New WHO histological classification of renal epithelial tumors

Napredak u dijagnostici proveden na temelju morfologije, imunohistokemije i molekularnih metoda doveo je do identifikacije novih entiteta u patologiji bubrežnih tumora. Iz tih je razloga Međunarodno društvo za urološku patologiju (ISUP) preporučilo izmjene klasifikacije tumora bubrega SZO-a 2004. pod nazivom ISUP Vancouver Modifikacija SZO histološke klasifikacije bubrega tumora koja je i službeno, s manjim izmjenama ove, 2016. godine, predstavljena u 4. izdanju SZO-ove klasifikacije tumora mokraćnog sustava i muških spolnih organa. Cilj je ovoga članka kroz pregled literature ukratko predstaviti novu podjelu karcinoma bubrežnih stanica i nove entitete prepoznate po histološkim i genetskim karakteristikama te usmjeriti pažnju na važnost onih osobina tumora koje određuju stupanj i stadij bolesti, a imaju velik prognostički značaj. Nova će klasifikacija omogućiti patolozima da usuglase svoje izvještaje, a ostalim strukama dati uvid u promjene u nalazima patologa.Progress in the diagnostics based on morphology and immunohistochemistry, genetic and molecular methods has led to the identification of new entities in renal tumor pathology. Therefore the International Society of Urological Pathology (ISUP) recommended modifications of the WHO 2004 renal tumor classification and called it ISUP Vancouver Modification of WHO (2004) Histologic Classification of Kidney Tumors which is officially published in new“ blue book“, The 2016 WHO Classification of Tumours of the Urinary System and Male Genital Organs. The aim of this article was to briefly introduce a new classification of renal cell carcinoma and new tumor entities identified by their histological and genetic characteristics. We also wanted to focus attention on the importance of those characteristics that determine the tumor grade and the stage of the disease, which have prognostic significance. The new classification will allow pathologists to harmonize their reports, and other disciplines to understand the changes in the findings of the pathologist

Pathohistological diagnosis of prostate cancer

Rak prostate najčešći je malignom u muškaraca u Europi i SAD-u, raznolik u kliničkoj prezentaciji, patohistološkoj slici, obrascima rasta i širenja. Kada se rak prostate otkrije u ranom stadiju postotak izlječenja je visok. Definitvna verifkacija je patohistološka s individualnom procjenom agresivnog potencijala tumora kroz prognostičke parametre kao što su Gleasonov gradus/gradusna skupina, postotak i broj zahvaćenih cilindara tumorom u iglenoj biopsiji, stadij i pozitvan rub kod prostatektomije. Ovi čimbenici danas značajno utječu na izbor i protokole terapija, ali u ranom stadiju ne mogu prepoznat lokalizirani, klinički značajan karcinom koji će sigurno izazvat metastatku bolest te zahtjeva liječenje. Stoga su se istraživanja danas usredotočila na molekularne biomarkere koji su važni u prognozi, patogenezi te kao ciljne molekule za moguću terapiju. Članak pridonosi boljem razumijevanju patohistološkog nalaza i novih činjenica u molekularnoj patogenezi tumora, što je važno za zbrinjavanje pacijenata s rakom prostate.Prostate cancer (PCa) is the most common male cancer in Europe and the US. The early diagnosis relies on prostate specifc antigen serum test, digito-rectal and ultrasound examinaton. Definitve verificaton is pathohistological with individual assesment of aggressiveness of the tumor potental through prognostc parameters such as Gleason gradus/grade groups, percentage and number of affected cilinders in the biopsy, stage and positve margins in prostatectomy. These parameters signifcantly affect the choice and protocol of therapies but can not identfy a localized, clinically signifcant cancer that will certainly cause metastatc disease and require treatment. Therefore, researchers focused on molecular biomarkers that are important in prognosis, pathogenesis, and as a target molecules for possible therapy. The article contributes to a better understanding of the pathohistological findings and new facts about the molecular pathogenesis of tumors, which are important for the care of patients with prostate cancer

Glomerular diseases: a review of the literature and of the epidemiology of biopsy proven glomerular diseases diagnosed in KBC Rijeka

