Updated: Dec 22, 2019
  • Author: Joel Moss, MD, PhD; Chief Editor: Zab Mosenifar, MD, FACP, FCCP  more...
  • Print


Lymphangioleiomyomatosis (LAM) is a rare lung disease, 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.

In 2015, the World Health Organization reclassified lymphangioleiomyomatosis with PEComa benign and malignant tumors in a new PEComatous tumors group. Previously, LAM was considered an interstitial lung disease but it is now considered to be a low-grade destructive metastasizing neoplasm. [4]

LAM is almost exclusively seen in adult women and occurs both sporadically and in patients with tuberous sclerosis complex (TSC), an inherited an autosomal dominant neoplastic syndrome due, in part, to mutations in the TSC1 or TSC2 gene. [5] Dyspnea with daily activities, recurrent pneumothoraces, and hypoxia requiring supplemental oxygen develop in most patients within 10 years of symptom onset. [6]

The 2017 American Thoracic Society/Japanese Respiratory Society guidelines support a clinical diagnosis of LAM based on high-resolution computed tomography (HRCT) findings typical for LAM (eg, diffuse, thin-walled, round) and accompanied by any of the following clinical features: TSC, renal angiomyolipoma, cystic lymphangioleiomyoma, or chylous pleural effusions in the chest and/or abdomen. The guidelines give a strong recommendation for the use of vascular endothelial growth factor D testing to establish the diagnosis of LAM before considering lung biopsy in patients with cystic abnormalities on HRCT characteristic of LAM, but no other confirmatory clinical features. [6]

Excellent patient resources can be found at the LAM Foundation and the National Heart Lung and Blood Institute.



Proliferation of lymphangioleiomyomatosis (LAM) cells may obstruct bronchioles, [1] 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. [7] Animal models suggest that estrogen may promote the metastasis of TSC2-deficient cells to the lungs. [8]

Lymphangioleiomyomatosis can be associated with micronodular type II pneumocyte hyperplasia, particularly in individuals with tuberous sclerosis. The TSC mutations that occur in LAM result in abnormal signaling through the mammalian target of rapamycin (mTOR) pathway. [4, 9]

The etiology of lymphangioleiomyomatosis (LAM) is unknown; however, the fact that the condition occurs primarily in premenopausal women and that it is exacerbated by high estrogen states suggests a role for hormones.



LAM is almost exclusively seen in adult women affecting approximately 1 in 200,000 [10] , but has also been reported in adult men [11] and children. [12] Sporadic LAM affects 1 in 400,000 adult females; [13] and in TSC, LAM occurs in 30–40% of adult females. [14] Although Europe and Japan report case series [10] , no racial predilection has been reported.



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. [15] The statistics may improve further as patients are diagnosed earlier (lead-time bias) or with more benign disease.

Poor prognostic factors include the following:

  • Reduced forced expiratory volume in 1 second and/or diffusing capacity for carbon monoxide [16, 17]

  • A low LAM histology score, which quantifies the involvement of the lung with both LAM cells and cysts [15]

Pneumothorax is a complication of LAM occurring in 40% of patients at presentation and 66% of patients during the course of the disease. The estimated rate of recurrence after the first episode is 75%. [13]

Angiomyolipomas are seen in 33-50% of patients with sporadic LAM and up to 80% of patients with TSC. [18] Angiomyolipomas usually manifest as multifocal, bilateral, asymptomatic disease, but as the lesions exceed 3 to 4 cm, they may become symptomatic and increase the risk for aneurysms that can lead to hemorrhage. [19]

Other complications of lymphangioleiomyomatosis (LAM) include the following:

  • Hemoptysis

  • Chylothorax

  • Ascites

  • Chyloptysis

  • Chyluria

  • Hematuria

  • Pericardial effusion

  • Pneumoperitoneum

  • Lymphedema

  • Respiratory failure

  • Osteoporosis

  • Meningioma