Aim: We present a rare case of simultaneous occurrence Concurrent occurrence of acute myeloid leukemia (AML) and monoclonal plasmacitosis (MP): Introduction: The simultaneous occurrence of acute myeloid leukemia (AML) and monoclonal plasmacytosis (MP) in bone marrow (BM) biopsy in patient without previous exposure to chemotherapy is very rare. Case report: We reported the case of a 45-year-old woman who presented with fatigue, fever, maculopapular rush, weight loss and bone pain. She was admitted to the Haematology Department of University CHC Bezanijska Kosa in November 2015. The complete blood count showed: white blood cell count 33x109/l (neutrophils 31%, myeloblasts 12%, monoblasts, promonocytes and monocytes 53%), hemoglobin 77gr/l, platelet count 34x109/l and 5% blastic cells in the peripheral smear. Serum immunoelectrophoresis showed increased monoclonal IgA (IgA 9,98, IgM 2,29, IgG 10,1), kappa/lambda 0,84, Beta2microglobulin 3,16. Biochemistry showed elevated creatinin level 93umol/l, uric acid 412 umol/l, high LDH 876U/l and sedimentation rate (50mm/h). Urine electrophoresis showed monoclonal heavy and light chains lambda type. Liquor immunophenotyping showed neuroleukemia. Skeletal survey showed no lytic lesions. The BM aspiration revealed around 10% plasma cells and BM biopsy showed infiltration by 20% monoclonal plasma cells (kappa-/lambda ) with 30% infiltration by cells with monocytes differentiation (without excess of blasts). Biopsy of skin lesion 17 MATERIA MEDICA • Vol. 34 • Issue 1, suplement 1 • april 2018. revealed myeloid sarcoma. Cytogenetic analysis detected normal karyiotype with FLT3 and NPM mutation. The patient was diagnosed as AML-M5, administered with induction therapy (DA Cytosar) and consolidation therapy (HiDAC) and she was successfully treated with allogenenic stem cell transplantation. She achieved and maintained complete remission. Conclusion: Monoclonal plasmacytosis of BM should be carefully examined due to possible association with other haematological malignancies

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: Report of two cases of benign skin tumors of different histogenesis with anaplastic lymphoma kinase (ALK) gene rearrangement. Introduction: ALK gene mutation or rearrangement positive tumors (ALKomas) are heterogeneous group in which such genetic finding has diagnostic or predictive value. ALK gene fusions are associated with tumorigenesis of some cutaneous tumors, e.g. plexiform Spitz nevus (PSN) and epithelioid fibrous histiocytoma (EFH). Cases reports: Histological, immunohistochemical (IHC) and genetic characteristics were analyzed in two skin tumors with ALK gene rearrangement proved by fluorescent in situ hybridization (FISH). First case is PSN localized on face in a 8-year-old boy. Tumor was consisted of spindle cells arranged in plexiform growth pattern throughout epidermis and dermis, with following IHC characteristics: HMB45  focally, p16 , Ki67  in 1% of cells. Deletion of CDKN2A gene was not detected in significant number, while ALK gene rearrangement was positive in 37/50 (74,2%) of cells. Second case is EFH localized on shoulder in a 16-year-old girl. This dermal based tumor was consisted of tightly packed large epithelioid cells, which were CD68 , p16 , S100-, HMB45-, SOX10-, CD1a-, Ki67 (<5% of cells). ALK gene rearrangement was positive in 24/100 (24%) of cells, and focal chromosome 2 polysomy was noted. Neither mitoses nor necrosis were present in any of presented cases. Conclusion: Skin ALKomas are tumors with heterogeneous histological and immunohistochemical characteristics, and also with variable extent of ALK rearrangement.

