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Eosinophilic Granuloma (Histiocytosis X) Workup

  • Author: Eleanor M Summerhill, MD, FACP, FCCP; Chief Editor: Zab Mosenifar, MD, FACP, FCCP  more...
 
Updated: Jun 03, 2016
 

Laboratory Studies

Results from routine laboratory testing in patients with pulmonary Langerhans cell histiocytosis X (PLCH) are nonspecific.

Peripheral eosinophilia is not observed.

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Imaging Studies

Chest radiographs in patients with pulmonary Langerhans cell histiocytosis X (PLCH) characteristically reveal bilateral, symmetric, ill-defined nodules and reticulonodular infiltrates. As the disease progresses, cystic lesions appear. An upper-zone predominance of radiographic findings with sparing of the costophrenic angles is typically observed.

  • Cystic lesions can be of various sizes and thin or thick walled.
  • Lung volume is normal or increased.
  • Honeycombing indicates advanced disease.
  • Bony lesions may occur on the ribs or any other site.
  • Hilar or mediastinal adenopathy is rare and should prompt the consideration of sarcoidosis or malignancy.
  • Pleural effusion is uncommon.

HRCT of the chest may be virtually diagnostic in the appropriate clinical setting. Pathognomonic findings include nodules and cysts, predominantly in the mid and upper lung zones, with sparing of the costophrenic regions. The nodules may be cavitary and variable in size. Likewise, the cysts may be of various diameters and wall thicknesses. A broad differential diagnosis must be considered in the following situations:

  • If only nodules are present on HRCT, the findings are nonspecific, and a number of other granulomatous disorders cannot be excluded radiographically.
  • When cysts are an isolated finding, LAM must be considered as well. Unlike PLCH, LAM is usually uniformly distributed throughout the lungs. Sparing of the costophrenic angles supports a diagnosis of PLCH.
  • Emphysema is usually distinguishable, as walls do not surround the cystic spaces found in emphysema. However, extensive emphysema is sometimes difficult to differentiate from PLCH.
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Other Tests

Pulmonary function testing in pulmonary Langerhans cell histiocytosis X (PLCH) patients can demonstrate all patterns of abnormality: Normal, restrictive, obstructive, or mixed.

  • Most patients have normal or near-normal total lung capacity with near-normal spirometry findings.
  • Gas exchange, as measured by the diffusing capacity for carbon monoxide, is generally reduced.
  • In rare cases, patients have reversible airflow limitation.

Gas exchange abnormalities may be present at rest. Although such abnormalities are most pronounced with exercise, most patients have a normal gradient of alveolar-arterial partial pressures.

Pulmonary exercise testing may demonstrate decreased exercise capacity with reduced oxygen utilization. Gas exchange, ventilatory, and pulmonary vascular abnormalities may also be present. Therefore, exercise limitation is generally multifactorial.

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Procedures

Analysis of bronchioalveolar lavage (BAL) fluid is sometimes diagnostic in pulmonary Langerhans cell histiocytosis X (PLCH).

  • A greater than 5% increase in the number of Langerhans cells in BAL specimens is almost pathognomonic for PLCH. Although this finding is highly specific, it is not particularly sensitive.
  • Langerhans cells can be recognized by their characteristic staining for S-100 protein or peanut agglutination antigen.
  • These cells are CD1a-positive, and may also be identified by a specific monoclonal antibody (MT-1).

Although the disease is present in a patchy distribution, sometimes transbronchial biopsy may be diagnostic if sampling is done in a number of areas and sufficient tissue is obtained.

  • Immunostaining for Langerhans cells (CD1a) improves the sensitivity and specificity of the biopsy sample.
  • The diagnostic yield is approximately 10-40%.

Open or thoracoscopic lung biopsy is the most sensitive and specific diagnostic modality, and is generally recognized as the criterion standard.

  • In addition to immunostaining, electron microscopy of tissue samples may be performed.
  • Langerhans cells demonstrate the characteristic intracytoplasmic Birbeck granules. These are found in all Langerhans cells, but they are present in increased numbers in the pathologic Langerhans cells found in the lesions of PLCH.
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Histologic Findings

The earliest lesions of pulmonary Langerhans cell histiocytosis X (PLCH) consist of Langerhans cells grouped around the small airways. These inflammatory lesions expand to form granulomatous nodules composed of Langerhans cells as well as eosinophils, macrophages, lymphocytes, plasma cells, and fibroblasts.

In addition to looking for the typical morphologic features of Langerhans cells, immunostaining for S-100 and CD1a may also be useful. Electron microscopy helps in identifying Langerhans cells by demonstrating the presence of diagnostic pentilaminar cytoplasmic inclusion bodies, or Birbeck granules (x-bodies).

Of note, eosinophils may not always be present. Therefore, the name eosinophilic granuloma, despite being a commonly accepted term, is a misnomer.

Granulomas are centered on distal bronchioles. Evidence of pulmonary vascular involvement and respiratory bronchiolitis are often present, as well as infiltration and destruction of airway walls. As the disease progresses, cavitation occurs as a result of this destruction. The nodule fibroses, eventually forming a stellate scar.

