Liječenje skvamozne neoplazije površine oka: prikaz slučaja

Aim: Ocular surface squamous neoplasia (OSSN) is a term that encompasses a wide and varied spectrum of very rare dysplastic disease of cornea and conjunctiva, ranging from conjunctival intraepithelial neoplasia (CIN), carcinoma in situ (CIS) to invasive squamous cell carcinoma (SCC) of conjunctiva and/or cornea. Case report: In our case report, we present squamous cell carcinoma of the conjunctiva and cornea in a 78-year old man. Our diagnostic algorithm included: slit lamp and fundus examination, gonioscopy, impression cytology (IC) andmagnetic resonance imaging (MRI). The patient underwentsurgical excisional biopsy of the lesion and intraoperativecryotherapy of the cut conjunctival edges and sclera-conjuctiva base region. Following surgical therapy, we started topical 0.02 % (0.2 mg/ml) Mitomycin C (MMC) application daily for 14 days. Control excisional biopsy of conjunctival edge and abrasion of involved cornea were performed following the last day of topical chemotherapy. Our controlexcisional biopsyrevealed tumor positive corneal tissue and the second cycle of topical 0.04 % (0.4 mg/ml) MMCchemotherapy wasstarted for next 3 weeks. The patient has been followed-up for 20 months through monthly–based visits, with no recurrence of the disease. Conclusions: OSSN is a surgical challenge requiring a specialized â€no-touch’ (NT) technique. In our case, the combination of surgical excision with intraoperative cryotherapy and topical chemotherapy with 0.02 % MMC application for 14 days, completed with second cycle of topical 0.04 % MMC drops for the next 21 days given the positive control biopsy, proved to be a good choice for eradication of OSSN with accurate further monitoring of the patient.Cilj: Skvamozna neoplazija površine oka (OSSN) vrlo je rijetka displastična bolest rožnice i spojnice oka, sa slikom u rasponu od konjunktivalne intraepitelne neoplazije (CIN), karcinoma in situ (CIS) do invazivnog skvamocelularnog konjunktive i/ili rožnice (SCC). Prikaz slučaja: Opisali smo slučaj invazivnog skvamocelularnog karcinoma konjunktive i rožnice kod 78-godišnjeg pacijenta. Dijagnostički plan uključio je kompletan oftalmološki pregled, gonioskopiju, impresijsku citologiju i magnetsku rezonanciju (MR), te je potvrđena dijagnoza karcinoma pločastih stanica bez širenja u orbitu i ostala intraokularna tkiva. Pacijent je podvrgnut kirurškoj ekscizijskoj biopsiji lezije, uz krioterapiju konjunktivalnih rubova i skleralne baze lezije. Nakon kirurške terapije, proveli smo topičku terapiju 0,02 % (0,2 mg/ml) Mitomycinom C (MMC) tijekom 14 dana. Kontrolna ekscizijska biopsija ruba spojnice i strugotine zahvaćene rožnice provedena je posljednjeg dana topičke kemoterapije. Zbog pozitivnog nalaza tumorskih stanica u rožničnom tkivu nastavljena je topička kemoterapija 0,04 % (0,4 mg/ml) MMC-om tijekom sljedeća 3 tjedna. Pacijent je redovito praćen tijekom posljednjih 20 mjeseci bez recidiva bolesti. Zaključci: OSSN je kirurški izazov jer zahtijeva specijaliziranu no-touch operativnu tehniku. U našem slučaju, kombinacija kirurškog zahvata s intraoperativnom krioterapijom, te nakon toga topička kemoterapija 0,02 % kapima Mitomycin tijekom 14 dana, uz nastavljen drugi ciklus topičke kemoterapije 0,04 % kapima Mitomycin tijekom sljedećeg razdoblja od 21 dana zbog pozitivne kontrolne biopsije dobar je izbor za liječenje OSSN-a uz pažljivo daljnje praćenje pacijenta

