Prognostic significance of clinical parameters and Epstein-Barr virus infection in non-endemic undifferentiated carcinoma of nasopharyngeal type: a Serbian report.

Undifferentiated carcinoma of nasopharyngeal type (UCNT) is very rare tumour in Serbia, like in most of the countries of Europe, with incidence less than 0.5 per 100,000 people per year. The aim of this study was to assess the presence of Epstein-Barr virus (EBV) in the UCNT of a non-endemic population in Serbia and identify the main clinical parameters that interfere with patients' survival rate. This study included 102 patients with UCNT who were diagnosed between 1996 and 2003. Biopsies were analysed for EBV-encoded RNA (EBER) by in situ hybridization of tumour tissue microarray. Of 102 patients, 76 were men and 26 were women with ages ranging between 18 and 82 years (median 52.5, mean 53.0±14.1). Survival rates were 80, 39 and 31% for one, three and five years, respectively. Ninety-three of 102 cases were EBER positive (92%). Factors with unfavourable prognostic values were age over 50 years at the time of diagnosis, advanced clinical stage, therapy other than chemoradiotherapy and EBER negative status. In regard to the clinical data, EBER expression in UCNT was shown to be a strong independent predictor of overall and progression-free survival. To our knowledge, the current report constitutes the largest European non-endemic series of UCNT samples from a single institution with correlation between survival and clinical parameters/EBER status.

Intravascular large B-cell lymphoma of central nervous system - a report of two cases and literature review.

Intravascular large B-cell lymphoma (IVL) is a rare form of diffuse large B cell lymphoma (DBCL) frequently presenting with skin and/or central nervous system (CNS) involvement. IVL involves CNS in 75 - 85% of patients and neurological symptoms include sensory and motor deficits or neuropathies, meningoradiculitis, paresthesia, hypostenia, aphasia, dysarthria, hemiparesis, seizures, transient visual loss, vertigo and impaired cognitive function. Neuroimaging discloses CNS involvement only in half of patients with neurological symptoms because there are no pathognomonic neuroradiological findings for IVL; ischemic foci are the most common presentation pattern and therefore vasculitis is the most common differential diagnosis. According to all mentioned data, diagnosis of CNS IVL requires a histopathological confirmation. Brain biopsy is absolutely indicated in patients with progressive neurological deterioration with unclear abnormalities in cerebral MR imaging. A general policy is that patients with IVL should be considered to have disseminated disease and should be treated with systemic chemotherapy. In younger patients with unfavorable features the high-dose chemotherapy with autologous stem cell transplantation should be used. Nevertheless, the course of IVL is rapidly progressive and ultimately fatal.

Primary extranodal marginal zone lymphoma of the uvea associated with massive diffuse epibulbar extension and focal infiltration of the optic nerve and meninges, clinically presented as uveitis masquerade syndrome: a case report.

To report a clinical, histopathological and immunohistochemical findings in a case of primary extranodal marginal zone lymphoma of the uvea associated with massive diffuse extraocular episcleral extension and focal infiltration of the optic nerve and meninges, clinically presented as longstanding uveitis masquerade syndrome. Interventional case reports with histopathological correlation. We describe a 80-year-old male patient with a 3-year history of chronic recurrent hypertensive (pan) uveitis associated with ocular pain, unresponsive to topical and systemic anti-inflammatory, immunosuppressive, antibiotic/antiviral and antiglaucomatous therapy. Because the eye was not salvageable with conservative treatment, enucleation of blind and painful eye was performed. Findings from histopathological and immunohistochemistry examination of the enucleated eye showed an extranodal marginal zone lymphoma of the uveal tract with massive epibulbar extension and optic nerve and meningeal penetration. During almost 3 years of clinical course and 6 months after the enucleation, there were no systemic manifestations of lymphoma, and patient has not required subsequent treatment. Primary lymphoproliferative lesions of the uvea, comprising the iris, ciliary body and choroid are very rare, associated with epibulbar extension extremely and with optic nerve and menigeal penetration exceptionally. Despite its rarity, primary lymphoma of the uvea should be included in the differential diagnosis particularly in older patients with longstanding recurrent uveitis.

Antiribosomal-P protein antibodies in a patient with systemic lupus erythematosus and non-Hodgkin's lymphoma: more than coincidental finding?

