije gornjih respiratornih puteva. Bolest je etiološki povezana i sa virusnim infekcijama (mumps, influenza, adenovirus, coxackie), genetskom predispozicijom (HLA-BW35) i primenom imunomodulatorne terapije (IFG, IL2, TNF). Makroskopski, ŠŽ je obično simetrično uvećana, ali postoje i lokalizovane forme sa nodularnom morfologijom, koje imitiraju neoplastične lezije. Mikroskopski je karakteristično prisustvo multifokalnih i difuzno raspoređenih folikulocentričnih granuloma. Granulomi se nalaze u različitim fazama, sačinjeni su od epiteloidnih histiocita, limfocita, plazmocita, neutrofila i multinuklearnih đžinovskih ćelija (MDžĆ). Diferencijalno dijagnostički (DDG) najvažnije je razlikovanje SAT od drugih granulomatoznih inflamacija. 1.2 Palpacioni tireoiditis (Multifokalni granulomatozni folikulitis) je najčešći patološki proces u ŠŽ sa mikroskopskom detekcijom granuloma. Radi se o incidentalnom, mikroskospkom nalazu koji zahvata pojedinačne ili manje grupe folikula. Promene nastaju kao posledica mehaničkih mikrotrauma nakon palpacije ŠŽ. Mikroskopski, promene karakteriše oštećenje folikula sa intrafolikularnim nakupljanjem pretežno histiocita uz prisustvo limfocita, plazmocita i MDžĆ. Pored DDG u odnosu na SAT značajno je patohistološko razlikovanje lezija PT u odnosu na primarne i sekundarne mikrofokuse papilarnog mikrokacinoma, hiperplaziju C ćelija i fokalne forme Langerhansove histiocitoze. 2. Granulomi tipa oko stranog tela su čest incidentalni mikroskospki nalaz u ŠŽ. Nastaju kao reakcija na nakupljanje endogenih supstanci u zonama spontane ili degeneracija indukovanih aspiracionom biopsijom tankom iglom (ABTI). Najzastupljenije forme GOST na endogeni materijal su holesterolski granulom u okolini polja nekroze i/ili krvarenja. Histološki ove granulome čine MDžĆ raspoređene oko kristalnih formacija, penasti histiociti i hemosiderofagi raspoređeni u okolini depozita kristala. U zavisnost od starosti lezije, mogu se naći fokusi nekroze, različit stepen fibroze, ekstracelularni depoziti hemosiderina kao i druge inflamatorne ćelije. Prisustvo GOST granuloma i histiocitnih nakupina ima značaja u preopeartivnoj citološkoj dijagnostici ali i postoperativnoj patohistološkoj analizi nodusa ŠŽ. Krupni nukleusi histiocita sa hipohromazijom i iregularnostima na nuklearnim membranama i prisustvo MDžĆ mogu imitirati citološku sliku papilarnog karcinoma ŠŽ (PKŠŽ). Citološka DDG je naročito teška u odnosu na retku formu PKŠŽ sa histiocitoidnim ćelijama. Egzogeni biomaterijali, retko predstavljaju uzrok GOST u ŠŽ. Granulomi u okolini hirurškog materijala se viđaju u tkivu ŠŽ nakon prethodno učinjene hiruške intervencije u vratu. U slučajevima dijagnostikovanih maligniteta ŠŽ nakon učinjene tireoidektomije, pojava sutura GOST u loži ŠŽ imitira recidiv ili rest maligniteta i razlog je ponovljenih hirurških intervencija. 3. Granulomi sa nekrozom u ŠŽ Granlomi sa nekrozom mogu biti infektivne ili neinfektivne etiologije. Tuberkuloza je najčešći uzrok nekrotizirajućih granuloma (NGR) u ŠŽ. Tubekuloza u ŠŽ se može prezentovati kao solitarna nodalna lezija, difuzne mikrolezije, nodularna struma, a retko i kao absces ili hronični kožni sinus. U literaturi je opisano manje od sto slučajeva tuberkuloze ŠŽ. Kao uzročnici sporadičnih slučajeva NGR u ŠŽ prijavljene su infekcije izazvane histoplazmozom, kokcidiomikozom i nokardijom. Retki neinfektivni NGR u ŠŽ ili 71

72 APSTRAKTI njenoj loži autoimune etiologije opisani su u sklopu Wegenerove granulomatoze i reumatoidnog artritisa. U okviru NGR neinfektivne prirode spadaju i post operativni granulomi. Smatraju se posledicom primene dijatermije u toku hirurškog lečenja. Mikroskopski, prisutna je morfologija koja odgovara postbiopsijskim granulomima u drugim organima (prostata, mokraćna bešika). 4.Granulomi bez nekroze u ŠŽ. Sarkoidoza je multisistemska hronična granulomatozna inflamacija nepoznate etiologije. Klinički može biti udružena sa autoimunim bolestima ŠŽ, ali je ŠŽ retko zahvaćena sarkoidozom. Makroskopski, žlezda je difuzno ili nodularno uvećana ili smanjenog volumena. Intersticijalno lokalizovani nenekrotizirajući granulomi (NNGR) predstavljaju tipičnu histološku prezentaciju sarkoidoze ŠŽ. Važna je i DDG sarkoidoze ŠŽ prema sarkoidnom tipu reakcije na PKŠŽ u žlezdi ili regionalnim limfnim čvorovima. U ovim slučajevima neophodno je klinički isključiti sistemsku bolest. 5. Granulomi i histiocitne reakcije u neoplastičnim procesima ŠŽ. Pored opisanih GOST i sarkoidnog tipa reakcije, u epitelnim tumorima ŠŽ mogu se videti i histiocitne reakcje ili nakupine (ne granulomi) načešće kao sekundarne promene nakon ABTI. Ove grupe histiocita su sačinjene od grupe hemosiderofaga i/ili penastih histiocita uz sporadično prisustvo MDžĆ. Intrafolikularno/intraluminalno prisustvo MDžĆ sa ili bez prisustva histocita i morfologijom nalik granulomima predstavljaju karaketrističan nalaz u PKŽŠ. Citološka i histološka detekcija ovih MDžĆ predstavlja jedan od dijagnostičkih kriterijuma za PKŠŽ. Njihovo prisustvo u tumorima može biti posledica reakcije na izmenjeni koloid ili reakcije imunskog sistema u sklopu imunološkog odgovora na tumorske ćelije. Zaključak: Granulomi u ŠŽ nisu retki. Poznavanje morfologije granuloma, patoloških procesa i okolnosti u kojima nastaju je značajno u DDG prema primarnim tumorima ŠŽ, njihovim recidivima i metastazama u limfne čvorove vrata. Dijagnozu granulomatoznih inflamacija u ŠŽ je moguće postaviti na osnovu histoloških karakteristika granuloma u korelaciji sa kliničkim i laboratorijskim nalazima. Ključne reči: granulomi, štitasta žlezda, diferencijalna dijagnoza. Granulomatous inflammation in the thyroid gland Bozidar Kovacevic Institute of Pathology and Forensic medicine, Military Medical Academy, Belgrade, Serbia To present pathological processes of the TG with histological detection of granulomas, analysis of morphological forms of granulomas, and their diagnostic significance. This paper is based on literature review and insight into the archival materials of the Institute of Pathology and Forensic Medicine of the Military Medical Academy.The presence of granulomas in the thyroid gland (TG) includes specific pathological processes such as subacute thyroiditis (SAT) and palpation thyroiditis (PT). The clinical manifestations of the granulomas may be accompanied by symmetrical or asymmetrical enlargement and palpatory pain in the gland, which requires further clinical examination. Granulomas in the TG can be associated with various benign and malignant processes. There are two large groups of granulomas: foreign-body giant cell granulomas (FBG) and immune granulomas (IGR). FBG are histiocytic reactions to chemically inert, exogenous or endogenous materials. Etiologically, IGRs arise in the framework of infectious, autoimmune, toxic, drug-induced or pathological processes of unknown etiology. According to the presence of necrosis IGRs can be further divided as necrotizing or non-necrotizing type. TG granulomas of the infectious, autoimmune or inflammatory nature of the unknown etiology are extremely rare. 1. Granulomas in specific pathological processes of the TG Subacute (de Quervain s) thyroiditis or granulomatous thyroiditis is an inflammatory process that is clinically presented as enlarged and painful TG. In most cases, the result is a complete recovery of the TG function. Permanent hypothyroidism is found in about 5% of patients. SAT is usually preceded by upper respiratory tract infection. The disease is etiologically related to viral infections, genetic predisposition and the use of immuno therapy. Macroscopically, TG is usually symmetrically enlarged, but there are also localized forms with nodular morphology, which imitate neoplastic lesions. The microscopic characteristic is the presence of multifocal and diffusely distributed folliculocentric granulomas. They are found in different phases and consist of epitheloid histiocytes, lymphocytes, plasma cells, neutrophils, and multinuclear giant cells (MGC). At the center of the granuloma, the colloid is reduced or absent. In later phases, fibrosis can develop perifollicularly. In terms of differential diagnosis (DDG), it is important to differentiate SAT from other granulomatous inflammations. Palpation thyroiditis (Multifocal granulomatous folliculitis) is the most common pathological process in TG with microscopic detection of granulomas. It is an incidental microscopic finding involving individual or minor follicular groups. Changes arise as a result of mechanical microtrauma after the palpation of the TG. Microscopic changes are characterized by damage to the follicles with interfollicular 72

73 ABSTRACTS accumulation mainly of histiocytes in the presence of lymphocytes, plasma cells and MGCs. In the DDG of PT, the following conditions must be considered: SAT, primary and secondary microscopic foci of papillary microcarcinoma, C-cell hyperplasia, and focal forms of Langerhans histiocytosis. 2. Foreign-body giant cell granuloma is frequent incidental microscopic finding in TG. It arises as a reaction to the accumulation of endogenous substances in the areas of spontaneous or degenerations induces by fine-needle aspiration biopsy (FNAB). The most common forms of FBGs on endogenous material are cholesterol granulomas. These FBGs are composed of MGCs, foamy histiocytes, and hemosiderophages arranged around crystal deposits. Depending on how old the lesion is, there may be a focal necrosis, a different degree of fibrosis, extracellular deposits of hemosiderin, and other inflammatory cells. The presence of FBGs and histiocytic aggregates is not only important in the preoperative cytological diagnostics, but also in the post-operative pathohistological analysis of TG nodules. Large nuclei of histiocytes with hypochromasia, nuclear membrane irregularities and the presence of MGC can imitate the cytological features of papillary thyroid carcinoma (PTC). Exogenous biomaterials are rarely cause of FBGs in TG. After thyroidectomy, in cases of diagnosed TG malignancies, the presence of suture FBGs in thyroid bed imitates recurrence or the rest of malignancy and is the cause of repeated surgeries. 3. Necrotizing granulomas (NGR) in TG Granulomas with necrosis may be of infectious and noninfectious etiology. Tuberculosis is the most common cause of NGR in TG. Tuberculosis in TG can be presented as a solitary nodal lesion, diffuse microlesions, nodular goiter, and rarely as an abscess or a chronic skin sinus. As a infectious cause of NGR in TG, sporadically reported cases have been caused by histoplasmosis, coccidioidomycosis and nocardiosis. Rare non-infectious NGR in TG or in the TG bed, of autoimmune etiologies, have been described as part of Wegener s granulomatosis and rheumatoid arthritis. Post-operative necrotizing granulomas also represent NGR of non-infectious cause. Microscopically, there is a morphology that matches post biopsy granulomas in other organs (prostate, urinary bladder). 4. Non-necrotizing granulomas (NNGR) in TG Sarcoidosis is a multi-systemic chronic granulomatous inflammation of unknown etiology. Thyroid is rarely affected by sarcoidosis. Macroscopically, the gland is diffusely or nodularly enlarged or reduced in volume. Interstitially localized NNGR represent a typical histological presentation. Sarcoidosis of TG should be distinguished from the sarcoid-like stromal reactions of PTC in the gland or regional lymph nodes. In these cases, it is necessary to clinically exclude the systemic disease. 5. Granulomas and histiocytic reactions in neoplastic processes of TG Apart from the described FBGs, PT and sarcoid-like reactions, in epithelial tumors of the TG histiocytic aggregates (not granulomas) may also be seen as secondary changes after FNAB. Interfollicular/ intraluminal presence of MGCs with or without the presence of histiocytes and granuloma-like morphology represents a characteristic finding in PTC. The cytological and histological detection of MGCs is one of the diagnostic criteria for PTC. Their presence in tumors may be due to a reaction to an altered colloid produced by PTC or as a non-specific immune response to due tumor cells. Conclusion: Granulomas in the TG are not rare. Knowing the morphology of granulomas, pathological processes and the circumstances in which they occur is significant in DDG of primary tumors of the TG, their recurrence and metastases in the cervical lymph nodes. The diagnosis of granulomatous inflammation in TG can be based on the histological characteristics of granulomas in correlation with clinical and laboratory findings. Key words: granulomas, thyroid gland, differential diagnosis. Literature: 1. Loyd VR. Endocrine pathology: Differential Diagnosis and Molecular Advances. Second edition, New York, Springer Shahab KK, Pritta BS, Alexander MP. Histopathologic review of granulomatous inflammation. Journal of Clinical Tuberculosis and Other Mycobacterial Diseases. 2017; 7, Shrestha RT, Hennessey J. Acute and Subacute, and Riedel s Thyroiditis. [Updated 2015 Dec 8]. In: De Groot LJ, Chrousos G, Dungan K, et al., editors. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; Available from: 4. Polyzos SA, Patsiaoura K, Zachou K. Histological alterations following thyroid fine needle biopsy: a systematic review. Diagn Cytopathol. 2009; 37(6): doi: /dc Muzaffar TH, Al-Ansari JM, Al-Humrani H. Brief review of sarcoidosis of the thyroid gland. International Journal of Medicine and Medical Sciences. 2009;1(3):

74 Granične neoplastične lezije: Gde je crvena linija? Tumori graničnog maligniteta gastrointestinalnog i hepatobilijarnog trakta Marjan Micev Služba patologije, Klinički Centar Srbije, Beograd, Srbija Ova mala kliničko-patološka kategorija tumora se odlikuje nepredvidljivošću kliničkog toka i/ili ishoda bolesti, a tome u prilog često govore i patohistološka obeležja tumora koja pružaju samo neke odlike maligniteta, sugerišu mogući maligni potencijal ili pokazuju odlike između benignih i malignih proliferacija 1. Boljim definisanjem dijagnostičkih kriterijuma danas su ovi tumori smanjeni na manje od 5% svih tumora u GI i HBP sistemima, a njihov maligni potencijal se često posredno izražava kao proliferativni, recidivni ili metastatski potencijal 2,3. Najveći broj njih odnosi se na dobro diferentovane neuroendokrine tumore (NET), gastrointestinalne stromalne tumore (GIST) i mucinozne cistične neoplazije (MCN). Od epitelnih neoplazija nejasnog malignog potencijala u digestivnoj cevi se posebno izdvajaju mucinozne neoplazije apendiksa i cekuma (do 0,2% tumora GIT) često praćene rupturom i peritonealnim pseudomiksomom kao tzv. diseminovana peritonealna mucinoza 4. One se odlikuju cistadenomskom morfologijom, ponekad kompleksne acinusne i mikrocistične organizacije sa displastičnim epitelom i mucinoznom (pseudo)invazijom zida, ali bez invazivnosti epitelnih elemenata 5. Slična histološka obeležja vide se u kod mucinoznih cističnih neoplazija (MCN) u biliopankreatičnom traktu i jetri, gde se displastične epitelne promene duktusa pankreasa (analogne pankreasnoj intraepitelnoj neoplaziji PanIN I-III), i bilijarnih duktusa (analogne bilijarnoj intraepitelnoj neoplaziji BilIN I-III) u perifernim zonama razgranavanja moraju jasno razlikovati od rane invazije, tj. od adenokarcinoma 6. Kad su u pitanju adenomatozni polipi sa pseudoinvazijom u digestivnom traktu, oni se moraju razlikovati od pravih malignih polipa tj. adenomatoznih polipa sa ranom invazijom koji pokazuju disekciju stromalnih elemenata mukoze i submukoze i izazivaju dezmoplastičnu reakciju. Pseudoinvazija se odlikuje odsustvom infiltrativnog tipa rasta, dezmoplazije, uočavanjem strome (lamine proprije) oko prolabiranih glandularnih struktura, hemoragijom, hemosiderofagijom, a nekada i invertnim rastom, bilo pulzionim ili limfovaskularnim, kao i stvaranjem limfoglandularnih kompleksa sa fokalnim limfoidnim agregatima 7. Kada su u pitanju dobro diferentovani NET, danas se pored klasične i imunohistohemijske dijagnostike obavezno moraju odrediti i korelirati mitotski indeks (MI) izražen na 10 polja velikog mikroskopskog uveličanja, ali određen na najmanje 50 polja, kao i procentualni proliferativni Ki-67 indeks određen u području najveće aktivnosti na najmanje 500 ćelija. Na taj način određuje se stepen maligniteta NET koji po novoj klasifikaciji iz godine koji pored NET-G1 i NET-G2 podrazumeva i novouvedeni dobro diferentovani NET visokog stepena (NET-G3) za tumore sa MI preko 20 /10HPF i Ki-67 indeks preko 20%, ali koji se moraju razlikovati od slabo diferentovanih neuroendokrinih karcinoma (NEC) istih ili viših vrednosti ovih parametara 8. Značajna je i grupa visceralnih mezenhimalnih tumora nejasnog malignog potencijala koji se pojavljuju u digestivnom sistemu, posebno za GIST kao najčešći od njih i koji čini oko 2% klinički značajnih tumora u abdomenu. Danas su jasno definisani AFIP kriterijumi malignog potencijala (Miettinen, 2005) i NIH kriterijumi metastaskog potencijala (Fletcher, 2002) koji čine i sastavni deo aktuelnih TNM klasifikacija. Oni uključuju obavezne podatke o preciznoj lokalizaciji i veličini tumora i mitotskom indeksu izraženom na 50 polja velikog mikroskopskog uveličanja 9. Na osnovu toga se prepostavljaju stepeni rizika malignog toka bolesti i uključivanja adjuvantnih terapijskih protokola, dok je za lečenje metastatske i/ili neresektabilne bolesti neophodno određivanje mutacionog statusa KIT, PDGFRA, SDHA i SDHB gena. Takođe je značajno prepoznavanje i nalčin dijagnostike inflamatornog miofibroblastnog tumora (IMT) koji najčešće zahvata adolescente i mlade ženske odrasle osobe (75% intra-abdominalno i ponekad multinodularno), a histološki se odlikuje karakterističnom mešavinom inflamatornih (posebno limfoplazmocitnih i histiocitnih) i stromalnih (posebno miofibroblastnih) elemenata 10. Karakteristična nuklearna imunoreaktivnost za ALK-1 protein se vidi samo u oko 50% slučajeva. Ovaj tip tumora ima nepredvidiv tok, ali se recidivi (29%) i metastaze (4%) češće javljaju kod epiteloidnih hipercelularnih i mitotski aktivnijih tumora sa pojavom nuklearne atipije stromalnih ćelija 11. Hepato-biliopankreatični tumori nejasnog malignog potencijala osim pomenutih MCN podrazumevaju i intraduktalne papilarne mucinozne neoplazme (IPMN) sa teškom epitelnom displazijom (analogne BilIN III, PanIN III) ali bez pridružene mikroinvazije ili jasnih adenokarcinoma 12. Takođe, hepatomi nejasnog malignog potencijala su hepatoidni tumori koji odgovaraju hepatocelularnim adenomima (HCA) s ati- 74

