Clinical and molecular epidemiology of lymphangioleiomyomatosis and lung involvement in tuberous sclerosis

Pulmonary lymphangioleiomyomatosis is characterized by a proliferation of a bnormal smooth muscle cells in peribronchial, perivascular and perilymphati c areas leading to cystic destruction of the pulmonary parenchyma. Recent c linical series of LAM have been helpful in better describing the various cl inical and radiological forms of the disease, although our understanding of the pathophysiological mechanisms of LAM remains very limited. Significian t progress has been noted in recent years with the discovery of probable an tigenic and genetic similarities between pulmonary lymphangioleiomyomatosis , Bourneville tuberous sclerosis and renal angiomyolipoma The prolieferatin g cells in LAM share with normal smooth muscle cells their reactivity with desmine, vimentin and actin but certain are different by their reactivity w ith the monoclonal antibody HMB45, a common antigen marker of melanocyte di fferentiation cells, clear-cell lung carcinomas or renal angiomyolipomas. A loss heterozygosity in the region of the TSC2 gene in renal angiomyolipoma s has been demonstrated in association with pulmonary lymphangioleiomyomato sis. The TSC2 gene is particularly implicated in the pathogenesis of Bourne ville tuberous sclerosis.