Multicenter harmonization study for PD-L1 IHC testing in non-small-cell lung cancer.

Background: Various programed death ligand 1 (PD-L1) immunohistochemistry (IHC) assays have been developed and used in clinical trials in association with different drugs. In order to harmonize and make PD-L1 testing in non-small-cell lung cancer (NSCLC) widely available, we conducted a multicenter study comparing PD-L1 standardized assays and laboratory-developed tests (LDTs). Methods: IHC with five anti-PD-L1 monoclonal antibodies (28-8, 22C3, E1L3N, SP142 and SP263) was performed concomitantly on 41 NSCLC surgical specimens in 7 centers using Dako Autostainer Link 48 (3 centers), Leica Bond (2 centers) or Ventana BenchMark Ultra (2 centers) platforms. For each matching platform, 22C3, 28-8 and SP263 assays were performed. For nonmatching platforms and other antibodies, LDTs were developed in each center. A total of 35 stainings were performed for each case across different platforms and antibodies. PD-L1 staining was assessed in tumor cells and immune cells by seven trained thoracic pathologists. For statistical analysis, 1%, 50% and 1%, 5%, 10% expression thresholds were used for tumor cells and immune cells, respectively. Results: 28-8, 22C3 and SP263 assays were highly concordant for tumor cells staining across the five Dako or Ventana platforms. Among 27 LDTs developed in 7 centers on Dako, Ventana and Leica platforms, 14 (51.8%) demonstrated similar concordance when compared with reference assays for tumor cell staining. Clone SP263 achieved the highest concordance rate across all platforms. Lower concordance was observed for immune cells staining when using a four categories scale. Conclusion: 28-8, 22C3 and SP263 assays had close analytical performance for tumor cell staining across seven centers. Some LDTs on Dako, Ventana and Leica platforms achieved similar concordance, but caution is warranted for their validation. These LDTs will be further validated in order to provide recommendations for the use of assays and LDT for PD-L1 testing in NSCLC.

Clinical and molecular characteristics of non-small-cell lung cancer (NSCLC) harboring EGFR mutation: results of the nationwide French Cooperative Thoracic Intergroup (IFCT) program.

BACKGROUND: EGFR mutations cause inconsistent response to EGFR tyrosine-kinase inhibitors (TKI). To better understand these features, we reviewed all cases of EGFR-mutated non-small-cell lung cancer collected in the Biomarkers France database. PATIENTS AND METHODS: Of 17 664 patients, 1837 (11%) with EGFR-mutated non-small-cell lung cancer were retrospectively analyzed for clinical and molecular characteristics. Results were correlated with survival and treatment response for the 848 stage IV patients. RESULTS: EGFR exon 18, 19, 20 and 21 mutations were found in 102 (5.5%), 931 (51%), 102 (5.5%) and 702 (38%) patients, respectively. Over 50% of exon 18 and 20 mutated patients were smokers. The median follow-up was 51.7 months. EGFR mutation type was prognostic of overall survival (OS) versus wild-type {exon 19: hazard ratio (HR)=0.51 [95% confidence interval (CI): 0.41-0.64], P < 0.0001; exon 21: HR = 0.76 (95% CI: 0.61-0.95), P = 0.002; exon 20: HR = 1.56 (95% CI: 1.02-2.38), P = 0.004}. EGFR mutation type was prognostic of progression-free survival versus wild-type [exon 19: HR = 0.62 (95% CI: 0.49-0.78), P < 0.0001; exon 20: HR = 1.46 (95% CI: 0.96-2.21), P = 0.07]. First-line treatment choice did not influence OS in multivariate analysis. First-line TKI predicted improved progression-free survival versus chemotherapy [HR = 0.67 (95% CI: 0.53-0.85), P = 0.001]. OS was longer for del19 versus L858R, which was associated with better OS compared with other exon 21 mutations, including L861Q. TKI improved survival in patients with exon 18 mutations, while chemotherapy was more beneficial for exon 20-mutated patients. CONCLUSION: EGFR mutation type can inform the most appropriate treatment. Therapeutic schedule had no impact on OS in our study, although TKI should be prescribed in first-line considering the risk of missing the opportunity to use this treatment.

High-throughput somatic mutation profiling in pulmonary sarcomatoid carcinomas using the LungCarta™ Panel: exploring therapeutic targets.

