Additional Cytomorphological Criteria in Diagnosis of Pilomatricoma – Benign Tumor with Bad Reputation

Pilomatricomas (PM) are benign skin appendageal tumors, with differentiation towards hair-forming cells, usually found in children. They are frequently misdiagnosed by clinicians, and there are also many reports of false positive diagnoses made on fine needle aspiration (FNA) cytology. PM are often mistaken for »small round blue cell« tumors in children, or for Merkel cell carcinoma, basalioma and metastatic small cell carcinoma in adults, with possible over-aggressive therapeutic approach. We present 6 cases of PM, correctly diagnosed preoperatively by FNA. Clinical, cytomorphologic and basic morphometric features were analyzed, and compared with 4 cases of malignant tumors with similar clinical presentation. Morphometric data (longest nuclear diameter) did not prove to be helpful, while basophilic cytoplasmatic protrusions, observed in all 6 analyzed cases, could be useful additional cytomorphologic feature of PM. We concluded that cytomorphologic characteristics of PM are reliable enough for correct preoperative diagnosis in adequate specimens, however the best results are achieved when FNA is performed by an experienced cytologist, and when all relevant clinical data are obtained

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

Clinical cytology

Klinička citologija je dijagnostička medicinska struka koja pomoću analize citoloških uzoraka pod svjetlosnim mikroskopom prepoznaje fiziološka stanja te dijagnosticira razne benigne, premaligne i maligne patološke procese, a uključena je u dijagnostiku gotovo svih organa i organskih sustava. Kod nas je gotovo 40 godina postojala kao samostalna specijalizacija iz medicinske, a potom kliničke citologije. Od 2015. godine uveden je novi program specijalizacije koji objedinjava citologiju i patologiju, pod nazivom specijalizacija iz patologije i citologije. Citologija je od svojih početaka neraskidivo vezana s klinikom i najbolji rezultati dobivaju se u uskom kontaktu pacijenta, kliničara raznih specijalnosti i citologa. Kao minimalno invazivna i brza metoda, gotovo bez kontraindikacija i značajnih komplikacija, citologija je izuzetno atraktivna dijagnostička metoda, a citološki uzorci prikladni su i za dodatne analize (imunofenotipizacija, citogenetika, molekularna analiza). U članku je prikazana primjena citologije u dijagnostici pojedinih organskih sustava, kao i prednosti i ograničenja citološke dijagnostike i čimbenici o kojima ovisi kvaliteta citoloških nalaza. Posebnu pažnju treba posvetiti pravilnom uzimanju uzoraka i pripremi preparata, i neophodno je da svaku fazu dijagnostičkog postupka izvode primjereno educirani zdravstveni djelatnici. Citološka analiza neizostavna je dijagnostička pretraga za rano otkrivanje, dijagnostiku i praćenje prvenstveno upalnih, benignih neoplastičnih, premalignih i malignih promjena gotovo svih organa i organskih sustava.Clinical cytology is a diagnostic medical branch that by means of light microscopic analysis of cell and tissue specimens recognizes various physiological variations, benign and malignant diseases. Cytology is involved in diagnostics of virtually every organ and tissue. Cytology has been a separate specialization in Croatia for almost 40 years, at first as Medical cytology, later as Clinical cytology. In 2015 a new specialization was introduced, synthesizing cytology and pathology, and is called “specialization in pathology and cytology”. From the very beginning, cytology is closely connected to clinics, and the best results are achieved in team work of the cytologists and clinicians of different specialities, and in direct contact with the patient. As minimally invasive and rapid diagnostic method, with almost no contraindications and rare and minor potential complications, cytology is extremely attractive diagnostic method, especially considering that cytological specimens are convenient for ancillary diagnostic methods such as flow cytometric immunofenotypization, cytogenetic, molecular techniques. In this paper we discuss the role of cytology in the diagnostics of some organ systems, as well as its advantages and limitations, and factors that influence the end the result and quality of cytological findings. Particular attention should be paid to the quality of sampling, and specimen preparation techniques. It is of utmost importance that all phases of the procedure are performed by adequately educated medical staff. Cytological analysis is an indispensable diagnostic procedure for early detection, diagnosis and follow-up of various, especially inflammatory, benign, premalignant and malignant conditions in various organs and organ systems

