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In 2019, only 1,790 occupational cancers were recognized, i.e., less than 1% of estimated occupational cancers. Our study aims to expand the methodology of a French cancer center to improve the detection and compensation of occupational bronchopulmonary cancers.Between November 2014 and December 2020, all patients diagnosed with primary bronchopulmonary cancer (including mesothelioma) received a free questionnaire (Curriculum Laboris) aimed at retracing their professional career but also socio-demographic data. After an initial analysis of the questionnaire, a consultation can be scheduled if exposures are suspected. They will then be confirmed or not, during a consultation of around 1hour 30minutes during which the patient's precise career path is explored.Among the 498 patient questionnaires received, 261 patients (52%) benefited from a consultation. Of all the patients seen in consultation, 198 (or 76%) had a proposal to declare an occupational disease. Among the 151 declarations of which the fate is known, 107 (i.e., 54% of the proposed declarations or 21% of the questionnaires concerning primary lung cancer) received an agreement of recognition.The massive underreporting of occupational cancers at present in France is a real public health problem. The two major issues in the recognition of occupational diseases are, on the one hand, reparation for the damage suffered by victims or their beneficiaries and, on the other hand, the adaptation of national prevention programs considering past, present and emerging.

Adenomatoid tumors are benign tumors from mesothelial origin, usually occurring in the genital tract. Extragenital locations, especially in the adrenal gland are extremely rare. Here we are reporting two cases of a 28-year-old and 50-year-old men with an adenomatoid tumor of the right adrenal gland. Usual morphological aspects join scattered and microcystic pattern with epithelioid or signet-ring cells. According to the morphological features, main differential diagnoses are adenocarcinoma metastasis, vascular tumors or mesotheliomas. Immunohistochemistry provides precious help to confirm the mesothelial origin thanks to positivity of epithelial markers (CK7, AE1-AE3, CK5/6) coupled to mesothelial markers (D2-40, Calretinin, WT1). On the other hand, there is no loss of BAP1 by immunohistochemistry and usually a surexpression of P16. Adrenal gland adenomatoid tumor is a benign tumor, which can be promoted by iatrogenous or constitutive immunodepression.

Malignant pleural mesothelioma: rare and aggressive but with new therapeutic perspectives. CMalignant pleural mesothelioma (MPM) is a rare tumour secondary to occupational asbestosis exposure. Its incidence has increased continuously since last thirty years, but has reached a plateau in France in men, earlier than anticipated. MPM incidence reaches 100 cases/million/year in an occupationally exposed population versus less than 1 case/million/year in general population, leading to 800 to 1000 new cases, yearly, in France. Molecular carcinogenesis of MPM is incompletely understood, but involves NF2, WT1 RASSF1, p16 gene alterations and the more recently described BAP-1. These genes are involved in apoptosis control, cell invasion and motility, cell division, and DNA repair control. Diagnosis relies on thoracoscopy and large pleural biopsies. Histological diagnosis remains an actual dilemma, relying on immunohistochemical analysis as described by the French MESOPATH group. Therapeutic strategy includes precocious tracts irradiation following drainage or thoracoscopy, to prevent permeation nodules. In selected patients, debulking surgery (pleurectomy-decortication) can still be discussed. First-line chemotherapy is based on a doublet of pémétrexed and cisplatin, for ten years, that demonstrated overall survival and quality of life improvement in a seminal phase 3 trial. As mesothelioma cells are known to secrete high amounts of VEGF, the monoclonal antibody targeting VEGF, bevacizumab (Avastin), in association with pemetrexed- cisplatin has been shown, in 448 patients, to improve overall survival (to nearly 19 months), and progression-free survival in the randomized phase 3 trial, Mesothelioma Avastin Pemetrexed Study (MAPS), sponsored by the French Intergroup (IFCT). Immune check-point inhibitors are currently tested in phase 2 trials and could then represent the future major therapeutic improvement in these patients.Mésothéliome malin pleural : rare et agressif mais des perspectives thérapeutiques nouvelles. Le mésothéliome pleural malin est une tumeur rare consécutive à l’exposition professionnelle aux fibres d’amiante. Son incidence semble avoir atteint un plateau en France, chez l’homme, plus tôt qu’anticipé. Elle est de 100 cas/million d’habitants/an dans la population exposée à l’amiante contre moins de 1 cas/million d’habitants/an dans la population générale non exposée, soit 800 à 1 000 nouveaux cas/an en France. Il constitue la 31e maladie à déclaration obligatoire. La carcinogenèse moléculaire implique les gènes NF2, WT1, RASSF1, p16 et BAP- 1, qui régulent l’apoptose, l’invasion et la motilité cellulaire, le contrôle de la division cellulaire et de la réparation de l’ADN. La thoracoscopie est l’examen diagnostique de base, permettant des biopsies profondes mais aussi une symphyse pleurale précoce en cas d’épanchement liquidien récidivant et/ ou abondant. Le diagnostic histologique reste en effet difficile, reposant sur une analyse immuno-histochimique bien codifiée, avec relecture centralisée nationale par le panel « tumeurs rares » MESOPATH. La thérapeutique repose sur l’irradiation précoce des trajets de ponction et de drain, la chirurgie de « debulking » par pleurectomie-décortication restant réservée à des patients très sélectionnés. La chimiothérapie par doublet de pémétrexed et sel de platine est restée le standard de traitement pendant une décennie. L’ajout du bévacizumab, dans cette tumeur qui sécrète du facteur de croissance de l’endothélium vasculaire (VEGF), testé dans l’essai de phase III MAPS de l’Intergroupe francophone de cancérologie thoracique (IFCT), a montré, chez 448 patients, une amélioration significative de la survie sans progression et de la survie globale par rapport au doublet de chimiothérapie standard, avec une médiane de survie globale de près de 19 mois. La place des inhibiteurs de points contrôles immunologiques est en cours d’investigation, et ces immunothérapies pourraient constituer la prochaine avancée thérapeutique des prochaines années..

