[The French mesothelioma network from 1998 to 2013]. / Mésothéliome: les dispositifs en place en France « le réseau mésothéliome ¼ 1998-2013.

Mesothelioma is a rare disease less than 0.3% of cancers in France, very aggressive and resistant to the majority of conventional therapies. Asbestos exposure is nearly the only recognized cause of mesothelioma in men observed in 80% of case. In 1990, the projections based on mortality predicted a raise of incidence in mesothelioma for the next three decades. Nowadays, the diagnosis of this cancer is based on pathology, but the histological presentation frequently heterogeneous, is responsible for numerous pitfalls and major problems of early detection toward effective therapy. Facing such a diagnostic, epidemiological and medico-legal context, a national and international multidisciplinary network has been progressively set up in order to answer to epidemiological survey, translational or academic research questions. Moreover, in response to the action of the French Cancer Program (action 23.1) a network of pathologists was organized for expert pathological second opinion using a standardized procedure of certification for mesothelioma diagnosis. We describe the network organization and show the results during this last 15years period of time from 1998-2013. These results show the major impact on patient's management, and confirm the interest of this second opinion to provide accuracy of epidemiological data, quality of medico-legal acknowledgement and accuracy of clinical diagnostic for the benefit of patients. We also show the impact of these collaborative efforts for creating a high quality clinicobiological, epidemiological and therapeutic data collection for improvement of the knowledge of this dramatic disease.

[Non transplant-related constrictive bronchiolitis in adults]. / Bronchiolites constrictives de l'adulte, hors contexte de transplantation.

INTRODUCTION: The term bronchiolitis refers to inflammatory disorders of the bronchioles. Constrictive bronchiolitis is the type most frequently encountered. STATE OF THE ART/PERSPECTIVES: The main clinical manifestations include the development of exertional dyspnoea and fixed airflow obstruction. Chest x-ray findings are usually unhelpful, but CT scanning may reveal a mosaic pattern on expiration. Peripheral micronodules are less frequently seen. The causes of constrictive bronchiolitis are numerous. The diagnosis may be clear from the clinical context when a causative event or predisposing condition can be identified (lung or bone marrow transplantation, toxic fume or gas inhalation, rheumatoid arthritis); in other conditions, a stepwise approach to the diagnosis is usually recommended in order to exclude other causes of subacute or chronic obstructive disease. Formal diagnosis requires histological examination of surgical lung biopsies. Despite corticosteroid administration, respiratory failure usually develops. Specific inhibitors of pro-inflammatory cytokines may offer a new and promising therapeutic approach. CONCLUSIONS: If the clinical context or the radiology and clinical findings are not highly suggestive of a constrictive bronchiolitis, a surgical lung biopsy should be considered.

Human allograft vein failure: immunohistochemical arguments supporting the involvement of an immune-mediated mechanism.

The aim of this study was to search for signs suggestive of an ongoing immune-mediated reaction in failed human cryopreserved venous allografts. In 15 samples, the authors analyzed: (1) the pattern of morphological changes; (2) the density, distribution, and phenotype of leukocytic infiltrate; and (3) the expression of class II major histocompatibility complex (MHC) antigens and inducible adhesion molecules. Two groups of samples could be recognized. In samples explanted before 3 months after grafting, the structure of the vessel wall was preserved. A dense leukocytic infiltrate was present within the intima and around the numerous vasa vasorum located in medial and adventitial layers. Class II MHC antigens and cytokine-dependent molecules were induced on endothelial cells lining the vasa vasorum and on residual smooth muscle cells. In samples explanted after 3 months of evolution, the vessel wall has lost its normal structure and contained few vasa vasorum. A few leukocytes were detected around capillary vessels located in the peripheral connective tissue surrounding the graft. Class II MHC antigens and adhesion molecules were induced on endothelial cells lining the peripheral capillary vessels. These results suggest the involvement of an immune-mediated mechanism at the early stage of the evolution of failed human venous allografts.

Endobronchial hamartoma associated with bronchioloalveolar cell carcinoma.

Computed tomographic findings in a 60-year-old man with lobar bronchioloalveolar cell carcinoma distal to endobronchial hamartoma are described.

Tracheal malacoplakia.

Malacoplakia is a rare granulomatous disease well described in the urinary tract but which rarely involves the lung. We report for the first time, to our knowledge, tracheal localization of this unusual disorder. The larynx and probably kidneys were also involved. Differential diagnosis, physiopathology, and treatments are discussed.

