First experiments with the negative ion source NIO1.

Neutral Beam Injectors (NBIs), which need to be strongly optimized in the perspective of DEMO reactor, request a thorough understanding of the negative ion source used and of the multi-beamlet optics. A relatively compact radio frequency (rf) ion source, named NIO1 (Negative Ion Optimization 1), with 9 beam apertures for a total H(-) current of 130 mA, 60 kV acceleration voltage, was installed at Consorzio RFX, including a high voltage deck and an X-ray shield, to provide a test bench for source optimizations for activities in support to the ITER NBI test facility. NIO1 status and plasma experiments both with air and with hydrogen as filling gas are described. Transition from a weak plasma to an inductively coupled plasma is clearly evident for the former gas and may be triggered by rising the rf power (over 0.5 kW) at low pressure (equal or below 2 Pa). Transition in hydrogen plasma requires more rf power (over 1.5 kW).

[Combined variable immunodeficiency with unusal features. A case report]. / Présentation atypique d'un déficit immun commun variable. À propos d'un cas.

INTRODUCTION: The association granulomatosis - combined variable immunodeficiency (CVID) - is well known from the clinicians. However, the association with a large granular lymphocyte (LGL) leukemia has not been yet reported. CASE REPORT: We report a 50-year-old woman, followed for CVID associated with a granulomatous disease. During the follow-up, the patient developed a granulomatous lymphocytic interstitiel lung disease (GLILD). Secondarily, she presented a LGL leukemia. CONCLUSION: To our knowledge, this is the first reported case of an association between CVID and LGL leukemia.

Pertinence of the Sysmex XE-5000™ parameters: rule of slide review in a context of 'normal' lymphocyte count (defined from control and mantle cell lymphoma blood specimens).

INTRODUCTION: As most hematology cell analyzers, the different parameters of Sysmex XE-5000™ are little informative in the qualitative analysis of lymphoid cells, and especially when the lymphocyte count is below 4 × 10(9) /L (i.e., 'normal'). The aim of our study was to investigate whether some parameters and/or 'flags' not routinely provided by this analyzer, but reachable by operator could be reliable to define rules of slide review in absence of common qualitative and quantitative alarms particularly in case of 'normal' lymphocyte count. METHODS: Blood samples from 13 mantle cell lymphoma fully annotated cases, and 180 control specimens were studied with Sysmex XE-5000™ analyzer. All cases did not present any anomalies in common quantitative and structural parameters. RESULTS: Using the method of area under the curve and ROC curve analysis, we described a novel threshold of alarm VAL_ABN LYMPH (≥40 instead of 100 defined by Sysmex), as well as a pertinent LyX threshold (≥89). The combination of these thresholds allowed defining a rule of slide review in context of 'normal' lymphocyte count. CONCLUSION: Among the parameters provided by the Sysmex XE-5000™ analyzer, the combination of the alarm VAL_ABN LYMPH and the LyX value, routinely available on a simple blood analysis appears particularly informative to trigger slide review in a context of 'normal' lymphocyte count with a good sensitivity (85%) to detect circulating lymphoma cells and with <1% of false positive results.

Splenic marginal zone B-cell lymphoma: a distinct clinicopathological and molecular entity. Recent advances in ontogeny and classification.

PURPOSE OF REVIEW: Indolent B-cell lymphomas that are supposed to derive from marginal zone encompass three distinct entities: extranodal marginal zone lymphoma (MZL) or mucosa-associated lymphatic tissue (MALT), nodal MZL (NMZL) and splenic MZL (SMZL). Although MALT lymphoma is well characterized and extensively studied at the clinical and molecular levels, SMZL and NMZL remain incompletely characterized. However, during the last years, the clinical and molecular heterogeneity of SMZL has been clarified. The recent 2008 WHO classification has maintained the distinction between the three diseases according to the organ where it arises and introduced a new provisional category of unclassified splenic lymphoma for overlapping entities, splenic diffuse red pulp lymphoma (SDRPL) and hairy cell leukemia-variant (HCL-V). RECENT FINDINGS: Recent findings in SMZL contributed to a better characterization, including the few cases associated with hepatitis C, the recurrence of 7q deletion and the possibility of CD5 expression. Furthermore, the peculiar pattern of immunoglobulin heavy chain genes mutations and the biased usage of immunoglobulin heavy chain variable region genes (IGHV)1-2 segment are suggestive of a T-independent antigen driven proliferation, at least at initial steps. This review will focus on recent findings and differential diagnosis with SDRPL and HCL-V. SUMMARY: The conjunction of morphologic, cytogenetic and clinical data has increased diagnosis reproducibility.

