Introduction: GD is the commonest lysosomal storage disease worldwide. The majority of the patients have Type1 GD which is the non-neuronopathic form of disease. There are data of increased risk of cancer in GD patients, such as: multiple myeloma and other haematological malignancies, hepatocellular carcinoma and renal carcinoma. Factors of cancerogenesis in GD are accumulation of bioactive lipids, alternatively activated macrophages, immune dysregulation, genetic modifiers underlying the GD, splenectomy and enzyme replacement therapy. Extra-osseous soft tissue masses are described in GD patients, like localised deposition od Gaucher macrophages (Gaucheroma). To the best of our knowledge, no other case of extra-osseous soft tissue sarcoma in association with GD has been described in literature. To present very rare case of high grade leiomiosarcoma in association with Gaucher disease (GD). Case report: The case concerns 81 years old female with leucopenia and thrombocytopenia since year 2000. In 2014 she was diagnosed with undifferentiated pleomorphic sarcoma with prominent inflammation on her thigh, which was not completely surgically removed. She was diagnosed with leucopenia, thrombocytopenia and splenomegaly in 2014 on control examination. Bone marrow biopsy was performed and histologically and immunohistochemically was diagnosed GD. The diagnosis was confirmed by enzyme activity test. In 2018 revision of pathohistological finding of thigh tumour was performed. High grade leiomiosarcoma was diagnosed. She is alive and refuses any treatment. Conclusion: GD is rarely diagnosed in older age. All soft tissue masses in GD should be carefully examined because of increased risk of cancer in GD patients.

Aim: To investigate co-expression of ATRX and HIF-1α in kidney neoplasm in relation to its origin. Introduction: A heterogenous group of kidney tumors is believed to arise from a variety of specialized cells along the nephron – proximal tubules [Clear cell Renal Cell carcinoma (ccRCC) and papillary RCC (pRCC)] and collecting tubules [chromophobe RCC (chRCC) and oncocytoma]. ATP-dependent helicase (ATRX) is a chromatin remodeling protein involved in gene regulation and aberrant DNA methylation during cancerogenesis. Activation of hypoxia inducible factor (HIF-1α) is an early event in most RCC following inactivation of the VHL tumor suppressor gene. Material and Methods: A total of 46 kidney tumors (n=33 ccRCC, n=1 mRCC, n=4 pRCC, n=5 chRCC and n=3 oncocytomas) was immunohistochemically analyzed for ATRX and HIF-1α expression. Results: Diffuse and focal positivity of ATRX expression was found in 51.5% of ccRCC, while 54.5% had HIF-1α positivity. Co-expression of ATRX/HIF-1α was not related to nuclear grade and stage of ccRCC. Metastatic ccRCC had strong expression of both markers. pRCC type II showed weak ATRX/HIF-1α expression, while pRCC type I was negative for both markers. Interestingly, all analyzed oncocytomas and chromophobe RCC were negative for ATRX/HIF-1α. Conclusion: Our results suggest that signaling pathways have different patterns of activation/suppression of ATRX/HIF-1α in oncocytomas and chRCC compared to other RCC types. Downregulation or loss of ATRX/HIF-1α coexpression in benign tumors should be further investigated in order to determinate mechanisms of ATRX/ HIF-1α signaling transport renal neoplasm with different origin.

