Analyse clinique, immunohistochimique et génétique de 50 tumeurs épithéliales thymiques prises en charge au CHU de Rennes de 2000 à 2011

Rationnel. Les tumeurs éptihéliales thymiques (TET) font l'objet d'un intérêt croissant. Patients et méthodes. Les données cliniques des sujets atteints de TET de 2000 à 2011 au CHU de Rennes ont été étudiées. L'expression des protéines ERCC1, VEGF, VEGFR2, PDGFR et HER2 a été évaluée par immunohistochimie. Des mutations ont été recherchées sur les gènes PIK3CA NRAS, BRAF, HER2. Un réarrangement de ALK a été recherché par FISH. Résultats. Les caractéristiques cliniques des 50 TET retrouvées étaient comparables aux séries publiées et leur prise en charge conforme aux recommandations. Une expression supérieure du VEGF et du VEGF1 était observée dans les carcinomes thymiques. Une mutation de NRAS étaité identifiée dans un thymome B1. L'analyse de ALK ne retrouvait pas de réarrangement. La survie était supérieure en cas de myasthénie et de chirurgie. Conclusion. Si l'analyse de l'angiogenèse est une piste intéressante, le gène ALK ne semble pas impliqué dans la biologie des TET.RENNES1-BU Santé (352382103) / SudocSudocFranceF

Danazol Treatment for Telomere Diseases

International audienceBackground - Genetic defects in telomere maintenance and repair cause bone marrow failure, liver cirrhosis, and pulmonary fibrosis, and they increase susceptibility to cancer. Historically, androgens have been useful as treatment for marrow failure syndromes. In tissue culture and animal models, sex hormones regulate expression of the telomerase gene. Methods - In a phase 1-2 prospective study involving patients with telomere diseases, we administered the synthetic sex hormone danazol orally at a dose of 800 mg per day for a total of 24 months. The goal of treatment was the attenuation of accelerated telomere attrition, and the primary efficacy end point was a 20% reduction in the annual rate of telomere attrition measured at 24 months. The occurrence of toxic effects of treatment was the primary safety end point. Hematologic response to treatment at various time points was the secondary efficacy end point. Results - After 27 patients were enrolled, the study was halted early, because telomere attrition was reduced in all 12 patients who could be evaluated for the primary end point; in the intention-to-treat analysis, 12 of 27 patients (44%; 95% confidence interval [CI], 26 to 64) met the primary efficacy end point. Unexpectedly, almost all the patients (11 of 12, 92%) had a gain in telomere length at 24 months as compared with baseline (mean increase, 386 bp [95% CI, 178 to 593]); in exploratory analyses, similar increases were observed at 6 months (16 of 21 patients; mean increase, 175 bp [95% CI, 79 to 271]) and 12 months (16 of 18 patients; mean increase, 360 bp [95% CI, 209 to 512]). Hematologic responses occurred in 19 of 24 patients (79%) who could be evaluated at 3 months and in 10 of 12 patients (83%) who could be evaluated at 24 months. Known adverse effects of danazol--elevated liver-enzyme levels and muscle cramps--of grade 2 or less occurred in 41% and 33% of the patients, respectively. Conclusions - In our study, treatment with danazol led to telomere elongation in patients with telomere diseases. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT01441037.)

To be malnourished or not to be malnourished: that is the question!

International audienc

Haemodynamically proven pulmonary hypertension in a patient with GATA2 deficiency-associated pulmonary alveolar proteinosis and fibrosis

International audienceOver the past few years, genetics has significantly improved the understanding of interstitial lung diseases (ILD)..

Une cause rare de maladie kystique pulmonaire : maladie à dépôts de chaînes légères d'immunoglobuline. [An unusual cause of cystic lung disease: Light chain deposition disease].

International audienceINTRODUCTION: Light chain deposition disease is a rare clinical entity characterized by deposition of monoclonal immunoglobulin light chains in organs. The kidneys are almost always affected, while the lung manifestations that have been reported, including nodular or diffuse disease, especially cystic lesions, are unusual. CASE REPORT: We report the case of a 60-year-old man with a diffuse infiltrative lung disease characterized by numerous apical cysts. The diagnosis of light chain deposition cystic lung disease was obtained by surgical lung biopsy. Light chain deposits in the salivary glands were the only extrapulmonary manifestation. Despite 12 chemotherapy cycles, the patient's lung function and radiological appearances worsened. CONCLUSION: This is the fourth case describing a cystic lung disease due to light chain deposition in the literature. It highlights the need for comprehensive investigations so as not to miss this rare cause of cystic lung disease, which appears to be related to a primary pulmonary lymphoproliferative disorder. The only treatment that appears to be effective is lung transplantation

Sarcoïdose pulmonaire apparue sous étanercept [Pulmonary sarcoidosis developing during treatment with etanercept]