Relevance of a scoring system including CD11c expression in the identification of splenic diffuse red pulp small B-cell lymphoma (SRPL).

'Splenic red pulp lymphoma with numerous basophilic villous lymphocytes' (SRPL), recently described, is characterized by clinical, morphologic, immunologic, cytogenetic and molecular features distinct from SMZL/SLVL and HCL. In particular, the intensity of CD11c staining (expressed as fluorescence intensity -RFI-) in SRPL is significantly different from the RFI in SMZL/SLVL and HCL. Moreover the use of a scoring system based on the expression of CD11c, CD22, CD76, CD38 and CD27 appears to improve the differential diagnosis between SRPL and SMZL/SLVL and emphasizes that SRPL is an entity closed to but distinct from SMZL/SLVL.

A clinicopathological study of nodal marginal zone B-cell lymphoma. A report on 21 cases.

AIMS: To report the clinicopathological findings of 21 cases of primary nodal marginal zone B-cell lymphoma (NMZL). NMZL is a recently characterized lymphoma and few series have been published. METHODS AND RESULTS: The clinical data were characteristic of a disseminated disease at presentation: presence of peripheral and abdominal lymph nodes, bone marrow involvement (62%), disease stage III and IV (76%), elevated lactate dehydrogenase (LDH) (48%). Other features included peripheral blood involvement (23%), anaemia (24%), thrombocytopenia (10%) and presence of serum M component (33%), while the previously reported association with hepatitis C virus and cryoglobulinaemia was not found. Relapses were frequent but the majority of patients receiving chemotherapy had a good initial response. Morphological features were heterogeneous and there were some differences compared with other marginal zone B-cell lymphomas (MZL). Pure monocytoid B-cell lymphomas were rare (10%) but a minor component of monocytoid B cell was observed more frequently (23%). Plasmacytoid or plasmacytic differentiation was a very common feature (61%). Large cells and a high mitotic count were also frequent (57%). CONCLUSION: NMZL can be distinguished from splenic MZL and extranodal MZL by its aggressive morphology and disseminated disease at presentation.

Identification of circulating CD10 positive T cells in angioimmunoblastic T-cell lymphoma.

In most cases of lymphomas with blood dissemination, the careful cytological analysis of peripheral blood smears provides a rapid orientation to diagnosis, even if the final subtyping is achieved by histology and eventually other techniques. Here, we evaluated if the analysis of blood smears may suggest the blood dissemination of angioimmunoblastic T-cell lymphoma (AITL) and if CD10 expression on neoplastic T cells, as recently reported on AITL, may contribute to the diagnosis. In all, 11 lymph nodes and six peripheral blood samples from 12 patients with AITL were studied using four-colour flow cytometry associated to histological, cytological and molecular data. According to previous results, a fraction of T cells expressed CD10 in 10/11 lymph nodes. Interestingly, all blood smears showed atypical lymphoid cells and a fraction of T cells expressed CD10 with a mean percentage of 18.75% (range 5.00-47.00%), regardless of lymphocytosis level and of rate of CD10 T cells in corresponding lymph node. In contrast, in all control samples (100), none CD10-positive T cell was identified. This is to our knowledge the first description of circulating CD10 neoplastic T cells in AITL. Therefore, they ought to be explored in further studies when aggressive lymphoma, in particular with lymphopenia and circulating atypical cells, is suspected.

Cytogenetic analysis delineates a spectrum of chromosomal changes that can distinguish non-MALT marginal zone B-cell lymphomas among mature B-cell entities: a description of 103 cases.

The purpose of this study was to document the frequency and distribution of karyotypic changes present at diagnosis in 103 non-MALT marginal zone cell lymphoma (MZL) patients. This cytogenetic analysis of a large cohort extends previous observations and allows the identification of new cytogenetic features. Abnormalities identified in more than 15% of patients included +3/+3q (37%), 7q deletions (31%), +18/+18q (28%), 6q deletions (19%), +12/+12q (15%) and 8p deletions (15%). Trisomy 3/3q, 7q deletions, +18 and +12 were seen in different combinations in more than 30% of patients in comparison to 2% in lymphocytic lymphomas/chronic lymphocytic leukemias, 1% in mantle cell lymphomas and 7% in follicular lymphomas. The marked propensity of these abnormalities to be recurrently associated with the same tumoral clone of individual karyotypes allowed the delineation of a cytogenetic profile that may help to distinguish non-MALT MZL among other mature B-cell neoplasms. If +3/3q, +12/+12q, and 6q, 7q and 8p deletions were significantly associated with clinical prognostic factors previously reported to influence survival and time to progression, patients displaying these abnormalities did not experience a significantly shorter time to progression.

