[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.

Expression of TTF-1 and cytokeratins in primary and secondary epithelial lung tumours: correlation with histological type and grade.

AIMS: To assess cytokeratin (CK) and thyroid transcription factor (TTF)-1 expression in primary epithelial lung tumours by comparison with non-pulmonary carcinomas and to correlate it with their histological type and grade. METHODS AND RESULTS: Immunohistochemistry using antibodies against CKs 5/6, 7, 19, 20 and TTF-1 was applied to 165 primary and 37 secondary epithelial lung tumours. CK5/6 is a sensitive and specific marker of lung squamous carcinomas being positive in 100% of cases. CK7 is a common marker of primary lung adenocarcinomas (100% of cases) but with a lower specificity since it is also observed in other primary lung carcinomas (70% of large-cell neuroendocrine carcinomas, 40% of large-cell carcinomas, 23% of squamous carcinomas) but also in 27% of non-pulmonary adenocarcinomas. Addition of an anti-CK20 may be useful to prove or disprove the pulmonary origin of an adenocarcinoma when there is a history of colon cancer. CK19 is ubiquitous but a predominant or exclusive 'dot-like' pattern is very suggestive of high-grade neuroendocrine carcinoma. TTF-1 is a very sensitive and specific marker to document the pulmonary origin of an adenocarcinoma if a thyroid origin is excluded. Its expression in neuroendocrine lung tumours depends on the tumour grade. CONCLUSIONS: Immunohistochemical expression of CKs and TTF-1 may be correlated with histological type and grade of lung primary epithelial tumours and may allow them to be distinguished from non-pulmonary carcinomas.

[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.

Angiogenesis and extracellular matrix remodelling in bronchioloalveolar carcinomas: distinctive patterns in mucinous and non-mucinous tumours.

AIM: Bronchioloalveolar carcinomas (BACs) are rare primitive lung adenocarcinomas growing along the alveolar septum without stromal, vascular or pleural invasion. We report an immunohistochemical study of their vascular microenvironment. METHODS AND RESULTS: In three mucinous BACs (M-BAC) and three non-mucinous BACs (NM-BAC) we examined the following parameters in comparison with the normal lung: (i) constituents of the alveolar extracellular matrix; (ii) qualitative and quantitative changes of alveolar capillaries; and (iii) expression of vascular endothelial growth factor (VEGF) by tumour cells. In M-BAC, the alveolar matrix was unchanged compared with the normal parenchyma. Capillaries expressed normal alveolar endothelial markers and their average surface was calculated, as in normal lung, as 8%. VEGF was negative in tumour cells. In NM-BAC, the alveolar wall was thickened by deposits of fibronectin and type III collagen containing myofibroblasts and the basement membrane was disrupted. Capillaries did not retain alveolar endothelial markers and their surface was calculated as 19%. Tumour cells expressed high levels of VEGF. CONCLUSIONS: In contrast to NM-BAC, M-BAC do not modify the alveolar structure and seem to exploit the normal alveolar vascular bed to grow, without inducing neoangiogenesis. A better understanding of the mechanisms of growth of lung cancers may have implications for future anti-angiogenic therapeutic strategies.

[Results of fine needle aspiration biopsy, frozen section diagnosis and definite histological results in thyroid pathology. Report of 163 cases]. / Analyse des résultats de la cytoponction, de l'examen histologique extemporané et définitif dans le traitement chirurgical de la pathologie thyroïdienne: à propos de 163 cas.

INTRODUCTION: In thyroid diseases, the place of fine needle aspiration biopsy still continues to be discussed: the sensibility and specificity vary greatly in the literature. Frozen section diagnosis is necessary to form a diagnostic strategy. The objective of this study was compare the results of fine needle aspiration biopsy, frozen section diagnosis, and definitive histologic results in a population of 163 patients and to draw conclusions about treatment. MATERIAL AND METHOD: From 1994 to 1999, 163 patients (132 females and, 31 males) undergoing thyroid surgery were included in this retrospective study, after a standard preoperative work-up. Those with a single palpable nodule and hypofixation on scintigraphy underwent fine needle aspiration before surgery. These results were compared with the definitive histologic results. RESULTS: A loboisthmectomy was performed in 88 cases (54%), a subtotal thyroidectomy in 34 cases (21%), and a total thyrodectomy in 41 cases (25%). In the latter group, an associated neck dissection was performed in 18 cases (11%); a frozen section diagnosis was obtained in all cases of thyroid nodules. This study demonstrated a single nodule in 97 cases (60%), multiple nodules in 27 cases (17%), multinodular goitre in 34 cases (21%), and 5 Basedow diseases (3%). Sixty-two cases (38%) of thyroid nodules underwent fine needle aspiration before surgery. In 25 cases (15%), definitive pathology showed a malignant lesion. The frozen section diagnosis had a sensitivity of 73% and a specificity of 99%, and the fine needle aspiration biopsy had a sensitivity of 40% and a specificity of 100%. CONCLUSION: The authors propose fine needle aspiration biopsy in the following cases: a single palpable nodule and hypofixation on scintigraphy or a surgical contra indication; and direct surgery in symptomatic thyroid disease or if there are one or several full nodules > 2 cm. In near future, these indications will be modified with the increasing reliability of fine needle aspiration biopsy.