In preparation for the 8th edition of the TNM classification for lung cancer the International Association for the Study of Lung Cancer (IASLC) collected data on 94,708 cases of lung cancer diagnosed between 1999 and 2010, donated by 35 institutions in 16 countries. After exclusions, 77,156 remained for analysis: 70, 967 cases of non-small cell lung cancer (NSCLC) and 6,189 cases of small-cell lung cancer (SCLC). Analysis of the cases of NSCLC has allowed proposals for revisions to the T, N and M descriptors and TNM Stage groupings. Size remained an important determinant and a descriptor for all of the T categories. A new cut points at 1 and 4 cm have been proposed and as a result new T categories have been created: T1a ≤1 cm, T1b > 1 to 2 cm, T1c > 2 to 3 cm, T2a > 3 to 4 cm, T2b > 4 to 5 cm, T3 > 5 to 7 cm and T4 > 7 cm. However, measuring precise tumor size can be challenging since it is known that tumor gross size depends on whether the size measurement is performed on fresh or formalin-fixed specimen. In about 10% of cases, formalin fixation can cause down-staging of pathologic T category as a result of tumor shrinking. Tumors invading the diaphragm have been reclassified as T4, and tumors extending within 2cms of the carina without its invasion, or tumors associated with collapse or consolidation of the whole lung have been down-staged to T2. Tis and T1mi were introduced for adenocarcinoma in situ, squamous cell carcinoma in situ and minimally invasive adenocarcinoma, respectively. Visceral pleural invasion, defined as the involvement of its elastic layer, remains unchanged as T2 category, but specific analysis of visceral pleural invasion, showed that there is two types of invasion: PL1 where tumor invades beyond the elastic layer and PL2 where tumor invades pleural surface and that these two had different prognosis, PL2 being associated with the worst outcome. Elastic stains are recommended to clarify the status of visceral pleural invasion for cases in which initial hematoxylin-and-eosin-stained slides failed to show presence of invasion. Mediastinal pleura invasion disappears as a T descriptor. N categories remained the same as in 7th edition. 8th did not bring guidelines about the minimum number of lymph nodes that should be assessed for pathohistological analysis. In M descriptor category M1a retained, while M1b has been reassigned to describe a form of limited disease with a single metastatic deposit in one distant organ. A new category of M1c has been proposed and it is reserved for situations in which there are multiple metastases in one or more distant sites. Assessment of multifocal lung tumors and the distinction of synchronous primary tumors from intrapulmonary metastases represent an important problem as this decision significantly influences tumor staging, as well as treatment approach. Four different clinical presentation of lung cancer with multifocal lung involvement are described: second primary cancer, intrapulmonary metastasis, multifocal lung adenocarcinoma with ground glass/lepidic features, and pneumonic-type lung adenocarcinoma. The tumors are considered second primary tumor if it have clearly a different histology or have a different radiographic appearance, metabolic uptake growth pattern or different biomarkers. Each tumor is staged separately based on current TNM staging system. The nodules are considered to be intrapulmonary metastasis if exact matching breakpoints are identified by genetic hybridization or have similar clinical features such as radiographic appearance, growth pattern or significant nodal and systemic SPECIAL SESSION: DEPARTMENT OF PATHOLOGY, MEDICAL FACULTY, UNIVERSITY NOVI SAD, SERBIA 32 MATERIA MEDICA • Vol. 34 • Issue 1, suplement 1 • april 2018. metastasis. TNM staging depends on location of the nodule relative to the primary tumor site. If it is in the same lobe, the tumor is designated as T3, if it is in the same lung, but in different lobe as T4, and it it is in the contralateral lung as M1a. Tumors are considered multifocal lung adenocarcinoma if there are multiple subsolid nodules with at least one suspected or proven to be a cancer. Ground glass nodule <5 mm or lesion suspected to be AAH is excluded. T stage is based on highest T lesion with indicating the multiplicity. Tumor is categorized as a pneumonic-type adenocarcinoma if there is a diffuse pneumonic infiltrate or consolidation with regional distribution. Stage IA is divided into IA1, IA2 and IA3 to accommodate T1a, T1b and T1cN0M0 tumors. All N1 disease is staged IIB except for T3-T4N1M0 tumors which are stage IIIA. A new stage IIIC is created for T3-T4N3M0 tumors and stage IV is divided into IVA (M1a and M1b) and IVB (M1c). In conclusion, multi-disciplinary approach and the close cooperation among medical and radiation oncologists, pulmonologists, surgeons, radiologists and pathologists is important in properly staging of lung cancer as well as, in treatment plans.

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: 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: We present an interesting case of unexpected metastatic deposit “signet ring cell” of the gastric cancer in the ureter. Introduction: Ureteral obstruction caused by gastric cancer may occur by any of the following three mechanisms: direct extension from the primary site, peritoneal deposit or lymph node metastasis. Material and Methods: We report the case of a patient with ureteral metastasis as the first and sole manifestation of gastric cancer dissemination two years after he was first diagnosed with gastric cancer. Results: A 52-year old male patient was admitted to the Department of Urology, Clinical Hospital Centre Zvezdara in Belgrade, with a 5-day history of right colic flank pain and high temperature. He had a partial gastrectomy for gastric cancer two years ago and received 8 cycles of chemotherapy. Routine blood test results were normal except elevated creatinine and C-reactive protein levels. An abdominal ultrasound examination and computed tomography revealed grade 3 hydronephrosis and hydroureter. Cystoscopy indicated a tumor measuring 2 cm in size which involved left ureteral orifice. A left nephroureterectomy and transurethral resection of bladder tumor were performed. Histopathological examination of surgical POSTER SESIJA 65 MATERIA MEDICA • Vol. 34 • Issue 1, suplement 1 • april 2018. specimen revealed signet ring cell carcinoma infiltrating lamina propria and tunica muscularis of the left lower ureter. Histopathological examination of the bladder specimen revealed signet ring cell carcinoma identical to those of the ureteral tumor. Conclusion: Ureteral metastases from gastric cancer are extremely rare. Shimoyama reviewed 27 cases of the true ureteral metastasis from gastric cancer. The prognosis is generally poor and the survival for more than 2 years has not been reported in literature.

