[French practical guidelines for the diagnosis and management of IPF - 2021 update, full version]. / Recommandations pratiques pour le diagnostic et la prise en charge de la fibrose pulmonaire idiopathique ­ Actualisation 2021. Version intégrale.

BACKGROUND: Since the previous French guidelines were published in 2017, substantial additional knowledge about idiopathic pulmonary fibrosis has accumulated. METHODS: Under the auspices of the French-speaking Learned Society of Pulmonology and at the initiative of the coordinating reference center, practical guidelines for treatment of rare pulmonary diseases have been established. They were elaborated by groups of writers, reviewers and coordinators with the help of the OrphaLung network, as well as pulmonologists with varying practice modalities, radiologists, pathologists, a general practitioner, a head nurse, and a patients' association. The method was developed according to rules entitled "Good clinical practice" in the overall framework of the "Guidelines for clinical practice" of the official French health authority (HAS), taking into account the results of an online vote using a Likert scale. RESULTS: After analysis of the literature, 54 recommendations were formulated, improved, and validated by the working groups. The recommendations covered a wide-ranging aspects of the disease and its treatment: epidemiology, diagnostic modalities, quality criteria and interpretation of chest CT, indication and modalities of lung biopsy, etiologic workup, approach to familial disease entailing indications and modalities of genetic testing, evaluation of possible functional impairments and prognosis, indications for and use of antifibrotic therapy, lung transplantation, symptom management, comorbidities and complications, treatment of chronic respiratory failure, diagnosis and management of acute exacerbations of fibrosis. CONCLUSION: These evidence-based guidelines are aimed at guiding the diagnosis and the management in clinical practice of idiopathic pulmonary fibrosis.

[French practical guidelines for the diagnosis and management of IPF - 2021 update, short version]. / Recommandations pratiques pour le diagnostic et la prise en charge de la fibrose pulmonaire idiopathique ­ Actualisation 2021. Version courte.

BACKGROUND: Since the previous French guidelines were published in 2017, substantial additional knowledge about idiopathic pulmonary fibrosis has accumulated. METHODS: Under the auspices of the French-speaking Learned Society of Pulmonology and at the initiative of the coordinating reference center, practical guidelines for treatment of rare pulmonary diseases have been established. They were elaborated by groups of writers, reviewers and coordinators with the help of the OrphaLung network, as well as pulmonologists with varying practice modalities, radiologists, pathologists, a general practitioner, a head nurse, and a patients' association. The method was developed according to rules entitled "Good clinical practice" in the overall framework of the "Guidelines for clinical practice" of the official French health authority (HAS), taking into account the results of an online vote using a Likert scale. RESULTS: After analysis of the literature, 54 recommendations were formulated, improved, and validated by the working groups. The recommendations covered a wide-ranging aspects of the disease and its treatment: epidemiology, diagnostic modalities, quality criteria and interpretation of chest CT, indication and modalities of lung biopsy, etiologic workup, approach to familial disease entailing indications and modalities of genetic testing, evaluation of possible functional impairments and prognosis, indications for and use of antifibrotic therapy, lung transplantation, symptom management, comorbidities and complications, treatment of chronic respiratory failure, diagnosis and management of acute exacerbations of fibrosis. CONCLUSION: These evidence-based guidelines are aimed at guiding the diagnosis and the management in clinical practice of idiopathic pulmonary fibrosis.

Lymphatic and blood microvasculature organisation in pulmonary sarcoid granulomas.

Pulmonary sarcoid granulomas are characterised by their elective distribution along collecting lymphatics. However, relationships between granulomas and intralobular lymphatics or blood microvascularisation have not been investigated. Therefore, we undertook a specific analysis of blood capillaries and lymphatics supplying sarcoid granulomas to identify additional clues to understanding the pathophysiogenesis of these lesions. Six pulmonary samples were immunolabelled with D2-40, anti-CD34 and anti-CD31 antibodies, paying particular attention to the relationships between lymphatics and granulomas, and the pattern of blood microvessels supplying sarcoid lesions. A morphometric study of granulomas included their distance to lymphatics and a three-dimensional reconstruction of a granuloma in its lymphatic context. Intralobular granulomas were closely associated with lymphatics; apart from a few granulomas, blood capillaries stopped at the outer border of the fibrous ring surrounding granulomas, and perigranuloma capillaries were particularly scarce. Our observations of the lymphatic and blood microvascular environment of intralobular pulmonary sarcoid granulomas provide evidence for the critical role of lymphatics in the emergence of these lesions. Moreover, pulmonary sarcoid lesions could be considered avascular structures, thereby providing new insights into the understanding of the granuloma physiology and the distribution of blood-borne therapeutic agents.

