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Objectives The aim of the study was to analyze the expression of calpain 2 and the degree of apoptosis of the cardiomyocytes and to compare them between the examined groups of people who died of sudden cardiac death (SCD) caused by early myocardial ischemia (EMI)/acute myocardial infarction (AMI) and control groups. Patients and Methods Respondents were divided into three groups. Group 1 consisted of 50 persons who died of SCD caused by EMI in the period from January 2013 to August 2019. The tissue samples were taken from the zone of ischemia/infarction and the opposite left ventricular wall during the forensic autopsy at the Department of Forensic Medicine and Criminalistics, Faculty of Medicine, University of Rijeka. Group 2 consisted of 51 persons who died of SCD caused by AMI. The control group included myocardial samples obtained from 50 persons who died of instant death by head gunshot. The expression of calpain 2 in the studied heart cells was analyzed immunohistochemically, while the degree of apoptosis was determined by the TUNEL method. Statistical data processing was performed using the computer program MedCalcStatistical Software version 20.011. Results Calpain 2 in myocytes showed greater expression in the zone of EMI (and even greater in AMI zone) compared to the opposite wall and control group (P

OBJECTIVE: The immunohistochemical characteristics of the inflammatory infiltrate in the gingiva of patients with titanium and/or nickel allergic sensitization have not been completely understood and investigated. The aim was to analyze the immunohistochemical profile of inflammatory infiltrate in the gingival tissue of patients undergoing orthodontic treatment and to compare it to patients’ titanium and/or nickel allergy status. MATERIALS AND METHODS: A total of 250 patients undergoing orthodontic treatment were invited to participate and 235 accepted (67% female). Patch test was performed on the allergens: nickel sulfate, titanium, titanium dioxide, titanium oxalate, titanium nitride, and petrolatum as control. Patients with gingival hyperplasia were subjected to initial periodontal therapy. In patients with persisting gingival enlargement after initial periodontal therapy, external gingivectomy was performed. Sample consisted of 44 subjects, 22 had allergic sensitization on titanium and/or nickel and 22 of them were used as control. Immunohistochemical analysis was performed on 44 formalin fixed and paraffin embedded gingival samples using antibodies against CD1a, CD3, CD4, CD8, CD20 and CD68 molecule. Computer assisted image analysis was used to evaluate the number of positive cells in gingival tissue for each immunohistochemical marker. RESULTS: Immunohistochemical analyzes showed that sensitized gingiva had slightly more Langerhans cells and helper T-lymphocytes and fewer T- lymphocytes, cytotoxic T-lymphocytes, macrophages and plasma cells than non-sensitized ones, but the differences were statistically significant only for macrophages with moderate effect size (82.8 vs. 133.9 ; p=0.041 ; r=0.308). No significant differences were noticed when analyzed separately by gender and separately by the type of metal to which the subject was sensitized. CONCLUSION: Immunohistochemical analyzes show that sensitized gingiva has slightly more Langerhans cells and helper T- lymphocytes and fewer T-lymphocytes, cytotoxic T- lymphocytes, macrophages, and plasma cells than non-sensitized ones.

Background: Peripheral T cell lymphoma (PTCL), NOS is heterogeneous category of nodal and extranodal mature T cell lymphoma and it accounts for 30% PTCLs in western countries. Its aberrant expression of B lineage markers can sometimes be very misleading especially in the setting of profound downregulation of T cell markers. Principals/Methodology: To describe a case of PTCL, NOS with down expression of T cell markers and aberrant expression of CD38. Results: A 66-year old woman presented with generalized lymphadenopathy, weight loss and left leg lymph-edema, one month in duration. Cytological examination of the enlarged cervical lymph node aspirate revealed lymphatic cells at different stages of transformation with some epithelioid cells. Conglomerate of enlarged right axillary lymph nodes measuring 3.6x2.6x2 cm was examined. Standard H&E and Giemsa staining showed obliterated lymph node architecture, interfollicular infiltration of polymorphic medium to large sized atypical lymphatic cells some with blastoid and plasmablastic morphology with numerous mitoses and apoptosis. Also there was lots of accompanying plasma cells, eosinophils, and histiocytes. By immunohistochemistry large atypical lymphoid cells were CD38+, CD138-, CD30-/+, MUM1+, PD-1-/+, CD20-, CD79a+/-, PAX-5-, CD3-, CD5-, CD4-/+, CD2-, CD8-, Bcl-2-, Bcl-6-, CD10-, HHV-8- and EBER in situ negative. CD68 staining showed lots of histiocytes and Ki-67 was around 50%. Therefore, initial provisional differential diagnosis was DLBCL. PCR of immunoglobulin heavy chain in FR2A and FR3A regions showed polyclonal distribution, while T cell receptor analysis of TCR gamma region showed bi-clonal and TCR beta region monoclonal distribution. It is only after additional molecular analysis of clonality that diagnosis of PTCL-NOS was made. Conclusion: PTCL, NOS with aberrant B lineage expression and down regulation of T cell markers represents a diagnostic challenge and PCR clonality analysis is crucial for accurate diagnosis.

Ciljevi: Osteopontin (OPN) je fosforilirani glikoprotein koji posjeduje različita djelovanja uključujući nastanak i metastaziranje tumora. Kočenje apoptoze jedan je od mehanizama kojim OPN doprinosi napredovanju tumora, a jezgreni čimbenik kappa B (NF-κB) je uključen u signalne putove kočenja apoptoze. Cilj ovog istraživanja je proučavanje izražaja OPN-a u normalnom tkivu bubrega i svijetlostaničnom karcinomu bubrežnih stanica (SKBS) i određivanje njegovog prognostičkog značenja te ujedno određivanje odnosa između NF-κB i izražaja OPN-a na proteinskoj i genskoj razini kao i njihovog odnosa prema apoptozi u uzorcima SKBS-a. Materijali i postupci: Izražaj proteina OPN-a istražen je metodom imunohistokemije na standardnim tkivnim rezovima 171 SKBS-a i uspoređen s uobičajenim kliničkopatološkim čimbenicima. Korištenjem imunohistokemijske metode i tehnike tkivnih mikroareja (TMA) na 94 SKBS-a određen je izražaj proteina OPN-a te p50 i p65 podjedinice NF-κB i međusobno uspoređen kao i s apoptotičkom aktivnosti. Korištenjem kvantitativne lančane reakcije polimerazom (QPCR) određena je količina OPN glasničke RNA (mRNA) iz svježe smrznutog tumorskog tkiva i uspoređena s izražajem proteina OPN-a i NF-κB u 22 SKBS-a. Rezultati: Izražaj OPN-a je u tumorskom tkivu bio veći u odnosu na normalno tkivo bubrega i primijećen je u 61 SKBS-u (35.7 %) kao citoplazmatsko bojanje različite jačine. Utvrđena je povezanost povećanog izražaja OPN-a s pokazateljima loše prognoze kao što su veličina tumora (p, Objectives: Osteopontin (OPN) is a phosphorylated glycoprotein with diverse functions including tumorigenesis and tumor cell metastasis. Apoptosis inhibition is one of the OPN’s mechanisms that contribute cancer progression and nuclear factor-kappa B (NF-κB) is involved in antiapoptotic signaling pathway. The aim of this study was to analyze the expression of OPN in normal renal tissue and clear cell renal cell carcinomas (CRCC), and to assess its prognostic significance together with determining relations between NF-κB and OPN expression at protein and gene level as well as their relation to apoptosis in specimens of CCRCC. Material and Methods: The expression of OPN protein was analyzed using immunohistochemistry in whole-tissue sections of 171 CRCC and compared to usual clinicopathological parameters. Using tissue microarray (TMA) and immunohistochemical technique the expression of OPN protein and p50 and p65 NF-κB subunits was analyzed in 94 CCRCC and compared mutually and to apoptotic index. Using real-time PCR OPN mRNA was quantified from snap frozen tumor tissue and compared to OPN and NF-κB protein expression in 22 CCRCC. Results: Compared to normal renal parenchyma OPN was upregulated in tumor tissue and was observed in 61 CRCC (35.7%) in the form of cytoplasmic staining of various intensities. The association of OPN expression and poor prognostic indicators as tumor size (p

Hodgkin lymphoma (HL) is an uncommon malignancy usually limited to the lymph nodes and lymphatic system while extranodal involvement is much less common than in non-Hodgkin lymphoma. The current report presents an unusual case of primary classical HL (cHL), nodular sclerosis type with mixed cellularity in buttock soft tissue of 78-year old man. Primary lymphoma of the gluteal muscle is a rare disease and primary cHL is even rarer. In addition, to this unusual extranodal presentation, the present case highlight a diagnostic challenge in fine-needle biopsy masquerading a low grade sarcoma, primarily myxoinflammatory fibrosarcoma or an inflammatory lesion. However, surgical biopsy and immunohistochemistry guided correct diagnosis that was of major interest for further successful treatment.