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

Carcinoma originating from branchiogenic cleft cyst – case report

Cilj: Prikazati rijedak slučaj pacijenta s karcinomom koji je nastao na bazi lateralne kongenitalne branhiogene ciste vrata, opisati dijagnostički postupak i konačni ishod nakon patohistološke analize. Prikaz slučaja: Osamdesetgodišnji pacijent primljen je na Kliniku za maksilofacijalnu kirurgiju zbog dijagnostike i terapije bezbolne otekline na lijevoj strani vrata, ispod donje čeljusti, koja se s vremenom povećavala. Ultrazvučni pregled ukazivao je na hipoehogenu promjenu, ispunjenu žućkastim sadržajem. Sadržaj je punktiran, a citološki razmaz ukazivao je na karcinoma pločastih stanica, te se u daljnjem tijeku ordinira operativni zahvat, a materijal prosljeđuje na patohistološku analizu. Patohistološka analiza potvrđuje branhio- geni karcinom koji je nastao na bazi kongenitalne branhiogene ciste. Zaključak: Kongenitalne branhiogene ciste vrata nisu česte, a pojava karcinoma unutar takve ciste je još rjeđa. Prikaz našeg slučaja ukazuje na važnost prepoznavanja branhiogenih karcinoma u sklopu cističnih lezija vrata. Dijagnoza se postavlja na temelju isključivanja u suradnji s kliničarima, odnosno na temelju literaturno opisanih kriterija za postavljanje dijagnoze branhiogenog karcinoma.Aim: To show a rare case of a patient with carcinoma originating from a lateral con- genital branchiogenic cleft cyst, describe the diagnostic pathway, treatment and the final diagnosis confirmed by the pathohistological analysis. Case report: An 80-year-old patient came to the Department of Maxillofacial Surgery, for diagnosis and treatment of a painless, slow growing mass on the left side of the neck, below the lower jaw. Ultrasound examination indicated a hypoechogenic mass filled with yellowish content. The content was aspirated and cytological smear showed squamous cell carcinoma. Furthermore, after surgery, the pathohistological analysis of the surgical material indicated branhiogenic carcinoma originating from a congenital branchiogenic cleft cyst. Conclusion: Congenital branchiogenic cysts are uncommon and carcinoma occurrence within cysts is even rarer. Our case emphasizes the importance of recognizing branhiogenic carcinoma arising within the cystic lesions of the neck. Diagnosis is based on exclusion in collaboration with clinicians, and based on the literature describing the criteria for the diagnosis of branhiogenic carcinoma

