EWSR1 rearrangement in papillary thyroid microcarcinoma is related to classic morphology and the presence of small-cell phenotype.

The EWSR1 rearrangements with unknown genes were detected in a high percentage of classic variants of papillary thyroid carcinoma. The small-cell carcinoma of the thyroid with Ewing family tumor elements (CEFTE) typically presents with EWSR1-FLI1 rearrangement suggesting the possible role of EWSR-FLI1 translocation in the loss of thyroid differentiation and acquisition of a small-cell phenotype. In order to determine the frequency and association of EWSR1 rearrangements, particularly the EWSR1-FLI1 fusion with clinicopathological features of papillary thyroid microcarcinoma (m-PTC) and the presence of small cells, we analyzed a series of 99 m-PTCs using the fluorescence in situ hybridization method.  Ninety cases (90.9%) of m-PTC were positive for small cells. This group of m-PTC has shown more often invasive growth, lymphatics invasion, and moderate/extended intratumoral fibrosis. Three cases out of 99 were inconclusive for EWSR1 rearrangement. Eighty-nine (92.7%) and twenty-seven (28.1%) out of 96 m-PTC cases were positive for EWSR1 rearrangement and EWSR1-FLI1 fusion, respectively. m-PTC with classical architectural pattern presented more frequently with EWSR1 rearrangement relative to m-PTC with other patterns (p = 0.005). Other clinicopathological features were not related to the presence of EWSR1 rearrangement or EWSR1-FLI1 fusion. The percentage of small cells present significantly correlated with the percentage of cells positive for EWSR1-FLI1 fusion (p = 0.05) and EWSR1 rearrangement (p <0.001). EWSR1-FLI1 fusion is not rare in m-PTC and it is associated with the acquisition of small-cell phenotype. The EWSR1 gene rearrangement is a frequent event in m-PTC and is related to the classical pattern of m-PTC.

Angiogenic and lymphangiogenic profiles in histological variants of papillary thyroid carcinoma.

INTRODUCTION: Papillary thyroid carcinoma (PTC) is a well­differentiated tumor that occurs in several histological variants whose biological behaviors remain unclear. Angiogenesis and lymphangiogenesis are critical processes that enable tumor progression. OBJECTIVES: The aim of this study was to evaluate the angiogenic and lymphangiogenic phenotypes of PTC, considering the differences between histological variants. PATIENTS AND METHODS: Angiogenic and lymphangiogenic profiles were analyzed by determining microvascular density (MVD) and lymphatic vessel density (LVD) in 73 cases of PTC, using immunohistochemistry. To assess the biological markers involved in blood and lymph vessel formation, the expression of vascular endothelial growth factor (VEGF), cyclooxygenase 2 (COX­2), and p27kip1 (p27) was determined. RESULTS: MVD was significantly higher in patients with high­risk PTC and in those with local extrathyroidal and vascular invasion. Positive VEGF expression was strongly associated with high MVD and age­related tumor enlargement. The presence of lymph vessel invasion was associated with the expression of either VEGF or COX­2. The analysis of angiogenesis and lymphangiogenesis in different histological variants of PTC revealed elevated LVD rather than MVD in the follicular variant of PTC (FV­PTC).Lower MVD was observed in FV­PTC relative to the classic variant of PTC (CV­PTC). The frequency of VEGF­positive tumors was higher in CV­PTC than in FV­PTC. A significant association between COX­2 and p27 expression was observed in FV­PTC but not in CV­PTC. CONCLUSIONS: These results suggest that VEGF, COX­2, and p27 may be important biological markers that determine the angiogenic and lymphangiogenic potentials of PTC, particularly between the follicular and classic variants.

Pseudomesotheliomatous carcinoma of the lung.

Introduction: Pseudomesotheliomatous lung carcinoma is a special, rare entity characterized by large pleural growth and minor invasion of lung tissue. Clinically, radiologically, macroscopically and even histologically this tumor can be misdiagnosed as malignant pleural carcinoma. Case report: We represent a 64-year-old male patient, former smoker. Due to difficulties in the form of dry cough, feeling of dis-comfort and pain in the right hemithorax, fatigue, heavy breathing, sweating, fever up to 39.6°C the patient was treated as with combined antibiotic therapy (macrolides, cephalosporins and penicillin), but without improving of his condition. Chest radiography showed a shadow of pleural effusion by the height of the front end of the third right rib. Chest MSCT showed the extremely thickened pleura apically and to the posterior along the upper right lobe in addition to existence of massive pleural effusion. Subpleural condensation of parenchyma ranging about 30 mm was described in the upper right lobe. Cytological analysis of the pleural effusion showed the presence of malignant cells impossible to differentiate whether they were metastasis of adenocarcinoma or malignant pleural mesothelioma. By histochemical and immunohistohemical analyses of a pleural sample, pseudomesotheliomataus lung adenocarcinoma was diagnosed. Conclusion: Pseudomesotheliomataus carcinoma of the lungs can be a diagnostic problem. Its diagnosis is based on recognition of histopathological characteristics which enable its discernment from the epithelial variant of malignant pleural mesothelioma.

