Aim: Determination of cut-off value for Ki67 index, it’s corelation in luminal breast carcinoma with patient’s age, tumor size, histological grade (HG), and expression of estrogen (ER) and progesterone (PR). Introduction: Breast cancer is a heterogeneous disease characterized by different morphology, immunohistochemical profile, clinical course and response to applied therapy. Ki67 proliferative index is one of the prognostic and predictive factors, whose methodological determination and analysis are still unstandardized. Material and Methods: Retrospectively, we analysed 120 pathohistological reports of patients who were treated in the period 01.01.2009. until 31.12.2011. at the Oncology Institute of Vojvodina, and to whom immunohistochemistry was proven luminal breast cancer (positive ER and PR, negative HER2), without axillary lymph node metastases. Results: The average patient’s age was 57.42±10.17 years; average tumor size 17.98±6.97mm; recurrence was registered in 8 (6.7%) patients with average recurrence time of 49±20.23 months. “Cut off” Ki67 value of prognostic significance for period without recurrence is 20.75%. For correlation testing χ2 and Kendal τ-b tests were used. It’s shown unsignificant relationship between Ki67 and patient’s age (p=0.401 and p=0.293), as well as the strength of expression ER (p=1.00, p=0.957) and PR (p=0.273, p=0.189). Significant correlation is present for Ki67 with size (p=0.035, p=0.20) and tumor’s HG (p=0.041, p=0.20). Conclusion: Breast carcinoma is heterogeneous disease, so it’s difficult to predict its course and outcome using standard histopathological factors and biomarkers. For prognostic-predictive purposes, it’s necessary to include additional biomarkers, where Ki67 stands out above all, whose high value correlates with factors of bad prognosis.

Aim: Determination of frequency of patologic findings and types of pathologic findings in enteric nerve plexus (ENP) in colon biopsies in children with impaired bowel motility, specifically chronic constipation. Introduction: Chronic constipation is relatively common in children, and is most often a functional disorder that is responsive to dietary regime treatment. Rarely, some cases require biopsy and histopathologic analysis of ENP. Materials and Methods: Research consists of 299 colon biopsies taken from children with impaired bowel motility. Biopsies were analysed in Institute of pathology, Medical faculty in Belgrade, in the period of time from the year 2008 to 2018. Data analysis included standard methods of descriptive and analytic statistics. Results: Number of analysed biopsies was 588. Biopsies were taken from 184(61,5%) boys and 115(38,5%) girls. Most common referral diagnosis for biopsy was Hirschspung’s disease (HD) (153/299, 51,2%). Pathologic changes in ENP were found in 46,1% of patients (138/299). Histopathologic analysis confirmed clinical suspicion for HD in 48,4%(74/153) of patients. Most frequent pathologic finding secondary to HD were immature ganglion cells (26/299, 8,7%), ectopic position of ganglia in muscle layer of colonic wall (6/299, 2%), and unclassified dysganglioses (5/299, 1,7%). In six patients, cause of constipation was eosinophilic proctitis and/or mienteric ganglionitis. Acetilcholin esterase as diagnositic metod was applied in 29 patients. Immunohistochemical analises were used in 24 patients. Conclusion: HD and immaturity of ganglion cells are by far most frequently diagnosed causes of constipation in colon biopsies in pediatric patients. Eosinophilic proctitis and/or mienteric ganglionitis are rare causes of constipation in children.

