Eosinophilic Granuloma

(aka Pulmonary Langerhans Cell Histiocytosis, Histiocytosis-X)

Epidemiology

  • Represents subset of Histiocytosis-X cases (other: Letterer-Siwe Disease and Hand-Schuller-Christian Disease)
  • Tobacco Use: >90% of cases are current or past smokers
  • Age: most cases diagnosed in 20-40 y/o (Range: 3 months-60 y/o)
  • Race: highest incidence in whites
  • Sex: M > F
  • Association with Pulmonary or Extrapulmonary Neoplasms: possible

Pathologic Patterns

Early

  • Stellate cellular granulomas with interstitial infiltrate (of macrophages/histiocytes/plasma cells, eosinophils/lymphocytes) along alveolar septa
  • Bronchocentric Distribution: causes loss of bronchial patency (as in BO)
  • DIP-Like Pattern: may be seen due to accumulation of histiocytes/macrophages/lymphocytes in air spaces (thought to be partially related to the high association of smoking with EG, which increases numbers of alveolar macrophages in alveolar spaces)
  • Langerhans’ cell (derived from the dendritic cell, a mononuclear antigen-presenting cell with pro-fibrotic capabilities): characteristic indented or clefted nucleus
    • Granules stain positive with S100-stain or OKT6
    • EM: intracytoplasmic pentalaminar rod-shaped Birbeck granules, aka X-bodies):
  • Reactive Eosinophilic Pleuritis: seen in 40-50% of cases with complicating PTX (effusions are uncommon)

Late

  • Honeycombing/extensive cystic changes/pericicatricial emphysema
  • Scars are characteristically stellate

Diagnosis

PFT’s

  • Early: restriction with decreased DLCO
  • Late in Course: obstruction may be superimposed on restriction
    • Increased RV/TLC ratio has been shown to correlate with cyst formation

FOB

  • BAL: markedly increased WBC count (around 100 x 109 cells) with normal percentages, most cells are alveolar macrophages with slight increase in neutrophils and eosinophils (this pattern is also seen in DIP and respiratory bronchiolitis)
    • Diagnostic criteria: >5% Langerhan cells suggests EG (Note: Langerhan cells also seen in lesser numbers in other ILD’s)/normal is <2%
  • TBB: may be diagnostic if adequate tissue

OLB

  • Usually required (unless other body sites are available for Bx)

CXR/Chest CT Patterns

  • Bilateral Reticular, Small Nodular (2-3 mm), or Reticulonodular Infiltrates and Cystic Densities: these often occur in combination
    • Mid-upper lung zone predominance (variable though) and may spare costophrenic angles
    • Nodules may appear stellate (early and may cavitate/bullae may form later
    • Characteristic feature: ILD disease with apparently preserved lung volumes on CXR
    • Mediastinal/hilar adenopathy and effusions are uncommon
  • Pneumothorax: classic manifestation
  • Solitary Lung Nodule: uncommon presentation
  • Honeycombing: late finding (often seen best in mid-upper lung zones: unusual for ILD’s)

HRCT

  • Nodules and cysts (upper lobe-predominance)
  • HRCT findings correlate better with DLCO abnormalities than do CXR findings
  • Ultrafast HRCT: diffuse air trapping

Serum Immune Complexes

  • May be seen

CBC

  • Absence of peripheral eosinophilia

Clinical

General Features

  • Many cases are asymptomatic

Lung Involvement

  • ILD: frequently have normal exam/decreased BS may appear late in course
    • Exertional Dyspnea:
    • Cough (common): due to bronchocentric involvement
    • Few Scattered Wheezes with Distinctive Absence of Crackles:
    • Pulmonary HTN/Cor Pulmonale:
  • Pneumothorax (occurs in 14% of cases): pleuritic chest pain
  • Chest Wall Mass: may impinge on lung
  • Pulmonary HTN (see Pulmonary Hypertension, [[Pulmonary Hypertension]])
    • Severe pulmonary HTN is a common feature in patients with end-stage pulmonary Langerhans cells histiocytosis
      [Dauriat G, Mal H, Thabut G, et al. Lung transplantation for pulmonary Langerhans’ cell histiocytosis: a multicenter analysis. Transplantation 2006;81:746–50]
    • In some patients, PH is probably related to chronic hypoxemia and/or abnormal pulmonary mechanics; in others, especially those patients with more severe elevation of PAP, PH is unrelated to lung parenchymal injury
    • Histopathologic examination has shown severe diffuse pulmonary vasculopathy (medial hypertrophy and intimal fibrosis) involving predominantly intralobular pulmonary veins and, to a lesser extent, muscular pulmonary arteries
      [Fartoukh M, Humbert M, Capron F, et al. Severe pulmonary hypertension in histiocytosis X. Am J Respir Crit Care Med 2000;161:216 –23]

Other System Involvement

(extrapulmonary involvement occurs in only 15% of EG cases)

  • “Punched-Out” Lytic Bone Lesions:
  • Panhypopituitarism:
  • DI:

Treatment

  • Asymptomatic: follow without treatment (usually resolve spontaneously)
    • Smoking cessation
  • Symptomatic: treat with steroids +/- cytotoxics (cytoxan/vinblastine/chrloambucil), alone or in combination
    • Cytotoxics are used mainly for rapidly progressive disease (but none have been shown to change course of EG)
    • Smoking cessation: one case report of EG resolving with smoking cessation
    • XRT: useful for impinging chest wall masses
    • Surgical Pleurodesis: for recurrent PTX

References

  • Dauriat G, Mal H, Thabut G, et al. Lung transplantation for pulmonary Langerhans’ cell histiocytosis: a multicenter analysis. Transplantation 2006;81:746–50
  • Fartoukh M, Humbert M, Capron F, et al. Severe pulmonary hypertension in histiocytosis X. Am J Respir Crit Care Med 2000;161:216–23