Second predominant subtype predicts outcomes of intermediate-malignant invasive lung adenocarcinoma†

OBJECTIVES: Acinar predominant and papillary predominant invasive adenocarcinomas are likely to be classified as intermediate-malignant types. Although these two types of adenocarcinoma are distinguished morphologically, the differences between their malignant behaviours and prognoses are not clear. The aim of this study is to provide a prognostically relevant stratification of these similar subtypes based on pathological features. METHODS: We retrospectively reviewed 347 consecutive clinically N0M0 lung adenocarcinomas of ≤3 cm in diameter that were resected between April 2006 and December 2010 at two institutes. Acinar and papillary predominant adenocarcinomas were classified into acinar/papillary-lepidic type and acinar/papillary-non-lepidic type according to whether the second predominant component was a lepidic or invasive component. RESULTS: Fifty-four acinar and 59 papillary predominant adenocarcinoma cases were classified as acinar/papillary-lepidic type (n = 65) or acinar/papillary-non-lepidic type (n = 48) cases. Acinar/papillary-non-lepidic type cases were accompanied by more vascular invasion (13.8% vs 31.3%, P = 0.0451) and pleural invasion (9.2% vs 25.0%, P = 0.0450) than were acinar/papillary-lepidic type cases. Five-year overall survival (OS) and recurrence-free survival (RFS) also differed significantly between these types (5-year OS: acinar/papillary-lepidic type, 96.3% vs acinar/papillary-non-lepidic type, 61.8%, hazard ratio = 6.315, P = 0.00650; 5-year RFS: acinar/papillary-lepidic type, 91.4% vs acinar/papillary-non-lepidic type, 68.8%, hazard ratio = 2.967, P = 0.0210). Multivariate analysis revealed that a second predominant component was an independent prognostic factor for RFS (acinar/papillary-non-lepidic type: hazard ratio = 3.784, 95% confidence interval 1.091–13.128, P = 0.036). CONCLUSIONS: The pathological second predominant component allows intermediate-malignant adenocarcinomas to be subclassified with prognostic significance. It can be utilized when assessing postoperative risks for recurrence and when considering therapeutic strategies.