부산대학교 도서관

Pulmonary lymphoepithelial carcinoma (PLEC) is a rare subtype of non-small cell lung cancer (NSCLC) primarily prevalent in Southeast Asia. Histologically, PLEC is characterized by undifferentiated tumor cells with vesicular nuclei and prominent nucleoli, often accompanied by extensive lymphocyte infiltration. Additionally, PLEC is commonly associated with Epstein-Barr virus (EBV) infection. Given the rarity of the disease and regional limitations, there are limited studies on PLEC, and prognostic factors of PLEC have still remained unclear. In this study, we aimed to identify prognostic factors for PLEC by analyzing various factors, including clinical characteristics (age, gender, smoking history, pleural invasion, tumor size, stage, surgical method), histopathological features (tumor pattern, T: L, TILs, TLS, STAS, granuloma, tumor necrosis, LVI, tumor budding), and immunohistochemical (IHC) markers (MTAP, cyclin D1, SSTR2A, PD-L1). We retrospectively reviewed tumor slides from surgically resected stage I-III PLEC cases (n=56) and conducted survival analysis using Kaplan-Meier method to assess overall survival (OS) and recurrence-free survival (RFS) to find out prognostic factors of PLEC. Our results revealed several factors significantly associated with shorter OS, including gender (p = 0.007), smoking history (p = 0.016), and STAS (p = 0.029). For RFS, significant negative prognostic factors included pleural invasion (p = 0.003), tumor size (p = 0.026), stage (p = 0.001), STAS (p = 0.040), and LVI (p = 0.002). To further validate our findings and exclude confounding factors, we performed multivariate Cox regression analysis separately for OS and PFS. The multivariable Cox regression model revealed that none of the analyzed factors were significantly associated with OS. However, STAS and stage (stage III vs stage I) emerged as independent prognostic factors for RFS, with hazard ratios of 3.748 (p = 0.036) and 10.631 (p = 0.007), respectively. Based on the significant association between STAS and RFS, we proposed a novel 3-tier grading system for PLEC that based on tumor border and the presence of STAS. According to this grading system, tumors were classified into three grades according to their tumor border patterns (TBP): TBP1 tumor (15, 26.8%) with well-defined tumor borders, TBP2 tumor (23, 41.1%) with spiculated borders without STAS, and TBP3 tumor (18, 32.1%) with spiculated borders and STAS. This grading system demonstrated significant prognostic value, as evidenced by the RFS rates observed in each tier: 92.9% for TBP1 tumors, 65.7% for TBP2 tumors, and 45.0% for TBP3 tumors. In conclusion, our study identified STAS and stage (stage III vs stage I) were independent prognostic factors for RFS in PLEC. Additionally, the newly proposed 3-tier TBP grading system showed significant prognostic value, providing valuable information for clinical decision-making in PLEC.