eMedicine Specialties > Pulmonology > Idiopathic Lung Disorders

Lymphangioleiomyomatosis: Differential Diagnoses & Workup

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

Differential Diagnoses

Other Problems to Be Considered

  • General conditions diagnosed in patients with lymphangioleiomyomatosis (LAM)
  • Tuberous sclerosis
    • Probably a predisposing condition
    • Several clinical features shared (lung, AML)
    • Genetic features shared (TSC2 gene mutations in LAM lung tissue and AML)1,2
  • Conditions with cysts, honeycombing, or interstitial pattern
    • Interstitial pulmonary fibrosis (unlike LAM, reduced lung volumes; however, patients with LAM who have had a pleurodesis may show decreased lung volumes)
    • Eosinophilic granuloma (EG) (like LAM has increased lung volumes but may also have nodules; cysts in EG tend to have thicker walls than those in LAM)
    • Bronchiolitis
  • Lymphatic disorders
    • Diffuse pulmonary lymphangiomatosis
    • Lymphangiomas
    • Pulmonary lymphangiectasis
  • Smooth-muscle proliferation
    • Leiomyosarcoma
    • Smooth-muscle proliferation in the lung
    • Benign metastasizing leiomyoma

Workup

Laboratory Studies

  • Several case reports show an elevated cancer antigen 125 in patients with LAM and chylous ascites and/or pleural effusion.

Imaging Studies

  • Chest radiograph findings
    • May be normal
    • Fine reticular or reticulonodular interstitial infiltrate - Lung volume not reduced
    • Delicate honeycombing - More advanced disease
    • Pleural effusions
    • Pneumothoraces
  • CT scan and high-resolution CT scan
    • Diffuse thin-walled cysts - The defining characteristic appearance in LAM
    • Intervening parenchyma usually normal
    • Normal or increased lung volumes
    • Adenopathy and thoracic duct dilatation
    • Pleural effusion
    • Pneumothorax
    • Ground-glass opacities - Pulmonary hemorrhage
    • Pericardial effusion
  • Abdominal imaging by either ultrasound or CT scan
    • Acute myelogenous leukemia (AML)
    • Benign tumors (kidney, liver, spleen) containing smooth muscle, thick-walled blood vessels, and mature adipose tissue
    • Retroperitoneal adenopathy

Other Tests

  • Pulmonary function tests
    • Decreased diffusing capacity for carbon monoxide - Most common abnormality seen, often markedly reduced. Hypoxemia at rest, worsening with exercise, is a common finding.
    • Spirometry - Airflow obstruction most frequent abnormality; restriction (previous pleural disease) or mixed obstruction and restriction also seen
    • Lung volumes - Increased total lung capacity (TLC) and increased residual volume to TLC ratio

Procedures

  • In the past, open or thorascopic lung biopsies were required for histologic confirmation of the diagnosis.
  • Histologic diagnosis now can be made by performing a transbronchial biopsy (TBB); the amount of tissue obtained from TBB may be insufficient to confirm a diagnosis. Lymphangioleiomyomatosis (LAM) cells react with human melanoma black (HMB)-45, an antibody generated against an extract of melanoma. HMB-45 staining is sensitive and specific for the presence of LAM cells and may help in confirming LAM on TBB.3 However, with classic high-resolution CT scans (particularly with extrathoracic features) and associated findings of LAM (eg, tuberous sclerosis complex, AML, lymphangioleiomyomas), histologic confirmation may be unnecessary.

Histologic Findings

Macroscopic pathology

  • Lung - Cysts evenly distributed in all lung fields
  • Lymph nodes (retroperitoneal and pelvic) - Pale and spongy; large chyle-filled cysts within the axial lymphatic system
  • Thoracic duct - Large, spongy, and sausagelike

Microscopic pathology

  • Lung
    • Proliferation of neoplastic LAM cells (spindle-shaped cells with small nuclei, larger epithelioid cells with clear cytoplasm and round nuclei) having a smooth muscle cell phenotype
    • Loss of alveoli with cyst formation
    • Cystic spaces with LAM cells in their walls
    • Smooth-muscle proliferation in bronchiolar walls, causing airway narrowing, thickened arterial walls with venous occlusion, and hemosiderosis
  • Involved lymph nodes and thoracic duct - Interlacing bundles of LAM cells, which may invade the wall of the lymphatics
  • Immunohistochemical staining
    • Reactivity with anti—alpha-smooth actin antibodies supports smooth-muscle differentiation.
    • ER and progesterone receptors are present, but their role is unclear.
    • Monoclonal antibody HMB-45, generated against melanoma extract and recognizing cells with epithelioid features (rarely, spindle cells are HMB-45 positive), may help confirm the diagnosis of LAM on biopsy.
    • Immunohistochemical staining may define renal and hepatic AML.

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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