Definition of Lymphangioleiomyomatosis

Lymphangioleiomyomatosis: A lung disease characterized by an unusual type of muscle cell that invades the tissue of the lungs, including the airways, blood vessels, and lymph vessels. Over time, these muscle cells form into bundles and grow into the walls of the airways and blood and lymph vessels, causing them to become obstructed. Although these cells are not considered cancerous, they act somewhat like cancer cells in that they grow uncontrollably throughout the lung. The muscle cells in time block the flow of air, blood, and lymph to and from the lungs, preventing the lungs from providing oxygen to the rest of the body.

"Lymphangioleiomyomatosis" is pronounced lim - fan' je - o - li' o - mi' o - ma - to' sis. "Lymph-" and "-angio-" refer to the lymph and blood vessels. "Leiomyomatosis" refers to the formation of the bundles of the unusual muscle cells. Lymphangioleiomyomatosis is abbreviated LAM.

Cause: LAM can occur in association with tuberous sclerosis due to mutations in the tuberous sclerosis complex (TSC) genes TSC1 or TSC2 genes. Sporadic (isolated) caes of LAM typically result from 2 somatic mutations in the TSC2 gene, although a fraction of sporadic LAM is caused by germline mutations in the TSC1 gene.

Frequency: The precise number of people with LAM is not known. It has been estimated that there may be up to several hundred women in the US with it.

LAM almost exclusively affects women of childbearing age, although several cases have been reported in which the disease was thought to have developed after menopause. The international literature also includes reports of a few cases in men.

Symptoms: A common symptom of LAM is shortness of breath (dyspnea). In the early stages of disease, there may be dyspnea only during strenuous exercise, but as the disease advances, even at rest there may be shortness of breath. Another common symptom is chest pain. Occasionally, patients cough up small amounts of blood.

The symptoms are caused by the excessive growth of the muscle cells around the airways, and blood and lymph vessels. The excess muscle cells can block the airways, trapping air in the smallest air compartments in the lung (alveoli) and causing the person to have difficulty moving air out of the lungs. This results in a breakdown of the lung tissue and the formation of small cysts (air-filled cavities).

Cysts near or on the surface of the lung (blebs) can rupture and, as air leaks from the lung into the chest cavity (pneumothorax), the lung or a part of the lung can collapse, causing pain. If the amount of air that leaks out is small, the lung may seal over the space and re-expand itself. If air continues to leak into the chest cavity, however, it may be necessary to re-expand the collapsed portion of the lung by removing the air that has leaked into the chest cavity. This is an in-patient procedure, done using tube inserted through the chest wall into the chest cavity.

The excessive muscle growth may also block blood vessels in the lung, causing them to become distended with blood and even to rupture. This can result in the patient coughing up blood-stained sputum or blood (hemoptysis).

Obstruction of the lymphatic vessels by the excess muscle growth can lead to leakage of fluid into the chest cavity (pleural effusion). The fluid may be straw-colored (lymph), or fat-containing, milky white (chyle), or pinkish-red if it contains blood. A physician can remove some of this fluid with a needle and syringe to determine its composition and origin. If large amounts of this fluid accumulate in the chest cavity, it may have to be removed through a tube surgically inserted into the chest.

About 30 to 50% of patients with LAM develop leakage of air into the chest cavity (pneumothorax), and up to 80% have leakage of fluid into the chest cavity (pleural effusions). Coughing up blood-stained sputum or blood (hemoptysis) is less frequent.

Course: LAM is generally progressive, leading to increasingly impaired lung function. The rate of development can vary considerably among patients. As the disease advances, there is more extensive growth of muscle cells throughout the lung and repeated leakage of fluid into the chest cavity (pleural effusions). As an increasing number of cysts are formed, the lung takes on a honeycomb appearance.

The survival time following diagnosis is uncertain, as the disease seems to be highly individual. It had been reported to be less than 10 years, but new reports show patients living more than 20 years after diagnosis.

