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

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)

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

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

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)

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]

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

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

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