Recognition of “aggressive” behavior in “indolent” ground glass opacity and mixed density lesions

Background: Radiologically characteristic ground-glass opacity (GGO) represents a special cohort of pulmonary adenocarcinomas that has been unanimously defined as biologically inert. Lymph node metastasis, however, occurs occasionally in these biologically "indolent" cancers. The incidence and underlying risk factors of nodal metastasis remain unknown. Methods: All surgically removed GGO lesions between January 2008 and December 2014 were retrospectively reviewed from a single treatment institution. Pathologically-confirmed adenocarcinomas with systemic lymph node dissection or sampling were enrolled into the present study. All the lesions were classified into three groups according to the proportion of solid densities: group I, pure GGO; group II, 1% to 50%; and group III, 50% to 79%. Risk factor analysis of lymph node involvement was performed by multivariate logistic regression. Results: Of the 867 patients eligible for this study, 553 (63.7%) presented as pure GGOs (Group I) and 314 (36.2%) were mixed GGOs, of which 160 (18.5%) were in group II and 154 (17.8%) in group III. Lymph node metastasis was confirmed in 25 patients, among these 25 cases, 11 (11/160) were group II and 14 (14/154) were group III; two of the 25 patients died from lung cancer metastases at their postoperative 23rd and 36th month, respectively. Statistical analysis revealed three predictors for lymph nodal metastasis: tumor size, preoperative serum carcinoembryonic antigen level and proportion of the mix density. Conclusions: A larger size, mixed GGOs with a higher proportion of solid component, and elevated serum CEA level were associated with a higher preference for nodal metastasis.