Fine Needle Aspiration Cytology (FNAC) in diagnosis of salivary gland tumours

Cilj: Tumori žlijezda slinovnica su rijetke neoplazme glave i vrata, no histološki čine vrlo heterogenu skupinu tumora. Važna metoda njihove dijagnostike je ultrazvučna pretraga žlijezda slinovnica uz citopunkciju tumorske promjene. Cilj rada je odrediti učestalost pojedine vrste tumora, specifičnost i senzitivnost citološkog nalaza te utvrditi stupanj podudarnosti između citološkog i patohistološkog nalaza. Ispitanici i metode: Ovim istraživanjem obuhvaćeno je 49 pacijenata operiranih zbog tumora velikih žlijezda slinovnica između 2015. i 2017. godine. Uključeni su samo pacijenti s prijeoperativnim citološkim nalazom i postoperativnim patohistološkim nalazom koji su međusobno uspoređeni. Rezultati: Najzastupljenija skupina pacijenata je ona iznad 60 godina (57 %). Doušna žlijezda bila je najčešće sijelo tumora u 94 % pacijenata. Prema citološkom nalazu dijagnosticirano je 40 dobroćudnih i 9 zloćudnih tumora. Patohistološkom analizom utvrđeno je 39 dobroćudnih i 10 zloćudnih tumora. Najčešće patohistološke dijagnoze bile su Warthinov tumor (cistadenolimfom) u 52,5 % i pleomorfni adenom u 37,5 % pacijenata. Senzitivnost citološkog nalaza iznosila je 90 %, dok je specifičnost bila 100 %. Kappa (κ) koeficijent bio je 0,93 (95 % CI = 0.687 – 0.979). Zaključak: U ovoj studiji citološka punkcija i analiza pokazala se kao vrlo dobra metoda u dijagnostici tumora velikih žlijezda slinovnica s visokom osjetljivošću i specifičnošću te izvrsnim stupnjem podudarnosti između citološkog nalaza i krajnje dijagnoze.Aim: Salivary gland tumours are rare head and neck neoplasms that histologically make up a very heterogeneous tumour group. The most important diagnostic method is an ultrasound exam of the salivary gland with cytopunction of a tumour. The aim of the paper is to determine the specificity and sensitivity of the cytological findings and to determine the degree of agreement between the cytological and histopathological findings. Patients and methods: This study encompassed 49 patients who underwent surgery due to salivary gland tumors between 2015-2017. Only patients with preoperative cytologic findings and postoperative histopathological findings were compared. Results: The most frequent group of patients were those over 60 years (57%). The salivary gland was the most common cancer site in 94% of patients. According to the cytological finding, 40 benign and 9 malignant tumours were diagnosed. In the histopathological study of lesions, 39 were diagnosed as benign and 10 as malignant. The most common histopathological diagnosis was Warthin’s tumor (cystenolymphoma) in 52.5% and pleomorphic adenom in 37.5% of patients. Based on the data, sensitivity was 90% and specificity was 100%. Kappa statistics for the degree of agreement between fine needle aspiration cytology and histological results were 0.93 (95% CI = 0.687-0.979). Conclusion: In our study, FNAC proved to be a very good method in the diagnosis of salivary gland tumours with high sensitivity and specificity, and excellent degree of agreement between FNAC and final diagnosis

Primitive neuroectodermal tumor of the lung with pleural effusion - a case report

Uvod: Primitivni neuroektodermalni tumor pluća (PNET) spada u skupinu izrazito malignih tumora, koji se najvećim dijelom javljaju u djece i adolescenata. Ovaj tumor rano metastazira i ima nisku stopu preživljavanja. Prikaz slučaja: 29-godišnja žena tijekom mjesec dana imala je bolove u desnoj strani prsišta i progresivnu zaduhu. Višeslojna kompjutorizirana tomografija (MSCT) prsnoga koša pokazivala je opsežan desnostrani pleuralni izljev i veliku ekspanzivnu tvorbu u gornjem desnom plućnom režnju. Učinjena je torakocenteza, a u pleuralnom izljevu nađene su maligne stanice. Bronhoskopski je viđena vanjska kompresija na bronhe, bez malignih stanica u uzetim uzorcima bronha. U transtorakalnoj, CT-om vođenoj biopsiji tvorbe pluća, histološkom analizom utvrđene su male stanice, s hiperkromatskim jezgrama i atipičnim mitozama. Imunohistokemijski stanice su bile pozitivne na CD99, NSE i CD56 markere. Pozitron-emisijska tomografija kombinirana s kompjutoriziranom tomografijom (PET/CT) pokazivala je jako nakupljanje 18F-fluorodeoksiglukoze u gornjem desnom plućnom režnju i medijastinalnim limfnim čvorovima. Scintigrafijom somatostatinskih receptora (oktreoskan) nađeno je nakupljanje radiofarmaceutika u gornjem desnom plućnom režnju i medijastinumu, čime su utvrđeni somatostatinski receptori u tim dijelovima tijela. Bolesnica je liječena kemoterapijom (cisplatin i etopozid) i oktreotid acetatom, ali PET/CT je pokazivao progresiju tumora, te je provedena palijativna radioterapija. Tumor je brzo progredirao i bolesnica je preminula jedanaest mjeseci nakon utvrđivanja dijagnoze. Zaključak: PNET je agresivni i smrtonosni tumor, te ga treba uzeti u obzir u diferencijalnoj dijagnostici tumora prsnoga koša, bez obzira na dob bolesnika.Introduction: Primitive neuroectodermal tumor (PNET) is a group of rare, highly malignant neoplasms usually found in children and adolescents. The tumor tends to metastasize early, and consequently the survival rate is low. Case report: A 29-year-old female presented with pain in the right side of the thorax and progressive breathlessness of one-month duration. Multi-slice computed tomography (MSCT) of the chest revealed a large pleural effusion in the right hemithorax, and a large expansive formation in the right upper lobe. Thoracentesis was performed, and malignant cells were found in pleural effusion. Bronchoscopic examination revealed extrinsic compression on the bronchi, without malignant cells in the samples taken. Transthoracic MSCT guided biopsy of the mass histologically revealed small cells, with hyperchromatic nuclei and atypical mitosis. Immunohistochemically, the cells were positive for CD99, NSE and CD56. Positron emission tomography (PET) CT revealed intense accumulation of 18F-fluorodeoxyglucose in the right upper lobe and in the mediastinal lymph nodes. Octreoscan showed pathological accumulation of radiopharmaceuticals in the right upper lobe and mediastinum, indicating a lesion with the expression of somatostatin receptor. The patient received chemotherapy (cisplatin and etoposide), and octreotide acetate. PET/CT showed tumor progression. Palliative radiotherapy was administered. The disease progressed rapidly and the patient died subsequently eleven months after the diagnosis. Conclusion: PNET is an aggressive and lethal disease, therefore should be considered in the differential diagnosis of thoracic tumors regardless of the age of the patient

