What is lymphangioleiomyomatosis?

Lymphangioleiomyomatosis (LAM) is a rare multisystem neoplastic disease characterized by diffuse cystic lesions in the lungs.

• The main clinical features include dyspnea, pneumothorax, chylothorax, and renal angiomyolipoma (AML).

• In recent years, the disease has been defined as a low-grade malignant, invasive, and metastatic tumor. Clinically, it is divided into two types: sporadic LAM (S-LAM) without a genetic background and LAM associated with the genetic disorder tuberous sclerosis complex (TSC-LAM).

Which department should be consulted for lymphangioleiomyomatosis?

English name: lymphangioleiomyomatosis, LAM.

Aliases: Lymphangiomyomatosis, pulmonary lymphangioleiomyomatosis, pulmonary lymphangiomyomatosis.

Departments: Respiratory Medicine, Thoracic Surgery.

What causes lymphangioleiomyomatosis?

The etiology of this disease remains unclear. The primary basis of its pathogenesis is mutations in the TSC1 or TSC2 genes, with TSC2 mutations being more common.

TSC1 and TSC2 proteins inhibit the mammalian target of rapamycin (mTOR) as a complex in the body. When TSC1 or TSC2 gene function is impaired, mTOR becomes overactivated, leading to excessive proliferation of LAM tumor cells. This is the most critical pathogenic mechanism of LAM and TSC.

Who is most commonly affected by lymphangioleiomyomatosis?

Almost all LAM cases occur in women, particularly those of childbearing age, with an average diagnosis age of around 40.

What are the main symptoms and manifestations of lymphangioleiomyomatosis?

• Early symptoms are mild, and some patients are discovered during physical examinations or lung high-resolution CT scans performed for respiratory symptoms or other reasons.

• LAM patients mainly exhibit varying degrees of dyspnea, which worsens as the disease progresses. Pulmonary function deteriorates progressively, leading to respiratory failure in advanced stages. Complications such as recurrent pneumothorax and chylothorax may occur during the course of the disease. Extrapulmonary manifestations include renal angiomyolipomas and retroperitoneal solid or cystic lymphangioleiomyomas.

• TSC-LAM occurs in adult female patients with tuberous sclerosis complex (TSC) and presents with other multisystem clinical features of TSC, including neurological changes (epilepsy, neurodevelopmental delays, autism, etc.) and skin changes (hypopigmented macules, facial angiofibromas, shagreen patches, periungual fibromas, etc.).

How is lymphangioleiomyomatosis diagnosed?

The diagnosis of LAM requires a clinical history and characteristic high-resolution CT findings (bilateral diffuse thin-walled cystic changes in the lungs). Additionally, one or more of the following features must be confirmed through medical history, laboratory tests, pleural/ascitic fluid analysis, or histopathological examination:

• Tuberous sclerosis complex (TSC);
• Renal angiomyolipoma;
• Serum vascular endothelial growth factor D (VEGF-D) ≥ 800 pg/ml;
• Chylothorax or chylous ascites;
• Lymphangioleiomyoma;
• Detection of LAM cells or LAM cell clusters in serous cavity effusions or lymph nodes;
• Histopathological confirmation of LAM (lung, retroperitoneal, or pelvic tumors).

How is lymphangioleiomyomatosis treated?

1. Specific treatment: Sirolimus is currently the specific molecular targeted therapy for LAM, as it inhibits mTOR. Given the long-term nature of treatment, potential adverse effects, and costs, a confirmed diagnosis is required before initiating therapy.

2. Comprehensive treatment: Inhaled bronchodilators may be considered for dyspnea, and home oxygen therapy is recommended for hypoxemia. A professionally guided pulmonary rehabilitation program is advised, along with vaccination to prevent respiratory infections. Lung transplantation may be considered if necessary.

3. Complication management: The disease has a high incidence of pneumothorax and chylothorax. Pleurodesis is recommended for the first episode of pneumothorax. Chylothorax treatment includes a fat-free or low-fat diet, substitution with medium-chain fatty acids, and consideration of sirolimus.

What is the prognosis for lymphangioleiomyomatosis?

The disease primarily affects lung function and generally has a poor prognosis. Early diagnosis, active treatment, infection prevention, and minimizing complications can help improve outcomes.

How can lymphangioleiomyomatosis be prevented?

• The cause of the disease is unclear. Since tuberous sclerosis is a genetic disorder, genetic counseling is recommended for families with similar conditions.
• Patients should avoid estrogen-containing medications or foods and undergo individualized assessment regarding pregnancy.
• Avoid triggers for pneumothorax, such as heavy lifting, sudden standing, or straining during bowel movements. Air travel should be temporarily avoided for those with recent pneumothorax or incomplete recovery from chest surgery.