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: 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: Purpose of this report is to present metastasis of lymph nodes melanoma with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) as an example of collision tumor of an uncommon synchronic occurrence in the lymph node. Introduction: Synchronic, composite tumors are rare and their simultaneous and synchronic occurence within the same tissue/organ is even more rare. CLL/SLL is an indolent, clonal disease of mature B-lymphocytes which occurs mostly with adults. After the treatment with chemotherapeutic agents the occurence of the secondary malignancies (melanoma,squamous-cell carcinoma). Material and Methods: We present a 77 year old male who, after right sided nephrectomy caused by clear-cell carcinoma was diagnosed with CLL/SLL with bone marrow and lymph node infiltration. After three years and chemotherapy, skin changes were excised which histomorphologically resembles melanoma. After the immunotherapy for melanoma, the enlarged lymph nodes were extripated from the neck and histomorphologically and immunohistochemically treated. Results: Histomorphologically, a diffused infiltration of small B-lymphocytes was found in the lymph node, with round nuclei, condensed chromatin, inconspicuous nucleoli, scant cytoplasm unique immunophenotype: CD20 ,PAX-5 ,CD5 ,CD23 ,Cyclin D1-,CD3-. A part of lymph node was infiltrated by epitheloid cells with immunohistochemic profile: S-100 ,Melan A ,HMB-45 . Histomorphological and immunohistochemical CLL/SLL with melanoma infiltration as an example of a collision tumor was proved. Conclusion: Lymphoproliferative neoplasms including CLL/SLL represent an risk of synchronous, metachronous development of secondary malignancies including melanoma itself and they can uncommonly present themselves as synchronic collision tumors within the same organ.

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 and introduction: Pediatric nodal marginal zone lymphoma (NMZL) is a rare, but distinct subtype of NMZL with characteristic clinical presentation, pathohistological and molecular features, therapy and prognosis. Results: We report the case of a 15-year-old boy with no remarkable past history, presented with painless enlargement of left submandibular lymph node (LN) for three months. He was admitted to the University Children’s Hospital in Belgrade in May 2016. The cervical ultrasound demonstrated moderate left submandibular lymphadenopathy, but also mild enlargement of two right submandibular LNs (17x7mm, 14x7mm). Physical examination, chest radiography and abdominal ultrasound revealed no hepatosplenomegaly and lymphadenopathy elsewhere. The result of blood count test was normal. Biochemistry showed elevated uric acid 499 umol/l, AST 45U/l, ALT 98U/l, and sedimentation rate (65mm/h). Urea, creatinine, alkaline phosphatase, LDH and CRP were normal. The patient underwent left submandibular LN excisional biopsy. The size of the LN was 47x37x20mm. The histopathological examination revealed partial architectural effacement: follicular hyperplasia and nodular B-cell infiltration with features of progressive transformation of germinal centers (PTGC) in the form of fragmentation of follicles. A CD20 immunostain shows an abnormal expansion of the marginal zone with infiltration of interfollicular space. These B-cells were negative for CD3, CD5, CD23, EBV-LMP1, bcl-6, CD10, EMA, CD30, CD15, MUM-1, and positive for bcl-2 and IgD. A CD21/ CD23/ fascin immunostain showed an expanded and disrupted follicular dendritic cell meshwork. Ki-67 highlighted residual follicular polarisation and a low proliferation rate in the interfollicular areas. Based on these pathohistological findings it was concluded that LN likely represent reactive follicular hyperplasia with atypical marginal zone hyperplasia or possible PNMZL, with APSTRAKTI 95 MATERIA MEDICA • Vol. 34 • Issue 1, suplement 1 • april 2018. recommendation of polymerase chain reaction (PCR) analysis of clonality. Additional IGH PCR analysis demonstrated biclonal heavy chain gene rearrangement. These findings were consistent with PNMZL. After consultation with members of International BFM study group for non-Hodgkin lymphomas, followup was recommended without any treatment. The patient has remained disease free for 22 months since diagnosis. Conclusion: We presented a rare case of PNMZL with morphological features of PTGC, but immunohistochemistry and additional PCR clonality analysis were crucial for final diagnosis. This case represents a diagnostic and therapeutic challenge because of their rarity in the pediatric population.

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.

Strano telo u disajnim putevima predstavlja životno ugrožavajuće stanje i zahteva urgentnu evaluaciju i lečenje. Prepoznavanje kliničke slike gušenja, anestezija i uklanjanje stranog tela u dečijem uzrastu predstavljaju veliki izazov za dečijeg anesteziologa i otorinolaringologa. U slučaju organskih stranih tela iritacija, inflamacija i bubrenje mogu dodatno komplikovati situaciju. Najuži deo disajnih puteva u deteta je subglotis i rigidni bronhoskop iritira ovo područje što može uzrokovati postoperativnu opstrukciju disajnog puta. Prikazujemo slučaj 13 mesečnog deteta koje je aspiriralo strano telo u levi bronh, kliničku sliku, preoperativnu pripremu, tehniku anestezije, tok rigidne bronhoskopije, kao i probleme sa kojima smo se susretali do izlečenja deteta.