Lung Cancers Associated With Cystic Airspaces: Natural History, Pathologic Correlation, and Mutational Analysis

The aim of the study was to investigate the natural history of non-small cell lung cancers (NSCLCs) associated with cystic airspaces, including histopathology and molecular analysis.

A total of 34,801 computed tomographic (CT) scans of 2954 patients diagnosed with NSCLC between 2010 and 2015 were evaluated for association with a cystic airspace. Characteristics on serial CT, 18F-fludeoxyglucose positron emission tomography, and pathologic analysis were recorded.

Cystic airspaces were associated with 1% of NSCLC cases (12 men and 18 women; median age, 66 y [range, 44 to 87 y]). Of the total number of patients, 97% had a smoking history. Twenty-four adenocarcinomas, 4 squamous cell carcinomas, and 2 poorly differentiated carcinomas were distributed throughout all lobes and were predominantly peripheral. Some cystic airspaces appeared in previously normal lungs, whereas others were preceded by subcentimeter nodules. Twenty of 30 cases demonstrated increased soft tissue due to wall thickening, increased loculations, enlargement and/or increased attenuation of a mural nodule, or replacement by a mass. 18F-fludeoxyglucose uptake was present if solid components measured >8 mm. Twenty of 30 patients demonstrated >1 cystic lesion or ground-glass nodule, lymphadenopathy, or evidence of prior lung resection. Pathologic analysis revealed that cystic airspaces correspond to a check-valve mechanism, adenocarcinoma superimposed on emphysema, cystification, and adenocarcinoma parasitizing a preexisting bulla. Fourteen of 26 tumors and 64% of adenocarcinomas tested positive for an alteration of KRAS with or without other alterations.

Cystic airspaces preceded by nodules can evolve into NSCLCs. Wall thickening and/or mural nodularity may develop. Location in the periphery of the upper lobes, emphysema, additional cystic lesions or ground-glass nodules, lymphadenopathy, and prior lung cancer should further increase suspicion. Cystic airspaces on CT can be due to a check-valve mechanism obstructing the small airways, lepidic growth of adenocarcinoma in an area of emphysema, cystification of tumor due to degeneration, or adenocarcinoma growing along the wall of a preexisting bulla. KRAS mutations are the predominant genetic alterations.