AUTHOR=Xie Huikang , Su Hang , Zhu Erjia , Gu Chang , Zhao Shengnan , She Yunlang , Ren Yijiu , Xie Dong , Zheng Hui , Wu Chunyan , Dai Chenyang , Chen Chang 

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

JOURNAL=Frontiers in Oncology

VOLUME=11

YEAR=2021

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2021.608353

DOI=10.3389/fonc.2021.608353

ISSN=2234-943X

ABSTRACT=<sec><title>Background</title><p>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.</p></sec><sec><title>Methods</title><p>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).</p></sec><sec><title>Results</title><p>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: <italic>P</italic> &lt; 0.001; OS: <italic>P</italic> &lt; 0.001) and solid nest STAS (RFS: <italic>P</italic> &lt; 0.001; OS: <italic>P</italic> &lt; 0.001), but similar survival compared with those with single cell STAS (RFS: <italic>P</italic> = 0.995; OS: <italic>P</italic> = 0.71). Multivariate analysis revealed micropapillary cluster (RFS: <italic>P</italic> &lt; 0.001; OS: <italic>P</italic> &lt; 0.001) and solid nest STAS (RFS: <italic>P</italic> = 0.001; OS: <italic>P</italic> = 0.003) to be an independent prognostic indicator, but not for single cell STAS (RFS: <italic>P</italic> = 0.989; OS: <italic>P</italic> = 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%).</p></sec><sec><title>Conclusions</title><p>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.</p></sec>