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Rad govori o osnovanju centra za liječenje raka dojke sa europskim certifikatom.

Rad govori o kirurškom pristupu karcinomu dojke u ranom stadiju bolesti.

Background:Triple-negative breast cancer (TNBC) has the worst prognosis and the highest immunogenic potential of all breast cancer subtypes. The tumour microenvironment (TME) of TNBC consists mostly of tumour-infiltrating lymphocytes (TILs), tumour-associated macrophages and dendritic cells. TILs are involved in host immunity against tumour cells through the activation of tumour-specific CD8+ cytotoxic T cells. However, there are opposing data about the prognostic value of TILs in TNBC. Programmed cell death receptor ligand 1 (PD-L1) from immune or tumour cells binding programmed cell death receptor 1 (PD-1) disable the effector role of CD8 T cells. Therefore, antibodies that block the target in the PD-1 signalling pathway elicit a stronger immune response. Cytotoxic T lymphocyte-associated protein 4 (CTLA-4) mediates immunosuppression and it is expressed in tumours on infiltrating Tregs, activated CD4+ T cells, exhausted T cells and tumour cells. In tumours with high TILs, PD-L1 and CTLA-4 blockades are more effective. Methods:We have performed a comprehensive IHC analysis of all major TIL components (CD8, CD4, FOXP3 Tregs) as well as inhibitory molecules PD-L1 and CTLA4) in a superficial (invasive tumour front, ITF) and deep tumour layer of TNBC, and compared it with established clinicopathological and prognostic parameters. Clinical data and surgical tissue samples from 68 TNBC patients who underwent initial surgery were included in the analysis and 36 control samples from benign breast tissue biopsies. Results:Several statistically significant associations between the TILs status of TNBC patients and the established prognostic factors were observed. In the ITF, the proportion of TILs and CD8+T cells were increasing toward second pathological T status (pT2), and decreasing thereafter toward higher pT status (P=0.017, P=0.021, Chi-square test). Similar trends for both variables were observed in association with anatomic (P=0.057, P=0.050, Chi- square test) and prognostic (P=0.059, P=0.048, Chi-square test) stages of the disease. Furthermore, the increase of CD8+T cells at ITF was statistically correlated with the increased expression of PDL-1, CTLA-4, FOXP3 and CD4+T cells (N=65, rho 0.31, P=0.011 ; N=65, rho 0.40, 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.

Uvod: Papilarni karcinom je najčešći karcinom štitne žlijezde koji ima tendenciju metastaziranja u limfne čvorove vrata gdje se uglavnom rano dijagnosticira ultrazvukom. Rijetki su slučajevi kada se pronađu metastatski čvorovi u vratu, a da primarni tumor u štitnjači nije moguće potvrditi. Cilj ovog rada je prikazati slučaj metastatskog papilarnog karcinoma porijekla folikularnih stanica štitnjače koji je dijagnosticiran jedino u limfnim čvorovima vrata, a niti nakon opsežne patohistološke analize nije potvrđen u štitnoj žlijezdi. Prikaz slučaja: Pedesetpetogodišnji pacijent primijetio je unatrag mjesec dana bezbolnu oteklinu na vratu. Učinjen je ultrazvuk vrata pri čemu je otkrivena cistična lezija na desnoj strani vrata, u regiji III te je postavljena sumnja na sekundarizam koja citološkom punkcijom nije potvrđena. CT-om vratnih organa uočeni su patološki limfni čvorovi u regijama III i IV i VB desne strane vrata kao i uvećanje desne palatalne tonzile. Patohistološki nalaz tkiva desne tonzile je opisao subkronični limfadenitis dok je nalaz limfnog čvora morfološki i imunohistokemijski govorio u prilog metastaze papilarnog karcinoma štitne žlijezde. U preparatima limfnih čvorova disektata desne strane vrata patohistološki je pronađeno šest metastatskih limfnih čvorova (1 u regiji II, 3 u regiji III, 1 u regiji IV i 1 u regiji VB) od kojih je najveći u regiji IV bio cistično promijenjen. Epitelne stanice nisu pokazivale jasne nuklearne karakteristike papilarnog karcinoma dok je imunohistokemijsko bojenje na Thyreoglobulin, TTF i CK19 bilo snažno i difuzno. U tkivu štitne žlijezde, koje je ekstenzivno uzorčeno, nije pronađeno tumorsko tkivo. Nakon totalne tireoidektomije i radikalne disekcije vrata desno provedena je terapija jodom-131 koju je pacijent podnio bez većih tegoba te je preporučena nadomjesna terapija levotiroksinom. Zaključak: Metastatski papilarni karcinom u limfnim čvorovima, bez dokazanog primarnog tumora u štitnoj žlijezdi, izuzetno je rijetka dijagnoza. Ponekad se prezentira cistično promijenjenim čvorovima u području vrata koji mogu predstavljati dijagnostički problem.