Glomerularne bolesti mogu biti uzrokovane hemodinamskim promjenama, infekcijom, nepravilnim imunološkim odgovorom, nasljednim metaboličkim poremećajima, djelovanjem toksičnih tvari, a katkada uzrok ostaje skriven. Bazična znanost i translacijska istraživanja u kombinaciji s kliničkim unaprijedili su naše razumijevanje etiopatogeneze ovih bolesti. Nova znanja dovela su do upotpunjavanja i izmjena postojeće klasifikacije glomerulopatija. Poznavanje molekularnih puteva staničnog ciklusa ili otkrivanje novih genetskih oštećenja pridonijela su kreiranju pametnijih terapeutskih pristupa i boljoj kvaliteti života pacijenata s bubrežnim oštećenjem uz odgodu renalne insuficijencije. Cilj preglednog članka je ukratko razmotriti opća načela u patologiji glomerularnih oštećenja i predočiti neka od novijih istraživanja podocitopatija; membranske glomerulopatije (MG); ANCA vaskulitisa; membranoproliferativnog glomerulonefritisa (GN) i C3 glomerulopatije te ulogu komplementa u oštećenju glomerularnih struktura. Također se ukazuje na vrijednost biopsije bubrega koja uz dijagnostičku i prognostičku ostaje nezaobilazna epidemiološka te istraživačka metoda.Glomerular disease could be caused by hemodynamic changes, infections, improper immune response, hereditary metabolic disorders, by the action of toxic substances, and sometimes the cause remains hidden. The basic science and translational research combined with clinical surveys, have improved our understanding of the etiopathogenesis of these diseases. This new knowledge has led to change of the existing classification of glomerulopathies. Advances in knowledge of molecularpathways of the cell cycle or the discovery of new genetic defects contributed to the creation of more patient oriented therapeutic approaches and better quality of life in patients with renal impairment . The aim of this review is to briefly discuss the general principles in the pathology of glomerular injury and to consider some of the recent researches about podocitopathies; membranous glomerulopathy (MG); ANCA vasculitis; C3 glomerulopathy and the role of complement in glomerular damage. Review also demonstrates the value of a kidney biopsy as an essential diagnostic and prognostic, as well as epidemiological and research tool

The Carcinoid Tumour in Meckel’s Diverticulum: How to Treat Young Adults with Appendicitis? – Case Report

This case reports the concomitant and unexpected finding of carcinoid tumour within a Meckel’s diverticulum presenting as an acute abdomen due to gangrenous appendicitis in a young adult male. Both Meckel’s diverticula and carcinoid tumour are rare clinical entities, and carcinoid tumours occurring within a Meckel’s diverticulum are even more uncommon. The initial clinical presentation of carcinoid tumours occurring in a Meckel’s diverticulum is usually similar to that of appendicle carcinoids.Carcinoid tumours are the most common primary tumour of the small bowel. They resemble appendicle carcinoids to the extent that they are usually small, single, and asymptomatic. Surgical treatment of Meckel’s diverticula is recommended procedure. By presenting this case we wished to stress the value of systematic identification and removal of the diverticulum during laparotomy and to underline the importance of exploration the Meckel’s diverticulum particularly in case of young adult subjects

Wünderlich syndrome as a first manifestation of renal cell carcinoma – case report

