You are in: eMedicine Specialties > Radiology > CHEST LymphangioleiomyomatosisArticle Last Updated: Aug 6, 2008AUTHOR AND EDITOR INFORMATIONSection 1 of 11
  Author: Ali Islam, MD, Staff Physician, Department of Radiology, University of Western Ontario Ali Islam is a member of the following medical societies: American College of Radiology, American Heart Association, American Roentgen Ray Society, Canadian Association of Radiologists, Canadian Medical Association, Canadian Medical Protective Association, College of Physicians and Surgeons of Ontario, Radiological Society of North America, and Royal College of Physicians and Surgeons of Canada Editors: Jeffrey A Miller, MD, Associate Professor of Clinical Radiology, University of Medicine and Dentistry of New Jersey; Associate Chief of Service, Department of Radiology, Veterans Affairs of New Jersey Health Care System; Bernard D Coombs, MB, ChB, PhD, Consulting Staff, Department of Specialist Rehabilitation Services, Hutt Valley District Health Board, New Zealand; John D Newell, Jr, MD, FACR, FCCP, FASER, Co-Director of Thoracic Imaging, UCDHSC; Director of Lung Imaging Center, Professor of Radiology and Professor of Medicine, Department of Radiology, University of Colorado Health Sciences Center, National Jewish Medical and Research Center; Univ. Colorado Hospital; Robert M Krasny, MD, Consulting Staff, Department of Radiology, The Angeles Clinic and Research Institute; Barry H Gross, MD, Professor, Department of Radiology, University of Michigan Medical School; Professor, University of Michigan Cancer Center Author and Editor Disclosure Synonyms and related keywords: lymphangioleiomyomatosis, lymphangiomyomatosis, LAM, lymphangiomyoma, lymphoproliferative disorder, dyspnea, interstitial lung disease, lung disease, tuberous sclerosis complex, TSC, vascular obstruction, pulmonary obstruction, lung dysfunction, lung cyst, pulmonary cyst INTRODUCTIONSection 2 of 11
  BackgroundLymphangioleiomyomatosis (LAM) is a rare idiopathic disease affecting women that was first described by von Stossel in 1937. LAM is characterized by nonneoplastic peribronchial, perivascular, and perilymphatic proliferation of atypical smooth muscle resulting in vascular and airway obstruction, cyst formation, and a progressive decline in lung function. Typical radiographic findings of reticular interstitial lung disease, recurrent pneumothoraces, and recurrent chylous effusions have been described.1, 2, 3, 4, 5 An association with renal angiomyolipomas is observed in as many as 50% of patients. The disease may occur sporadically or as part of the tuberous sclerosis complex (TSC) that includes mental retardation, seizures, and skin abnormalities.1 However, less than 5% of patients with TSC have pulmonary disease. When pulmonary features of LAM are identified in males, consider a diagnosis of TSC.2, 6, 7, 8 PathophysiologyIn lymphangioleiomyomatosis (LAM), a proliferation of closely packed, spindle-shaped, smooth muscle cells causes occlusion of the lymphatic system, resulting in chylous effusions or ascites. Similarly, obstruction of blood vessels can result in pulmonary hemorrhage, and obstruction of bronchioles can result in distal air trapping that causes cyst formation and the destruction of lung tissue. Rupture of subpleural cysts results in pneumothoraces. Others have proposed that the breakdown of lung tissue is caused by metalloproteinase enzymes present in cytoplasmic granules in the LAM smooth muscle cells, which destroy interstitial collagen and elastin fibers. The proliferation of LAM cells typically is not associated with fibrosis. Some LAM cells express estrogen and progesterone receptors, which may account for the role of hormones in disease predilection, progression, and treatment. Etiology of the disease is unclear, but evidence suggests a link to tuberous sclerosis complex (TSC).2, 3 The gene associated with TSC (TSC2) encodes a tumor-suppressor protein termed tuberin. A mutation that results in loss of heterozygosity of this gene (and possibly deficient tuberin activity) was discovered in LAM smooth muscle cells, in the lymph nodes of a patient with retroperitoneal LAM, and in LAM-associated angiomyolipomas. Note that other cell lines in the same patients did not possess this mutation; therefore, patients with LAM may have a mosaic genotype, unlike patients with TSC. FrequencyInternationalThe prevalence of lymphangioleiomyomatosis (LAM) historically has been underestimated as a result of either delay in diagnosis or misdiagnosis. For example, the estimated prevalence of 1 case per million population in France, the United Kingdom, and the United States has been revised by a French group to 2.6 cases per million population. The increase in prevalence may be the result of a broader awareness of the disease among physicians and the establishment of international patient registries. Mortality/MorbidityLymphangioleiomyomatosis (LAM) is a disease of progressive decline of pulmonary function resulting in respiratory failure, although the rate of deterioration is highly variable. Initial reports quoted survival periods of less than 10 years, but a retrospective study of the largest LAM patient series to date calculated 5-, 10-, and 15-year survival rates of 91%, 79%, and 71%, respectively. Patients can live more than 20 years after the initial diagnosis. If lung transplantation is performed in patients with end-stage LAM, survival is similar to that seen in patients receiving lung transplantation for other diseases (1- and 3-y survival rates of 70% and 50%, respectively). Common presenting symptoms include dyspnea, cough, and chest pain. In the course of one series, over an 18-month period in patients with known LAM, the prevalence of pneumothorax and chylothorax was 68% and 29%, respectively. Recurrent pneumothoraces and chylous effusion were present in 29% and 