Skin melanoma heterogeneity and its molecular aspects

U Hrvatskoj je zabilježen 2,7 postotni godišnji porast mortaliteta od melanoma kože. U više studija otkriveno je da osobe koje razviju melanom na abdomenu imaju znatno veći broj madeža od osoba koje razviju melanom na glavi ili vratu. Suprotno tome, melanomi na glavi i vratu povezani su sa solarnom keratozom, ali vrlo slabo s brojem madeža. Otkrivena je povezanost podtipa lentigo maligna melanoma sa značajnim izlaganjem suncu, ali nikakve konstantne korelacije nisu pronađene kod drugih histoloških podtipova. Nova molekularno genetska istraživanja snažno podržavaju koncept da su melanomi nastali na centralnim dijelovima tijela kod mlađih osoba s velikim brojem melanocitnih madeža biološki različiti od melanoma nastalih kumulativnim djelovanjem na suncem oštećenoj koži starijih ljudi i da su madeži i melanomi istog puta nastanka vođeni istim genetskim promjenama. Epidemiološke stručne analize brzo su utvrdile da visok stupanj izloženosti suncu znači veći broj madeža u ranom djetinjstvu. Višestruka istraživanja pokazala su da BRAF-mutirajući melanomi najčešće spadaju u superficijalno-šireći podtip i pojavljuju se na koži koja je povremeno bila izložena suncu kao i da češće metastasiziraju u regionalne limfne čvorove nego melanomi bez BRAF mutacija. KIT-mutiranimelanomi se pojavljuju u koži, na noktima, na mukozi ili na koži koja je oštećena suncem te najčešće isključuju BRAF mutaciju. Melanomi s ovom mutacijom vrlo često imaju in situ komponente koje su slabo ograničene, što je rezultat pojačane lateralne mobilnosti neoplastičnih melanocita nakon aktivacije SCF KIT puta.Croatia has recorded a 2.7 percent annual increase in melanoma of the skin mortality. Several studies have found that people who develop melanoma on the abdomen carry a significantly higher number of nevi than people who develop melanoma on the head or neck. In contrast, melanoma on the head and neck is associated with solar keratosis, but not with the number of nevi. The correlation was found between lentigo maligna melanoma incidence and exposure to the sun. No similar correlation was found in other histological subtypes of melanoma. New molecular genetic studies support the concept that melanomas arising in the central parts of the body of young people carring multiple nevi are biologically different from melanoma caused by cumulative action of the sun-damaged skin in older patients. Epidemiological expert analysis quickly determined that a high degree of exposure to the sun means a larger number of moles in early childhood. Multiple studies have shown that BRAF-mutant melanoma most often fall into the superficial-spreading subtype and appear on skin that has occasionally been exposed to the sun and that they more often methasize to regional lymph nodes than melanomas without the BRAF mutation. KITmutated melanoma appear in the skin, the nails, the mucosa or the skin, which is damaged by the sun and usually exclude BRAF mutations. Melanomas with this mutation often carry na poorly delimited in situ components as a result of enhanced lateral mobility of neoplastic melanocytes after the SCF KIT pathway activation

Strong nuclear EGFR expression in colorectal carcinomas is associated with cyclin-D1 but not with gene EGFR amplification

<p>Abstract</p> <p>Background</p> <p>Prognostic and predictive significance of epidermal growth factor receptor (EGFR) in colorectal carcinomas (CRCs) is still controversial. The aim of the present study was to explore and correlate membrane and nuclear EGFR and cyclin-D1 protein expression with EGFR gene status of tumor cells.</p> <p>Methods</p> <p>Immunohistochemical and FISH analysis was performed on 135 archival formalin fixed and paraffin embedded CRCs.</p> <p>Results</p> <p>Strong membrane and strong nuclear EGFR staining was detected in 16% and 57% of cases, respectively, and strong cyclin-D1 expression in 57% samples. Gene EGFR amplification was identified in 5.9% and polysomy in 7.4% of cases, while 87% showed no EGFR gene changes. A statistically significant difference was only found between tumor grade and expression of membrane EGFR, while nuclear EGFR and cyclin-D1 expression was not associated with the clinicopathologic characteristics analyzed. Tumor cells displaying gene amplification and strong protein membrane EGFR expression overlapped, while EGFR gene status showed no correlation with nuclear EGFR and cyclin-D1. There was no association between membrane EGFR and cyclin-D1, whereas nuclear EGFR expression was strongly related to cyclin-D1 expression.</p> <p>Conclusions</p> <p>Study results revealed heterogeneity among CRCs, which could have a predictive value by identifying biologically and probably clinically different subsets of tumors with the possibly diverse response to anti-EGFR therapies.</p