International audienceINTRODUCTION: TNF blockers are widely used to treat inflammatory rheumatic diseases and also in the treatment of extrapulmonary sarcoidosis. TNFα plays a major role in the development and persistence of sarcoid granulomata. However, recent studies have reported the involvement of anti-TNF therapies in the development of granulomatosis associated with the clinical and radiological features of sarcoidosis. CASE REPORT: A 54-years-old man with ankylosing spondylitis was treated with etanercept for two years. He was admitted with symptoms of bronchitis associated with radiological evidence of bilateral pulmonary nodules and a right upper lobe infiltrate. Anti-TNF therapy was stopped even though the patient had received 3 months of prophylactic treatment with rifampicin and isoniazid before starting etanercept. Bronchoalveolar lavage excluded infection, particularly tuberculosis. The chest CT-scan showed bilateral pulmonary nodules with peribronchovascular micronodules and enlarged mediastinal lymph nodes. Surgical lung biopsy was performed and revealed non-caseating granulomata. All the data were consistent with a diagnosis of pulmonary sarcoidosis. The patient remained symptomatic despite discontinuation of etanercept for ten months. Corticosteroids were then introduced, leading to a clinical, functional and radiological improvement. CONCLUSION: This case report underlines the importance of studying the pulmonary complications of TNF blockers. The first priority is to exclude tuberculosis but a diagnosis of sarcoid-like granulomatosis has to be considered. Twenty-three cases have been described in the literature to date

A case report of Covid-19 in an autoimmune pulmonary alveolar proteinosis: An association in tune with the times!

International audienceAutoimmune pulmonary alveolar proteinosis (PAP) is a rare disease characterized by the alveoli accumulation of surfactants proteins and lipids, which diagnosis is confirmed by the presence of GM-CSF antibodies in serum. PAP can be evoked when its characteristic images on chest computed-tomography (CT) are present: bilateral and multifocal ground-glass opacities and crazy-paving appearance. Patients with PAP are at an increased risk of opportunistic infections caused by Nocardia, mycobacteria and fungal pathogens due to impaired processing of pulmonary surfactant. We here report a typical case of newly diagnosed autoimmune PAP, with initial indication to realize a whole-lung lavage. Despite this treatment the patient presented a marked clinical worsening, with increasing need for oxygen and finally the need for mechanical ventilation. The chest CT was controlled and found to be typical of PAP, while the search for opportunistic infections remained negative. Finally, SARS-CoV-2 PCR was performed on bronchoalveolar lavage fluid, and was positive, whereas it had previously been negative twice. Our case report highlights the difficulty of distinguishing SARS-CoV-2 infection in the context of PAP, as the chest CT features are similar. We believe that a SARS-CoV-2 RT-PCR should be systematically realized in case of respiratory deterioration in PAP patients

Absence de récidive sous adalimumab, chez une patiente ayant présenté un asthme induit par l’infliximab

National audienceIntroduction Les cas d’asthmes induits par les anti-TNF-α sont rares, et il n’a jamais été décrit de tentative de réintroduction d’une molécule de même classe. Il n’existe pas de recommandations concernant la conduite à tenir dans ces situations. Observation Nous rapportons le cas d’une femme de 45 ans, non-fumeuse, sans antécédent personnel d’asthme, qui était atteinte d’une maladie de Crohn depuis l’adolescence. En 2009, elle a été traitée par infliximab. La réponse digestive a été rapidement efficace, cependant après 4 semaines de traitement, elle commençait à présenter une toux sèche associée à une dyspnée inhabituelle. Ces symptômes évocateurs d’hyperréactivité bronchique s’aggravèrent progressivement, et les explorations fonctionnelles respiratoires confirmèrent le diagnostic d’asthme. Malgré des traitements adaptés, la sévérité de la situation imposa l’arrêt de l’infliximab. L’asthme s’est alors amélioré, mais en raison de l’atteinte digestive un nouveau traitement dut être débuté : l’adalimumab, sans rechute d’asthme à ce jour. Conclusion Ce cas clinique met en évidence la possibilité de réintroduire un nouvel anti-TNF-α après un premier épisode d’asthme induit par cette classe médicamenteuse. Cette option pourrait être extrêmement utile chez les patients présentant des atteintes sévères (polyarthrite rhumatoïde, maladies inflammatoires chroniques de l’intestin) en l’absence d’alternative thérapeutiqu

Le cancer bronchique de la femme enceinte : prise en charge diagnostique et thérapeutique en 2012. [Diagnosis and management of lung cancer during pregnancy].

International audienceThe incidence of lung cancer during pregnancy is very low, but it is becoming more frequent in industrialized countries both because of the increase in smoking in young women and because women are becoming pregnant later in life. Usually, the cancer has a poor prognosis due to the presence of metastatic disease at the time of diagnosis. Diagnosis and management are delicate, and should deal with the gestational age, the maternal prognosis, the fetal toxicity of treatments, but also with the worsening of maternal prognosis and the risk of neoplastic cells being transmitted to the fetus in case of delayed treatment. Psychological and ethical considerations complicate the decision process. We present a review of the epidemiology, clinical characteristics, management, and prognosis concerning lung cancer during pregnancy. Finally, it is important to remember that young women with lung cancer should be advised to use a reliable form of contraception

Syndrome de détresse respiratoire aiguë sur hémorragie intra-alvéolaire révélant une vascularite. [Acute respiratory distress syndrome related to intra-alveolar hemorrhage revealing a vasculitis].

International audienceIntra-alveolar hemorrhage (IAH) could be revealed by acute respiratory failure. The classic association of hemoptysis - anemia - radiological infiltrates is suggestive and has to be confirmed by broncho-alveolar lavage with Golde score. Etiologies included immune and non-immune diseases, with specific treatment for each. We report a case of IAH revealed by acute respiratory distress syndrome and anemia (3 g/dL), related to pulmonary and cerebral vasculitis without renal involvement. The patient was efficiently treated with corticosteroids and cyclophosphamide. This case highlights the critical role of BAL cytological analysis with Golde score, and the need for a rapid and accurate diagnosis in order to guide specific treatment. If histology is needed, renal biopsy even without renal involvement, or surgical lung biopsy is possible