Growth Patterns and Risk Stratification of Incidental Small Pure Ground-Glass Nodules across Independent Cohorts

Background The widespread adoption of low-dose CT has increased the detection of small pure ground-glass nodules (pGGNs). The management of this type of nodule currently remains a clinical challenge. Purpose To characterize long-term growth trajectories of incidental small pGGNs, identify risk factors for nodule growth and progression, and assess the reproducibility of these findings in an independent cohort. Materials and Methods This retrospective study included patients with incidental small pGGNs (<10 mm) detected with low-dose chest CT during routine wellness assessments at Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University (center 1) and the First Affiliated Hospital of Wenzhou Medical University (center 2) from June 2017 to June 2019. All patients underwent annual CT follow-up for 5 years. To adjust for intrapatient clustering, all nodule-level and risk factor analyses used mixed-effects models with the individual patient as a random effect. Latent class trajectory modeling was used to identify growth patterns, with independent risk factors evaluated via multivariable mixed-effects logistic regression. Results This study included 910 patients (median age, 47 years [IQR, 41-57 years]; 422 men, 488 women; 1206 pGGNs). At center 1 (n = 754 pGGNs), 8.6% (65 of 754) of nodules exhibited growth, and bubble lucency (hazard ratio = 2.39; P = .02), vessel sign (hazard ratio = 2.98; P = .006), and family history of lung cancer (hazard ratio = 2.83; P = .02) were independent risk factors associated with nodule growth. At center 2 (n = 452 pGGNs), vessel sign (hazard ratio = 2.98; P = .04) and family history (hazard ratio = 3.94; P = .01) were associated with nodule growth. Latent class trajectory modeling identified a distinct progressive growth pattern in patients from both centers, for which family history of lung cancer was an independent risk factor at center 1 (odds ratio = 4.23; P = .01) and center 2 (odds ratio = 5.01; P =.003), with vessel sign being another risk factor at center 2 (odds ratio = 4.38; P = .01). Conclusion Across two independent clinical cohorts, a distinct progressive growth pattern associated with family history of lung cancer was identified in patients with incidental pGGNs detected at low-dose chest CT. © The Author(s) 2026. Published by the Radiological Society of North America under a CC BY 4.0 license. Supplemental material is available for this article. See also the editorial by Lee and Um in this issue.