Pancreatic cancer is high aggressive malignant neoplasm with very poor prognosis and about only 5% a five-year survival. It is the fourth leading cause of cancer death in USA, as well in Serbia, although in terms of the incidence of this disease the mortality is rising and it takes seventh place. Speaking about the southern Backa, the mortality rate is slightly lower and it is the fifth place, according to the available literature. This can be explained by the lack of highly specific and sensitive diagnostic tests, which makes pancreatic cancer most often detected by an advanced, inoperable stage of the disease (>60%), although surgical resection is the only curative therapy. Analogous to other carcinomas, there is a gradual progression of the pancreatic duct epithelial cells, so every invasive carcinoma arises from the previous intraepithelial neoplasia. There are three different types of common precancerous lesions known for pancreatic cancer which clinical detection and treatment can stop the progression to invasive cancer and reduce mortality. The first one is Pancreatic Intraepithelial Neoplasia (PanIN), and the other two types of precancerous lesions are both larger fluid-filled types- Intraductal Papillary Mucinous Neoplasms (IPMNs) and Mucinous Cystic Neoplasms (MCNs). PanIN is an asymptomatic, small (usually <5 mm in diameter), nonfluid flat or papillary lesion arising in the small intralobular pancreatic ducts. It is the most common and important precursor of invasive pancreatic carcinoma. Histologically, it’s consisted of columnar to cuboidal cells with varying amounts of mucin. Accordingly to different degrees of cytological and architectural atypia, PanIN is classified into three grades- low, intermediate and high grade. PanIN-1A (flat) and PanIN-1B (papillary) are low grade lesions with minimal atypia, while PanIN-2 belongs to intermediate lesion showing mild to moderate atypia with frequent papillae. PanIN-3, also referred as “carcinoma in situ”, is characterized by severe cytological and architectural atypia amd it can be flat, papillary or cribriform pattern. The immunohistochemical profile of PanINs vary with the grade of dysplasia. Low grade lesions show positivity for gastric foveolar mucin MUC5AC, pyloric gland mucin MUC6, while MUC1 is almost exclusively expressed by high grade PanINs lesions. Among fluid-filled types of precancerous pancreatic lesions, IPMNs are the most common lesions. IPMNs vary in their location and size within the pancreas size, and these two features correlate with how dangerous they are. Because they can be detected by imaging procedures, it is possible to detect them before they become cancer. They are most often detected in patients who are routinely monitored due to a high familial risk, or incidentally in people who were imaged for another reason. Those lesions belong to group of the heterogeneous group of cystic pancreatic lesions because papillary epithelial proliferation and mucin production lead to cystic dilatation of involved ducts. SPECIJALNA SESIJA: KATEDRA ZA PATOLOGIJU MEDICINSKOG FAKULTETA, UNIVERZITETA NOVI SAD, SRBIJA 29 MATERIA MEDICA • Vol. 34 • Issue 1, suplement 1 • april 2018. Those lesions are slightly more common in the head and uncinate process (55%) compared with the body and the tail of the pancreas and about 30% of them are multifocal. IPMNs are subdivided into main duct IPMN (MD-IPMN) which are localized in the main pancreatic duct and measured ≥5 mm, while the other branch duct type (BD-IPMN) is >5 mm in diameter andcommunicates with the main pancreatic duct but it is uninvolved by the process. Mixed IPMN combines both types. Microscopically, the lining epithelial component is represented by tall mucin producing columnar cells but lack the “ovarian-type” seen in mucinous cystic neoplasms. Like PanINs, IPMNs are graded on the basis of the greatest degree of dysplasia into low grade, moderate and high grade dysplasia or carcinoma in situ and IPMN with associated invasive carcinoma. Many studies have showed that approximately one-third of patients with IPMN are associated with invasive carcinoma, so precise basement membrane micro analysis is an imperative. Accordingly to their histological characteristics there are intestinal, pancreatobiliary, oncocytic and gastric subtype of IPMN with different immunohistochemical profiles. Intestinal-type IPMN is characterized by tall columnar cells with elongated nuclei and amphophilic cytoplasm and MUC2, MUC5AC, MUC4 and CDX-2 positivity. In contrast, pancreatobiliary subtype of IPMN is characterised by branched papillae with high grade intraepithelial neoplasms and MUC1 And MUC5AC immuno positivity. The third are oncocytic type, predominantly occurs in main duct and presented with a complex branched papillary structures covered by oncocytic cells mixed with goblet cells and mucin-containing cells. This type shows diffuse positivity for MUC5AC, MUC6 and focal positivity for MUC1 or MUC2. The gastric subtype is low grade lesions mainly found in branched ducts and characterised by papillae covered by foveolar glandular epithelium with MUC5AC and sometimes MUC6 positivity. The last and the most infrequent type of pre-cancerous pancreatic lesions are MCNs. The principle difference between IPMNs and MCNs is how they look under a microscope, and how they behave in the patient. These cystic lesions are almost solitary, typically located in the pancreatic body and tail. Grossly, this lesion can grow very large, it is usually septated and with fibrous pseudocapsule often with calcifications. Histologically, the epithelium og noninvasive MCN is consisted of columnar cells with varying degree of dysplasia (low grade, moderate and high grade dysplasia) and underlying ovarian-like stroma. Immunohistochemically, thode epithelial cells are EMA, CEA, MUC5AC, MUC2, cytokeratins 7, 8/18 and 19 positive, while the underlying ovarian-like stroma shows ER, PR, vimentin and SMA immune reactivity. Precancerous lesions of the pancreas are important changes whose visualization and detection in a significant number would reduce the incidence of pancreatic cancer and, consequently, the mortality of this highly aggressive neoplasm with an unfavorable therapy outcome.