75 ABSTRACTS pijom neoplastičnih ćelija i koji ne ispunjavaju sve ostale parametre maligniteta (elementi invazivnosti, trabekularna dezorganizacija i povećanje broja gredica, evidentna mitotska aktivnost) a po pravilu su beta-katenin aktivišući tip HCA koji se imunohistohemijski može dokazati i koji pokazuje visok stepen maligne transformacije 13. Usled toga je neophodno ekstezivno uzorkovanje velikih HCA tumora da se ne bi previdela fokalna maligna alteracija. U jetri se retko može videti i epiteloidni hemangioendoteliom (EHE), nepredvidivog kliničkog toka, koji se često pogrešno interpretira kao (adeno)karcinom. Po pravilu se javlja kod osoba srednjeg životnog doba, kao multipla nodularna promena (80%) i javlja se s ekstrahepatičnim širenjem u 50% slučajeva. Neophodno je da se kod mladih jasno razlikuje od infantilnog hemangioendotelioma. Mikroskopski se odlikuje zonalnošću sa centralnom miksohondroidnom i sklerotičnom promenom u kojoj se vide dendritične tumorske ćelije, dok se periferno uočavaju delom obliterisani a delom prošireni sinusoidi sa papilarnim projekcijama atipičnog endotela 14. Često se u tumorskim ćelijama vide intracitoplazmatske vakuole koje mogu sadržati eritrocite. Mora se razlikovati od dobro diferentovanog angiosarkoma visokom celularnošću i jačom atipijom, što je povezano i sa malignom alteracijom EHE. Pankreasna solidno-pseudopapilarna neoplazija se odlikuje češćim benignim kliničkim tokom nego recidivima i veoma retkim metastaziranjem. Opisala ju je Virginia Franz (1959) kao pedijatrijski benigni tumor, ali se danas izdvaja boljom mikroskopskom karakterizacijom kod adolescenata i mladih (10-45 god.). Obilno se javlja u distalnom pankreasu, promera od 3-15 cm kao jasno ograničen, lobuliran, hemoragičan tumor. Histološki ga odlikuju papilarnost, pseudorozete, holegranulomi i fokalna hijalinizacija 15. Maligni potencijal i rizik metastaziranja se povezuju sa hipercelularnošću, atipijom i izraženijom mitotskom aktivnošću. Literature: 1. McGraw-Hill Concise Dictionary of Modern Medicine. (2002). Retrieved January from 2. Wallace Park W. A Philosophy of Cancer Diagnosis by Microscopy. In The Histology of Borderline Cancer. Ed. Wallace Park W. Springer-Verlag Berlin, Heidelberg, New York; pp. 1-12, Rosai J. The benign versus malignant paradigm in oncologic pathology: a critique. Seminars in Diagnostic Pathology 25: , Ronnett BM, Zahn CM, Kurman RJ, Kass ME, Sugarbaker PH, Shmookler BM. Disseminated peritoneal adenomucinosis and peritoneal mucinous carcinomatosis. A clinicopathologic analysis of 109 cases with emphasis on distinguishing pathologic features, site of origin, prognosis, and relationship to pseudomyxoma peritonei. Am J Surg Pathol Dec;19(12): Tirumani SH, Fraser-Hill M, Auer R, et al. Mucinous neoplasms of the appendix: a current comprehensive clinicopathologic and imaging review. Cancer Imaging. 2013;13(1): doi: / Crippa S, Salvia R, Warshaw AL, et al. Mucinous Cystic Neoplasm of the Pancreas is Not an Aggressive Entity: Lessons From 163 Resected Patients. Annals of surgery. 2008;247(4): doi: /sla.0b013e31811f Byun TJ, Han DS, Ahn SB, et al. Pseudoinvasion in an Adenomatous Polyp of the Colon Mimicking Invasive Colon Cancer. Gut and Liver. 2009;3(2): doi: /gnl Klöppel G, Klimstra D, Hruban RH, Adsay V, Capella C, Couvelard A, Komminoth P, La Rosa S, Ohike N, Osamura RY, Perren A, Scoazec J-Y, Rindi G. Pancreatic Neuroendocrine Tumors: Update on the New World Health Organization Classification. AJSP: Reviews & Reports. 22(5): , Rammohan A, Sathyanesan J, Rajendran K, et al. A gist of gastrointestinal stromal tumors: A review. World Journal of Gastrointestinal Oncology. 2013;5(6): doi: /wjgo.v5.i Cantera JE, Alfaro MP, Rafart DC, et al. Inflammatory myofibroblastic tumours: a pictorial review. Insights into Imaging. 2015;6(1): doi: /s Mariño-Enríquez A, Wang WL, Roy A, Lopez-Terrada D, Lazar AJ, Fletcher CD, Coffin CM, Hornick JL. Epithelioid inflammatory myofibroblastic sarcoma: An aggressive intra-abdominal variant of inflammatory myofibroblastic tumor with nuclear membrane or perinuclear ALK. Am J Surg Pathol Jan;35(1): doi: / PAS.0b013e318200cfd Machado NO, al Qadhi H, al Wahibi K. Intraductal Papillary Mucinous Neoplasm of Pancreas. North American Journal of Medical Sciences. 2015;7(5): doi: / Bedossa P, Burt AD, Brunt EM, Callea F, Clouston AD, Dienes HP et al. Well-differentiated hepatocellular neoplasm of uncertain malignant potential: Proposal for a new diagnostic category. Human Pathology Mar;45(3): Available from, DOI: /j.humpath Sardaro A, Bardoscia L, Petruzzelli MF, Portaluri M. Epithelioid Hemangioendothelioma: An Overview and Update on a Rare Vascular Tumor. Oncology Reviews. 2014;8(2):259. doi: /oncol

76 APSTRAKTI 15. Sanhueza CT, Jin Z, Smyrk TC, Hartgers ML, Alberts SR, Mahipal A. Clinical and pathological features of solid pseudopapillary neoplasm (SPN) of the pancreas: A retrospective review of cases at Mayo Clinic. Journal of Clinical Oncology 2017; 35:15 Suppl. e15757-e15757 Androgen insensitivity (testicular feminization) syndrome and XY gonadal dysgenesis (Swyer syndrome) Neli Basheska University Clinic of Radiotherapy and Oncology, Ss Cyril and Methodius Faculty of Medicine, Skopje, Republic of Macedonia Case 1: Clinical History -The patient was an 18-year-old woman with a history of primary amenorrhea. The physical examination revealed normal female external genitalia, moderate breast development, scarce pubic hair, and scant axillary hair. Pelvic examination revealed an absence of a uterus. The vagina ended in a blind pouch and measured 6cm in length. An abdominal ultrasonogram showed solid bilateral gonadal structures measuring 31x15mm right, and 30x 6mm left in the pelvic cavity without any evidence of a uterus. These findings were confirmed by MRI scan. Serum levels of estradiol and testosterone were 45.7pg/mL and 7.5nmol/L, respectively. FSH and LH levels were 8.46mlU/ml and 20.2mlU/ml. Cytogenetic analysis of peripheral blood lymphocytes revealed a 46,XY karyotype, with translocation t(13,14) inherited from her father. The molecular investigation confirmed active SRY with amplification of 6 nonpolymorphic loci on AZFa, AZFb, and AZFc regions on Y chromosome. Three months after her first referral the patient underwent bilateral prophylactic laparoscopic gonadectomy. The patient is being followed up regularly and she has no complaints after five years. Pathological Findings- Grossly, the right gonad was 4.3x1.8x1.8cm and the left gonad was 4.5x2.0x1.7cm. The right fallopian tube was 3.8cm long and 0.2cm in diameter, while the left one was 1.5cm long and 0.2cm in diameter. In addition, 4 cysts measuring 0.3-1cm in diameter were found in the fat tissue on the surface of the left fallopian tube. The cut surface of the right gonad resembled testicular tissue showing two discrete, firm, well-demarcated, slightly bulging, homogenous, light grey-tan colored nodules, measuring 0.1 and 0.9cm in maximal dimension. Three similarly looking nodules were present in the left gonad measuring cm in diameter. In addition, a white whorled, firm, smooth muscle body fused to one pole of the gonad was found bilaterally measuring 1.2cm right, and 1.3cm left. Microscopically, both gonads were composed of varying proportions of small and solid, or less frequently larger, with early lumen formation seminiferous tubules lined by immature Sertoli cells, surrounded with fibrous, focally edematous stroma in which prominent Leydig cells were present. Rare tubules contained Sertoli cells with abundant cytoplasm filled with coarse, eosinophilic granules. The nodules were composed of solid immature tubules lined by cylindrical immature Sertoli cells separated by fibrous stroma containing fewer Leydig cells. Fallopian tubes were hypoplasic, while the cysts were lined by a single layer of cuboidal to columnar cells some of which had cilia. Thus, the clinical, laboratory, imaging, genetic and histological findings confirmed the diagnosis of complete androgen insensitivity syndrome with bilateral testicular hamartomas.discussion Androgen insensitivity syndrome (AIS) is a disorder where there is resistance to androgen actions influencing both the morphogenesis and differentiation of androgen-responsive body structures. It is the most common type of male pseudohermaphroditism, characterized by an absence of androgen receptor activity due to a mutation at Xq11 q12 localization on the androgen receptor gene. the. In the largest series of 43 patients with the AIS published by Rutgers and Scully hamartomas were present in 63% of the cases, while Sertoli cell adenomas were reported in 23% and malignant tumors including two seminomas, one intratubular germ cell neoplasm with early stromal invasion and a malignant sex cord tumor in 9% of the cases. Case 2: Clinical History- The patient was a 17-year-old girl with primary amenorrhea. On external examination, she had an unambiguous female phenotype albeit with poor breast development. Her external genitalia had a normal appearance but internal examination showed a hypoplastic uterus. Ultrasonography failed to show follicular activity in the gonads. Her gonadotropins were high (FSH, 55.6mU/ml; LH, 18.3mU/ml) and estradiol was low (20.0pg/ml). Nonmosaic 46,XY karyotype was detected in patient s leukocytes by cytogenetic analysis. Under the tentative clinical diagnosis of pure gonadal dysgenesis, a prophylactic bilateral laparoscopic gonadectomy with bilateral salpingectomy was performed. A biopsy specimens from the gonads were sent for cytogenetic analysis. The sequencing of the SRY gene of the proband revealed a C/G substitution at the first nucleotide of codon 133, leading to Arg/Gly replacement in the SRY protein. The mutation was also present in patient s father, who is a phenotypically normal male. 76

77 ABSTRACTS The patient is alive and well 12 years after the operation without any evidence of disease. Pathological Findings- Macroscopically, both fallopian tubes were 4cm long and 0.4cm in diameter, while the gonads were measuring 3x2.2x1.2cm the right, and 2.2x0.8x1cm the left. Upon dissection, both gonadal streaks had a similar, variegated appearance with multiple areas of microcalcification. The histological evaluation of the gonads confirmed a gonadoblastoma of 3cm in diameter in the right gonad and a predominantly burnt-out gonadoblastoma of 2.2cm in the left gonad with only a microscopic focus of recognizable gonadoblastoma less than 1mm in diameter. The tumors were composed of primordial germ cells intimately admixed with sex cord elements, which surrounded round spaces filled with eosinophilic basement membrane-like material. The atypical germ cells had abundant clear or pale, slightly granular cytoplasm and round vesicular nuclei with prominent nucleoli. The small, often fusiform sex cord element cells had uniform round or oval nuclei with indiscernible nucleoli and scant cytoplasm. The uninvolved gonadal tissue bilaterally had the morphology of a streak gonad composed largely of ovarian-type stroma, with extended calcification and small germinal inclusion cysts present, without any follicles. The fallopian tubes were infantile. Therefore, the histopathological findings confirmed the diagnosis of bilateral gonadoblastoma in streak gonads, FIGO Stage IB, in a patient with a XY gonadal dysgenesis (Swyer syndrome). Discussion: XY gonadal dysgenesis (GD) is a result of abnormal testis development in utero. Pure 46,XY GD should be considered when an adolescent presents as a phenotypic female with delayed puberty and primary amenorrhea. Rarely, they may present with a detectable abdominal or pelvic gonadoblastoma mass. When the presumptive diagnosis suggests GD, further criteria may strengthen the diagnosis, while ultimately, the most definitive diagnosis is through biopsy of the gonads. Bilateral streak gonads are seen in pure XY GD. The risk of otherwise undetected gonadoblastoma in XY GD patients is high, and prophylactic or therapeutic gonadectomy is therefore often indicated when XY GD is diagnosed. Literature: 1. Brown CJ, Goss SJ, Lubahn DB, Joseph DR, Wilson EM, French FS, Willard HF. Androgen receptor locus on the human X chromosome: regional localization to Xq11-12 and description of a DNA polymorphism. Am J Hum Genet. 1989;44(2): Chaudhry S, Tadokoro-Cuccaro R, Hannema SE, Acerini CL, Hughes IA. Frequency of gonadal tumours in complete androgen insensitivity syndrome (CAIS): A retrospective case-series analysis. J Pediatr Urol. 2017;13(5): Kurman RJ. (editor) Blaustein`s Pathology of the Female Genital Tract. 5th edition. New York: Springer, 2002: Rutgers JL, Scully RE. The androgen insensitivity syndrome (testicular feminization): a clinicopathologic study of 43 cases. Int J Gynecol Pathol 1991;10: Uehara S, Funato T, Yaegashi N, Suziki H, Sato J, Sasaki T, Yajima A. SRY mutation and tumor formation on the gonads of XY pure gonadal dysgenesis patients. Cancer Genet Cytogenet. 1999;113(1): Sarkomatoidna diferencijacija u karcinomima bubrega Ljubinka Janković Veličković Centar za Patologiju, Klinički cenar Niš Sarkomatoidna diferencijacija u karcinomu bubrega (sarkomatoidni karcinom bubrega - srcc) predstavlja dediferentovanu neoplazmu bubrega visokog gradusa koja sadrži karcinomsku i sarkomsku komponentu. srcc su relativno retki tumori sa incidencom od 5-8% u karcinomu bubrega. Sarkomatoidna diferencijacija je rezultat divergentne diferencijacije malignih epitelnih ćelija. U ovom procesu tumorske ćelije gube fenotipske karakteristike epitelnih, a zadobijaju mezenhimske karakteristike, što im obezbeđuje veću sposobnost za migraciju i metastaziranje. Ovaj fenotip se može javiti u svim podtipovima RCC, uključujući svetloćelijski, papilarni, hromofobni RCC i karcinom sabirnih kanalića. Sarkomatoidna komponenta može pokazivati sliku fibrosarcoma ili ne diferentovanog pleomorfnog sarkoma. Ređe je prisutna heterologna diferencijacija, sa slikom koja podseća na rhabdomyosarcom, chondrosarcom, ili osteosarcom. Rabdoidni fenotip predstavljaju agresivnu formu divergentne diferencijacije koja je opisana u clear cell RCC, papilarnom RCC, kao i hromofobnom RCC (CRRCC). CRRCC se javlja u oko 6% svih RCC i ima bolju prognozu u odnosu na ostale podtipove RCC. Sarkomatoidna diferencijacija u CRRCC se sreće u oko 8% ovih tumora i indikator je loše prognoze, kao i u ostalim RCC. Sarkomatoidna komponenta može da predstavlja terminalno dediferentovan klon koji se može razviti iz bilo kog podtipa RCC ili se može razviti iz posebnog klona. Iako se srcc najčešće vidi u high grade tumorima, pojava sarkomatoidne diferencijacije u RCC, Fuhrman ½, što je detektovano u >30%, osporava tvrdnju da je sarkomatidna diferencijacija 77