Cilj: Prikazati spontano, netraumatsko perirenalno krvarenje (Wünderlich sindrom) kao prvu manifestaciju karcinoma bubrega te dijagnostički i terapijski postupak kod takvog bolesnika. Prikaz slučaja: Bolesnica stara 37 godina je došla na hitni medicinski trakt s intenzivnim, naglo nastalim bolovima u lijevom lumbalnom predjelu abdomena; uredno mokri, negira traumu i nema makrohematuriju. Zbog općeg lošeg stanja bolesnica je poslana na hitnu višeslojnu kompjuteriziranu tomografiju (Multi-slice computed tomography, MSCT) abdomena i zdjelice na kojoj je utvrđena inhomogena formacija u gornjem polu lijevog bubrega uz zaključak radiologa da se radi o perirenalnom krvarenju, najvjerojatnije uzrokovanog angiomiolipomom. Urolog se odlučio za hitni operacijski zahvat koji uključuje djelomičnu nefrektomiju lijevog bubrega te evakuaciju hematoma. Patohistološki pregled uputio je na karcinom bubrega kromofobnog tipa koji je uzrokovao krvarenje. Bolesnica se redovito kontrolira, nema znakova recidiva. Zaključak: Wünderlich sindrom je rijetka, potencijalno životno ugrožavajuća manifestacija karcinoma bubrega koja zahtijeva hitni operacijski zahvat. MSCT abdomena i zdjelice je radiološka metoda izbora za akutnu abdominalnu/lumbalnu bol u hemodinamski nestabilnog bolesnika.Aim: To present a case with spontaneous, non-traumatic, perirenal haemorrhage (Wünderlich syndrome) as a first manifestation of renal cell carcinoma. Case report: A 37-year-old female was admitted to the emergency unit with sudden and severe pain in the left lumbar area of abdomen. She has normal voiding, without macrohaematuria or trauma in her medical history. Because of her generally instable state she was referred to emergency multi-slice computed tomography (MSCT) exam of the abdomen and pelvis which reveals inhomogeneous mass in the upper pole of the left kidney. Radiology report indicated perirenal haemorrhage most likely caused by an angiomyolipoma. The patient was operated on by urologist who performed a partial nephrectomy of the left kidney and evacuation of haematoma. Samples were taken for histopathology and cromophobe renal cell carcinoma which caused the perirenal haemorrhage was diagnosed. Our patient is controlled on regular basis, without signs of tumour recurrence. Conclusion: Wünderlich syndrome as the first manifestation of renal cell carcinoma is a very rare but life-threatening manifestation of renal cancer that warrants urgent surgery. MSCT of the abdomen and pelvis is a method of choice in haemodynamically unstable patients with acute abdominal/lumbar pain

Impact of bone marrow angiogenesis, expression of osteopontin and vascular endothelial growth factor on myeloma patient response to the first line therapy

Cilj: Istražiti utjecaj angiogenih parametara, izražaja osteopontina (OPN) i vaskularnog endotelnog čimbenika rasta (VEGF; engl. vascular endothelial growth factor) u koštanoj srži na odgovor na prvu liniju terapije u pacijenata s multiplim mijelomom (MM). Ispitanici i metode: U istraživanje je uključeno 68 pacijenata s MM-om, liječenih na Odjelu hematologije Kliničkog bolničkog centra u Rijeci. Za kvantifikaciju angiogenih parametara uz klasičnu metodu utvrđivanja gustoće krvnih žila (MVD; engl. microvessel density) koristili smo i računalno potpomognutu analizu slike koja nam je omogućila izračunavanje broja krvnih žila po mm2, površine krvnih žila po mm2, srednjeg promjera krvnih žila i ukupne vaskularne površine (TVA; engl. total vascular surface) na bioptičkim uzorcima koštane srži obojanim s anti-CD34. Za određivanje izražaja OPN-a i VEGF-a u plazma stanicama korištena je dvostruka imunohistokemijska metoda CD138+OPN i CD138+VEGF. Rezultati: Utvrđeno je da su viši angiogeni parametri, MVD (P = 0,004) i broj krvnih žila po mm2 (P = 0,028) značajni negativni prognostički pokazatelji odgovora na prvu liniju terapije u pacijenata s MM-om. Zaključak: Objektivna metoda procjene angiogeneze u uzorcima koštane srži mogla bi postati dio rutinske patohistološke obrade pacijenata koja bi pomogla u prepoznavanju podskupina pacijenata s eventualnim agresivnijim tijekom i lošijim odgovorom na terapiju.Objective: To investigate the effect of angiogenic parameters, expression of osteopontin (OPN) and vascular endothelial growth factor (VEGF) in the bone marrow in order to predict response to first-line therapy in patients with multiple myeloma (MM). Patients and Methods: The study included 68 patients with MM, treated at the Department of Hematology, Clinical Hospital Centre in Rijeka. For quantification of angiogenic parameters besides the classical method of determining microvessel density (MVD) we used a computer assisted image analysis which enabled us to calculate the number of blood vessels per mm2, the surface of blood vessels per mm2, an average diameter of blood vessels and total vascular surface (TVA) in the bone marrow biopsies stained with anti-CD34. To determine the expression of OPN and VEGF in plasma cells we used double staining immunohistochemistry method, CD138+OPN and CD138+VEGF. Results: We found that a higher angiogenic parameters, the MVD (P = 0.004) and the number of blood vessels per mm2 (P = 0.028), were significantly negative prognostic indicator of response to the first-line therapy in patients with MM. Conclusion: An objective method of the assessment of angiogenesis in the bone marrow samples could become a part of the routine histopathological analysis which could help to identify a subgroup of patients with possible aggressive course and poor response to the therapy