Pathologists often have a dilemma is a lymph node biopsy reactive or corresponds to a lymphoproliferative or other malignant disease. In everyday routine work, we rely on morphologic criteria and immunohistochemical analyzes. In better-equipped labs additional cytogenetic and molecular methods are used if morphology and immunohistochemical analyzes are not sufficient for getting correct diagnoses. It is important to know clinical presentation and the opinion of a clinician who runs the case. In reactive lymph nodes general morphology is mostly preserved. Distribution of B and T cells, histiocytes, dendritic cells and proliferation is adequate. Foreign cells are not present. Ways of reaction in lymph nodes are follicular hyperplasia, paracortical expansion, sinus histiocytosis and granuloma formation. If metastases are present, most often from carcinomas and melanomas, the initial deposits are usually sub capsular or less often in sinuses. One should be careful to differentiate sinus histiocytes and metastatic tumor cells, what can easily be verified by immunohistochemical stains.If it is a lymphoma, one should decide is it a Hodgkin or a non-Hodgkin lymphoma. In non-Hodgkin lymphomas, one should decide between small cell and large cell lymphomas. In non-Hodgkin lymphomas, tumor cells are dominant and background inflammation is scant and mostly consisted of small T cells and rare histiocytes. In T cell lymphomas background inflammation can be quite various. In Hodgkin lymphomas background inflammation most often is various and almost always outnumbers tumor cells. Tumor cells are large, with lobulated or multiple nuclei and conspicuous nucleoli. The immunophenotype is usually clearly different from non-Hodgkin lymphomas. The differentiation of small cell and large cell non-Hodgkin lymphomas is easily made by comparing cell sizes. If tumor cell size is closer to size of histiocytes or endothelium it is a large cell lymphoma, but if it SPECIJALNA SESIJA: KATEDRA ZA PATOLOGIJU MEDICINSKOG FAKULTETA, UNIVERZITETA NOVI SAD, SRBIJA 31 MATERIA MEDICA • Vol. 34 • Issue 1, suplement 1 • april 2018. is closer to small lymphocytes and red blood cells it is a small cell lymphoma. Differentiation of small cell lymphomas is based on morphology, distribution of cells and on immunophenotype. Differentiation of large cell non-Hodgkin lymphomas requires immunohistochemical analyzes because morphology is often very similar among entities. Correct diagnosis is important due to application of optimal therapy and reaching the best prognosis for the patient.

Aim: Analysis of two cases of IPA with an emphasis on the radiological and pathohistological findings of this entity. Introduction: Aspergillus spp. can cause a wide range of lung diseases, depending on the current state of immunity and the existing pulmonary diseases. Invasive pulmonary aspergillosis (IPA) is severe form of pulmonary mycosis, with the appearance of granulomatous inflammation with the development of necrosis and suppuration, as well as the invasion of hyphae into pulmonary parenchyma and the blood vessels and spreading the disease out of the lungs. Material and Methods: In the five-year period, two cases of IPA were diagnosed at the Institute of Pulmonary Diseases of Vojvodina. Material for pathohistological analysis, obtained by surgical method and on autopsy, was stained with standard H E staining, as well as with special staining methods: PAS and Grocott. Results: Patients were 67 and 48 years old and both were treated for acute lymphoblastic leukemia. They were admitted to our hospital in respiratory insufficiency and severe neutropenia with a radiologically diagnosed IPA based on HRCT finding of “halo sign”. This sign pathohistologically corresponds to foci of necrosis of lung parenchyma surrounded with the zone of hemorrhage. In addition to these foci of necrosis, in the wall and lumen of blood vessels, numerous septate hyphae with dichotomous branching at 45° were found. Conclusion: Although the pathohistological diagnosis is golden standard for diagnosis of IPA, given the invasiveness of the techniques for obtaining material for analysis, diagnosis can be made based on HRCT finding of “halo sign”.

