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.

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.

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.

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.

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: 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: 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.

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.

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.

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.