Even though in the classical specialty literature, the combination of cavitary nodules and cysts had a high specificity for Langerhans Cell Histiocytosis, we emphasize the importance of distribution, aspect, additional interstitial findings and clinical context for an accurate diagnosis.

Although pulmonary Langerhans cell histiocytosis (PLCH) is a rare pathology, accounting for only 3-5% of diffuse infiltrative lung diseases in most studies, its prevalence significantly increases among young smokers who present with a suggestive clinical history. Historically, the combination of lung nodules—some of which are cavitated—and cysts in young patients with a history of tobacco use has been considered nearly pathognomonic for PLCH. However, we emphasize the broad spectrum of possible mimickers and differential diagnoses.

The progression of the disease varies greatly and is unpredictable for each individual patient. Around 50% of patients experience a positive outcome, either spontaneously or with glucocorticoid treatment, leading to partial or complete resolution of radiological abnormalities and symptom relief. About 10–20% of patients present with early severe manifestations, such as recurrent pneumothorax or progressive respiratory failure accompanied by chronic cor pulmonale. In 30–40% of patients, symptoms persist with varying severity, and radiological nodules may transform into thick-walled, and eventually thin-walled, cysts that remain stable over time. Even in patients with stable cysts and apparent disease inactivity, LC granulomas may still be present in the pulmonary parenchyma. Therefore, long-term monitoring is essential, as it may reveal exacerbations in respiratory function after many years or, in rare cases, a relapse with new nodule formation.

High-resolution computed tomography (HRCT) is the optimal tool for elucidating the full extent of the disease. It accurately describes the morphology and distribution of lung abnormalities, thereby facilitating the preparation for lung biopsy; however, it is limited in its capacity to predict histopathological activity.

As a general rule, the lesions in pulmonary Langerhans cell histiocytosis follow a predictable pattern, being diffusely distributed with a predominance in the upper and mid portions of the lungs, while the lung bases are relatively spared. Another useful indicator is the sparing of medial tips of the middle lobe and lingula.

CT Features of LCH:

1. Nodules (Early Stages)

• Typically 1-5 mm in diameter (rarely >1 cm).
• Centrilobular distribution (peribronchial or peribronchiolar), which aids in differentiating from sarcoidosis, silicosis, and carcinomatosis, which are typically characterized by perilymphatic nodules.
• Often exhibit irregular margins, particularly in the presence of perilesional reticular disease.
• Usually homogeneous in appearance.
• Some nodules (especially those >1 cm) may demonstrate lucent centers (cavitating nodules).
• The intervening lung parenchyma typically appears normal.

• Variable wall thickness:
• Thin: < 2 mm—may sometimes mimic centrilobular emphysema (which lacks perceptible walls).
• Thick: > 2 mm.
• Shape:
• Round.
• Bizarre shapes (e.g., bilobed, cloverleaf-shaped, or branching), occasionally with persistent septations.

• Ground-glass opacities.
• Mosaic perfusion.
• Fine reticular opacities.
• Interlobular septal thickening.

Unusual presentation patterns may include cases with few, larger, smooth-marginated, or highly asymmetrical nodules. Rare instances of PLCH exhibiting consolidations, single nodules, or air-fluid cystic features have also been documented in the literature.

In the early stages of PLCH (Fig 6), the predominant CT feature is the presence of multiple nodules organized in a centrilobular distribution, reflecting the bronchial development of the disease. Given the high frequency of this finding, the differential diagnosis is extensive; however, certain strategies can help narrow the potential pathologies involved.

Firstly, the nodules should be differentiated from perilymphatic nodules (seen in sarcoidosis, silicosis, or lymphangitic carcinomatosis), which characteristically occur in subpleural regions, along fissures, interlobular septa, and bronchovascular bundles. Secondly, the distribution of lesions serves as a valuable tool: in PLCH, nodules are predominantly localized in the upper lobes while sparing the costodiaphragmatic recesses.

The appearance of nodules is also critical to consider; in PLCH, they typically have ill-defined margins, some may be cavitating, and their diameters range from 1 to 10 mm. Although other parenchymal lesions (e.g., ground-glass opacities, interlobular septal thickening) may be observed, if they are the dominant feature, the pathology may differ. For instance, large areas of ground-glass opacities could suggest hypersensitivity pneumonitis or PJP (Pneumocystis jirovecii pneumonia)  as alternative diagnoses to consider.

Another potential differential to consider is Wegener’s granulomatosis (Fig 9), a necrotising vasculitis which affects the lungs, the kidneys and upper respiratory tract. Being a heterogenous disease, it can present as centrilobular micronodularity with some cavitated nodules, resembling the ‘’florid’’ phase of PLCH. The laboratory abnormalities can partially resolve the problem.

Metastatic nodular cavitation may occur in the squamous cell type. Cavitary metastases generally display an irregular thickening of the walls, although thin-walled cysts are not uncommon (Fig 8).

Septic emboli (Fig 17) and excavated pneumocystosis may present on CT imaging in a manner that is indistinguishable from the nodules seen in PLCH. A thorough differential diagnosis should be considered, particularly in patients at risk or when constitutional symptoms are evident.

In some cases, the early stages of PLCH characterised by bronchiolocentrice ill defined micronodules can be indistinguishable from Rb-ILD pattern, but fortunately, clinical management is the same, smoking cessation being the most effective treatment for both.

Late stages (Fig 11 ) are characterized by the predominance of fibrocystic disease, with fewer nodular lesions and a variable appearance: ranging from thin-walled to thick-walled cysts (> 2 mm); from round, homogeneous shapes to bizarre forms (e.g., cloved, bilobed, or cloverleaf).

Initially, true cysts must be differentiated from centrilobular emphysema – Fig 18 (imperceptible walls; ’’central dot’’ sign) and cystic bronchiectasis – Fig 20 (easy demonstration of saccular dilatation of bronchi, with the aid of coronal and sagittal reconstructions; ’’signet ring’’ sign).

The next differential to exclude is the “honeycombing” appearance – Fig 19 (cysts of similar size, conglomerated in a few subpleural layers), typically seen in the UIP pattern (Usual Interstitial Pneumonia).

The distribution and appearance of cysts (Table 1) are key features in distinguishing them from LAM – Fig12,13 (round, diffuse cysts), LIP – Fig 14( often subpleural and perivascular, with a tendency to predominate in the lower lobes), or Birt-Hogg-Dubé syndrome.

Although the combination of nodules, cavitary nodules, and cysts is highly suggestive of PLCH, in many cases, the findings may be subtle, with lung biopsy remaining the definitive diagnostic method.