Exercise-induced bronchoconstriction and non-specific airway hyperreactivity in patients suffering from bronchial asthma.

BACKGROUND/AIM: Physical activity is a common stimulus of asthmatic symptoms manifestation. Airway hyperreactivity is a predisposing cause of exercise induced bronchial obstruction, diagnosed by histamine inhalation. The aim of this study was to determine the relation between the amounts of histamine needed to induce non-specific airway hyperreactivity and exercise-induced bronchial obstruction. METHODS: This randomized cross-over study included 160 male patients (age 19-27 years) suffering from bronchial asthma who showed positive results as the reaction after the histamine bronchial provocation test. Histamine concentrations were in a range of 0.03 to 4 mg/mL. Each patient participated in the exercise stress test conducted on a conveyor belt. The results of the exercise stress test were considered positive if the FEV1 level dropped by at least 15% from its initial value, 5-10 minutes after the test. RESULTS: All the patients showed positive results as the reaction after the histamine bronchial provocation test, while 50 of them showed positive results after the exercise-induced stress test. There was a statistically highly significant difference in administrated histamine concentrations between the group of patients that had positive results on exercise stress test and those who did not (1 mg/mL vs 0.5 mg/mL; U = 1678; p < 0.01). Also, there was a statistically significant difference concerning the frequency of the positive results regarding histamine concentration after induced stress test (chi2 = 10.885; p = 0.001). Among the patients with positive results, there was a statistically highly significant number of patients with bronchial obstruction induced by less than 2 mg/mL of histamine (p < 0.01). A statistically significant relation between the amount of histamine needed to induce bronchial obstruction and the results of the exercise stress test (p < 0.01) was also observed after the testing. CONCLUSION: In the group of patients with positive results after the exercise-induced stress test, there were significantly more patients with positive results to non-specific bronchial provocation test with lower histamine concentrations. Histamine concentrations needed to induce non-specific hyperreactivity of asthmatic airway were shown to be related to the reactivity to physical effort.

Myeloma multiplex with pulmonary dissemination.

INTRODUCTION: Multiple myeloma is a hemathological malignancy characterized by the clonal proliferation of plasma cells in the bone the marrow. Extramedullary dissemination of multiple myeloma is uncommon. In several cases only, the multiple myeloma malignant plasma cells had diseminated to the lung parenchyma. CASE REPORT: We presented a case of multiple myeloma with lung plasmacytoma, in a 79 year-old patient, hospitalized for febrility and infiltrative mass in the right lung. Two months before the patient was admitted, because of developing terminal renal failure, hemodialysis treatment had started three times a week. Since then, the patient was oliguric, but because of febrility and hemoptysis that appeared, at first he was treated with dual antibiotic therapy which resulted in temporary improvement of his general condition, but pleural effusion remained. After thoracocentesis, followed by myelogram, the multiple myeloma diagnosis was established. CONCLUSION: In patients of middle and older age, with general weakness, exhaustion, loss of weight, renal failure which progresses to the end stage rapidly, if symptoms of respiratory tract occur, consider this uncommon disease--extramedullary dissemination of multiple myeloma.

Disseminated typical bronchial carcinoid tumor.

INTRODUCTION: Bronchial carcinoids belong to a rare type of lung tumors. If they do not expose outstanding neuroendocrine activity, they develop without clearly visible symptoms. They are often detected during a routine examination. According to their clinical pathological features, they are divided into typical and atypical tumors. Typical bronchial carcinoids metastasize to distant organs very rarely. Localized forms are effectively treated by surgery. The methods of conservative treatment should be applied in other cases. CASE REPORT: We presented a 65-year-old patient with carcinoid lung tumor detected by a routine examination. Additional analysis (chest X-ray, computed tomography of the chest, ultrasound of the abdomen, skeletal scintigraphy, bronhoscopy, histopathological analysis of the bioptate of bronchial tumor, as well as bronchial brushing cytology and immunohistochemical staining performed with markers specific for neuroendocrine tumor) proved a morphologically typical lung carcinoid with dissemination to the liver and skeletal system, which is very rarely found in typical carcinoids. CONCLUSION: The presented case with carcinoid used to be showed morphological and pathohistological characteristics of typical bronchial carcinoid. With its metastasis to the liver and skeletal system it demonstrated unusual clinical course that used to be considered as rare phenomenon. Due to its frequent asymptomatic course and varied manifestation, bronchial carcinoid could be considered as a diagnostic challenge requiring a multidisciplinary approach.

[Epithelioid vascular tumor]. / Epiteloidni vaskularni tumor.

