Pulmonary Langerhans cell histiocytosis
Pulmonary Langerhans cell histiocytosis (PLCH) can be seen as part of widespread involvement in patients with disseminated LCH or more frequently as a distinct entity in young adult smokers. This article focuses on the latter. You may want to refer to the following articles:
- Langerhans cell histiocytosis: general discussion
- Letterer-Siwe disease: disseminated fulminant disease, typically seen in infants
- Hand-Schuller-Christian disease (HSC): chronic disseminated disease, typically seen in children
- eosinophilic granuloma (EG): isolated to bone, most common form
Unlike systemic Langerhans cell histiocytosis or that confined to bone (eosinophilic granuloma) which is seen in pediatric population, pulmonary LCH is usually identified in young adults (20-40 years of age). A history of current or previous cigarette smoking is identified in up to 95% of cases 1,4. It is a rare disorder with no well established gender predilection, which appears to be more common in Caucasian populations 4.
Presentation is usually with dyspnea or a non-productive cough. Other symptoms include constitutional symptoms (fatigue and weight loss), pleuritic chest pain, or spontaneous pneumothorax 1,4. Up to a quarter of patients are asymptomatic.
There is proliferation of Langerhans cells in the bronchiolar and bronchial epithelium, forming granulomas. It is postulated that as these cellular granulomas evolve, peripheral fibrosis forms resulting in traction on the central bronchiole which becomes cyst-like 3. This explains the presumed evolution from nodule, through cavitating nodule and thick walled cysts, to the 'stable' thin-walled cysts 3,4. An immune-mediated mechanism has been postulated, although an inciting agent has not been isolated 4. This proliferation is accompanied by inflammation and granuloma formation. Electron microscopy may reveal characteristic Birbeck granules 1-2.
Pulmonary Langerhans cell histiocytosis has variable appearance depending on the stage of disease, ranging from small peribronchiolar nodular opacities to multiple irregularly-shaped cysts. There is a mid and upper zone predilection 1,3-4.
The earliest change is a diffuse bilateral reticulonudolar pattern with predilection for the mid and upper zones. Later, cyst formation may be seen or may mimic a honeycomb appearance due to summation of air filled cysts. Cysts can be identified in only 1-15% of cases 1. There is preservation of lung volumes, or even hyperinflation 1,3-4. Reduced lung volumes are uncommon and only seen in end-stage fibrotic cases 4.
Lymph node enlargement visible on chest x-rays is rare 4.
As is usually the case, CT and especially HRCT is superior to plain chest radiography in identifying both the reticulonodular opacities and cysts 1,3-4. Distribution is the key in differentiating PLCH from other cystic lung disease with predilection for the mid and upper zones and regional sparing of the costophrenic recesses, anterior right middle lobe and lingula left upper lobe.1,3-4
- more pronounced early in the disease
- may range in number from a few to innumerable
- 1-10 mm in diameter (typically 1-5 mm 4)
- centrilobular distribution
- usually irregular margin
- surrounding lung parenchyma appears normal
- may cavitate and become cysts
- more pronounced later in the disease
- usually less than 10 mm in diameter
- may measure up to 2-3 centimeters in size
- the extreme bases may be preserved
- usually thin-walled, but on occasion may be up to a few millimeters thick
- confluence of 2 or more cysts results in bizarre shapes:
- internal septations
Other common findings include 1,3:
The appearance of new nodules later in the disease (when cystic change is established) indicates disease progression but is a rare finding 3.
Treatment and prognosis
Overall prognosis is generally good with over 50% of patients demonstrating spontaneous resolution or stabilization even without treatment 3. This is especially the case in patients who stop smoking.
In a minority of patients (~20%) and more frequently in those who continue to smoke, the disease is progressive with deterioration in respiratory function and eventual end-stage pulmonary fibrosis 3.
Treatment may not be required once smoking has ceased. Corticosteroids are frequently used and appear beneficial. In patients with rapidly progressive disease no proven therapy has been found. In some selected patients lung transplantation may be an option, provided smoking has ceased. Recurrence in the transplanted lung has been described 4.
- cyst rupture:
- interstitial fibrosis:
Differential depends on whether nodular or cystic change is the dominant feature.
Early in the disease, when nodules are the dominant feature, consider:
Later in the disease, when cysts are prominent, consider:
- diffuse distribution
- regular shaped and sized cysts
- cystic bronchiectasis from ABPA
- central distribution
- mucous plugging
- lack of visible cyst wall 1-3
- Pneumocystis jiroveci pneumonia
idiopathic pulmonary fibrosis
- basal and subpleural distribution
- reduced lung volumes