Uvod: Povećanje štitnjače može biti tumorske ili netumorske prirode, a tumori mogu biti benigni i maligni. Cilj ovog istraživanja je prikazati učestalost netumorskih i tumorskih promjena štitnjače operiranih u šestogodišnjem periodu, u KBC-u Rijeka, raspodjelu po spolu, proširenosti te usporedba sa svjetskim statistikama. Materijali i metode: Iz baze podataka Zavoda za patologiju Medicinskog fakulteta Sveučilišta u Rijeci prikupljeni su podatci o tipovima patohistoloških promjena štitnjača operiranih u periodu od 2013. do 2018. godine u KBC-u Rijeka. Rezultati: U navedenom periodu operacija štitnjače izvedena je na 964 pacijenata od kojih se u 84% slučajeva radilo o ženama. Kod 46% slučajeva učinjena je totalna tireoidektomija te se u gotovo polovici slučajeva radilo o netumorskim promjenama. Od toga je u 38% slučajeva patohistološki potvrđena dijagnoza strume, a u 15% dijagnoza strume sa tireoiditisom. Benignih tumorskih promjena je ukupno bilo 30%, od čega 23% folikularna adenoma i 6% Hürthle cell adenoma. Dijagnoza malignog tumora postavljena je u 20% od ukupnog broja operiranih štitnjača. Papilarni karcinomi su bili zastupljeni sa 84% slučajeva. Prema učestalosti slijede devet slučajeva folikularnih karcinoma, devet Hürthle cell karcinoma, sedam medularnih karcinoma i dva slučaja anaplastičnog karcinoma. U jednom slučaju radilo se o SETTLE tumoru (spindle epithelial tumor with timus-like differentiation), a u dva slučaja o limfomu. Više od polovice karcinoma otkriveno je u fazi T1 (< ; 2 cm). Tumori veličine 2-4 cm (T2) otkriveni su u 30% pacijenata. 12% tumora bilo je veće od 4 cm (T3) dok je samo 3% otkriveno u fazi T4 (tumor probija čahuru i invadira okolno tkivo). Zaključak: Rezultati ove analize ukazuju na pojavu strume u polovini slučajeva, dok ostatak čine benigni i maligni tumori. Četiri puta je veća učestalost karcinoma štitnjače u ženskoj populaciji. Prevladava papilarni karcinom, najčešće otkriven u najranijoj fazi bolesti (T1). Rezultati su u skladu sa navodima svjetske literature.

Background: Tumor infiltrating lymphocytes (TILs) are involved in host imunity against tumor cells. However, in later phases of the disease high TIL infiltration is related to disease progression. Tumor immunogenicity is strongly correlated with the higher tumor mutation burden. Triple negative (TN) and HER-2 enriched breast cancers have the highest immunogenic potential so the aim of our study was to investigate the TIL infiltration and expression of PD-L1, HSP-70 in such tumors. Material and Methods: TIL infiltration was investigated in the 112 tissue samples of TN and HER-2 enriched breast cancers of women diagnosed and treated in the Clinical Hospital Centre Rijeka, Croatia, in the period between 2008 and 2016. The invasive front of the tumor (host-tumor interface), the surface layer, as well as the deep layer of the tumor were analysed. Immunohistochemistry staining of PDL-1 (SP142), HSP70 (ab2787), CD4 (SP35 Cell Marque) and CD8 (144B DakoCytomation) was performed. The results were analysed using Statistica 13 software. Results: Overall, there is a statistically significant correlation of high (over 50%) TIL infiltration with longer 5-year survival (p = 0.035, Long rank test). In the surface layer of the tumor (invasive front) there is statistically significant correlation of the intermediate TIL infiltration with the higher survival (p = 0.051, Long rank test) whereas there is no significant difference in the deep layer of the tumor. There is significant association of TIL infiltration with CD8+ T lymphocyte expression in the surface and deep layers of the tumor (Mann Whitney U test, p = 0.004 and p < 0.001, respectively), CD4+ lymphocyte expression (p < 0.001, p < 0.001, respectively) and PDL-1 expression (p < 0.001, p < 0.001, respectively). Statistically significant correlation of TIL infiltration and HSP-70 protein was only detected in the deep tumor layer (Mann Whitney U test, p < 0.001). Furthermore, in the TIL infiltrated deep tumor layer there is statistically significant positive correlation of PD-L1 and HSP-70 expression (Mann Whitney U test, p = 0.029) as well as positive European Journal of Cancer 138, Suppl. 1 (2020) correlation of the HSP-70 expression and the stage of the disease (Anova, p = 0.08). Conclusion: Although TIL infiltration in the surface layer of the tumor is corellated with higher survival rate, there is no such correlation in the deep layer. We have shown that in both layers there is increased expression of CD4 and CD8 positive T lymphocytes. However, the increased expression of inhibitory molecules PD-L1, and in the deep layer HSP-70 protein is noted as well. It is possible that in this context HSP-70 is involved in activation of Tregs and thus inducing immunotolerance to oncoproteins and along with PD-L1 molecule stimulates the development of immunosuppressive environment in the deep tumor layer thus supporting tumor immune evasion.