BACKGROUND: Pulmonary sarcomatoid carcinomas (SC) are tumors characterized by poor prognosis and resistance to conventional platinum-based chemotherapy. This study sought to describe the mutational profile of SC using high-throughput genotyping technology. PATIENTS AND METHODS: We used mass spectrometry to test 114 surgical biopsies from 81 patients with SC for 214 mutations affecting 26 oncogenes and tumor suppressor genes. RESULTS: In total, 75 (92.6%) patients were smokers. Within the total 81 tumors, 67 distinct somatic alterations were identified, with 56 tumors (69.1%) harboring at least one mutation. The most frequent mutations were KRAS (27.2%), EGFR (22.2%), TP53 (22.2%), STK11 (7.4%), NOTCH1 (4.9%), NRAS (4.9%), and PI3KCA (4.9%). The EGFR mutations were almost always rare mutations (89%). In 32 tumors (39.5%), two or more mutations co-existed, with up to four mutations in a single case. In six different cases, comparative genetic analysis of different histological areas from the same tumor (giant, spindle, or epithelial component) revealed a 61% concordance rate for all the mutations with a 10% detection threshold, compared with 91.7% with a 20% detection threshold. CONCLUSION: Our results demonstrated a high mutation rate and frequent co-mutations. Despite SC tumors exhibiting a high histological heterogeneity, some intratumoral molecular homogeneity was found. Now with newly developed targeted therapies, SC patients may be eligible for new target mutations, and can now therefore be screened for clinical trials.

Rare EGFR exon 18 and exon 20 mutations in non-small-cell lung cancer on 10 117 patients: a multicentre observational study by the French ERMETIC-IFCT network.

BACKGROUND: There is scarce data available about epidermal growth factor receptor (EGFR) mutations other than common exon 19 deletions and exon 21 (L858R) mutations. PATIENTS AND METHODS: EGFR exon 18 and/or exon 20 mutations were collected from 10 117 non-small-cell lung cancer (NSCLC) samples analysed at 15 French National Cancer Institute (INCa)-platforms of the ERMETIC-IFCT network. RESULTS: Between 2008 and 2011, 1047 (10%) samples were EGFR-mutated, 102 (10%) with rare mutations: 41 (4%) in exon 18, 49 (5%) in exon 20, and 12 (1%) with other EGFR mutations. Exon 20 mutations were related to never-smoker status, when compared with exon 18 mutations (P < 0.001). Median overall survival (OS) of metastatic disease was 21 months [95% confidence interval (CI) 12-24], worse in smokers than in non-smoker patients with exon 20 mutations (12 versus 21 months; hazard ratio [HR] for death 0.27, 95% CI 0.08-0.87, P = 0.03). Under EGFR-tyrosine kinase inhibitors (TKIs), median OS was 14 months (95% CI 6-21); disease control rate was better for complex mutations (6 of 7, 86%) than for single mutations (16 of 40, 40%) (P = 0.03). CONCLUSIONS: Rare EGFR-mutated NSCLCs are heterogeneous, with resistance of distal exon 20 insertions and better sensitivity of exon 18 or complex mutations to EGFR-TKIs, probably requiring individual assessment.

Improvement of the cytological diagnostic accuracy of follicular thyroid lesions by the use of the Ki-67 proliferative index in addition to cytokeratin-19 and HBME-1 immunomarkers: a study of 61 cases of liquid-based FNA cytology with histological controls.