Malignant pleural mesothelioma (MPM) is a rare and highly aggressive disease, whose incidence is increasing. Asbestos is the primary causal agent.Knowledge about MPM has evolved. Thoracoscopy is essential for diagnosis of MPM. It allows performing pleural biopsies, to study the extent of the disease and to relieve dyspnea. The pathological diagnosis is also better codified with immunohistochemistry and with analysis by expert of Mesopath group. Curative surgical treatments are pleurectomy decortication and extended pneumonectomy in combination with chemotherapy and/or radiotherapy. Those heavy treatments improve survival in highly selected patients. For the other patients, supportive measures will be considered to reduce pain and dyspnea.Radical surgical treatment is only offered in therapeutic trials or multimodal treatment. Its place is not formally established. New therapies associated to surgical treatment are being studied.Surgical management of MPM has to be operated in specialized teams where the survival benefit and quality of life is discussed case by case.

In the context of underreporting of occupational diseases, the aim was to study the validity of silica and asbestos job-exposure matrices in screening occupational exposure in the field of thoracic oncology.Fifty patients hospitalized with primitive lung cancer or mesothelioma in a university hospital center in the Hauts-de-Seine department of France were included between November 2016 and September 2017. For each patient 1/the job history was collected, from which data was entered single-blindly into the job-exposure matrices by a resident in occupational medicine, 2/a questionnaire (Q-SPLF) was completed similarly, and 3/the patients also had a consultation with a chief resident in occupational medicine, considered the gold standard. The main outcome was the diagnostic performance of the matrices. The Q-SPLF diagnostic performance was also studied.The asbestos and silica matrices had sensitivities of 100%, specificities of respectively 76.1% and 87.8%, the positive likelihood ratios were at 4.19 [2.5-6] and 8.17 [3.8-10], and the negative likelihood ratios were at 0. The Q-SPLF diagnostic performance was comparable to that of the matrices.The matrices and the questionnaire have a great diagnostic performance which seems interesting for a use as a screening tool for occupational exposures. These results have yet to be confirmed by large-scale studies.