Spindle epithelial tumor with thymus-like elements is a rare, biphasic and initially indolent tumor of thyroid with a low malignant potential in young patients (median age 18 yrs). Delayed metastases can occur in lymph nodes, mediastinum, vertebrae or lungs even many years after the initial diagnosis. There are less than 50 cases reported in the literature and few reported metastases. The cytologic descriptions of SETTLE are rare and tend to focus on a hypercelular biphasic appearance. Macroscopic description is a well-circumsribed encapsulated or infiltrative tumor with white tan cut surface separated by sclerotic stroma. Microscopically, it has a biphasic pattern made by spindle cells and epithelial structures (cords, tubules, papillae or glandular appearance, but there are also rare monomorfic variants which have spindle or glandular appearance only. There are no or rare lymphocytes, mitotic activity and necrosis. SETTLE may have a good prognosis if appropriately treated at the initial presentation and if a patient undergo long-term monitoring with a regular clinical and morphological evaluation. The golden standard is surgery and in advanced stages of disease also chemotherapy and radiotherapy. We report findings in a 17 years old girl through ultrasound and cytologic findings, surgical procedures and histopatological findings . After finding a small, hypoechogenic node only 5 mm in diameter on ultrasound examine by a specialist of nuclear medicine, we made a fine needle aspiration biopsy. The node was interpreted morphologically by a cytologist as “probably SETTLE“ although the basic immunocytochemistry was partially done. The patient underwent a recommended left lobectomy of the thyroid and the diagnosis was confirmed by pathologist (morphology and immunohistochemistry). The follow-up ultrasound almost 4 years later revealed no local recurrence or metastatic disease.

Uvod: Debljina odnosno indeks tjelesne mase (ITM) je etiološki i prognostički čimbenik te ima ulogu u imunološkom odgovoru u žena oboljelih od karcinoma dojke. Cilj ove preliminarne studije je utvrditi odnos između ITM-e i odgovora na neoadjuvantno liječenje u bolesnica s karcinomom dojke te utvrditi odnos ITM-e prema imunološkom odgovoru tumor infiltrirajućih limfocita (TIL) u stromi tumora. Slučajevi i metode: U analizu je uključeno 66 bolesnica s uznapredovalim rakom dojke koje su na Klinici za onkologiju i radioterapiju KBC-a Rijeka liječene neoadjuvantnom kemoterapijom i bioterapijom te operirane od 2016. do 2017. godine. Materijal su uzorci iglenih biopsija i tkiva dojke uzetih na Klinici za radiologiju KBC-a Rijeka i na Klinici za opću i onkološku kirurgiju KBC-a Rijeka, preparati kojih su napravljeni na Zavodu za Patologiju KBC-a Rijeka, Medicinskog fakulteta Sveučilišta u Rijeci. ITM je izračunat uz pomoć formule koja koristi omjer tjelesne težine i visine bolesnica nakon čega je kategoriziran prema vrijednostima navedenim definicijom Svjetske Zdravstvene Organizacije te za potrebe statistike dodatno podijeljen u dvije skupine koje čine bolesnice normalne odnosno smanjene tjelesne težine i bolesnice povećane tjelesne težine odnosno adipozne. Na HE obojenim rezovima iglenih biopsija procijenjen je postotak stromalne limfocitne upalne infiltracije na četiri područja na granici tumora prema zdravom tkivu, te je izračunata srednja vrijednost postotka TIL-a. Nakon kompletne kirurške obrade na operacijskom materijalu je procijenjen rizik za nastanak recidiva karcinoma uz pomoć sustava Pathologic Residual Burden Calculator (PRCB) kojim se klasificira ostatni primarni tumor i ostatni metastatski tumor u lokalnom limfnom čvoru nakon neoadjuvantnog liječenja. Statistička analiza je napravljena uz pomoć programa Statistica 13.3. Rezultati: Uspoređene su dobivene vrijednosti ITM-e s PRCB odgovorom, veličinom ostatnog tumora, statusom limfnih čvorova, postotkom stromalnih limfocita, histološkim gradusom tumora u iglenoj biopsiji, imunofenotipom tumora i Ki-67 indeksom proliferacije. Nađen je pozitivan odnos ITM-e i PRCB-a (p=0.007, hi kvadrat test), ITM-e i veličine ostatnog tumora (p=0.005, T-student test) kao i ITM-e i statusa limfnih čvorova (p=0.006, hi kvadrat test). Odnos ITM-e prema histološkom gradusu tumora nije statistički značajan (p=0.211, hi kvadrat test). Dobivena je statistički značajna povezanost između ITM-e i limfocitnog upalnog infiltrata pri čemu bolesnice s većim ITM-e imaju niži postotak limfocitnog upalnog infiltrata (p=0.005, hi kvadrat test). Nađena je statistički značajna povezanost između ITM i postotka izraženosti progesteronskih receptora (PR) pri čemu porast ITM-e prati porast PR –a (p=003, Mann Whitney test). Odnos ITM i izraženosti estrogenskih receptora nije statistički značajan (p=0.085, Mann Whitney test) kao niti odnos ITM-e i Ki-67 indeksa proliferacije (p=0.481, hi kvadrat test). Zaključak: Pozitivan odnos ITM-e i izražaja hormonskih receptora prikazan je u više studija s naglaskom na poslijemenopauzalnu životnu dob. Navedeni rezultati pozitivnog međuodnosa ITM –e i veličine tumora kao i statusa limfnih čvorova odgovaraju rezultatima nekoliko studija. Međutim rezultati studija o povezanosti ITM-e i odgovora na neoadjuvantno liječenje nisu ujednačeni. Pojedine studije ITM prikazuju kao nezavisan prognostički čimbenik lošijeg odgovora na neoadjuvantno liječenje i čimbenik ranijeg povrata bolesti. Odgovor imunološkog sustava u karcinomu dojke ovisi o više čimbenika od kojih je debljina samo jedan od modulatora. Na prikazani rezultat najvjerojatnije utječe veći broj slučajeva s visokom ekspresijom hormonskih receptora u skupini visokog ITM-e koji negativno posreduju imuni odgovor.