The skin is the largest organ in our body.Receiving information from the environment allows the role barrier between the human organism and the environment. The histological structure of the skin is variable depending on the part of the organism. The diseases of skin also vary depending on the region. The reason is the local immune status and the external physical, chemical and microbiological environment. The histopathological diagnosis of skin lesions request detailed clinical information. On the other side the histopathological diagnosis of skin lesions provides information on local disease , as well as potential other associated pathological conditions.˝ Extramammary Paget‘s vulvar disease is rare. The pathology of the skin of the vulva is specific both for specific localization, as well as for specific friction and microbiological flora. It is clinically presented as erythematosus or eczematous lesion. It can be local or extensive. Histopathologically, it is characterized by relatively large glandular atypical Paget cells, which are pathognomonic for this disease. These cells have abundant cytoplasm that is granular or vacuolated. Tumor cells are typically localized individually or in groups in the basal and parabasal layers. Immunochemical analyzes are necessary in the diagnosis of Paget‘s disease. The main reason is that Paget‘s disease can be a primary skin disease or associated with non-cutaneous carcinoma primarily of the urothelial or rectal carcinoma . Therefore, it is necessary to recommend that a detailed clinical trial of a patient be conducted in all diagnosed cases of vulvar Paget‘s disease. Mycobacterium marinum is etiological factor of Fish tank granuloma.This Mycobacterium more often causes diseases of fish, both marine and river fish. The humans become infected with Mycobacterium marinuim after contact with skin after micro/trauma Infection is usually localized to the skin.In immunocompromised patients the infection may disseminate or spread to the subcutis and bone. After incubation of few weeks after infection the lesion appear as solitary nodules or plaques.In some cases the disease progresses like suppurative ulcers. Histopathologically there is a wider range of histopathological presentations. Most often you can see abscess, necrosis of wheat and fatty tissue. However, granuloma inflammation is a key morphological substrate. After granuloma inflammation, fibrosis occurs. Since the microscopic image may be somewhat non-specific, clinical data are of great importance for the diagnosis. Multidisciplinarity in the final diagnosis includes microbiological confirmation of the presence of Mycobacterium marinum.