Prognosis of patients with advanced idiopathic pulmonary fibrosis requiring mechanical ventilation for acute respiratory failure.

STUDY OBJECTIVE: To evaluate the beneficial effect of mechanical ventilation (MV) in patients with idiopathic pulmonary fibrosis (IPF) who develop acute respiratory failure (ARF), with special emphasis on prognosis. DESIGN: Retrospective study. SETTING: Ten-bed respiratory ICU that is a part of a respiratory department actively involved in lung transplantation (LTx). PATIENTS: From 1991 to 1999, 23 patients (mean age, 52.9 years; range, 21 to 82 years) with IPF required MV for ARF. At admission to the ICU, 16 patients were potential candidates for LTx, with 5 patients already on the waiting list. MEASUREMENTS AND RESULTS: Survival and gas exchange under MV were assessed. The precipitating cause of ARF was also analyzed. With the exception of 1 patient who successfully received a single-lung transplant 6 h after initiation of MV, all the remaining 22 patients died while receiving MV (median survival, 3 days; range, 1 h to 60 days). The duration of MV correlated positively with baseline vital capacity (percent predicted) (R = 0.54; p = 0.01) and baseline total lung capacity (percent predicted) (R = 0.71; p < 0.001), and correlated negatively with baseline PaCO(2) (R = - 0.47; p = 0.03) and the duration of evolution of IPF (R = -0.50; p = 0.01). Duration of MV did not correlate with the duration of immunosuppressive therapy (R = - 0.24; p = 0.27) or duration of oxygen therapy (R = - 0.32; p = 0.14) prior to admission. The precipitating cause of ARF was most often not identified. CONCLUSIONS: Our data support the general belief that MV does not benefit IPF patients presenting with ARF. Initiation of MV in IPF patients is thus questionable and should, in our opinion, be restricted to patients in whom LTx can be performed within a few days after initiation of MV.

Morbidity and mortality related to the native lung in single lung transplantation for emphysema.

It has been advocated that a major drawback of single lung transplantation (SLT) is the risk of serious complications arising from the native lung. The morbidity and mortality related to the native lung in 46 patients who underwent SLT for pulmonary emphysema in Clichy from 1988 to 1997 were reviewed retrospectively. In particular, infectious complications and native lung hyperinflation were searched. Complications arising from the native lung are not unusual after SLT for subjects with emphysema, and it was concluded they are not responsible for a substantial mortality.

Ectopic hepatocellular carcinoma arising in the left chest wall: a long-term follow-up.

We report the case of a 66-year-old man with chronic hepatitis C and a slowly growing left chest wall mass. Two years after the patient first noticed the mass, it was resected. A diagnosis of hepatocellular carcinoma (HCC) was established. The liver was studied by ultrasound, computed tomography (CT), magnetic resonance imaging (MRI) and angiography, but no mass was found. Blind liver biopsy showed mild chronic hepatitis without cirrhosis or HCC. Three years after the discovery of the chest wall HCC, no liver mass had appeared at CT and MRI. We conclude that solitary extrahepatic HCC (i) may arise in ectopic liver tissue; (ii) should not be considered as a metastasis of an occult HCC; and (iii) can be amenable to cure through resection.

[Evaluation of bidimensional echography in the etiological orientation of pericardial disease. Apropos of 39 anatomo-echographic comparisons]. / Evaluation de l'échographie bidimensionnelle dans l'orientation étiologique des maladies du péricarde. A propos de 39 confrontations anatomo-échographiques.

Echocardiography provides a firm diagnosis of pericardial effusion and evaluates its repercussions on the cardiac cavities. The images obtained with two-dimensional echocardiography are of such quality that the anatomical lesions can be analyzed, but the predictive value of this examination for the aetiological diagnosis has not yet been established. To investigate this point we have compared the images recorded in 39 episodes of pericardial disease with the corresponding anatomical data provided by surgery (n = 38)) or necropsy (n = 1) less than 48 hours after the ultrasonic examination. In one case, the purely solid nature of the pericardial content, suspected on the presence of an echo-filled cavity with adherent membranes, was confirmed at surgery. Conversely, the totally or partly liquid nature of the effusion was ascertained whenever the two pericardial membranes were separated by an echo-free cavity in at least one portion of the region examined, and there was no false-positive result (n = 38). The images obtained could be compared with the anatomical lesions in 28 out of 38 cases of partly or totally liquid pericarditis. The pericardial cavity was entirely echo-free in 12 of these cases, and this was confirmed by the anatomical examination, except in one case where epicardial nodules were found at surgery. Abnormal intrapericardial images were detected in the other 16 echocardiographic examinations, viz.: round masses in 2 cases, linear echoes in 2 cases and mattress-like deposits in 12 cases. In 9 of these 16 cases corresponding intrapericardial formations were discovered at surgery.(ABSTRACT TRUNCATED AT 250 WORDS)

