The presence of lepidic and micropapillary/solid pathological patterns as minor components has prognostic value in patients with intermediate-grade invasive lung adenocarcinoma

Background: The acinar- and papillary-predominant histological subtypes are the most common types of invasive lung adenocarcinoma and are considered “intermediate-grade” carcinomas with heterogeneous prognosis. This study investigated the prognostic significance of the lepidic and micropapillary/solid pathological patterns as minor components in patients with intermediate-grade lung adenocarcinomas. Methods: A total of 697 patients with pathological N0M0 acinar/papillary-predominant lung adenocarcinomas ≤3 cm in diameter, who underwent curative resection in our institution between June 1, 2014 and August 31, 2016, were retrospectively enrolled in this study. Acinar/papillary-predominant lung adenocarcinomas were classified into four subtypes according to the presence of the minor pathological components lepidic (Lep), micropapillary (MP), and solid (S). The subtypes were MP/S⁻Lep⁺, MP/S⁻Lep⁻, MP/S⁺Lep⁺, and MP/S⁺Lep⁻. The 5-year recurrence-free survival (RFS) and overall survival (OS) were recorded. Factors affecting survival were analyzed by Cox regression method. Results: Among 697 intermediate-grade lung adenocarcinomas, the distribution of patients was as follows: MP/S⁻Lep⁺ type (n=314; 45.0%), MP/S⁻Lep⁻ type (n=144; 20.7%), MP/S⁺Lep⁺ type (n=133; 19.1%), and MP/S⁺Lep⁻ type (n=106; 15.2%). The 5-year RFS rates were 98.7%, 94.4%, 94.0%, and 81.9%, respectively (P<0.001). The 5-year OS rates were 98.4%, 94.4%, 96.6%, and 87.7%, respectively (P<0.001). Multivariate analysis revealed that the MP/S⁺Lep⁻ subtype was an independent poor prognostic factor of both RFS and OS. Conclusions: Acinar/papillary-predominant adenocarcinoma is an “intermediate-grade” carcinoma that can be further classified into subtypes according to the presence of lepidic and micropapillary/solid pathological patterns with significantly different prognosis. This classification may be useful in evaluating the recurrence risk and guiding adjuvant therapies in patients with acinar/papillary-predominant stage I lung adenocarcinoma.