[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.

[Precocious mediastinal lipomatosis: a rare complication of systemic corticosteroid therapy]. / Lipomatose médiastinale précoce: une complication exceptionnelle de la corticothérapie generale.

BACKGROUND: Corticosteroid-induced lipomatosis results from hypertrophy within adipose tissue; the condition is frequently asymptomatic and its incidence is underestimated. We report a case of mediastinal lipomatosis that is rare in terms of both site and presenting symptoms. CASE REPORT: A 46-year-old woman with no disease history other than obesity with a weight of 90 kg had been treated since 2002 for mixed connective tissue disease (profound lupus and dermatomyositis). She had been treated with oral corti costeroids (1 mg/kg/d). Two months after the start of treatment, she presented chest pains, resting dyspnea particularly aggravated in dorsal decubitus, chest edema in the subclavicular space and jugular turgescence. Chest x-ray revealed widening of all levels of the mediastinum. The chest CT scan showed lipomatosis throughout the entire mediastinum with no associated chest abnormalities or pericardial effusion. Rapid downward dosage adjustment ofcorticosteroids to 10 mg/d coupled with synthetic antimalarials resulted in gradual reduction of symptoms. The chest scan performed two months later short stabilization of the patient's mediastinal lipomatosis. DISCUSSION: The effects of long-term of glucocorticosteroid therapy are well-known, in particular Cushing's syndrome. Lipomatosis has been described more recently and affects different axial regions. Mediastinal localization is seen in 15% of patients treated. This presentation is less common than orbital and epidural localizations. Although often asymptomatic, as in our own report, it may present with worrying symptoms that pose real diagnostic problems. The diagnostic examinations of choice are CT scan or MRI. Regression following discontinuation or reduction of corticosteroids is inconsistent and often gradual.

[Massive intraatrial mass?] / Panique dans l'oreillette.

Posterior mediastinal hematoma in a rare and potentially lethal disease and is frequently consecutive to a traumatism. We report the original case of a 88-year-old male admitted to our department for lipothymia and syncope related to a severe compression of the left atrium by an important mediastinal hematoma mimicking in transthoracic echocardiography an obstructive intraatrial mass.

Spontaneous mediastinal hemorrhage. A complication of intracoronary streptokinase infusion for coronary thrombosis.

A 72-year-old man with a recent inferior-wall myocardial infarction complicated by continued ischemic cardiac pain underwent an intracoronary streptokinase infusion in an attempt to re-establish coronary perfusion. Although the cardiac catheterization and streptokinase infusion were technically uncomplicated, signs of an enlarging mediastinal mass associated with a drop in the hematocrit reading developed in the patient 12 hours after the procedure. Aortography showed no evidence of aortic dissection or laceration. The patient was believed to have a spontaneous mediastinal hemorrhage related to streptokinase infusion.

[Sarcoidosis after adalimumab treatment in inflammatory rheumatic diseases: a report of two cases and literature review]. / Sarcoïdose survenant chez des patients traités par adalimumab pour un rhumatisme inflammatoire: à propos de deux cas et revue de la littérature.

CONTEXT: TNF α antagonists (anti-TNF α) are widely used in inflammatory rheumatic diseases: rheumatoid arthritis (RA) and spondylarthropathy (SpA). The efficacy of the anti-TNF α monoclonal antibodies was also observed in unresponsive sarcoidosis to conventional therapy. In contrast, sarcoidosis in patients with inflammatory rheumatic disease treated with anti-TNF α keep on growing, with a suspected role of anti-TNF α in this pathological process. METHODS: We presented here two cases of sarcoidosis developing while the patient was on adalimumab (ADA) therapy for inflammatory rheumatic disease. In one case, the reintroduction of ADA led to increase in symptomatology. We also analyzed the 16 other cases of sarcoidosis developing under ADA treatment published in literature, mostly in RA patients. RESULTS: These cases show a possible paradoxical effect of ADA in sarcoidosis development in patients treated with anti-TNFα monoclonal antibodies. The iatrogenic mechanism remains unclear. These cases underline the importance of a drug-induced etiology survey facing any symptomatology suggesting the development of sarcoidosis in patients treated with anti-TNF α for an inflammatory rheumatic disease.