Allele-specific binding to the -308 single nucleotide polymorphism site in the tumour necrosis factor-alpha promoter.

Single nucleotide polymorphisms in the tumour necrosis factor alpha (TNF-alpha) promoter region may modulate TNF-alpha gene transcriptional activity by modifying the binding of transcription factors. Here we confirm that a specific DNA complex binds preferentially the variant TNF2 allele in various cell types and demonstrate that activating protein (AP)-2, myeloid zinc finger gene 1 (MZF-1) and Sp1 are not involved in this complex.

Higher LPS-stimulated TNF-alpha mRNA levels in peripheral blood mononuclear cells from non-Hodgkin's lymphoma patients.

OBJECTIVE: The aim of the present study was to investigate the capacity of normal immune blood cells from non-Hodgkin's lymphoma patients to produce tumor necrosis factor (TNF) after lipopolysaccharide (LPS) stimulation and the influence of the TNF (-308) polymorphism in this production. MATERIALS AND METHODS: A whole peripheral blood cell assay was utilized following LPS stimulation. At selected incubation times, supernatants were harvested for protein dosage, while mRNA was extracted and reverse-transcribed. The amount of TNF mRNA was quantified using real-time quantitative polymerase chain reaction (PCR) and genomic DNA was typed for TNF (-308) polymorphism. RESULTS: Upon LPS stimulation, TNF-secreted protein was slightly but not significantly increased in lymphoma patients when compared to controls. In contrast, the relative TNF mRNA amounts were significantly higher in lymphoma patients at 30 minutes (median 27.75 vs. 16.00; Mann-Whitney U-test p < 0.05), at 4 hours (52.00 vs. 31.00; p < 0.05), and at 24 hours (19.50 vs. 9.00; p < 0.05). In addition, patients carrying the variant TNF2 allele had higher relative TNF mRNA levels than TNF1 homozygotes (p = 0.02). CONCLUSION: The LPS-induced TNF mRNA levels are higher in peripheral blood cells (PBC) from lymphoma patients than from controls, while TNF protein secretion is not strikingly different. Altered regulation of TNF mRNA translation or TNF protein secretion may contribute to these observations. Taken together, an increased susceptibility for TNF gene transcription after LPS stimulation was observed in PBC (mainly in monocytes) from lymphoma patients, and especially those carrying the TNF2 allele.

Non-MALT marginal zone B-cell lymphomas: a description of clinical presentation and outcome in 124 patients.

Marginal zone B-cell lymphoma (MZL) is a recently individualized lymphoma that encompasses mucosa-associated lymphoid tissue (MALT) lymphoma, splenic lymphoma with or without villous lymphocytes, and nodal lymphoma with or without monocytoid B-cells. If the clinical description and outcome of MALT lymphoma is well known, this is not the case for the other subtypes. We reviewed 124 patients presenting non-MALT MZL treated in our department to describe the morphologic and clinical presentation and the outcome of these lymphomas. Four clinical subtypes were observed: splenic, 59 patients; nodal, 37 patients; disseminated (splenic and nodal), 20 patients; and leukemic (not splenic nor nodal), 8 patients. These lymphomas were usually CD5-, CD10-, CD23-, and CD43-, but the detection of one or, rarely, two of these antigens may be observed. Bone marrow and blood infiltrations were frequent, except in the nodal subtype, but these locations were not associated with a poorer outcome. Splenic and leukemic subtypes were associated with a median time to progression (TTP) longer than 5 years, even in the absence of treatment or of complete response to therapy. Nodal and disseminated subtypes were associated with a median TTP of 1 year. However, in all these subtypes, survival was good with a median survival of 9 years, allowing these lymphomas to be classified as indolent. Because of the retrospective nature of this analysis, no conclusion may be drawn on the therapeutic aspects, but conservative treatments seem recommended for leukemic and splenic subtypes. (Blood. 2000;95:1950-1956)