OBJECTIVES: To evaluate HBME-1, cytokeratin-19 (CK-19) and Ki-67 immunomarkers in order to increase the diagnostic accuracy of preoperative thyroid fine needle aspiration (FNA) cytology. METHODS: Immunocytochemistry against HBME-1, CK-19 and Ki-67 was performed on 123 thyroid FNAs processed by liquid-based cytology (LBC). Statistical analysis was carried out on 61 cases with histological control and sufficient material for one or more of the three markers. The Bethesda System was used for cytological diagnosis. RESULTS: Taking into account all the cytological categories, with a cut-off of 30% of positive cells, HBME-1 (n = 47) and CK-19 (n = 53) showed a sensitivity for malignancy of 66.7% (95% confidence interval, 53.2-80.1) and 90.5% (82.6-98.4) and a specificity of 90.6% (82.3-99) and 75% (63.3-86.7), respectively. For Ki-67 (n = 54) with a cut-off of 1% of positive cells, the sensitivity was 85.0% (75.5-94.5) and the specificity 70.6% (58.4-82.7). In the follicular neoplasm/suspicious for follicular neoplasm (FN/SFN) category (n = 37), which was the focus of the study, papillary thyroid carcinomas (PTCs) were less numerous (four cases, three of which were the follicular variant), the positivity of the three immunomarkers combined showed an overall accuracy of 91% (21/23). The mean percentage of Ki-67-positive cells was increased in malignant lesions, with the exception of follicular variant PTCs: 16% ± 15.6% in two follicular carcinomas, 4.8% ± 3.2% in 13 classical PTCs, 1% ± 1.2% in five follicular variant PTCs and 0.5% ± 1.9% in 34 non-malignant lesions. CONCLUSIONS: Immunocytochemistry using HBME-1, CK-19 and the Ki-67 proliferative index increased the diagnostic accuracy of FNA in the FN/SFN category of the Bethesda System, which may help to distinguish lesions in this category with a low or high risk of malignancy. Thus, clinical management would be improved.

[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.

Immunohistochemistry to identify EGFR mutations or ALK rearrangements in patients with lung adenocarcinoma.

BACKGROUND: Immunohistochemistry has been proposed as a specific and sensitive method to identify EGFR mutations or ALK rearrangements in lung tumours. PATIENTS AND METHODS: We assessed EGFR and KRAS by direct sequencing in 154 patients with lung adenocarcinoma. ALK rearrangements were assayed by FISH and RT-PCR. Immunohistochemistry was carried out and evaluated closely following published methods using recommended monoclonal rabbit or mouse antibodies. RESULTS: Thirteen of 36 exon 19 EGFR-mutated tumours (36%)-including 12 of 22 with p.Glu746_Ala750del (55%)-were positive with the 6B6 antibody that was raised against p.Glu746_Ala750del. One hundred eleven of 114 EGFR exon 19 wild-type tumours (97%) were negative with 6B6. Four of 21 exon 21 EGFR-mutated tumours (19%)-including 4 of 17 with p.Leu858Arg (24%)-were positive with the 43B2 antibody that was raised against p.Leu858Arg. One hundred twenty-two of 124 (98%) EGFR exon 21 wild-type tumours were negative with 43B2. Two of four ALK rearrangements-including two of three with ELM4-ALK fusion transcripts-were identified with the 5A4 antibody. Eleven of 13 tumours without ALK rearrangement (85%) were negative with 5A4. CONCLUSIONS: Immunohistochemistry is a specific means for identification of EGFR mutations and ALK rearrangements. It suffers, however, from poor sensitivity.

A comparison of low vs conventional-dose heparin for minimal cardiopulmonary bypass in coronary artery bypass grafting surgery.

The biocompatibility of minimal extracorporeal circuits has improved; however, anticoagulation is still required. We compared standard high-dose anticoagulation with a low-dose heparin regimen in a retrospective study of patients who underwent coronary bypass surgery using minimal cardiopulmonary bypass. One hundred patients who received 300 IU.kg(-1) heparin were compared with 68 patients who received heparin according to an individually adjusted activated coagulation time target of 300 s, resulting in a mean (SD) heparin dose of 145 (30) IU.kg(-1) . There were no thromboembolic events in either group; however, patients in the low-dose group had lower 24-hour mean (SD) postoperative blood loss than the conventional group (545 (61) vs 680 (88) ml, p=0.001) and a reduced rate of transfusion of allogeneic blood (15% patients transfused vs 32%, p=0.01). An individually tailored low-dose heparin regimen for minimal cardiopulmonary bypass is safe and may be associated with reduced bleeding and lower transfusion requirements.

[Management of a patient with a double EGFR and MET anomaly by combined treatment]. / Prise en charge d'un patient par traitement combiné d'une double anomalie EGFR et MET.