78 APSTRAKTI kontinuirani proces dediferencijacije klasičnog RCC već posledica aktivacije sarkomatoidne stem ćelije unutar tumora. Kod postojanja sarkomatoidne diferencijacije u karcinomu bubrega neophodno je detektovati fokuse karcinoma bubrega bilo kog morfološkog tipa ili verifikovati imunohistohemijsku pozitivnost sarkomatoidne komponente na epitelne i mezenhimne markere. Njihovo epitelno poreklo potvrđuje ekspresija citokeratina ili EMA.PAX8, CAIX i CD10 mogu se koristiti kako bi se dokazalo bubrežno poreklo, što je naročito značajno kod postojanja sarkomatoidnih ćelija u iglenoj biopsiji bubrega ili metastatskom srcc. CAIX, p53 i Bcl-2 mogu imati značajnu ulogu u transformaciji RCC u visoko malignu neoplazmu sa sarkomatoidnom diferencijacijom. Ekspresija CAIX, p53 i Bcl-2 je pokazatelj loše prognoze i slabijeg preživljavanja pacijenata sa srcc. Značajni mikromorfološki parametri koji mogu uticati na klinički tok bolesti obuhvataju procenat sarkomatoidne diferencijacije (>50%), prisustvo vaskularne invazije, rasprostranjenost nekroze i uznapredovali TNM stadijum. Tip i gradus sarkomatoidne komponente, kao i podtip RCC nemaju uticaja na klinički tok. Prognoza pacijenata sa srcc je gora u odnosu na prognozu ostalih histoloških formi RCC. Sarkomatoidna diferencijacija u RCC je značajan uzročnik mortaliteta, sa prosečnim preživljavanjem od 4-9 meseci nakon dijagnostike. Većina neklasifikovanih RCC sadrži različiti procenat tumorskih ćelija sa sarkomatoidnom morfologijom, bez prepoznatljive epitelne komponente. Oko 3% RCC su isključivo sarkomatoidni. Oni su veći, češće vrše invaziju nadbubrežne žlezde ili drugih susednih organa, češće metastaziraju u regionalne limfne noduse i kosti i imaju značajno kraće preživljavanje (prosek je 4,3 meseca). Diferencijalno dijagnostički u srcc treba isključiti primarni sarkom bubrega, sarkomatoidni urotelni karcinom i angiomyolipom. Mikromorfološki srccs može izgledati poput klasičnog sarcoma, mada treba imati u vidu da su primarni sarkomi bubrega izuzetno retki kod odraslih i čine <1% malignih tumora bubrega. Polovina primarnih sarkoma bubrega su leiomyosarcomi koji sadrže glatkomišićnu komponentu i koja je izuzetno retka u srccs. U sarkomatoidnom urotelnom karcinomu značajna je lokalizacija tumora, prisustvo carcinomain situ, postojanje recidiva urotelnog carcinoma, kao i imunohistohemijska pozitivnost na CKhmw i p63. U angiomyolipomu imunoreaktivnost na HMB45, kaoi prisustvo fokusa sa klasičnom morfologijom isključuju sarkomatoidni RCC. Zaključak: Sarkomatoidna diferencijacija u karcinomu bubrega je rezultat divergentne diferencijacije malignih epitelnih ćelija i može se razviti u svim podtipovima karcinoma bubrežnih čelija. U ovom procesu tumorske ćelije gube fenotipske karakteristike epitelnih, a zadobijaju mezenhimske karakteristike, što im obezbeđuje veću sposobnost za migraciju i metastaziranje. Jako je značajno uočiti prisustvo sarkomatoidne diferencijacije u karcinomu bubrega s obzirom da je indikator loše prognoze bez obzira na podtip RCC. Literature: 1. Gira FA, Barbieri A, Fellegara G, Zompatori M, Corradi D. Dedifferentiated chromophobe renal cell carcinoma with massive osteosarcoma-like divergent differentiation: a singular entity in the spectrum of retroperitoneal calcifying tumors. Int J Surg Pathol. 2010; 18: Li L, Teichberg S, Steckel J, Chen Q. Sarcomatoid renal cell carcinoma with divergent 3. sarcomatoid growth patterns. A case report and review of the literature. Arch Pathol Lab Med. 2005; 129: ShuchB, BratslavskyG, Linehan WM, SrinivasanR. Sarcomatoid renal cell carcinoma: a comprehensive review of the biology and current treatment strategies. Oncologist. 2012; 17: Tan PH, Cheng L, Rioux-Leclercq N, Merino MJ, Netto G, Reuter VE, et al. Renal tumors: diagnostic and prognostic biomarkers. Am J Surg Pathol 2013; 37: Yu W, Wang Y, Jiang Y, Zhang W, Li Y. Distinct immunophenotypes and prognostic factors in renal cell carcinoma with sarcomatoid differentiation: a systematic study of 19 immunohistochemical markers in 42 cases.bmc Cancer 2017; 17:293, Sarcomatoid differentiation in renal carcinoma Ljubinka Jankovic Velickovic Centre of Pathology, Clinical Centre Nis, Serbia Sarcomatoid differentiation in renal cell carcinoma (sarcomatoid renal cell carcinoma srcc) represents a dedifferentiated high grade neoplasm of the kidney that contains carcinomatous and sarcomatous component. srcc is an uncommon tumor, with the incidence of 5-8% of renal carcinoma. Sarcomatoid differentiation is a result of divergent differentiation of malignant epithelial cells. During this process tumor cells lose their epithelial features, and acquire mesenchymal characteristics, which provides them higher 78

79 ABSTRACTS capacity for migration and metastasis.this phenotype can be encountered in all RCC subtypes, including clear cell, papillary, chromophobe RCC, and carcinomaof collecting duct. Sarcomatoid component may resemble fibrosarcoma or undifferentiated pleomorphic sarcoma. Less often heterologous differentiation can be found, with histologic patterns resembling rhabdomyosarcoma, chondrosarcoma, or osteosarcoma. Rhabdoid phenotype is an aggressive form of divergent differentiation which has been described in clear cell RCC, papillary RCC, as well as in chromophobe RCC (CRRCC). CRRCC comprise about 6% of RCC, and has better prognosis compared to other RCC subtypes. Sarcomatoid differentiation is found in 8% of these tumors, and is an indicator of poor prognosis, as it is in other RCC types. Sarcomatoid component may represent terminally dedifferentiated clone which can arise from any RCC subtype, or can develop from a special clone. Although srcc is most frequently found in high grade tumors, the occurrence of sarcomatoid differentiation in RCC, Fuhrman 1/2, detected in 30% of the cases, denies the claim that sarcomatoid differentiation is a continual process of classic RCC dedifferentiation, but a consequence of sarcomatoid stem cell activation within the tumor. In a case of sarcomatoid differentiation in renal carcinoma it is necessary to detect focuses of any morphological type of renal cell carcinoma, and to verify the immunohistochemical positivity of sarcomatoid component to epithelial and mesenchymal markers. Their epithelial origin is confirmed by the expression of cytokeratins, and EMA. PAX8, CAIX, and CD10 can be used to confirm the renal origin, which is of particular importance in finding of sarcomatoid cells in needle biopsy, as well as in metastatic RCC. CAIX, p53, and Bcl-2 can play a major role in transformation of RCC to highly malignant neoplasm with sarcomatoid differentiation. The expression of CAIX, p53, and Bcl-2 is indicator of poor prognosis and worse survival of the patients with srcc. Significant micromorphological parameters that may influence the clinical course of the disease comprise percentage of sarcomatoid differentiation (>50%), presence of vascular invasion, extent of necrosis, and advanced TNM stage. Type and grade of sarcomatoid component, as well as RCC subtype do not influence the clinical outcome. The prognosis of patients with srcc is worse compared to prognosis of other histologic forms of RCC. Sarcomatoid differentiation in RCC is a significant cause of mortality, with average survival of 4-9 months after diagnosis. The majority of unclassified RCCs contains variable percent of tumor cells with sarcomatoid morphology, without recognizable epithelial component. About 3% of RCC are exclusively sarcomatoid. These tumors are larger, more often invade adrenal glands and other adjacent organs, metastasize more frequently into regional lymph nodes and bones, and have significantly shorter survival (average is 4.3 months). Differential diagnosis of srcc should exclude primary renal sarcoma, sarcomatoid urothelial carcinoma, and angiomyolipoma. Micromorphologically srcc may resemble classic sarcoma, however it should be taken into account that primary renal sarcomas are extremely rare in adults, and comprise less than 1% of renal malignancies. The half of primary renal sarcomas are leiomyosarcomas, consisting of smooth muscle component, which is extremely rare in srcc. In sarcomatoid urothelial carcinoma, the location of tumor is of significance, also the presence of carcinoma in situ, recurrence of urothelial carcinoma, and immunohistochemical positivity to CKhmw and p63. In angiomyolipoma, immunoreactivity to HMB45, as well as the presence of focuses with classic morphology, excludes sarcomatoid RCC. Conclusion: Sarcomatoid differentiation in renal cell carcinoma is a result of divergent differentiation of malignant epithelial cell, and can be found in all renal cell carcinoma subtypes. During this process tumor cells lose their epithelial features, and acquire mesenchymal characteristics, which provides them higher capacity for migration and metastasis. It is very important to recognize the presence of sarcomatoid differentiation in renal cell carcinoma, since it is an indicator of poor prognosis irrespective of RCC subtype. Von Meyenburg-ov kompleks Filip Vukmirović, Ljiljana Vučković, Mileta Golubović Centar za patologiju, Klinički centar Crne Gore Uvod: Hamartom žučnih vodova (von Meyenburg-ov kompleks) je benigna promjena koju čine dilatirani žučni vodovi okruženi vezivnom stromom. Incidenca je starosno zavisna i ova promjena se javlja u oko 1% djece i 5-6% odraslih. Hamartom žučnih puteva se javlja u formi sitnih nodusa koji su locirani ispod Glisonove capsule i čija se veličina kreće od 1 do 10 mm. Obično ova lezija nema poseban patološki značaj i uglavnom se slučajno otkriva na laparotomiji kod asimptomatskih pacijenata. Promjena se može naći u normalnoj jetri, ali može biti udružena sa Carolijevim sindomom, kongenitalnom hepatičkom fibrozom, autosomno dominantnom policističnom bolešću bubrega, portalnom hipertenzijom i holangitisom. Nema jasnih dokaza da je ova promjena povezana sa češćim nastankom holangiokarcinoma, mada neki autori navode mogućnost ra- 79

80 APSTRAKTI zvoja displazije lakog I teškog stepena u ovoj leziji, koja može progredirati u holangiokarcinom.ovako nastali holangokarcinom je obično dobro direferentovan, nižeg stadijuma i bolje prognoze u odnosu na holangiokarcinom koji nije povezan sa ovom bolešću. Ultrazvučno promjene mogu različito izgledati, bilo kao hiperehogeni nodusi sa lođe definisanom marginom, bilo kao promjene sa hipoehogenom periferijom koje su jasno ograničene. MR holangiografija predstavlja najbolju radiološku metodu za dijagnostiku ove promjene koja može diferentovati različite forme dilatacije žučnih vodova. Histološki promjene karakteriše različiti broj dilatiranih žučnih kanalića koji su uklopljeni u fibroznu stromu, kojafokalno može biti hijalinizovana. Žučni vodovi su zreli, različite veličine. Epitel koji oblaže ove vodove čine sitnije kubične ćelije sa okruglastim ili ovalnim jedrima. Dilatirani žučni vodovi mogu biti nepravilnog oblikai mogu u lumenu sadržati eozinofilni debris ili zgusnutu žuč. Prikaz slučaja. U radu je prikazan pacijent starosti 68 godina kod koga su ultrazvučno i na MSCT detektovane multiple nodularne promjene na jetri koje su upućivale na metastatske depozite. Anamnestički, pacijent je zadnjih mjesec dana imao povrmeno povraćanje I gubitak na težini. Urađena je hirurška eksploracija pri čemu su uočene bjeličaste subkapsularne lezije različite veličine kojesu zahvatale veći dio površine. Urađene su biopsije tri promjene sa jetre. U ostalom dijelu trbušne duplje pri eksploraciji nijesu nađene patološke promjene. Dobijeni uzorci tkiva su bili sivo-žuto-smeđe boje, srednje čvrste konzistencije. Histološki uočene su multiplenodularne lezije u tkivu jetre koje su bile sagrađene od žučnih puteva inkorporiranih u vezivnu stromu (slika 1). Slika 1. Von Meyenburg-ov kompleks intrahepatički bilijarni duktusi okruženi vezivnom stromom Figure 1. The Von Meyenburg complex - intrahepatic biliary ducts surrounding by fibrotic tissue (HE 100x) Žučni vodovi su uglavnom dilatiranog lumena sa nepravilnim, uglastim ivicama, obloženi uniformnim epitelom (slika 2). Slika 2. Von Meyenburg-ov kompleks dilatirani intrahepatički žučni vod (HE 400x) Figure 2. The Von Meyenburg complex - dilatations of intrahepatic biliary duct (HE 400x) Epitel žučnih kanalića je imunohistohemijski bio Epthelial Membrane Antigen pozitivan, Pan-Cytokeratin pozitivan, Cytokeratin 7 negativan, Cytokeratin5/6 negativan i Carcinoembryonic antigen negativan. Dijagnoza von Meyenburg-ovog kompleksa postavljena je nakon histološkog pregleda promjena sa jetre. Zaključak: von Meyenburg-ovog kompleks je rijedak entitet, čiji je najveći značaj diferencijacija u odnosu na metastatski tumor jetre. Od drugih entiteta u obzir mogu doći i druge benigne lezije jetre, kao hemangiom, adenoma ili infektivne promjene. Prisustvo metastaza na jetri je krucijalno za odluku o liječenju malignih bolesnika, pa je stoga i značaj poznavanja i prepoznavanja ovog entiteta izuzetan. S obzirom da je von Meyenburgov complex često manji od 5 mm, preoperativno može proći neprimijećen na radiološkoj dijagnostici. Makroskopski ova promjena može imitirati metastaze na jetri. Ključne riječi: Hamartom žučnih duktusa, von Meyenburg-ovog kompleks, metastaze na jetri Literatura: 1. Redston MS, Wanless IR. The hepatic von Meyenburg complex: prevalence and association with hepatic and renal cysts among 2843 autopsies. Mod Pathol 1996; 9:

81 ABSTRACTS 2. Rocken C, Pross M, Brucks U, Ridwelski K, Roessner A. Cholangiocarcinoma occurring in a liver with multiple bile duct hamartomas (von Meyenburg complexes). Arch Pathol Lab Med 2000; 124: Jain D, Sarode VR, Abdul-Karim FW, Homer R, Robert ME. Evidence for the neoplastic transformation of Von- Meyenburg complexes. Am J Surg Pathol 2000; 24: Mortele B, Mortele K, Seynaeve P, Vandevelde D, Kunnen M, Ros PR. Hepatic bile duct hamartomas (von Meyenburg Complexes): MR and MR cholangiography fi ndings. J Comput Assist Tomogr 2002; 26: Wei SC, Huang GT, Chen CH, Sheu JC, Tsang YM, Hsu HC, et al. Bile duct hamartomas. A report of two cases. J Clin Gastroenterol 1997;25: The von Meyenburg complex Filip Vukmirovic, Ljiljana Vuckovic, Mileta Golubovic Center for Pathology, Clinical Center of Montenegro, Podgorica, Montenegro Introduction: Hamartomas of the bile duct named von Meyenburg complex are benign liver lesions consisting of dilated bile duct structures with a surrounding fibrous stroma. Their incidence is age-dependent and they are observed about 1% in children and 5%-6% in adults. Von Meyenburg complexes are infrequently observed lesions, characterized by multiple small nodular lesions located below the Glisson s capsule, and ranging from 0.1 to 1.0 centimeters in diameter. Von Meyenburg complex of the liver are usually detected during laparotomy or autopsies an incidental finding. Multilocular occurrence is possible although they are rarely spread throughout the whole liver, as it was observed in our patient. They are normally asymptomatic, and are incidental findings in asymptomatic patients. They may be found in normal liver tissue, but also in association with Caroli s syndrome, congenital hepatic fibrosis, autosomal dominant polycystic renal diseas, cholangiocarcinomas and cholangitis. Cholangiocarcinoma which arise from these lesions are usually lower stage and better differentiations than other type of cholangiocarcinoma. The sonographic findings of von Meyenburg complex are variable, including multiple, small, hyperechogenic images, with poorly delimited margins, or even hypoechogenic images with a target pattern with a hyperechogenic center and a hypoechogenic periphery, and well delimited margins. A magnetic resonance cholangiography is the best imaging examination of hamartomas of the bile duct, which can distinguish the different forms of dilatation of the bile duct. Histology of von Meyenburg complexes consists of a variable number of dilated small bile ducts, embedded in a fibrous, sometimes hyalinizing stroma. Microscopically, they are characterized by cystic dilatations of the bile duct or clusters of mature bile duct of various sizes, peri-ductal glands, and encompassed by fibrous stroma. The ductules are lined by small cuboidal or flattened cells, with round to oval nuclei. Bile duct hamartomas contain cysts that are more irregularly shaped then normal ducts, and they may also contain eosinophilic debris or inspissated bile. Case report: A 68-year-old male patient with multiple hepatic lesion which ultrasonic and MSCT appearance suggestive of multiple liver metastases was accepted for surgical exploration and liver biopsy. The patient had one mounts symptoms of vomits and weight loss. During surgery numerous whitish irregular lesions of various sizes scattered in the hepatic surface imitating metastatic deposits were noted trough both liver lobe and trough all liver quadrants. Explorations of the rest of abdominal cavity not found any pathological changes or peritoneal carcinomatosis. Liver biopsy was done and taken three samples for analysis. Tissue was brown-yellow-gray color and medium-firm consistency. Histological analysis demonstrated multiple lesions composed of biliary ducts incorporated in fibrotic tissue (Figure 1).There are usually cystic dilatations of some intrahepatic biliary ducts with irregular shape lined with uniform epithelium (Figure 2). The epithel of biliary ducts in von Meyenburg complex were immunohistochemicaly Epithelial Membrane Antigen positive, Pan-Cytokeratin positive, Cytokeratin 7 negative, Cytokeratin 5/6 negative and Carcinoembryonic antigene negative. Also present were signs of cholestasis with small lakes of bile.conclusion: Von Meyenburg complexes are an important differential diagnosis of liver metastases. Differential diagnosis of liver metastases also includes other benign liver lesions, including hemangiomas, adenomas or infectious lesions e.g. miliary tuberculosis. As the existence of liver metastases is crucial for therapeutic decision making in malignant diseases, this differential diagnosis must be carefully clarified. Since VMC are usually less than 5 mm in size, they can escape preoperative radiologic diagnostics. The macroscopic appearance of von Meyenburg complexes can mimic liver metastasis as demonstrated in our reported patients. Key words: Hamartoma of the bile duct; Von Meyenburg complex; liver metastases 81