Medicolegal application of a simple histopathological analysis

Cilj: cilj ove studije je ukazati na ulogu patohistološke analize (PHA) preparata tkiva bojenih hemalaun-eozin (HE) bojom u sudskomedicinskoj praksi. Metode: Radi se o retrospektivnoj studiji obdukcija izvršenih na Zavodu za sudsku medicinu i kriminalistiku Medicinskog fakulteta u Rijeci u periodu od 2000.-2014. Istražena je zastupljenost prirodnih prema nasilnim smrtima, te vrsta prirodnih smrti koje su kod sudskomedicinskih obdukcija najzastupljenije. Također ćemo prikazati koji udio u srčanim smrtima čine smrti uslijed ishemijske bolesti srca (IBS) te koliki je udio preminulih od infarkta miokarda (IM). Rezultati: temeljem analiziranih podataka proizlazi da se u istraživanom petnaestogodišnjem periodu odnos između nasilnih i prirodnih smrti nije značajnije mijenjao (p=0,052) te je tijekom tog razdoblja broj obdukcija relativno konstantan. Uočen je trend porasta prirodnih u odnosu na nasilne smrti od 2010. godine. Kod prirodnih, srčane smrti su vodeći uzrok, a udio smrti uslijed ishemijske bolesti srca (IBS) u tim srčanim smrtima iznosi 87%. Od ukupnih smrti uslijed IBS-a, u provedenom istraživanju IM je zastupljen 21%. Zaključak: PHA je neizostavna kod naglih srčanih smrti (NSS) u koje, kao smrt uslijed IBS spada i IM. To je pretraga koja pomaže kada pri na obdukciji nije moguće utvrditi stvaran uzrok smrti; pretraga koja omogućava vizualizaciju infarktom zahvaćenog srčanog mišića i unutar 24 sata od nastanka lezije (što se ne može uočiti makroskopski), te pretraga koja u sudskom postupku može otkloniti dvojbe. Osim što može potvrditi makroskopski nalaz s obdukcije, može katkad biti pretraga koja utvrđuje stvarni uzrok smrti, a kod naglih srčanih smrti ta pretraga je neizostavna. Predstavlja materijal koji se može koristiti za pregled duže vrijeme nakon smrti, za znanstvena istraživanja i edukaciju.Aim: We aimed this study to highlight the role of histopathological analysis (HPA) using Hemalaun-eosin (H&E) staining technique in forensic medical practice. Methods: This is a retrospective study of autopsies performed at the Department of Forensic Medicine and Criminology, School of Medicine in Rijeka in the period from year 2000 to 2014. We reviewed our data for the natural or a violent death, and whether natural death was of cardiac origin, we reviewed the number of deaths due to ischemic heart disease (IHD) and myocardial infarction (MI). Results: during the fifteen years, the relationship between violent and natural death did not changed significantly (p=0.052) and during this period the number of autopsies remained relatively constant. There has been an increase of natural in relation to the violent deaths since 2010. In natural deaths, cardiac death is the leading cause of death, and the proportion of deaths due to IBS in total cardiac deaths was 87%. Of the total deaths caused by IBS, in the conducted research IM is represented by 21%. Conclusion: HPA is indispensable to sudden cardiac death (SCD). This is a test that helps whenever the autopsy alone cannot bring out the real cause of death; this assessment allows visualization of the infarction-affected cardiac muscle within 24 hours (what cannot be observed macroscopically), and the results could help eliminate doubt in legal proceedings. It represents a material that can be used to check for a long time after the death, for scientific research and education

Primary testicular necrotizing vasculitis clinically presented as neoplasm of the testicle: a case report

We present a case of necrotizing vasculitis with the testicle as the isolated affected organ. A 25-year-old man, pretreated for epididymo-orchitis, presented with a presumed testicular neoplasm. Radical orchiectomy was performed and diagnosis of necrotizing vasculitis was established. In the absence of any other sign of systemic disease, the diagnosis of isolated necrotizing vasculitis of the testis was confirmed. Two years after the operation, the patient showed no symptoms of systemic disease