Introduction: Chronic myeloid leukaemia (CML) is characterized by the Bcr-Abl genetic translocation which leads to constitutive tyrosine kinase signaling. Treatment with tyrosine kinase inhibitors (TKI) should be monitored in order to define the molecular response (MR) which correlate with the quantity of BCR-ABL transcript levels and number of CML cells, respectively. To date, only clinical and laboratory data have been used in predicting MR leaving aside the information given by the tumor itself in the bone marrow at the time of diagnosis to which the therapy has being administered. The aim of the study is to analyze the standard patohistological parameters in bone marrow biopsy of the patients with CML and to compare to MR status. Materials and Methods: Thirty-two bone marrow biopsy cases were examined using H&E and standard histochemistry staining after standard formalin fixation and mild decalcification procedure under the light microscope. Additional immunohistochemical staining using anti-CD34 antibody (clone….) was performed and computer assisted image analysis was used to determine the angiogenesis parameters, the quantity of microvessels per 1mm2 (MVD) and the percentage of microvessel area in total section area (TVA). The MR status was defined as positive if ⩽0.1% BCR-ABL mRNA transcripts were detected in peripheral patient's blood... Results: Among 26 patients with positive MR status the bone marrow morphometric characteristics were: overall hypercellularity of bone marrow (p=0.037), diffuse distribution of multiplied megakaryocytes (p=0.041), non-compact megakaryocyte clusters (p=0.007) and cloud-like megakaryocyte nuclei (p=0.027). Other morphologic parameters like myelofibrosis, erythrocyte content and morphology, megakaryocyte distribution, megakaryocyte nuclear lobulation, staghorn nuclei, naked and dysmorphic nuclei were not in statistically significant association with MR status. Blood vessel morphometry determined by MVD and TVA showed no connection to MR status as well. Conclusions: Our results are showing that some, mainly megakaryocyte, morphologic characteristics could serve as predictors of MR in patients on TKI inhibitors at the time of CML diagnosis before given therapy that could be modified perhaps according to the bone marrow biopsy status.

Cilj: glatkomišićni tumori su lejomiomi i lejomiosarkomi. Postoji rijetka skupina, u kojoj se biološki potencijal tumora ne može utvrditi; to su glatkomišićni tumori nepoznatog malignog potencijala. Cilj je prikazati pacijenta s takvim tumorom, koji je nastao iz glatkog mišićnog tkiva medijastinuma. Prikaz slučaja: 48-godišnji muškarac, subfebrilan, bolovi u grudnom košu sa širenjem u leđa. Kompjutorizirana tomografija toraksa pokazala je oštro ograničenu cističnu tvorbu stražnjeg medijastinuma. Ezofagogastroduodenoskopija je otkrila u srednjoj trećini jednjaka pritisak izvana, a rendgen pasaža jednjaka jednjak lučno potisnut izvana prema desno i ventralno. Bronhoskopijom je utvrđeno da je membranozni dio lijevog glavnog bronha blago ekstramuralno komprimiran. Učinjen je kirurški zahvat, torakotomija lijevo i potpuno odstranjenje tumora medijastinuma. Patohistološki nalaz pokazao je područje nekroze, tumorsko tkivo građeno od vretenastih stanica, koje pokazuju blagu polimorfiju. Imunohistokemijska analiza tumora bila je pozitivna na glatkomišićni aktin (SMA) i dezmin, a negativna na S100 i CD34, što potvrđuje podrijetlo tumora iz glatkomišićnih stanica. Dodatna imunohistokemijska analiza utvrdila je da proliferacijski biljeg Ki-67 iznosi 5,9 %, a p16 je pozitivan u više od 50 % tumorskih stanica. Zaključni patološki nalaz je glatkomišićni tumor nepoznatog malignog potencijala. Pacijent je praćen 48 mjeseci nakon operacije, bez recidiva tumora ili znakova metastaza. Zaključak: Patohistološka dijagnoza može biti otežana, općenito, ali posebno u rijetkim novotvorevinama. Prikazani slučaj pokazuje da ponekad nije moguće utvrditi radi li se o benignom ili malignom glatkomišićnom tumoru. Tada se postavlja dijagnoza glatkomišićnog tumora nepoznatog malignog potencijala, ovdje smještenog u medijastinumu. Nakon kirurškog odstranjenja neoplazme potrebno je redovito pratiti pacijenta, kako bi se utvrdio recidiv bolesti i provelo dodatno liječenje., Aim: Smooth muscle tumors are divided into leiomyomas and leiomyosarcomas. The aim is to present a patient with a rare tumor called smooth muscle tumor of uncertain malignant potential. Case report: The reported patient was a 48-year-old male, subfebrile, with chest pain. Chest computed tomography showed a sharply limited cystic formation of the posterior mediastinum. Esophagogastroduodenoscopy revealed outside compression in the middle third of the esophagus, and X-ray of the esophageal passage showed that the esophagus was pressed from the outside to the right and ventral. Bronchoscopy determined that the membranous part of the left main bronchus was slightly extramurally compressed. A left thoracotomy and an extirpation of the mediastinal tumor were performed. In pathohistology area of necrosis and tumor tissue composed of spindle cells were identified, which showed mild polymorphia. Immunohistochemical findings included positive smooth muscle actin (SMA) and desmin markers, negative S100 and CD34 markers, Ki-67 was 5.9%, and p16 was positive in more than 50% of tumor cells. The patient was followed up for 48 months, with no signs of tumor recurrence. Conclusion: Pathohistological diagnosis can be difficult, particularly in cases of rare neoplasms. The reported case shows that sometimes it is not possible to determine if smooth muscle tumor is benign or malignant. Therefore, the diagnosis of smooth muscle tumor of uncertain malignant potential is established, in our case the tumor was located in the mediastinum. After surgical removal of the neoplasm, the patient should be followed up regularly in order to detect disease recurrence and to give additional treatment.

AIM: Due to oral corrosion of alloys during orthodontic treatment allergic reactions on titanium and/or nickel can occur. Mechanisms of delayed-type hypersensitivity reactions are mostly studied in allergic contact dermatitis and allergic reaction to orthopaedic implant metals but not in orthodontic patients. Delayed type of hypersensitivity reactions are mediated by antigen-specific T lymphocytes. Th1 cells control cellular immunity by recognizing antigens and releasing IFN-y to activate effector cells. Even though delayed type of hypersensitivity is mostly related to Th1 lymphocytes other phenotypic T cells can also be involved such as cytotoxic lymphocytes. The aim was to analyze the immunohistochemical profile of lymphocytic infiltrate in gingival tissue of patients undergoing orthodontic treatment and to compare it to patients’ titanium and/or nickel allergy status. Materials and Methods: External gingivectomy of enlarged gingiva was performed. Immunohistochemical profile of lymphocytic infiltrate was analyzed using antibodies against CD3 (lymphocytes T) CD20 (lymphocytes B) CD4 (Th1 lymphocytes) and CD8 (cytotoxic lymphocytes) molecules on 26 formalin fixed and paraffin embedded gingival tissue samples. Seven patients had confirmed allergy on titanium and/or nickel and 19 were non-allergic and used as control group. The density of a particular lymphocyte type was determined as a percentage of the surface of the stroma where the infiltrate was present using x10 objective lens. Results: There was a tendency towards an increase in CD3 CD4 and CD20 while a decrease in CD8 in allergic patients. Also increased CD3/CD20 ratio and decreased CD4/CD8 ratio is observed in allergic patients. But the differences were not statistically significant. Conclusion: Results indicate that gingival tissue reaction to titanium and/or nickel engages more T than B lymphocytes and also more helper lymphocytes than cytotoxic ones.

U članku „Medijastinalni glatkomišićni tumor nepoznatog malignog potencijala: prikaz slučaja i pregled literature”, čiji su autori Veljko Flego, Darian Volarić, Koviljka Matušan Ilijaš, Ljiljana Bulat-Kardum, tiskanom u časopisu Medicina Fluminensis 2019;55:89-94, objavljena je pogrešna slika 4. U nastavku objavljujemo ispravnu sliku 4.