82 APSTRAKTI Differential diagnosis of benign spindle cell pancreatic lesions: report of two cases Radoslav Gajanin Universitiy of Banja Luka, Faculty of Medicine, Banja Luka, Republic of Srpska, Bosnia and Herzegovina; University clinical center of the Republic of Srpska, Banja Luka, Republic of Srpska, Bosnia and Herzegovina; Introduction: Pancreatic lesions, made of spindle cells, are a heterogeneous group of lesions, ranging from reactive, inflammatory changes to tumors. Differentiation of an individual lesion is difficult and requires the use of additional analytical methods (histochemical, immunohistochemical and molecular), and a comparison of morphological characteristics with other characteristics of the changes (radiologic and laboratory characteristics). We will present two cases of benign spindle cell lesions of the pancreas, with reference to the differential diagnosis. Material and Metods: The first patient was a female, aged 51 years, with a change localized in the pancreatic head, diameter of 9.5 cm. The second patient was a male, aged 35 years, with a change in the pancreatic tail, with maximum diameter of 5.5 cm. Results: In a female patient, the lesion was an inflammatory myofibroblastic pancreatic tumor, built of fascicles of mostly spindle cells (fibroblasts/myofibroblasts). The cells had uniform, elongated, spindle nuclei and eosinophilic cytoplasm. They were arranged in short fascicles that occasionally made storiformn formations. Mitotic activity of spindle cells was low (0-2 mitosis/ HPF 10, FD 0.65). In the stroma, there was a mixed inflammatory infiltrate, consisting of lymphocytes, plasma cells, histiocytes, eosinophils and neutrophils. In between, there were fascicles of collagen, together with the parts of the pancreas (excretory ducts, lobules, acini, and parts of the endocrine pancreas) (Figure 1). Immunohistochemically, spindle cells showed a diffuse immunohistochemical positivity to: Vimentin, SMA and Desmin. Negative immunohistochemical reaction was showed to S-100, p53, CDX2 and ALK-1. Figure 1. Inflammatory myofibroblastic tumor. Fascicles of fibroblasts/myofibroblasts, mixed inflammatory infiltrate and the parts of the pancreas can be seen. HE x100. Slika 1. Inflamacijski miofibroblastni tumor. Na slici se nalaze snopovi fibroblasta/miofibroblasta, mješoviti inflamacijski infiltrat i dijelovi pankreasa. Hex100. In a male patient, a desmoid-type fibromatosis (desmoid tumor) was diagnosed. This change had an infiltrative growth pattern. It was made of uniform spindle cells (fibroblasts), with low mitotic activity (up to 2 mitosis /10HPF, FD 0.65). Cells have built fascicles, which were arranged differently. In the background, there was a plentiful collagen. In between, there were parts of the pancreas. Immunohistochemical positivity was present to the SMA and beta-catenin. A negative immunohistochemical reaction was seen to S-100, CD3, CD68, desmin, Caldesmon H and MSA. Figure 2. Desmoid tumor. Fascicles of fibroblasts, collagen, and parts of the pancreas can be seen. HE x100. Slika 2. Dezmoid tumor. Na slici se nalaze snopovi fibroblasta, kolagena i dijelovi pankreasa. Hex100 82

83 ABSTRACTS Discussion: Benign spindle cell lesions are difficult to diagnose and differentiate prior to a surgical treatment (resection of the change). In most cases, on the basis of clinical and radiological features, they are interpreted as a primary, usually a malignant tumor (cancer) of the pancreas. The inflammatory myofibroblastic tumor is a rare, benign lesion of the pancreas. The primary treatment option is surgery. In the differential diagnosis, special attention should be paid to the differentiation from the inflammatory fibrosarcoma (myxoinflammatory fibroblastic sarcoma), gastrointestinal stromal tumor and spindle cell carcinoma. Desmoids tumor is a benign, slow-growing tumor characterized by the invasive growth and tendency to recur. A radical surgical resection is the first treatment option. In addition to the necessary differentiation of these two benign lesions from each other, it is necessary to differentiate the desmoid tumor from fibrosarcoma, fibromyxoid sarcoma, the malignant tumor of sheaths of peripheral nerves and monophasic synovial sarcoma. Conclusion: Benign lesions of spindle cells of the pancreas are rare, different and often morphologically have similar characteristics. Differentiation requires a detailed histological analysis, the use of histochemical and immunohistochemical methods, correlation with the clinical and radiological image of the change. Careful use of all available clinical and morphological characteristics determine the definitive, accurate diagnosis of such changes. Keywords: Pancreas, Spindle cell lesions, Inflammatory myofibroblastic tumor, Desmoid tumor, Differential diagnosis. Diferencijalna dijagnoza benignih vretenasto-ćelijskih lezija pankreasa: Prikaz dva slučaja. Radoslav Gajanin Univerzitet u Banjoj Luci, Medicinski fakultet Banja Luka, Republika Srpska, Bosna i Hercegovina; Univerzitetski klinički centar Republike Srpske Banja Luka, Republika Srpska, Bosna i Hercegovina; Uvod: Lezije pankreasa sagrađene od vretenastih ćelija predstavljaju heterogenu grupu od reaktivnih, inflamacijskih do tumorskih promjena. Diferencijacija pojedinačnih lezija je teška i zahtijeva primjenu dodatnih analitičkih metoda (histohemijskih, imunohistohemijskih i molekularnih), te komparaciju morfoloških karakteristika sa drugim karakteristikama promjene (radiološke i laboratorijske karakteristike). Prikazujemo dva slučaja benignih vretenasto-ćelijskih lezija pankreasa, sa osvrtom na diferncijalnu dijagnozu. Materijal i metode: Prvi pacijent je žena starosti 51 godinu, sa promjenom koja je lokalizovana u području glave pankreasa promjera 9,5cm. Drugi pacijent je muškarac starosti 35 godina, sa promjenom lokalizovanom u području repa pankreasa maksimalnog promjera 5,5cm. Rezultati: Kod ženskog pacijenta lezija je inflamacijski miofibroblastni tumor pankreasa, sagrađena od snopova pretežno vretenastih ćelija (fibroblasta / miofibroblasta). Ćelije su uniformnih, izduženih, vretenastih jedara, eozinofilne citoplazme. Ćelije su aranžirane u kraće snopove koji mjestimično grade storiformne formacije. Mitotska aktivnost vretenastih ćelija je niska (0 2 mitoze /10 HPF, FD 0,65). U stromi se nalazi mješoviti inflamacijski infiltrate koga čine limfociti, plazma ćelije, histiociti, eozinofilni i neutrofilni granulociti. Između se nalaze snopovi kolagena, te dijelovi pankreasa (izvodni kanali, lobulusi, acinusi i dijelovi endokrinog pankreasa) (Slika 1). Imunohistohemijski, vretenaste ćelije pokazuju difuznu imunohistohemijsku pozitivnost na: Vimentin, SMA, Desmin. Negativna imunohistohemijska reakcija je S-100, p53, CDX2, ALK-1. Kod muškog pacijenta dijagnostikovana je fibromatoza, dezmoidni tip (dezmoid tumor). Promjena je infiltrativnog načina rasta. Sagrađena je od uniformnih vretenastih ćelija (fibroblasta), niske mitotske aktivnosti (do 2 mitoze /10HPF, FD 0,65). Ćelije grade snopove, različito aranžirane. U pozadini se nalazi obilan kolagen. Između se nalaze dijelovi pankreasa. Imunohistohemijska pozitivnost je prisutna na SMA i beta katenin. Negativna imnunohistohemijska reakcije je na: S-100, CD3, CD68, Desmin, Caldesmon H, MSA. Diskusija: Benigne vretenasto-ćelijske lezije je teško dijagnostikovati i diferencirati prije hirurškog tretmana (resekcije promjene). U većini slučajeva, na osnovu kliničkih i radioloških karakteristika, se interpretiraju kao primarni, obično maligni (karcinom) tumor pankreasa. Inflamacijski miofibroblastni tumor je rijetka benigna lezija pankreasa. Primarna opcija liječenja je hirurška. U diferncijalnoj dijagnozi posebnu pažnju je potrebno posvetiti diferencijaciji od inflamacijskog fibrosarkoma (miksoinflamacijski fibroblastni sarkom), gastrointestinalnog stromalnog tumora i vretenastoćelijskog karcinoma. Dezmoid tumor je benigni, spororastući tumor koga karakteriše invazivni rast i sklonost recidiviranju. Radikalna hirurška resekcija je prva opcija liječenja. Pored potrebne diferencijacije ove dvije benigne lezije jedne od druge, potrebno desmoid tumor diferencirati od fibrosarkoma, fibromiksoidnog sarkoma, malignog tumora ovojnica perifernih nerava, monofaznog sinovijalnog sarkoma. Zaključak: Benigne lezije vretenastih ćelija pankreasa 83

84 KRATKI APSTRAKTI KURSEVI su rijetke, različite i često morfološki sličnih karakteristika. Diferencijacija zahtijeva detaljnu histološku analizu, upotrebu histohemijskih i imunohistohemijskih metoda, korelaciju sa kliničkom slikom, te radiološkom slikom promjene. Pažljivim korišćenjem svih raspoloživih kliničkih i morfoloških karakteristika utvrđuje se definitivna, tačna dijagnoza promjene. Ključne riječi: Pankreas, Vretenastoćelijske lezije, Inflamacijski miofibroblastni tumor, Dezmoid tumor, Diferencijalna dijagnoza. Literature: 1. Devasis Panda D, Mukhopadhyay D, Datta C, Chattopadhyay BK, Chatterjee U, Shinde R. Inflammatory Myofibroblastic Tumor Arising in the Pancreatic Head: a Rare Case Report. Indian J Surg (November December 2015) 77(6): Pungpapong S, Geiger XJ, Raimondo M. Inflammatory Myofibroblastic Tumor Presenting as a Pancreatic Mass: A Case Report and Review of the Literature. JOP. J Pancreas (Online) 2004; 5(5): Sim A, Lee MW, Nguyen GK. Inflammatory myofibroblastic tumour of the pancreas. Can J Surg, 2008; 51 (1): Słowik-Moczydłowska Z, Rogulski R, Piotrowska A, Małdyk J, Kluge P, Kamiński A. Desmoid tumor of the pancreas: a case report. Journal of Medical Case Reports (2015) 9: Benign lymphadenitis imitating malignant lymphoma Djengis Jasar, Katerina Kubelka-Sabit, Vanja Filipovski Laboratory of Histopathology, Clinical Hospital Acibadem Sistina, Skopje, Republic of Macedonia Aim: The aim of this study is to present a case of benign lymphadenitis that cytologically was interpreted as suspicios for malignant lymphoma. Introduction: This study represents a case of a patient with cervical lymph node swelling in which the cyto-diagnosis performed by fine needle aspiration cytology was suspicious for lymphoma. The correct diagnosis was assessed by subsequent histology after the removal of the enlarged cervical lymph node. Material and Methods: For cytologic study the material was obtained by fine needle aspiration biopsy and syringe washings, air-dried smears and alcohol-fixed smears, which were prepared and appropriately stained by PAP and May Gruenwald-Giemsa stains. For correct diagnosis an extirpated lymph node was properly fixed and processed with routine haematoxylin eosin staining as well as with an additional immunohistochemical analyses. Results: The cyto-histologic features were characterized by a polymorphous population of cells, germinal center cells with large nuclei, a few epithelioid-type cells and histiocytes with intracellular inclusions The cytological diagnosis implied suspicion for malignant lymphoma probably of Hodgkin type. Histologic features revealed a reactive lymph node architecture that immunohistochemically revealed the diagnosis of Toxoplasma lymphadenitis. Serologic testing for toxoplasma in other institution revealed elevated titres that established the histopathological diagnosis. Conclusion: Lymphadenitis due to Toxoplasma infection is common and should be considered in the diagnosis of unexplained lymphadenopathy at all sites, especially the cervical region. Serologic confirmation should be recommended for all suspected cases and unlike in this case, fine needle aspiration cytodiagnosis can eliminate the need for hospitalization and surgery. Key words: lymphadenitis, cytology, toxoplasmosis Diagnostic challenges in pulmonary pathology: between morphology and immunohistochemistry Mileta Golubovic, Ljiljana Vuckovic, Filip Vukmirovic Centre for Pathology, Clinical Centre of Montenegro the Medical Faculty of the University of Montenegro, Podgorica, Montenegro Aim: The aim of this paper is to point out the importance and the role of immunohistochemistry in diagnosing rare benign epithelial tumours of the lung and a very similar malignant tumour of well-differentiated lepidic adenocarcinoma. Introduction: In pulmonary pathology diagnostic dilemmas are frequent. One of the most complex challenges is to differentiate between benign tumours of pneumocytes and other forms of similar tumours. In particular, it is difficult to differentiate between the tumours of the same or similar histogenetic origin and morphological characteristics. However, dilemmas can also be related to whether a tumour has benign or malignant potential. In order to be able to have proper diagnostics, we need to have a detailed insight in the morphological and immunohistochemical features of these tumours. One of the best 84

85 ABSTRACTS examples of this are two very rare and morphologically very similar benign epithelial tumours: sclerosing pneumocytoma (according to the 2015 World Health Organisation Classification of Lung Tumours; new terms changed or entities added since 2004; the 2004 World Health Organisation Classification called it sclerosing haemangioma) 1 and alveolar adenoma on the one hand; and well-differentiated lepidic adenocarcinoma on the other hand. These are most often cited as the most problematic in terms of their differential diagnostics. When it comes to first two tumours, as it can be concluded from their original names, they were considered to be the tumours of completely different histogenetic origin. However, their immunohistochemical profile and all current data show that they have identical structure and origin. Immunohistochemical diagnostics enabled the demystification of neoplastic processes, as is the case with rare benign tumours of pneumocytes. This diagnostics can also point out the biological potential and help differentiate between benign and malign tumours. Additional dilemma is posed by the fact that sclerosing pneumocytoma may even give metastases into regional lymph nodes, which do not affect disease prognosis 2,3. Histopathological differential diagnosis includes, apart for the above mentioned, other benign epithelial tumors, hemangioma, primary and metastatic carcinoma 4. Materials and methods: We analysed two very rare and morphologically very similar benign epithelial tumours, (sclerosing pneumocytoma and alveolar adenoma) and welldifferentiated lepidic adenocarcinoma. It was also performed their immunohistochemical analysis using the following markers: Cytokeratin 7 (CK7), Thyroid transcription factor 1 (TTF-1), Epithelial membrane antigen (EMA), Pan-cytokeratin (CK), Carcinoembryonic Antigen (CEA), FVIII, Ki67 and p53. Results: The first tumour, at the microscopic level, showed sclerosing and haemorrhagic arrangement, with ectatic spaces filled by blood and solid areas and papillary-like formations. Basic cell population was epithelial cells, dominantly with eosinophilic and partially with granular cytoplasm. The nucleus was in the centre, round, without prominent nucleoli and mitoses. Stroma was moderately pronounced and centrally it was denser and composed of bundles of oval and spindle-shaped fibroblasts. Some of the cavities within the tumour had wide, cavernous space, lined with endothelium-like attenuated cells. Mainly in the middle part of the tumour, we could see the areas of hyalinisation of connective tissue. The tumour borders were expansive. The tumour did not infiltrate the pleura. On the final histopathological slides, the second tumour had a microcystic appearance. In central parts there was pale amorphous, homogenous content. Spaces were lined with cylindrical cells containing acidophilic and clear cytoplasm. Stroma was scarcely developed and sometimes with more pronounced parts and composed of groups of elongated spindle-like fibrocytes and fibroblasts. Immunohistochemical analysis of both tumours showed very similar reactivity: Ck7, TTF-1, EMA and CK showed diffuse positivity, k67 showed low proliferation index <1%. Cea in the major part of sclerosing pneumocytoma was negative and focally individual cells had reactivity, while alveolar adenoma was negative in its entirety. P53 and FVIII in both cases showed negative results. After all analyses, the definitive diagnosis of the first tumour is pneumocytoma and for the second one alveolar adenoma. The third tumour showed similar morphology as the previous two. At the microscopic hematoxylin eosin stain, it was dominantly composed of alveolar-adenoid formations. Tumour cells were bulky, cubic or polygonal; foamy, pale acidophilic, with homogenous cytoplasm and hyperchromatic roundish nuclei without prominent nucleoli. The immunohistochemical analysis of the third tumour showed positive reactivity with Ck7, TTF-1, CK, Cea, EMA, k67 proliferation index > 32%, while p53 proliferation index 1%, while the FVIII had a negative result. Final diagnosis for this tumour is well-differentiated lepidic adenocarcinoma. Conclusion: Due to almost identical histopathological and immunohistochemical characteristic, there may be a diagnostic dilemma: are these two separate tumours or this is the same tumour. Taking into consideration that sclerosing pneumocytoma give positive epithelial immunohistochemical reaction, their earlier name is wrong. Previous examples are good indicators of how we should adapt the names of tumours to their real nature and this is a good recommendation in terms of how we should organise future classifications. All of the above mentioned points to the fact that with these tumours it is necessary to have immunohistochemical evaluation and that we have to introduce new immunohistochemical predictive and prognostic markers. It is necessary to determine the cut off values for proliferative markers. Keywords: pneumocytic tumors, morphology, immunohistochemistry Dijagnostički izazovi u pulmonarnoj patologiji: između morfologije i imunohistohemije Mileta Golubović, Ljiljana Vučković, Filip Vukmirović Centar za Patologiju, Klinički Centar Crne Gore Medicinski Fakultet Univerziteta Crne Gore, Podgorica, Crna Gora 85