Utjecaj količine i distribucije masnog tkiva na tumorske karakteristike invazivnog karcinoma dojke u postmenopauzalnih žena

Uvod: Mogućnost neoadjuvantnog liječenja uznapredovanog karcinoma dojke s jednakim imunofenotipom, a različitim odgovorom bolesnica na isto potiče na razmatranje utjecaja imunološkog sustava prije svega tumorskog infiltrata limfocita (TIL) u odgovoru na neoadjuvantno liječenje (1). Cilj ove preliminarne studije je bio utvrditi mogući prediktivni značaj TIL-a u odgovoru na neoadjuvantno liječenje, neovisno o molekularnim podtipovima invazivnog karcinoma dojke. Ispitanici i metode: U analizu je uključeno 30 bolesnica s uznapredovalim rakom dojke koje su na Klinici za radioterapiju i onkologiju KBC-a Rijeka liječene neoadjuvantnom kemoterapijom i bioterapijom te operirane tijekom 2016. godine. Materijal su uzorci iglenih biopsija i tkiva dojke uzetih na Klinici za radiologiju KBC-a Rijeka i na Klinici za opću i onkološku kirurgiju KBC-a Rijeka, preparati kojih su napravljeni na Zavodu za Patologiju KBC-a Rijeka, Medicinskog fakulteta Sveučilišta u Rijeci. Na HE bojenim rezovima iglenih biopsija procijenjen je postotak stromalnih TIL-a na četiri mjesta u tumoru, te je izračunata srednja vrijednost. Na operativnom materijalu procijenjen je rizik za nastanak recidiva karcinoma uz pomoć sustava Pathologic Residual Burden Calculator (PRCB) kojim se klasificira ostatni primarni tumor i ostatni metastatski tumor u lokalnom limfnom čvoru nakon neoadjuvantnog liječenja. Uspoređene su dobivene vrijednosti postotka stromalnih TIL-a s PRCB odgovorom, veličinom ostatnog tumora, statusom limfnih čvorova, histološkim gradusom tumora u iglenoj biopsiji, imunofenotipom tumora i Ki-67 indeksom proliferacije. Statistička analiza je napravljena uz pomoć programa Statistica 13.2. Rezultati: Dobivena je statistički značajna povezanost između postotka TIL-a i odgovora na neodjuvantno liječenje (p=0.04, Student T-test) pri čemu se uz patološki kompletan odgovor nalazi veći postotak limfocita. Također je nađena značajna povezanost između postotka TIL-a i veličine ostatnog tumora i statusa limfnih čvorova (p