The malignant pleural mesothelioma (MPM) is a rare tumour usually associated to asbestos exposure. The delay between the exposure and the occurrence of the cancer can reach 40 years. This caused the pick of incidence described in many countries including Tunisia. The diagnosis is suspected based on clinical features but positive diagnosis is microscopic. Our aim was to describe the clinical and microscopic features of MPM through a single institution experience.We conducted a retrospective study about 30 MPM diagnosed over a 20-year-period (1995-2015). We included only patients with complete records including clinical, radiologic and microscopic features. All the microscopic diagnoses were reviewed by 2 pathologists. A mean of 12 slides per case was reviewed. The diagnosis was based on the 2015 WHO classification.The mean age of the patients was 61 years, average 22 to 80 years. The sex ratio was 6,5. An asbetose exposition was reported in 21 cases. The most frequent symptoms was chest pain reported in 25 cases. Physical exam was normal in 9 cases. It revealed pleural syndorm in most patients (60 %). Imaging findings consisted mainly in diffuse pleural thickening in 17 cases. Twelve tumours were classified as stage I, 3 stage II, 14 stage III et 1 stage IV. Pleural biopsy was performed using needle in 18 cases, through thoracoscopy in 16 cases, thoracotomy in 3 cases and allowed the diagnosis in respectively 7 cases/18, 16 cases/16 and 3 cases/3. A lymph node biopsy was performed through mediastinoscopy in one case and yelded the diagnosis. The diagnosis was performed on surgical specimen in 2 patients: one bullectomy and one right upper lobectomy. The microscopic exam concluded to an EM in 17 cases, sarcomatoid mesothelioma (SM) in 4 cases and biphasic mesothelioma (BM) in 9 cases. Pan-cytokeratin antibody was used in all cases in association with 2 antibodies with positive diagnostic value and 2 antibodies with negative diagnostic value. It was repeated in 15 cases and the most used antibodies were the anti-calretinin and the TTF1. This was due to the lack of fixation in one case and in order to reach a quality criteria in the other cases. Surgical resection was possible in 2 patients. 15 patients were lost of view after a mean follow-up period of 3 months. Thirteen patients died before or during the follow-up.This work was about a Tunisian experience in the diagnosis and management of MPM. The major limits faced were the incomplete databases, the small number of patients included. Microsocpic positive diagnosis necessitates a degree of expertise and every laboratory has to determine the most valuable antibodies through its experience in order to optimize the diagnosis and to reduce the delay of diagnosis.

Mesothelioma is a rare malignant serous tumor with a poor prognosis of which asbestos exposure is the major known risk factor. It occurs with a latent period about 30 years after exposure, reaches mainly the pleura and affects mainly the men. The study of this pathology, recognized as an occupationnal disease and for which a Mandatory Declaration of Disease was introduced in January 2012, focused until then mainly on men, both epidemiologically and biologically. However, there are significant gender differences in the international literature.These results raise the question of investigating other risk factors, in particular the hypothesis of genetic predisposition, the biological mechanisms involved in mesothelioma carcinogenesis pathways being partially known. This encourages the study of epidemiological, clinical, biological and immunohistochemical factors predisposing women to the development of pleural and peritoneal mesothelioma, and to evaluate their prognostic impacts, based on cases diagnosed between 1980 and 2015, from the largest French database. It also encourages the establishment of an updated epidemiological inventory by gender in France for pleural and peritoneal mesothelioma; these data are non-existent for peritoneum., Le mésothéliome est une tumeur maligne rare des séreuses, au pronostic sombre, dont le facteur de risque principal connu est l’exposition à l’amiante. Il se déclare avec un temps de latence d’environ 30 ans après le début de l’exposition, atteint principalement la plèvre et touche majoritairement les hommes. L’analyse de cette pathologie, reconnue comme une maladie professionnelle et pour laquelle une Déclaration Obligatoire de maladie a été instituée en janvier 2012, s’est focalisée jusqu’alors essentiellement sur l’homme, tant sur le plan épidémiologique que sur le plan biologique. Il apparaît pourtant dans la littérature internationale des différences notables par sexe.Ces constations posent la question d’investiguer d’autres facteurs de risque, en particulier l’hypothèse d’une prédisposition génétique, les mécanismes biologiques intervenant dans les voies de la carcinogenèse du mésothéliome étant partiellement connus. Ceci incite à étudier les facteurs épidémiologiques, cliniques, biologiques et immunohistochimiques, prédisposant chez la femme au développement du mésothéliome pleural et péritonéal, et d’évaluer leurs impacts pronostiques, à partir des cas diagnostiqués entre 1998 et 2013, issus de la plus importante base de données française. Elle incite également à établir un état des lieux épidémiologique actualisé par sexe en France pour le mésothéliome pleural et péritonéal ; ces données étant inexistantes pour la France pour le péritoine.