86 APSTRAKTI Cilj: Cilj ovog rada je da ukaže na značaj i ulogu imunohistohemije u dijagnozi rijetkih benignih pneumocitnih plućnih epitelnih tumora i njima najsličnijeg malignog tumora dobro diferentovanog lepidičnog adenokarcinoma. Uvod: U pulmonarnoj patologiji su česte dijagnostičke dileme. Jedan od najkompleksnijih izazova je diferenciranje unutar benignih pneumocitnih tumora i drugih njima sličnih tumora. Pogotovo je teško razdvojiti ako su tumori istog ili sličnog histogenetskog porijekla i morfoloških karakteristika. Međutim, dileme mogu biti i u odnosu da li se radi o benignom ili malignom potencijalu tumora. Da bismo mogli da napraviti adekvatnu dijagnostiku neophodan je detaljan uvid i u morfološke i u imunohistohemijske karakteristike ovih tumora. Jedan od najboljih primjera za to su dva vrlo rijetka i morfološki veoma slična benigna epitelna tumora: sklerozirajući pneumocitom (prema klasifikaciji Svjetske zdravstvene organizacije 2015., koji se prema Klasifikaciji Svjetske zdravstvene organizacije iz godine zvao se skleroziranim hemangiom) 1 i alveolarni adenom s jedne strane; i dobro diferentovani lepidični adenokarcinom sa druge. Oni se najčešće navode kao međusobne diferencijalno dijagnostičke dileme. Kada su u pitanju prva dva tumora, a kao što se može zaključiti njihovim prvobitnim imenima, oni su se smatrali tumorima potpuno različitog histogenetskog porijekla. Međutim, njihov imunohistohemijski profil i svi aktuelni podaci su pokazali da oni imaju identičnu strukturu i porijeklo. Imunohistohemijska dijagnostika omogućila je demistifikaciju neoplastičnih procesa, što je slučaj i sa rijetkim benignim tumorima pneumocita. Ona takođe može ukazati i na biološki potencijal i pomoći da se razdvoje benigni od malignih tumora. Dodatnu dilemu predstavlja činjenica da sklerozirajući pneumocitomi mogu čak davati metastaze u regionalne limfne čvorove, koje ne utiču na prognozu bolesti 2,3. Histopatološka diferencijalna dijagnoza uključuje, pored pomenutih, druge benigne epitelne tumore, hamatrome, hemangiome, primarne i metastatske karcinome 4. Materijali i metode: Posmatrana su dva vrlo rijetka i morfološki veoma slična benigna epitelna tumora (Sklerozirajući pneumocitom i alveolarni adenom) i dobro diferentovani lepidični adenokarcinom. Rađena je njihova imunohistohemijska analiza upotrebom sljedećih markera: Citokeratin 7 (Ck7), Tiroidni transkripcioni faktor 1 (TTF1), Epitelni membranskim antigen (EMA), Pancitokeratin (CK), Karcinoembrionalni antigen (Cea), FVIII, Ki67 i p53. Rezultati: Prvi tumor je na mikroskopskom planu pokazivao sklerotičan i hemoragičan aranžman, sa ektatičnim prostorima ispunjenim krvlju, zatim solidna polja i papiloidne formacije. Osnovna ćelijska populacija su bile epitelne ćelije, dominantno eozinofilne, a manjim dijelom granulirane citoplazme. Jedro je bilo središnje postavljeno, okruglo, bez prominentnih jedaraca i mitoza. Stroma je u najvećem dijelu srednje obilna, a centralno je bila gušća i komponovana od snopova ovalnih i vretenastih fibroblasta. Neke od šupljina u tumoru su imale široke, kavernozne prostore, obložene endotelu-sličnim atenuiranim ćelijama. Uglavnom u srednjem dijelu tumora nalazila su se područja hijalinizovanog veziva. Granice tumora bile su ekspanzivne. Pleura nije infiltrovana tumorom. Na konačnim histopatološkim preparatima drugi tumor je pokazivao mikrocističan izgled. U centralnim djelovima nalazio se blijedi amorfni, homogeni materijal. Prostori su bili prekriveni cilindričnim ćelijama acidofilne i svijetle citoplazme. Stroma je bila slabo razvijena, sa nešto obilnijim djelovima i građena od izduženih vretenastih fibrocita i fibroblasta. Imunohistohemijskom analizom oba tumora su imala sličnu reaktivnost: Ck7, TTF1, EMA i CK su pokazali je difuznu pozitivnost, k67 nizak proliferativni indeks <1%. Cea je u najvećem dijelu sklerozirajućeg pneumocitoma bio negativan, a tek fokalno su neke pojedinačne ćelije imale reaktivnost, dok je alveolarnom adenomu u cjelosti bio negativan. P53 i FVIII su u oba slučaja imali negativan rezultat. Nakon svih analiza definitivna dijagnoza prvog tumora je bila: Sklerozirajući pneumocitom, a drugog Alveolarni adenom. Treći tumor je pokazivao sličnu morfologiju kao prethodna dva. Na mikroskopskim hematoksilin eozin preparatima dominantno je bio građen od alveolo-adenoidnih formacija. Tumorske ćelije su bile krupne, kubične ili poligonalne; mjehuraste, blijedo acidofilne, homogene citoplazme i hiperhromatičnih okruglastih jedara bez prominentnih nukleolusa. Imunohistohemijskom analizom treći tumor je pokazao pozitivnu reaktivnost sa Ck7, TTF1, CK, Cea, EMA, k67 proliferacioni indeks >32% i p53 proliferacioni indeks 1%, dok je FVIII imao negativan rezultat. Njegova konačna dijagnoza glasila je: Dobro diferentovani lepidični adenokarcinom. Zaključak: Zbog gotovo identičnih histopatoloških i imunohistohemijskih svojstava u dijagnozi rijetkih pneumocitnih plućnih epitelnih tumora postoji dilema: jesu li to različiti tumori ili isti tumor. S obzirom da sklerozanti pneumocitomi daju pozitivnu epitelnu imunohistohemijsku reakciju njihov raniji naziv je bio pogrešan. Prethodni primjer je dobar pokazatelj kako treba prilagođavati nazive tumora njihovoj realnoj prirodi i dobra preporuka kako treba koncipirati buduće klasifikacije. Sve navedeno ukazuje, da je u ovim tumorima imunohistohemijska evaluacija obavezna i da se moraju uvesti novi imunohistohemski prediktivni i prognostički markeri. Takođe je neophodno odrediti granične vrijednosti za proliferativne markere. Ključne riječi: pneumocitni tumori, morfologija, imunohistohemija 86

87 ABSTRACTS Literature: 1. Travis WD, Brambilla E, Nicholson AG, Yatabe Y, Austin JH, The 2015 World Health Organization Classification of Lung Tumors: Impact of Genetic, Clinical and Radiologic Advances Since the 2004 Clasification, September, 2015; Kim KH, Sul HJ, Kang DY. Sclerosing hemangioma with lymph node metastasis. Yonsei Med J. 2003;44: Miyagawa Hayashino A, Tazelaar HD, Langel DJ, Colby TV. Pulmonary sclerosing hemangioma with lymph node metastases: report of 4 cases. Arch Pathol Lab Med Mar;127(3): Keylock JB, Galvin JR, Franks TJ. Sclerosing Hemangioma of the Lung. Arch Pathol Lab Med.Vol 133, 2009: Vulvarna Pagets-ova bolest i Fish tank granulom kože: dijagnostički izazov Biserka Vukomanović Đurđević VMA Beograd, Srbija Koža predstavlja najveći organ u našem organizmu. Primajući informacije iz spoljašnje sredine predstavlja barijeru između ljudskog organizma i spoljašnje sredine.histološka struktura kože je varijabilna u zavisnosti od dela organizma koji pokriva. Patološki procesi kože takođe se razlikuju zavisno od regiona.tome su uzroci kako lokalni imunološki status tako i spoljašnje fizičko, hemijsko i mikrobiološko okruženje. Histopatolška dijagnostika kožnih lezija zahteva detaljne kliničke informacije.na drugoj strani histopatološka dijagnostika kožnih lezija daje informacije kako o lokalnoj promeni, tako i o potencijalnim drugim udruženim patološkim stanjima. Patologija kože vulve je specifična kako po specifičnoj lokalizaciji, tako i po spcifičnom trenju i mikrobiološkoj flori. Ekstramamarna Pagetova bolest vulve je retka. Klinički se prezentuje kao eritematozma ili ekcematozna lezija. Može biti lokalna ili ekstenzivna.histopatološki se karakteriše relativno velikim žlezdanim atipičnim ćelijama, koje su patognomonične za ovu bolest. Ove ćelije imaju obilnu citoplazmu koja je granularna ili vakuolizovana. Tumorske ćelije su tipično lokalizovane pojedinačno ili u grupama u bazalnim i parabazalnim slojevima.imunohistohemijske analize su neophodne u procesu postavljanja dijagnoze Pagetove bolest.osnovni razlog je što Pagetova bolest može biti primarna kožna bolest ili udružena sa ne-kožnim karcinomima prvenstveno porekla urotela ili rektalnim karcinomom. Stoga je neophodna preporuka da se kod svih dijagnostikovanih slučajeva vulvarne Pagetove bolesti sprovede detaljno kliničko ispitivanje pacijentkinja. Akvarijumska bolest kože je izazvana Mycobacterium marinum. Ova mikobakterija je izazivač bolesti riba i to kako morskih tako i rečnih.kod čoveka je najčpešće zahvaćena koža ruku.kožna manifestacija bolesti je prvi simptom i to u vidu plakova,pustula i ulceracija.bolest može širiti i u dublje strukture.histopatološki postoji širi dijapazon mikrokopske slike. Najčešće se može videt absces, nekroza kjože i masnog tkiva. Međutim granulomska inflamacija je ključni morfološki supstrat. Nakon granulomske inflamacije se javlja fibroza. Obzirom da mikroskopska slika može biti donekle nespecifična klinički podatci su od ogromnog značaja za postavljanje dijagnoze. Multidisciplinarnost u donošenju finalne dijagnoze uključuje i mikrobiološku potvrdu prisustva Mycobacterium marinum. Ključne reči: Fish tank granuloma, akvarijumska bolest kže, extramammary Paget disease, vulvarna Pagetova bolest Figure 1. Extramammarz Paget disease 87

88 APSTRAKTI Vulvar Paget disease and Fish tank granuloma -diagnostic challenge Biserka Vukomanovic-Djurdjevic Military Academy, Belgrade, Serbia The skin is the largest organ in our body.receiving information from the environment allows the role barrier between the human organism and the environment. The histological structure of the skin is variable depending on the part of the organism. The diseases of skin also vary depending on the region. The reason is the local immune status and the external physical, chemical and microbiological environment. The histopathological diagnosis of skin lesions request detailed clinical information. On the other side the histopathological diagnosis of skin lesions provides information on local disease, as well as potential other associated pathological conditions. Extramammary Paget s vulvar disease is rare. The pathology of the skin of the vulva is specific both for specific localization, as well as for specific friction and microbiological flora. It is clinically presented as erythematosus or eczematous lesion. It can be local or extensive. Histopathologically, it is characterized by relatively large glandular atypical Paget cells, which are pathognomonic for this disease. These cells have abundant cytoplasm that is granular or vacuolated. Tumor cells are typically localized individually or in groups in the basal and parabasal layers. Immunochemical analyzes are necessary in the diagnosis of Paget s disease. The main reason is that Paget s disease can be a primary skin disease or associated with non-cutaneous carcinoma primarily of the urothelial or rectal carcinoma. Therefore, it is necessary to recommend that a detailed clinical trial of a patient be conducted in all diagnosed cases of vulvar Paget s disease. Mycobacterium marinum is etiological factor of Fish tank granuloma.this Mycobacterium more often causes diseases of fish, both marine and river fish. The humans become infected with Mycobacterium marinuim after contact with skin after micro/trauma Infection is usually localized to the skin.in immunocompromised patients the infection may disseminate or spread to the subcutis and bone. After incubation of few weeks after infection the lesion appear as solitary nodules or plaques.in some cases the disease progresses like suppurative ulcers. Histopathologically there is a wider range of histopathological presentations. Most often you can see abscess, necrosis of wheat and fatty tissue. However, granuloma inflammation is a key morphological substrate. After granuloma inflammation, fibrosis occurs. Since the microscopic image may be somewhat non-specific, clinical data are of great importance for the diagnosis. Multidisciplinarity in the final diagnosis includes microbiological confirmation of the presence of Mycobacterium marinum. Key words: Fish tank granuloma, Extramammary Paget desease Literature 1. LopesL, Filho,LopesIMR, LopesLRS, EnokiharaM, OsoresA et al. Mammary and extramammary Paget s disease. An Bras Dermatol. 2015; 90(2): Helm KF1, Goellner JR, Peters MS..Immunohistochemical stains in extramammary Paget s disease.am J Dermatopathol Oct;14(5): Flondell M, Ornstein K, Björkman A. Invasive Mycobacterium marinum infection of the hand. J Plast Surg Hand Surg. 2013; 47(6): Ang P, Rattana-Apiromyakij N, Goh CL: Retrospective study of Mycobacterium marinum skin infections. Int J Dermatol ; Palenque E, Skin disease and nontuberculous atypical mycobacteria. Ann Rev Microbiol ;641. Cytological findings of pleural effusions Vesna Skuletic Institute of Pathology and Forensic Medicine, Military Medical Academy, Belgrade, Serbia Introduction: A pleural effusion describes an excess of fluid in the pleural cavity, usually resulting from an imbalance in the normal rate of pleural fluid production or absorption, or both. Pleural effusions are associated with a number of pathological medical conditions. In the vast majority of these cases the cellular response is quite nonspecific and will show varying proportions of mesothelial cells, macrophages, erythrocytes, lymphocytes, neutrophils and other leukocytes. Certain diseases may occasionally show cellular changes in the effusion that will reflect their presence. Examples of these include infections such as tuberculosis, blastomycosis, aspergillosis, viral infections, echinococcosis and cryptococcosis. Noninfectious, nonneoplastic diseases diagnosable by cytopathologic methods include rheumatoid arthritis, lu- 88

89 ABSTRACTS pus erythematosus, eosinophilic pleural effusion, pleural endometriois and sickle cell disease. In spite of these occasional specific cytopathologic diagnoses which can be rendered for the nonneoplastic diseases named above, the most significant role of cytopathology by far is in the examination of effusion fluid for the presence of cancer cells. Cytologic examination of pleural effusions is an important initial step in management of malignant effusions. Although most patients with a malignant effusion have a known history of cancer, a positive effusion may be the first sign of an unsuspected malignancy. Cytologic examination of a serous effusion may offer the possibility of an early and accurate diagnosis by using a minimal intervention. The presence of pleural effusions typically signals an advanced stage of disease so it is associated with poor prognosis. The accuracy of cytologic examinations of malignant pleural effusion is in high range (from 40% to 87%). Lung, breast, ovarian, and gastrointestinal cancers are most likely to cause malignant effusions. The histologic type of cancer most commonly seen in serous effusions is adenocarcinoma but a variety of other cancers can cause effusions. Less common malignancies are squamous cell carcinoma, small cell carcinoma (SCC), hematopoietic malignancies, melanoma, germ cell tumours and sarcomas. Mesotheliomas often present with recurrent serous effusions. One of the most important diagnostic doubts in pleural effusion analysis is distinguishing adenocarcinoma from mesothelioma and mesothelioma from benign mesothelial cells. In most cases the diagnose is based on regular cytomorphology analysis and immunocytochemistry is necessary in low percent of cases to establish the diagnose. The specimens are collecting by thoracentesis, processing in a routine fashion and staining by hematoxylin-eosin (H&E) and Papanicolaou stain after wet fixation with 95% ethanol and May-Grunwald-Giemsa stain after air drying. It is important to evaluate the same cells when constructing coordinate immunoreactivity pattern for various immunomarkers. Since the same cells cannot be followed on different cytology smears, they are not ideally suited for routine immunocytochemical evaluation of effusion fluids. Serial sections of cell-blocks show the same cells in adjacent levels which allow proper evaluation of the coordinate immunoreactivity pattern. Conclusion: Pleural fluid cytological analysis has important diagnostic role in most cases so primary aim should be to establish the correct diagnosis with minimal investigation. Cytology is the only method by which one may retrieve cells from fluid, often in the absence of solid lessions or when obtaining a biopsy from the latter is more difficult and costly and entails much greater discomfort or risk for the patient. Effusion cytology is important for: primary diagnosis of cancer, staging, diagnosis of recurrence or disease progression. Evaluation of effusion cytology is one of the most challenging areas in diagnostic cytopathology. A remarkably wide cytomorphological spectrum of reactive mesothelial cells overlaps with various benign and malignant processes. Due to these limitations, a significant proportion of effusion fluids are difficult to interpret with objective certainty by cytomorphology alone. Fig.1. Malignant mesothelioma showing hypercellularity with three.dimensional groups and knobbycontoured clusters. a) MGG,x 200, b) Calretinin, x 200, c) HMBE-1, x 400. Fig.2. Adenocarcinoma presenting as variably sized clusters and single malignant cells in a background of benign mesothelial cells ( medium-sized cellular spheres with scalloped surface mimicking mesothelioma.a) MGG, x 200, b) CEA x 400, c) PAS, x

90 APSTRAKTI The use of immunocytochemical panel of antibodies with combination of high sensitivity and specificy is the only way for precise distinguishing of adenocarcinomas from mesothelioma, especially in cases with scant tumor cells particularly in metastatic disease from well differentiated carcinoma, and reactive mesothelial cells from mesothelioma. Other stains are used to confirm pulmonary origin and should be selected as a complement to the panel once adenocarcinoma is confirmed. Molecular diagnostics are feasable on routine cytopreparations, primary diagnostics as well as molecular monitoring during targeted therapy. Keywords: Cytopathology; differential diagnosis; malignant; pleural effusion. Literature: 1. Davidson B, Firat P, Michael CW. Serous Effusions. Etiology, Diagnosis, Prognosis and Therapy.London: Springer; Cibas ES, Ducatman BS. Cytology. Diagnostic principles and clinical correlates.2 nd ed. Edinburgh: Sanders; Chapter 4, Pleural, pericardial and peritoneal fluids; p A review of uncommon cytopathologic diagnoses of pleural effusions from a chest diseases center in Turkey. Cakir E, Demirag F, Aydin M, Erdogan Y. Cytojournal. 2011;8:13. doi: / Epub 2011 Jul Cytopathological spectrum of unusual malignant pleural effusions at a tertiary care centre in north India. Awasthi A, Gupta N, Srinivasan R, Nijhawan R, Rajwanshi A. Cytopathology. 2007; 18(1): Cytomorphological profile of neoplastic effusions: an audit of 10 years with emphasis on uncommonly encountered malignancies. Gupta S, Sodhani P, Jain S. J Cancer Res Ther. 2012; 8(4): Novine u novom izdanju Bethesda sistema za citologiju štitne žlezde Panjković Milana 1,2 1 Medicinski fakultet Univerziteta u Novom Sadu 2 Klinički centar Vojvodine, Centar za patologiju i histologiju Ažuriran je Bethesda sistem za citopatologiju štitne žlezde (TBSRTC), sa kojim je pokušano standardizovanje izveštavanja i citoloških kriterijuma za citološke uzorke dobijene aspiracijom čvorova tankom iglom (FNA), koji je prvi put je uveden Godine. Iako je veći deo TBSRTC-a ostao isti, u verziji od godine uvedeno je nekoliko poboljšanja na temelju novih podataka i razvoja na tom polju. Revizija godine potvrđuje da svaki FNA citološki izveštaj štitne žlezde, treba započeti sa jednom od šest dijagnostičkih kategorija, čiji se nazivi nisu promenili od njihovog prvog uvođenja: nedijagnostički ili nezadovoljavajući; benigno; atipija neodređenog značaja (AUS) ili folikularna lezija neodređenog značenja (FLUS); folikularna neoplazma ili sumnja na folikularnu neoplazmu; sumnjana malignitet; i maligno. U prvom izdanju TBSRTC, izračunat je rizik za nastanak maligniteta (MOP) za svaku dijagnostičku kategoriju i dat je kao raspon na temelju pregleda literature u tom periodu: 0-3% za benignu kategoriju, ~ 5-15% za atipiju neodređenog značaja (AUS) ili folikularnu leziju neodređenog značenja (FLUS), 15-30% za folikularnu neoplazmu ili sumnju na folikularnu neoplazmu, 60-75% za sumnju na malignitet i 97-99% za malignu kategoriju nalaza. U drugom izdanju, ti rasponi MOP su revidirani, posebno za takozvane neodređene kategorije, na osnovu procena iz studija i meta-analiza velikog broja slučajeva rezultata FNA citologije štitne žlezde pod vođstvom ultrazvuka, koje su objavljene nakon godine. Značajno je da novo izdanje reinterpretira prethodnu verziju na jedan važan način, a to je pažljivo smeštanje u TBSRTC nove nekarcinomske kategorije -neinvazivna folikularna neoplazma štitne žlezde sa papilary like karakteristikama jedra (NIFTP), koja je pre aprila godine bila kategorizovana kao karcinom štitne žlezde. NIFTP tumori imaju citološke nuklearne promene koje su identične drugim oblicima karcinoma štitne žlezde, no tokom dugotrajnog kliničkog praćenju ne recidiviraju i ne metastaziraju, pa se stoga klinički ne ponašaju kao karcinom štitne žlezde. Tumori NIFTP se obično svrstavaju u kategorije 3, 4 ili 5 TBSRTC i mogu se dijagnostikovati samo kao ne rak nakon potpune hirurške ekscizije tumora i patohistološkog pregleda celokupnog tumorskog tkiva Brojna su druga poboljšanja nove verzije iz godine: Uvedeno je molekularno testiranje kao standard za AUS / FLUS i FN / SFN Definicija i dijagnostički kriterijumi za FN / SFN su izmenjeni: slučajevi koji ukazuju na blage nuklearne promene povezane s papilarnim karcinomom štitne žlezde sada su uključeni u ovu kategoriju Definicija i dijagnostički kriteriji za papilarni karcinom štitne žlezde sada upućuju na ograničenu primenu kod slučajeva sa klasičnim karakteristikama papilarnog karcinoma štitne žlezde 90