AIMS: Nickel (Ni) and titanium (Ti) are constituent elements of orthodontic alloys and both can cause contact allergic stomatitis. The spectrum of signs and symptoms of oral contact allergy is wide. There is no single pathognomonic sign or specific clinical picture. The aim of this research was to assess the pathohistological changes in gingival tissue in orthodontically treated patients with an allergy to Ni and/or Ti. SUBJECTS AND METHOD: Patients undergoing orthodontic therapy with gingival hyperplasia were subjected to initial periodontal therapy. In those with persisting gingival enlargement after initial periodontal therapy, an external gingivectomy was performed (N = 29). Gingival fragments were processed with the paraffin- embedding histological technique and stained with haematoxylineosin. Allergy to Ni and Ti was diagnosed after performing a patch test on the upper arm skin. Allergens included nickel sulphate, titanium, titanium dioxide, titanium oxalate, titanium nitride and petrolatum as the control. RESULTS: An allergy was present in 35 per cent of the subjects. The gingiva of allergic subjects demonstrated a slightly higher severity of inflammation and fibrosis, somewhat more frequently epithelial changes (mild hyperplasia, spongiosis but also colliquation of basal layers), and focal inflammatory infiltrates. Also, in allergic subjects inflammation was often localized near the basal membrane. Lymphocytes, histiocytes, plasma cells, eosinophils and neutrophils were present. However, the majority of pathohistological findings did not differ between groups at a statistically significant level. Pronounced exocytosis and band-like inflammatory infiltrates were significantly more often present in allergic subjects (P < 0.05). CONCLUSION: The presence of exocytosis and band- like inflammatory infiltrates appear to be the most characteristic signs of allergy to Ni and Ti in gingival tissue.

The cell block method is a procedure of preparing a cytological sample that can be analyzed using pathohistological methods. Historically, the first attempts to create a cell block date back to the 1880s. Throughout history, numerous methods of building a cell block have been developed that we have at our disposal even today. At the Department of Pathology and Clinical Cytology of Clinical Hospital Rijeka, the most used method to build cell blocks is agar method. It has been shown that we have achieved optimal results using this method. It should be noted that the classical cytological material is suitable for all types of morphological, immunocytochemical and molecular analyses ; however, most of the present-day immunoassay tests for predictive markers are validated on histological material, which, although much more representative, currently limits the use of cytological material. The cell block method is rarely used alone for itself, meaning that it is only used to evaluate morphology alone. Still, there are studies that have shown the diagnostic advantage of this method in cytology, such as tumor classification, owing to its ability to have insight into tumor architecture. Since cell blocks behave as small biopsies, they can be used for morphological studies of apoptosis evaluation on standard HE preparations or by using a TUNEL method that provides visualization of specific DNA fractures due to the apoptosis process. Immunohistochemistry can be used to analyze the presence of different proteins due to the dysregulation of the apoptosis process in cells encapsulated in a cell block, and their detection serves simultaneously for diagnostic purposes of distinguishing precancerous conditions and benign and malignant tumors. In general, studies evaluating the presence of various apoptosis markers in cell block material are extremely rare and have been appearing just recently. The disadvantages of agar-method compared to classical cytological samples are less pronounced cellularity resulting from initially scarce cellular material or loss of material during processing, which reduces the representativeness of the sample itself to the observed process. Although the cell blocks generally obtain enough cells of well-preserved morphology sometimes the cells are damaged by thermal treatment alone. The main advantage of using cell blocks is the ability to analyze different immunohistochemical parameters in standardized and automated systems using tissue samples along with cell block samples for positive and negative control. In conclusion, although the cell block method has been present over a century, a major shift in its application has occurred over the last 15 years due to the need for standardization of cytology diagnostics, as well as the assessment of prognostic and predictive tumor factors in patients where only cytological material is available.

Introduction: The cytological examination of pleural effusions has been well-established method. It helps in staging, prognosis and management of patients with malignancies. Therefore cell blocks prepared from pleural effusions can be used as adjuncts for establishing a more precise cytopathological diagnosis. The aim of this study was to asess the utility of the cell block method in the cytological diagnosis of malignant pleural effusions. Methods: The cell block obtained from pleural effusion were done using Agar method. The pleural effusion is centrifuged for 5 minutes at 3000 RPM. After decanting, 2 ml of 10% formalin is added to the sediment and the material kept for 4-24 hours at room temperature for fixation. The material is afterward centrifuged for 5 minutes at 3000 RPM in order to separate formalin and agar gel is added to the sediment. Preparing of agar gel consists in boiling of 0.9% saline which is added to bacteriological powder, mixed to make crystals disappear and cooled to 450C. Mixing the material with a glass stick makes cells bind to the gel. The cell block obtained is stored at 40C and ready for further processing as histological material suitable for immunohistochemical and molecular analysis. Results: In this study among a total of 85 malignant pleural effusion 56 were further processed to cell blocks. In 43 cases a definitive diagnosis could be achieved by cell block cytology using immunohistochemistry. Ancillary molecular testing for prognostic parameters were performed on cell blocks in 11 cases. Conclusion: The preparation of cell blocks from pleural effusion has confirmed to be a simple safe and cost-effective procedure that can improve cytological diagnosis and increase the usage of the material for further analysis.

Internistička patologija relativno je nov pojam koji obuhvaća dio patologije koji se bavi patohistološkom dijagnostikom pretežito netumorskih stanja, a u manjoj mjeri tumora, u različitim granama interne medicine, poput pulmologije, hematologije, nefrologije, gastroenterologije, dermatologije i imunologije. Uvidom u morfološke promjene bolesnih tkiva patolog postavlja dijagnozu koja se uz dodatne kliničke podatke dorađuje, međutim, patolog često odmah postavlja i definitivnu dijagnozu koja određuje daljnji tijek liječenja pacijenta. Internistička patologija obuhvaća vrlo složen i sofisticiran sustav dijagnostike u patologiji koji implementira bazičnu patohistološku dijagnostiku upotpunjenu histokemijskim, imunohistokemijskim, imunofluorescentnim i molekularnim tehnikama te elektronskomikroskopskom analizom. Oskudnost tkiva dobivenog pretežito tijekom različitih endoskopskih procedura te putem biopsije iglom jedna je od osobitosti ove grane patologije. Interpretacija promjena u analiziranim stanicama i tkivima često je ograničena dostupnošću kliničkih podataka o pacijentovu stanju, a korelacija morfoloških promjena s kliničkim podacima neophodna za ispravno postavljanje konačne dijagnoze. Iz navedenog se može zaključiti kako je internistička patologija dijagnostički vrlo zahtjevna i izazovna grana patologije koja koristi najsuvremenije pomoćne alate u cilju spoznaje patološkog supstrata bolesti, kako poznatih tako i novih internističkih entiteta., Internistic pathology is a relatively new term that covers a part of the pathology which deals with the histopathologic diagnosis of predominantly non-tumor conditions, and to a lesser extent of the tumor, inside the various branches of internal medicine, such as pulmonology, hematology, nephrology, gastroenterology, dermatology and immunology. After examination of the morphological changes of diseased tissue the pathologist designates diagnosis that is worked out with additional clinical data. However, a pathologist often sets the definitive diagnosis immediately that determines the further course of the patient’s treatment. Internistic pathology includes a complex and sophisticated system of diagnostics in pathology that implements basic pathohistological diagnostics integrated with histochemical, immunohistochemical, immunofluorescence and molecular techniques as well as electron microscopic analysis. Paucity of tissue obtained mainly during various endoscopic procedures and through the needle biopsy is one of the peculiarities of this pathological branch. Interpretation of changes in the analyzed cells and tissues is often limited by the availability of clinical data on the patient’s condition and the correlation of morphological changes with the clinical data is necessary to complete the diagnosis properly. From the above it can be concluded that from the diagnostic point of view the internistic pathology is very demanding and challenging branch of pathology that uses the most recent tools to acquire the knowledge of pathological substrate of disease for known as well as for unknown clinical entities. Key words: biopsy; diagnosis; internal medicine; microscopy; pathology

INTRODUCTION & OBJECTIVES: Keratoacanthoma (KA) is a neoplasm composed of keratinizing squamous cells that usually presents as a solitary, rapidly evolving, dome-shaped nodule with central keratin- filled crater. Due to its potential for spontaneous and complete regression, it has been considered a borderline or low- grade malignancy. Both clinically and histopathologically, KA can show overlapping features with squamous cell carcinoma. We present a case of a giant KA, a rare variant of this type of neoplasm. RESULTS: A 74-year old male with a history of psoriasis and excessive sun exposure presented with an asymptomatic, progressively growing lesion on the scalp. Physical examination revealed a plaque measuring 10x12 cm on the patient’s scalp vertex, with crusted, verrucous surface, elevated margins and slightly depressed central area comprising several foci of scarring. Multiple- site small incisional skin biopsies identified acanthotic and papillomatous epidermis, microabscesses of neutrophils and eosinophils but no evidence of malignancy. As this did not correlate with the clinical presentation, a subsequent larger biopsy was performed, which showed hyperkeratosis, epidermal hyperplasia with glassy-pink, large keratinocyte downgrowths, mild cellular atypia and rare mitoses at the deepest portions of the tumor, along with intraepidermal microabscesses and dermal inflammatory infiltrate containing eosinophils. The clinicopathological correlation supported a diagnosis of giant KA, although the final excisional specimen comprised also several areas indicative of verrucous carcinoma, a well-differentiated variant of squamous cell carcinoma (SCC). There was no regional lymphadenopathy and routine laboratory work-up was unremarkable. The patient was treated by radical surgical intervention and Thiersch-plasty. At the 6-month follow-up, multiple crusted lesions measuring up to 1 cm were noted at the periphery of the postsurgical scar and within the graft, indicating a recurrence. However, the patient opted not to undergo any active therapy at that point. CONCLUSIONS: This case presents a rare variant of KA with even a few foci of SCC arising within it. It also showcases the diagnostic pitfalls arising in the setting of small or superficial skin biopsies. Thus, a correlation of clinical findings and histopathology is oftentimes necessary to avoid misdiagnosis and undertreatment of KA and KA-like malignant neoplasms.