INTRODUCTION: Lung cancer displays molecular anomalies for which targeted therapies are the standard first line treatment. The EGFR mutation is present in 10% of cases of non-small cell lung cancer in Caucasians. MET amplification associated with an exon 19 EGFR mutation has been identified though it is usually regarded as a mechanism of resistance. CASE REPORT: We report the case of a 74-year-old never-smoking woman who was diagnosed with stage IV bronchial adenocarcinoma showing both EGFR mutation and MET amplification. Initial treatment with gefitinib did not control the disease. Platinum-based chemotherapy with pemetrexed maintenance allowed a temporary response. Treatment with durvalumab for 27 months was associated with disease stability. Single agent crizotinib was associated with a slight response followed by progression. The concomitant introduction of crizotinib and gefitinib led to a spectacular and durable response with no safety issues. CONCLUSIONS: This case highlights the efficacy of concomitant treatment in a patient with two oncogenic drivers.

[Sarcoid-like granulomatosis in cancer patients treated with immune checkpoints inhibitors]. / Granulomatose sarcoïdosique survenant sous inhibiteurs de point de contrôle immunitaire.

INTRODUCTION: Immune checkpoint inhibitors are becoming a standard treatment for many different cancers. Their toxicities are variable and include organ-specific dysimmune injuries and the development of systemic diseases. CASE REPORT: We report 3 cases of sarcoid-like granulomatosis that occurred during treatment of various types of primary cancer by immune checkpoint inhibitors: lung adenocarcinoma, small cell lung cancer and melanoma. The clinical presentation, radiologic pattern and severity of this toxicity were variable. The diagnosis was made on biopsy with pathological examination and exclusion of differential diagnoses, particularly infection. In such cases, immunotherapy should be discontinued and subsequent rechallenge discussed later. Systemic corticosteroids should be considered depending on the severity of symptoms. CONCLUSIONS: Knowledge of this toxicity is crucial as the clinical signs and radiological patterns may suggest tumour progression.

New Insights on Diagnostic Reproducibility of Biphasic Mesotheliomas: A Multi-Institutional Evaluation by the International Mesothelioma Panel From the MESOPATH Reference Center.

INTRODUCTION: The 2015 WHO classification of tumors categorized malignant mesothelioma into epithelioid, biphasic (BMM), and sarcomatoid (SMM) for prognostic relevance and treatment decisions. The survival of BMM is suspected to correlate with the amount of the sarcomatoid component. The criteria for a sarcomatoid component and the interobserver variability between pathologists for identifying this component are not well described. In ambiguous cases, a "transitional" (TMM) subtype has been proposed but was not accepted as a specific subtype in the 2015 WHO classification. The aims of this study were to evaluate the interobserver agreement in the diagnosis of BMM, to determine the nature and the significance of TMM subtype, and to relate the percentage of sarcomatoid component with survival. The value of staining for BRCA-1-associated protein (BAP1) and CDKN2A(p16) fluorescence in situ hybridization (FISH) were also assessed with respect to each of the tumoral components. METHODS: The study was conducted by the International Mesothelioma Panel supported by the French National Cancer Institute, the network of rare cancer (EURACAN) and in collaboration with the International Association for the Study of Lung Cancer (IASLC). The patient cases include a random group of 42 surgical biopsy samples diagnosed as BMM with evaluation of SMM component by the French Panel of MESOPATH experts was selected from the total series of 971 BMM cases collected from 1998 to 2016. Fourteen international pathologists with expertise in mesothelioma reviewed digitally scanned slides (hematoxylin and eosin - stained and pan-cytokeratin) without knowledge of prior diagnosis or outcome. Cases with at least 7 of 14 pathologists recognizing TMM features were selected as a TMM group. Demographic, clinical, histopathologic, treatment, and follow-up data were retrieved from the MESOBANK database. BAP1 (clone C-4) loss and CDKN2A(p16) homozygous deletion (HD) were assessed by immunohistochemistry (IHC) and FISH, respectively. Kappa statistics were applied for interobserver agreement and multivariate analysis with Cox regression adjusted for age and gender was performed for survival analysis. RESULTS: The 14 panelists recorded a total of 544 diagnoses. The interobserver correlation was moderate (weighted Kappa = 0.45). Of the cases originally classified as BMM by MESOPATH, the reviewers agreed in 71% of cases (385 of 544 opinions), with cases classified as pure epithelioid in 17% (93 of 544), and pure sarcomatoid in 12% (66 of 544 opinions). Diagnosis of BMM was made on morphology or IHC alone in 23% of the cases and with additional assessment of IHC in 77% (402 of 544). The median overall survival (OS) of the 42 BMM cases was 8 months. The OS for BMM was significantly different from SMM and epithelioid malignant mesothelioma (p < 0.0001). In BMM, a sarcomatoid component of less than 80% correlated with a better survival (p = 0.02). There was a significant difference in survival between BMM with TMM showing a median survival at 6 months compared to 12 months for those without TMM (p < 0.0001). BAP1 loss was observed in 50% (21 of 42) of the total cases and in both components in 26%. We also compared the TMM group to that of more aggressive patterns of epithelioid subtypes of mesothelioma (solid and pleomorphic of our large MESOPATH cohort). The curve of transitional type was persistently close to the OS curve of the sarcomatoid component. The group of sarcomatoid, transitional, and pleomorphic mesothelioma were very close to each other. We then considered the contribution of BAP1 immunostaining and loss of CDKN2A(p16) by FISH. BAP1 loss was observed in 50% (21 of 41) of the total cases and in both component in 27% of the cases (11 of 41). There was no significant difference in BAP1 loss between the TMM and non-TMM groups. HD CDKN2A(p16) was detected in 74% of the total cases with no significant difference between the TMM and non-TMM groups. In multivariate analysis, TMM morphology was an indicator of poor prognosis with a hazard ratio = 3.2; 95% confidence interval: 1.6 - 8.0; and p = 0.003 even when compared to the presence of HD CDKN2A(p16) on sarcomatoid component (hazard ratio = 4.5; 95% confidence interval: 1.2 - 16.3, p = 0.02). CONCLUSIONS: The interobserver concordance among the international mesothelioma and French mesothelioma panel suggests clinical utility for an updated definition of biphasic mesothelioma that allows better stratification of patients into risk groups for treatment decisions, systemic anticancer therapy, or selection for surgery or palliation. We also have shown the usefulness of FISH detection of CDKN2A(p16) HD compared to BAP1 loss on the spindle cell component for the separation in ambiguous cases between benign florid stromal reaction from true sarcomatoid component of biphasic mesothelioma. Taken together our results further validate the concept of transitional pattern as a poor prognostic indicator.