Electron microscopy in diagnostic practice

Cilj ovog preglednog članka je ukazati na značaj, mjesto i dostupnost elektronske mikroskopije (EM) u rutinskoj dijagnostici bioptičkih uzoraka. Elektronska mikroskopija relativno je mlada metoda, koja se 70-ih godina prošlog stoljeća prvenstveno koristila u dijagnostici tumora nepoznatog primarnog sijela, no danas ima daleko širu primjenu, kao npr. u bolestima bubrega, kongenitalnim i metaboličkim bolestima nakupljanja, bolestima poprečno-prugastih mišića i perifernih živaca te brojnim drugim stanjima. Preduvjet analize EM dobro je poznavanje ultrastrukturalne građe koja se u članku ukratko opisuje. Preanalitičkoj fazi EM prethodi pravilno uzorčenje, adekvatna obrada uzoraka i izrada ultratankih rezova, što je posebno istaknuto u ovom radu. Metoda je relativno zahtjevna, kako svojim postupcima, tako i financijski, stoga treba voditi računa o indikacijama za EM, a u trenutku odabira metode i o pravilnom načinu uzimanja materijala. Slikovno i tekstualno su opisane neke od važnijih indikacija za EM koje se koriste u rutinskom radu, kao što su to bolesti glomerula i poprečno-prugastih mišića te tumora, gdje svjetlosna mikroskopija i imunohistokemijska analiza u većini slučajeva nisu dostatne za postavljanje konačne dijagnoze.The aim of the present review is to highlight the importance, placement and availability of the electron microscopy (EM) analyses in routine diagnostic work with biopsy samples. Electron microscopy is a relatively new method dating from the 1970es, when it was primarily used in the diagnosis of tumors of unknown primary sites. Today it has a much wider application, such as in kidney, congenital, metabolic and accumulation diseases, neuromuscular disorders and numerous other conditions. Prerequisite for adequate EM analysis is good knowledge of ultrastructural cellular formation of which the article gives a brief review. In addition, the pre-analytical phase for EM analysis, which includes proper sampling, adequate processing of tissue and acceptable the sections, necessary for satisfactory analysis is also described in the paper. As the method is the method is relatively complex and financially demanding the use of EM should be. Finally, the article describes some of the most important indications for the use EM in routine work, documented with images, such as in glomerular and muscular diseases and tumor pathology, where light microscopy and immunohistochemical analysis, are very often not sufficient for the final diagnosis

Combined evaluation of bone marrow aspirate and biopsy is superior in the prognosis of multiple myeloma

<p>Abstract</p> <p>Background</p> <p>Estimation of plasma cell infiltrates in bone marrow aspirates (BMA) and bone marrow biopsy (BMB) is a standard method in the diagnosis and monitoring of multiple myeloma (MM). Plasma cell fraction in the bone marrow is therefore critical for the classification and optimal clinical management of patients with plasma cell dyscrasias. The aim of the study was to compare the percentage of plasma cells obtained by both methods with the patient clinical parameters and survival.</p> <p>Methods</p> <p>This retrospective study included BMA and BMB of 59 MM patients. The conventional differential count was determined in BMA to estimate the percentage and cytologic grade of plasma cells. The pattern of neoplastic infiltration and percentage of plasma cells were estimated on CD138 immunostained BMB slides microscopically and by computer-assisted image analysis (CIA).</p> <p>Results</p> <p>Significantly higher values of plasma cell infiltrates were observed in pathologist (47.7 ± 24.8) and CIA (44.1 ± 30.6) reports in comparison with cytologist analysis (30.6 ± 17.1; <it>P </it>< 0.001 and <it>P </it>< 0.0048, respectively). BMB assessment by pathologist counting and using CIA showed strongest correlation (r = 0.8; <it>P </it>< 0.0001). Correlation was also observed between the pathologist and cytologist counts (r = 0.321; <it>P </it>= 0.015) as well as comparing the percentage of plasma cells in BMA and CIA (r = 0.27; <it>P </it>= 0.05). Patients with clinical stage I/II had a significantly lower CIA plasma cell count than those with clinical stage III (<it>P </it>= 0.008). Overall survival was shorter in patients with more than 25% of atypical plasma cell morphology estimated in BMA (<it>P </it>= 0.05) and a higher percentage of tumor cell infiltrates estimated by the pathologist and CIA (<it>P </it>= 0.0341 and <it>P </it>= 0.013, respectively).</p> <p>Conclusion</p> <p>Study results suggested the combined analyses to be useful as a routine procedure to achieve more accurate and informative diagnostic data.</p