Background: Programmed cell death ligand-1 (PD- L1) is a transmembrane protein expressed on different non-tumor as well as on tumor cells, serving them to evade detection and elimination by immune system. Lung cancer is the most common cancer in the world and non-small cell lung cancer (NSCLC) represents approximately 80% to 85% of all lung cancers. In the era of new molecular targeted therapies there is a constant need for the investigation of molecular substrate of cancer progression. Aim: To analyze the PDL-1 expression in NSCLC tumor cells (TC) and immune stromal cells (IC) and to compare it to usual clinicopathological parameters. Materials and Methods: Expression of PDL-1 was analyzed immunohistochemically in 110 surgically resected NSCLC tissue microarray samples, using Ventana ready-to-use PD-L1 (SP263) primary antibody. The histological score (H-score) was calculated by multiplying percentage and intensity of staining separately on TC and IC, and was compared to clinicopathological parameters. Results: The expression of PDL-1 was seen in TC as well as in different types of IC as membranous and cytoplasmic staining of different intensity. The median TC H-score was 8.12 (range 0-300), IC H-score was 14.04 (range 0-60) and they showed a significant correlation (p=0.002, rp=0.286). There was no significant difference in PDL-1 expression between different NSCLC histological types. Statistical analysis showed the association between higher level of TC and IC PDL-1 expression and higher histological grade (p=0.002 and p

Cilj: Cilj je ovog rada prikazati dijagnostički postupak rezidualnog melanoma prsta ruke. Prikaz slučaja: U laboratorij Zavoda za patologiju iz kirurške ambulante primljen je isječak kože četrdesetčetverogodišnjeg muškarca pod dijagnozom tumora četvrtog prsta desne ruke u vidu kupolastog odignuća površine kože najvećeg promjera od 1 centimetra. Lezija je bila boje kože i u cijelosti je preuzeta za patohistološku analizu koja je pokazala da diferencijalno dijagnostički u obzir dolazi melanocitna lezija. S obzirom na izostanak epidermalne komponente lezije bila je potrebna dodatna molekularna analiza za isključivanje svjetlostaničnog sarkoma. Iz naknadno primljenih kliničkih podataka zaključuje se da se zapravo radi o rezidui melanoma koji je prethodno odstranjen bez popratne patohistološke analize. Zaključak: Patohistološka dijagnoza može, općenito, pa tako i u slučaju melanoma, biti otežana zbog nedostatka kliničkih podataka. Suvremena patohistološka dijagnostika ima dobre pomoćne alate za postavljanje točne dijagnoze koja rukovodi daljnji dijagnostički i terapijski protokol pacijenta. No, klinički dermatološki pregled suspektne pigmentne lezije upotpunjen patohistološkom dijagnostikom nezaobilazan je korak, nužan za pravovremeno postavljanje dijagnoze, čime se izbjegava odgađanje početka terapije važne za ishod pacijenta., Objective: The objective of this paper is to present a diagnostic procedure in a case of residual melanoma of the finger. Case report: We received a dome shaped, skin specimen from a forty-four year old man. The skin sample was taken from the fourth finger of his right hand and it was 1 cm in diameter. The skin coloured lesion was serially sectioned and submitted for histopathologic analysis. Microscopic examination showed that it was melanocytic lesion and considering it had no epidermal component, additional molecular analyses were needed to exclude a clear cell sarcoma. A diagnosis of residual melanoma was made, from subsequently received clinical data, however there was no accompanying histopathological analysis from the first excision. Conclusion: A histopathological diagnosis, in general, as well as in the case of melanoma may be difficult due to the lack of clinical data. Contemporary histopathological diagnostics has a good support tools for establishing an accurate diagnosis, which governs the further diagnostic and therapeutic patient’s protocol. However, clinical dermatological examination of doubtful pigmented lesions, complemented by histopathologic diagnostics is a crucial step important for timely diagnosis in order to avoid delay in the therapy which is important for patient’s disease outcome. Key words: clear cell sarcoma; differential diagnosis; fluorescence in situ hybridization; immunohistochemistry; melanoma

hrcak.srce.hr/medicina 408 medicina fluminensis 2016, Vol. 52, No. 3, p. 408-414 Sažetak. Cilj: Utvrditi gradus invazivne tumorske fronte (GITF) u karcinomu pločastih stanica usne šupljine (KPSUŠ), usporediti ga s tradicionalnim histološkim gradusom te ispitati prognostičku vrijednost obaju načina gradiranja. Materijali i metode: Na HE-obojanim mikroskopskim preparatima 86 KPSUŠ-a, odstranjenim na Klinici za maksilofacijalnu kirurgiju KBC-a Rijeka, određen je gradus invazivne tumorske fronte i ispitana njegova povezanost s kliničkopatološkim prognostičkim parametrima kao što su patološki T stadij (pT stadij), patološki N stadij limfnih čvorova (pN stadij), klinički stadij bolesti (TNM stadij) te dužina preživljavanja pacijenata. Podatci o tradicionalnom histološkom gradusu dobiveni su iz patohistološkog nalaza. Rezultati: Tradicionalni histološki gradus nije bio značajno povezan s kliničkim parametrima niti preživljavanjem pacijenata (P = 0,906). Visoki GITF bio je povezan s pozitivnim limfnim čvorovima (P = 0,006) i kliničkim stadijem bolesti (P = 0,025), dok s patološkim T stadijem nije dobivena statistička povezanost (P = 0,086). U univarijatnoj analizi visoki GITF bio je povezan s kraćim preživljavanjem pacijenata (P = 0,001), a u multivarijatnoj analizi se pokazao prognostičkim čimbenikom (P = 0,006). Za pojedinačne parametre koji određuju GITF poput upalnog infiltrata, načina invazije te stupnja keratinizacije također je utvrđena prognostička vrijednost u univarijatnoj (P < 0,001, P = 0,013, tj. P = 0,009) i multivarijatnoj analizi. Zaključak: GITF ima veću prognostičku vrijednost u odnosu na tradicionalni histološki gradus. Njegovo određivanje može pomoći u prepoznavanju pacijenata s većim rizikom za povrat bolesti nakon kirurškog odstranjenja tumora, kojima bi koristile dodatne metode liječenja., Aim: To establish invasive tumor front grade (ITFG) in squamous cell carcinoma of the oral cavity (OCSCC), compare it with traditional histological grade and to investigate the prognostic value of both. Materials and methods: The whole tumor-tissue sections, stained with HE of 86 OCSCC cases were evaluated for the invasive tumor front grade and compared with the clinicopathological prognostic parameters such as pathological stage (pT stage), pathological lymph node stage (pN stage), clinical stage (TNM stage) and length of survival of patients. Tissue has been disposed at the Department of Maxillofacial Surgery, University Hospital Rijeka. Data of traditional histological grade were obtained from previous histological findings. Results: Traditional histological grade was not significantly associated with clinical parameters or survival of patients (P = 0.906). High ITFG was associated with positive lymph nodes (P = 0.006) and clinical stage of disease (P = 0.025), but not to pathological T stage (P = 0.086). In univariate analysis high ITFG was associated with shorter survival of patients (P = 0.001), and multivariate analysis showed it as the independent prognostic factor (P = 0.006). For individual parameters that determine ITFG like inflammatory infiltrate, way of invasion and degree of keratinization was also established statistically significant prognostic value in univariate (P < 0.001, P = 0.013, i.e., P = 0.009) and multivariate analysis. Conclusion: ITFG has greater prognostic value than the traditional histological grade. Determination of ITFG may help identify patients with a higher risk of disease recurrence after surgical removal of the tumor, which would use additional methods of treatment.

