Pulmonary Langerhans cell histiocytosis (PLCH) may be seen as part of widespread involvement in patients with disseminated Langerhans cell histiocytosis or more frequently as a distinct entity in young adult smokers. This article focuses on the latter.
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Epidemiology
Pulmonary Langerhans cell histiocytosis 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 White populations 4.
Associations
Haematopoietic neoplasms:
Clinical presentation
Presentation is usually with dyspnoea or 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.
Pathology
Langerhans cells proliferate 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 a 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.
Evidence suggests that pulmonary Langerhans cell histiocytosis represents a myeloid neoplasm with inflammatory properties 9.
Radiographic features
Pulmonary Langerhans cell histiocytosis has variable appearance depending on the stage of the disease, ranging from small peribronchiolar nodular opacities to multiple irregularly-shaped cysts. These have a mid and upper zone predilection 1,3,4.
Plain radiograph
The earliest change is a diffuse bilateral symmetrical reticulonodular pattern with a predilection for the mid and upper zones. The ill-defined nodules range from 1 to 10 mm in size. Later, cyst formation may be seen or may mimic a honeycomb appearance due to a summation of air-filled cysts. Cysts can only be identified in less than 15% of cases 1 and range from 1 to 3 cm in diameter. 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-ray is rare 4.
CT
CT (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 pulmonary Langerhans cell histiocytosis from other cystic lung diseases with a predilection for the mid and upper zones and regional sparing of the costophrenic recesses, anterior right middle lobe and lingula of the left upper lobe 1,3,4.
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nodules
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: may also be peribronchial or peribronchiolar
usually have irregular margins
may be cavitary nodules with thick walls, later becoming cysts
surrounding lung parenchyma appears normal
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cysts
more pronounced later in the disease
usually less than 10 mm in diameter
may measure up to 2-3 cm in size
the extreme bases may be preserved
usually thin-walled, but on occasion may be up to a few millimetres thick
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confluence of 2 or more cysts results in bizarre shapes
bilobed
cloverleaf
branching
internal septations
octopus sign: one study has suggested the presence of strands within the cyst aggregating into a nodule centre being presence in those with nodular mixed cystic stage of disease 13
Other common findings include 1,3:
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ground-glass and/or reticular opacities
DIP-like change 1
In late disease, other findings include:
coalescent cysts
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 stabilisation 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.
Complications
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cyst rupture
spontaneous pneumothorax: may be the first presentation
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interstitial fibrosis
end-stage pulmonary fibrosis and respiratory failure
Differential diagnosis
Differential depends on whether the nodular or cystic change is the dominant feature.
Early in the disease, when nodules are the dominant feature, consider:
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granulomatous disease
metastases
See differential of multiple pulmonary nodules and differential of miliary opacities for more comprehensive lists.
Later in the disease, when cysts are prominent, consider:
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lymphangioleiomyomatosis (LAM)
diffuse distribution
regular shaped and sized cysts
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cystic bronchiectasis from allergic bronchopulmonary aspergillosis (ABPA)
central distribution
mucous plugging
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lack of visible cyst wall 1-3
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basal and subpleural distribution
reduced lung volumes
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protein deposition diseases such as Sjogren syndrome and light-chain deposition disease
smooth-walled simple cysts
associated with autoimmune disease