[Can nivolumab be used safely in idiopathic pulmonary fibrosis?] / Le nivolumab peut-il être utilisé dans les fibroses pulmonaires idiopathiques ?

Anti-PD1 immunotherapies have become an essential treatment for bronchial cancer. According to published studies, PD1 and PD-L1 inhibitors have a better toxicity profile than chemotherapy. Nevertheless, some immune related toxicities can be potentially severe, such as induced interstitial lung disease (ILD). Currently, ILD patients are excluded from clinical trials using immunotherapy in lung cancer. IPF is the most frequent and severe form of ILD. Lung cancer represents a major complication of this disease and to date few data exist on the safety of immunotherapy in this context. We report 3 cases of IPF with lung cancer treated by nivolumab. All had a clinically mild to moderate IPF. The patients had received at least one line of chemotherapy before nivolumab and had progressive, metastatic lung cancer. Two patients experienced rapid cancer progression without immune toxicities. The third had a partial response but developed grade III immune colitis that led to discontinuation of the treatment. None developed lung toxicity or worsening of IPF on CT during follow-up, and death was always related to progression of the cancer. In our series of three patients with IPF, nivolumab was well tolerated with regard to their pulmonary condition. As inflammation and autoimmunity are probably marginal mechanisms in the pathogenesis of IPF, we do not believe that the presence of IPF should definitely disqualify potential candidates for treatment with nivolumab. Decisions should be taken, case-by-case, in selected patients without severe IPF and with no evidence of autoimmunity. In view of the epidemiology of lung cancer in IPF and the critical role of immunotherapy in the management of lung cancer, studies of prospective cohorts are urgently needed in this population.

[Thoracic endometriosis]. / Endométriose thoracique.

INTRODUCTION: Endometriosis is defined as the abnormal presence of endometrial tissue, including endometrial glands and stroma, outside the uterine cavity. The term "thoracic endometriosis" is classically referred to the respiratory manifestations which classically result from the presence and the cyclical changes of endometrial tissue in one of the thoracic structures. STATE OF ART: Although thoracic endometriosis is rare, four clinical entities are well-recognized: pneumothorax, hemothorax, haemoptysis and pulmonary nodule, with a respective frequency of 73%, 14%, 7% and 6%. These are characterized by the recurrence of symptoms within the menstruations, in women aged between 30 and 40, and mainly in the right hemi-thorax. Pelvic endometriosis is usually, if not constantly, associated. Catamenial pneumothorax is not always related to thoracic endometriosis and its mechanisms remain unclear. An exploratory and therapeutical surgery is required in most of the cases. Video-assisted-thoracoscopy is the best current approach of catamenial pneumothorax. It may visualize pathognomonic pleuro-diaphragmatic abnormalities, including diaphragmatic fenestrations and/or endometrial implants, in about one third of the patients. Surgical treatment is justified because of the frequent relapses under medical treatment alone. Surgery consists of diaphragmatic repair and excision of all apparent endometrial implants; pleural abrasion may complete the procedure. A combined prolonged hormonal therapy is increasingly recommended, Danazol or GnRH analogs being advantaged. PERSPECTIVES: Further prospective studies are needed to estimate the real incidence of thoracic endometriosis and to devise the best therapeutical option. CONCLUSIONS: Thoracic endometriosis is probably rare but its diagnosis is easy when accurately raised. The approach is multidisciplinary involving a pneumologist, a thoracic surgeon and a gynecologist.

[Interstitial lung disease in systemic sclerosis]. / Pneumopathie infiltrante diffuse de la sclérodermie systémique.

INTRODUCTION: Interstitial lung diseases (ILD) in systemic sclerosis (SSc) are mainly encountered in patients with diffuse disease although they may occur less frequently in patients with limited cutaneous disease. BACKGROUND: In SSc early detection of ILD should be achieved by high resolution computed tomography and pulmonary function tests, including measurement of DLCO. In total up to 75% of patients with SSc develop ILD but it is progressive in only a minority of patients. Unlike idiopathic ILD, SSc associated ILD corresponds to non-specific interstitial pneumonia rather than usual interstitial pneumonia in the majority of cases. This explains the better prognosis of SSc associated ILD compared with idiopathic ILD. Nevertheless ILD represents one of the two main causes of death in SSc. VIEWPOINT: The treatment of SSc associated ILD is not well established. Anti-fibrosing treatments have failed to demonstrate benefit and cyclophosphamide, which has been used for about 15 years in the treatment of this condition, has recently been evaluated in two prospective randomised studies which showed a significant but modest effect on respiratory function. CONCLUSION: A subgroup of patients with rapidly progressive ILD might benefit from pulsed intravenous cyclophosphamide combined with prednisone 15 mg daily, but this remains to be confirmed.

