Lymphome B diffus à grandes cellules de morphologie anaplasique

International audienceLes lymphomes B diffus de morphologie anaplasique sont des entités remarquables appartenant à la catégorie des lymphomes B diffus à grandes cellules et non à celle des lymphomes anaplasiques. Leurs caractéristiques histologiques sont celles d'une tumeur à cellules pléomorphes, nécessitant d'éliminer différents diagnostics comme celui d'une métastase d'un mélanome, d'une tumeur germinale ou encore d'un sarcome. Nous rapportons ici le cas d'une patiente de 64 ans ayant présenté une atteinte ganglionnaire aortico-cave en insistant sur les caractéristiques histologiques et immunohistochimiques de ce lymphome

Regulation of MMP/TIMP balance as therapeutic target in pulmonary diseases

International audienceMatrix metalloproteinases (MMPs) are a family of zinc endopeptidases, regulated by endogenous tissue inhibitors (TIMPs) and inducer (EMMPRIN). The demonstration of a functional role of MMPs in pulmonary diseases raises the possibility of therapeutic intervention targeting MMP/TIMP balance to prevent pathological processes

Age-related Epstein-Barr virus-associated B-cell lymphoproliferative disorders in elderly white patients.

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Increased extracellular matrix metalloproteinase inducer (EMMPRIN) expression in pulmonary fibrosis.

International audienceExtracellular matrix metalloproteinase inducer (EMMPRIN) was examined on bronchoalveolar lavage fluids (BALFs) and lung tissue from patients with fibrosis (usual interstitial pneumonia-idiopathic pulmonary fibrosis [UIP-IPF], n = 15; diffuse parenchymal lung diseases without IPF characteristics on computerized tomography scan, n = 8) and without fibrosis (n = 6). In UIP-IPF, EMMPRIN staining was increased in areas of fibrosis, mainly in macrophages and in epithelial cells. EMMPRIN was also found in the extracellular medium with significant levels in patients with lung fibrosis compared to subjects without fibrosis. Moreover, macrophages from patients with lung fibrosis spontaneously produce EMMPRIN. These findings show that EMMPRIN is increased in lung fibrosis

Indications des antifongiques systémiques, spécialité par spécialité

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Human mesenchymal stem cells isolated from bone marrow and lymphoid organs support tumor B-cell growth: role of stromal cells in follicular lymphoma pathogenesis.

International audienceAccumulating evidence indicates that the cellular microenvironment plays a key role in follicular lymphoma (FL) pathogenesis, both within tumor lymph nodes (LNs) and in infiltrated bone marrow where ectopic LN-like reticular cells are integrated within malignant B-cell nodular aggregates. In normal secondary lymphoid organs, specific stromal cell subsets provide a highly specialized microenvironment that supports immune response. In particular, fibroblastic reticular cells (FRCs) mediate immune cell migration, adhesion, and reciprocal interactions. The role of FRCs and their postulated progenitors, that is, bone marrow mesenchymal stem cells (MSCs), in FL remains unexplored. In this study, we investigated the relationships between FRCs and MSCs and their capacity to sustain malignant B-cell growth. Our findings strongly suggest that secondary lymphoid organs contain MSCs able to give rise to adipocytes, chondrocytes, osteoblasts, as well as fully functional B-cell supportive FRCs. In vitro, bone marrow-derived MSCs acquire a complete FRC phenotype in response to a combination of tumor necrosis factor-alpha and lymphotoxin-alpha1beta2. Moreover, MSCs recruit primary FL cells that, in turn, trigger their differentiation into FRCs, making them able to support malignant B-cell survival. Altogether, these new insights into the cross talk between lymphoma cells and their microenvironment could offer original therapeutic strategies

¹³¹I-labeled lipiodol-induced interstitial pneumonia: a series of 15 cases.

International audienceBACKGROUND: The drug (131)I-labeled lipiodol is used as internal radiotherapy for unresectable hepatocellular carcinoma. Although the drug was considered safe during preapproval studies, we observed several cases of interstitial pneumonia following its administration. METHODS: Cases were retrospectively identified through the drug safety unit database of Rennes University Hospital. RESULTS: From 1994 to 2009, interstitial pneumonia developed in 15 patients following (131)I-labeled lipiodol administration, with an estimated prevalence of 15.5 cases (95% CI, 7.7-23.2) per 1,000 treated patients. Mean age of the patients was 60 ± 8 years, and the male to female ratio was 6.5:1. All patients had cirrhosis, mainly related to long-term alcohol intoxication (n = 12). Most (n = 10) cases occurred after the second (131)I-labeled lipiodol injection. The median delay between last (131)I-labeled lipiodol administration and first respiratory symptoms was 30 days (interquartile range, 16.5-45 days). All patients presented with shortness of breath. Physical examination mostly revealed fever (n = 11) and bilateral crackles (n = 12). Chest CT scan showed bilateral ground-glass opacities (n = 8) with septal thickening, retraction, or both (n = 8). BAL (n = 7) was remarkable for increased neutrophils (n = 4) or CD8(+) T cell count (n = 3). Despite corticosteroids, 12 (80%) patients died, mostly of untractable respiratory failure (n = 9). Median delay between last (131)I-labeled lipiodol injection and death was 63 days (interquartile range, 34-129 days). CONCLUSIONS: Interstitial pneumonia may be a serious and not uncommon complication of (131)I-labeled lipiodol administration