[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.

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.

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.

Is high-resolution computed tomography a reliable tool to predict the histopathological activity of pulmonary Langerhans cell histiocytosis?

High-resolution computed tomography (HRCT) has proved to be very useful in the diagnosis and follow-up of pulmonary Langerhans cell histiocytosis (PLCH), but the precise relationships between nodules and thin-wall cysts observed by HRCT, and granulomatous or cystic lesions present in lung tissue, remain to be established. The aim of this study was to compare quantitative data obtained by HRCT and those obtained by histopathological examination of corresponding lung tissue specimens in patients with biopsy-proven PLCH. The results demonstrated that the extent of nodular abnormalities was strongly correlated with the density of florid granulomatous lesions in lung tissue. A strong correlation was also found between the extent of cystic abnormalities and the density of cavitary lesions, but the latter included both still inflammatory cavitary granulomas and cicatricial fibrous cysts. Interestingly, small isolated florid granulomas were found in lung tissue from most patients with a predominant cystic CT scan pattern. Taken together, these results demonstrate that HRCT has to be considered with caution to evaluate the histopathological activity of PLCH. Patients presenting with predominant HRCT cystic abnormalities should benefit from a long-term follow-up. Because these patients are susceptible to developing severe respiratory insufficiency, they should also be considered for treatment as soon as an effective therapy for LCH is available.

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.

Severe tracheobronchial stenosis in a patient with Crohn's disease.

Tracheobronchial involvement in Crohn's disease is rare, usually associated with symptoms of tracheobronchitis, and typically responds well to steroids. The authors report a case of a 29-yr old patient with Crohn's disease, who presented with dyspnoea, fever, and a productive cough. Computed tomography of the chest revealed extensive nodular tracheobronchial stenosis, that was accompanied by severe mucosal inflammation at bronchoscopy. High-dose oral steroids diminished the mucosal inflammation, but had limited efficacy on the underlying tracheobronchial stenosis. It is speculated that this relative ineffectiveness of steroids may be due to the persistence of the untreated inflammatory process.

[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.

[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.

Isolated pulmonary arteries involvement in a patient with Takayasu's arteritis.

Pulmonary arteries involvement is well described in Takayasu's arteritis (TA), a condition which is mainly associated with involvement of the systemic arteries. We report a case of TA with documented isolated pulmonary arteries involvement. Symptoms were quite similar to those encountered in chronic thromboembolic disease. A pulmonary angiogram showed bilateral stenosis and occlusion of pulmonary arteries. Diagnosis of TA was suspected, and as such a complete aortogram was made but proved to be normal. Massive haemoptysis suddenly occurred, which resulted in death. Autopsy disclosed characteristic pathological lesions of TA in pulmonary arteries and confirmed the lack of involvement of the aorta and its branches. The frequency of such a clinical form could be underestimated, given the difficulties of diagnosis and features similar to those of chronic thromboembolic disease.

Bronchial Kaposi's sarcoma after single lung transplantation.

Kaposi's sarcoma (KS) has been reported in 6% of malignancies of solid organ transplant recipients. Most of the observations have been in recipients of renal allografts but, so far, KS has not been described in lung transplantation. We report a case of bronchial KS occurring in a black patient 6 months after single lung-transplantation. Skin lesions were absent and, interestingly, KS lesions were observed solely in the trachea and the native lung. Following reduction of the immunosuppressive regimen a complete remission was obtained 1 year later. Up to the present time, this clinical remission is very encouraging, but close surveillance remains necessary to detect rejection episodes or the reappearance of KS following manipulation of the immunosuppressive therapy.

Progressive obstructive lung disease associated with microscopic polyangiitis.

Small airway involvement and progressive severe airflow obstruction are unexpected features in patients with microscopic polyangiitis. We report the case of a patient with microscopic polyangiitis and circulating anti-neutrophil cytoplasmic antibodies (ANCA), who developed pulmonary hyperinflation and airflow obstruction over a 7-yr period. Systemic manifestations of this vasculitis improved under corticosteriods and cyclophosphamid therapy, a treatment that did not influence either the very high level of anti-myeloperoxidase antibodies or the ventilatory impairment. Small airway involvement was suspected on the basis of pathologic small airway lesions and a mild emphysematous pattern on computed tomography (CT) scan, which was out of proportion with the severity of the obstructive lung disease.

[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.

Fluoxetin-induced pulmonary granulomatosis.

A patient treated with fluoxetin for a manic depressive disorder developed pulmonary inflammatory nodules with noncaseating giant cell granulomas, interstitial pneumonia and non-necrotizing vasculitis, whilst remaining asymptomatic. A progressive resolution of pulmonary nodules occurred after withdrawal of the offending agent, and the chest radiograph returned to normal in 9 months. The diagnosis was assessed by an open lung biopsy.

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.