Histopatološke značajke karcinoma dojke uključuju brojne podatke koji su neophodni za daljnji odabir terapije pacijentica, stoga oni moraju biti jasni, nedvojbeno navedeni i pouzdani. Osim tradicionalnih podataka o invaziji, metastatskom potencijalu i odgovoru na terapiju, sve više informacija o prognostičkim i prediktivnim čimbenicima koji utječu na terapiju pacijentica daju i genetska istraživanja na temelju kojih su tumori prema ekspresiji određenih gena stratificirani u podtipove., Histopathological features of breast cancer include numerous details that are essential for the further choice of patient’s therapy because it must be clear, unambiguously stated and reliable. In addition to traditional data on invasion, metastasis and response to therapy more information on prognostic and predictive factors that affect the treatment provide patients and genetic research on the basis of which tumors according to the expression of certain genes in the stratified subtypes.

Background Mammary myofibroblastoma is a very rare benign tumor of stromal breast fibro-myofibroblasts with extremely diverse morfological features, including epitheloid, cellular, deciduoid- like, infiltrative, lipomatous, mixoid, collagenized and mixed variant. According to A. Kajava (1915) accessory breast tissue is classified in to eight classes depending on the clinical and histopathological finding of nipple , areola and glandular parenchyma of the breast. Case report A 71 year-old women presented with supernumerary breast tissue in the rear left axillary fold, with clinically well developed nipple and areola, which was, according to history of patients, slowly increasing since puberty, with the acceleration of growth in the last year. Physical examination found dense node 4 cm in diameter. Ultrasound has described a well-defined formation that has been punctured. Fine needle aspiration cytology showed moderate cellularity, mostly single atypical cells, eccentrically placed oval nuclei with coarse chromatin and inconspicuous nucleoli, medium abundant basophilic cytoplasm. This cytological appearance led to diagnosis of adenocarcinoma. Macroscopic examination o f cross section of the material determined well -defined, swirling and gray colored node. Histologically, the tumor was composed of bundles of tumor cells predominantly epitheloid appearance, which were separated by a thick bands of collagen. Immunohistochemical profile of tumor cells was: vimentin +, CD10 +, calponin +, AE1 / AE3-, and led to final diagnosis of mammary myofibroblastoma. Microscopically, the nipple was made of skin like tissue with subcutaneous fat, which was prevalent in the remaining brea st tissue, while collecting ducts nor acini were not found. Described clinico-pathological changes in the supernumerary breast correspond to class V of A. Kajava classification, called pseudomamma. Conclusion Cytological specimen and small biopsy sample e valuation of myofibroblast tumor is always very challenging due to the high diversity of its growth pattern. The main diagnostic problems are malignant epithelial tumors of the breast and the other types of spindle cells tumors of the breast, phyllodes tumor as well as hemangiopericytoma. On the opposite side, very frequent finding of supernumerary breast tissue becomes clinically interesting only when it is joined with other conditions and diseases of the breast.

Cilj: Sekundarni angiosarkom dojke rijetka je ali ozbiljna dugoročna komplikacija karcinoma dojke kod pacijenata koji su liječeni poštednim kirurškim zahvatom i radioterapijom. Prikazan je slučaj pacijentice kojoj se sekundarni angiosarkom pojavio sedam godina nakon radioterapije uz naglasak na ulogu pažljivog histološkog pregleda tih tumora. Prikaz slučaja: Pacijentici staroj 66 godina kojoj je 2006. godine dijagnosticiran invazivni duktalni karcinom dojke učinjen je konzervativni kirurški zahvat i odstranjen je limfni čvor čuvar (pT1c, pN0). Postoperativni tretman uključivao je radioterapiju i endokrinu terapiju. Sedam godina nakon radioterapije, 2013. godine pacijentica je primijetila purpurno crveno mjesto na koži u ozračenom području desne dojke. Patohistološka dijagnoza promjene je angiosarkom. Zaključak: Razvoj sekundarnog angiosarkoma dojke povezan je s radioterapijom (RIA) i kroničnim limfedemom (Stewart-Treves sindrom nakon latentnog perioda od 4 do 8 godina). Zbog njegove rijetkosti i naizgled bezopasne prezentacije, jer se često radi o bezbolnoj promjeni nalik modrici na koži, pacijenti i liječnici često zanemaruju početne simptome, što vodi kasnom postavljanju dijagnoze. U vrijeme postavljanja dijagnoze pacijenti često imaju lokaliziranu bolest koja je ograničena na dojku, ali s multifokalnim rastom., Aim: Secondary angiosarcoma of the breast is a rare but severe long-term complication of breast carcinoma treated with breast-conserving surgery and radiotherapy. We report here a case which occurred seven years after radiotherapy to highlight the awareness of the disease and the role of careful histological evaluation of these tumours. Case report: The 66-year-old patient with right breast infiltrating ductal carcinoma in December 2006. She underwent conservative breast surgery and sentinel lymph node dissection (pT1c, pN0). Her postoperative treatment included radiotherapy and endocrine therapy. Seven years after the radiotherapy (2013), the patient noticed a purplish spot in the skin of the previously irradiated field of the right breast. The histopathology reviewed a diagnosis of angiosarcoma. Conclusion: The development of secondary angiosarcoma has been linked to radiotherapy (RIA) and chronic lymphedema (Stewart–Treves syndrome) after median latency period of 4–8 years. Because of their rarity and seemingly harmless presentation, frequently comprising painless and bruise like skin lesions, both patients and doctors often neglect the initial symptoms and diagnosis is delayed.

