Diagnosis

Imaging

X-Ray of the chest shows initially a reticulo-micronodular pattern. In a more progressed disease additionally cysts may be visible within the infiltrates symmetrically in both lungs predominating in the middle and upper lung fields and sparing the costophrenic angles. Lung volumes are normal or increased. Pneumothorax may be visible and is of valuable diagnostic orientation. An unspecific picture of an emphysema-like lung is observed in end stage PLCH [Tazi 2006].

High resolution CT (HRCT) is the most important visualizing tool for PLCH [Tazi 2006]. It even shows parenchymal abnormalities in patients with normal X-ray and allows selection of the preferable surgical biopsy site. Furthermore HRCT displays different stages of disease. The typical HRCT pattern combines small poorly limited nodules, cavitated nodules (both may resolve), thick- and finally thin-walled cysts. As the disease evolves, cystic lesions become a predominant finding.

Differential diagnoses

The differential diagnoses vary according to the clinical and HRCT presentation. In patients with systemic symptoms, hemoptysis or of an older age, other diagnoses (particularly cavitary infection such as mycobacteria and pneumocystis and cavitary metastatic carcinoma) should be considered [Tazi 2006].

The differential diagnosis in women with a cystic lung picture includes lymphangioleiomyomatosis (LAM); in this condition, however, the cysts have thinner walls, are evenly distributed and are associated to abdominal (mainly renal) angiomyolipomas [McCormack 2008]. Extensive cystic disease may be difficult to differentiate from emphysema. In these young patients an alpha-antitrypsin deficiency should be searched. Recently, a pulmonary cystic disease related to light chain deposition in the lung has been identified [Colombat et al 2006].

In case of a familial history of pneumothorax, the genetic Birt Hogg Dubé syndrome should be considered (skin fibrofolliculomas, mutation of folliculin gene, kidney tumor) [Toro et al 2007].

Pulmonary lung function, BAL and biopsies

Pulmonary lung function tests most frequently show reduced diffusing capacity of the lung for carbon monoxide (DLCO), 70–90% of the patients. Lung volumes are impaired in a majority of patients with decreased vital capacity and air trapping (elevated residual volume). Total lung capacity is within normal values in most cases. An obstructive pattern is observed in a sizeable proportion of patients, particularly in advanced disease. Rarely a restrictive component may appear [Tazi et al 2012].

A predominantly nodular pattern suggestive for an active inflammatory disease can have only moderate functional consequences. A strong relationship between lung function or gas exchange impairment and the extent of cysts on HRCT was found. [Tazi et al 2012]

Bronchoalveolar lavage (BAL) provides additional orientation by showing high alveolar macrophage counts, reflecting the smoking consumption of the patients. Infection should be systematically ruled out. BAL yielding more than 5% CD1-positive cells has previously reported to support the diagnosis of pulmonary LCH [Auerswald/Barth/Magnussen 1991], has a high specificity but lacks sensitivity.

Diagnostic recommendations in pulmonary LCH (pLCH)

Bronchial biopsies are not helpful in the diagnosis of PLCH but are useful in ruling out other diagnoses in patients with atypical manifestations. The diagnostic yield of transbronchial biopsies for LCH is low, because of the focal distribution of lung lesions.

The diagnostic method of choice is therefore videothoracoscopic lung biopsy after HRCT evaluation. In asymptomatic patients with a typical HRCT pattern and a macrophage alveolitis by BAL, for whom no systemic therapy is required, a presumptive diagnosis may be acceptable with a close follow-up. In patients with extensive cystic lesions, the risk of invasive procedures has to be balanced with the need for a definitive diagnosis. (Grade D2 *)

It is important to exclude the existence of multi system LCH. Thus, a thorough history, comprehensive physical examination, and baseline radiographic, blood and urine tests should be performed in any patient presenting with PLCH to avoid undertreatment. (see table 3 and table 4).

Table 7: Diagnostic recommendations in pLCH
Recommendation
Grade *
Confirm definitive diagnosis
  • in all patients before start of systemic therapy
D2
  • prefer lung biopsy
D2
  • HRCT is required in all patients
D2
Exclude Existence of multisystem LCH
D2

* Grades of recommendation see here.