9% of these patients, respectively. Approximately 50% of patients have renal angiomyolipomas, which commonly are present at the time of diagnosis, although small and asymptomatic. Multiple angiomyolipomas or tumors larger than 4 cm occasionally may cause shock or death as a result of massive hemorrhage. Chyloptysis, hemoptysis, wheezing, chest pain, chylous ascites, lymphangiomyoma masses, chylous vaginal discharge, chyluria, uterine fibroids, and lower-extremity lymphedema have been reported. RaceNo racial predilection for lymphangioleiomyomatosis (LAM) is known. SexLymphangioleiomyomatosis (LAM) almost exclusively affects women. Disease exacerbation has been reported with pregnancy and the use of oral contraceptives.9 AgeThe mean age of onset of lymphangioleiomyomatosis (LAM) is 33 years. Postmenopausal presentation is unusual and is more common in patients receiving exogenous estrogen. AnatomyThe lungs in patients with lymphangioleiomyomatosis (LAM) contain multiple air-filled cysts distributed uniformly and bilaterally and ranging from 2-50 mm, with most from 5-15 mm. Cysts are surrounded by relatively normal lung tissue. While most cysts are round, they can be polygonal or bizarre. The number and size of cysts increase as the disease progresses. Clinical DetailsAn absence of family history, epilepsy, mental retardation, or cutaneous lesions can differentiate lymphangioleiomyomatosis (LAM) from tuberous sclerosis complex (TSC). Initial symptoms usually are thoracic and (uncommonly) can precede abnormality on chest radiograph or pulmonary function tests (PFTs), resulting in misdiagnosis. Crackles, pleural effusion, ascites, or cor pulmonale may be detected on physical examination. PFT findings vary. A reduction in the diffusion capacity of carbon monoxide is the most common initial abnormality. Obstructive physiology is more common than restrictive, but findings may be mixed. A trend toward hyperinflation and increased total lung capacity is seen. The ratio of forced expiratory volume in 1 second to forced vital capacity (FEV1/FVC) can be used to monitor disease progression. Pregnancy, estrogen replacement therapy, prolonged air travel, or trips to high-altitude locales are not advised for LAM patients. Although no evidence indicates a direct relationship between estrogen and LAM, the treatment of LAM has focused on reducing the production or effects of estrogen. No therapy has been found that is effective for all LAM patients. The only known cure for patients with severe disease is lung transplantation.10 The mainstay of conservative management is hormonal therapy with progesterone, although the response is highly variable. Oxygen therapy may become necessary with worsening lung function. Treatment with cyclophosphamide, steroids, nitrogen mustard, and radiation has been reported to be unsuccessful. Tamoxifen alone or in combination with progesterone, oophorectomy, or gonadotropin-releasing hormone agonists has also been tried. Management of pneumothorax is conventional, but recurrent episodes are managed with medical or surgical pleurodesis. Supportive management of chylous effusions includes nutritional modifications to low-fat diets containing medium-chain triglycerides. In patients with end-stage disease, oxygen inhalation is the final therapy prior to lung transplantation. Preferred ExaminationWith clinical suspicion, lymphangioleiomyomatosis (LAM) has been diagnosed on the basis of compatible chest radiograph, pulmonary function tests (PFTs), and CT findings. CT is the most specific imaging test for diagnosing LAM. Compared to open lung biopsy, transbronchial biopsy followed by immunohistochemical staining of sampled tissue with homatropine methylbromide 45 (HMB45) is less invasive. HMB45, a monoclonal antibody that binds to proteins produced by melanoma cell lines, is both sensitive and specific for making the diagnosis of LAM.11, 12, 13 Limitations of TechniquesChest radiograph and pulmonary function test (PFT) findings, while suggestive of lymphangioleiomyomatosis (LAM), can be nonspecific and may be normal despite the presence of symptoms. Plain radiography may not detect the thin-walled cysts identified on CT and may underestimate the extent of the disease. PFT results vary depending on the extent of disease. CT, and especially high-resolution scanning, may reveal distinct findings that obviate the need for biopsy; however, diseases such as emphysema occasionally must be excluded. CT detection of a renal angiomyolipoma or chylous ascites further supports the diagnosis. Transbronchial biopsy without staining with HBM45 usually does not provide enough lung tissue for diagnosis. Open-lung biopsy may make lung transplant more difficult technically. DIFFERENTIALSSection 3 of 11
Bronchiectasis Cystic Fibrosis, Thoracic Emphysema Eosinophilic Granuloma, Thoracic Idiopathic Pulmonary Fibrosis Neurofibromatosis Type 1 Neurofibromatosis Type 2 Tuberous Sclerosis
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| Media file 1: Lymphangioleiomyomatosis. Subtle interstitial reticular pattern in a female patient with slightly increased lung volumes. | |
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| Media file 2: Lymphangioleiomyomatosis. A high-resolution CT in a female patient showing numerous well-defined, thin-walled cysts evenly distributed throughout both lungs (same patient as in Image 1). | |
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| Media file 3: Lymphangioleiomyomatosis. Sagittal view of left kidney showing large fat-containing angiomyolipoma (arrows) arising from lower pole. | |
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| Media file 4: Lymphangioleiomyomatosis. Large angiomyolipoma of left kidney with recent hemorrhage. | |
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Lymphangioleiomyomatosis excerpt
Article Last Updated: Aug 6, 2008