Primitive neuroectodermal tumor of the lung with pleural effusion - a case report

Uvod: Primitivni neuroektodermalni tumor pluća (PNET) spada u skupinu izrazito malignih tumora, koji se najvećim dijelom javljaju u djece i adolescenata. Ovaj tumor rano metastazira i ima nisku stopu preživljavanja. Prikaz slučaja: 29-godišnja žena tijekom mjesec dana imala je bolove u desnoj strani prsišta i progresivnu zaduhu. Višeslojna kompjutorizirana tomografija (MSCT) prsnoga koša pokazivala je opsežan desnostrani pleuralni izljev i veliku ekspanzivnu tvorbu u gornjem desnom plućnom režnju. Učinjena je torakocenteza, a u pleuralnom izljevu nađene su maligne stanice. Bronhoskopski je viđena vanjska kompresija na bronhe, bez malignih stanica u uzetim uzorcima bronha. U transtorakalnoj, CT-om vođenoj biopsiji tvorbe pluća, histološkom analizom utvrđene su male stanice, s hiperkromatskim jezgrama i atipičnim mitozama. Imunohistokemijski stanice su bile pozitivne na CD99, NSE i CD56 markere. Pozitron-emisijska tomografija kombinirana s kompjutoriziranom tomografijom (PET/CT) pokazivala je jako nakupljanje 18F-fluorodeoksiglukoze u gornjem desnom plućnom režnju i medijastinalnim limfnim čvorovima. Scintigrafijom somatostatinskih receptora (oktreoskan) nađeno je nakupljanje radiofarmaceutika u gornjem desnom plućnom režnju i medijastinumu, čime su utvrđeni somatostatinski receptori u tim dijelovima tijela. Bolesnica je liječena kemoterapijom (cisplatin i etopozid) i oktreotid acetatom, ali PET/CT je pokazivao progresiju tumora, te je provedena palijativna radioterapija. Tumor je brzo progredirao i bolesnica je preminula jedanaest mjeseci nakon utvrđivanja dijagnoze. Zaključak: PNET je agresivni i smrtonosni tumor, te ga treba uzeti u obzir u diferencijalnoj dijagnostici tumora prsnoga koša, bez obzira na dob bolesnika.Introduction: Primitive neuroectodermal tumor (PNET) is a group of rare, highly malignant neoplasms usually found in children and adolescents. The tumor tends to metastasize early, and consequently the survival rate is low. Case report: A 29-year-old female presented with pain in the right side of the thorax and progressive breathlessness of one-month duration. Multi-slice computed tomography (MSCT) of the chest revealed a large pleural effusion in the right hemithorax, and a large expansive formation in the right upper lobe. Thoracentesis was performed, and malignant cells were found in pleural effusion. Bronchoscopic examination revealed extrinsic compression on the bronchi, without malignant cells in the samples taken. Transthoracic MSCT guided biopsy of the mass histologically revealed small cells, with hyperchromatic nuclei and atypical mitosis. Immunohistochemically, the cells were positive for CD99, NSE and CD56. Positron emission tomography (PET) CT revealed intense accumulation of 18F-fluorodeoxyglucose in the right upper lobe and in the mediastinal lymph nodes. Octreoscan showed pathological accumulation of radiopharmaceuticals in the right upper lobe and mediastinum, indicating a lesion with the expression of somatostatin receptor. The patient received chemotherapy (cisplatin and etoposide), and octreotide acetate. PET/CT showed tumor progression. Palliative radiotherapy was administered. The disease progressed rapidly and the patient died subsequently eleven months after the diagnosis. Conclusion: PNET is an aggressive and lethal disease, therefore should be considered in the differential diagnosis of thoracic tumors regardless of the age of the patient

