Tuberous sclerosis complex (TSC) causes benign tumors and cysts to develop in many organ systems, including the lungs. Wherever such lesions occur in the body, they tend to crowd normal tissues and, in some cases, inhibit organ function. Lesions that form in the lungs can lead to a lung disease called lymphangioleiomyomatosis (LAM) that can profoundly compromise the lungs' ability to supply oxygen to the body.
Women with TSC stand the greatest risk of developing TSC-related lung abnormalities. Despite the prevalence of lung involvement among women, the majority of these cases remain asymptomatic, meaning that the lesions have no impact on lung function. Only about 1 to 3 percent of women with TSC develop cases of LAM that compromise pulmonary function, causing such symptoms as chronic and progressive shortness of breath and lung collapse. Despite the low incidence of severe complications, the health risks posed by these symptoms make LAM a legitimate cause for concern among women with TSC.
As the name suggests, lymphangioleiomyomatosis is caused by the excessive growth (matosis) of abnormal smooth muscle-like cells (leiomyo), also called LAM cells, around the bronchial tubes, blood vessels (angio), and lymphatic vessels (lymph) of the lung. As these cell masses grow, their impact on lung function becomes more pronounced. The tissue becomes pockmarked with pulmonary cysts. These air- or fluid-filled sacs crowd functional lung tissue and further reduce pulmonary efficiency. Cysts can also rupture, causing much more serious complications, including lung collapse.
Specialists aren't certain why women with TSC stand a greater risk than men or children of developing LAM. However, the predominance of LAM in women and the disease's relatively late onset have led some researchers to conclude that the hormone estrogen plays a role.
LAM typically affects women of childbearing age. The average age of onset among women with TSC is 30 years. The most common symptom is shortness of breath, particularly during exertion. This symptom typically worsens over time as a result of the proliferation of and damage caused by LAM cell masses and cysts in the lining of the lung.
For some, the first sign of LAM is a collapsed lung, also called a pneumothorax. This occurs when a cyst ruptures, creating a small hole in the lining of the lung. The rupture allows air to escape into the surrounding chest cavity, and causes the lung to collapse. A pneumothorax requires immediate medical attention, involving removal of air from the chest cavity to allow the collapsed lung to re-inflate.
To better predict such severe complications, TSC specialists periodically examine the lungs of adult women with TSC using high-resolution computed tomography (CT). Images from these scans allow physicians to see existing LAM cell masses and cysts. Periodic exams enable doctors to track the size and number of these lesions to determine if the disease is progressing and requires treatment.
LAM is a major feature in the diagnostic criteria of TSC and, in some cases, provides the first indication of the disorder. More often, however, those who develop LAM have already been diagnosed with TSC and their lung involvement has been carefully monitored.
Periodic chest exams may also reveal another pulmonary manifestation of TSC, but fortunately one that does not produce clinical symptoms. Multifocal micronodular pneumocyte hyperplasia (MMPH) may appear in CT scans as lumpy, or nodular, lesions in the lining of the lungs. These growths may resemble lesions associated with LAM. However, they present little cause for concern.