eMedicine Specialties > Pulmonology > Idiopathic Lung Disorders

Lymphangioleiomyomatosis

Author: Joel Moss, MD, PhD, Deputy Chief, Translational Medicine Branch, National Heart, Lung, and Blood Institute, National Institutes of Health
Coauthor(s): John A Kelly, MB, BCh, MD, Assistant Professor of Medicine and Micro-Immunology, Dartmouth Medical School; Staff Pulmonologist, White River Junction Veterans Affairs Medical Center
Contributor Information and Disclosures

Updated: Nov 19, 2008

Introduction

Background

Lymphangioleiomyomatosis (LAM) is a rare disorder resulting from proliferation in the lung, kidney, and axial lymphatics of a neoplastic cell having a smooth muscle cell phenotype (LAM cell). Cystic destruction of the lung with progressive pulmonary dysfunction and the presence of abdominal tumors (eg, angiomyolipomas [AML], lymphangioleiomyomas) characterize the disease. Because this condition typically occurs in premenopausal women, involvement of the female hormones in disease pathogenesis is a current hypothesis.

Pathophysiology

Lymphangioleiomyomatosis (LAM) cell proliferation may obstruct bronchioles, possibly leading to airflow obstruction, air trapping, formation of bullae, and pneumothoraces. Obstruction of lymphatics may result in chylothorax and chylous ascites. Obstruction of venules may result in hemosiderosis and hemoptysis. Excessive proteolytic activity, which relates to an imbalance of the elastase/alpha1-antitrypsin system or metalloprotease (MMPs) and their inhibitors (tissue inhibitors of metalloproteases [TIMPS]) may be important in lung destruction and formation of cystlike lesions.

Frequency

United States

The frequency of Lymphangioleiomyomatosis (LAM) is unknown. To date, more than 500 cases exist in the United States. As the disease becomes better recognized because of increased awareness and better diagnostic techniques, the prevalence may increase.

International

The international frequency of LAM is unknown, though Europe and Japan report case series.

Mortality/Morbidity

Earlier reports indicate a grim prognosis with progressive respiratory failure and death within 10 years of diagnosis. Recent reports are more favorable, with 78% of patients who are affected alive at 8.5 years. The statistics may improve further as patients are diagnosed earlier (lead time bias) or with more benign disease.

Race

No racial predilection for LAM exists.

Sex

LAM primarily is a disease of women; however, rare case reports of LAM in men exist, primarily in men with tuberous sclerosis complex, an inherited disorder having shared features with LAM.

Age

Although primarily a disease of women of childbearing age, LAM has been reported in patients aged 12 years to patients older than 70 years. Some of the latter patients have been on hormone replacement therapy.

Clinical

History

  • Common lymphangioleiomyomatosis (LAM) symptoms
    • Dyspnea
    • Manifestations of pneumothorax
    • Cough
  • Less common symptoms
    • Chest pain
    • Chylothorax
    • Chyluria
    • Pericardial effusion
    • Pneumoperitoneum
    • Lymphedema
  • Exacerbations of LAM are described during pregnancy, menstruation, and estrogen (ER) use.

Physical

  • Lymphangioleiomyomatosis (LAM) examination usually normal
  • Less common findings
    • Crackles
    • Wheezes
    • Clubbing
    • Pleural effusion
    • Pneumothorax
    • Ascites
  • Signs of tuberous sclerosis
    • Facial angiofibromas
    • Ungual fibromas
    • Hypomelanotic macules, ash-leaf spot
    • Shagreen patch, a cluster of hamartoma typically located on the lower back
    • Forehead plaque
    • Retinal hamartoma

Causes

  • The etiology of lymphangioleiomyomatosis (LAM) is unknown; however, the fact that the condition occurs primarily in women who are premenopausal and is exacerbated by high ER states suggests a role for hormones in this condition.
  • The link with tuberous sclerosis (TSC) suggests a genetic component (see Other Problems to be Considered).

More on Lymphangioleiomyomatosis

Overview: Lymphangioleiomyomatosis
Differential Diagnoses & Workup: Lymphangioleiomyomatosis
Treatment & Medication: Lymphangioleiomyomatosis
Follow-up: Lymphangioleiomyomatosis
References
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References

  1. Carsillo T, Astrinidis A, Henske EP. Mutations in the tuberous sclerosis complex gene TSC2 are a cause of sporadic pulmonary lymphangioleiomyomatosis. Proc Natl Acad Sci U S A. May 23 2000;97(11):6085-90. [Medline].

  2. Smolarek TA, Wessner LL, McCormack FX, Mylet JC, Menon AG, Henske EP. Evidence that lymphangiomyomatosis is caused by TSC2 mutations: chromosome 16p13 loss of heterozygosity in angiomyolipomas and lymph nodes from women with lymphangiomyomatosis. Am J Hum Genet. Apr 1998;62(4):810-5. [Medline].

  3. Bonetti F, Chiodera PL, Pea M, Martignoni G, Bosi F, Zamboni G, et al. Transbronchial biopsy in lymphangiomyomatosis of the lung. HMB45 for diagnosis. Am J Surg Pathol. Nov 1993;17(11):1092-102. [Medline].

  4. Boehler A, Speich R, Russi EW, Weder W. Lung transplantation for lymphangioleiomyomatosis. N Engl J Med. Oct 24 1996;335(17):1275-80. [Medline].

  5. Kitaichi M, Nishimura K, Itoh H, Izumi T. Pulmonary lymphangioleiomyomatosis: a report of 46 patients including a clinicopathologic study of prognostic factors. Am J Respir Crit Care Med. Feb 1995;151(2 Pt 1):527-33. [Medline].