[Thrombosis of a valve prosthesis: fatal cerebral embolism during thrombolytic treatment]. / Thrombose de prothèse valvulaire: embolie cérébrale mortelle lors du traitement thrombolytique.

The authors report the first case of lethal cerebral embolism complicating thrombolytic therapy administered for thrombosis of a mitral valve prosthesis. The incidence of systemic embolism during this form of therapy appears to be at least one in five cases. It may be underestimated and should lead to further discussion as to the indications of thrombolytic therapy and surgery for thrombosis of a left heart valve prosthesis.

[Bronchiolitis with airflow obstruction in adults]. / Bronchiolites avec trouble ventilatoire obstructif de l'adulte.

PURPOSE: The purpose of this paper is twofold: to describe the clinical and anatomical characteristics of bronchiolitis associated with airflow obstruction in adults; to present through a clinical approach, a classification of the main aetiologies or pathological frames associated with that entity. KEY POINTS: The constrictive bronchiolitis type is the most frequently encountered. On clinical grounds, cough, crackles, and a progressive dyspnea develop usually within a few weeks. Radiological signs of bronchiolar abnormalities are best visualized on high resolution expiratory CT scan. The decrease in maximal airflows and oxygen tension is of limited amplitude and poorly reversible with bronchodilators. Diagnosis is easily performed when a causative event, or the clinical context, can be delineated: inhalation of toxic fumes, diffuse bronchiectasis, rheumatoid arthritis, lung or bone marrow transplantation. Delayed formation of bronchiectasis in the central airways is common. The treatment is not standardized; corticosteroids are usually prescribed as a first line therapy; the benefit of the addition of, or substitution with immunosuppressive drugs has not been adequately evaluated, but is, on the mean, of limited amplitude. PERSPECTIVES: Recent advances in the identification of inhaled agents toxic for the distal airways help in establishing appropriate measures of prevention. When the aetiology of the bronchiolitis cannot be suspected, extensive search of a causative agent should be performed, including microbial and mineral analysis of bronchoalveolar products. Negative results should lead to perform a surgical lung biopsy. The study of chronic rejection processes in animal models of lung transplantation, the identification of inhibitory factors of bronchiolar fibrogenesis, and the efficacy of some anti-cytokines on inflammatory processes could result in new therapeutic approaches.

[Spindle cell carcinoma of the breast with neuroendocrine differentiation. A rare entity simulating a benign tumor]. / Carcinome mammaire à cellules fusiformes et différenciation neuro-endocrine. Une entité rare pouvant simuler une tumeur bénigne.

We report a case of spindle cell carcinoma of the breast with neuroendocrine and mucinous differentiation. Histological diagnosis can be difficult as macroscopic appearance and low grade cytologic features suggest a benign tumor. Differential diagnosis with a fusiform benign tumor of myoepithelial origin should be discussed. Immunohistochemistry is essential to confirm the diagnosis.

[Bronchocentric granulomatosis. A new case and review of the literature]. / Granulomatose bronchocentrique. Nouvelle observation et revue de la littérature.

One the basis of one case, a review is undertaken of this recently described condition. The special interest of this case lies in its reticulo-nodular type radiological appearances and above all the presence of aspergillus within the lesions, rarely reported in non-asthmatics.

[Failure factors in X-ray computed tomography-guided biopsy of pulmonary lesions: analysis of 103 consecutive biopsies]. / Facteurs d'échec de la biopsie guidée par tomodensitométrie des lésions pulmonaires: analyse de 103 biopsies consécutives.

