Reviews

Lymphangioleiomyomatosis: A Review

Historical Perspective

The 1966 article by Cornog and Enterline⁶ is the first significant collection of patients with what is now known as LAM. In this article, the authors reported six cases of what they termed “lymphangiomyoma.” In addition to their cases, the authors included 14 cases from the literature that they believed, based on histologic features, represented the same disease entity. These cases had been published under various terms, including lymphangioma, lymphangiomyoma, lymphangiopericytoma,

The Relationship between Lam and TSC

TSC is an autosomally inherited disorder characterized by mental retardation, seizures, and facial angiofibromas. Twenty-five to 50% of patients with TSC have a family history of the disorder; the remaining cases are believed to be caused by either spontaneous mutation or incomplete penetrance.⁸ TSC was first reported by von Recklinghausen in 1862.⁹ Later, in 1880, Bourneville termed it “tuberous sclerosis” in reference to the potato-like CNS lesions that are found.¹⁰

Pulmonary parenchymal

Clinical Features and Epidemiology of LAM

LAM occurs exclusively in women.^1,25 An early report of the histopathologic finding of LAM in a man²⁶ was later corrected.²⁵ In most case series, the mean age at disease onset is in the early 30s.2, 3, 4 The youngest patient described experienced dyspnea at age 9 years and was eventually diagnosed by lung biopsy specimen at age 11 years.²⁷ Several patients have been diagnosed as having LAM after menopause,2, 3, 4^,28, 29, 30, 31 even as late as 75 years old.²⁶ Many of the patients diagnosed as

Clinical Features of Associated Angiomyolipomas

Renal angiomyolipomas are rare hamartomatous tumors of the kidneys that are composed of smooth muscle, blood vessels, and adipose tissue. They may occur in isolation or be part of the TSC.⁶⁹ Renal angiomyolipomas are often seen in patients with LAM.^21,22,70 In three recent case series, renal angiomyolipomas were present in 7 of 21 (33%),²¹ 8 of 17 (47%),⁷⁰ and 8 of 14 (57%)²² patients with LAM. Thus, 23 of these 52 patients (44%) with LAM had renal angiomyolipomas and in 11 of these patients,

Pathologic Features of LAM

In the lung, the pathologic characteristics of LAM are diffuse cystic changes associated with the proliferation of atypical smooth muscle cells (LAM cells) (Figs 1 and 2). These smooth muscle cells are characterized by elongated, closely packed, spindle-to-oval-shaped cells. LAM may involve any structure in the lung, including the pleura and the walls of the bronchioles, pulmonary arteries, venules, and small airspaces.^1,49 The most common complications of LAM-pneumothorax, chylous pleural

Radiographic Features of LAM

The CXR in LAM classically shows a generalized, symmetric reticulonodular interstitial infiltrate, which is a nonspecific appearance that may be seen in many ILDs. In a recent collection of 46 patients by Kitaichi et al,⁴ bilateral reticulonodular infiltrates were seen on initial CXR in 39 (85%). Unlike many of the ILDs, however, the lung volumes are either normal or increased in LAM. In addition to LAM, this unusual finding of increased interstitial markings and preserved lung volumes may also

Pulmonary Physiology of LAM

The pulmonary physiologic features of patients with LAM are variable and include obstructive, restrictive, or mixed patterns.^3,4 The diffusing capacity for carbon monoxide (DLCO) is reduced in most patients.^3,4

Burger et al¹⁰¹ assessed pulmonary mechanics in eight patients with LAM to describe the pattern of abnormality and to clarify the cause of airflow obstruction. All eight patients had abnormal results of pulmonary function tests (PFTs) and seven had decreased FEV₁/FVC ratios (mean, 61% of

Diagnosis, Treatment, and Prognosis of LAM

As mentioned above, many cases of LAM are initially misdiagnosed as more common diseases, such as asthma or COPD. Such a mistake is understandable because of the rarity of LAM and because of the frequent nonspecific nature of the symptoms and findings on plain radiographs. The diagnosis of LAM is often initially considered when a young woman presents with ILD, pneumothorax, or chylothorax. In other cases, the diagnosis is not suspected until the grossly abnormal appearance of the lung surface

Other Treatments

In addition to hormonal medications intended to interrupt the proliferation of LAM cells, numerous reports describe various interventions aimed at preventing or treating the complications of LAM, such as pneumothorax and chylous pleural or peritoneal fluid collections. Drainage of chylous pleural fluid collections can be hazardous, lead to protein loss, and is not always necessary. Chemical^6,32,39,99 or surgical^39,55,73 pleurodesis has been performed with variable success in preventing

Current Developments

LAM is a devastating disease that strikes young women and carries a poor prognosis. Because it is rare, little is known regarding its pathogenesis and treatment, but several new avenues of research have recently emerged. First, to address the lack of understanding of the clinical features and natural history of LAM, a national registry of patients with LAM has recently been initiated.¹²¹ Funded by the National Heart, Lung, and Blood Institute in cooperation with the Cleveland Clinic Foundation,

Acknowledgment

The author thanks doctors Elizabeth Petri Henske, Janet Maurer, Francis McCormack, and James Stoller for their support and thoughtful review of this manuscript, as well as Drs. Peter O'Donovan and Carol Farver for their help with the radiographic and pathologic images.