Primitive neuroectodermal tumor of the lung with pleural effusion - a case report

Uvod: Primitivni neuroektodermalni tumor pluća (PNET) spada u skupinu izrazito malignih tumora, koji se najvećim dijelom javljaju u djece i adolescenata. Ovaj tumor rano metastazira i ima nisku stopu preživljavanja. Prikaz slučaja: 29-godišnja žena tijekom mjesec dana imala je bolove u desnoj strani prsišta i progresivnu zaduhu. Višeslojna kompjutorizirana tomografija (MSCT) prsnoga koša pokazivala je opsežan desnostrani pleuralni izljev i veliku ekspanzivnu tvorbu u gornjem desnom plućnom režnju. Učinjena je torakocenteza, a u pleuralnom izljevu nađene su maligne stanice. Bronhoskopski je viđena vanjska kompresija na bronhe, bez malignih stanica u uzetim uzorcima bronha. U transtorakalnoj, CT-om vođenoj biopsiji tvorbe pluća, histološkom analizom utvrđene su male stanice, s hiperkromatskim jezgrama i atipičnim mitozama. Imunohistokemijski stanice su bile pozitivne na CD99, NSE i CD56 markere. Pozitron-emisijska tomografija kombinirana s kompjutoriziranom tomografijom (PET/CT) pokazivala je jako nakupljanje 18F-fluorodeoksiglukoze u gornjem desnom plućnom režnju i medijastinalnim limfnim čvorovima. Scintigrafijom somatostatinskih receptora (oktreoskan) nađeno je nakupljanje radiofarmaceutika u gornjem desnom plućnom režnju i medijastinumu, čime su utvrđeni somatostatinski receptori u tim dijelovima tijela. Bolesnica je liječena kemoterapijom (cisplatin i etopozid) i oktreotid acetatom, ali PET/CT je pokazivao progresiju tumora, te je provedena palijativna radioterapija. Tumor je brzo progredirao i bolesnica je preminula jedanaest mjeseci nakon utvrđivanja dijagnoze. Zaključak: PNET je agresivni i smrtonosni tumor, te ga treba uzeti u obzir u diferencijalnoj dijagnostici tumora prsnoga koša, bez obzira na dob bolesnika.Introduction: Primitive neuroectodermal tumor (PNET) is a group of rare, highly malignant neoplasms usually found in children and adolescents. The tumor tends to metastasize early, and consequently the survival rate is low. Case report: A 29-year-old female presented with pain in the right side of the thorax and progressive breathlessness of one-month duration. Multi-slice computed tomography (MSCT) of the chest revealed a large pleural effusion in the right hemithorax, and a large expansive formation in the right upper lobe. Thoracentesis was performed, and malignant cells were found in pleural effusion. Bronchoscopic examination revealed extrinsic compression on the bronchi, without malignant cells in the samples taken. Transthoracic MSCT guided biopsy of the mass histologically revealed small cells, with hyperchromatic nuclei and atypical mitosis. Immunohistochemically, the cells were positive for CD99, NSE and CD56. Positron emission tomography (PET) CT revealed intense accumulation of 18F-fluorodeoxyglucose in the right upper lobe and in the mediastinal lymph nodes. Octreoscan showed pathological accumulation of radiopharmaceuticals in the right upper lobe and mediastinum, indicating a lesion with the expression of somatostatin receptor. The patient received chemotherapy (cisplatin and etoposide), and octreotide acetate. PET/CT showed tumor progression. Palliative radiotherapy was administered. The disease progressed rapidly and the patient died subsequently eleven months after the diagnosis. Conclusion: PNET is an aggressive and lethal disease, therefore should be considered in the differential diagnosis of thoracic tumors regardless of the age of the patient