Epithelioid vascular tumors are neoplasms formed by endothelial cells, morphologically similar to epithelial cells. Morphological shape of the cells in this tumors varies from benign to malignant forms, causing the diverse biological potential of the tumors. This case-report presents immunophenotypically interesting epithelioid vascular tumor of the upper vena cava manifested in thrombotic complications. It is characterized by solid growth of tumor cells and the attempt of forming vascular channels. According to immunophenotype, tumor cells corresponded to endothelial cells with low proliferative potential and vasoformative capability of forming intracellular lumina. For that reason this tumor manifested similarity with epithelioid hemangioendothelioma. However, it differentiated from the hemangioendothelioma by benign cytomorphological characteristics of tumor cells, absence of pathological mitoses, more intensive inflammatory infiltrate with eosinophylia and good tissue control, of tumor growth because of the presence of pericites. According to histological features and histochemical analyses the diagnosis of this tumor was established as an intravascular, solid, epithelioid hemangioma.

[Umbilical metastasis (Sister Mary Joseph's nodule) diagnosed by fine-needle aspiration]. / Umbilikusna metastaza--cvor sestre Meri Dzozef dijagnostikovana aspiracijom tankom iglom.

Sister Mary Joseph's nodule is the eponym for metastatic involvement of the umbilicus. This less common entity is the sign of disseminated malignant disease, mainly of digestive and gynecologic origin, and is associated with a poor prognosis. A case of Sister Mary Joseph's nodule in a 76-year-old woman in whom the umbilical metastasis was the first sign of malignant disease in presented. The diagnosis of metastatic adenocarcinoma was established by fine needle aspiration cytology of the umbilical nodule. Radiological and ultrasonographic investigation disclosed carcinoma of the gallbladder with pancreas, stomach, and colon invasion as well as peritoneal dissemination. The diagnosis was confirmed by exploratory laparatomy and histological examination of the excised umbilical nodule.

[Diagnosis of multiple myeloma based on the material obtained by fine needle aspiration biopsy of the lungs]. / Dijagnoza multiplog mijeloma na osnovu materijala dobijenog perkutanom iglenom biopsijom pluca.

The patient presented in this paper was admitted to the hospital for the evaluation of radiologically revealed shadow in both lungs. In the course of diagnostic procedures, fine needle aspiration biopsy of the intrathoracic mass was performed. Cytologic analysis of the smear was performed because of clinical suspicion of plasma cell proliferative disease that was confirmed by bone marrow aspiration. Thus, the cytologic finding of intrathoracic lesion preceded the diagnosis of multiple myeloma.

[Cytologic features of ameloblastoma]. / Citoloska slika ameloblastoma.

Ameloblastoma is a rare tumor of the jaw arising from odontogenic epithelium. There are sparse reports in the literature concerning cytologic features of this tumor. This paper presents two cases of ameloblastoma, diagnosed by imprint cytology and confirmed histopathologically. The imprints were hypercellular, with single cells and the groups of basaloid and polygonal squamous cells with huge vacuoles in cytoplasm. Stellate and fusiform cells were found in the background of the preparation. These morphologic parameters were sufficient for the cytologic diagnosis of ameloblastoma.

[Importance of cytologic examination of urine in the diagnosis of renal transplant function disorders]. / Znacaj citoloskog pregleda urina u dijagnostici poremecaja funkcije transplantovanog bubrega.

BACKGROUND: This paper presents our experience with cytologic examination of urine in diagnosing renal allograft dysfunction. METHODS: The study group included 23 patients with renal allograft dysfunction, selected from 56 patients who underwent renal transplantation. Etiologic diagnosis was made according to the clinical picture, histological findings during allograft biopsy, and cytologic examination of urine. Urine sediment was obtained in cytocentrifuge and was air dried and stained with May Grunwald Giemsa. RESULTS: Out of 23 patients with allograft dysfunction in 18 (78.3%) patient it was caused by acute rejection, and in 5 (8.9%) patients by allograft infarction, cyclosporine nephrotoxicity, acute tubular necrosis and chronic nephropathy. In eighteen patients (78.3%) cytologic examination of urine was pathologic, while in 16 (70%) clinical and histology findings coincided with urine cytology findings. Out of 18 patients with acute allograft rejection in 15 patients cytologic examination of urine coincided with acute rejection. Out of 7 patients with expressed cyclosporine nephrotoxicity, in 5 cytologic examination of urine confirmed the cause of allograft dysfunction, as well as in one of 2 patients with acute tubular necrosis. Cytologic examination of urine indicated parenchymal damage in 2 patients with recurrent disease (membranoproliferative and focal sclerosing glomerulonephritis). In 4 of 5 patients suffering from chronic rejection in a year's monitoring period, urine sediment periodically consisted of lymphocytes, neutrophilic leucocytes, monocyte/macrophages, tubular cells and cylindres, without the predominance of any cell type. In 3 patients allograft dysfunction was caused by infective agents (bacteria, fungus, cytomegalovirus). CONCLUSION: Cytologic examination of urine might be an alternative to histological in diagnosing acute allograft rejection and acute tubular necrosis or nephrototoxicity. Also it might indicate parenchymal disease while the importance of urine cytology in chronic allograft nephropathy needs to be investigated further.