Clinicopathologic and Longitudinal Imaging Features of Lung Cancer Associated With Cystic Airspaces: A Systematic Review and Meta-Analysis

BACKGROUND. Lung cancer (LC) associated with cystic airspaces is an uncommon presentation that is underrecognized on imaging. Additionally, understanding of its underlying pathology and risk factors is limited, which can contribute to delays in diagnosis. OBJECTIVE. The purpose of this analysis was to systematically review, analyze, and synthesize the medical literature to determine the imaging features of LC associated with cystic airspaces. EVIDENCE ACQUISITION. In accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we included published research reporting the clinical, pathologic, and imaging features of LC associated with cystic airspaces. We then performed a pooled analysis of continuous and categoric data with respect to patient clinical characteristics, tumor pathologic features, underlying driver mutation, CT features, and evolution of these features over time. EVIDENCE SYNTHESIS. The analysis included eight original observational studies with a combined total of 341 patients with LC associated with cystic airspaces (weighted mean age, 61.8 years; range, 30-87 years; 135 women and 206 men). Most patients were current or previous smokers (127/192 [66.1%]). The most common histologic finding was adenocarcinoma (289/328 [88.1%]) followed by squamous cell carcinoma (30/328 [9.1%]). The most common driver mutations were EGFR (46/122 [37.7%]) and KRAS (21/122 [17.2%]). The cysts in LC associated with cystic airspaces commonly had nonuniform (104/114 [91.2%]) and thick (83/222 [37.4%]) walls, irregular margins (53/142 [37.3%]), and were unilocular (173/272 [63.6%]). Most cysts had a nodular component (210/328 [64.0%]). Over time, most cysts showed development or enlargement of the nodular component (61/89 [68.5%]), approximately half showed wall thickening (43/89 [48.3%]), and a minority evolved into completely solid lesions (11/89 [12.4%]). The size of the cystic component increased in 36 of 89 patients (40.4%), decreased in 28 (31.5%), and remained stable in 24 (27.0%). CONCLUSION. LC associated with cystic airspaces occurs most commonly as adeno-carcinoma and is seen in both smokers and nonsmokers. The cysts associated with LC show wall thickening and mural nodularity, which may evolve over time. LC associated with cystic airspaces can be indolent, and long-term surveillance with imaging should be considered if cysts are not resected. CLINICAL IMPACT. Familiarity with the imaging features and temporal evolution of LC associated with cystic airspaces can minimize delays in LC diagnosis. Future management guidelines should include protocols for follow-up and management of cystic lung lesions identified during diagnostic and LC screening CT.