The Prognostic Significance of the Second Predominant Histological Pattern in Resected Early-Stage Lung...

Background: Lung adenocarcinoma is morphologically heterogeneous, composed of various histological patterns. The International Association for the Study of Lung Cancer (IASLC) grading system, based on the predominant pattern and the presence of high-grade components, underscores this heterogeneity's prognostic relevance. However, the specific impact of the non-predominant "second component" on survival outcomes in early-stage disease remains inadequately characterized. Methods: We conducted a retrospective, single-center study including 95 patients with pathological stage 0, I, and II (TNM 8th edition) lung adenocarcinoma who underwent complete anatomical resection (lobectomy or segmentectomy) between January 2020 and December 2021. Histopathological evaluation followed the WHO 5th edition classification, with patterns quantified in 5% increments. The second predominant component was defined as the second most represented histological pattern, irrespective of a fixed percentage threshold. Overall survival (OS) and disease-free survival (DFS) were analyzed. Results: A second predominant component was identified in 55 patients (57.9%). The most common second components were lepidic (30.5%), solid (18.9%), and micropapillary (10.5%). With a median follow-up of 36 months, the presence of a lepidic second component was an independent factor for improved OS (Hazard Ratio [HR] 0.70, 95% CI 0.52-0.95, p = 0.022) and DFS (HR 0.62, 95% CI 0.41-0.93, p = 0.021). Conversely, a micropapillary second component was a strong independent predictor of worse OS (HR 1.81, 95% CI 1.24-2.64, p = 0.002) and DFS (HR 2.03, 95% CI 1.32-3.12, p = 0.001). The solid second component showed an intermediate adverse effect on DFS (HR 1.45, 95% CI 1.01-2.08, p = 0.043). Conclusions: The second predominant histological pattern provides additional prognostic information beyond the IASLC grading system and may improve postoperative risk stratification in early-stage lung adenocarcinoma. A lepidic second component portends a favorable prognosis, while micropapillary and solid components denote aggressive tumor biology and higher recurrence risk. Incorporating the evaluation of second components into routine pathological reporting and clinical decision-making could enhance postoperative risk stratification and personalize adjuvant therapy strategies.