Intratumor Heterogeneity Predicts Prognosis in Lepidic Predominant Lung Adenocarcinoma

• DOI: 10.1111/1759-7714.15536
• Publication Date: 2025-01-14T09:49:18Z
• Authors: Benedikt Niedermaier; Michael Allgäuer; Thomas Muley; Marc A. Schneider; Martin E. Eichhorn; Hauke Winter; Laura V. Klotz
• Keywords: histology; lung cancer; Neoplasms. Tumors. Oncology. Including cancer and carcinogens; Original Article; prognosis; lepidic; survival; RC254-282

ABSTRACTObjectiveAmong the different subtypes of invasive lung adenocarcinoma, lepidic predominant adenocarcinoma (LPA) has been recognized as the lowest‐risk subtype with good prognosis. The aim of this study is to provide insight into the heterogeneity within LPA tumors and to better understand the influence of other sub‐histologies on survival outcome.MethodsOverall, 75 consecutive patients with LPA in pathologic stage I (TNM 8th edition) who underwent resection between 2010 and 2022 were included into this retrospective, single center analysis. The proportions of different growth patterns were reported in 5% increments according to the WHO classification.ResultsAll tumors exhibited a predominantly lepidic growth pattern (median proportion 70%, IQR 60%–85%). The invasive component included acinar (n = 66, 88%), papillary (n = 41, 55%), micropapillary (n = 14, 19%), and solid growth patterns (n = 4, 5%), with most tumors exhibiting more than one invasive growth pattern. The presence of high‐risk growth, that is, micropapillary and solid, was associated with higher T stage (r = 0.423, p = 0.0002). A classification of patients as lepidic/high‐risk or lepidic/low‐risk based on the presence of micropapillary and solid growth patterns resulted in a significantly worse disease‐free survival (p = 0.0169, 5‐year DFS: lepidic/high‐risk 73% vs. lepidic/low‐risk: 95%) for the lepidic/high‐risk group, while the groups did not differ in age, gender, smoking status, or extent of resection.ConclusionPatients with stage I LPA exhibit considerable intratumor heterogeneity regarding growth patterns, which can be used for prognostic stratification. The occurrence of micropapillary and solid growth patterns in LPA is associated with poorer disease‐free survival.