Breast cancer is the most common cancer in women. It can be diagnosed in early stage through screening, early detection and educational programs, and when diagnosed early it can be efficiently treated. Treatment modalities include surgery, chemotherapy, radiotherapy, hormonal therapy and targeted biologic therapy, according to the stage of the disease and patient condition. Treatment decisions should be made after multidisciplinary team discussion. Due to the significance of this disease it is important to define and implement standardized approach for diagnostic, treatment and monitoring algorithm as well. The following text presents the clinical guidelines in order to standardize the procedures and criteria for diagnosis, management, treatment and monitoring of patients with breast cancer in the Republic of Croatia.

Rak dojke najčešći je zloćudni tumor u žena koji se može probirom, redovitim kontrolama i zdravstvenim odgojem otkriti u ranim stadijima bolesti i uspješno liječiti. Metode liječenja uključuju kirurgiju, kemoterapiju, radioterapiju, hormonsku terapiju i ciljanu biološku terapiju ovisno o stadiju bolesti, biološkim obilježjima tumora i općem stanju bolesnice. Odluku o liječenju donosi multidisciplinarni tim. S obzirom na važnost ove bolesti, potrebno je definirati i provoditi standardizirani pristup u dijagnostici, liječenju i praćenju ovih bolesnica. U tekstu koji slijedi iznesene su kliničke smjernice s ciljem implementacije standardiziranih postupaka u radu s bolesnicama s rakom dojke u Republici Hrvatskoj.

Aim: Nuclear factor κB (NF-κB) is transcriptional factor involved in cancerogenesis and metastatic spread of tumors cells. The aim of this study was to evaluate expression of NF-κB in breast cancer and to correlate the immunohistocemical expression of this marker with clinicopathological parameters and patient outcome. Materials and metods: This retrospective study included 208 consecutive newly diagnosed ductal invasive breast cancer patients operated at Department of Surgery, Clinical Hospital Center Rijeka, Croatia between 2000 and 2004 with long term follow up over 10 years. Immunohistochemical staining for NF-kB was done on tissue microarray and expression in more than or equal to 10% nuclei of entire tumor area was considered positive. Results: NF-κB was positive in 62 or 31% of tumors. Activation of NF-kB showed inverse correlation with expression of estrogen receptor (p=0.005) and positive correlation with expression Ki-67 proliferation index (p=0, 015). Tumors were classified as Luminal A (ER and/or PR positive, Her-2 negative, Ki-67

Accurate assessment of HER -2 status is essential for identifying patients who will benefit from HER -2 targeted therapy. The aim of the present study was to show results on the concordance between local and central laboratory testing results in HER -2 positive breast cancer patients. In cases with discordant findings, the immunohistochemical (IHC) and/or in situ hybridization (FISH/SISH) analysis was performed in central laboratories. A total of 104 out of 143 (72.72%) breast carcinoma cases were HER -2 positive (score 3+), while nearly 14% of tumors (20/43) showed weak (score 2+) and 12% (19/143) negative IHC staining (score 0 and 1+). After repeated IHC and ISH, 88% (126/143) were classified as HER -2 positive and 12% (17/143) as HER -2 negative cases. The results obtained are in agreement with many studies that confirmed similar discordance in HER -2 testing by IHC and/or FISH between local and central laboratory. Thus, our findings as well as those from other studies support the importance of regular quality assessment of the staining procedures performed and consistency of interpretation of HER -2 test results., Ispravna procjena HER -2 statusa je osnova za pronalaženje bolesnika kojima će koristiti HER -2 ciljana terapija. Cilj istraživanja je bio prikazati rezultate podudarnosti između testiranja HER -2 pozitivnih bolesnika oboljelih od raka dojke pri mjesnom i centralnom laboratoriju. U slučajevima nepodudarnih rezultata analize imunohistokemije (IH) i/ili in situ hibridizacije su se izvodile u centralnim laboratorijima. Ukupno 104 od 143 (72,72%) slučaja karcinoma dojke su bili HER -2 pozitivni (biljeg 3+), dok je skoro 14% tumora (20/43) prikazalo nisko (biljeg 2+) i 12% (19/143) negativno imunohistokemijsko bojenje (biljeg 0 i 1+). Nakon ponovljene analize IH i ISH 88% (126/143) se klasificiralo kao HER -2 pozitivni i 12% (17/143) kao HER -2 negativni slučajevi. Dobiveni rezultati su sukladni mnogim istraživanjima koja potvrđuju slične nepodudarnosti pri HER -2 testiranju imunohistokemijom i/ili FISH analizom između mjesnog i centralnog laboratorija. Prema tome, naši rezultati kao i rezultati drugih istraživanja podupiru značenje pravilnog procjenjivanja izvođenja protokola bojenja i dosljednosti interpretacija rezultata HER -2 testiranja.

