대한흉부영상의학회 Korean Society of Thoracic Radiology

Discussion

Diagnosis With Brief Discussion

Diagnosis

Lymphangioleiomyomatosis in Tuberous Sclerosis

Radiologic Findings

Chest radiograph shows reticular opacities in both lungs and right costophrenic angle blunting. Thin-section CT scans show numerous discrete, round, thin-walled lung cysts. Contrast-enhanced scan shows right pleural effusion. Thoracentesis from the right hemithorax revealed chylous effusion.

Brain CT scan of the patient shows multiple calcified subependymal nodules. Abdominal CT scan shows huge fatty mass of both kidneys presenting angiomyolipomas.

Brief Review

Tuberous sclerosis (TSC) is a rare, genetically determined disorder/familial tumor syndrome, including the presence of multiorgan hamartomas. Two predisposing genes has been found in families affected by TSC (TSC1 & TSC2); TSC genes are considered to be tumor suppressor genes, and mutations in them may lead to abnormal differentiation and proliferation of cells.
Pulmonary involvement in TSC is well known as pulmonary lymphangioleiomyomatosis (LAM), which has an incidence of 34 % in TSC patients. Histologically, there are two phases of proliferation in LAM. The early phase is characterized by proliferation of immature muscle cells covering alveolar walls, bronchioles, pleura and vessels, including lymphatic routes. In the late phase, there are cystic spaces and proliferation of muscle cells all over the lung.
Lymphangioleiomyomatosis (LAM) can occur as a rare sporadic disease or as a complication of tuberous sclerosis (TSC). Sporadic LAM has no familial association. In more than 80% of patients, pneumothorax occurs during the course of the disease. Most patients with LAM die within 10 years of diagnosis. Deaths are generally due to progressive respiratory failure. Because the condition is limited to females and may be dependent on estrogens, the possibility of hormonal influence has been recognized for many years, and there have been suggestions that progesterone therapy would be effective.
Patients with TSC often present with an insidious onset of dyspnea whilst non-TSC patients present more commonly with acute breathlessness secondary to pneumothorax. Patients with TSC are also less likely to suffer from chylothorax. The age of onset of symptoms and of diagnosis are similar. LAM is rare in children and even less common in males in both groups. Although symptomatic LAM is uncommon it causes a significant amount of morbidity and mortality both in the TSC and general population, but asymptomatic LAM is not uncommon in TSC.
The chest radiographic findings of LAM include the classic triad of reticular interstitial pattern, chylous pleural effusions, and recurrent pneumothoraces. The principal pulmonary finding in patients with lymphangioleiomyomatosis is cysts. Some observers think that the cysts develop as a result of air trapping distal to small airways narrowed by smooth muscle proliferation. Others have shown lymphangioleiomyomatosis cells producing matrix metalloproteinases that destroy both collagen and elastin in the pulmonary interstitium. This suggests a role for these enzymes and the breakdown of pulmonary parenchyma in the pathogenesis of the cysts.
Another type of pulmonary lesion in TSC is multifocal micronodular pneumocyte hyperplasia (MMPH). CT scan demonstrates multiple minute nodules present throughout both lung fields. Histologically, the nodules were well demarcated, and were composed of thickened, fibrotic, alveolar septa lined by pleomorphic, type II pneumocytes. This type of MNPH is extremely rare, and appears to be a hamartomatous proliferation occurring in patients with TS.

References

1. Maruyama H, Ohbayashi C, Hino O, Tsutsumi M, Konishi Y. Pathogenesis of multifocal micronodular pneumocyte hyperplasia and lymphangioleiomyomatosis in tuberous sclerosis and association with tuberous sclerosis genes TSC1 and TSC2. Pathol Int 200; 51:585-94
2. Moss J, Avila NA, Barnes PM, Litzenberger RA, Bechtle J, Brooks PG, Hedin CJ, Hunsberger S, Kristof AS. Prevalence and clinical characteristics of lymphangioleiomyomatosis (LAM) in patients with tuberous sclerosis complex . Am J Respir Crit Care Med 2001; 164:669-71
3.Avila NA, Chen CC, Chu SC, Wu M, Jones EC, Neumann RD, Moss J. Pulmonary lymphangioleiomyomatosis: correlation of ventilation-perfusion scintigraphy, chest radiography, and CT with pulmonary function tests. Radiology 2000 ;214:441-6

Keywords

Lung, Idiopathic interstitial pneumonia, LAM, IIP,