Aim: We present an unusual case of malignant gastrointestinal stromal tumor filling the entire abdominal cavity. Introduction: Gastrointestinal stromal tumors are the most common mesenchymal neoplasms of the gastrointestinal tract. Small tumors are generally benign, but large tumors disseminate to the liver, omentum and peritoneal cavity. They rarely occur in other abdominal organs. Material and Metods: The operative material consisted of segment of ileum where a tumor mass of 8 cm was found originating from the wall and fragments of small intestinal serosa and omentum where multiple nodular tumor mases were found. Representative samples were taken, and were paraffin embedded and stained routinely with Hematoxyllin-Eosin. Additionally immunohistochemical analyses were performed using the antibodies c-kit, CD34, Vimentin, CKAE1/AE3, Ki67 and others. Results: Microscopic analysis revealed a malignant gastrointestinal stromal tumor with a high mitotic rate of 58/50 HPF mitoses. However clinical reports stated that an additional large 12 cm tumor mass was found in the liver that was not removed. Conclusion: Gastrointestinal stromal tumors are the most common gastrointestinal mesenchymal neoplasms but presence of multiple tumor masses on various organs and sites is rare. Presence of multiple tumors in various organs brings about the issues of possibility of multiple primaries or the proper detection of the original tumor mass.

Aim: The aim of the study is to classify tumors into four main molecular subtypes using immunohistochemistry and in situ hybridisation methods, as well as to determine frequency of different carcinoma subtypes. Introduction: Four molecular subtypes of breast carcinoma can be identified: Luminal A and Luminal B (hormone receptors positive), HER2 enriched (HER2 overexpression) and Triple Negative / Basal-like (absence of HER2 amplification and steroid receptors expression). Materials and Methods: Cross-sectional study, conducted in Institute of pathology, Medical Faculty, University in Belgrade, during the ten months period in 2017, included 337 patients with diagnosed breast carcinoma. Using the methods of immunohistochemistry, all four markers (estrogen, progesteron, HER2, and Ki67) were evaluated on breast carcinoma tissues. As additional methods, “in situ” hybridisation (FISH, SISH) was used in cases if HER2 oncoprotein results on immunohistochemistry were equivocal. Results: Luminal A, Luminal B, HER2 enriched, and Triple Negative carcinomas were present in 133 (39,45%), 147 (43,62%), 22 (6,5%), 34 (10,08%) cases, respectively. For 55 (16,35%) cases, in situ hybridisation had been done in order to classify carcinomas in proper molecular subtype. Conclusion: Frequency of molecular subtypes of breast carcinomas in our study are similar to literature data for European countries. Breast carcinoma subtyping has prognostic and predictive values for further patient treatment, and should be done in institutions with adequately trained personnel and equipment, in order to achive best results in the shortest time.

Aim: Our aim is to examine the expression of CD34 in the endometrioid carcinoma (EC) of the uterine body and association of neoangiogenesis with classical clinical and prognostic parameters. Introduction: The incidence rate increases with age, so in about 75% of cases it occurs in postmenopausal women.Material and Methods: On the biopsy samples obtained after the hysterectomy of 36 patients operated from EC of the uterine body, operated in the General hospital Pirot, where applied routine H E and the imunohistochemical ABC method with anti-CD34 antibodies. Based on the expression of CD 34, the microvascular density per mm2 of the tissue was calculated stereometrically. For statistical analysis SPSS software package were used (version 19.0). Results: The significantly pronounced expression of CD34 is present in all cases of tumors in pT2a to pT3a, and in all cases of the IIA-IIIA FIGO stage. A significantly high neoangiogenesis index is present in 72% of moderately differentiated tumors, in about 70% of tumors with moderate/expressed nuclear atypies, in 92% of cases with microvascular invasion and in 76,5% of tumors affecting over 50% of myomterium. CD34 expression is in positive, moderate and significant correlation with invasion of lymph vessels, pathological stage of the tumor and invasion of blood vessels and myometrium (kk=0,636 - 0,587). The correlation between this marker and the histological and nuclear tumor grade is weaker (kk=0,444 and 0,410). Conclusion: Significant association of CD34 with the aggressive phenotype of the EC of uterine body has significant prognostic implications.

