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 intermediatemalignant 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.