The aim of this study is to investigate the differences of clinical and laboratory parameters between patients with JAK2-V617F positive myeloproliferative neoplasms (MPNs) and JAK2 wild type MPNs. DNA was isolated from peripheral blood granulocytes of 106 patients treated at Rijeka University Hospital Center: 41 with polycythemia vera (PV), 43 with essential thrombocythemia (ET), 9 with primary myelofibrosis (PMF) and 13 with myeloproliferative neoplasm- -unclassifiable (MPN-u). The JAK2-V617F mutation was detected using allele specific PCR. Laboratory and clinical parameters were obtained from patient’s medical records. The JAK2-V617F mutation was detected in 69% (73/106) patients with MPNs. The results revealed significantly different prevalence of JAK2-V617F mutation, between MPNs entities: 88% in PV, 58% in ET, 56% in PMF and 54% in MPNs-unclassified disorders. The JAK2-V617F mutation significantly correlated with higher leukocyte count and alkaline phosphatase score in ET group and with higher platelets count, leukocyte alkaline phosphatase score and serum lactate dehydrogenase in PV group. Vascular events were associated with elevated platelets count in wholeMPNs group, with higher platelets and leukocyte count in ET and with splenomegaly in PV patients. Clinical and laboratory data revealed significant contribution of JAK2-V617F mutation to the development of clinical phenotype in patients with distinct subgroups of MPNs.

Prikaz slučaja dobroćudnog tumora mioblastoma u dojci s osvrtom na histogenezu, imunohistokemijski profil, kliničku prezentaciju i prognozu te terapiju neoplazme.

Prikaz gradiranja invazivne tumorske fronte u karcinomu usne šupljine te usporedba s kliničko-patološkim čimbenicima i preživljenjem bolesnika. Također se analizira povezanost izražaja osteopontina s parametrima invazivne fronte te kliničko-patološkim parametrima te preživljenjem bolesnika.

Antiphospholipid syndrome (APS) is a disorder mediated by the characteristic antiphospholipid antibodies with subsequent arterial and venous thromboembolic incidents. There is increasing evidence of an association between autoimmune events on the one side and lymphoproliferative disorders on the other side. The association of APS and splenic marginal zone lymphoma is recognized, but according to our knowledge the association with nodal marginal zone lymphoma so far has not yet been documented. We present the case of 64-year old female with abnormal coagulation test that was admitted to the Clinical Hospital Centre Rijeka for a surgical excision of slow growing tumor mass of the left femoral region. Pathological analysis of surgical specimen revealed an increased lymph node measuring 4 cm in greatest dimension. Histological, immunohistochemical and molecular analysis confirmed a diagnosis of nodal marginal zone non- Hodgkin lymphoma (NHL), while serological test revealed the presence of lupus anticoagulants and anticardiolipin antibodies while antinuclear antibodies were negative. Activated partial thromboplastin time as well as factor V, VII and X was reduced. This case is presenting a synchronous appearance of a specific type of non-Hodgkin lymphoma and antiphospholipid syndrome. So, it highlights the importance of targeted diagnostic processing of NHL patient with coagulation disorder in order to exclude the possibly associated APS.

The matrix metalloproteinases (MMPs) comprise a family of zinc-dependent endopeptidases that are secreted as inactive precursors, which are activated by cleavage of an N-terminal pro- peptide. Their basic mechanisms of action include cancer cell growth, differentiation, apoptosis, migration and invasion, and the regulation of tumour angiogenesis and immune surveillance. The expression of MMP9 has been associated with high potential of metastasis in several human carcinomas including breast cancer. The 29 female patients, 9 premenopausal and 20 postmenopausal, aged from 37 to 79 years were included in this study. Tissue samples were examined in 29 primary and 48 recurrent carcinomas using the tissue microarrays which included 102 cores of primary breast carcinomas and 96 of recurrent breast carcinomas. Immunohistochemistry determined a pattern of expression for MMP9. The staining was diffuse cytoplasmic, strong, moderate, faint/weak and negative. The majority of the breast carcinomas stained homogenously for MMP9 on tumor cells. Statistically significant correlation was found for the expression of MMP9 between primary and recurrent breast carcinomas in general (p

The matrix metalloproteinases (MMPs) comprise a family of zinc-dependent endopeptidases that are secreted as inactive precursors, which are activated by cleavage of an N-terminal pro-peptide. Their basic mechanisms of action include cancer cell growth, differentiation, apoptosis, migration and invasion, and the regulation of tumour angiogenesis and immune surveillance. The expression of MMP2 and MMP9 has been associated with high potential of metastasis in several human carcinomas including breast cancer. The 29 female patients, 9 premenopausal and 20 postmenopausal, aged from 37 to 79 years were included in this study. Tissue samples were examined in 29 primary and 48 recurrent carcinomas using the tissue microarrays which included 102 cores of primary breast carcinomas and 96 of recurrent breast carcinomas. Immunohistochemistry determined a pattern of expression for MMP9. The staining was diffuse cytoplasmic, strong, moderate, faint/weak and negative. The majority of the breast carcinomas stained homogenously for MMP9 on tumor cells. Statistically significant correlation was found for the expression of MMP9 between primary and recurrent breast carcinomas in general (p

Renal cell carcinoma (RCC) has been characterized based on histology, stage and grading to predict behavior and guide therapy ; however RCC is still unpredictable and regardless of tumor size and histology, the molecular attributes of a RCC can determine its risk of recurrence and metastasis (1). Several molecular markers have been investigated for their role in the pathogenesis and progression of RCC. Among them, p53 gene have been reported with wide variation in the literature, and its prognostic significance for this tumor is still unknown (2). Mutations of p53 permit damaged cells to persist in the cell-cycle, thereby promoting carcinogenesis. Mutant p53 protein has a long half-life, and therefore can be detected by immunohistochemistry as a nuclear stain (3, 4, 5). The aim of this retrospective immunohistochemical study was to examine the associations between p53 immunostaining and tumor grade, size and stage (pT), proliferation rate and survival of patients with clear cell renal cell carcinoma (CCRCC). Tissue microarrays (TMA) were built from the cohort of 94 archival formalin fixed paraffin embedded CCRCC. Immunohistochemistry was performed for p53 and Ki67 using the D07 monoclonal antibody and MIB 1. The staining was evaluated as a percentage of nuclear positive tumor cells per 500 cells in each TMA. The median percentage of p53 positive tumor cells was 40.5 (12-90.9). High expression of p53 protein was associated with lower pT stage and tumor size smaller then 7 cm, while there was no correlation with Ki 67 proliferation rate and nuclear grade. Log-rank test did not connect the survival and p53 median split on higher and lower percentage of positive cells in CCRCC (Table 1). Studies show that over-expression of p53 in RCC is frequent and occurs in about 36% of 97cases (6), and in larger series, about 29.5% of 246 tumors , irrespective of the type of RCC.). In the study of Zigeuner et al, p53 multivariate analysis showed a correlation with tumor grade and stage of disease and the period of survival without metastases only in the group of CCRCC, so p53 proved to be an independent prognostic factor that predicts worse disease outcome. The same results was achieved by Ulman and coworkers who concluded that mutations of the p53 gene may allow or contribute to the acquisition of metastatic potential.(2). Study of Iranian author Kabir and colleagues in a group of 125 RCC with different histology found no connection between p53 over-expression with relevant clinicopathological prognostic factors (9). It is likely that the mechanism of over-expression of p53 and its activity in various types of RCC, especially in CCRCC is different than in other types of cancer what was shown by Gurova et al. who hypothesize that RCC cells may use an existing kidney-specific mechanism of p53 attenuation to achieve complete inhibition of the p53 pathway (10). Further studies are needed to determinethe impact of p53 expression and clinical outcomes in RCC.

Ciljevi: Osteopontin (OPN) je fosforilirani glikoprotein koji posjeduje različita djelovanja uključujući nastanak i metastaziranje tumora. Kočenje apoptoze jedan je od mehanizama kojim OPN doprinosi napredovanju tumora, a jezgreni čimbenik kappa B (NF-κB) je uključen u signalne putove kočenja apoptoze. Cilj ovog istraživanja je proučavanje izražaja OPN-a u normalnom tkivu bubrega i svijetlostaničnom karcinomu bubrežnih stanica (SKBS) i određivanje njegovog prognostičkog značenja te ujedno određivanje odnosa između NF-κB i izražaja OPN-a na proteinskoj i genskoj razini kao i njihovog odnosa prema apoptozi u uzorcima SKBS-a. Materijali i postupci: Izražaj proteina OPN-a istražen je metodom imunohistokemije na standardnim tkivnim rezovima 171 SKBS-a i uspoređen s uobičajenim kliničkopatološkim čimbenicima. Korištenjem imunohistokemijske metode i tehnike tkivnih mikroareja (TMA) na 94 SKBS-a određen je izražaj proteina OPN-a te p50 i p65 podjedinice NF-κB i međusobno uspoređen kao i s apoptotičkom aktivnosti. Korištenjem kvantitativne lančane reakcije polimerazom (QPCR) određena je količina OPN glasničke RNA (mRNA) iz svježe smrznutog tumorskog tkiva i uspoređena s izražajem proteina OPN-a i NF-κB u 22 SKBS-a. Rezultati: Izražaj OPN-a je u tumorskom tkivu bio veći u odnosu na normalno tkivo bubrega i primijećen je u 61 SKBS-u (35.7 %) kao citoplazmatsko bojanje različite jačine. Utvrđena je povezanost povećanog izražaja OPN-a s pokazateljima loše prognoze kao što su veličina tumora (p