91 ABSTRACTS TBSRTC je danas najčešća klasifikacija širom sveta za citologiju FNA uzoraka štitne žlezde. Novi predlozi će biti korisni za različite aspekte FNA citologije štitne žlezde uključujući nomenklaturu, diferencijalnu dijagnozu, potencijalni uticaj NIFTP na neodređene dijagnostičke kategorije, efekat molekularnih i imunocitohemijskih analiza i kasnije kliničke postupke. Literature: 1. Ali SZ, Cibas ES, editors. The Bethesda system for reporting thyroid cytopathology. NewYork: Springer; Nikiforov YE, Seethala RR, Tallini G, et al: Nomenclature revision for encapsulated follicular variant of papillary thyroid carcinoma: a paradigm shift to reduce overtreatment of indolent tumors. JAMA Oncol 2016;2: Pusztaszeri M.Rossi E.D.Auger M. Baloch Z. Bishop J. Bongiovanni M. et al.the Bethesda System for Reporting Thyroid Cytopathology: Proposed Modifications and Updates for the Second Edition from an International Panel. Acta Cytologica 2016;60: David N. Poller MD, FRCPath, Zubair W. Baloch MD, PhD, Guido Fadda MD, MIAC, Sarah J. Johnson MD, PhD, FRCPath, Massimo Bongiovanni MD,Alfredo Pontecorvi MD, PhD, Béatrix Cochand-Priollet MD, MIAC, PhDThyroid FNA: New classifications and new interpretations. Cancer Cytopathology 2016; Ali SZ, Cibas ES, editors. The Bethesda system for reporting thyroid cytopathology. NewYork: Springer; Second Edition News about the revised Bethesda system for thyroid cytopathology Panjkovic Milana 1,2 1 Medical Faculty, University of Novi Sad 2 Clinical Cener of Vojvodina,Department of Pathology The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC), which attempts to standardize reporting and cytological criteria for fine-needle aspiration of thyroid nodules and was first introduced in 2009, has been updated. Although much of the original TBSRTC remains the same, several enhancements have been introduced in the 2017 version based on new data and developments in the field. The 2017 revision reaffirms that every thyroid FNA report should begin with one of six diagnostic categories, the names of which remain unchanged since they were first introduced: nondiagnostic or unsatisfactory; benign; atypia of undetermined significance (AUS) or follicular lesion of undetermined significance (FLUS); follicular neoplasm or suspicious for a follicular neoplasm; suspicious for malignancy; and malignant. In the frst edition of TBSRTC, the implied risk of malignancy (MOP) for each diagnostic category was calculated and provided as a range based on a review of the literature at that time: 0 3% for benign, ~5 15% for atypia of undetermined signifcance (AUS) or follicular lesion of undetermined signifcance (FLUS), 15 30% for follicular neoplasm or suspicious for follicular neoplasm, 60 75% for suspicious for malignancy, and 97 99% for the malignant category. In the second edition, these ranges have been revised, especially for the so-called indeterminate categories, representing estimates calculated primarily from studies of large case cohorts and meta-analyses of ultrasound-guided thyroid FNA published after Notably, the new document reinterprets the previous version in one major way, and that is TBSRTC s careful accommodation of the new noncancer category of noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) tumors, which prior to April 2016 were categorized as thyroid cancer. NIFTP tumors have nuclear changes on cytologic evaluation that are identical to other forms of thyroid cancer, but on close long-term clinical follow-up they do not appear to recur or metastasize, and therefore, they do not behave clinically like thyroid cancer. NIFTP tumors typically fall into categories 3, 4, or 5, and can only be diagnosed as not cancer after a full surgical excision is performed and the entire tumor specimen is examined under a microscope. There have also been a number of other enhancements with the 2017 update: The option of molecular testing in the standard management of AUS/FLUS and FN/SFN has been included. The definition and diagnostic criteria for FN/SFN has been modified: cases demonstrating mild nuclear changes associated with papillary thyroid carcinoma are now included. The definition and diagnostic criteria for the papillary thyroid carcinoma subset of the malignant category now suggest limiting use to cases with classical features of papillary thyroid carcinoma. TBSRTC is now the most common classification worldwide for the reporting of thyroid FNA specimens. In view of this, 91

92 APSTRAKTI new suggestions will be useful for various aspects of thyroid FNA including nomenclature, differential diagnosis, the potential impact of NIFTP on the indeterminate diagnostic categories, utility of molecular and IHC markers, and clinical management. References: 1. Ali SZ, Cibas ES, editors. The Bethesda system for reporting thyroid cytopathology. NewYork:Springer; Nikiforov YE, Seethala RR, Tallini G, et al: Nomenclature revision for encapsulated follicular variant of papillary thyroid carcinoma: a paradigm shift to reduce overtreatment of indolent tumors. JAMA Oncol 2016;2: Pusztaszeri M.Rossi E.D.Auger M. Baloch Z. Bishop J. Bongiovanni M. et al.the Bethesda System for Reporting Thyroid Cytopathology: Proposed Modifications and Updates for the Second Edition from an International Panel. Acta Cytologica 2016;60: David N. Poller MD, FRCPath, Zubair W. Baloch MD, PhD, Guido Fadda MD, MIAC, Sarah J. Johnson MD, PhD, FRCPath, Massimo Bongiovanni MD,Alfredo Pontecorvi MD, PhD, Béatrix Cochand-Priollet MD, MIAC, PhDThyroid FNA: New classifications and new interpretations. Cancer Cytopathology 2016; Ali SZ, Cibas ES, editors. The Bethesda system for reporting thyroid cytopathology. NewYork: Springer; Second Edition Fine needle aspiration cytology: current perspective and the role in diagnosis of the breast lesions Ljiljana Vuckovic, Filip Vukmirovic, Mileta Golubovic Medical faculty, University of Montenegro, Clinical centre of Montenegro Breast cancer (BC) is the most prevalent cancer in the world among women and there are nearly 1.7 million new cases worldwide each year. Due to a number of remarkable advances made in both diagnosis and therapy, the survival rates for BC patients have increased in those regions with adequate medical facilities. According to contemporary recommendations, any pathological diagnosis of breast lesions, before any treatment, should be based on a Core Needle Biopsy (CNB), or on a Fine Needle Aspiration Cytology (FNAC), if CNB is not available. The prognosis of the newly diagnosed breast cancer patient depends on a number of factors, among which the most important is the extent of the spread of the disease to the axillary lymph nodes. Because any further treatment is influenced by the presence and number of axillary lymph nodes involved, a complete evaluation of the axillary lymph nodes is performed on every patient that is able to tolerate it, after a formal diagnosis of invasive carcinoma. At the very least an ultrasound with guided fine needle aspiration or core biopsy of suspicious lymph nodes should be undertaken.although CNB is the main method employed in breast lesions diagnostics, FNAC still plays a significant role in the evaluation of pathological processes in the breast, a fact that has been well documented in the relevant literature in the last 20 years. The advantages of FNAC are: the sampling is quicker; the sampling technique usually does not require the use of anaesthetics; the trauma is small, and therefore more convenient for women using anticoagulant therapy; complications are rare; the availability of the results is within a few hours; skilled operators and pathologists regard this method as being highly sensitive in the detection of any malignant cells and the equipment is less expensive. The United Kingdom National Health Service Breast Screening Program (UK NHSBSP), began in Its guidelines have been published with regards to the mode of categorizing cell changes that may be seen in cytological samples obtained by needle aspiration. Five categories have been identified: C1 (unsatisfactory specimen - non-representative), C2 (benign), C3 (atypical - most likely benign), C4 (suspected - most likely malignant) and C5 (malignant). In 1996, the American National Cancer Institute (NCI) also suggested 5 categories for cytological diagnostics of breast lesions: benign, atypical, suspected, malignant and unsatisfactory. Patients with C3 and C4 categories, namely, atypical and suspected, which carry the risk of a malignant tumour, need to undergo further examination. C1 and C2 categories have to be correlated with the results of clinical and radiological examinations. C3 and C4 categories should not be represented in more than 5% of all analyzed aspirates. Currently, there is no individual morphological criterion that cytological diagnostics of malignant breast tumours could be based on. The most important cytological criteria that indicate whether it is a benign pathological process or a malignant tumor are: cellularity of the sample (a very important criterion, but it should be carefully interpreted), loss of cell cohesiveness (characteristic of malignant tumors), cellular arrangements, cell size, biphasicity in smear, the characteristics of the nucleus (size, contour, the appearance of chromatin, the appearance of nucleolus), characteristics of cytoplasm, nuclear-cytoplasmic ratio, 92

93 ABSTRACTS mitotic figures, background appearance (necrosis, peripheral blood cells, mucus ) and the presence of inflammatory cells. It is also possible to perform immuno-histochemical staining on cytological samples, flow cytometry and molecular analyses. The FNAC treatment is characterised by solid sensitivity, specificity and predictive value. The sensitivity of FNAC ranges from 89% to 98% and the specificity is between 98% and 100%. Major shortcomings of this method are the impossibility of diagnosing in situ carcinoma and lesions followed by any abundant production of connective tissue. The CNB treatment has gained remarkable popularity since the 1980s and in many institutions has replaced FNAC. The limitations of both methods are; atypical ductal hyperplasia, fibroepithelial tumours, radial scarring and papillary lesions. In the diagnosis of breast lesions apart from aspiration cytology, other sampling techniques for cytological analysis are also applied. In the era of breast conservation therapy, breast tissue is most commonly sent for intraoperative consultation. A frozen section analysis is performed through freezing and sectioning the surgical specimen with subsequent staining, in order to obtain an extemporaneous assessment of the margins. Although this technique is extensively used by many surgeons to avoid the need for a postponed rescission, some pitfalls have been reported, such as the occurrence of artefacts due to the freezing and thawing of the adipose tissue in the specimen. A different intraoperative method for margins evaluation is imprint cytology, which consists of pressing each of the 6 faces of the specimen on 6 different slides, so that any malignant cell on any involved margin is theoretically present on the cytology of the respective slide, because of the tendency of tumour cells to adhere to glass as compared to adipocytes. Imprint cytology can also be used in assessing the representational value of the CNB samples. A significant number of authors suggest that the application of the imprint of cytology reduces the number of inadequate samples obtained by CNB and can also provide a preliminary diagnosis, especially in cases of adequately sampled malignant tumours. Nipple discharge (ND) accounts for approximately 5% of the breast-related symptoms and is the third most common reason women seek medical attention. Approximately 7% to 15% of unilateral NDs are caused by malignant lesions, primarily ductal carcinoma in-situ (DCIS). A cytological examination of the obtained content is significant in the final treatment decision. Cytological analysis, in particular FNAC, continues to play an important role in the diagnoses of breast cancer. Skilled professionals can determine breast cancer through an analysis of the cytological sample as a reliable and accurate method. Key words: breast carcinoma, cytology, FNAC 1. Senkus E, Kyriakides S, Ohno S, et al. Primary breast cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2015; 26(Suppl 5):S Gipponi M, Fregatti P, Garlaschi A, et al. Axillary ultrasound and fine needle aspiration cytology in the preoperative staging of axillary node metastasis in breast cancer patients. Breast 2016; 30: Wang M, He X, Chang Y, et al. A sensitivity and specificity comparison of fine needle aspiration cytology and core needle biopsy in evaluation of suspicious breast leasons: a systemic review and meta-analysis. Breast 2017; 31: Corsi F, Sorrentino L, Bossi D, et al. Preoperative Localization and Surgical Margins in Conservative Breast Surgery. Int J Surg Oncol 2013; 2013: Castellano I, Metovic J, Balmativola D, et al. The impact of malignant nipple discharge cytology (NDc) in surgical management of breast cancer patients.plos One 2017 Aug 14; 12(8): Pedijatrijski nodalni limfom marginalne zone prikaz slučaja Tatjana Terzić 1, Jelena Lazić 2, Nataša Tošić 3 1 Institut za patologiju Prof. dr Ðorđe Joannović, Medicinski fakultet, Univerzitet u Beogradu, Srbija 2 Univerzitetska dečja klinika, Beograd, Srbija 3 Institut za molekularnu genetiku i genetičko inženjerstvo, Univerzitet u Beogradu, Beograd, Srbija Cilj i uvod: Pedijatrijski nodalni limfom marginalne zone (NMZL) je redak, ali specifičan podtip NMZL sa karakterističnom kliničkom prezentacijom, patohistološkim i molekularnim obeležjima, terapijom i prognozom. Rezultati: Prikazujemo dečaka uzrasta 15 godina koji se javlja zbog bezbolnog uvećanja leve submandibularne limfne žlezde (LN), koje traje tri meseca. U maju godine primljen je u Univerzitetsku dečju bolnicu u Beogradu. Ultrazvukom vrata uočeno je umereno uvećanje leve submandibularne limfne žlezde, kao i blago uvećanje dve desne submandibularne LN (17x7mm, 14x7mm). Fizikalnim pregledom, radiografijom grudnog koša i ultrazvukom abdomena nisu otkriveni hepatosplenomegalija ni limfadenopatija na drugim lokalizacijama. Krvna slika je bila normalna. U biohemijskom nalazu uočene 93

94 APSTRAKTI su povećane vrednosti mokraćne kiseline (499 umol/l), AST (45 U/l), ALT (98 U/l), kao i ubrzana sedimentacija (65mm/h). Urea, kreatinin, alkalna fosfataza, LDH i CRP su bili normalni. Pacijentu je odstranjena leva submandibularna LN u dijagnostičke svrhe. Veličina LN je bila 47x37x20mm. Histopatološki, uočena je fokalno narušena građa: folikularna hiperplazija udružena sa nodularnim agregatima B-ćelija sa karakteristikama progresivne transformacije germinalnih centara (PTGC) u smislu fragmentacije folikula. Imunohistohemijsko bojenje na CD20 pokazalo ekspanziju marginalne zone sa infiltracijom interfolikularnog prostora. Ove B-ćelije bile su negativne na CD3, CD5, CD23, EBV-LMP1, bcl-6, CD10, EMA, CD30, CD15, MUM-1 i pozitivne za bcl-2 i IgD. Imunohistohemijsko bojenje na CD21/CD23/fascin pokazalo je proširenu i iregularnu mrežu folikularnih dendritičnih ćelija. Ki-67 je u rezidualnim folikulima pokazivao polarizaciju, a u interfolikularnim područjima proliferativna aktivnost je bila niska. Na osnovu ovih patohistoloških karakteristika zaključeno je da bi nalaz mogao odgovarati reaktivnoj folikularnoj hiperplaziji sa atipičnom hiperplazijom marginalne zone ili eventualno PNMZL, uz preporuku da se primenom analize polimerazne lančane reakcije (PCR) ispita klonalnost. Dodatna IGH PCR analiza je pokazala da je rearanžman u IgH genskom lokusu biklonalan. Ovi nalazi su govorili u prilog PNMZL. Posle konsultacija sa članovima međunarodne studijske grupe BFM za non-hodkinove limfome, savetovano je praćenje pacijenta, bez uključivanja terapije. Pacijent je do danas bez znakova bolesti, 22 meseca posle postavljanja dijagnoze. Zaključak: Prikazali smo redak slučaj PNMZL sa morfološkim karakteristikama PTGC-a, ali imunohistohemijska analiza i dodatna analiza PCR klonalnosti su bile ključne za konačnu dijagnozu. PNMZL predstavlja dijagnostički i terapijski izazov u pedijatrijskoj populaciji. Ključne reči: Pedijatrijski nodalni limfom marginalne zone, limfni čvor, pedijatrijski Literatura: 1. Aqil B, Merritt BY, Elghetany MT, Kamdar KY, Lu XY, Curry CV. Childhood nodal marginal zone lymphoma with unusual clinicopathologic and cytogenetic features for the pediatric variant: a case report. Pediatr Dev Pathol 2015;18: Rizzo KA, Streubel B, Pittaluga S et al. Marginal zone lymphomas in children and the young adult population; characterization of genetic aberrations by FISH and RT-PCR. Mod Pathol 2010;23: Koo M, Ohgami RS. Pediatric-type follicular lymphoma and pediatric nodal marginal zone lymphoma: recent clinical, morphologic, immunophenotypic, and genetic insights. Adv Anat Pathol 2017;24: Pediatric Nodal Marginal Zone Lymphoma- A Case Report Tatjana Terzic 1, Jelena Lazic 2, Natasa Tosic 3 1 Institut of Pathology Prof. dr Djordje Joannovic, Faculty of Medicine, University of Belgrade, Serbia 2 University Children s Hospital, Belgrade, Serbia 3 Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Serbia Aim and introduction: Pediatric nodal marginal zone lymphoma (NMZL) is a rare, but distinct subtype of NMZL with characteristic clinical presentation, pathohistological and molecular features, therapy and prognosis. Results: We report the case of a 15-year-old boy with no remarkable past history, presented with painless enlargement of left submandibular lymph node (LN) for three months. He was admitted to the University Children s Hospital in Belgrade in May The cervical ultrasound demonstrated moderate left submandibular lymphadenopathy, but also mild enlargement of two right submandibular LNs (17x7mm, 14x7mm). Physical examination, chest radiography and abdominal ultrasound revealed no hepatosplenomegaly and lymphadenopathy elsewhere. The result of blood count test was normal. Biochemistry showed elevated uric acid 499 umol/l, AST 45U/l, ALT 98U/l, and sedimentation rate (65mm/h). Urea, creatinine, alkaline phosphatase, LDH and CRP were normal. The patient underwent left submandibular LN excisional biopsy. The size of the LN was 47x37x20mm. The histopathological examination revealed partial architectural effacement: follicular hyperplasia and nodular B-cell infiltration with features of progressive transformation of germinal centers (PTGC) in the form of fragmentation of follicles. A CD20 immunostain shows an abnormal expansion of the marginal zone with infiltration of interfollicular space. These B-cells were negative for CD3, CD5, CD23, EBV-LMP1, bcl-6, CD10, EMA, CD30, CD15, MUM-1, and positive for bcl-2 and IgD. A CD21/ CD23/ fascin immunostain showed an expanded and disrupted follicular dendritic cell meshwork. Ki-67 highlighted residual follicular polarisation and a low proliferation rate in the interfollicular areas. Based on these pathohistological findings it was concluded that LN likely represent reactive follicular hyperplasia with atypical marginal zone hyperplasia or possible PNMZL, with 94

