Aim: To reported extremely rare case of collision adenocarcinomma et small cell neuroendocrine carcinomma of the gallbladder (SCNEC). Introduction: Collision cancers are malignancies in the same organ or anatomical site that comprises et least two different tumor components, with no mixed or transitional area between two component. Case report: 76 year old woman with abdominal pain, underwent ultrasonography evaluation which demonstrated cholelithiasis and gallbladder wall thickening. Cholecystectomy due to cholelithiasis was performed.The macroscopic analysis revealed 2,5cm sized round nodular lesions in the fundus of the gallbladder.Formalin fixed, paraffin embedded tissues were stained with H.E. Selected samples were stained immunochistochemically with chromogranin, synaptophysin et CK7. Microscopicaly, the tumor was composed of two components. Dominant component is adenocarcinomma, composed of tubular glands lined predominantly by columnar cells with pseudostratified et ovoid or elongated nuclei.In the area close to this component there was neuroendocrine carcinomma that came in touch with the previous one, but didnt infiltrate it. Neuroendocrine carcinomma was composed of round or fusiform cells, arranged in sheets, nests and cords.Tumor cells have round hyperchromatic nuclei with inconspicuous nucleoli. Neuroendocrine tumor cells were immunoreactive for chromogranin, synaptophysin. Epithelial cells were positive for CH7.The final pathologycal diagnosis was SCNEC. The tumor stage was II, T2, Nx, Mx. Conclusion: Prognosis for patient is poor.About 40-50 percent of patients have disseminated disease at the time of the diagnoses.SCNEC appear to be highly responsive to chemotherapy as well as radiotherapy and survival time more than one year have been reported.

Aim: The aim of this research is to analyze the profile of Ezh2 expression in superficial urothelial bladder cancer, to investigate its correlation with clinicopathological parameters, as well as to determine the prognostic significance of Ezh2. Introduction: Superficial urothelial bladder cancer, without invasion of muscle layer, is associated with frequent recurrence, and represents significant burden for health care system. Ezh2 is epigenetic regulator with a major role in urothelial oncogenesis. Clinical investigations of Ezh2 inhibitors in treatment of solid cancers have already given encouraging results. Materials and Methods: Tumor samples from 410 patients with superficial bladder cancer (172 pTa, 238 pT1), obtained by transurethral resection, were incorporated in tissue microarrays, and analyzed immunohistochemically to Ezh2 expression. Correlation analysis with clinicopathological parameters was performed using SPSS 18.0. Results: High nuclear expression was found in 33.4% tumors, and it was significantly more frequent in pT1 (46.6%), compared to pTa tumors (15.1%) (p<0.001). Ezh2 expression was associated with high histologic grade, presence of carcinoma in situ, and cancer specific death (p<0.001, respectively). In Kaplan-Mayer survival analysis high Ezh2 expression was significantly associated with poor prognosis and shorter patients survival (p<0.001). There was no significant correlation between Ezh2 and recurrence of the disease, and recurrence free interval (p<0.05). Conclusion: Immunohistochemical expression of transcription repressor Ezh2 in superficial urothelial bladder cancer indicates aggressive behavior of the tumor, and poor prognosis. Ezh2 could be used as pronostic marker in selection of the patients that might require more intense clinical treatment, and as potential target of anticancer therapy.

Aim: Case report for rare complication rectorrhagia induced by rectal lipoma incarcerated in the anus . Introduction: Colorectal lipomas are rare tumors that are commonly diagnosed in the right colon, accidentaly during colonoscopy. When the lipomas are larger then 2 cm, they cause pain, bleeding, obstruction, incarceration and torsion. Material and Methods: We present the case of 50-year old man who comes to emergency ambulance with abundant rectorrhagia and blood presented on underwear and thighs. It is noted prolapse of the soft structure through the anus which is reponated into the anus. Anoproctoscopy was performed, which determines that it is polyp of rectum, although it seemed to be incarcerated hemorrhoids, due to the fact that the patient has been suffering from hemorrhoids with bleeding for several years,which is treated conservatively. It was found that it was not hemorrhoids prolaps or bleeding from them. Flexibile rectoscopy was performed on the untreated gut. The polypoid structure on peduncle,was verified in the distal rectum,3,5 cm from the pectinate line. Polypoid formation was electroresected and sent for pathohistological examination. Results: The patient was well tolerated intervention. Resected specimen revealed sessile pseudopolypoid tumor,eroded mucosa , diameter 28x25x24 mm.Histopathology revealed submucosal lipoma . Eroded mucosa is accompanied by focuses microbloods. Microcircuits of fatty necrosis are visible inside the lipoma. Conclusion: Lipom of the rectum is rare entity which is accidentaly diagnosed during colonoscopy. Extremly rare, lipom causes bleeding, which we present here.