Ekspresija CD44 i MMP9 kod bolesnika s karcinomom prostate.

Biopsija limfnog čvora čuvara (LČČ) pouzdana je metoda za detekciju aksilarnih metastaza kod bolesnica s ranim rakom dojke koja omogućava izbjegavanje nepotrebne disekcije aksile. Međutim, u svakodnevnoj praksi i sad se rabe različiti protokoli za detekciju i patohistološku evaluaciju čvora zbog čega postoji potreba za standardiziranjem načina rada, analize i pisanja izvješća kako bi se bolesnice pouzdano raščlanile u odgovarajuće prognostičke grupe. Cilj ovog rada bio je prikazati naše iskustvo u pregledu LČČ-a kod bolesnica s ranim rakom dojke i kliničkim stadijem bolesti T1-2 i N0. U razdoblju od 2003. do 2011. pregledana je 1071 uzastopna bolesnica, odnosno ukupno 1915 LČČ-a ili prosječno 2, 1 po bolesnici. Protokol je uključivao intraoperacijski pregled histoloških smrznutih rezova, odnosno citoloških otisaka, a potom pregled parafinskih rezova prema protokolu koji uključuje narezivanje cijelog LČČ-a u intervalima od 250 μm. Ovakvom analizom utvrđen je negativan LČČ u oko 75% slučajeva. Postignuti rezultati analize LČČ-a uspoređeni su s literaturnim podatcima.

Maligni melanom kože nastaje malignom transformacijom melanocita. Karakterizira ga lokalna agresivnost i sklonost ranom limfogenom i hematogenom metastaziranju. Iako se nekoliko posljednjih godina bilježi bolje preživljenje, što je rezultat dijagnoze u ranoj fazi bolesti, i dalje se nastoje naći prognostički pokazatelji koji bi omogućili pouzdanije predviđanje tijeka bolesti uz modifikaciju terapije. Stoga je svrha ovog preglednog rada bila utvrditi koji patohistološki i klinički parametri imaju ulogu u prognozi bolesnika s malignim melanomom i mogu li nam ti pokazatelji pomoći u određivanju terapije kod bolesnika. Ovisno o histološkom tipu tumora, spol, histološka razina invazije, debljina tumora i mitotski indeks važni su za prognozu bolesnika s malignim melanomom kože, dok neovisno o histološkom tipu tumora u prognozi bolesnika ulogu ima histološka razina invazije kože, debljina tumora i mitotski indeks., Malignant melanoma of the skin arises due to neoplastic transformation of melanocytes. Its behavior is characterized not so much by the local agressiveness of the primary tumor but rather by the pronounced and often very early tendency to produce lymphogenous and hematogenous metastases. In the last few years a better rate of survival has been observed as a result of early diagnosis. However, recent studies have been focused on determining reliable prognostic parameters which would allow more consistent and predictable course of disease with modification of therapy. The aim of this review was to determine the most important histopathological and clinical parameters which influence the prognosis and outcome of patients with malignant melanoma, and whether they can aid in the choice of the most suitable form of therapy. Depending of the histological type of tumor, patient gender, histological level of tumor progression according to Clark, tumor thickness according to Breslow and mitotic rate are considered to be the parameters of crucial importance for the prognosis of patients with malignant melanoma of the skin. The histological level of tumor progression according to Clark, tumor thickness according to Breslow and mitotic rate were proven to be independent, statistically significant parameters relevant for the outcome of patients with this disease.