[Lung sarcoidosis: Clinical features and therapeutic issues]. / Sarcoïdose pulmonaire : aspects cliniques et modalités thérapeutiques.

Sarcoidosis is a granulomatous disease of unknown cause. This proteiform disease is characterized by an almost constant and often predominant lung involvement. The natural history of disease is difficult to predict at presentation. Diagnosis is based on a compatible clinical and radiological presentation and evidence of non-caseating granulomas. Exclusion of alternative diseases is also required according to clinical presentation. Biopsy samples of superficial lesions should be considered before other sites like per-endoscopic bronchial biopsies or endobronchial ultrasound-guided transbronchial needle aspiration. Therapeutic strategy for lung disease has to take into account the possible spontaneous resolution observed in newly diagnosed patients. Corticosteroids are the first choice when a treatment is decided, which concerns half of patients. Second and third line therapy are based respectively on immunosuppressive drugs and anti-TNFα drugs. Sarcoidosis mortality and morbidity are mainly linked to advanced pulmonary sarcoidosis - lung fibrosis, pulmonary hypertension, bronchial stenosis and chronic pulmonary aspergillosis. "Non anti-inflammatory" treatments have to be considered as well. Clinicians have an essential role in treatment indication, end-point targets and evaluation of response to treatment during follow-up and in finding the best benefice to risk balance. Progress made on pharmacogenetics may offer more personalized treatments for the patients.

Diagnostic efficacy of ultrasound-guided core-needle biopsy of peripheral lymph nodes in sarcoidosis.

BACKGROUND: Core-needle biopsy guided by ultrasound can be performed for investigating peripheral lymph node (PLN). The aim of this study was to determine the efficacy of this technique in sarcoidosis. METHODS: Retrospective review of files of all patients in the database of the radiology department of Avicenne university hospital who underwent PLN biopsies guided by ultrasound from January 2008 to June 2011 (n=292). Cases with either granulomas at histology with the procedure or with a final diagnosis of sarcoidosis were included in the study. RESULTS: The histological specimens were adequate in 282 out of 292 cases (96%) showing non-caseating granulomas in 22 cases (n=20 patients with a final diagnosis of sarcoidosis and n=2 patients with tuberculosis). After reviewing clinical files of the 282 patient, 22 were confirmed to have sarcoidosis, at initial presentation (n=19) or later during flare-up or relapse (n=3) with only 2 patients having no granuloma on PLN biopsy. PLN were palpable in 18 cases and only detected by (18F)FDG-PET/CT showing increased PLN uptake in 4 cases. The sensitivity and specificity of adequate biopsy were 91 and 99% and the positive and negative predictive values were 91 and 99%, respectively. CONCLUSION: Core-needle biopsy guided by ultrasound has a high efficacy for evidencing granulomas in sarcoidosis patients with PLN involvement either clinically palpable or in the presence of (18F)FDG-PET/CT uptake.

[Pulmonary manifestations of antisynthetase syndrome]. / Les manifestations pulmonaires du syndrome des antisynthétases.

Antisynthetase syndrome is an inflammatory myopathy frequently associated with pulmonary manifestations, especially interstitial lung diseases, and uncommonly pulmonary hypertension. In the context of a suggestive clinical and radiological picture, positive anti-RNA synthetase antibodies confirm the diagnosis. Anti-Jo1, anti-PL7, and anti-PL12 antibodies are the more commonly encountered. The presence of a number of extra-thoracic manifestations in association with pulmonary disease may suggest the diagnosis. These include: myalgia or muscular deficit, Raynaud's phenomenon, polyarthritis, fever, mechanics hands. Serum creatine kinase levels are usually increased. Electromyogram, muscular magnetic resonance imaging or muscle pathology are not mandatory to make the diagnosis. There is a high variability in symptoms and severity, between patients but also during the course of the disease in the same patient. The presence of an interstitial lung disease is a major prognostic factor and an indication for more intensive treatment, principally with systemic corticosteroids with or without immunosuppressive drugs. Improving respiratory physicians' knowledge of this disease, which is often revealed by its pulmonary manifestations, should help diagnosis, therapeutic management, and possibly prognosis.