Dapsone hypersensitivity syndrome-related lung injury without eosinophilia in the bronchoalveolar lavage fluid.

A 73-year-old man was admitted in respiratory failure that had subacutely progressed after five weeks of dapsone treatment for a skin rash. He also presented with fever, systemic erythroderma and liver dysfunction. Chest computed tomography showed diffuse reticular shadows with ground-glass opacity and bilateral mediastinal lymphadenopathy. Lymphocytes, but not eosinophils, were increased in the bronchoalveolar lavage fluid. Moreover, reactivation of human herpes virus-6 was confirmed on a paired serum test. Finally, we diagnosed the patient with dapsone hypersensitivity syndrome (DHS), a rare adverse event of this drug. Lung injury unaccompanied by eosinophilia in the bronchoalveolar lavage fluid is even more rare as a DHS-related lung manifestation.

Corticosteroid-induced mediastinal widening in myasthenia gravis.

Corticosteroid-induced mediastinal widening with simulated focal lymphadenopathy was found in a patient having myasthenia gravis. To my knowledge, this is the first report of such changes occurring in a patient having myasthenia gravis. As the use of corticosteroids in the treatment of myasthenia gravis becomes more common, this association can be expected to occur more often. Reemphasis of this phenomenon should help to avoid unnecessary surgical intervention in these patients.

Spontaneous hemomediastinum complicating steroid-induced mediastinal lipomatosis.

Spontaneous hemomediastinum is a rare event, occurring in association with bleeding disorders, intratumoral bleeding, or following an abrupt increase in intrathoracic pressure. We report the case of a patient with systemic lupus erythematosus, nephrotic syndrome, and renal failure, in whom mediastinal lipomatosis (ML) developed following increased corticosteroid therapy. Anticoagulant therapy likely precipitated a massive spontaneous hemomediastinum secondary to diffuse hemorrhage of mediastinal fat, which required emergency decompressive surgery. Steroid-induced ML is common and usually well tolerated, but clinicians should be aware of its potential risk of bleeding when associated with anticoagulant therapy. This case further emphasizes the bleeding complications of treatment with low-molecular-weight heparin in patients with renal failure.

Relation of preoperative use of aspirin to increased mediastinal blood loss after coronary artery bypass graft surgery.

To evaluate the potential effect of aspirin, a platelet inhibitory agent, on postoperative bleeding complications after coronary artery bypass graft surgery, we compared each of nine patients who had taken aspirin within 7 days prior to operation to one or two control subjects (total 16 patients) matched for age, sex, extent of coronary disease, number of grafts placed total operative time, bypass time, and preoperative use of propranolol. Preoperative prothrombin time, partial thromboplastin time, and platelet counts were normal for all patients. Mean mediastinal blood loss was significantly greater in the aspirin group (919 +/- 164 ml., S.E.) than in the control group (437 +/- 61 ml., p less than 0.001). The degree of mediastinal blood loss did not correlate with patient age, total operative time, bypass time, number of vessels diseased, or grafts placed. In addition, compared to controls the aspirin group required prolonged chest tube drainage (33 +/- 5 hours versus 19 +/- 1 hour, p less than 0.001).

Metastatic teratocarcinoma following chemotherapy. Maturation to a mass pathologically indistinguishable from a mediastinal enteric cyst.

A case of testicular teratocarcinoma metastatic to a mediastinal lymph node and associated with a mediastinal lesion indistinguishable from an enteric cyst is presented. It is postulated that the mediastinal enteric cyst-like lesion resulted from histologic maturation of metastatic teratocarcinoma after intensive chemotherapy. The basis in the medical literature for this postulate is detailed.

Heparin-induced thrombocytopenia in open heart surgical patients: sequelae of late recognition.