Rak dojke najčešća je maligna bolest u žena. Razvoj preventivnih mjera i dijagnostike i svih oblika liječenja (kirurgije, radioterapije, kemoterapije, hormonske i ciljane biološke terapije) doveo je do produljenja preživljenja i poboljšanja kvalitete života bolesnica. S ciljem optimalizacije i standardizacije liječenja, a slijedeći smjernice medicine temeljene na dokazima, donosimo smjernice za dijagnostiku, liječenje i praćenje bolesnica s rakom dojke koje su rezultat rada multidisciplinarnog tima stručnjaka., Breast cancer is the most common malignancy in women. Preventive measures, early diagnosis and development of all treatment modalities (surgery, radiotherapy, chemotherapy, hormonal and targeted biologic therapy) led to improvement in survival and quality of life of the patient. In order to standardize and optimize the approach, following good clinical practice standards, we bring consensus guidelines for diagnosis, treatment and monitoring of breast cancer patients as a result of consensus of a multidisciplinary team of experts for breast cancer.

Breast cancer is the most common malignancy in women. Preventive measures, early diagnosis and development of all treatment modalities (surgery, radiotherapy, chemotherapy, hormonal and targeted biologic therapy) led to improvement in survival and quality of life of the patient. In order to standardize and optimize the approach, following good clinical practice standards, we bring consensus guidelines for diagnosis, treatment and monitoring of breast cancer patients as a result of consensus of a multidisciplinary team of experts for breast cancer.

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

Aim: The aim of this study was to examine accuracy of touch imprint cytology in intraoperative assessment of the sentinel lymph node (SLN) in breast cancer in correlation with the final histopathology results. Methods: Five hundred and twenty four consecutive patients who underwent SLNB in KBC Rijeka between January 2008 and December 2012 were analyzed. All patients had preoperative diagnosed breast carcinoma and clinically negative axillary nodes. Intraoperative touch imprint cytology (TIC) was correlated with definitive pathohistological and immunohistological results. Results: Sensitivity was 61% and specificity 97%, positive predictive value 88% and negative predictive value 88%. The main source of false negative or false positive results were micrometastasis and isolated tumor cells. There were 12% of false negative intraoperative results (4, 7% macrometastasis and 7, 1% micrometastasis). There also were12% of false positive results which were after revision considered as isolated tumor cells that were lost in permanent section. Our results are in concordance with most published data. Conclusion: We concluded that imprint cytology is an accurate and relatively simple method for the intraoperative assessment of the SLN status.

Breast cancer is the most common malignancy in women. Preventive measures, early diagnosis and development of all treatment modalities (surgery, radiotherapy, chemotherapy, hormonal and targeted biologic therapy) led to improvement in survival and quality of life of the patient. In order to standardize and optimize the approach, following good clinical practice standards, we bring consensus guidelines for diagnosis, treatment and monitoring of breast cancer patients as a result of consensus of a multidisciplinary team of experts for breast cancer.

Breast cancer is the most common malignancy in women. Preventive measures, early diagnosis and development of all treatment modalities (surgery, radiotherapy, chemotherapy, hormonal and targeted biologic therapy) led to improvement in survival and quality of life of the patient. In order to standardize and optimize the approach, following good clinical practice standards, we bring consensus guidelines for diagnosis, treatment and monitoring of breast cancer patients as a result of consensus of a multidisciplinary team of experts for breast cancer.

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

AIM: Although EGFR targeted agents showed promising anti-tumor activity in patients, only 10-20% of them manifest major clinical response which suggests that criteria for patient selection are still suboptimal. Emerging evidences suggest existence of direct EGFR signaling pathway in breast cancer, involving transport of EGFR into the nucleus and transcriptional regulation of the target genes. Thus nuclear localization and action of EGFR constitutes additional mechanism of resistance to the EGFR targeted therapy. MATERIAL AND METHODS: Tissue microarrays (TMAs) were built from the cohort of 113 archival formalin fixed paraffin embedded invasive ductal carcinoma. Immunohistochemistry was performed for mEGFR and nEGFR with subsequent FISH analysis of EGFR gene status. RESULTS: mEGFR overexpression and EGFR gene amplification were detected in 2% cases while nEGFR was detected in 40% of cases, with 12% having high nEGFR staining. nEGFR correlated with tumor size (p= 0.0005), lymph node metastasis (p=0.0288), Nottingham prognostic index (p=0.0011) and estrogen receptor expression (p=0.0258). On univariate analysis nEGFR showed correlation with shorter overall survival in whole cohort as well in pre-menopausal group of patients. Multivariate analysis revealed nEGFR to be independent prognostic factor and showed 3.4 times greater mortality risk for high nEGFR expressing tumors comparing to nEGFR negative patients (hazard ration = 3.402 ; p=0.0026). CONCLUSION: These findings suggest that nEGFR might be a future marker in identifying breast cancer patients sensitive to EGFR inhibitors.