Diagnosis:The diagnosis of LAM can be difficult because many of the early symptoms are similar to those of other lung diseases, such as asthma, emphysema, or bronchitis. Often the person first goes to the physician complaining of chest pain and shortness of breath that was caused by a pneumothorax. Some patients first consult their physician because of shortness of breath upon exertion. There are a number of tests the physician can do to gather information about LAM:

• Chest X-ray -- This picture of the lungs and other tissue in the chest is used to diagnose a pneumothorax or the presence of fluid in the chest cavity (pleural effusion). Smooth muscle cysts, consistent with LAM, do not usually appear on X-ray.
• Pulmonary function tests -- The patient breathes through a mouthpiece into a machine (spirometer) that measures the volume of air in the lungs, the movement of air into and out of the lungs, and the movement of oxygen from the lungs into the blood.
• Blood test -- Blood is analyzed to determine whether the lungs are providing an adequate supply of oxygen to the blood.
• Computed tomography (CT) -- The most definitive imaging test for diagnosing LAM. On a CT scan, the presence of thin-walled cysts spread relatively uniformly throughout the lungs usually means LAM. An abdominal CT scan may disclose a benign kidney tumor called angiomyolipoma that is associated with LAM.
• Lung biopsy -- Two or more of the characteristic findings of LAM (cysts, fluid in the lungs, benign kidney tumor, and collapsed lung) may be considered diagnostic of LAM. An open lung biopsy should be performed as a last resort to diagnose LAM. In this procedure, a few small pieces of lung tissue are removed through an incision made in the chest wall between the ribs. Another procedure, thoracoscopy, is also being used in some patients to obtain lung tissue. In this procedure, tiny incisions are made in the chest wall, and a small lighted tube (endoscope) is inserted so that the interior of the lung can be viewed, and small pieces of tissue are removed. Both of these biopsy procedures must be done in the hospital under general anesthesia.

  Another technique, called transbronchial biopsy, may also be used to obtain a small amount of lung tissue. A long, narrow, flexible, lighted tube (bronchoscope) is inserted down the windpipe (trachea), and into the lungs. Bits of lung tissue are sampled, using a tiny forceps. This procedure is usually done in a hospital on an outpatient basis under local anesthesia. It is less reliable than an open lung biopsy because the amount of tissue that can be sampled is sometimes inadequate for diagnostic studies. After the lung tissue is removed, it is examined in a pathology laboratory for the presence of the abnormal muscle cells and cystic changes characteristic of LAM.

Treatment: Because LAM affects almost exclusively women of childbearing age, it has been thought that the hormone estrogen might be involved in the abnormal muscle cell growth that characterizes the disease, just as it is in the growth of smooth muscle in the uterus in a woman's childbearing years. Although there is no firm evidence that there is a relationship between estrogen and LAM, the treatment of ther disease has focused on reducing the production or effects of estrogen. The response to treatment has been highly individual, and no therapy has been found to be effective for all LAM patients. Oxygen therapy may be necessary if the disease continues to worsen and lung function is impaired.

For LAM patients with severe disease, lung transplantation is an established therapy. One year survival following transplant is approximately 70 percent, and 3-year survival is approximately 50 percent.

Effect on lifestyle: In the early stages of the disease, most patients can go about their daily activities, including attending school, going to work, and performing common physical activities, such as walking up a hill. In more advanced stages, the patient may have very limited ability to move around and may require oxygen full-time. Patients with LAM should follow the same healthy lifestyle recommended for the general population, including eating a healthy diet, getting as much exercise as they can, as well as plenty of rest, and, of course, not smoking. Traveling to remote areas where medical attention is not readily available or to high altitudes where the blebs can expand and rupture should be considered carefully before undertaken.

In patients with normal lung function, there is probably no increased risk associated with pregnancy. However, in patients with compromised lung function, pregnancy is not advised. There do not appear to be complications associated with oral contraceptives, but this issue should be discussed with the patient's pulmonologist and gynecologist.