BACKGROUND. The incidence rate of early-stage prostate cancer has dramatically increased since the introduction of prostate-specific antigen (PSA) screening in developed countries. Nowadays, besides PSA levels and Gleason score, age is considered to be a key prognostic factor in terms of treatment decisions. The present study wanted to establish the differences of clinico morphological parameters for prostate cancer between group of elderly and young men treated with radical prostatectomy according to low and intermediate risk EAU criteria. PATIENTS AND METHODS. A database of 97 men aged ≥65 years and 134 aged ≤65 years was reviewed to compare the clinico pathological features between the groups which were surgically treated in the period from 1998 and 2009. Pretreatment PSA, Gleason score, and postoperative Gleason score, pT stage, and positive surgical margins were correlated. RESULTS. The median age for a group of elderly patients was 69 years while the group of younger patients was 60 years. Younger group had a statistically significant higher preoperative Gleason score (p = 0.015 ; ), with the median value of 6 (range 2-9). Other parameters were not statistically different between two groups. DISCUSSION AND CONCLUSION. The preoperative prognostic factors identified by histological analysis of needle biopsy prostate specimens Gleason grading score, serum markers (PSA), and clinical staging could predict pathological stage and outcome of individual patients with clinically localized prostate cancer. In our study significantly higher preoperative Gleason score in younger patients was presented differently from other studies, which revealed that there were no diversity regarding preoperative variables, however, younger patients have lower prostatectomy Gleason scores and less extra-prostatic extension and positive surgical margins. In our study overall positive surgical margin rate was 34, 32 % what is in concordance with the results of large studies indicating that the positive rate of surgical margin after radical prostatectomy is 20%–40% (4). We can conclude that finding of significantly higher preoperative Gleason score in the group of men younger than 65 years suggests that these patients were still included in the population of surgically treated patients.

Ciljevi: Osteopontin (OPN) je fosforilirani glikoprotein koji posjeduje različita djelovanja uključujući nastanak i metastaziranje tumora. Kočenje apoptoze jedan je od mehanizama kojim OPN doprinosi napredovanju tumora, a jezgreni čimbenik kappa B (NF-κ B) je uključen u signalne putove kočenja apoptoze. Cilj ovog istraživanja je proučavanje izražaja OPN-a u normalnom tkivu bubrega i svijetlostaničnom karcinomu bubrežnih stanica (SKBS) i određivanje njegovog prognostičkog značenja te ujedno određivanje odnosa između NF-κ B i izražaja OPN-a na proteinskoj i genskoj razini kao i njihovog odnosa prema apoptozi u uzorcima SKBS-a. Materijali i postupci: Izražaj proteina OPN-a istražen je metodom imunohistokemije na standardnim tkivnim rezovima 171 SKBS-a i uspoređen s uobičajenim kliničkopatološkim čimbenicima. Korištenjem imunohistokemijske metode i tehnike tkivnih mikroareja (TMA) na 94 SKBS-a određen je izražaj proteina OPN-a te p50 i p65 podjedinice NF-κ B i međusobno uspoređen kao i s apoptotičkom aktivnosti. Korištenjem kvantitativne lančane reakcije polimerazom (QPCR) određena je količina OPN glasničke RNA (mRNA) iz svježe smrznutog tumorskog tkiva i uspoređena s izražajem proteina OPN-a i NF-κ B u 22 SKBS-a. Rezultati: Izražaj OPN-a je u tumorskom tkivu bio veći u odnosu na normalno tkivo bubrega i primijećen je u 61 SKBS-u (35.7 %) kao citoplazmatsko bojanje različite jačine. Utvrđena je povezanost povećanog izražaja OPN-a s pokazateljima loše prognoze kao što su veličina tumora (p

Aim. The role of angiogenesis in the pathogenesis of renal cell carcinoma is well recognized, however the influence of tumor cells in this activity is still not well-known. The aim of this study was to analyze the expression of VEGF-A and VEGF-C, recognized to be involved in blood and lymph vessel neoangiogenesis, in comparison to HIF-1α , regulatory factor of angiogenic switch. ...

Osteopontin (OPN) is a phosphorylated glycoprotein with diverse functions including the role in angiogenesis, bone remodelling, T-cell mediated immunity, ability to act as a cytokine in cell signalling, and as a cell-attachment protein. OPN has also been detected in a number of human tumor tissues and assessed as a potential marker of tumor progression. This study was aimed to analyze the expression of OPN in 50 glioblastomas, and its correlation with tumor cell proliferation and patient outcome. By immunohistochemistry we found cytoplasmic OPN expression in 43 tumors with heterogenous staining pattern ranging from focal and faint to strong and diffuse staining of whole tumor tissue. In 14 cases (28%) high staining intensity of more than 25% of tumor cells was observed and these cases were considered positive, while those with faint OPN positivity or strong positivity in less than 25% of tumor cell were considered negative. In 25 cases (50%) OPN was also present in the interstitium, between tumor cells. This staining pattern was accentuated around necrosis and, in most of the cases, also around blood vessels. In addition to tumor cells, microglial cells and some endothelial cells were also positive for OPN protein. The association of staining for OPN with survival times of the patients has been evaluated using life tables and analysed using log rank test. Patients whose tumors have been classified as OPN positive had lower survival rate compared to those with OPN negative tumors (p=0.02). OPN expression was associated with higher proliferative activity of tumor cells measured as Ki67 labelling index (Student’ s t test, p=0.03). Our results showed that OPN protein is expressed in glioblastoma cells and suggest the role of OPN in glioblastoma progression.

The role of epidermal growth factor receptor (EGFR) in the pathogenesis of clear cell renal cell carcinoma (CCRCC) is still not well recognized. The aim of study was to analyze the expression of EGFR on tumor cells in CCRCC, to correlate its value with EGFR gene copy number and to compare analyzed parameters with clinicopathological characteristics of CCRCC including the patients’ survival. Tissue microarrays (TMA) from the cohort of 94 archive formalin fixed and paraffin embedded CCRCC were immunohistochemically stained for EGFR expression and evaluated as a percentage and intensity of membranous staining (histoscore, HS). EGFR gene copy number changes was investigated by means of fluorescence in situ hybridization (FISH). Clinicopathologic data included tumor size, stage and nuclear grade (NG). Membranous EGFR expression was detected in 84/91 cases (92.3%), with moderate to strong staining (HS 2 and 3) in 52 cases (57.14%), and only week cytoplasmic EGFR in 29 cases (31.86%). Overexpression of EGFR was related to worse prognostic parameters, bigger tumors (p=0.018), higher NG (p=0.0002), pT stage (p=0.036) and lower overall survival (p=0.046). FISH method revealed polysomy 7 associated with protein EGFR overexpression in CCRCC tumor cells (p

Ozljede vratne kralježnice su zbog anatomske građe i položaja vrlo česte, a iz istog razloga trauma manjeg intenziteta može dovesti do većeg oštećenja. Rizične skupine za ozljede su muškarci u dobi 16-30 i iznad 65 godina, a najveći rizični faktor su prometne nesreće. Najčešći tipovi ozljeda vratne kralježnice u sudskomedicinskoj praksi jesu atlantoaksijalni rotacijski pomak, prijelom odontoidnog nastavka C2, traumatska spondilolisteza C2 ili fraktura obješenika, rotacijska fraktura s dislokacijom, hiperfleksijska fraktura, hiperekstenzijske frakture te, kao poseban entitet, trzajna ozljeda vrata. Trzajna ozljeda vrata najčešća je ozljeda u prometnim nesrećama i klasificira se u pet stupnjeva numerirana brojevima od 0 do 4 ovisno o težini simptoma. Razlog zašto se trzajna ozljeda vrata klasificira kao poseban entitet jest zato što nastaje kombinacijom hiperfleksije i hiperekstenzije. Česta komplikacija povezana sa ozljedama vrata je tupa cerebrovaskularna ozljeda gdje zbog sile kretanja koštanih i ligamentnih struktura kralježnice dolazi do oštećenja integriteta krvnih žila vrata i posljedično može dovesti do cerebrovaskularnog inzulta. Sudskomedicinsko vještačenje vratne kralježnice uzima u obzir smanjenje životne aktivnosti ozljeđenika kao i 3 ključne komponente: opseg anatomskog oštećenja, opseg funkcionalnog oštećenja i prognozu bolesti. Samo oštećenje koštane strukture ukoliko je očuvana funkcija klasificira se kao tjelesna ozljeda, dok samo oštećenje kralježnične moždine i ako nije oštećen koštani sustav smatra se običnom ili osobito teškom tjelesnom ozljedom zbog ispada funkcije., Injuries to the cervical spine are very common due to its anatomical structure and position, and for the same reason, lower-intensity trauma can lead to greater damage. The risk groups for injury are men aged 16 - 30 and over 65, and the biggest risk factor is car accidents. The most common types of cervical spinal injuries in forensic medicine are: atlantoaxial rotational displacement, fracture of the odontoid processus, C2 extension, traumatic spondylolisthesis C2 or hanging fracture, rotational fracture with dislocation, hyperflexion fracture, hyperextension fractures and, as a separate entity, whiplash injury. Whiplash neck injury is the most common injury in road accidents and is classified in five degrees numbered from 0 to 4 depending on the severity of symptoms. The reason why whiplash neck injury is classified as a separate entity is because it arises from a combination of hyperflexion and hyperextension. A common complication associated with neck injuries is blunt cerebrovascular injury where due to the force of movement bone and ligamentous structures of the spine, damage to the integrity of the blood vessels of the neck occurs and consequently can lead to cerebrovascular insult. Forensic examination of the cervical spine takes into account the reduction of life activity of the injured as well as 3 key components: the extent of anatomical damage, the extent of functional damage and the prognosis of the disease. Only damage to the bone structure of cervical spine is classified as physical injury if all function is intact, while only damage to the spinal cord is considered ordinary or particularly serious physical injury even if bone structures are intact due to the loss of function.