95 ABSTRACTS recommendation of polymerase chain reaction (PCR) analysis of clonality. Additional IGH PCR analysis demonstrated biclonal heavy chain gene rearrangement. These findings were consistent with PNMZL. After consultation with members of International BFM study group for non-hodgkin lymphomas, followup was recommended without any treatment. The patient has remained disease free for 22 months since diagnosis. Conclusion: We presented a rare case of PNMZL with morphological features of PTGC, but immunohistochemistry and additional PCR clonality analysis were crucial for final diagnosis. This case represents a diagnostic and therapeutic challenge because of their rarity in the pediatric population. Keywords: Nodal marginal zone lymphoma, lymph node, pediatric Literature: 1. Aqil B, Merritt BY, Elghetany MT, Kamdar KY, Lu XY, Curry CV. Childhood nodal marginal zone lymphoma with unusual clinicopathologic and cytogenetic features for the pediatric variant: a case report. Pediatr Dev Pathol 2015;18: Rizzo KA, Streubel B, Pittaluga S et al. Marginal zone lymphomas in children and the young adult population; characterization of genetic aberrations by FISH and RT-PCR. Mod Pathol 2010;23: Koo M, Ohgami RS. Pediatric-type follicular lymphoma and pediatric nodal marginal zone lymphoma: recent clinical, morphologic, immunophenotypic, and genetic insights. Adv Anat Pathol 2017;24: Genetic features of selected adnexal tumors of the skin Martina Bosic Institute of Pathology Prof. Dr Djordje Joannović, School of Medicine, University of Belgrade Adnexal tumors of the skin comprise heterogenous group with over 40 defined entities, classified by predominant differentiation into lesions with apocrine and eccrine, follicular, sebaceous, or multilineage differentiation. Some, but not all these entities are represented by benign and malignant counterparts. Their occurrence may be sporadic or as a part of inherited syndromes (e.g. Muir-Torre syndrome, Brooke-Spiegler Syndrome, or Cowden s syndrome). Adnexal tumors may arise de novo or within hamartomatous lesions such as nevus sebaceous of Jadassohn. Adnexal carcinomas are very rare tumors (the incidence is less than 0.001%), with variable local recurrence, metastatic potential, and survival. Porocarcinoma, hidradenocarcinoma and sebaceous carcinoma (especially ocular type) are considered to have a poor prognosis, with the highest risk of local recurrence and distant metastases. Mortality of the patients with porocarcinoma is very high (65-80%) if regional or distant metastases are present. The treatment of malignant adnexal tumors is usually surgical or less frequently with radiation therapy. Patients with metastases are usually treated with chemotherapy, mostly with cytotoxic reagents, and rarely with estrogen receptor antagonists. The detailed knowledge of genetic features of adnexal tumors is still lacking. Most of the studies examined only few of the genes using low throughput techniques. Development of new generations of genome sequencing methods led to better understanding of tumors with apocrine and eccrine differentiation. For many of their subtypes, it is still unknown whether there are specific genetic changes, that could even be of diagnostic significance. Hotspot mutations in HRAS (p.g13x and p.q61x) were found in a subset of eccrine poromas and porocarcinomas. These mutations were found in tumors with other lines of differentiation and suggesting overlapping genetical characteristics among adnexal tumors. Due to their similar histological features, cylindroma and spiradenoma are usually considered as phenotypic variations of the same entity. Their histological features can be mixed, in which case a diagnosis of spiradenocylindroma is made. In cylindroma, MYB is upregulated either by mutations in CYLD gene (syndromic cases) or due to a rearrangement of MYB gene (sporadic cases). Genetic characteristics of spiradenomas, including the status of CYLD and MYB genes, are largely unknown. It is still unclear if these two are both histological and genetical relatives and what is the level of heterogeneity among tumors arising sporadically or within syndromes. The presence of chromosomal rearrangements in adnexal tumors is also unexplored. TORC1-MAML2 and EWSR1-POU5F1 fusions were found in significant number of hidradenomas. Initially it was thought these fusions could be characteristic for clear cell variant of hidradenomas, but no true correlation with histology was found. Molecular alterations that differ between benign and malignant counterparts and could enable targeted therapy of adnexal carcinomas are unknown. Mutations in TP53, often UV-associated, are frequent in malignant tumors with eccrine and apocrine differentiation and can drive malignant transformation in such tumors. Porocarcinomas and 95

96 APSTRAKTI hidradenocarcinomas harbor various molecular alterations affecting PI3K-AKT or MAPK pathways that could enable targeted therapy in the future. Actionable mutations in EGFR were not found in carcinomas with eccrine and apocrine differentiation thus far. Her2 amplifications are rarely found, mostly in hidradenocarcinomas, but its therapeutic potential has only been utilized only once.16,25 Mutations of PTCH1 and TCF7L1 in hidradenocarcinomas could also enable the treatment with the inhibitors of Hedgehog and WNT/Hippo signaling pathways. It seems that current knowledge gained from genomic studies of adnexal tumors is only a scratch on the surface. In addition, there is no data on epigenetic characteristics or transcriptome of adnexal skin tumors. Taken altogether, further and detailed investigation of genome, epigenome and transcriptome of adnexal tumors is necessary. Such integrated knowledge could explain mechanisms of their development, malignant alteration and progression, so the treatment of patients with metastatic adnexal carcinomas could be changed toward targeted therapy. Literature: 1. Kazakov D V., Michal M, Kacerovska D, Mckee PH. Cutaneous Adnexal Tumors. 1st Ed. Philadelphia: Lippincot Williams & Wilkins Health; Kazakov DW, Michal M, Kacerovska D, Mckee PH, eds. Inherited Syndromes Accompanied by Cutaneous Adnexal Neoplasms and Related Lesions. In: Cutaneous Adnexal Tumors. 1st Ed. Philadelphia: Lippincot Williams & Wilkins Health; 2012: Soni A, Bansal N, Kaushal V, Chauhan AK. Current management approach to hidradenocarcinoma: a comprehensive review of the literature. Ecancermedicalscience. 2015;9: Salih AM, Kakamad FH, Essa RA, et al. Porocarcinoma : A systematic review of literature with a single case report. Int J Surg Case Rep. 2017;30: Knackstedt T, Samie FH. Sebaceous Carcinoma: A Review of the Scientific Literature. Curr Treat Options Oncol. 2017;18(8):47. What have I learned about lung transplantation? Aleksandra Lovrenski Pathology Department, Medical Faculty Novi Sad, Institute for pulmonary diseases of Vojvodina, Sremska Kamenica, Serbia Lung transplantation remains the definitive treatment for end-stage lung diseases and an option when medical and surgical care has been exhausted. The first human single lung transplant was performed in 1963, and the patient, survived for 18 days. From 1963 to 1978, multiple attempts at lung transplantation failed because of rejection and problems with anastomotic bronchial healing. It was only after the invention of the heart-lung machine, coupled with the development of immunosuppressive drugs, that organs such as the lungs could be transplanted with a reasonable chance of patient recovery. The first clinically successful long-term single lung transplant was performed in 1983, and since then over 25,000 lung transplants performed worldwide. Indications include diverse spectrum of pulmonary diseases of airway, parenchyma and vasculature, most commonly: chronic obstructive pulmonary disease fibrotic lung disease cystic fibrosis pulmonary hypertension The donors are hospital patients who have died and who had indicated that they want to be organ donors. Death is defined as cessation of cardiopulmonary function or irreversible cessation of all brain functions as the result of severe brain injury (a gunshot wound, major car accident, stroke, aneurysm rupture, or other significant injury to the brain). In some ocacsions, donor can be living person who can donate just one lung lobe. Although the demand for lung transplants far outweighs the number of donor lungs available, the use rate of potential donor organs in lung transplantation is the lowest among solid organ transplantation, between 15% and 20%. The majority (about 80%) of lungs donated are not usable due to: infection, damage or excess fluid. Also, although maintaining organ viability using static hypothermic preservation is the widely accepted method of preserving donor lung viability after removal, the inhibition of cellular metabolism induced by hypothermia hinders the process of recovery and negates the possibility of assessment 96

97 ABSTRACTS (testing the organ before transplant) or repair during the organ preservation period. These were the main reasons why a new technique for preserving organ viability ex vivo lung perfusion was discovered. This technique, pioneered by Cleveland Clinic surgeons, allows many of these lungs to be converted to lungs that are transplantable, allowing more lives to be saved. It involves attaching the lungs outside of the body to a machine that perfuses them with a solution that helps remove excess water while they are being ventilated. Candidates for recipient organ undergo rigorous testing which include: physical exam, X-ray or CT scan, laboratory testing, measuring a nicotine blood level, spirometry tests, a six-minute walk test, EKG, VQ scan, left and right heart catheterization in some occasions, skin testing to check exposure to TBC, gynecology exam and PAP-smear, prostate exam with measuring PAS, and dental exam. Despite the increase in the number of transplants, the number of organ donors is outpaced by the number of patients on the waiting list. Therefore, efforts are focused on the efficient utilization and distribution of available organs. Major criteria for organ distribution are the geographic location of an organ donor, donor age and additional clinical criteria which include: ABO blood type, thoracic size, immunologic compatibility and Lung Allocation Score (LAS). The LAS was implemented in 2005 and is a weighted score that incorporates both medical urgency (estimated survival without transplant) and transplant benefit (difference between estimated survival with and without transplant). The LAS is a composite of 17 variables which are given different weightings to estimate both the patient s likely survival time on the waiting list and the patient s likely survival time after lung transplantation. The score ranges from 0 to 100 and the higher the score, the higher the priority for transplant. An LAS of 50 or above is called high. Candidate recipients under age 12 are automatically given an LAS of 100. The centers are required to update each patient s LAS every three months if the last LAS was below 50. For patients with an LAS of 50 or above, the LAS must be updated every 14 days. There are four types of lung transplants: single lung transplant, double lung transplant (usually in patients with cystic fibrosis), heart-lung transplant and, rarely, living lobar transplant (in living donation, this procedure requires the donation of lobes from two different people, replacing a lung on each side of the recipient, while in deceased lobar transplantation, one donor can provide both lobes). Pathohistological examination of lung explant usually serves for confirmation of previously set diagnosis. Pathologist contributes to the transplantation process at initial assessment of recipient lung and in the post-transplant period by diagnosing rejection or infection. The grafted lungs have a high incidence of acute rejection when compared to other solid organ allografts and this is most reliably diagnosed by transbronchial biopsy. The lung rejection study group of the International Society of Heart Lung Transplantation has recommended that at least five pieces of alveolated lung parenchyma are examined to confidently grade acute pulmonary rejection. Acute pulmonary rejection is manifested by perivascular infiltrates, which increase in density and frequency with increasing severity. Connective tissue stains are essential for the diagnosis of airway and vascular fibrosis when chronic rejection is suspected and silver stains are mandatory for fungi and pneumocystis in all biopsies. The evaluation of transplant biopsies is a challenging task for the pathologist. The diagnosis should be made as soon as possible because of urgent therapeutic consideration. Contraindications to transplantation include: malignancy in last 2-5 years untreatable coronary disease severe congestive heart failure chronic illness (heart, kidney, liver, brain) HIV, HBV, HCV, TBC Untreatable psihyatric illness Substance addiction (tobacco, narcotics, alcohol) active or within the last 6 months Body mass index greater than 35 Leading causes of death in transplanted patients in the first month after the surgery are usually graft failure and cardiovascular complications, in first year non-cmv infection, after one year most commonly bronchiolitis, and after five years most commonly malignant disease (PTLD) and chronic lung allograft dysfunction. 97

98 APSTRAKTI References 1. Yusen RD, Edwards LB, Kucheryavaya AY, et al. The registry of the International Society for Heart and Lung Transplantation: thirty-second official adult and heart-lung transplantation report 2015; focus theme: early graft failure. J Heart Lung Transplant 2015;34: Kreider M, Hadjiliadis D, Kotloff R. Candidate selection, timing of listing, and choice of procedure for lung transplantation. Clin Chest Med 2011;32: Tsuang WM. Contemporary issues in lung transplant allocation practices. Curr Transplant Rep 2017;4: Valapour M, Skeans MA, Smith JM, et al. OPTN/SRTR 2015 annual data report: lung. Am J Transplant 2017;17(suppl 1): Omara M, Okamoto T, Arafat A, Thuita L, Blackstone EH, McCurry KR. Lung transplantation in patients who have undergone prior cardiothoracic procedures. J Heart Lung Transplant 2016;35: Learning Pathology in the R n R Capital of the World Zlatko Marušić University Hospital Centre Zagreb The presentation will reflect on a one-month period of education that the author spent with the Cleveland Clinic soft tissue pathology team. Cleveland is a US city in the state of Ohio. One of its nicknames is The Rock and Roll Capital of the world, due to the fact that the term R n R was coined in the 1950s by a Cleveland-based disc jockey Alan Freed. The city hosts the Rock and Roll Hall of Fame, established in It is also home to the Cleveland Clinic, a multispecialty academic hospital currently ranked as the #2 hospital by U.S. News & World Report1. In 2014, Cleveland Clinic had a total revenue of $11.63 billion, making it the #2 hospital in US on the Becker s Hospital Review revenue list2. The author spent one month on a UICC ICRETT fellowship in November 2016 with the Cleveland Clinic soft tissue pathology team. The main strength of the soft tissue team is the presence of several internationally known experts with diverse interests within the field of soft tissue and beyond, with team philosophy highlighting the synergy of team work and individual reputation. Among various topics that were covered during the one-month fellowship, certainly one of the most interesting was differentiation among different fibrohistiocytic neoplasms. Fibrohistiocytic tumors are among the most frequent soft tissue tumors and they are most commonly encountered in the skin. Fibrohistiocytic is in fact a merely descriptive term for cells that resemble both normal fibroblasts and histiocytes, and not a true line of differentiation3. Like other soft tissue tumors, fibrohistiocytic neoplasms are divided into benign, intermediate and malignant categories. In presentation, the author will reflect on the key points in the pathology diagnosis within this category of tumors, and these are: -- being able to give a common denominator to numerous variants of benign fibrous histiocytoma -- awareness of the pitfalls in the diagnosis of dermatofibrosarcoma protuberans -- discrimination of malignant fibrohistiocytic skin-based tumors from other, more adverse cutaneous malignancies. References: Goldblum JR, Folpe AL, Weiss SW. Enzinger and Weiss s Soft Tissue Tumors, 6th edition. Philadelphia: Mosby, Between fjords and cytology Zorana Vukasinovic Bokun Departmen of Pathology, CHC Zemun, Serbia The Norvegian University of Science and Technology is the largest educational institution in Norway. It was founded in 1760 as the Trondheim Academy. The Faculty of Medicine and Health Sciences is part of the St Olav s Hospital in Trondheim, and being there, as participant of the Annual Cytology Tutorial of the European Federation of Cytology Societies, was an outstanding experience. Colleagues from all over the world had the opportunity to meet and learn from experts in various fields of cytology. Particularly, differences between conventional and Thin Prep Pap smears, as well as immunocytochemistry of air-dried smears were thoroughly discussed. 98

99 ABSTRACTS Literature 1. Bofin AM, Nygård JF, Skare GB, Dybdahl BM, Westerhagen U, Sauer T.: Papanicolaou smear history in women with low-grade cytology before cervical cancer diagnosis. Cancer Aug 25;111(4): Nygård JF, Sauer T, Skjeldestad FE, Skare GB, Thoresen SØ.: CIN 2/3 and cervical cancer after an ASCUS pap smear. A 7-year, prospective study of the Norwegian population-based, coordinated screening program. Acta Cytol Nov-Dec;47(6): Skoog L, Tani E.: Immunocytochemistry: an indispensable technique in routine cytology. Cytopathology Aug;22(4): doi: /j x. 4. Desai M, Davies O, Menon-Johansson A, Sethi GC. Higher specialty training in genitourinary medicine: A curriculum competencies-based approach. Int J STD AIDS Jan 1: Introducing new terminology in mixed colorectal tumors Nenad Solajic Institute of Oncology Vojvodine, Sremska Kamenica, Serbia Aim: To review current terminology of mixed exocrine and endocrine tumors of the large intestine. Introduction: Previous classification of colorectal tumors contained category called mixed adenoneuroendocrine carcinoma (MANEC) which encompassed neoplasms of the large intestine with features of both adenocarcinoma and a neuroendocrine carcinoma. Indeed, the vast majority of the mixed colorectal tumors have these two malignant components. However, this designation is no more suitable as other combinations of neuroendocrine and non-neuroendocrine tumors are recognised. Material and Metods: A detailed review of the literature on classification of mixed neuroendocrine-nonneuroendocrine tumors has been done. Results: The nonneuroendocrine component in a mixed colorectal tumor can be either exocrine or squamous and can be either benign or malignant. The histological grade of the nonneuroendocrine component may also vary. Therefore in several recent papers a new term has been coined mixed neuroendocrine-nonneuroendocrine neoplasms (MiNENs) in order to convey all possible combinations of the two components. According to the histologically estimated malignant potential, MiNENs are further subdivided into three categories low grade, intermediate grade and high grade. Conclusion: The new terminology is much more comprehensible than the previous ones and ensures a more accurate assessment of biological behaviour of the mixed colorectal tumors thus avoiding overtreatment of clinically innocent lesions. Key words: Mixed tumor, neuroendocrine neoplasm, classification 99