OBJECTIVE: Percutaneous biopsy of pulmonary lesions with use of CT-guidance is well established and relatively safe. Reported accuracy rates are 64%-90% and major complications are rare. To determine the failure factors of CT-guided biopsy of lung lesions, we retrospectively analyzed 103 consecutive procedures. MATERIALS AND METHODS: Fourteen characteristics of the biopsy procedure were analyzed, including size, location, skin-lesion and chest wall-lesion distances, operator experience, procedure type (histology and/or cytology), histologic definite diagnosis, and other. RESULTS: Overall success rate was 88%. Success rate was correlated with the size of the lesion 4.3 +/- 2.9 cm for the positive results versus 2 +/- 1.2 cm for the negative results (p < 0.01). Skin- and chest wall-lesion distances were 5.8 +/- 2.2 and 1.5 +/- 1.8 respectively for positive results and 8.3 +/- 2.9 and 3.7 +/- 2.5 for negative results (p < 0.001). The overall complication rate for pneumothorax was 17%. Chest wall-lesion distances were 3.3 +/- 1.8 cm for complicated procedures and 1.5 +/- 1.9 cm for uncomplicated procedures (p < 0.001). No other factor was significantly correlated with the risk of pneumothorax. CONCLUSION: Small lesion size, long skin- and chest wall-lesion distances are significant predictive failure factors. Long chest wall-lesion distance is significantly correlated with the complication rate for pneumothorax.

[Pathologic anatomy of bronchiolitis with the exclusion of acute forms]. / Anatomie pathologique des bronchiolites à l'exclusion des formes aiguës.

ANATOMIC DEFINITION: Bronchiolitis is an inflammatory condition of the small airways, membranous and respiratory bronchioles. PATHOPHYSIOLOGY: The lesions result from exogenous or endogenous aggression of the epithelium. The inflammatory reactions caused by this aggression may regress spontaneously or after treatment or may progress to fibrosis. HISTOLOGIC ASPECTS: Obliterating bronchiolitis is the best understood form. There are two types: polypoid obliterating bronchiolitis and constrictive bronchiolitis. This latter form is the only one which causes an obstructive syndrome. Other histological forms have been described. PATHOLOGY AND CLINICAL PRESENTATION: Certain lesions have particular morphological features allowing their identification (smokers bronchiolitis, follicular bronchiolitis, diffuse panbronchiolitis) and others occur in classical associations (rheumatoid polyarthritis, chronic lung graft rejection). In many cases however, the lesions are relatively monomorphous and result from many different causes. Rigorous comparison between pathological findings and the clinical presentation is needed to classify these types and integrate them into a particular context.

[Graft dysfunction, acute rejection and bronchiolitis obliterans in lung and heart-lung transplantation]. / Dysfonction du greffon, rejet aigu et bronchiolite oblitérante dans la transplantation pulmonaire et cardiopulmonaire.

Three complications which influence both survival and quality of life in transplanted patients will be the object of this chapter. Graft dysfunction: this is a severe re-implantation oedema leading to inefficiency of the graft as regards haemostasis whether or not associated with haemodynamic complications. The liberation of free radicals and/or cytokines induced by ischemia-reperfusion of the graft plays an important role in the pathogenesis of this syndrome. Acute rejection: the mechanism is complex leading to the intervention of an immune response stimulated by the detection of allo-antigens. The clinical picture is often non-specific. Treatment requires boluses of methyl prednisolone completed by decreasing dose of corticosteroid therapy orally. The syndrome of bronchiolitis obliterans: this is a progressive failure of the airways. This syndrome occurs in the long term in 50% of patients and presents with progressive dyspnoea associated with persistent or recurrent cough. The pathogenesis is brought about principally by a chronic rejection with a specific cytotoxic reaction of T lymphocytes against the airway epithelium which expresses Class II major histocompatibility antigens. Attempts at curative treatment can be extremely deceptive and leads to, at best, a slowing in decline of respiratory function.

[Bronchiolitis obliterans after lung transplantation]. / Bronchiolite oblitérante après transplantation pulmonaire.

Lung transplantation has become a realistic treatment in some patients with severe respiratory impairment or severe pulmonary arterial hypertension. Immunosuppression therapy is about the same in all transplantation units and includes cyclosporin, corticosteroids and azathioprine. The diagnosis of acute rejection episodes has been greatly facilitated by the histological study of transbronchial biopsies obtained by endoscopy. Improvements in the short-term prognosis of these patients have made it possible to individualize an unusual and delayed complication: bronchiolitis obliterans. This progressive and diffuse obstruction followed by destruction of the transplant's bronchioles is interpreted as a consequence of chronic rejection. The diagnosis of bronchiolitis obliterans is difficult and rests essentially on degradation of the respiratory function resisting to increased immunosuppression. Some viral infections perhaps contribute to its development, and it may be so severe as to require another lung transplantation.

