Néoplasties intra-epitheliales basales "potentiellement sévéres" de la cavité buccale (profil clinico-biologique et évaluation du risque de transformation carcinomateuse)

Les néoplasies intra-épithéliales orales (NIEO) précèdent souvent les carcinomes épidermoïdes buccaux (CEB) qui posent un problème majeur de santé publique. Une meilleure connaissance de ces lésions devrait permettre de diagnostiquer les CEB à un stade précoce et d améliorer ainsi leur pronostic. Peu d études ont été réalisées sur les NIEO de grade 1. Nous nous sommes intéressés plus particulièrement à un sous-type de NIEO1 avec des atypies et une désorganisation architecturale marquées mais toujours localisées aux couches basales, que nous appelons NIEO basales potentiellement sévères (NIEOBPS). 34 patients ont été étudiés. 27 d entre eux ont présenté également des lésions de NIEO de grade 2-3 dans le temps ou l espace. Dans les 7 autres cas, les lésions de NIEOBPS étaient isolées. Alors que les NIEOBPS non isolées semblent survenir sur le même terrain que les CEB décrits dans la littérature, les NIEOBPS isolées seraient plutôt observées chez des femmes non alcoolo-tabagiques souvent atteintes de lichen plan buccal. Au cours du suivi, 9 CEB ont été diagnostiqués, dont 4 parmi les patients atteints de NIEOBPS isolées (4/7). L expression de la protéine p16 observée dans seulement 3 cas sur 34 était en faveur de lésions HPV-indépendantes. La NIEOBPS, en particulier isolée, semble présenter un risque élevé de transformation en CEB. Par analogie à ce qui a été décrit en pathologie vulvaire et pénienne, ces lésions ne devraient-elles pas être considérées comme des lésions de haut grade et leur dénomination modifiée, par exemple en NIEO différenciée ? De nouvelles études prospectives sont nécessaires afin de confirmer ces travaux préliminaires.PARIS6-Bibl.Pitié-Salpêtrie (751132101) / SudocSudocFranceF

Maladie du greffon contre l'hote (étude de la plasticité des cellules souches hématopoïétiques in situ)

PARIS7-Bibliothèque centrale (751132105) / SudocSudocFranceF

Exogenous lipoid pneumonia due to chronic occult aspiration in a patient with oesophageal colonic interposition

International audienceNo abstract availabl

Extracavitary tumor after primary effusion lymphoma: relapse or second distinct lymphoma?

International audienceHHV-8-associated solid lymphomas which develop in extracavitary sites during the course of primary effusion lymphoma (PEL) could represent the relapse of original PEL tumors in different anatomical sites, or newly occurring distinct HHV-8-associated lymphomas, such as multicentric Castleman disease-related microlymphomas. HHV-8 episome clonality might help identify which event takes place

Endothelial cell chimerism associated with graft rejection after human lung transplantation.

International audienceEndotheliitis is a major sign of graft rejection. Recipient-derived endothelial cells found in two series of liver and kidney transplants were related to graft rejection. Here, we assessed the presence and the number of chimeric endothelial cells in lung transplants, and their relation with graft rejection. In six males grafted with female lungs out of 193 lung transplantations, endothelial chimerism was studied by combined XY-fluorescent in situ hybridization with CD31 and CD45 immunostainings and blood group antigens. On samples graded according to the revised working formulation for lung allograft rejection, we found chimeric macrophages (73.1 to 87.2%) in all cases and chimeric endothelial cells (1.3 to 2.1%) in four patients. Another method using ABO blood group also showed endothelial cells positive for recipient-type blood group antigens in three patients. By both methods, presence of chimeric endothelial cells was related to pathological signs of acute rejection (P<0.05)

Case Report Lung Abnormalities after Dasatinib Treatment for Chronic Myeloid Leukemia A Case Series

Tyrosine kinase inhibitors have revolutionized the treatment of chronic myeloid leukemia and are increasingly used for other indications. Fluid retention, however, including pleural effusions, are a significant side effect of imatinib, the first-line treatment for chronic myeloid leukemia. We investigated pleural and pulmonary complications in patients treated with dasatinib, a novel multitargeted tyrosine kinase inhibitor, as part of clinical trial protocols. Of 40 patients who received dasatinib (70 mg twice daily) for imatinib resistance or intolerance, 9 (22.5%) developed dyspnea, cough, and chest pain. Of these nine patients, six had pleural effusions (all were exudates) and seven had lung parenchyma changes with either ground-glass or alveolar opacities and septal thickening (four patients had both pleural effusions and lung parenchyma changes). Lymphocytic accumulations were detected in pleural and bronchoalveolar lavage fluids in all patients except for one who presented with neutrophilic alveolitis. Pleural biopsies revealed lymphocytic infiltration in one patient and myeloid infiltration in another. After dasatinib interruption, lung manifestations resolved in all cases and did not recur in three of four patients when dasatinib was reintroduced at a lower dose (40 mg twice daily). Thus, lung physicians should be aware that lung manifestations, presumably related to an immune-mediated mechanism rather than fluid retention, may occur with dasatinib treatment

Genomic and functional impact of Trp53 inactivation in JAK2V617F myeloproliferative neoplasms

International audienceAbstract Classical myeloproliferative neoplasms (MPNs) are characterized by the proliferation of myeloid cells and the risk of transformation into myelofibrosis or acute myeloid leukemia (AML) and TP53 mutations in MPN patients are linked to AML. However, JAK2V617F has been reported to impact the TP53 response to DNA damage, suggesting potential overlapping role of TP53 inactivation in MPN. We established a mouse model showing that JAK2V617F/Vav-Cre/Trp53 −/− mice displayed a similar phenotype to JAK2V617F/Vav-Cre mice, but their proliferation was outcompeted in competitive grafts. RNA-Seq revealed that half of the genes affected by JAK2V617F were affected by p53-inactivation, including the interferon pathway. To validate this finding, mice were repopulated with a mixture of wild-type and JAK2V617F (or JAK2V617F/Vav-Cre/Trp53 −/− ) cells and treated with pegylated interferonα. JAK2V617F-reconstituted mice entered complete hematological remission, while JAK2V617F/Vav-Cre /Trp53 −/− -reconstituted mice did not, confirming that p53 loss induced interferon-α resistance. KEGG and Gene Ontology analyses of common deregulated genes showed that these genes were mainly implicated in cytokine response, proliferation, and leukemia evolution, illustrating that in this mouse model, the development of MPN is not affected by TP53 inactivation. Taken together, our results show that many genetic modifications induced by JAK2V617F are influenced by TP53, the MPN phenotype may not be. Trp53 loss alone is insufficient to induce rapid leukemic transformation in steady-state hematopoiesis in JAK2V617F MPN, and Trp53 loss may contribute to interferon resistance in MPN