Prognostic histologic subtyping of dominant tumor in resected synchronous multiple adenocarcinomas of lung

The prognostic role of histological patterns of dominant tumor (DT) and second dominant tumor (sDT) in synchronous multiple adenocarcinoma (SMADC) of lung remains unclear. SMADC patients diagnosed between 2003 and 2015 were retrospectively reviewed. DT and sDT were defined as two maximum diameters of consolidation among multiple tumors. Histological pattern was determined using IASLC/ATS/ERS classification system. DTs were divided into low- (lepidic), intermediate- (acinar, papillary) and high-grade (micropapillary, solid) subtypes, and sDTs into non-invasive predominant (lepidic) and invasive predominant (acinar, papillary, micropapillary, solid) subtypes. During mean 74-month follow-up among 149 nodal-negative patients having SMADC resected, recurrence was noted in 44 (29.5%), with significantly higher percentage in high-grade DT (p < 0.001). Five-year overall (OS) and disease-free (DFS) survivals in low-, intermediate- and high-grade DT were 96.9%, 94.3%, 63.3% (p < 0.001) and 100%, 87.2%, 30.0%, respectively (p < 0.001). Cox-regression multivariate analysis demonstrated high-grade DT as a significant predictor for DFS (Hazard ratio [HR] 5.324; 95% CI 2.570–11.462, p < 0.001) and OS (HR 3.287; 95% CI 1.323–8.168, p = 0.010). Analyzing DT and sDT together, we found no significant differences in DFS, either in intermediate- or high-grade DT plus invasive or non-invasive sDT. DT was histologically an independent risk factor of DFS and OS in completely resected nodal-negative SMADCs.