100 UPUTSTVO ZA AUTORA Časopis Materia Medica izlazi četiri puta godišnje i objavljuje radove iz različitih oblasti biomedicine. Za publikovanje se primaju sledeće vrste radova: uvodnici (do 5 strana), originalni radovi (do 10 strana), revijalni radovi (do 12 strana), seminarski radovi (do 10 strana) prikazi slučaja (do 5 strana), pisma uredniku (do 2 strane), prikazi knjiga (do 2 strane), dopisi za rubriku u spomen - In memoriam (do 5 strana), istorija medicine (do 5 strana) i konferencijska saopštenja (do 5 strana). Uređivački odbor se striktno pridržava principa Dobre naučne prakse. Kada pripremaju rad za publikovanje autori moraju da se pridržavaju uputstva koje je predložio Internacionalni komitet za urednike medicinskih časopisa, a koje je publikovano na web sajtu Internacionalnog komiteta urednika medicinskih časopisa UPUTSTVO ZA PRIPREMU RUKOPISA Koristite Time New Roman, font 12, justify orjentaciju (Ctrl + J) i prored 1,5 1. strana Naslov rada (do 12 reči ili 100 slovnih mesta sa proredima, pisati malim slovima poštujući pravopis o velikim slovima, ne stavljati tačku na kraju) Prvi A. Autor 1, Drugi B. Autor 2, Treći C. Autor 3 (puno ime i prezime sa srednjim slovom) 1 Ustanova iz koje su autori (pun naziv) 2 Ustanova iz koje su autori (pun naziv) 3 Ustanova iz koje su autori (pun naziv) Autor za korespondenciju Ime Prezime, institucija, adresa, telefon, 2. strana Apstrakt (do 250 reči, strukturiran) Pišite ga u: originalnom naučnom članku, preglednom članku, prikazu slučajačeva, rubrici aktuelno i u rubrici seminarski radovi, a ne pišite ga u uvodnicima i pismima uredništvu Apstrakt treba da sadrži sledeće delove Cilj (Objective, Aims), Metod (Methods), Rezultate (Results) Zaključak (Conclusion). Ključne reči: ili kratke fraze do 10 (obavezno sa MeSH liste koja se može naći na web sajtu nih.gov/tsd/serials/lji.html I SADA PONOVITE SVE NA ENGLESKOM 3. strana Uvod (idealan uvod je uvod do 25 rečenica na jednoj strani A4 formata) 1. Paragraf uvodne rečenice za centralnu rečenicu Centralna rečenica, ključna rečenica prvog paragrafa je odgovor na pitanje Šta mi znamo (polje istraživanja). Posle centralne rečenice slede 1-2 završne rečenice za 1. paragraf ili 1-2 prelazne na sledeći paragraf. Poželjno je ovaj deo potkrepiti sa 1-2 reference, ne više od 5, a najbolje je da to budu poglavlja iz udžbenika ili revijalni radovi. 2. Paragraf 1-2 uvodne rečenice ka centralnoj rečenici drugog paragrafa. Centralna rečenica, ključna rečenica prvog paragrafa je odgovor na pitanje Šta mi ne znamo (problem istraživanja). Čitaoca upoznajete sa postojećim podacima (tuđim i sopstvenim) o problemu koji istražujete, o ograničenjima da se taj problem reši i o pitanjima na koja odgovori još nisu dati. Citirati samo one reference koje se neposredno odnose na istraživanje istog predmeta i koja su prethodila vašem istraživanju. 3. Paragraf - Cilj vašeg istraživanja. 100

101 UPUTSTVO ZA AUTORA Sugestije: Ako preterate sa referencama u Uvodu izgubićete blago za diskusiju i opteretićete spisak literature (većina časopisa dozvoljava, pa i mi najviše referenci. Prilikom prikupljanja reference neophodno je citirato reference novijeg datuma, naravno da neka stara ( kapitalna ) može naći svoje mesto. Redosled referenci koje citirate treba da sledi logičan raspored paragrafa uvoda. Prve reference su one koje se odnose na uopšteno znanje o problem i reference o istraživačkom problem. Zatim slede reference vezane za nova istraživanja - prethodna, aktuelna istraživanja i njihove limitacije Nikada u Uvodu ne iznositi svoje rezultate Konkretan cilj se obično navodi u jednoj rečenici (poslednjoj rečenici Uvoda) koja postavlja očekivanja zbog kojih je istraživanje započeto i zbog kojeg se rad piše. Vodite računa cilj je prva rečenica strukturiranog apstrakta i poslednja rečenica Uvoda. 4. strana Materijal i metode Opišite kako ste došli do rezultata (precizan dizajn studije, metoda koju ste koristili i kako ste analizirali podatke). Tačni podaci gde je studija sprovedena. Budite koncizni ( ne pišete turistički vodič). Ukoliko koristite standatdni metod citirajte referentnu literaturu. Sve mere koje saopštavate u poglavlju rezultati, u poglavlju metode moraju imati opisan način kao se do njih došlo. Prilikom čitanja ovog metoda, treba omogućiti čitaocima da imaju kritički uvid u vaš radi i da ponove vašu studiju baš na onaj način kako ste je vi uradili. Podnaslovi koji se koriste u poglavlju metoda kao što su: učesnici, dizajn studije, specifične metode, analiza podataka... klasično određuju njen sadržaj. Neophodno je da date detalje o odobrenju vaše studije, koje je dao etički komitet vaše institucije u kojoj je istraživanje sprovedeno. Zbog toga što su etnički principi fundamentalni za dobru istraživačku praksu, mnogi časopisi ne žele da publikuju članke koji ne uključuju detalje o etničkim odobrenjima (Materia Medica je prihvatila Principe dobre naučne prakse). Čitaoci žele da znaju na koji ste način uključili ljude u vašu studiju. Stoga, izbor učesnika mora biti jasno opisan i uključujući i isključujući detalji moraju biti opisani u sitnice. Prilikom opisivanja učesnika studije, njihova privatnost mora biti poštovana. Ne smete uključiti bilo kakve indentifikacione infomacije o njima, u tekstu, tabelama ili fotografijama. Ako se koristi fotografija, pismeni pristanak mora biti uzet od pacijenta ili ako su deca, od njihovih roditelja. Veličinu i karakteristike uzorka, ne stavljajte u poglavlje materijal i metode nego stavite na početak poglavlje rezultati. Mnoge istraživačke studije koriste upitnike pa u poglavlju metode morate dati precizne detalje o upitiniku, koje ste koristili, kako ste ga razvili, i testirali za ponovljivost. U eksperimentalnim studijama, detalji intervencija i kako su primenjeni moraju biti u potpunosti opisane. 5. Strana Rezultati Posle metoda, predstavlja najlakše poglavlje za pisanje. Možete koristiti interesantne kombinacije teksta, tabli i figura da odgovorite na pitanje studije u vidu jasne priče. Ovo poglavlje iz praktičnih razloga je poželjno pisati posle poglavlja metode, a pre pisanja uvoda i diskusije. Osnovno je da sopstvene rezultate učinite jasnim za čitaoca kako bi razumeli šta ste radili i dokle ste stigli. Ovo poglavlje mora voditi čitaova kroz proces istraživanja. Dužina ovog poglavlja je određena isključivo brojem rezultata koje želite da prikažete, a ne onim što vi želite da kažete o tome. Rezultate treba prikazivati postepeno. Prvo se prikazuju elementi deskriptivne statistike koja opisuje karakteristike uzorka studije. To je prvi paragraf poglavlja rezultati i njegov cilj je da precizno i jasno prikaže detalje vašeg uzorka. To je veoma važno, jer epidemolozi žele da znaju kako ste definisali karakteristike vašeg uzorka, a kliničari žele da znaju koliko su učesnici u vašoj studiji slični sa njihovim pacijentima. Po završetku statističke analize podaci i rezultati se mogu prikazati na tri načina: tekstualno, tabelama i figurama. Tekst pojedine rezultate je bolje prikazati jednostavnim rečenicama sa podacima stavljenim u zagradu. Primer: srednja vrednost proliferativnog potencijala za PCNA (2.20%) je veća nego srednja vrednost za Ki- 67 P (1.64%) i Cyclin D1 (1.36%). 101

102 UPUTSTVO ZA AUTORA Tabele predstavljaju popis brojeva ili teksta u rubrikama pri čemu je svaka rubrika obeležena. Tabele pored prikazivanja podataka na pregledan način omogućavaju i ekonomično raspologanje prostorom u članku. Ne treba ih koristiti da bi se pokazao način kretanja nekih rezultata (trend) ili veza između pojedinih rezultata i to je bolje prikazati figurama (dijagramima). Na primer ukoliko želite da prikažete veličinu uzorka i odnos polova vaših ispitanika bolje je da koristite tabelu. Međutim, ukoliko želite da prikažete način na koji je pol povezan sa uzorkom populacije onda je bolje koristiti dijagrame. Legenda tabele se stavlja ispod tabele, levo orjentisana. U mnogim eksperimentalnim i opservacionim studijama je neophodno da prikažete osnovo upoređivanje studijskih grupa koje takođe definišu sposobnost generalizacije vaših rezultata. Nikada ne nazovite osnovnu karakteristiku vašeg uzorka,,demografskim jer shodno Oksfordskom rečniku, demografija je grana antropolologiju u kojoj se proučava statistika, rođenja, smrti i bolesti i stoga, to nije prikladno za ovaj kontekst. U bilo kojoj studiji, procenat, srednja vrednost i njena standardna devijacija ili medijana i njen rang su najprikladnije metode deskriptivne karakteristike i zavise od informacija koje opisuju. Figure prikazivanje rezultata figurama podrazumeva korišćenje dijagrama, fotografija, šema, mapa i crtreža kako bi se na jasan i pregledan način prikazali rezultati dobijeni u istraživanju. Postoji više vrsta dijagrama (štapišasti dijagram (engl. bar chart), histogrami učestalosti (engl. histogram), pogačasti dijagrami (engl. pie chart), linijski dijagrami (engl. line graph), i grafikoni sa slikama (engl. pictograph) prilagođenih za opisivanje i prikazivanje različitih vrsta obeležja i rezultata. Sledeći paragraf poglavlja rezultati se odnosi na opisivanje bivarijantnih analiza. U trećem paragrafu se opisuju multivarijantne analize i to je mesto gde se završava cilj ili testiranje hipoteze, navedeno na kraju poglavlje uvod. Prilikom pisanja ovog paragrafa jedino je bitno da kažete čitaocu ono što on želi da zna. Nemojte dodavati ili uključivati bilo kakave podatke koji se udaljavalju od glavnog cilja. Podsećamo vas da rezultati i podaci nisu ista stvar, nije potrebno da ponavljate brojeve u tekstu koje ste prikazali u tabelama ili figurama. Čitaoci žele da prime poruku iz tabela ili figura i ne treba im dozvoliti da sami interpretiraju. 6. Strana Diskusija (1/3 vašeg teksta) Diskusija je vrlo često najslabiji deo članka. Pojedine stvari u poglavlju diskusija praktično NE SMETE uraditi: 1. ne ponavljajte činjenice iz uvoda 2. izbegavajte ponavljanje rezultata 3. ne prikazujte rezultate koje niste prikazali u poglavlju rezultati 4. ne postoji ni jedan razlog da podvlačite koliko je sjajan vaš rezultat, dozvolite da čitaoci sami o tome prosude Diskusija ne predstavlja jednostavno ponavljanje rezultata ili potvrde njihove tačnosti. Svaka diskusija iznosi ono izvan očiglednosti (engl. beyond the evidence). Svaki članak sadrži zaključak koji se ne nalazi u poglavlju rezultati. Takođe svaki statistički značajan nalaz nema klinički značaj. Diskusiju bi trebalo započeti, po mogućstvu jednom rečenicom - ponavljanjem glavnog nalaza. 1. paragraf poglavlja diskusija se jednostavno može početi: Naša studija pokazuje... i izneti sažeto nalaz naše studije, po mogućstvu u jednoj rečenici. 2. paragraf - treba izneti jasno i precizno (praktično opširno) prednosti i nedostatke studije sa podjednakim naglaskom na oba elementa. Posebno treba imati na umu da će i urednici i čitaoci biti najzainteresovaniji baš za taj paragraf diskusije. Ukoliko urednik ili čitalac otkriju nedostatke u vašoj studiji, a vi ih niste opisali izgubiće poverenje u vašu studiju, jer praktično se postavlja pitanje: Kolika je snaga vaše studije ako vi niste uočili nedostatak. 3. paragraf se odnosi na studiju koja je izvedena. Neophodno je izneti doprinos studije. Ne treba iznositi da li je i u kojoj meri bolja od prethodnih studija na osnovu kvaliteta ili nedostataka koje ste izneli u prethodnom paragrafu, nego treba prednosti i nedostatke sopstvene studije uporediti sa prednostima i nedostacimma drugih studija. Vrlo je važno da naglasite zašto ste vi dobili drugačije rezultate od ostalih ukoliko ste ih dobili. Pažnja! U ovom trenutku postoji opasnost da uđete u sferu špekulacija. Ukoliko ne znate zašto se vaši rezultati razlikuju od drugih iznesite to i ne pretendujte da su vaši ispravni, a tuđi pogrešni. 102

103 U trećem paragrafu možete diskutovati saglasnost ili kontradiktornost vaših rezultata sa rezultatima drugih studija ili opšteprihvaćenih dogmi. 4. Paragraf Vi sada iznosite šta vaša studija stvarno znači. Objasnite jasno doprinos vaših rezultata kliničarima ili drugim čitaocima. Ali, vi ste i ovde na opasnoj zemlji. Mnogi urednici i čitaoci prihvataju vaše rezultate sa opravdanom opreznošću. To je zato što vaši rezultati tek publikovanjem ulaze u fazu kritičkog mišljenja naučne javnosti i budućeg prihvatanja ili odbacivanja. Dozvolite čitaocu da izgradi sopstveni stav o vašem istraživanju. Opišite novinu koju je doneo vaš nalaz u odnosu na rezultate drugih studija. Samo se početnici u pisanju trude da referišu sve članke koje su publikovali identičan aktuelni problem (engl. topic). Sugestije Ni jedan časopis nema dovoljno sredstava da štampa svaki detalj i duge članke. Neophodno je izabrati prikladan broj referenci koje će prikazati željeni uvid (najviše 30). Izbegavajte da citirate apstrakte, a nikada ne citirajte apstrakte starije od dve godine ukoliko nije publikovan originalan članak koji je predstavljen apstraktom na nekom kongresu ili sastanku. Možete sebi dozvoliti još jedan paragraf ukoliko želite da diskutujete o pojedinim pitanjima koja ostaju nejasna i da predložite npr. pravce dajih istraživanja. Na tome će neupadljivo uživati i urednik i čitaoci. Zašto? Urednik vidi potencijalnu mogućnost za nove članke a čitalac ideju za sopstvena istraživanja. Vi naravno ne morate iznositi stavove po pitanju novih istraživanja i vaša diskusija može biti bez tog dela. Praktično ne posedujete argumente za sigurnost onoga što predlažete i može biti domen špekulacija. Sada možete izneti jasan zaključak. Zaključak Kratko i sažeto iznesite potencijalni značaj vašeg nalaza i koliki je njegov doprinos dotadašnjem znanju. Pojedine stvari u zaključku praktično NE SMETE uraditi: 1. Ne iznosite zaključke koji nisu potkrepljeni rezultatima 2. Ne iznosite vaše mišljenje kako da se reši neki problem, a da ga pritom niste analizirali u svojoj studiji 3. Ne pišite pregled svih mogućih mehanizama ako ih niste uključuli u svoju studiju POSLEDNJA STRANA VAŠEG RADA Literatura Izvore za istraživačke ideje i sopstveni rad naučnici nalaze u originalnim naučnim člancima. Pravilno citiranje članaka je važno jer predstavlja sa jedne strane izvor informacija, a sa druge strane način izražavanja poštovanja prema naučniku/cima koji su autori originalnog dela i koji su ga prvi objavilu. Korišćenje ideja drugih istraživača ili bilo kog dela njihovog pisanja kao sopstvenog, čini se težak etički prekršaj poznat kao plagijarizam. Reference numerički navodite kroz članaki u vidu liste na kraju članka, koristeći Vancouver stil Pravila za citiranje originalnih naučnih članaka prema Vancouver stilu podrzumevaju da se autori navode prezimenima posle kojih slede inicijali imena, bez tačke i pojedini se autori odvajaju samo zarezima. Navodi se prvih 6 autora(ako ih ima), a posle toga sledi sentenca,,at al. Spisak autora se završava tačkom, pa sledi jedan prazan prostor i tada se piše naslov, koji se završava tačkom pa sledi jedan prazan prostor, pa potom ime časopisa prema previlima index medicus-a. Ne stavlja se tačka, već postoji samo jedan prazan prostor, pa se posle piše godina publikovanja članka, sledi tačka zarez, pa volumen, dvetačke, a potom broj strane i tačka. Broj sveske ili datum volumena nisu uključeni u citiranje. Sve detalje o pravilnom citiranju možete naći na web adresi: I naravno posetite web adresu International Committee of Medical Journal Editors. Uniform requirements for manuscripts submitted to Biomedical Journals ( za sva dodatna pitanja ILI SE OBRATITE REDAKCIJI. I na kraju to pošaljite na redakciju časopisa kbczpatologija@open.telekom.rs Obavestićemo vas o prispelom radu i proslediti ga u postupak recenziranja, a vama poslati da potpišete izjavu o sukobu interesa. Naši recenzenti će zajedno sa uredništvom pomoći da dođemo do publikovanog članka. 103

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