Aim: The aim of this paper is to point out the importance and the role of immunohistochemistry in diagnosing rare benign epithelial tumours of the lung and a very similar malignant tumour of well-differentiated lepidic adenocarcinoma. Introduction: In pulmonary pathology diagnostic dilemmas are frequent. One of the most complex challenges is to differentiate between benign tumours of pneumocytes and other forms of similar tumours. In particular, it is difficult to differentiate between the tumours of the same or similar histogenetic origin and morphological characteristics. However, dilemmas can also be related to whether a tumour has benign or malignant potential. In order to be able to have proper diagnostics, we need to have a detailed insight in the morphological and immunohistochemical features of these tumours. One of the best KRATKI KURSEVI APSTRAKTI 85 MATERIA MEDICA • Vol. 34 • Issue 1, suplement 1 • april 2018. examples of this are two very rare and morphologically very similar benign epithelial tumours: sclerosing pneumocytoma (according to the 2015 World Health Organisation Classification of Lung Tumours; new terms changed or entities added since 2004; the 2004 World Health Organisation Classification called it sclerosing haemangioma)1 and alveolar adenoma on the one hand; and well-differentiated lepidic adenocarcinoma on the other hand. These are most often cited as the most problematic in terms of their differential diagnostics. When it comes to first two tumours, as it can be concluded from their original names, they were considered to be the tumours of completely different histogenetic origin. However, their immunohistochemical profile and all current data show that they have identical structure and origin. Immunohistochemical diagnostics enabled the demystification of neoplastic processes, as is the case with rare benign tumours of pneumocytes. This diagnostics can also point out the biological potential and help differentiate between benign and malign tumours. Additional dilemma is posed by the fact that sclerosing pneumocytoma may even give metastases into regional lymph nodes, which do not affect disease prognosis 2,3. Histopathological differential diagnosis includes, apart for the above mentioned, other benign epithelial tumors, hemangioma, primary and metastatic carcinoma4. Materials and methods: We analysed two very rare and morphologically very similar benign epithelial tumours, (sclerosing pneumocytoma and alveolar adenoma) and welldifferentiated lepidic adenocarcinoma. It was also performed their immunohistochemical analysis using the following markers: Cytokeratin 7 (CK7), Thyroid transcription factor 1 (TTF-1), Epithelial membrane antigen (EMA), Pan-cytokeratin (CK), Carcinoembryonic Antigen (CEA), FVIII, Ki67 and p53. Results: The first tumour, at the microscopic level, showed sclerosing and haemorrhagic arrangement, with ectatic spaces filled by blood and solid areas and papillary-like formations. Basic cell population was epithelial cells, dominantly with eosinophilic and partially with granular cytoplasm. The nucleus was in the centre, round, without prominent nucleoli and mitoses. Stroma was moderately pronounced and centrally it was denser and composed of bundles of oval and spindle-shaped fibroblasts. Some of the cavities within the tumour had wide, cavernous space, lined with endothelium-like attenuated cells. Mainly in the middle part of the tumour, we could see the areas of hyalinisation of connective tissue. The tumour borders were expansive. The tumour did not infiltrate the pleura. On the final histopathological slides, the second tumour had a microcystic appearance. In central parts there was pale amorphous, homogenous content. Spaces were lined with cylindrical cells containing acidophilic and clear cytoplasm. Stroma was scarcely developed and sometimes with more pronounced parts and composed of groups of elongated spindle-like fibrocytes and fibroblasts. Immunohistochemical analysis of both tumours showed very similar reactivity: Ck7, TTF-1, EMA and CK showed diffuse positivity, k67 showed low proliferation index <1%. Cea in the major part of sclerosing pneumocytoma was negative and focally individual cells had reactivity, while alveolar adenoma was negative in its entirety. P53 and FVIII in both cases showed negative results. After all analyses, the definitive diagnosis of the first tumour is pneumocytoma and for the second one alveolar adenoma. The third tumour showed similar morphology as the previous two. At the microscopic hematoxylin eosin stain, it was dominantly composed of alveolar-adenoid formations. Tumour cells were bulky, cubic or polygonal; foamy, pale acidophilic, with homogenous cytoplasm and hyperchromatic roundish nuclei without prominent nucleoli. The immunohistochemical analysis of the third tumour showed positive reactivity with Ck7, TTF-1, CK, Cea, EMA, k67 proliferation index > 32%, while p53 proliferation index ≥1%, while the FVIII had a negative result. Final diagnosis for this tumour is well-differentiated lepidic adenocarcinoma. Conclusion: Due to almost identical histopathological and immunohistochemical characteristic, there may be a diagnostic dilemma: are these two separate tumours or this is the same tumour. Taking into consideration that sclerosing pneumocytoma give positive epithelial immunohistochemical reaction, their earlier name is wrong. Previous examples are good indicators of how we should adapt the names of tumours to their real nature and this is a good recommendation in terms of how we should organise future classifications. All of the above mentioned points to the fact that with these tumours it is necessary to have immunohistochemical evaluation and that we have to introduce new immunohistochemical predictive and prognostic markers. It is necessary to determine the cut off values for proliferative markers.

Moebius syndrome is rare and complex disorder which due to clinical expression poses a great challenge for pediatric anesthesiologist. The most significant problem for anesthesia, due to craniofacial malformations, is difficulties to provide a safe airway. The need for anesthesia is imposed sometime in the age of the newborn and later in childhood because of necessary diagnostic and surgical procedures. We present the case of a two-month old infant with Moebius syndrome, potential anesthetic implications, as well as the safe application of the caudal block as an anesthetics technique for operations of Achilles tendons and correction of congenital deformities of both feet.

Implementation of IMRT offers possibility to escalate radiation therapy dose without increased acute and late toxicity. The aim of this study is to compare acute and late genitourinary and gastrointestinal toxicity in patients treated with IMRT and 3DCRT technique. This study included 35 patients in study group A treated with IMRT technique, and 35 patients in study group B treated with 3DCRT technique. Patients were selected and referred to radical radiotherapy treatment prostate cancer. Acute genitourinary and gastrointestinal toxicity was evaluated during radiotherapy treatment according to recommendation of RTOG group. Late gastrointestinal and genitourinary toxicity was evaluated during regular control exams after radical radiotherapy treatment for six months. Based on the results χ2 test there was no statistical significant difference (p>0,05) between study group A i B in terms of acute gastrointestinal and genitourinary despite escalated radiotherapy dose in study group B treated with IMRT technique. Based on the results χ2 test there was no statistical significant difference (p>0, 05) between study group A i B in terms of late gastrointestinal and genitourinary toxicity. Intensity modulated radiation therapy is optimal technique in the radical treatment prostate cancer. This technique allows clinical benefit compared with 3D conformal radiotherapy-escalation of radiotherapy dose without increased toxicity in patients treated with IMRT technique.