Morphological Subtypes of Tumor Spread Through Air Spaces in Non-Small Cell Lung Cancer: Prognostic Heterogeneity and Its Underlying Mechanism

• Published in: Frontiers in oncology Vol. 11; p. 608353
• Main Authors: Xie, Huikang, Su, Hang, Zhu, Erjia, Gu, Chang, Zhao, Shengnan, She, Yunlang, Ren, Yijiu, Xie, Dong, Zheng, Hui, Wu, Chunyan, Dai, Chenyang, Chen, Chang
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 04.03.2021
• Subjects: non-small cell lung cancer; Oncology; prognosis; spread through a knife surface; spread through air spaces; artifact; non-small cell lung cancer; spread through a knife surface; prognosis; spread through air spaces
• ISSN: 2234-943X; 2234-943X
• DOI: 10.3389/fonc.2021.608353

Tumor spread through air spaces (STAS) has three morphologic subtypes: single cells, micropapillary clusters, and solid nests. However, whether their respective clinical significance is similar remains unclear. We retrospectively reviewed 803 patients with resected non-small cell lung cancer (NSCLC) from January to December 2009. Recurrence-free survival (RFS) and overall survival (OS) were compared among patients stratified by STAS subtypes. We also performed a prospective study of NSCLC resection specimens to evaluate the influence of a prosecting knife on the presence of STAS subtypes during specimen handling (83 cases). STAS was found in 370 NSCLCs (46%), including 47 single cell STAS (13%), 187 micropapillary cluster STAS (50%), and 136 solid nest STAS (37%). STAS-negative patients had significantly better survival than patients with micropapillary cluster STAS (RFS: < 0.001; OS: < 0.001) and solid nest STAS (RFS: < 0.001; OS: < 0.001), but similar survival compared with those with single cell STAS (RFS: = 0.995; OS: = 0.71). Multivariate analysis revealed micropapillary cluster (RFS: < 0.001; OS: < 0.001) and solid nest STAS (RFS: = 0.001; OS: = 0.003) to be an independent prognostic indicator, but not for single cell STAS (RFS: = 0.989; OS: = 0.68). Similar results were obtained in subgroup analysis of patients with adenocarcinoma. The prospective study of NSCLC specimens suggested that 18 cases were considered as STAS false-positive, and most were singe cell pattern (13/18, 72%). Single cell STAS was the common morphologic type of artifacts produced by a prosecting knife. A precise protocol of surgical specimen handling is required to minimize artifacts as much as possible.