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Introduction

Lymphangioleiomyomatosis (LAM) is a multisystem disorder, predominantly affecting women, which is characterized by cystic lung lesions, abdominal angiomyolipomas (AML) and lymphatic abnormalities, for example, lymphatic tumors, chylous effusions.15 These pathologic features are caused by the proliferation of a neoplastic smooth muscle–like LAM cell that also has characteristics of melanocytes.6 Inherited and sporadic forms of LAM have been described. Sporadic LAM is caused by somatic mutations in an unknown susceptible cell of the tuberous sclerosis complex (TSC) 2 (TSC2) gene.7,8 LAM also occurs in TSC, an autosomal dominant disorder resulting from germline mutations in the TSC1 or TSC2 genes that is characterized by widespread hamartomas in several organs including the brain, heart, skin, kidney, eyes, lung, and liver, and occurs in 1 of 6000 live births.9

Epidemiology

Until the establishment of LAM registries,1 LAM was considered to be a fatal disease of women of child-bearing age for which oophorectomy, antiestrogen therapy, and lung transplantation were the only therapeutic options.1013 LAM is now best defined as a chronic disease of post- and premenopausal women with a life expectancy spanning decades.14 Sporadic LAM is an uncommon disease occurring in approximately 4.9/1,000,000 women.15 Although the association of TSC and cystic lung disease has long been recognized,1113 little is known about the prevalence and the natural history of LAM in TSC (TSC-LAM). The prevalence of cystic lung disease in women with TSC was reported to range from 30% to 40%; in male patients, it has been estimated to be 13%.16 Males with TSC tend to have milder, subclinical lung involvement.

Clinical Presentation

Patients with LAM often present with a history of progressive dyspnea. Pneumothorax, another common presentation of LAM, is often recurrent, occurring in about 50% to 60% of patients.14 The size of the lung cysts, as seen on high-resolution computed tomography (HRCT) scans (Fig. 62-1A), appears to parallel the incidence of pneumothorax; higher incidence of pneumothorax is seen in patients with larger cysts.17 Other modes of presentation include chylothorax, abdominal lymphangioleiomyomas, chylous ascites, hemoptysis, chyluria, chyloptysis, and hemorrhage caused by renal AML (Table 62-1).1,5,18 Lymphatic involvement in LAM occurs in the posterior mediastinum, retroperitoneal and pelvic areas and includes lymphadenopathy, chylous effusions, and lymphangioleiomyomas.5,18 AML are benign tumors, usually localized in the kidneys and found in approximately 90% of patients with TSC-LAM and 30% of those with sporadic LAM (Table 62-1).1,5,18 The physical examination of LAM patients may disclose wheezing, pleural effusions, ascites, or intra-abdominal masses. In patients with TSC, typical skin lesions or signs of brain involvement may be evident.9

Figure 62-1

Computed tomography scans showing pulmonary and extrapulmonary images of patients with LAM, and ...

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