International audience; Malignant pleural mesothelioma (MPM) is predominantly an occupational cancer, most often linked to asbestos exposure. Malignant pleural mesothelioma prognosis is poor with a short survival median, due to the aggressiveness of tumor cells and the weak efficiency of conventional anti-cancer therapies. Clinical, histological, and molecular data suggest tumor heterogeneity between patients as it was also shown for other cancer types. Consequently, there is an urgent need to develop new therapies that take into account this heterogeneity and the molecular characteristics of malignant pleural mesothelioma, in particular by identifying new anti-cancer drugs targeting the molecular specificities of each malignant pleural mesothelioma. Malignant pleural mesothelioma is characterized by numerous molecular alterations at the chromosomal, genetic and epigenetic levels. Molecular classification based on gene expression profile has firstly defined two tumor groups, C1 and C2, and more recently, four groups. By integrating genetic and transcriptomic analysis, a C2LN tumor subgroup of the C2 group has been identified and characterized. In addition to tumor heterogeneity between patients, intra-tumor heterogeneity is supported by several evidences. Most therapeutic strategies that take into account the tumor molecular characteristics have focused on targeted therapies based on mutated genes. A more appropriate strategy would be to consider better-defined tumor groups on the basis of several molecular alterations types as it has been proposed for the C2LN subgroup. A robust definition of homogeneous tumor groups sharing common molecular characteristics is necessary for the development of effective precision medicine for malignant pleural mesothelioma.; Le mésothéliome pleural malin (MPM) est un cancer majoritairement d'origine professionnelle, lié le plus souvent à une exposition à l’amiante. Le pronostic du MPM est sombre avec une médiane de survie courte, car ce cancer est très agressif et les thérapies conventionnelles anti-cancéreuses sont peu efficaces. Comme pour d’autres types de cancer, les données cliniques, histologiques et moléculaires suggèrent l’existence d’une hétérogénéité tumorale entre les patients. Il est donc urgent de développer de nouvelles thérapies qui prennent en compte cette hétérogénéité et les caractéristiques moléculaires des MPM, notamment en identifiant de nouveaux agents anti-cancéreux ciblant les spécificités moléculaires de chaque MPM.Le MPM est caractérisé par de nombreuses altérations moléculaires au niveau chromosomique, génétique et épigénétique. Une classification moléculaire sur la base du profil d’expression génique a défini deux groupes tumoraux C1 et C2 et, plus récemment, quatre groupes. En couplant analyse génétique et transcriptomique, un sous-groupe tumoral C2LN du groupe C2 a été identifié et caractérisé. Outre l'hétérogénéité entre les tumeurs des patients, de nombreuses évidences supportent également l’existence d’une hétérogénéité intra-tumorale. La plupart des stratégies thérapeutiques prenant en compte les caractéristiques moléculaires de la tumeur ont proposé des thérapies ciblées visant les gènes présentant des mutations. Il pourrait être plus judicieux de cibler des groupes tumoraux mieux définis, en intégrant plusieurs types d’altérations moléculaires, comme cela a été proposé pour le sousgroupe C2LN. Une définition robuste de groupes homogènes de tumeurs partageant descaractéristiques moléculaires communes est nécessaire au développement d’une médecine de précision efficace pour le MPM.

Malignant pleural mesothelioma (MPM) is a quite rare cancer, but with increasing incidence, that is usually induced by previous asbestos exposure. Its prognosis is poor and there is no validated curative therapy to date. Surgery of MPM, done only by few expert teams within a multimodal treatment is of limited and still disputed value. The standard treatment of MPM, relying on first-line chemotherapy by combined cisplatin-pemetrexed is often poorly effective, even if combination with bevacizumab anti-VEGF antibodies has slightly improved the results. Moreover, no second line treatment is recommended in case of failure of this chemotherapy. Therefore, the search of new therapies or strategies is crucial and the recruitment of patients in clinical trials is highly encouraged.Among the treatments under investigation, various anti-tumour immunotherapies, in particular immune checkpoints inhibitors (ICI), currently exhibit the most promising preliminary results. First data from the phase II, randomized "IFCT MAPS-2", recently presented during the 2017 ASCO meeting, confirmed the value of ICI in MPM patients in cases of chemotherapy failure.However, several exciting immunotherapies other than ICI are presently being evaluated in MPM and are reported in this article. Moreover, many questions still need to be answered about immunotherapy: what is its potential value as first line treatment? How to target the best candidates for these treatments? Which combinations between immunotherapy and standard chemotherapy, targeted therapies, surgery or radiotherapy? Finally, it is now essential that every clinician has sufficient knowledge about the possible toxicities of immunotherapy.