COX-2 independent effects of Celecoxib sensitize Lymphoma B cells to TRAIL-mediated apoptosis.

4 supplemental figures and supplemental methodsInternational audiencePURPOSE: Despite therapeutic advances, Non-Hodgkin lymphomas (NHL) remain incurable. They form a group of neoplasms strongly dependent on their inflammatory microenvironment, which plays an important supportive role in tumor B-cell survival and in the resistance to anti-tumor immune response. New therapies must consider both tumor cells and their surrounding microenvironment EXPERIMENTAL DESIGN: Stromal cells, derived from bone marrow or lymph nodes, and B cells from follicular lymphoma patients were co-cultured or cultured alone with Celecoxib treatment, a non-steroidal anti-inflammatory drug and/or TRAIL, a promising cytotoxic molecule for cancer therapy. RESULTS: In this study, we show that follicular lymphoma (FL) stromal cells produce large amounts of PGE2. This production is abrogated after Celecoxib treatment, targeting the COX-2 isoenzyme involved in PGE2 synthesis. Furthermore, we demonstrate that Celecoxib increases apoptosis in NHL B-cell lines and in primary FL B-cells co-cultured with stromal cells, but independently of the PGE2/COX-2 axis. Finally, Celecoxib increases the apoptotic activity of TRAIL. We provide evidence that Celecoxib affects proliferation and sensitizes NHL B-cell lines to apoptosis through COX-2 independent effects by slowing down the cell cycle and decreasing the expression of survival proteins, such as Mcl-1. CONCLUSIONS: These data suggest new potent strategies for NHL therapy combining drugs targeting both tumour B cells and survival signals provided by the tumor microenvironment

T-cell lymphoid aggregates in bone marrow after rituximab therapy for B-cell follicular lymphoma: a marker of therapeutic efficacy?

International audienceRituximab, an anti-CD20 monoclonal antibody, is widely used in the treatment of B-cell lymphoma. Some reports have outlined histologic modifications in bone marrow specimens from patients treated with this antibody, notably the presence of CD3(+) lymphoid aggregates morphologically mimicking residual lymphoma. To gain insight into the significance of such infiltrates, serial BM trephines obtained in 39 patients with B-cell follicular lymphoma treated by rituximab and enrolled in the GOELAMS-GELA intergroup FL2000 protocol were reexamined. The 39 patients were 22 women and 17 men with a median age of 50 years (range, 29-75 years). All pretreatment bone marrow biopsies showed CD20(+) lymphomatous cells. A second biopsy was obtained between 30 and 100 days after the last rituximab injection: 19 (48%) were morphologically diagnosed as negative (no lymphoid infiltrates or only minor lymphoid aggregates) and 20 (51%) as positive because of persistent lymphoid nodules. After immunohistochemical analysis, 13 (33%) cases were reinterpreted as false-positive because of the complete absence of CD20(+) cells, with the lymphoid nodules consisting of CD3(+) and CD5(+) T cells. Most of them also expressed CD4(+), whereas only a few CD8(+) cells were present. Among these 13 false-positive cases, 12 were BCL2-IGH polymerase chain reaction-negative in the bone marrow aspirate at the time of biopsy. The 13th case turned out to be negative in the 18th-month bone marrow aspirate. In all of these cases, lymphoid aggregates had disappeared on bone marrow biopsies performed 18 months after treatment. After a mean follow-up of 4.5 years, 9 of 13 patients were in remission as compared with only 2 among the 7 patients with postrituximab persistent CD20(+) lymphomatous cells. There was no statistically significant difference between this false-positive group of patients and that with negative postrituximab bone marrow regarding sex, age, medullar involvement pattern before treatment, delay between rituximab treatment, and molecular status. Interestingly, we noted a more favorable outcome (70% versus 52% remission) for the false-positive cases, suggesting that these T-cell reactions could be the hallmark of specific antitumoral immunity after rituximab treatment and should be properly investigated