Vještačenje prijeloma u osteologiji predstavlja izazovno područje koje zahtijeva visoku stručnost i pažljiv pristup. Identifikacija uzroka prijeloma, procjena težine i vrste prijeloma, procjena vremena ozljede i zacjeljivanja, identifikacija komplikacija i posljedica te vjerodostojnost vještačenja ključni su aspekti koji se moraju uzeti u obzir prilikom vještačenja prijeloma kostiju. Iako prijelomi mogu zahvatiti bilo koju regiji ljudskog kostura, njihovo predvidljivo ponašanje pogodno je za razumijevanje okolnosti pod kojima bi moglo doći do prijeloma u određenoj kosti. Razumijevanje najčešćih mehanizama nastanka određenih prijeloma kostiju kao i utjecaja unutarnjih i vanjskih čimbenika koji djeluju na kost od ključne su važnosti pri razjašnjavanju mehanizma i okolnosti pri kojima je došlo do prijeloma. Kako bi se osigurao holistički pristup u rješavanju složenijih slučajeva potreban je multidisciplinarni pristup od strane medicinskih stručnjaka. Navedeni stručnjaci koriste se raznim metodama, od proučavanja medicinske dokumentacije do forenzičke rekonstrukcije kako bi formirali stručno mišljenje koje služi kao važan dokazni materijal u sudskim postupcima. Osnovni dijagnostički postupci spadaju u grupu slikovnih postupaka (MR, CT, radiografija, ultrazvuk), iako se i u određenim slučajevima može provoditi i biopsija kosti. Krajnji cilj vještačenja prijeloma kostiju u Hrvatskoj je pružiti objektivne i stručne informacije koje će pomoći sudu u donošenju pravične odluke temeljene na medicinskim činjenicama i dokazima. Navedeno osigurava pravilno vrednovanje ozljede i adekvatnu pravnu zaštitu za pacijente s prijelomima kostiju., Forensic assessment of fractures in osteology represents a challenging field that requires high expertise and careful approach. Identification of fracture causes, assessment of severity and type of fractures, estimation of the timing of injury and healing, identification of complications and consequences, as well as the credibility of forensic examination, are key aspects that need to be considered in the forensic evaluation of bone fractures. Although fractures can affect any region of the human skeleton, their predictable behavior is suitable for understanding the circumstances under which a fracture could occur in a specific bone. Understanding the most common mechanisms of certain bone fractures and the impact of internal and external factors acting on the bone is crucial in elucidating the mechanism and circumstances of the fracture. To ensure a holistic approach in addressing complex cases, a multidisciplinary approach by medical experts is necessary. These experts employ various methods, ranging from studying medical documentation to forensic reconstruction, to form an expert opinion that serves as important evidentiary material in legal proceedings. Basic diagnostic procedures fall into the category of imaging techniques (MRI, CT, radiography, ultrasound), although bone biopsy may also be conducted in certain cases. The ultimate goal of forensic assessment of bone fractures in Croatia is to provide objective and expert information that will assist the court in making a fair decision based on medical facts and evidence. This ensures proper evaluation of the injury and adequate legal protection for patients with bone fractures.

Sporting events are generally considered to be regulated activities with healthy and fit participants; therefore, when deaths occur, they attract a great deal of public interest. Sudden death during sports activities is defined as an unexpected loss of life that occurs during or immediately after sports activities. Most often, it occurs in otherwise healthy individuals. When it comes to epidemiology, there are significant variations due to the multitude of different studies that use different methodologies to collect data. Despite this, it is important to study epidemiology in order to have an insight into the seriousness of such deaths and to raise awareness about the prevention of similar events. The most common causes of such deaths are of cardiovascular origin, but there are also other causes. The two major categories of causes of sudden death during sports activities are cardiovascular and non-cardiovascular causes. Cardiovascular causes of sudden death during sports activities include various heart diseases. The most common among them are arrhythmias, structural and non-structural congenital heart defects and coronary heart disease. Non-cardiac sudden death is categorized into four groups: neurological, metabolic/endocrine, respiratory and immunological. Forensic medicine plays an important role in the diagnosis of sudden deaths during sports activities. Investigations performed to determine sudden cardiac death require correlation of circumstantial data with autopsy results and laboratory data. Prevention based on cardiovascular screening plays a major role in preventing these tragic events. The survival rates depend significantly on fast and efficient emergency medical intervention and the availability and use of AVD., Sportski događaji općenito se smatraju reguliranim aktivnostima sa zdravim i spremnim sudionicima; stoga, kada se dogode smrti, one privlače velik interes javnosti. Nagla smrt tijekom sportskih aktivnosti definira se kao neočekivani gubitak života koji je uslijedio tijekom bavljenja sportskom aktivnošću ili neposredno nakon nje. Najčešće se javlja kod inače zdravih pojedinaca. Kada se govori o epidemiologiji, prisutne su velike varijacije zbog mnoštva različitih istraživanja koja koriste različite metodologije za prikupljanje podataka. Unatoč tome, važno je proučavati epidemiologiju da bismo imali uvid o ozbiljnosti ovakvih smrti te pobudili svijest o prevenciji sličnih događaja. Najčešći uzroci ovakvih smrti su kardiovaskularnog podrijetla; no, postoje i drugi uzroci. Dvije velike kategorije uzroka iznenadne smrti tijekom sportskih aktivnosti su kardiovaskularni i ne-kardiovaskularni uzroci. Kardiovaskularni uzroci iznenadne smrti tijekom sportskih aktivnosti uključuju različite srčane bolesti. Najčešće među njima su: aritmije, strukturne i nestrukturne kongenitalne srčane greške te koronarna srčana bolest. Nekardijalna iznenadna smrt kategorizira se u četiri skupine: neurološku, metaboličku/endokrinu, respiratornu i imunološku. Važnu ulogu u dijagnostici iznenadnih smrti tijekom sportskih aktivnosti ima sudska medicina. Pretrage koje se rade kako bi se utvrdila iznenadna srčana smrt zahtijevaju korelaciju posrednih podataka s obdukcijskim i laboratorijskim podacima. U sprečavanju ovih tragičnih događaja glavnu ulogu ima prevencija, koja se temelji na kardiovaskularnom probiru. Na stopu preživljavanja uvelike utječe brza i efikasna hitna medicinska pomoć te dostupnost i uporaba AVD-a. Sportski događaji općenito se smatraju reguliranim aktivnostima sa zdravim i spremnim sudionicima; stoga, kada se dogode smrti, one privlače velik interes javnosti. Nagla smrt tijekom sportskih aktivnosti definira se kao neočekivani gubitak života koji je uslijedio tijekom bavljenja sportskom aktivnošću ili neposredno nakon nje. Najčešće se javlja kod inače zdravih pojedinaca. Kada se govori o epidemiologiji, prisutne su velike varijacije zbog mnoštva različitih istraživanja koja koriste različite metodologije za prikupljanje podataka. Unatoč tome, važno je proučavati epidemiologiju da bismo imali uvid o ozbiljnosti ovakvih smrti te pobudili svijest o prevenciji sličnih događaja. Najčešći uzroci ovakvih smrti su kardiovaskularnog podrijetla; no, postoje i drugi uzroci. Dvije velike kategorije uzroka iznenadne smrti tijekom sportskih aktivnosti su kardiovaskularni i ne-kardiovaskularni uzroci. Kardiovaskularni uzroci iznenadne smrti tijekom sportskih aktivnosti uključuju različite srčane bolesti. Najčešće među njima su: aritmije, strukturne i nestrukturne kongenitalne srčane greške te koronarna srčana bolest. Nekardijalna iznenadna smrt kategorizira se u četiri skupine: neurološku, metaboličku/endokrinu, respiratornu i imunološku. Važnu ulogu u dijagnostici iznenadnih smrti tijekom sportskih aktivnosti ima sudska medicina. Pretrage koje se rade kako bi se utvrdila iznenadna srčana smrt zahtijevaju korelaciju posrednih podataka s obdukcijskim i laboratorijskim podacima. U sprečavanju ovih tragičnih događaja glavnu ulogu ima prevencija, koja se temelji na kardiovaskularnom probiru. Na stopu preživljavanja uvelike utječe brza i efikasna hitna medicinska pomoć te dostupnost i uporaba AVD-a.

