ArticleDiagnostic pathology2026
Comprehensive clinicopathological and prognostic analysis of primary pulmonary lymphoepithelial carcinoma: a retrospective cohort study.
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Abstract
backgroundPrimary pulmonary lymphoepithelial carcinoma (PPLEC) is an extremely rare subtype of lung squamous cell carcinoma (LUSC). This study aims to comprehensively characterize clinicopathological and molecular characteristics, evaluate treatment strategies, and identify prognostic factors of PPLEC.
methodsThis retrospective study was conducted on 152 pathologically confirmed PPLEC patients in our center between April 2012 and December 2024. Data on clinicopathological characteristics, driver gene mutations (n = 40), PD-L1 expression (n = 65), treatment regimens, and survival outcomes were collected. Survival analyses were performed with Kaplan-Meier analysis and Cox regression model.
resultsThe median age at diagnosis in the PPLELC cohort was 55 years, with a slight female predominance (52.6%) and strong nonsmoking association (75.7%). Despite the presence of CYFRA21-1, most of the serum tumor marker levels were normal. Immunohistochemical (IHC) staining revealed characteristic epithelial differentiation with high expression of CK5/6 (100.0%), P40 (98.5%), P63 (96.9%), and pan-CK (95.5%). All patients (100%) were EBV-encoded RNA (EBER) -in situ hybridization (ISH) positive. Driver mutations were rare (2 of 40, 5.0%), while PD-L1 expression was prevalent (60 of 65, 92.3%). The TNM stage distributions were I (38.2%), II (17.8%), III (28.9%), and IV (14.5%). Early-stage patients who underwent surgical resection (n = 102) achieved a 5-year overall survival (OS) rate of 91%. For locally advanced PPLEC (n = 14), neoadjuvant therapy is a potential strategy with an objective response rate (ORR) of 50.0%. Compared with chemotherapy alone, combination therapies yielded superior outcomes in advanced-stage patients (n = 30). Multivariate survival analysis revealed TNM stage was the independent prognostic factor for progression-free survival (PFS).
conclusionsPPLEC is a distinct LUSC subtype characterized by an Epstein–Barr virus (EBV) association, a nonsmoking phenotype, epithelial differentiation, few driver mutations, and high PD-L1 expression. Surgical resection plays a pivotal role in the management of early-stage disease, whereas multimodal therapeutic approaches have considerable potential for advanced-stage cases. TNM stage was the independent prognostic factor for PFS. These findings provide valuable insights for optimizing management strategies for this rare malignant entity.
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