Prophylactic radiotherapy to prevent procedure-tracts metastases from malignant pleural mesothelioma remains controversial and clinical practice varies. The purpose was to assess the efficacy of local radiotherapy in a single fraction of 10Gy in preventing malignant seeding at intervention pleural site in patients with malignant pleural mesothelioma.This is a retrospective cohort study, including patients with histological confirmed malignant pleural mesothelioma treated by prophylactic irradiation to prevent interventional site metastases with a unique fraction of 10Gy with 6 to 18MeV, from January 1990 to December 2013 in the institut de cancérologie de Lorraine (Nancy, France).Ninety-one patients were treated by irradiation in intervention site, involving 120 intervention pleural sites, 91 thoracoscopies, 17 thoracotomies with chest drain and 12 CT or ultrasound guided needle biopsies. The median follow-up was 7 months (interquartile between 3 and 15 months). The overall survival was 43.5% at 12 months. The local progression free survival was 43.7% at 12 month. The incidence of local recurrence was 8% at 12 months. The median interval from radiotherapy to local recurrence was 4 months (2; 32). No grade II or higher toxicity was observed.Irradiation of pleural intervention sites with a single fraction of 10Gy is effective, well tolerated, simple, fast and cost effective.

Malignant mesothelioma is a rare tumour, usually the result of asbestos exposure. Several cases of familial aggregation have been reported and recently shown to be associated with constitutional mutations of the BAP1 gene. BAP1 is a deubiquitinating enzyme implicated in several different cellular mechanisms such as the repair or differentiation of DNA. About a half of malignant mesotheliomas present a somatic, bi-allelic inactivation of BAP1, demonstrated by nuclear extinction on histochemistry. Constitutional alterations of BAP1 are extremely rare. Present in the heterozygous state they are transmitted as an autosomal dominant. They are associated with a risk of developing other tumours such as uveal and cutaneous melanomas, benign melanocytic tumours (melanocytic BAP1-mutated atypical intradermal tumour or MBAITS) and clear cell renal carcinomas. The causal link between mesothelioma and germinal mutations of BAP1 has still not been clearly identified. At present there is, in France, no consensus on recommendations for the management of patients with these mutations. This article is a synthesis of the literature on the functions of the BAP1 gene, the tumour risks related to its alteration and the follow up of patients bearing a constitutional mutation.

Tumoral immune environment is a major component of cancer. Its composition and its organization represent a reproducible characteristic of tumors and a validated prognostic factor. In non-small cell lung cancer (NSCLC), cytotoxic T CD8+ lymphocyte density, associated with a Th1 environment and tertiary lymphoid structures impacts survival. Tumor cell-immune cell interaction is targeted by PD1/PD-L1 inhibitors. In advanced NSCLC, PD1/PD-L1 inhibitors are more effective than second-line chemotherapy. Pembrolizumab outperforms first-line chemotherapy in NSCLC strongly positive for PD-L1. PD1/PD-L1 inhibitors are currently tested in mesothelioma and thymic tumors. PD-L1 expression evaluated with immunochemistry is the most studied predictive biomarker of PD1/PD-L1 inhibitor efficacy. Tumor and immune cell expression of PD-L1 is still difficult to evaluate because of intra-tumoral heterogeneity and expression modulation by the microenvironment. Four commercial diagnostic antibodies are in development, with differences concerning recognized epitopes, methodology of evaluation of PD-L1 expression, positivity threshold, kit and platforms used. Clinical trials in NSCLC have shown that patients with tumors strongly positive for PD-L1 derived the best clinical benefit with PD1/PD-L1 inhibitors whereas clinical benefit is less common in tumors negative for PD-L1. PD-L1 expression is not a perfect biomarker since some PD-L1 negative NSCLC respond to PD1/PD-L1 inhibitors and some PD-L1 positive NSCLC do not. PD-L1 testing is likely to be implemented in daily practice for selection of advanced NSCLC that will be treated with pembrolizumab, underscoring the relevance of ongoing harmonization studies of the use of the different antibodies available for PD-L1 testing.

