Introduction: Hyperostosis frontalis interna is progressive, irregular thickeness of the frontal bone s internal table. It has been associated with a wide range of syndromes, though we know now that it can occur as an independent entity. Etiology is still unclear, but the most probable hyphothesis is alteration of steroid sex hormons, proven in high frequency among postmenopausal women. It is mostly asympthomatic or it has been accidentally diagnosed after endocranial trauma or postmortal. Because of its progression, in some cases it can cause cerebral cortical compression and varible neurological symptoms. Case report: We present a case of 27 years-old women, hospitalized in Neurosurgical Clinic, because of severe headaches lasting for 3 month. The head CT scan showed a massive, expansive lesion in right frontal bone, with spearing of the superior sagittal sinus and skull midline. Bone bulging does not affect outer table of the frontal bone, but only diploic space and inner table. Pathological analysis of the frontal bone showed marked trabecular thickening both cortical and spongy bone, with corticalisation of spongy bone. Haversian canals showed reduction in number and size, and light fibrosis. The lamellas of the spongy bones were enlarged, with prominent interlamellar bridges and the reduction of interlamellar spaces.In purpose of closer determination of etiopathogenesis,we did immunohystochemical analysis of Estrogen, Progesteron and Androgen receptors in dural tissue. Immunohistohemical stain confirmed nuclear expression of Estrogen and Androgen receptors in dural fibroblasts.Progesterone receptors were negative on immune stain. Conclusion: These results could support the hormonal theory of the cause of hyperostosis frontalis interna.

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.

The fourth Edition of the World Health Organization’s Classification of Tumours of Endocrine Organs from 2017 introduced some novelties based primarily on genetic research, compared to the previous edition from 2004. The most common primary tumors of the adrenal cortex are adenomas, and of the adrenal medulla are pheochromocytomas. As such, these tumors have their specificities in pathohistological diagnosis, by which they differentiate from tumors of other localizations. In the daily work of the pathologist dealing with the diagnosis of the tumor of the adrenal gland, differential diagnostic problems can occur, where biological behavior of the tumor cannot be predicted based on its morphological appearance; this primarily refers to cortical neoplasms and phaeochromocytomas. Scoring systems are used in these cases, Weiss and Lin-Weiss-Bisceglia criteria for cortical neoplasms, and PASS criteria for pheochromocytomas, where by recognizing the suggested morphological parameters, value or score is obtained which predicts the biological behavior of the tumor, i.e. differentiates benign from malignant neoplasms. The accepted algorithm of diagnostics of adrenocortical neoplasms also includes immunohistochemical staining for ki-67, which potentially can differentiate adrenocortical adenoma from carcinoma. Despite the introduction of these scoring systems, the only safe indicator of malignancy is still distant metastasis.

Aim: To evaluate surgical lung biopsies in patients with a clinically and radiologically set diagnosis of ILD. Introduction: Interstitial lung diseases (ILDs) are a group of lung diseases affecting the lung interstitium. These entities share similar clinical and radiological features and are distinguished primarily by the histopathologic patterns on surgical lung biopsy. Material and Methods: The study included 30 patients with a surgical lung biopsy performed in 10-year period at the Institute for Pulmonary Diseases of Vojvodina in Sremska Kamenica. Standard H E stain, special stains for conective tissue and smooth muscle, as well as immunohistochemistry in some cases were used. The patient’s age, sex, clinical symptoms, surgical biopsy type and histological findings were analyzed. Results: Of the 30 patients who underwent surgical lung biopsy, an open lung biopsy according to Claassen was performed in 14 patients, in 12 biopsies biopsy according to Maassen was obtained, while in 4 patients material for histopathological analysis was taken by VATS (Video - Assisted Thoracoscopic Surgery). The most common biopsy site was upper lobe in 16 cases, then lingula in 10, middle lobe in 2, and lower lobe and lung base in 1 patient. By histopathological analysis, diagnosis of UIP in 8, PLCH in 7, sarcoidosis in 6, hypersensitivity pneumonitis in 3, NSIP in 2, LAM, LIP, DIP and ACIF in 1 patient. Conclusion: Diagnosis of ILD is based on history, physical examination, high-resolution CT imaging, pulmonary function tests, and lung biopsy which presents golden standard in diagnostic approach.

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.

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”.

Aim: The aim of this case was a correct diagnosis of mediastinal tumor in a 41-years old female patient. Introduction: The rarity of primary extraneural ependymomas, its great variations in morphology and rare occurrence of metastasis, increase chances of misdiagnosis. Case report: Macroscopic examination of received specimen was performed, followed by histological and immunohistochemical analysis of the tissue samples. In presented case, onset of the disease was 14 years ago, when after right salpingo-oophorectomy, patient was diagnosed with malignant mesothelioma. In following years patient had multiple and extensive surgical procedures, resulting in different patohistological diagnosis, and after seven years, a diagnosis of extraneural ependymoma was established. Later on, patient was surgically treated in several medical centers across the region, again with different patohistological diagnosis. At present, tumor metastasized to mediastinum, presenting as grey to brown, multicystic formation, with cysts filed with clear serous fluid or red-brown hemorrhagic fluid. Inner surface of the cysts had smooth to partly papillary appearance. Tumor cells exhibited several architectural paterns (solid, pseudorosette or rosette formations, papillary and pseudopapilary structures), and immunophenotype specific for extraneural ependymoma (GFAP, ER, PR positive, calretinin, WT-1, S100, synaptophysin, chromogranin, CK7 and pan-cytokeratin negative). Conclusion: This case demonstrates an important principle in tumor pathology. Neoplasms may occur in unusual and unexpected primary and metastatic sites. Pathologists need to be familiar with histologic features of a wide range of neoplasms and not just the appearance of neoplasms within their own limited subspecialty area.

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.

Introduction: Pancreatic lesions, made of spindle cells, are a heterogeneous group of lesions, ranging from reactive, inflammatory changes to tumors. Differentiation of an individual lesion is difficult and requires the use of additional analytical methods (histochemical, immunohistochemical and molecular), and a comparison of morphological characteristics with other characteristics of the changes (radiologic and laboratory characteristics). We will present two cases of benign spindle cell lesions of the pancreas, with reference to the differential diagnosis. Material and Metods: The first patient was a female, aged 51 years, with a change localized in the pancreatic head, diameter of 9.5 cm. The second patient was a male, aged 35 years, with a change in the pancreatic tail, with maximum diameter of 5.5 cm. Results: In a female patient, the lesion was an inflammatory myofibroblastic pancreatic tumor, built of fascicles of mostly spindle cells (fibroblasts/myofibroblasts). The cells had uniform, elongated, spindle nuclei and eosinophilic cytoplasm. They were arranged in short fascicles that occasionally made storiformn formations. Mitotic activity of spindle cells was low (0 - 2 mitosis/ HPF 10, FD 0.65). In the stroma, there was a mixed inflammatory infiltrate, consisting of lymphocytes, plasma cells, histiocytes, eosinophils and neutrophils. In between, there were fascicles of collagen, together with the parts of the pancreas (excretory ducts, lobules, acini, and parts of the endocrine pancreas) (Figure 1). Immunohistochemically, spindle cells showed a diffuse immunohistochemical positivity to: Vimentin, SMA and Desmin. Negative immunohistochemical reaction was showed to S-100, p53, CDX2 and ALK-1.

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.