Aim: We present the case of a rare localization of the alveolar soft part of the sarcoma in the visceral organ. Introduction: Alveolar soft part sarcoma (ASPS) is a rare mesenchymal tumor typically occurring in young patients, more frequently in females. Common localization of ASPS is skeletal musculature of lower extremities. ASPS in visceral organs usually represents a metastasis from the more common primary location in skeletal muscles. ASPS is characterized by a tumor-specific translocation which causes the fusion of the TEF3 with a ASPL gene (also known as ASPSCR1). Case report: Female 47 years old was admitted to hospital due to abdominal pain. Urgent surgery was performed due to ileus. Ileal tumor was detected intraoperatively as a cause of ileus. Tumor was infiltrated whole intestinal circumference, with dimension 70mm x 47cm and evident perforation. Histology showed well-defined nests of pleomorphic cells separated by delicate fibrovascular septae. Within described nests there is a prominent lack of cellular cohesion, representing for the distinctive pseudoalveolar pattern. Immunohistochemical stadies were diffusely positive for TFE3 and focally positive for CD34 and alpha-SMA and negative for panCK, DOG-1, CD117, S-100, HMB45, Desmin. Immunopositivity for Ki67 was present in 20% of tumor cells. FISH analysis was done using locus specific dual color break-apart TFE3 (3 and 5 ) probe and rearrangement in the TFE3 gene was confirmed. Conclusion: Despite the fact that ASPS is rare mesenchymal tumor in visceral organs it have to be considered as possible diagnosis especially in cases with typical histological features and immunohistochemical profile. Definitive diagnosis of ASPS must be confirmed by FISH 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: Determining the immunohistochemical characteristic of parathyroid glands (PG) proliferative activity in patients with primary and secondary hyperparathyroidism (HPT) using cell cycle and proliferation immunohistochemical markers, Ki -67 and PCNA. Introduction: A few studies results have shown A few studies results have shown significant detection of Ki-67 in hyperplasia due to secondary hyperparathyroidism (sHPT), whereas it s demonstrated only in adenomas in primary HPT (pHPT). The highest PCNA expression is detected in hyperplastic PG in sHPT and in adenoma in pHTP, but in pHTP hyperplasia it s extremely low. Material and Methods: We analyzed the surgically removed PG of 96 patients with HPT. In POSTER SESIJA 64 MATERIA MEDICA • Vol. 34 • Issue 1, suplement 1 • april 2018. addition to standard histopathological parameters the results of immunohistochemical reaction of Ki-67 and PCNA in 23 normal, 73 hyperplastic PG and 23 adenoma were analyzed. Results: 41 (42.7%) patients had pHPT, and 55 (57.3%) sHPT. Within pHPT adenoma was diagnosed in 23 (56.1%) patients and hyperplasia in 18 (43.9%). Detection of PCNA was 94.4% in pHPT hyperplasia, 91% in sHPT hyperplasia, and 83% in adenoma. 22 (98%) of the normal PG didn t have PCNA expression. The expression of Ki-67 was found in 13 (56.5%) adenomas and in 11 (18.3%) nodular hyperplasia. The high statistical significance for Ki-67 (p <0.0001) was found between adenoma and pHPT and sHPT. Conclusion: The results of our analysis showed high Ki-67 and PCNA expression in parathyroid adenomas. Increased Ki-67 expression corresponds with increased cellular proliferation and contributes to tumorigenesis in many organs, but doesn t distinguish accurately benign from malignant PG tumors.