Pineal parenchymal tumor of intermediate differentiation – case report

Cilj: Prikazati slučaj pacijentice s pinealnim parenhimnim tumorom intermedijarnog stupnja diferencijacije gradus II, s naglaskom na patohistološku dijagnozu ovog kliničkog entiteta. Prikaz slučaja: Tridesetosmogodišnja pacijentica primljena je na Kliniku za neurokirurgiju Kliničkog bolničkog centra Rijeka radi operativnog liječenja ciste pinealne regije. Osnovni i jedini simptomi bile su glavobolje unatrag četiri godine. Magnetska rezonanca mozga ukazivala je na cističnu tvorbu pinealne regije. Učinjena je osteoklastična subokcipitalna medijana kraniotomija s ekstirpacijom ciste pinealne regije te je bioptički uzorak poslan na patohistološku analizu. Histološki je utvrđeno oskudno tkivo mozga infiltrirano umjereno celularnim tumorskim tkivom građenim od difuzno raspoređenih, malih uniformnih stanica oskudne citoplazme s tendencijom stvaranja perivaskularnih acelularnih područja i diskretnim pineocitomatoznim rozetama. Jezgre tumorskih stanica bile su ovalne, monomorfnog izgleda s mjestimičnom blagom polimorfijom. Mitotska aktivnost bila je niska i iznosila je manje od 0,5%. U bioptičkom uzorku bilo je nekoliko manjih žarišta kalcifikacije, ali bez prisustva nekroze. Imunohistokemijska analiza pokazala je izrazitu difuznu obojenost na neuron specifičnu enolazu (engl. neuron-specific enolase, NSE) i znakove neuroendokrine diferencijacije o čemu svjedoči snažna difuzna obojenost na sinaptofizin. Na temelju histološke slike i imunohistokemijskog profila zaključeno je da pregledani materijal predstavlja pinealni parenhimni tumor intermedijarnog stupnja diferencijacije - WHO gradus II. Pacijentica se nakon operacije osjećala dobro i otpuštena je na kućno liječenje. Zaključci: Jedino ispravno postavljena patohistološka dijagnoza može dovesti do odgovarajućeg izbora terapije i ispravnog kliničkog pristupa bolesniku s pinealnim parenhimnim tumorom intermedijarnog stupnja diferencijacije. Daljnja molekularna istraživanja bila bi od koristi patologu u postavljanju standarda i izradi smjernica, koje bi pomogle u postavljanju točne dijagnoze.Aim: To report a case of a patient with the pineal parenchymal tumor of intermediate differentiation grade II, with emphasis on histopathological diagnosis of this clinical entity. Case report: A 30-year-old patient was admitted at the Clinic for Neurosurgery within the Clinical Hospital Centre Rijeka in order to surgically remove a cyst in the pineal region. The only and main symptoms were headaches in the past four years. Magnetic resonance was performed to visualize the pineal cyst. Osteoclastic suboccipital median craniotomy with extirpation of the cyst had been done and the biopsy specimen was sent to the Pathology Department of the Clinical Hospital Centre Rijeka. Histologically, the tissue of the brain was infiltrated by a moderately cellular tumor tissue consisting of diffusely distributed small uniform cells with scarce cytoplasms and with the tendency to form perivascular acellular areas with discrete pineocytomatous rosettes. Nuclei of the tumor cells were oval and monomorphic with an occasional mild polimorphism. Mitotic activity was low and measured less than 0,5%. The biopsy specimen included several smaller foci of calcification without the presence of necrosis. Immunohistochemistry showed strong diffuse positivity for neuron-specific enolase and synaptophysin, which suggests neuroendocrine differentiation. According to the histological findings and immunohistochemistry profile the pineal parenchymal tumor of intermediate differentiation - WHO gradus II has been diagnosed. The patient was feeling well after the operation and had been dismissed for further home treatment. Conclusions: Only precisely determined histopathological diagnosis will result in adequate choice of therapy and accurate clinical approach to any patient with this type of tumor. Further molecular research needs to be conducted in order to form standardized guidelines which would help in process of confirming the exact diagnosis