Aim: Lobular endocervical glandular hyperplasia is very rare, differential diagnostic difficult entity, which often mimics more aggressive endocervical lesions, with worse prognosis. Introduction: Lobular glandular endocervical hyperplasia(LEGH) is benign lesion with lobular proliferation of endocervical glands and endocervical epithelium without or with minimal nuclear atypia. Lobular structure can be deep into the cervical tissue without stromal invasion, which is important difference between adenocarcinoma of minimal deviation(MDA), well-differentiated endocervical type of adenocarcinoma, similar to LEGH. Case report: The patient is 50 years, with demarcated, nodular, multicystic tumor, localized deep in cervical tissue. Microscopic analysis shows numerous cystically dilated endocervical glands with lobular presentation, surrounded by hyperplastic fibrous stroma. Glandular acini are diffusely localized, with centrally dilated acinus and peripheral smaller tubular structures. Glands are without the presence of architectural changes and cytonuclear atypia, with uniform, endocervical epithelium.Immunochemical analysis showed:CEA- /CA125focal /p16 focal /Er and Pr focal epithelium, diffusely in stroma. Because structures were described deep in the cervical tissue, MDA is considered diagnostically differential. However, glands do not show signs of distortion(architectural atypia), which is important feature of this entity, as well as no pronounced surrounding desmoplastic stromal reaction. Macroscopic tumor is well demarcated, and the CEA marker is negative, which also suggested LEGH. Conclusion: LEGH and MDA show a quiet clinical and histological similarity. Association of LEGH(50%) with MDA and 40% with cervical adenocarcinoma has been demonstrated, suggesting the possible precancerous potential of LEGH. Research of the lesion microenvironment could be an interesting subject for further research.

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: We present a rare case of gastrointestinal tumor in a boy. Introduction: Gastrointestinal stromal tumors (GISTs) represent rare mesenchymal tumors in pediatric population. Most of these tumors originate in the stomach and very rarely in the oesophagus. They are more frequent in young girls. As opposed to adult GISTs, those that occur in childhood show mutations in PDGFRA receptors or so called “Wild type” mutations. Case report: A fifteen years and 2 months old boy with symptoms of dysphagia and stenocardia for the last six months. Endoscopy showed nodular solid lesion at the distal part of the thoracal oesophagus, later surgically removed. Dimensions of the lession were 35x25x20mm with whitishPOSTER SESIJA 57 MATERIA MEDICA • Vol. 34 • Issue 1, suplement 1 • april 2018. yellow cut surface and areas of hemorrhage. Histology showed predominant spindle cell pattern with minor epithelioid component, with pronounced cellular and nuclear pleomorphism, rare areas of necrosis and hemorrhage, with the mitotic count more than 18 per 50 high power fields and numerous atypical mitotic figures. Immunohistochemical studies were CD117 and DOG-1 negative, but positive for PDGFRA. Tumor expressed focal alpha-SMA and CD34 positivity. Conclusion: Informations regarding pediatric gastrointestinal stromal tumors are still insufficient. Even though these tumors are rare in childhood, when analysing mesenchymal neoplasms potential GISTs should be considered.

Aim: We present the case of a patient aged 68 years who died of chronic heart failure caused by untreated cardiac sarcoidosis (CS). Introduction: Sarcoidosis is a multisystem disorder of unknown etiology, characterized by granulomatous infiltration and the development of noncaseating granulomas in many organ systems. Although the lungs, eyes, and skin are most commonly affected, virtually any body organ can be involved. Clinical evidence of CS is seen only in 5% of patients and the disease may present with tachyarrhythmias, conduction disturbance, heart failure, or sudden cardiac death. Case report: The patient was received in the hospital due to symptoms and signs of global cardiac decompensation with difficulties in the form of dyspnea, orthopnea, and edematous legs. Echocardiographic, cardiac cavities are very dilated with globally reduced systolic function, severe mitral regurgitation and ejection fraction about 20%. Very soon after receiving the patient is died. At autopsy, the heart was dilated, primarily the left ventricle. Histologically, the myocardium was infiltrated by numerous granulomas built of lymphocytes, epitheloid cells, and giant multicellular cells of the Langhans type. As a consequence of severe chronic heart failure, the lungs were edematous with both sides of massive plural effusions. The coronary arteries were non-significantly stenosed. Conclusion: Early diagnosis and treatment can prevent significant morbidity and mortality in patients with CS. It is very important that patients with CS in the early stage of the disease be treated with corticosteroids.

Aim: To analyze age and sex distribution of the cardiac tumors, the most common clinical symptoms, POSTER SESIJA 70 MATERIA MEDICA • Vol. 34 • Issue 1, suplement 1 • april 2018. pathohistological types, tumor localization and compare the echocardiographic with the pathohistological size of the tumor. Introduction: The incidence of primary cardiac tumors are very rare and amounts to about 0.02%. Incidence of secondary cardiac tumors are significantly higher. Primary malignant cardiac tumors are very rare and represent to the rarest tumors in the human organism. Materials and Methods: The study covered 49 patients who were operated in the period from 2008 to 2017. Patients data are obtained from the history of the disease, the information system and pathohistological findings. Results: The average age of the patients is 53.9 years. The most common symptoms were light fatigue, heart palpitations, vertigo, dizziness, dyspnea, exhaustion, cough and stenocardia. The most commonly diagnosed are myxomas (67.3%), papillary fibroelastomas 28.6%, cavernous hemangiomas 4.1%, and metastatic tumors 2.04%. The most common tumor localization is in the left atrium 63.3%, aortic cusps 16.3%, right atrium 8.2%, mitral valve 8.2%, left ventricle 2.04% and interventricular septum 2.04%. The difference in mean echocardiographic tumor size and tumor size after surgical extirpation was not statistically significant (p = 0.706). Conclusion: Although, cardiac tumors are rare, they have a large clinical importance, primarily because of the potential for severe complications such as embolization of the arteries of the brain with the development of cerebral infarction and even the appearance of sudden death. However, timely diagnosis and surgical removal of tumors lead to patient curing in most cases.