THE ROLE OF OSTEOPONTIN IN NON-SMALL CELL LUNG CANCER PROGRESSION

Cilj: Osteopontin je multifunkcionalna proteinska molekula koja ima važnu ulogu u nastanku i progresiji malignih tumora. Svoje djelovanje ostvaruje preko integrinskih i neintegrinskih receptora (molekula CD44v6), te djeluje na procese proliferacije, apoptoze, angiogeneze, invazije i metastaziranja tumora. Cilj ovog istraživanja bio je istražiti ekspresiju osteopontina u normalnom tkivu pluća, te u tumorskom tkivu nesitnostaničnog raka pluća (NSSRP) i njegovih osnovnih histoloških podtipova, ispitati odnos osteopontina prema kliničkopatološkim parametrima poput veličine tumora, stupnja diferencijacije, statusa limfnih čvorova, pT, TNM i petogodišnjeg preživljenja, ispitati odnos osteopontina prema receptorskim molekulama u tumorskim stanicama, te procijeniti utjecaj osteopontina na apoptozu i proliferaciju tumorskih stanica. Ispitanici i metode: Ekspresija osteopontina i njegovih receptorskih molekula, kao i proliferativna aktivnost tumorskih stanica (Ki67) istražena je imunohistokemijskom metodom na uzorku izgrađenih tkivnih mikroregija iz točno određenih regija (centralne tumorske regije, invazivna fronta i tkivo metastaze) 110 NSSRP-a, dok je apoptotička aktivnost stanica određena TUNEL metodom. Ekspresija osteopontina uspoređena je sa kliničko-patološkim parametrima, ekspresijom αv-integrina i molekule CD44v6, te sa indeksom proliferacije i apoptoze. Rezultati: Ekspresija osteopontina i receptorskih molekula u tumorskom tkivu je jača nego u normalnom tkivu pluća. U skupini NSSRP-a jača je ekspresija osteopontina u adenokarcinomima (p<0.001), a ekspresija αv-integrina (p<0.001) i molekule CD44v6 (p<0.001) je jača u karcinomima pločastih stanica. Nije primjećena značajna korelacija ekspresije osteopontina i promatranih kliničkopatoloških parametara. Ekspresija IV osteopontina je jača u invazivnoj fronti adenokarcinoma (p=0.041) i karcinoma pločastih stanica (p=0.011) u odnosu na centralne regije, te u metastatskom tkivu NSSRP-a (p=0.042) u odnosu na primarni tumor. Utvrđena je jača ekspresija osteopontina u bolje diferenciranim tumorskim regijama NSSRP-a (p=0.006), te jača ekspresija αv-integrina (p=0.038) i molekule CD44v6 (p=0.001) u područjima lošije diferencijacije adenokarcinoma, kao i jača ekspresija molekule CD44v6 u bolje diferenciranim regijama karcinoma pločastih stanica (p=0.011). Apoptotička aktivnost se između histoloških podtipova nije značajno razlikovala (p=0.455), dok je proliferativna aktivnost bila viša u karcinomu pločastih stanica (p<0.001). Ekspresija osteopontina u adenokarcinomima je povezana uz niski indeks apoptoze (p=0.006) što upućuje na antiapoptotičku ulogu osteopontina u adenokarcinomima. Utvrđena je pozitivna korelacija ekspresije osteopontina i αv-integrina u adenokarcinomima početnog TNM stadija (p=0.033), kao i snažna pozitivna korelacija ekspresije obje receptorske molekule u skupinama NSSRP-a (p<0.001) i karcinoma pločastih stanica (p=0.008). Kod adenokarcinoma je istovremena koekspresija osteopontina i αv-integrina povezana sa niskim apoptotičkim indeksom (p<0.01). Pozitivni status limfnih čvorova i inicijalni TNM stadij NSSRP-a udruženi su sa kraćim preživljenjem. Zaključak: Pojačana ekspresija osteopontina je u adenokarcinomu pluća povezana sa niskim apoptotičkim indeksom, vjerojatno preko αv-integrinskog receptorskog kompleksa, te na taj način promovira preživljenje tumorske stanice. Jača ekspresija osteopontina u invazivnoj fronti tumora i u metastazi sugerira njegovu ulogu u progresiji i metastaziranju NSSRP-a.Objectives: Osteopontin is a