Lymphangioleiomyomatosis (LAM) is a rare interstitial lung disease that typically occurs in women of child-bearing age. It is characterized by widespread abnormal proliferation of smooth muscle in the lung, mediastinal and retroperitoneal lymph nodes, and the major lymphatic ducts. It rarely occurs in males. Approximately 30% of patients with tuberous sclerosis (TS) have LAM. Patients present with shortness of breath, cough, and recurrent pneumothorax. Chylothorax is present in 70% of cases of LAM. Angiomyolipomas may precede pulmonary manifestations and are present in about half of patients. Spirometry usually shows normal lung volumes in contrast to abnormally large lungs due to air trapping on chest x-ray examination.

Most patients with LAM die of progressive respiratory failure within 10 years. Hormonal manipulation has yielded mixed results. Lung transplantation has been used successfully, although recurrence of LAM may occur. The cells in the recurrence are of recipient origin.

Pathogenesis is unknown. Cyst formation in LAM may be from uninhibited action of matrix metalloproteinases (MMP-2 and MMP-9), which are capable of degrading both elastic tissue and collagen. The proliferative and invasive nature of LAM cells may be due, in part, to somatic mutations in the TSC-1 and TSC-2 genes on chromosomes 9q34 and 16p13, respectively. The abnormal smooth-muscle cell in LAM may be related to the perivascular epithelioid clear cell. These cells give rise to a variety of tumors, such as angiomyolipomas, which are seen in LAM and are HMB-45 positive.

Grossly the lungs are diffusely enlarged with extensive cystic changes resembling honeycomb lung.