Adnexal tumors of the skin comprise heterogenous group with over 40 defined entities, classified by predominant differentiation into lesions with apocrine and eccrine, follicular, sebaceous, or multilineage differentiation. Some, but not all these entities are represented by benign and malignant counterparts. Their occurrence may be sporadic or as a part of inherited syndromes (e.g. Muir-Torre syndrome, Brooke-Spiegler Syndrome, or Cowden’s syndrome). Adnexal tumors may arise de novo or within hamartomatous lesions such as nevus sebaceous of Jadassohn. Adnexal carcinomas are very rare tumors (the incidence is less than 0.001%), with variable local recurrence, metastatic potential, and survival. Porocarcinoma, hidradenocarcinoma and sebaceous carcinoma (especially ocular type) are considered to have a poor prognosis, with the highest risk of local recurrence and distant metastases. Mortality of the patients with porocarcinoma is very high (65-80%) if regional or distant metastases are present. The treatment of malignant adnexal tumors is usually surgical or less frequently with radiation therapy. Patients with metastases are usually treated with chemotherapy, mostly with cytotoxic reagents, and rarely with estrogen receptor antagonists. The detailed knowledge of genetic features of adnexal tumors is still lacking. Most of the studies examined only few of the genes using low throughput techniques. Development of new generations of genome sequencing methods led to better understanding of tumors with apocrine and eccrine differentiation. For many of their subtypes, it is still unknown whether there are specific genetic changes, that could even be of diagnostic significance. Hotspot mutations in HRAS (p.G13X and p.Q61X) were found in a subset of eccrine poromas and porocarcinomas. These mutations were found in tumors with other lines of differentiation and suggesting overlapping genetical characteristics among adnexal tumors. Due to their similar histological features, cylindroma and spiradenoma are usually considered as phenotypic variations of the same entity. Their histological features can be mixed, in which case a diagnosis of spiradenocylindroma is made. In cylindroma, MYB is upregulated either by mutations in CYLD gene (syndromic cases) or due to a rearrangement of MYB gene (sporadic cases). Genetic characteristics of spiradenomas, including the status of CYLD and MYB genes, are largely unknown. It is still unclear if these two are both histological and genetical “relatives” and what is the level of heterogeneity among tumors arising sporadically or within syndromes. The presence of chromosomal rearrangements in adnexal tumors is also unexplored. TORC1-MAML2 and EWSR1-POU5F1 fusions were found in significant number of hidradenomas. Initially it was thought these fusions could be characteristic for clear cell variant of hidradenomas, but no true correlation with histology was found. Molecular alterations that differ between benign and malignant counterparts and could enable targeted therapy of adnexal carcinomas are unknown. Mutations in TP53, often UV-associated, are frequent in malignant tumors with eccrine and apocrine differentiation and can drive malignant transformation in such tumors. Porocarcinomas and ABSTRACTS 96 MATERIA MEDICA • Vol. 34 • Issue 1, suplement 1 • april 2018. hidradenocarcinomas harbor various molecular alterations affecting PI3K-AKT or MAPK pathways that could enable targeted therapy in the future. Actionable mutations in EGFR were not found in carcinomas with eccrine and apocrine differentiation thus far. Her2 amplifications are rarely found, mostly in hidradenocarcinomas, but its therapeutic potential has only been utilized only once.16,25 Mutations of PTCH1 and TCF7L1 in hidradenocarcinomas could also enable the treatment with the inhibitors of Hedgehog and WNT/Hippo signaling pathways. It seems that current knowledge gained from genomic studies of adnexal tumors is only a scratch on the surface. In addition, there is no data on epigenetic characteristics or transcriptome of adnexal skin tumors. Taken altogether, further and detailed investigation of genome, epigenome and transcriptome of adnexal tumors is necessary. Such integrated knowledge could explain mechanisms of their development, malignant alteration and progression, so the treatment of patients with metastatic adnexal carcinomas could be changed toward targeted therapy.

Lung transplantation remains the definitive treatment for end-stage lung diseases and an option when
medical and surgical care has been exhausted. The first human single lung transplant was performed in
1963, and the patient, survived for 18 days. From 1963 to 1978, multiple attempts at lung transplantation
failed because of rejection and problems with anastomotic bronchial healing. It was only after the invention of the heart-lung machine, coupled with the development of immunosuppressive drugs, that organs
such as the lungs could be transplanted with a reasonable chance of patient recovery. The first clinically
successful long-term single lung transplant was performed in 1983, and since then over 25,000 lung transplants performed worldwide.