Hematoxylin-eosin staining is demonstrated in the image below:

Low-power photomicrograph of a lung-tissue specime Low-power photomicrograph of a lung-tissue specimen that demonstrates the classic stellate nodule of pulmonary histiocytosis X (hematoxylin-eosin stain).
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Contributor Information and Disclosures
Author

Eleanor M Summerhill, MD, FACP, FCCP Associate Professor of Medicine, Division of Pulmonary and Critical Care Medicine, Warren Alpert Medical School of Brown University; Director, Internal Medicine Residency Program, Memorial Hospital of Rhode Island

Eleanor M Summerhill, MD, FACP, FCCP is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, American Thoracic Society, Rhode Island Medical Society, Association of Program Directors in Internal Medicine

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Daniel R Ouellette, MD, FCCP Associate Professor of Medicine, Wayne State University School of Medicine; Chair of the Clinical Competency Committee, Pulmonary and Critical Care Fellowship Program, Senior Staff and Attending Physician, Division of Pulmonary and Critical Care Medicine, Henry Ford Health System; Chair, Guideline Oversight Committee, American College of Chest Physicians

Daniel R Ouellette, MD, FCCP is a member of the following medical societies: American College of Chest Physicians, Society of Critical Care Medicine, American Thoracic Society

Disclosure: Nothing to disclose.

Chief Editor

Zab Mosenifar, MD, FACP, FCCP Geri and Richard Brawerman Chair in Pulmonary and Critical Care Medicine, Professor and Executive Vice Chairman, Department of Medicine, Medical Director, Women's Guild Lung Institute, Cedars Sinai Medical Center, University of California, Los Angeles, David Geffen School of Medicine

Zab Mosenifar, MD, FACP, FCCP is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, American Federation for Medical Research, American Thoracic Society

Disclosure: Nothing to disclose.

Additional Contributors

Michael Peterson, MD Chief of Medicine, Vice-Chair of Medicine, University of California, San Francisco, School of Medicine; Endowed Professor of Medicine, University of California, San Francisco-Fresno, School of Medicine

Michael Peterson, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, American Thoracic Society

Disclosure: Nothing to disclose.

Acknowledgements

The authors and editors of eMedicine gratefully acknowledge the contributions of previous author, Robert S. Crausman, MD, MMS, to the development and writing of this article.

References
  1. Podbielski FJ, Worley TA, Korn JM, Connolly MM. Eosinophilic granuloma of the lung and rib. Asian Cardiovasc Thorac Ann. 2009 Apr. 17(2):194-5. [Medline].

  2. Szturz P, Rehak Z, Koukalova R, Adam Z, Mayer J. FDG-PET positive pilomatrixoma--reconsidering multicentricity in Langerhans cell histiocytosis. Nucl Med Rev Cent East Eur. 2014. 17(2):94-6. [Medline].

  3. Gaensler EA, Carrington CB. Open biopsy for chronic diffuse infiltrative lung disease: clinical, roentgenographic, and physiological correlations in 502 patients. Ann Thorac Surg. 1980 Nov. 30(5):411-26. [Medline].

  4. Colby TV, Lombard C. Histiocytosis X in the lung. Hum Pathol. 1983 Oct. 14(10):847-56. [Medline].

  5. Thomeer M, Demedts M, Vandeurzen K. Registration of interstitial lung diseases by 20 centres of respiratory medicine in Flanders. Acta Clin Belg. 2001 May-Jun. 56(3):163-72. [Medline].

  6. Watanabe R, Tatsumi K, Hashimoto S, Tamakoshi A, Kuriyama T. Clinico-epidemiological features of pulmonary histiocytosis X. Intern Med. 2001 Oct. 40(10):998-1003. [Medline].

  7. Vassallo R, Ryu JH, Schroeder DR, Decker PA, Limper AH. Clinical outcomes of pulmonary Langerhans'-cell histiocytosis in adults. N Engl J Med. 2002 Feb 14. 346(7):484-90. [Medline].

  8. Delobbe A, Durieu J, Duhamel A, Wallaert B. Determinants of survival in pulmonary Langerhans' cell granulomatosis (histiocytosis X). Groupe d'Etude en Pathologie Interstitielle de la Société de Pathologie Thoracique du Nord. Eur Respir J. 1996 Oct. 9(10):2002-6. [Medline].

  9. DiCaprio MR, Roberts TT. Diagnosis and Management of Langerhans Cell Histiocytosis. J Am Acad Orthop Surg. 2014 Oct. 22(10):643-652. [Medline].

  10. Stacher E, Beham-Schmid C, Terpe HJ, Simiantonaki N, Popper HH. Pulmonary histiocytic sarcoma mimicking pulmonary Langerhans cell histiocytosis in a young adult presenting with spontaneous pneumothorax: a potential diagnostic pitfall. Virchows Arch. 2009 Aug. 455(2):187-90. [Medline].

  11. Alalawi R, Whelan T, Bajwa RS, Hodges TN. Lung transplantation and interstitial lung disease. Curr Opin Pulm Med. 2005 Sep. 11(5):461-6. [Medline].

  12. Misaki H, Yamauchi T, Arai H, et al. Secondary malignant fibrous histiocytoma following refractory langerhans cell histiocytosis. J Clin Exp Hematop. 2009 May. 49(1):33-7. [Medline].

  13. Harari S, Torre O, King Jr TE, Moss J. Pulmonary Langerhans' Cell Histiocytosis. Elias JA, Fishman JA, Kotloff RM, Pack A, Senior RM, eds. Fishman's Pulmonary Diseases and Disorders. 5th ed. New York, NY: McGraw-Hill; 2015. 919-27.

 
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Low-power photomicrograph of a lung-tissue specimen that demonstrates the classic stellate nodule of pulmonary histiocytosis X (hematoxylin-eosin stain).
 
 
 
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