multifunctional protein molecule that plays an important role in the development and progression of malignant tumors. Its action is achieved via integrin receptor molecules or the non-integrin receptor (CD44v6), and acts on the processes of proliferation, apoptosis, angiogenesis, invasion and metastasis. The aim of this study was to investigate the expression of osteopontin in normal lung tissue, in tumor tissue non-small cell lung cancer (NSCLC) and its major histologic subtypes, to examine the relationship of osteopontin to clinicopathological parameters such as tumor size, degree of differentiation, lymph node status, pT, TNM and five-year survival, to examine the relationship of osteopontin and its receptor molecules in the tumor cells, and to assess the possible effect of osteopontin on apoptosis and the proliferation of tumor cells. Patients and Methods: The expression of osteopontin and its receptor molecules, as well as the proliferative activity of tumor cells (Ki67) was investigated by an immunohistochemical method using tissue microarrays from precise tumor regions (central tumor tissue, invasive front and metastatic tissue) of 110 NSCLC, while the apoptotic activity of the cells was determined by the TUNEL method. Osteopontin expression was compared to the clinicopathological parameters, expression of αv-integrins and CD44v6 molecule, and the proliferation index and apoptosis index. Results: Expression of osteopontin and its receptor molecules in the tumor tissue is stronger than in the normal lung tissue. In the NSCLC group, osteopontin expression was stronger in adenocarcinomas (p <0.001), and the expression of αv-integrins (p <0.001) and molecules CD44v6 (p <0.001) was stronger in squamous cell carcinoma. No significant correlation was noticed between the expression of osteopontin and clinicopathological parameters. VI Osteopontin expression was stronger in invasive front of adenocarcinoma (p = 0.041) and squamous cell carcinoma (p = 0.011) compared to the central tumor region, and in metastatic tissue of NSCLC group (p = 0.042) compared to the primary tumor. We observed highly expressed osteopontin in well differentiated tumor regions of NSCLC (p=0.006), higher αv-integrin (p=0.038) and CD44v6 (p=0.001) expression in the areas of lower differentiated adenocarcinoma, and highly expressed molecule CD44v6 in well differentiated areas of squamous cell carcinoma (p=0.011). Among the histological subtypes apoptotic activity was not significantly different (p=0.455), whereas the proliferative activity was higher in squamous cell carcinoma (p<0.001). Expression of osteopontin in adenocarcinomas is associated with a low index of apoptosis (p = 0.006) suggesting an antiapoptotic role of osteopontin. A positive correlation between expressions of osteopontin and αv-integrin in initial lung adenocarcinomas stage was found (p=0.033), as well as strong positive correlation of expressions of the two receptor molecules in a NSCLC group (p<0.001) and squamous cell carcinomas group (p=0.008), when the simultaneous co-expression of osteopontin and αv-integrin correlated with low apoptotic index (p <0.01). The positive lymph node status and higher TNM stage are associated with shorter survival. Conclusion: In adenocarcinoma, osteopontin overexpression is associated with low apoptotic index, probably through the activation of an αv-integrin receptor molecule. As a result, osteopontin promotes the survival of tumor cells. A stronger expression of osteopontin in the invasive front of the tumor and metastasis suggests a role in the progression and metastasis of NSCLC