Low grade marginal zone B cell lymphoma of the breast associated with localised amyloidosis and corpora amylacea in a woman with long standing primary Sjögren's syndrome.

Primary low grade marginal zone B cell lymphoma (MZL) of the breast and localised mammary amyloidosis are exceedingly rare entities. This report describes the case of a woman with long standing Sjögren's syndrome presenting with asymptomatic MZL of the breast showing plasmacytic differentiation, associated with local ductular amyloidosis. The lesion was discovered incidentally in breast tissue resected for microcalcifications. Immunohistochemistry revealed kappa light chain restriction, supporting the neoplastic nature of the infiltrate. A retrospective molecular study of the salivary gland biopsy showed a B cell clone. This is the first report of the association of human mammary ductular amyloidosis with cartwheel shaped material identical to corpora amylacea, usually seen in brain, lung, and prostate, but unknown in the human breast. The excellent outcome without treatment seen in this patient further emphasises the need to distinguish between MZL with plasmacytic differentiation and extramedullary plasmacytoma.

Long-term survival of patients given hormonal therapy for metastatic endometrial stromal sarcoma.

Endometrial stromal sarcoma (ESS) is a rare neoplasm, mainly observed in premenopausal women. We describe two women 44 and 34 years old at the time ESS diagnosis, who developed lung metastases 3 and 6 years, respectively, after initial treatment: hysterectomy without (case 1) or with oophorectomy (case 2), followed by hormone replacement therapy (HRT) for the latter. Their estrogen (ER) and progesterone receptors (PR) were analyzed biochemically in metastatic lung tissue, yielding respective concentrations of ER 242 and 184, and PR 910 and 100 fmol/mg of cytosol protein. Both patients started treatment with the aromatase inhibitor aminoglutethimide (500 mg qid) after surgery for the first patient and after stopping HRT for the second. Under aromatase-inhibitor therapy, both patients achieved a complete response, patient 1 remains disease- free with 14+ years of follow-up, and patient 2 with 7+ years. Our data suggest that an aromatase inhibitor may be an effective treatment for ESS. Furthermore, routine ER and PR analyses could be useful to predict the response to hormonal therapy in ESS.

[Sarcoidosis and non-Hodgkin's lymphoma. A non-fortuitous association]. / Sarcoïdose et lymphome non hodgkinien. Une association non fortuite.

The simultaneous disclosure of a lymphoblastic B cell lymphoma and sarcoidosis is reported herein. The initially undiagnosed sarcoidosis leads to discuss the differential diagnosis of a sarcoid-like reaction associated to the lymphoma. The association of sarcoidosis and malignant lymphoproliferative disease is not fortuitous; nevertheless the simultaneity of the two diagnoses, the lymphoblastic type of the lymphoma and the colocalization of granulomatous and lymphomatous lesions in lung and liver are unusual features.

[Pulmonary lymphangioleiomyomatosis and sex hormones]. / Lymphangioléiomyomatose pulmonaire et hormones sexuelles.

The authors having prepared for a case of pulmonary lymphangioleiomatosis point out the diagnostic boundaries of this condition with benign metastasizing intravenous leiomyomas of the uterus, pulmonary localisation of Bourneville's tuberous sclerosis and the important aetio pathologic role of sex hormones. Finally they deal with the therapeutic management and the various uses of hormones to inhibit oestrogenic activity.

[A rare ovarian pseudotumor: massive edema of the ovary]. / Une pseudo-tumeur ovarienne rare: l'oedème massif de l'ovaire.

The authors report a case of massive ovarian edema which declared itself by pain in the abdomen and pelvis and an ovarian mass measuring 13 cm in diameter, occurring in a 22-year-old woman. Since it was not possible to make a diagnosis by any frozen-section examination, histology was carried out on the ovary that had been removed. This showed that the stroma of the ovary had become separated by massive edema preserving the albuginea and the superficial cortex. This case history of massive edema of the ovary shows the characteristics of this ovarian pseudotumour as described in the literature. The principal differential diagnoses of the condition are oedematous fibroma, and myxoma of the ovary. Apart from the fact that torsion of the adnexae can occur in some of these cases, the pathogenesis is still unexplained. When an ovarian tumour is found in a young woman a frozen-section examination must be carried out to make the diagnosis and perhaps avoid oophorectomy, particularly when untwisting a torsion can lead to resorption of the edema.