[Alveolar capillary dysplasia and persistent pulmonary hypertension of the newborn]. / La dysplasie alvéolo-capillaire: une cause exceptionnelle d'hypertension artérielle pulmonaire persistante du nouveau né. A propos d'un cas.

Alveolar capillary dysplasia is a rare cause of persistent pulmonary hypertension of the newborn. The diagnosis of this condition is made by histological study of a pulmonary biopsy. Familial forms and associated genitor-urinary and gastrointestinal malformations have been reported. Despite optimal management, the prognosis remains poor. The authors report the case of a neonate who developed cyanosis and cardiogenic shock on the 10th day of life. There was no associated neonatal pathology. Echocardiography showed supra-systemic pulmonary hypertension with normal cardiac structure. Pulmonary vasodilator therapies (inhaled NO, prostacyclin, sildenafil, bosentan) were ineffective and the child died on the 25th day of life. Autopsy revealed alveolar capillary dysplasia.

[Lung cancer in women and pregnancy: towards a hormonal origin?]. / Cancer bronchique de la femme et de la femme enceinte: vers une origine hormonale?

INTRODUCTION: The incidence of lung cancer is increasing dramatically in women in France. It is now the leading cause of cancer deaths among women in the USA and the second in France. STATE OF THE ART: Lung cancer occurring in women displays some specific epidemiological, radiological, clinical and pathological characteristics. Moreover, both prognosis and response to treatment appear to be different from men. In line with these findings, lung carcinogenesis is, at least in part, distinct in women and involves different mechanisms and signalling pathways. We emphasize in this review genetic and hormonal specificities based upon epidemiological and biological studies. Moreover, we focus on lung cancer developing during pregnancy by reporting an individual case and discussing the published literature. PERSPECTIVES AND CONCLUSIONS: Recent works suggest that lung cancer in women is a distinct entity with specific carcinogenesis. We propose that a better knowledge of this entity will permit the identification of specific genetic alterations or hormonal profiles that may serve as new therapeutic targets.