Cilj istraživanja: Cilj doktorskog rada bio je analizirani izražaj kalpaina 2, kalpaina 10 i stupnja apoptoze stanica srca (miocita i nemiocita) uključenih u mehanizme stanične smrti te ih usporediti između skupine preminulih osoba od iznenadne srčane smrti (engl. sudden cardiac death, SCD) s i bez šećerne bolesti uzrokovane ranom srčanom ishemijom (engl. early myocardial ischemia, EMI) i akutnim infarktom miokarda (engl. acute myocardial infarction, AMI) i kontrolne skupine. Također cilj je bio utvrditi postojanje povezanosti između ispitivanih parametara kao i izražaj kalpaina i apoptotičke aktivnosti stanica srca s obzirom na spol. Ispitanici i metode: Ispitanici su bili podijeljeni u tri skupine: u prvoj skupini je bio 101 ispitanik koji je preminuo od SCD-a uzrokovanog EMI i AMI-em kojem je tijekom sudskomedicinske obdukcije uzet uzorak tkiva iz zone ishemije/infarkta i suprotne stijenke miokarda lijeve klijetke. U drugoj skupini je bilo 54 ispitanika koji su preminuli od SCD-a uzrokovanog EMI i AMI-em, a bolovali su od šećerne bolesti tip II. U kontrolnoj skupini je bilo 50 ispitanika koji su preminuli od nagle moždane smrti uslijed prostrijelne rane glave i kojima je tijekom sudsko-medicinske obdukcije uzet uzorak tkiva iz prednje i stražnje stijenke miokarda lijeve klijetke. lzražaj kalpaina 2 i kalpaina 10 u stanicama srca analiziran je imunohistokemijskom metodom dok je stupanj apoptoze analiziran TUNEL-metodom. Rezultati: Kalpain 2 miocita pokazuje veći izražaj u zoni rane ishemije (te još veći u zoni infarkta) u odnosu na suprotnu stijenku i kontrolnu grupu (P

Bolesti miokarda, ponajprije ishemijska srčana bolest, veliki su javnozdravstveni problem u svijetu i vodeći uzrok smrti u većini razvijenih zemalja svijeta. U posljednjih 30-ak godina broj smrtnih slučajeva od IHD u tim zemljama se smanjio, ali u mnogim dijelovima svijeta taj broj i dalje raste (Rusija i neke istočnoeuropske zemlje). Mogućnost da sustav kalpaina igra ulogu u ovim bolestima eksperimentalno je istražena u literaturi i neke studije su se fokusirale na efekte inhibicije kalpaina u poboljšanju disfunkcije miokarda. Kalpaini su skupina nelizosomskih cisteinskih proteaza koji se aktiviraju u prisutnosti kalcija. Nekontrolirana aktivnost kalpaina povezana je s patogenezom reperfuzijske ozljede miokarda, hipertrofije miokarda, srčanog zastoja i ishemije miokarda. Inhibicija kalpaina može znatno usporiti proces zatajivanja srca i reducirati veličinu infarkta nakon ishemije-reperfuzije. Pretjerana aktivacija kalpaina igra ulogu u oštećenju mitohondrija i oksidativnoj fosforilaciji za vrijeme IRI. Stoga inhibicija kalpaina predstavlja potencijalnu terapijsku strategiju u liječenju bolesti miokarda., Miocardial diseases, primarily IHD, are a major public health problem worldwide and leading cause of death in the most developed countries. In the last thirty years the number of deaths from IHD has decreased, but in many parts of the world this number continues to grow (Russia and some Eastern European countries). The possibility that the calpain system could play a role in these deseases has been experimentally investigated in the literature and several studies have focused on the effects of calpain inhibitors in improving myocardial dysfunction. Calpains are a group of non-lysosomal calcium-activated cystein proteases. Uncontrolled activation of calpain has been found to be involved in the pathogenesis of IRI, cardiac hypertrophy, myocardial stunning and cardiac ischemia. Calpain inhibition significanty attenuate myocardial stunning and reduced infarct size after ischemia-reperfusion. Calpain inhibition therefore serves as a potential medical therapy for patients suffering of myocardial diseases.

Limfoproliferativne bolesti su zloćudne bolesti limfnog sustava koje zahvaćaju neku od staničnih linija limfnog sustava sa zastojem u sazrijevanju i kasnijom akumulacijom patoloških limfnih stanica u organima koji su uključeni u limfni sustav. Kronična limfoproliferacija urokovana Helicobacter pylori može dovesti do razvoja raznh oblika gastrointestinalnih limfoma. Gastrointestinalni limfomi najčešće se javljaju oko šestog desetljeća života. Čimbenici rizika koji su uključeni u patogenezu gastrointestinalnog limfoma su neke infekcije uzrokovane Helicobacter pylori, infekcija virusom humane imunodeficijencije, Campylobacter jejuni, Epstein-Barrov virus, virus hepatitisa B, te limfotropni virus humanih T-stanica. Gastrointestinalni limfom ima širok spektar morfoloških značajki snimanja kod konvencionalnih i presječnih slika. Imaging tehnike imaju presudnu ulogu u dijagnosticiranju faze bolesti i u prepoznavanju potencijalnih komplikacija, kao što su perforacija, opstrukcija i fistule zahvaćenog gastrointestinalnog zida sa susjednim strukturama. Endoskopski ultrazvuk (EUS) najčešća je metoda koja se koristi kod pregleda želuca, te lako možemo prepoznati razliku između limfoma i karcinoma želuca. Što se tiče konvencionalnih rendgenskih zraka, uloga pregleda barijem je ograničena na otkrivanje lezije, te na prikaz lokalizacije i opsega lezije. Što se tiče limfoma tankog crijeva, tanko crijevo obično proučavamo pomoću endoskopskih pretraga ili radioloških tehnika snimanja. Endoskopska video kapsula poželjna je slikovna tehnika za vizualizaciju abnormalnosti sluznice u bolesnika s nejasnim krvarenjem. CT i MR enterokliza i enterografija imaju sve važniju ulogu u proučavanju tumora tankog crijeva. Nadalje, primarni limfom debelog crijeva može se pojaviti kao lokalizirana, velika, ekstraluminalna masa ili stezajući karcinom prstenastog tipa. Na barijevim pretragama i na CT-u najčešći uzorak je onaj polipoidni., Lymphoproliferative diseases are malignant diseases of the lymphatic system that affect one of the cell lines of the lymphatic system with a delay in maturation and subsequent accumulation of pathological lymph cells in the organs involved in the lymphatic system. Chronic lymphoproliferation caused by Helicobacter pylori can lead to the development of various forms of gastrointestinal lymphomas. Gastrointestinal lymphomas most commonly occur around the sixth decade of life. Risk factors involved in the pathogenesis of gastrointestinal lymphoma include some Helicobacter pylori infections, human immunodeficiency virus infection, Campylobacter jejuni, Epstein-Barr virus, hepatitis B virus, and human T-cell lymphotropic virus. Gastrointestinal lymphoma has a wide range of morphological imaging features in conventional and cross-sectional images. Imaging techniques play a crucial role in diagnosing the stage of the disease and in recognizing potential complications, such as perforation, obstruction, and fistulas of the affected gastrointestinal wall with adjacent structures. Endoscopic ultrasound (EUS) is the most common method used to examine the stomach, and we can easily recognize the difference between lymphoma and gastric cancer. As for conventional X-rays, the role of barium examination is limited to detecting the lesion, and to showing the location and extent of the lesion. As for small bowel lymphoma, the small intestine is usually studied using endoscopic examinations or radiological imaging techniques. An endoscopic video capsule is the preferred imaging technique for visualizing mucosal abnormalities in patients with obscure bleeding. CT and MR enteroclysis and enterography play an increasingly important role in the study of small bowel tumors. Furthermore, primary colon lymphoma may appear as a localized, large, extraluminal mass, or a constricting ring-type cancer. On barium tests and on CT, the most common sample is the polypoid one.