[Isolated pleural metastases from an atypical meningioma]. / Métastases pleurales isolées d'un méningiome atypique.

INTRODUCTION: Less than 2 per 1,000 meningiomas are complicated by extra-cranial metastases. These are most often found in the lung parenchyma, liver or lymph nodes. They almost always occur in anaplastic meningiomas (grade III according to OMS) and much more rarely in atypical meningiomas (grade II). CASE REPORT: We report a case of pleural metastases from a primary frontal atypical meningioma with no other extra-cranial spread. CONCLUSION: Poorly differentiated meningioma presents many morphological and immuno-histochemical similarities to malignant mesothelioma. For this reason the diagnosis of pleural metastase from a meningioma cannot be made without knowledge of the primary meningeal tumour and its histological type.

[Chronic diffuse interstitial pneumonia associated with chronic active hepatitis. 2 cases]. / Pneumopathie interstitielle diffuse chronique associée à une hépatite chronique active. 2 observations.

Two cases of chronic active hepatitis associated with diffuse interstitial pneumonia (lymphoid in one patient, lymphoid and fibrosing in the other) are reported. Histopathological data from the lungs, together with the parallel course of pulmonary and hepatic manifestations observed under corticosteroid therapy, suggest that these two diseases shared a common dysimmune pathogenesis. A few cases identical with these have been found in the literature. The clinical, laboratory and histopathological elements obtained from these cases also suggest an immune cause in most patients.

[Inflammatory pseudotumors of the lung with severe course]. / Pseudo-tumeurs inflammatoires pulmonaires d'évolution sévère.

Pulmonary inflammatory pseudotumors are usually unique lesions of unknown etiology with good prognosis. We report two severe cases with mediastinal invasion, local recurrence, extrathoracic locations, one of them with a fatal evolution. Certain microscopic features, which were present in our cases (increased cellularity, nuclear pleomorphism, mitotic activity, focal necrosis, bizarre giant cells, vascular invasion), may have prognostic relevance in determining an aggressive behavior of these tumors. Surgical resection is the recommended treatment, and incomplete resection, as in our cases, seems to be a risk factor for developing recurrent inflammatory pseudotumor. Immunosuppressive therapy was ineffective as well as radiotherapy in one of our cases. Only high doses of corticosteroids seemed to slow the evolution of the disease.

[The small airways: normal histology and the main histopathological lesions]. / Voies aériennes distales : histologie normale et lésions anatomopathologiques.

Lesions of the small airway are observed in a wide variety of pulmonary conditions, most of which are due to infection, tobacco and connective tissue diseases. They are sometimes isolated or, more often, associated with involvement of other pulmonary structures such as the bronchi, the lung parenchyma and the pleura. The pathological spectrum of the bronchiolar response to injury is relatively limited. Thus, the same lesion is observed in various clinical settings. There is no correlation between the severity of the small airway involvement seen by the pathologist and the clinical and functional manifestations of bronchiolitis. The causes of bronchiolitis may be classified on a clinical basis, on aetiology or on histological appearance, yet no single classification appears to be suitable. An integrated clinical, radiological, functional and histological approach is needed. As they are seen by the pathologist microscopically, small airway lesions may be subdivided into three categories: (1) simple nonspecific lesions (bronchiolitis - cellular, follicular, granulomatous, obliterative, constrictive) that are never exclusively related to one clinical picture, (2) or displaying a more specific pattern like the respiratory bronchiolitis of the smoker or the histolgical changes of asthma, (3) bronchiolar lesions in conditions described as "interstitial", predominantly centrilobular, involving the small airways and the lung parenchyma, and visible radiologically. After recalling the normal histological appearances of the bronchioles, this review describes the diversity of the histopathological lesions of the small airways.

[Lymphatics in non-tumoral pulmonary diseases. Review]. / Les lymphatiques dans les pathologies pulmonaires acquises non tumorales.

Whereas lymphatics in pulmonary non-tumoral diseases have been less studied than blood microcirculation, they clearly play a significant role. This review is a short update on lymphatics in various non-tumoral pulmonary diseases, from asthma to interstitial pneumonitis, excluding lymphangioleiomyomatosis. A lymphatic remodelling has been evidenced in asthma as well as in acute or chronic (UIP as NSIP) interstitial lung diseases. Such a remodelling can be explained as a side effect of local changes in fluidics but could also be an active player in the fibrosing process. Moreover the association of juxta-alveloar lymphatics and granulomas provides new insights in the emergence of these lesions in pulmonary sarcoidosis.