  6. Adema GJ, de Boer AJ, Vogel AM, Loenen WA, Figdor CG. Molecular characterization of the melanocyte lineage-specific antigen gp100. J Biol Chem. Aug 5 1994;269(31):20126-33. [Medline].

  7. Bonetti F, Pea M, Martignoni G, Zamboni G, Iuzzolino P. Cellular heterogeneity in lymphangiomyomatosis of the lung. Hum Pathol. Jul 1991;22(7):727-8. [Medline].

  8. Corrin B, Liebow AA, Friedman PJ. Pulmonary lymphangiomyomatosis. A review. Am J Pathol. May 1975;79(2):348-82. [Medline].

  9. Eliasson AH, Phillips YY, Tenholder MF. Treatment of lymphangioleiomyomatosis. A meta-analysis. Chest. Dec 1989;96(6):1352-5. [Medline].

  10. Kalassian KG, Doyle R, Kao P, Ruoss S, Raffin TA. Lymphangioleiomyomatosis: new insights. Am J Respir Crit Care Med. Apr 1997;155(4):1183-6. [Medline].

  11. Moss J. LAM and Other Diseases Characterized by Smooth Muscle Proliferation. ed. New York, NY: Marcel Decker; 1999.

  12. Moss J, DeCastro R, Patronas NJ, Taveira-DaSilva A. Meningiomas in lymphangioleiomyomatosis. JAMA. Oct 17 2001;286(15):1879-81. [Medline].

  13. Ryu JH, Moss J, Beck GJ, Lee JC, Brown KK, Chapman JT, et al. The NHLBI lymphangioleiomyomatosis registry: characteristics of 230 patients at enrollment. Am J Respir Crit Care Med. Jan 1 2006;173(1):105-11. [Medline].

  14. Steagall WK, Glasgow CG, Hathaway OM, Avila NA, Taveira-Dasilva AM, Rabel A, et al. Genetic and Morphologic Determinants of Pneumothorax in Lymphangioleiomyomatosis. Am J Physiol Lung Cell Mol Physiol. Jul 6 2007;[Medline].

  15. Steagall WK, Taveira-DaSilva AM, Moss J. Clinical and molecular insights into lymphangioleiomyomatosis. Sarcoidosis Vasc Diffuse Lung Dis. Dec 2005;22 Suppl 1:S49-66. [Medline].

  16. Taveira-DaSilva AM, Stylianou MP, Hedin CJ, Hathaway O, Moss J. Decline in lung function in patients with lymphangioleiomyomatosis treated with or without progesterone. Chest. Dec 2004;126(6):1867-74. [Medline].

  17. Taylor JR, Ryu J, Colby TV, Raffin TA. Lymphangioleiomyomatosis. Clinical course in 32 patients. N Engl J Med. Nov 1 1990;323(18):1254-60. [Medline].

  18. Urban T, Kuttenn F, Gompel A, Marsac J, Lacronique J. Pulmonary lymphangiomyomatosis. Follow-up and long-term outcome with antiestrogen therapy; a report of eight cases. Chest. Aug 1992;102(2):472-6. [Medline].

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Further Reading

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Keywords

LAM, progressive pulmonary dysfunction, abdominal tumors, angiomyolipomas, AML, abdominal mass, tuberous sclerosis, TSC, pulmonary disease, pneumothorax, lung disease, lung transplantation, lymphangioleiomyomatosis, LAM cell, lung cysts

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Contributor Information and Disclosures

Author

Joel Moss, MD, PhD, Deputy Chief, Translational Medicine Branch, National Heart, Lung, and Blood Institute, National Institutes of Health
Joel Moss, MD, PhD is a member of the following medical societies: Alpha Omega Alpha, American Society for Biochemistry and Molecular Biology, American Society for Clinical Investigation, American Thoracic Society, Association of American Physicians, and Phi Beta Kappa
Disclosure: Nothing to disclose.

Coauthor(s)

John A Kelly, MB, BCh, MD, Assistant Professor of Medicine and Micro-Immunology, Dartmouth Medical School; Staff Pulmonologist, White River Junction Veterans Affairs Medical Center
John A Kelly, MB, BCh, MD is a member of the following medical societies: American Association of Immunologists, American College of Chest Physicians, and American Thoracic Society
Disclosure: Nothing to disclose.

Medical Editor

Ryland P Byrd Jr, MD, Professor, Department of Internal Medicine, Division of Pulmonary Medicine and Critical Care Medicine, James H Quillen College of Medicine, East Tennessee State University; Chief of Pulmonary Medicine, Medical Director of Respiratory Therapy, Intensive Care Unit, Program Director of Pulmonary Diseases and Critical Care Medicine Fellowship, James H Quillen Veterans Affairs Medical Center
Ryland P Byrd Jr, MD is a member of the following medical societies: American College of Chest Physicians, American Thoracic Society, and Southern Medical Association
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

Harold L Manning, MD, Associate Professor, Departments of Medicine, Anesthesiology and Physiology, Section of Pulmonary and Critical Care Medicine, Dartmouth Medical School
Harold L Manning, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, and American Thoracic Society
Disclosure: Nothing to disclose.

CME Editor

Timothy D Rice, MD, Associate Professor, Departments of Internal Medicine and Pediatrics and Adolescent Medicine, Saint Louis University School of Medicine
Timothy D Rice, MD is a member of the following medical societies: American Academy of Pediatrics and American College of Physicians
Disclosure: Nothing to disclose.

Chief Editor

Zab Mosenifar, MD, Director, Division of Pulmonary and Critical Care Medicine, Director, Women's Guild Pulmonary Disease Institute, Executive Vice Chair, Department of Medicine, Cedars Sinai Medical Center; Professor of Medicine, David Geffen School of Medicine at UCLA
Zab Mosenifar, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, American Federation for Medical Research, and American Thoracic Society
Disclosure: Nothing to disclose.

 
 
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