Background: Malignant pleural mesothelioma (MM) with abundant myxoid stroma (MMM) is a rare entity reported in pleura, which prognostic is still controversial. The objective of this study was to define this form of MMM on a large series, to decipher its clinicopathological characteristics and confirm its prognostic significance. Materials: 140 cases of MM with myxoid changes retrieved from MESOPATH files were compared to 3236 cases of epithelioid MM without myxoïde changes. Methods: Clinical features (age, gender, asbestos exposure, survival), histopathological and immunohistochemical (IHC) characteristics were evaluated and compared in the two populations. Results: There was a female predominance in MMM (40% vs 56% in epithelioid MM; p50%) harbored a better survival (29months median vs 19months; HR=2.0 [1.0; 4.2]; p=0.05). Conclusion: We confirmed that MMM is a clinical entity which more frequently affects young patients, females, harboring a better prognostic if myxoid stroma was predominant (multivariate analysis). Molecular profiles characterization are still on go.; Contexte : Le mésothéliome malin pleural (MMP) avec un stroma myxoïde (MMM) est une forme rarement rapportée au niveau pleural. Son rôle pronostique est encore controversé. Le but de cette étude a été de définir cette entité sur une série de plus grande ampleur, afin de déchiffrer ses caractéristiques clinico-pathologiques, ainsi que de confirmer sa signification pronostique. Matériel : 140 MMP présentant un stroma myxoïde ont été sélectionnés dans la base de données CRN/MESOPATH et comparés à 3236 cas de MMP épithélioïdes (MME) dépourvus de stroma myxoïde. Méthodes : Les caractéristiques cliniques (âge, genre, survie, exposition à l’amiante), histopathologiques et immunohistochimiques ont été pris en compte et comparées dans les deux populations. Résultats : Le MMM s’est rencontré dans une population significativement plus jeune (69 ans contre 73 ; p50% de la surface tumorale) est un facteur pronostique indépendant (médiane de survie de 29 mois contre 19 ; p=0,05). Conclusion : Nous avons confirmé que le MMM est bien une forme atteignant préférentiellement la femme, jeune, revêtant un meilleur pronostic, surtout si le stroma myxoïde est abondant (analyse multivariée). Leur profil moléculaire est en cours de caractérisation.

Previous occupational asbestos exposure (more rarely environmental or domestic exposure) may induce various pleural and/or pulmonary, benign or malignant diseases, sometimes with a very long latency for malignant mesothelioma (MM). Asbestos has been widely extracted and used in Western countries and in emerging or developing countries, resulting in a peak of MM incidence in France around 2020 and likely in a world pandemic of asbestos-induced diseases. These patients have mostly benign respiratory diseases (pleural plugs) but may also be diagnosed with lung cancer or malignant pleural mesothelioma, and have a global poor outcome. New therapeutic tools (targeted therapies, immunotherapy…) with first promising results are developed. However, it is crucial to obtain a full ban of asbestos use worldwide, and to do a regular follow-up of asbestos-exposed subjects, mostly if they are already diagnosed with benign respiratory diseases. Finally, new cancers (larynx and ovary) were recently added to the list of asbestos-induced tumors.

