- Author: Joel Moss, MD, PhD; Chief Editor: Zab Mosenifar, MD, FACP, FCCP more...
Lymphangioleiomyomatosis (LAM) is a rare disorder resulting from proliferation in the lung, kidney, and axial lymphatics of abnormal smooth muscle–like cells (LAM cells) that exhibit features of neoplasia and neural crest origin.[1, 2, 3] Cystic destruction of the lung with progressive pulmonary dysfunction and the presence of abdominal tumors (eg, angiomyolipomas [AML], lymphangioleiomyomas) characterize the disease. LAM typically occurs in premenopausal women, suggesting the involvement of female hormones in disease pathogenesis. LAM can occur with increased frequency in patients with tuberous sclerosis complex (TSC), an autosomal dominant disorder due, in part, to mutations in the TSC1 or TSC2 gene.
Proliferation of lymphangioleiomyomatosis (LAM) cells may obstruct bronchioles, possibly leading to airflow obstruction, air trapping, formation of bullae, and pneumothoraces. Obstruction of lymphatics may result in lymphangioleiomyomas, chylothorax, and chylous ascites. Excessive proteolytic activity, which relates to an imbalance of the elastase/alpha1-antitrypsin system or metalloprotease (MMPs) and their inhibitors (tissue inhibitors of metalloproteases [TIMPs]), may be important in lung destruction and formation of cysts. Animal models suggest that estrogen may promote the metastasis of TSC2-deficient cells to the lungs.
Lymphangioleiomyomatosis (LAM) may occur sporadically or in association with tuberous sclerosis complex (TSC). To date, more than 1500 cases of sporadic LAM exist in the United States; LAM may occur in approximately 30-40% of patients with TSC.
The international frequency of lymphangioleiomyomatosis (LAM) is unknown, although Europe and Japan report case series.
No racial predilection has been reported for lymphangioleiomyomatosis (LAM).
Lymphangioleiomyomatosis (LAM) primarily is a disease of women; however, rare case reports describe LAM in men with TSC.
Although primarily a disease of women of childbearing age, lymphangioleiomyomatosis (LAM) has also been reported in postmenopausal patients.
Earlier reports indicated a grim prognosis for lymphangioleiomyomatosis (LAM), with progressive respiratory failure and death within 10 years of diagnosis. Recent reports, however, are more favorable, with 71% of affected patients alive at 10 years. The statistics may improve further as patients are diagnosed earlier (lead-time bias) or with more benign disease.
Poor prognostic factors include the following:
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