The significance of pathohistological analysis of operative material and tumor immunophenotype in differential diagnosis of sarcomatoid carcinoma and carcinosarcoma rare malignant lung neoplasms. Introduction: Lung carcinosarcoma, biphasic tumor, composed of non-small caracinomatous and sarcomatous heterogeneous components, is a rare neoplasm and represents less than 1% of all malignant lung tumors. Case report: A 64-year old man reported to physician complainig of fever that lasted for two months. Chest CT showed signs of right lung infiltration, close to the hilus and mediastinal lymphadenopathy. After bronchoscopy and biopsy of the suspected changes pathohistological finding was: carcinoma squamosum invasivum. Lobectomy of upper right lobe and mediastinal lymphadenectomy were performed. On gross examination, distanced 5 mm from the resection margin, withish tumor (22x7x5mm) infiltrating the wall of the lobar bronch was found. Histological analysis found that tumor tissue was partly consisted of atypical epithelial cells, with larger, mitotically active nuclei with focuses of keratinization and partialy of atypical oval and spindle cells,with hyperchromatic, pleomorphic nuclei, with high mitotic index. Lymph nodes were negative for tumor tissue. Results of immunohistochemical tumor tissue analysis: Cytokeratin - positive in carcinomatous component, Vimentin - positive in sarcomatous component, Actin, Desmin and S100 - negative. According to the results of morphological and immunohistochemical analysis of the tumor tissue lung carcinomsarcoma was diagnosed. Conclusion: For establishing definitive pathohistological diagnosis in biphasic tumor cases, a pathohistological examination of operative material is necessary, and morphological assessment should be suported by immunohistochemical analysis.

Aim: We present a case wherein the information obtained from autopsy examination was of critical importance to a doctor and a family. Introduction: A 24-year-old,multipara,delivered a term born male baby with a birth weight 3100gr and body length 46cm.Soon after birth the neonate developed signs of POSTER SESIJA 63 MATERIA MEDICA • Vol. 34 • Issue 1, suplement 1 • april 2018. a respiratory insufficiency and died within 2 hours.Anamnestic data from the mother revealed uncontrolled pregnancy. Material and Methods: Standard autopsy technic and standard procedure of paraffin embedded section routinely stained with H E was performed. Results: At autopsy,the external examination revealed characteristic facial features suggestive of Potter s face including posterior rotated low-set ears,flat nose,widely separated eyes,micrognatia and short neck. Autopsy revealed presence of bilateral hypoplastic lungs with total weigh of 28g,less than the expected range (normal 49g).On dissection lungs were airless, non-crepitant and sank in the water. Histologically findings were consistent with a diagnosis of pulmonary hypoplasia.The abdominal cavity was completely filled with markedly symmetrical enlarged kidneys.Total weight of both kidneys was 156g (normal 25g).On the dissection section showed multiple small cysts measuring 1-3 mm in size,completely replacing the cortex and medulla giving it a spongy like appearance and typical honeycomb structure.On microscopical examination we found cysts uniformly lined by cuboidal to flattened epithelium. Zaključak: We consider that this is a Potter Syndrome Type I due to Autosomal Recessive Polycystic Kidney Disease and is linked to a mutation in the gene PKHD1.2. Through this case,we are aware of the importance and benefit of autopsy,although the trend of autopsies in the world is decreasing.

Aim: The aim of this study is to present a case of benign lymphadenitis that cytologically was interpreted as suspicios for malignant lymphoma. Introduction: This study represents a case of a patient with cervical lymph node swelling in which the cyto-diagnosis performed by fine needle aspiration cytology was suspicious for lymphoma. The correct diagnosis was assessed by subsequent histology after the removal of the enlarged cervical lymph node. Material and Methods: For cytologic study the material was obtained by fine needle aspiration biopsy and syringe washings, air-dried smears and alcohol-fixed smears, which were prepared and appropriately stained by PAP and May Gruenwald-Giemsa stains. For correct diagnosis an extirpated lymph node was properly fixed and processed with routine haematoxylin eosin staining as well as with an additional immunohistochemical analyses. Results: The cyto-histologic features were characterized by a polymorphous population of cells, germinal center cells with large nuclei, a few epithelioid-type cells and histiocytes with intracellular inclusions The cytological diagnosis implied suspicion for malignant lymphoma probably of Hodgkin type. Histologic features revealed a reactive lymph node architecture that immunohistochemically revealed the diagnosis of Toxoplasma lymphadenitis. Serologic testing for toxoplasma in other institution revealed elevated titres that established the histopathological diagnosis. Conclusion: Lymphadenitis due to Toxoplasma infection is common and should be considered in the diagnosis of unexplained lymphadenopathy at all sites, especially the cervical region. Serologic confirmation should be recommended for all suspected cases and unlike in this case, fine needle aspiration cytodiagnosis can eliminate the need for hospitalization and surgery.

