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Pulmonary Langerhans Cell Histiocytosis

Definition

  • Multinodular lung infiltrates of Langerhans cells

Alternate/Historical Names

  • Eosinophilic granuloma
  • Histiocytosis X

Diagnostic Criteria

  • Includes all cases in which the lung is the principal site of involvement
    • Approximately 10-15% of cases also involve other sites
      • Primarily bone
    • Systemic disease in which lung involvement is not dominant is not covered here
      • Usually seen in children
    • Predominantly pulmonary disease may be seen in children, but is rare
  • Clinical
    • Virtually all are smokers
    • Presentation ranges from asymptomatic to rapidly progressive
      • Usually dyspnea, occasionally fevers, pneumothorax
    • Variable outcomes
      • Spontaneous remission
      • Remission following cessation of smoking
      • Progression to end stage fibrosis
  • High resolution computed tomography
    • Centrilobular/peribronchiolar reticulonodular infiltrates
      • Nodules 1-15 mm
      • Diffusely scattered, primarily upper and mid lung fields
    • Frequently forms patchy or diffuse cysts
      • 1-3 mm, may be irregular
    • If clinical and radiographic findings are classic, biopsy confirmation may not be necessary
  • Pathology
    • Multiple centrilobular, discrete nodular infiltrates
      • Peribronchiolar with stellate extension into surrounding alveolar walls
        • Intervening lung tissue is normal
      • Composed of Langerhans cells
        • Uniform, bland nuclei
          • Pale chromatin, thin nuclear membrane, inconspicuous nucleoli
          • Characteristic folded, grooved nucleus
        • Moderate amount of pale eosinophilic cytoplasm
        • Positive for S100, CD1a, langerin
      • Infiltrate frequently also contains eosinophils
        • May also contain lymphocytes, plasma cells, histiocytes and neutrophils
      • Intra-alveolar organizing pneumonia frequently seen at periphery of nodules
      • Intra-lumenal macrophages may be prominent in alveoli adjacent to nodule
        • Not a diffuse finding
    • Nodules frequently cavitate, leading to cyst formation
    • Increasing fibrosis with time leads to characteristic centrilobular stellate scars
      • Infiltrate decreases, ultimately leading to scars with few or no Langerhans cells
      • If bronchiole is obliterated, recognize by location adjacent to terminal arteriole
      • Merging of scars and confluent cysts may lead to honeycomb change
    • Although rare in children, pediatric cases are not infrequently associated with hematolymphoid or solid neoplasms
      • In adults it has been reported associated with lymphoma and rarely carcinoma

Gerald J Berry MD
Robert V Rouse MD
Department of Pathology
Stanford University School of Medicine
Stanford CA 94305-5342

Original posting/updates: 11/20/10

Differential Diagnosis

Langerhans Cell Histiocytosis Usual Interstitial Pneumonia
Scars frequently stellate and centrilobular with extension to subpleura Irregular subpleural scarring
Honeycomb change only occasionally seen Honeycomb change frequent
Frequently some typical active LCH lesions present Lacks peribronchiolar nodules of Langerhans cells
Langerhans cells are positive for CD1a and langerin CD1a and langerin negative
HRCT shows centrilobular nodule and cyst pattern HRCT shows honeycombing, peripheral accentuation

 

Langerhans Cell Histiocytosis Hypersensitivity Pneumonitis
Lacks granulomas and giant cells Granulomas and giant cells generally present but may be infrequent in late stage
Smoking history only Possible exposure history
CD1a and langerin positive Langerhans cells present No Langerhans cells
Late fibrotic stage may be impossible to separate if active foci cannot be found

 

Respiratory Bronchiolitis Associated Interstitial Lung Disease Langerhans Cell Histiocytosis
Predominantly intra-alveolar process Predominantly interstitial process, intra-alveolar macrophages only focally present
Eosinophils rare Eosinophils may be numerous
No cystic change Cystic change frequent
Lacks scarring Produces stellate scars
Histiocytes with round nuclei Histiocytes with folded nuclei
Macrophages CD1a and langerin negative Langerhans cells positive for CD1a and langerin
Both are highly associated with smoking, thus foci or respiratory bronchiolitis are expected to be present in the lung tissue of cases of Langerhans cell histiocytosis

 

Langerhans Cell Histiocytosis Desquamative Interstitial Pneumonia
Intra-alveolar macrophages only focally present Diffuse intra-alveolar macrophages
Temporal heterogeneity Temporally uniform
Focal or multifocal disease Diffuse disease
Numerous eosinophils Occasional eosinophils
Cystic change frequent No cystic change
Produces stellate scars Lacks scarring
Histiocytes with folded nuclei Histiocytes with round nuclei
Langerhans cells positive for CD1a and langerin Macrophages CD1a and langerin negative

 

Langerhans Cell Histiocytosis Chronic Eosinophilic Pneumonia
Predominantly interstitial process, intra-alveolar macrophages only focally present Predominantly intra-alveolar process
Composed of Langerhans cells with variable numbers of eosinophils Prominent eosinophils, no Langerhans cells
Produces stellate scars Lacks scarring
Histiocytes with folded nuclei Histiocytes with round nuclei
S100, CD1a, langerin positive S100, CD1a, langerin negative

 

Langerhans Cell Histiocytosis Eosinophilic Pleuritis
Predominantly a parenchymal interstitial process Pleural process, no parenchymal involvement
Langerhans cells with variable numbers of eosinophils Predominantly eosinophils with proliferating mesothelial cells
HRCT shows centrilobular nodule and cyst pattern HRCT shows localized pleural lesion

Classification / Lists

Idiopathic Interstitial Lung Diseases

Other Diffuse Parenchymal Lung Diseases

 

Bibliography

  • Travis WD, Colby TV, Koss MN, Rosado-de-Christenson ML, Müller NL, King TE Jr.  Non-neoplastic Disorders of the Lower Respiratory Tract, AFIP Atlas of Nontumor Pathology, First Series, Fascicle 2, 2002.
  • Travis WD, Borok Z, Roum JH, Zhang J, Feuerstein I, Ferrans VJ, Crystal RG. Pulmonary Langerhans cell granulomatosis (histiocytosis X). A clinicopathologic study of 48 cases. Am J Surg Pathol. 1993 Oct;17(10):971-86.
  • Yousem SA, Colby TV, Chen YY, Chen WG, Weiss LM. Pulmonary Langerhans' cell histiocytosis: molecular analysis of clonality. Am J Surg Pathol. 2001 May;25(5):630-6. PubMed PMID: 11342775.
  • Vassallo R, Ryu JH, Colby TV, Hartman T, Limper AH. Pulmonary Langerhans'-cell histiocytosis. N Engl J Med. 2000 Jun 29;342(26):1969-78.
  • Egeler RM, Neglia JP, Aricò M, Favara BE, Heitger A, Nesbit ME, Nicholson HS. The relation of Langerhans cell histiocytosis to acute leukemia, lymphomas, and other solid tumors. The LCH-Malignancy Study Group of the Histiocyte Society. Hematol Oncol Clin North Am. 1998 Apr;12(2):369-78.
  • Neumann MP, Frizzera G. The coexistence of Langerhans' cell granulomatosis and malignant lymphoma may take different forms: report of seven cases with a review of the literature. Hum Pathol. 1986 Oct;17(10):1060-5.
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