Aim: To examine the quality of tested lung carcinoma samples, frequency and type of EGFR mutations, and their correlation with patients clinical characteristics (gender, age, smoking habits, clinical stage). Introduction: Mutations in Epidermal Growth Factor Receptor (EGFR) have a role in lung carcinoma development and they are more prevalent in women and non-smokers. Evaluation of EGFR mutations in lung carcinomas in mandatory for targeted therapy with tyrosine kinase inhibitors. Test performance depends on the quality of tested samples and a test type. Material and Methods: We evaluated reports of EGFR mutation real-time PCR analyses in lung carcinoma samples performed from June 2017 till February 2018. Presence of mutations was correlated with clinical characteristics of lung carcinoma patients. Results: A total of 341 samples was received for testing, among which 40 (11.7%) was unsuitable for analysis due to a low tumor cell content (<5%). Three types of mutations were detected in a total of 24 (8%) cases: L858R in 12 (50%) cases, exon 19 deletion in 10 (41.7%) cases, and G719A/C/S in two cases (8.3%). Mutations were more prevalent in women (13.7%) then in men (4.3%) (p=0.004). Patients with EGFR mutated tumors were older (67,6ą9,4 years), compared to those with non-mutated tumors (62,3ą8,8 years) (p=0,003). Smoking habits and clinical stage were not associated with mutation status in lung carcinomas. Mutations were detected only in adenocarcinomas. Conclusion: Our results suggest the low frequency of EGFR mutations in tested patients, but they are more prevalent in women and older patients.

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: To investigate immunohistochemical expression and the localization of connexin-43 (Cx-43) in primary lung cancer and its metastases. Introduction: Connexins are transmembrane proteins forming gap junctions that allow intercellular communication. Significance of gap junctions and connexins in lung cancer are not clear enough. Material and Methods: We analyzed autopsy samples of primary and metastatic lung carcinoma from Institute of Pathology in Belgrade. There were 11 primary lung carcinomas, 7 lung cancer metastases in lymph nodes, and 12 haematogenic metastases. We performed immunohistochemical staining for connexin-43 (Cx43) and measured expression (percentage of positive cells and intensity of staining) and localization of Cx43 in primary tumor and its metastases. Results: Lymphatic and hematogenous metastases of lung cancer showed a stronger expression of connexin-43 than primary tumor itself. Unlike 9% of primary carcinoma, 28% of lymphatic metastases and 50% of hematogenous metastases had expression of connexins in more than 50% of tumor cells (p=0.11). The intensity of connexin-43 expression was statistically significantly less in primary lung cancer than in all the metastases together(p=0.04). The expression of this marker was different in different histological types, where small cell carcinoma rarely expressed connexin, while the squamous carcinoma was mostly positive to immunohistochemical staining on Cx43. Dominant localization of expression was the combined cytoplasmic-membranous. Conclusion: Our results showed that lung cancer expresses connexin-43 mostly in cytoplasm as well as on the cell membrane. Further research on a larger sample is required to establish whether Cx-43 could be used as a prognostic biomarker in lung cancer.

Aim: We present a case of a patient with pneumothorax and subcutaneous emphysema as the first manifestation of miliary tuberculosis. Introduction: Miliary tuberculosis is the result of hematogenous dissemination of Mycobacterium tuberculosis in patients with weak immuno-defensive mechanisms. Pneumothorax and subcutaneous emphysema are possible complications of miliary tuberculosis. Case report: A woman aged 64 years old reported to the regional institution because of breathing difficulties. On the radiograph of the chest, pneumothorax was observed left, and the left thoracic drain was placed. Subcutaneous emphysema and global respiratory insufficiency were reported an hour later after which the patient was transferred to our facility. At the admission the patient was in poor general condition, intubated, hemodynamically unstable, markers of inflammation were elevated with the presence of electrolyte imbalance and severe anemia. On the chest radiogram, there was recorded: pneumothorax left, pneumonia right and generalized subcutaneous emphysema, and thoracal drain that was placed. Intensive therapy had improved the condition of the patient, after which she was extubated. Progression of respiratory insufficiency and lethal outcome occurred on the second day of admission. An autopsy was performed. A macroscopic examination and pathohistological analysis found: massive subcutaneous emphysema in the chest, well-placed thoracal drain, bilateral pleural effusion, bilateral acute tuberculous caverns in the lungs and necrotizing granulomas in: the lungs, liver, spleen and larynx which have led to asphyxiation and aviation outcome. Conclusion: In poorly-fed patients with the development of pneumothorax, subcutaneous emphysema and severe respiratory disorders, it is necessary to suspect tuberculosis.