International audience; INTRODUCTION: Diffuse malignant mesothelioma (MMD) is a rare disease. The diagnosis is difficult and needs an antibody panel. The tumor suppressor gene BRCA1 associated protein 1 (BAP1) is involved in several cancers, including MMD. Loss of BAP1 expression is correlated with BAP1 somatic or constitutional genetic defects. Our work assesses the value of integrating BAP1 in the panel of antibodies used for the diagnosis of MMD. MATERIALS AND METHODS: Immunohistochemical techniques were performed on cytological and histological specimens of MMD and adenocarcinoma pleural metastasis. RESULTS: Of the 26 patients with MMD and the 24 patients with adenocarcinoma pleural metastasis, loss of BAP1 expression was observed in 11 (48%) and one adenocarcinoma (6%) on cytological specimens and in 12 MMD (48%) and in one adenocarcinoma (5%) on biopsy specimens. The concordance between immunocytochemistry and immunohistochemistry was 100%. The specificity of BAP1 was 100% on cytological and biopsy specimen for the diagnosis of malignancy in case of mesothelial proliferation. DISCUSSION AND CONCLUSION: Loss of BAP1 expression is an indicator of MMD in a context of mesothelial proliferation. This immunohistochemistry could be integrated in the panel of immunostaining used for MMD diagnosis, either on histological or cytological samples. Furthermore, loss of BAP1 expression guides the patient to an oncology genetic counseling in order to eliminate a MMD developed as part of a constitutional genetic defect

Malignant pleural mesothelioma is a rare disease originating from mesothelial cells of the pleura and is related to asbestos exposure. The tumor is generally extended at the time of diagnosis and the treatment consists of a systemic palliative therapy. Radical approach is limited to very selected patients and is performed in expert centers but without validated schema. Radiotherapy alone is mainly used in palliative intent. Platinum-based chemotherapy in association with pemetrexed is the frontline standard of care and provides a 12-month overall survival. The addition of bevacizumab, an antiangiogenic drug, shows an improvement in median survival. To date, there is no second-line treatment approved for this disease and therefore inclusion in trials is recommended. Currently, various studies are investigating target therapy, immunotherapy and intrapleural perioperative treatment.

Peritoneal malignant mesothelioma is a rare and extremely aggressive tumor that is sometimes difficult to diagnose. We report two cases of metastatic malignant peritoneal mesothelioma. In one case, malignant metastatic cells were identified in cervical lymph nodes while in the other case, the cells were found in the liver. In both cases, metastases were identified before discovering the primary tumor. This led to the misdiagnosis of carcinoma of unknown origin. Nevertheless, the histological and immuno-histochemical patterns were typical of malignant mesothelioma. Regarding metastasis of unknown origin, a differentiation of epithelioid peritoneal malignant mesothelioma and adenocarcinoma proved to be difficult. Therefore, we discuss the diagnostic usefulness of immuno-histochemical mesothelioma markers.

International audience; Introduction : Sonic Hedgehog (Shh) pathway is physiologically activated during embryogenesis and development. It plays a role in idiopathic lung fibrosis and is also activated in several solid cancers.State of the art : Shh pathway is reactivated in thoracic cancers, as small cell lung carcinoma, non-small cell lung carcinoma and malignant pleural mesothelioma. Shh pathway is associated with cancer stem cells and seems to have a crucial role in tumor proliferation, aggressiveness and chemoresistance in these cancers. This review describes the activation mode of Shh pathway in thoracic cancers and its role in small cell lung carcinoma, non-small cell lung carcinoma and malignant pleural mesothelioma, using in vitro and in vivo models. Notably, data from literature show that inhibition of Shh pathway has an antitumor action and sensitizes to chemotherapy.Perspectives : These results incite to develop targeted therapies against Shh pathway in the treatment of thoracic cancers.; Introduction : La voie de signalisation Sonic Hedgehog (Shh) est une voie physiologiquement activée durant l’embryogenèse et le développement. Elle jouerait un rôle dans la fibrose pulmonaire idiopathique et est aussi réactivée dans plusieurs cancers solides.État des connaissances : La voie Shh est réactivée dans les cancers thoraciques, comme le cancer bronchique à petites cellules, le cancer bronchique non à petites cellules et le mésothéliome pleural malin. Cette voie est intimement liée aux cellules souches cancéreuses et semble jouer un rôle important dans la prolifération tumorale, l’agressivité et la chimiorésistance de ces cancers. Cette revue décrit le mode d’activation de la voie Shh dans les cancers thoraciques et son rôle dans les formes à petites cellules, non à petites cellules et les mésothéliomes malins, à partir de modèles in vitro et in vivo. Les données de la littérature montrent que l’inhibition de la voie Shh a une action antitumorale et permet une sensibilisation à la chimiothérapie.Perspectives : Ces résultats incitent à développer des thérapies ciblant la voie Shh dans la prise en charge thérapeutique des cancers thoraciques.