Recurrent Pleomorphic Adenoma of Epipharynx Following Irradiation Therapy

We present a case of a 67-year-old female patient having a pleomorphic adenoma of epipharynx with intact fibrous capsula, which despite its benignity recurred and, moreover, responded quite well to irradiation therapy. The patient, at first, refused any therapy. Three years later, when the CT showed tumor enlargement she accepted only irradiation therapy, resulting in significant reduction of tumor size. Five years later the tumor recurred but without malignant transformation. She still refused surgery, but accepted re-irradiation therapy. After a three-year follow-up the patient has no symptoms of the tumor enlargement. This case shows that the irradiation therapy might be quite effective in the treatment of pleomorphic adenoma of epipharynx, but it is clear that much better results could be accomplished in combination with the surgery. In cases when the surgery is rejected or not possible because of the vicinity of the vital structures, we recommend the irradiation therapy as a therapy of the choic

Electron microscopy in diagnostic practice

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

Case report of calcifying odontogenic cyst through history of the nomenclature and classification of odontogenic tumors

Cilj: Prikazati slučaj pacijenta s rijetkim entitetom odontogene kalcificirajuće ciste, kroz povijest preobrazbe nomenklature i klasifikacije odontogenih tumora. Prikaz slučaja: Mlada zdrava muška osoba javila se na Kliniku za dentalnu medicinu zbog spororastuće bolne otekline u području desnog umnjaka. Slikovna dijagnostička metoda CBCT ukazivala je na dijelom solidno, dijelom cistično unilokularno prosvjetljenje. Cista se enukleirala, a materijal je proslijeđen na patohistološku analizu. Patohistološkom analizom moglo se zaključiti da se radi o dobroćudnoj tvorbi odontogenog podrijetla, a predstavlja odontogenu epitelnu kalcificirajuću cistu. Rasprava i zaključak: Zbog raznolikog ponašanja kalcificirajuće odontogene ciste postoji širok raspon opisnih nazivlja do danas dodijeljen ovoj leziji. Istraživanja u budućnosti, koja bi uključivala molekularne i genetske dijagnostičke metode, mogla bi s vremenom predložiti univerzalno prihvatljivu klasifikaciju.Aim: To show a case of a patient with a rare entity, calcifying odontogenic cysts, through the history of the transformation of the nomenclature and classification of odontogenic tumors. Case: A young healthy male visited the Clinic for Dental Medicine because he had, slow growing painful swelling in the right wisdom tooth. Diagnostic imaging, CBCT is indicated partly solid, partly cystic unilocular enlightenment. The cyst was enucleated and material was forwarded to the histopathologic analysis. Pathological analysis revealed a benign formation of odontogenic origin and represents calcifying odontogenic epithelial cyst. Discussion and conclusion: Because of diverse behavior of calcifying odontogenic cyst there is a wide range of descriptive nomenclature assigned to date this lesion. Research in the future, which would include molecular and genetic diagnostic methods, could eventually propose a universal acceptable classification

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

The Relevance of Assessing the Cell Proliferation Factor Ki-67 in Squamous Cell Carcinoma of the Larynx

The aim of study was to investigate the expression of the proliferation factor Ki-67 and its relationship with histological grade, cancer stage, and treatment outcome in squamous cell carcinoma of the larynx. Samples from 78 patients with laryngeal cancer were analysed retrospectively. Paraffin sections of tumors were immunohistochemically stained for Ki-67 expression. The patients were divided in two groups according to the proliferative factor values (a low Ki-67 index group - Ki-67≤34 and high Ki-67 index group-Ki-67 >34). Statistical analysis of the data shows significant correlation among histological tumor grade and the value of the Ki-67 proliferative index. There was no correlation between tumoral Ki-67 expression and diagnosis, stage of the disease, or treatment outcome. In conclusion, Ki-67 expression in laryngeal cancer is not the most reliable marker for making precise diagnosis and predicting the clinical course