Pulmonary Lymphangioleiomyomatosis: A Study of 69 Patients

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Abstract
Pulmonary lymphangioleiomyomatosis (LAM) is a rare disorder of unknown cause characterized by peribronchial, perivascular, and perilymphatic proliferation of abnormal smooth muscle cells leading to cystic lesions. The hypothesis of hormonal dependence and the effectiveness of hormonal therapy have not yet been demonstrated conclusively, and the prevalence of extrathoracic manifestations and the survival of patients with LAM are somewhat contradictory. A multicentric retrospective study was conducted in an attempt to describe better the initial features, the diagnostic procedures, the associated lesions, and, above all, the management and course of LAM in a large homogeneous series of 69 stringently selected patients, with a majority of cases diagnosed since 1990. The aim of the study, based on a review of the literature, also was to provide a comprehensive view of this uncommon disease. The clinical features were in keeping with previous studies, but we found that exertional dyspnea and pneumothorax were the most common features, and chylous involvement was less frequent. LAM was diagnosed after menopause in about 10% of cases. The onset of LAM occurred during pregnancy in 20% of cases, and a clear exacerbation of LAM was observed in 14% of cases during pregnancy. Pulmonary LAM was diagnosed on lung histopathology in 83% of cases, but renal angiomyolipoma, observed in 32% of our patients, may be a useful diagnostic criterion when associated with typical multiple cysts on chest CT scan or with chylous effusion. Chest CT scan was more informative than chest X-ray (normal in 9% of cases), and may be indicated in spontaneous pneumothorax or renal angiomyolipoma in women of childbearing age. About 40% of the patients had a normal initial spirometry, while an obstructive ventilatory defect (44%), a restrictive ventilatory defect (23%), was observed in other patients. Initial diffusing capacity for carbon monoxide was frequently decreased (82%). Hormonal therapy was administered in 57 patients, but a clear > or = 15% improvement of FEV1 was observed in only 4 evaluable patients, treated with tamoxifen and progestogens (n = 2), progestogen (n = 1), and oophorectomy (n = 1). Probably 1 of the most urgent needs for clinical research in LAM is to test the currently available hormonal treatments in the context of international multicenter prospective controlled studies. Pleurodesis was performed in 40 patients. Lung transplantation was performed in 13 patients, 7.8 +/- 5.2 years after onset of LAM, in whom the mean FEV1 was 0.57 +/- 0.15 L. After a follow-up of 2.3 +/- 2.2 years, 9 patients were alive. Mean follow-up from onset of disease to either death or closing date was 8.2 +/- 6.3 years. Overall survival was better than usually reported in LAM, and Kaplan-Meier plot showed survival probabilities of 91% after 5 years, 79% after 10 years, and 71% after 15 years of disease duration.