[Post-lung transplantation bronchiolitis obliterans]. / Bronchiolite oblitérante post-transplantation pulmonaire.

Bronchiolitis obliterans is an anatomical lesion with multiple aetiologies. In the lung transplant patient the pure forms of bronchiolitis obliterans are probably the consequence of a process of chronic rejection; in fact necropsy tissue or lungs removed which have been transplanted show that the lesions of bronchiolitis obliterans are often associated with parenchymal disorders, vascular and proximal bronchial disease, which are sequelae of phenomena of rejection or infection. The effect of bronchiolitis obliterans on lung function is constant; this may appear progressively or in stages. Increasing immunosuppressive treatment may arrest the progress. This rarely occurs and the development of respiratory failure tends to be the rule. It is exceptional to achieve the diagnosis of bronchiolitis obliterans from the examination of a transbronchial biopsy. It is a combination of features, both clinical and respiratory function, negative bacteriology and virological investigations as well as the absence of any efficacy of conventional treatment for rejection which leads to the diagnosis. In certain cases the question of a pulmonary re-transplantation is raised.

[Pulmonary lesions in Wegener's disease. Report of the French Anatomo-clinical Research Group. Study of 40 pulmonary biopsies]. / Les lésions pulmonaires de la maladie de Wegener. Rapport du groupe français de recherche anatomo-clinique. Etude de 40 biopsies pulmonaires.

We report the results of a morphological analysis of 60 pulmonary biopsies gathered from a multi center study, organised by the clinico-pathological research group on Wegener's Disease under the auspices of the French Language Society of Thoracic Medicine. Forty of the sixty cases analysed were retained after indexing the histological aspects in order to specify their diagnostic value. Two groups of lesions were distinguished, which had different significance. Group A: These include the three major diagnostic criteria, which reinforce one another as they associate: 1) The polymorphoneutrophil microabscesses with limited central necrosis or an extended necrosis like the contours of a relief map. 2) An angiitis (arteries, veins, capillaries) with eccentric focal parietal crescent-shaped microabscesses. 3) Polymorphous granulomas with giant cells. Group B: In this group are the minor morphological observations (table II) of a lesser value and significance. 1) Acute or chronic lesions with alveolar haemorrhage, endogenous lipid pneumonia, xanthomatous granulomas, an organising pneumonia with an alveolitis. 2) Bronchial lesions: Bronchitis and necrotising bronchiolitis, which is more rarely follicular. 3) Sero-fibrinous or infiltrative neutrophil pleural lesions with focal microabscesses, elastolysis and elastophagia with giant cells in the elastic lamina. Thirteen cases presented with misleading lesions, which was a possible source of diagnostic error and led to a discussion of several associated disorders (Goodpasture's syndrome, and collagen disorder syndrome) or there may be systemic angiitis (Giant cell or lymphocytic) or also systemic or tissue eosinophilia (Churg-Strauss syndrome, bronchocentric granulomatosis) or necrotising bronchitis (atrophic polychondritis) or other forms of nodular interstitial fibrosis, such as histiocytosis X. We would like to stress the great polymorphic variation of the lesions and the difficulties which confront pathologists in the diagnosis of Wegener's Disease, above all when it is localised to the lung. There is value in finding at least one major diagnostic criteria which is associated with a minor criteria and with the help of the C.ANCA levels may lead to a narrow clinicopathological correlation and allows for a fairly precise approach to the diagnosis and identification of early or unusual lesions and thus to the early treatment of patients before irreversible renal failure appears.

[Epidural aspergillosis secondary to lung aspergilloma despite long-term itraconazole treatment]. / Aspergillose épidurale secondaire à un aspergillome pulmonaire malgré un traitement au long cours par itraconazole.

A 58-year-old man developed spinal cord compression at the T2-T3 level due to an Aspergillus epidural abscess. This presumably immunocompetent patient had been treated for two years by oral itraconazole (200 mg/day) for a lung aspergilloma that occurred seven years after removal of a lung adenocarcinoma. Surgical debridement was performed via a wide posterior approach associated with high-dose amphotericin B. Five months later, the patient's neurological deficit had not improved and the patient died from respiratory failure. Despite a long-term treatment with itraconazole, the infection spread locally from a lung aspergilloma to the epidural space.