Lymphangioleiomyomatosis: New Concepts in Pathogenesis, Diagnosis, and Treatment

Abstract

Lymphangioleiomyomatosis (LAM) is a slowly progressive lung disease that is associated with mutations in tuberous sclerosis complex genes, infiltration of the pulmonary parenchyma and lymphatics with neoplastic smooth muscle cells, extensive tissue remodeling and architectural distortion of the lung, and tumors of the chest and abdomen, including lymphangiomyomas and angiomyolipomas. LAM occurs in women in the general population and in patients of both genders with tuberous sclerosis. Overt clinical manifestations of LAM occur almost exclusively in females, however, and include progressive dyspnea on exertion, recurrent pneumothorax, and chylous effusions. The molecular basis of LAM has been extensively characterized over the past decade, resulting in the development of a targeted therapy. This article reviews emerging approaches to the diagnosis and treatment of LAM.

NK cell activating receptor ligand expression in lymphangioleiomyomatosis is associated with lung function decline

“…NKG2DLs ULBP2 and/or ULBP3 were present in all nodules and cystic lung lesions tested. NKG2DL expression within LAM tissue is consistent with the classification of LAM as a neoplasm (2,28). The role of TSC1/2 mutations in the expression of NKG2DL is unknown, but intersections between signaling pathways that regulate NKG2DL cell surface expression and PI3K/Akt/mTOR signaling known to play a role in LAM pathogenesis have been described in the literature.…”

Severity and outcome of cystic lung disease in women with tuberous sclerosis complex

“…Lymphangioleiomyomatosis (LAM), a multisystem disease affecting predominantly women, is characterised by cystic lung destruction, abdominal angiomyolipomas, lymphatic tumours and chylous effusions [1][2][3]. The pathological features of LAM are caused by proliferation of a neoplastic smooth muscle-like LAM cell that has characteristics of both smooth muscle cells and melanocytes [1,4].…”

Birt-Hogg-Dubé syndrome: characteristic CT findings differentiating it from other diffuse cystic lung diseases

“…This disorder predominantly affects women of reproductive age and may be developed in patients with tuberous sclerosis complex. Pulmonary function tests in LAM often show a chronic obstructive pattern, unlike BHD syndrome (11). The lung cysts in LAM are usually smaller and more uniform in size and shape.…”

“…Common chest CT findings of BHD syndrome include multiple irregular shaped cysts of various size with medial and basal predominance, subpleural and fissural cysts, cysts abutting or including the proximal portion of the lower pulmonary veins or arteries, and spontaneous pneumothorax. cysts in LAM progress slowly increasing in size and number and leading to respiratory failure within a decade after diagnosis in 10% to 20% of patients (11). Conservative management or treatment of complications such as pneumothorax or pleural effusion are usually suggested in patients with normal or mildly impaired lung function.…”