[Interest of crizotinib in a lung cancer patient with de novo amplification of MET]. / Intérêt du crizotinib chez un patient porteur d'un cancer bronchique avec amplification de novo de MET.

Targeted therapy in lung cancer changes the prognostic and treatment of patients. MET is an oncogene including exon 14 mutations and gene amplification associated with worse prognosis. We here report the case of a 47-year-old former smoker, woman, with a stage IV lung adenocarcinoma with multiple chemotherapy failure. A MET amplification was identified and the patient consequently received crizotinib. A major response was observed after eight weeks of treatment. MET amplification screening appears to be interesting with some oncogenic-addicted tumor response rate. Those patients should be enrolled in clinical trials dedicated to tumor with MET alteration.

[Peripheral polyneuropathy after heat stroke]. / Polyneuropathie périphérique après coup de chaleur.

The authors report the case of a woman who developed a peripheral polyneuropathy after heat stroke. All the classical aetiologies of neuropathy were excluded. The final diagnostic was residual peripheral neuropathy provoked by heat stroke. The sequella of heat stroke are dominated by cerebellar compromise, but this case shows that peripheral polyneuropathies exist even if they are rare. They raise the issue of care because of severe neurological sequella.

[Organization of an operational site. Comparison of the durations of intervention planned and real]. / Organisation d'un site opératoire. Comparaison des durées d'intervention prévues et réelles.

OBJECTIVE: To improve planning of our operational site by comparing the durations of intervention scheduled by the surgeons and the real durations of occupation of room of intervention, surgical procedure and surgical operation. STUDY DESIGN: Prospective study carried out of December 8, 2003 to February 27, 2004. PATIENTS AND METHODS: Anaesthetic and surgical times of the interventions of visceral and gynaecological surgery were raised. From these data several durations were calculated like the duration of occupation of the room of intervention, surgical procedure and surgical operation. These durations were compared with the durations envisaged by the surgeons to carry out the planning of the operational activity. RESULTS: Two hundred and ten interventions were studied. The analysis showed that there was a significant difference between the duration planned and the real duration of occupation of the room of intervention 45 minutes [5-125] (p<0.0001). The duration planned corresponded with duration of surgical operation, duration which did not take into account anaesthetic induction and surgical installation. CONCLUSIONS: The effectiveness of the planning of an operational site depends on the exactness of the durations scheduled, which are used for its realization. It is significant that all the actors of the operating theatre suite use the durations closest to reality.

Papillary neoplasm of the endolymphatic sac in a patient with von Hippel-Lindau disease.

Glandular tumours involving the middle ear and the mastoid are rare, and distinguishing between adenoma and adenocarcinoma is difficult. Two distinct histopathological patterns are accepted. While their clinical presentation differs, both require primary surgical treatment and both have a high rate of local recurrence. The papillary form takes a more aggressive course and wider regional spread. This pattern occurs predominantly in women. Its microscopic appearance and clinical course have been extensively described by Heffner who considered it as "low-grade adenocarcinoma of probable endolymphatic sac origin". A few cases have been associated with von Hippel-Lindau disease. The case of a 32 year old black woman is described. It is suggested that papillary adenocarcinoma of the endolymphatic sac should be considered in the spectrum of neoplasms seen in von Hippel-Lindau disease.

[Specific respiratory manifestations associated with hemorrhagic rectocolitis. Analysis of a case and review of the literature]. / Manifestations respiratoires spécifiques associées à la rectocolite hémorragique. Analyse d'un cas et revue de la littérature.

Respiratory impairments occurring as systemic manifestations of ulcerative colitis are often misinterpreted. We report a case of chronic productive bronchitis associated with ulcerative colitis; symptoms appeared after colectomy. Clinical features distinguished it from common chronic bronchitis: it occurred in a woman without respiratory disease or smoking history, a chronic productive cough without bronchiectasis, negative infectious investigations, severe endoscopic and histologic lesions, and above all remarkable steroid efficacy. Systematic research and early treatment of these manifestations avoids aggravating pulmonary disease, especially secondary bronchiectasis. Though less frequent, other respiratory manifestations of ulcerative colitis have been described, such as asphyxiating tracheal stenosis, pneumonia or interstitial pulmonary diseases, pleurisy or pleuro-pericarditis.