Patients with systemic lupus erythematosus (SLE) are at an increased risk of lymphomas, but mechanisms underlying this association are obscure. Recently, it has been shown that antiribosomal-P protein (anti-P) antibodies cross-react with phospholipids and enhance the production of cytokines which may influence lymphomagenesis. We report a 46-year-old woman who suffered high grade diffuse large B-cell non-Hodgkin's lymphoma (DLBCL) 28 months after the diagnosis of SLE. Development of lymphoma was associated with occurrence of serum monoclonal IgM, and pronounced prolongation of phospholipid-dependent clotting tests. Anti-P IgG antibodies were highly positive both on HEp-2 cells and in ELISA test. Anticardiolipin, anti-beta2 glycoprotein I, and antiprothrombin IgM antibodies have also been found in high concentrations. Complete remission of DLBCL and SLE, with normalisation of clotting tests, and disappearance of M component was achieved with administration of rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone. The progression of SLE to DLBCL associated with presence of anti-P antibodies has not been previously reported. This association may not be coincidental, but further investigations are required to confirm this hypothesis.

The concentration of TNF-alpha correlate with number of inflammatory cells and degree of vascularization in radicular cysts.

OBJECTIVE: To correlate values of tumor necrosis factor-alpha (TNF-alpha) depending on the count of inflammatory cells with degree of vascularization in cystic fluid of radicular cysts. MATERIAL AND METHODS: We investigated TNF-alpha concentration in 43 radicular cysts obtained from patients undergoing surgery, under local anaesthesia, and after aspiration of cystic fluid from non-ruptured cysts by enzyme-linked immunosorbent assay assay in respect of different clinical parameters as well as by histomorphometric analyses. RESULTS: Significantly higher concentration of TNF-alpha is associated with smaller radicular cysts, higher protein concentration in cystic fluid as well as with higher presence of inflammatory cells, and increased degree of vascularization in pericystic tissues and cyst wall thickness. CONCLUSIONS: We believe that determination of TNF-alpha in cystic fluid simultaneously with other parameters can be an additional parameter for clinical diagnosis of inflammed cysts.

Granulocytic sarcoma of the brain in a patient with acute myeloid leukemia.

Granulocytic sarcoma is extramedullary tumor composed of immature leukemic cells most frequently located in close proximity to bone, but it also can be found in the skin, breast, gastrointestinal tract, ovaries and brain. Granulocytic sarcoma may arise during the course of leukemia or precede its development in the bone marrow. The majority of reported cases of granulocytic sarcomas in acute myleoid leukemia have chromosome translocation t(8;21). We report a 46-year-old man with acute myeloid leukemia, type M2 involving the marrow and peripheral blood and chromosome t(8;21) who developed granulocytic sarcoma in the brain, as a first manifestation of relapse 6 months after complete remission was achieved. During a neurosurgical operation a cortically located tumour (3.5 x 5 cm) in the brain was partially removed. Histology showed tumor consisted of homogenous infiltrate of blasts, admixted with more mature haematopoietic cells. The blasts have large round to oval nuclei, delicate chromatin, one or more small well-defined nucleoli and scant basophilic cytoplasm. Immunohistochemistry showed that blast cells were myeloperoxidase positive, confirming the diagnosis of myeloblastic sarcoma in the brain. The patient died two days after surgery.

Rat thymic epithelial cells in culture constitutively secrete IL-1 and IL-6.

To study the in vitro interactions between rat thymic non-lymphoid cells and thymocytes, we established a system for long-term cultivation of thymic epithelial cells (TEC). TEC were cultivated and successfully propagated for over 8 months in RPMI 1640 medium containing 15% FCS, dexamethasone, insulin, epidermal growth factor, and poly-L-lysin as an adhesive matrix. Their epithelial nature has been confirmed using monoclonal anti-cytokeratin (CK) antibodies. More than 95% of these cells were reactive with K 8.13 and CK 8 mAbs, which are pan-epithelial markers for rat TEC in situ. An epithelial cell clone (TE-R 2.5) established from a long-term TEC culture was 100% reactive with these anti-CK antibodies. Phenotypic analysis of TEC cultures was performed by a large panel of mAbs reactive with a subset of rat TEC or CK polypeptides as well as UIex europaeus agglutinin I using a streptavidin-biotin immunofluorescence assay. Although the results obtained demonstrated phenotypic heterogeneity among these cells, most cultures, including the TE-R 2.5 clone, were of subcapsular/medullary phenotype. Medium conditioned by TEC cultures exhibited IL-1 and IL-6 activities when tested on D10S and B9 sensitive cell lines, respectively. Cytokine activities were neutralized (IL-1) or significantly inhibited (IL-6) by specific polyclonal antibodies. In addition, both anti-IL-1 and anti-IL-6 antibodies reacted with TEC in culture and epithelial (CK-positive) cells on thymic cryostat sections, indicating that thymic epithelium provides an important intrathymic source for molecules contributing to T cell activation.