Kadmijum (Cd) je mekan srebtrnasto-beli metal, jedan od 126 prioritetnih zagađivača, a svrstan je i u grupu humanih karcinogena I kategorije.Cilj rada je mikromorfološko i funkcionalno ispitivanje endokrinog pankreasa pacova hronično tretiranih kadmijumom. Za istraživanje su korišćeni beli Wistar pacovi ženskog pola, starosti 35-37 dana, težine 120-140 g.Ukupno je bilo 22 životinje koje su podeljene na kontrolnu (n=11) i eksperimentalnu grupu (n=11). Eksperimentalna grupa je svakodnevno tretirana sa 15mg/kg CdCl2 rastvorenog u pijaćoj vodi. Kontrolna grupa nije bila podvrgnuta nikakvom tretmanu. Svi pacovi su čuvani u kontrolisanim laboratorijskim uslovima. Posle tri meseca, sve životinje su žrtvovane. Tkivo pankreasa je rutinski obrađeno i kalupljeno u parafi n. Na 4μm presecima su primenjene HE i imunohistohemijska ABC metoda sa antitelima na: chromogranin A, insulin,glucagon,somatostatin, pankreasni polipeptid, i peptid YY. U životinja eksperimentalne grupe su nađene guste, hiperplastične B ćelije koje zaposedaju skoro čitavu površinu insule. Prisutna je i hiperplazija A ćelija sa izraženom funkcionalnom aktivnošću. Osim po obodu hiperplastičnih insula, pojedinačne A ćelije se nalaze i u acinusima u kojima je njihova aktivnost znatno povećana. Zapažen je povećan mitotski indeks i odsustvo citoplazmatskih produžetka D ćelija. Izražena je hiperplazija PP ćelija, sa znacima kako morfološkog tako i funkcionalnog polimorfi zma. Prisustvo PP ćelija je evidentirano i u hiperplastičnom i displastičnom epitelu većih duktusa. Samo u životinja eksperimentalne grupe smo našli ćelije koje sekretuju peptid YY. Ove ćelije imaju identičnu topografi ju kao i A ćelije, ali je njihov broj znatno manji. Hronično izlaganje kadmijumu remeti strukturu i funkciju endokrinog pankreasa.Sve pankreasne endokrine ćelije su pogođene.

Atipične ciste bubrega klasifikovane kaoBosniak III ili IV sususpektne na malignitet ali je u nekimslučajevima teško uspostaviti pravu dijagnozu uprkos savremenim radiološkim metodama i predložiti odgovarajući terapijski pristup. Evaluiramo slučaj komplikovane hemoragične bubrežne ciste kod 73 –godina starog pacijenta. Pacijent je primljen u našu bolnicu na dalju evaluaciju zbog nespecifičnih bolova u leđima i trbuhu i zbog hroničnih urinarnih infekcija. Ultrazvukom su verifikovane bilateralne ciste bubrega od kojih neke sa gustim sadržajem. Nakon CT pregleda jedna od tih cista je klasifikovana kao Bosniak II F, zbog diskretne opacifikacije zida ciste u jednom segmentu, dok je MR nalaz ukazao na suspektnu malignu leziju, pri čemu je opisana restrikcija difuzije intraluminalno, što ukazuje na prisustvo solidnog dela, te je pacijent nefrektomisan. Patohistološki pregled je verifikovao inflamiranu hemoragičnu cistu bez prisustva malignih ćelija. Atipična cista bubrega može odgovarati komplikovanoj cisti sa infekcijom ili krvarenjem, ali takođe i cističnom tumoru. Radiološki pregled često nije dovoljan za jasnu diferencijaciju. Lažno negativne biopsije kod cističnih promena su vrlo izvesne i često je neophodno izvršiti hiruršku intervenciju za preciznu dijagnozu.