Most patients undergoing open heart operations have had exposure to heparin for diagnostic and/or therapeutic procedures. Heparin antibody formation and heparin-induced thrombocytopenia with repeat heparin administration can cause high morbidity and mortality from thrombotic complications, especially when delay in diagnosis occurs. From 1981 to 1991, heparin-induced thrombocytopenia was diagnosed in 82 of 4,261 open heart surgical patients (1.9%). Platelet counts less than 100 x 10(9)/L (100,000/microL) or new or recurring thrombotic events prompted suspicion of heparin-induced thrombocytopenia. Heparin-dependent antibody was diagnosed preoperatively in 12 patients (group I) and postoperatively in 70 patients (group II). Heparin was not given postoperatively in group I patients, and complications in this group were limited to bleeding in 3 patients. There were no thromboembolic events and all patients survived. Group II patients had late recognition of heparin-dependent antibody postoperatively, and heparin exposure was continued for varying periods postoperatively. Thirty-seven group II patients (53%) had bleeding complications and 31 (44%) had thromboembolic complications. These complications led to death in 23 group II patients (33%). Heparin-dependent antibody may occur in patients having open heart operations and is a major cause of morbidity and mortality if not diagnosed early with cessation of heparin therapy.

Sarcoidosis following chemotherapy for Hodgkin's disease.

A case report describing persistent paratracheal lymphadenopathy after doxorubicin, bleomycin, vinblastin, and dacarbazine (ABVD) chemotherapy for a patient with Hodgkin's disease (HD) is presented. Mediastinoscopy and biopsy of the paratracheal lymph nodes showed non-caseating granulomas characteristic of sarcoidosis. The authors discuss the relationship between sarcoidosis and HD and hypothesize that the development or progression of sarcoidosis in a patient with HD is a potential consequence of chemotherapy. Two possible mechanisms are proposed. The first includes the immunosuppressive effect of chemotherapy and the second implicates the influence of a specific chemotherapy agent, bleomycin, which is known to have relatively higher lymph node, skin and lung tissue concentrations than other agents included in the ABVD regimen, and a predilection for those tissues that are prone for the development of sarcoidosis. With the incidence of sarcoidosis exceeding that of HD for the general population, the authors emphasize the importance of considering the presence of sarcoidosis in the differential diagnosis of patients who do not respond radiographically to HD chemotherapy.

Drug-related pleural and mediastinal disorders.

The full range of mediastinal and pleural toxic effects of various drugs is reviewed. The importance of clinical information in suggesting the diagnosis of drug-induced disorders is emphasized. A separate section on the pleural and mediastinal toxic effects of illicit drugs is included.

The clinical diagnosis of drug-induced pulmonary disorders.

An increasing number of drugs have been implicated in the pathogenesis of a broad spectrum of pulmonary diseases. The clinical and radiographic manifestations are often nonspecific, requiring a high index of suspicion by both the clinician and the radiologist. The review focuses on patterns of drug-induced pulmonary disease, including parenchymal disorders, pulmonary vascular disease, pleural processes, airway disease, mediastinal abnormalities, and neuromuscular disorders. In each category, the differential diagnosis, clinical assessment, and diagnostic evaluation are discussed.

Pleural and mediastinal disorders related to drug use.

The full range of mediastinal and pleural effects of a variety of drugs both therapeutic and illicit has been reviewed. The importance of clinical information in making the diagnosis of these drug-induced disorders is emphasized.

New-onset mediastinal and central nervous system sarcoidosis in a patient with metastatic melanoma undergoing CTLA4 monoclonal antibody treatment.

BACKGROUND: Ipilimumab, a cytotoxic monoclonal antibody that inhibits cytotoxic T lymphocyte-associated antigen-4 (CTLA-4), has been established as an effective therapy in the management of advanced melanoma. Immune-mediated adverse events are a common side effect. CASE REPORT: A 37-year-old male patient was diagnosed with nodal and osseous metastatic melanoma 15 months after the initial surgical treatment for lower limb melanoma. Therapy with the anti-CTLA-4 antibody, ipilimumab, was started. Follow-up staging imaging after treatment initiation showed symmetrical bihilar adenopathy. Transbronchial biopsy showed sarcoidosis. The patient had associated systemic symptoms of fatigue, joint pains, anorexia and weight loss. Brain magnetic resonance imaging (MRI), which was performed for the investigation of headaches, showed abnormal enhancing tissue in the sella turcica and adjacent to the pituitary infundibulum, consistent with neurosarcoidosis. The condition was successfully treated with corticosteroids. CONCLUSIONS: We report a case of immunotherapy-induced mediastinal/hilar sarcoidosis, with pituitary involvement, mimicking tumour progression. This highlights the need for awareness amongst radiologists and oncologists of the mechanism of action and potential side effects of new immunotherapies.