Histopathologic features from preoperative biopsies to predict spread through air spaces in early-stage lung adenocarcinoma: a retrospective study

Cao et al. BMC Cancer (2021) 21:913 https://doi.org/10.1186/s12885-021-08648-0 RESEARCH ARTICLE Open Access Histopathologic features from preoperative biopsies to predict spread through air spaces in early-stage lung adenocarcinoma: a retrospective study Lanqing Cao, Meng Jia, Ping-Li Sun* and Hongwen Gao Abstract Background: Although spread through air spaces (STAS) is a robust biomarker in surgically resected lung cancer, its application to biopsies is challenging. Moreover, limited resection is not an effective treatment for STAS-positive lung adenocarcinoma. This study aimed to identify histologic features from preoperative percutaneous transthoracic needle biopsies (PTNBs) to predict STAS status in the subsequently resected specimens, and thus help in selecting the surgical extent. Methods: Between January 2014 and December 2015, 111 PTNB specimens and subsequent resection specimens from consecutive lung adenocarcinoma patients were retrospectively examined. Histopathologic features of PTNB specimens and presence of STAS in subsequent resection specimens were evaluated and correlations between them were analyzed statistically. Results: The study participants had a mean age of 59 years (range, 35–81) and included 50 men and 61 women. Thirty-six patients were positive for STAS whereas 75 were negative. The micropapillary/solid histologic subtypes of lung adenocarcinoma (26 of 39; 66.7%; P < 0.001), necrotic/tumor debris (31 of 42; 73.8%; P < 0.001), intratumoral budding (ITB) (20 of 33; 60.6%; P < 0.001), desmoplasia (35 of 41; 85.4%; P < 0.001), and grade 3 nuclei (12 of 14; 85.7%; P < 0.001) were more common in STAS-positive tumors. Micropapillary/solid histologic subtype (OR, 1.35; 95% CI: 1.06, 1.67), ITB (OR, 1.64; 95% CI: 1.09, 2.83), desmoplasia (OR, 1.83; 95% CI: 1.36, 3.12), and N stage (N1 stage: OR, 1.37; 95% CI: 1.19, 1.87) (N2 stage: OR, 1.29; 95% CI: 1.07, 1.73) were independent predictors of STAS. Conclusions: Micropapillary/solid histologic subtype, ITB, and desmoplasia in preoperative PTNB specimens were independently associated with STAS in the subsequent resection specimens. Therefore, these can predict STAS and may help to optimize therapeutic planning. Keywords: Histopathologic features, Lung adenocarcinoma, PTNB, Risk stratification, Spread through air spaces Background Lung adenocarcinomas (LAC) have a unique pattern of invasion compared to malignancies originating in other organs. Apart from non-lepidic histologic invasion * Correspondence: Department of Pathology, The Second Hospital of Jilin University, 218 Ziqiang Road, Changchun, Jilin 130041, China subtypes, infiltrating myofibroblastic stroma, lymphovascular invasion, and pleural invasion, tumor spread through air spaces (STAS), a new distinct invasion concept, was recognized as a pattern of tumor spread in LACs [1]. STAS is defined as micropapillary clusters, solid nests, or single cells beyond the edge of the © The Author(s). 2021 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Cao et al. BMC Cancer (2021) 21:913 primary tumor spreading into the air spaces of the surrounding lung parenchyma [1]. STAS is correlated with a considerable reduction in the recurrence-free survival (RFS) and overall survival (OS) in LACs. The presence of STAS has been associated with more aggressive features and poor prognosis in several histological variations of lung cancer. Furthermore, STAS has been recognized as an exclusion criterion for the diagnosis of adenocarcinoma in situ and minimally invasive adenocarcinoma (MIA) [1]. Specifically, STAS is a robust predictor for the local recurrence of early-stage LACs treated with limited resection [2, 3]. Since STAS status can be determined only after the operation to date, it cannot offer substantial assistance for operative decisions. No reliable standard assessment system has been reported for evaluating STAS status by frozen tissue sections during surgical procedures [4]. Thus, determining the potential ability to predict STAS status from preoperative biopsy studies can optimize therapeutic planning for LACs. In this study, the histologic features of percutaneous transthoracic needle biopsy (PTNB) of LACs were reviewed, and we further correlated the histologic findings of the PTNB specimens with those of the corresponding resected tissues. The main goal of this study was to identify the histologic features that can predict Fig. 1 Flowchart of patient inclusion and exclusion Page 2 of 8 tumor behavior in lung biopsy specimens, thus providing clues for optimal surgical treatment planning. Methods Patients This retrospective study was approved by the Ethics Committee of the Second Hospital of Jilin University (Jilin, China). The requirement for informed consent was waived due to the retrospective nature of the study. Between January 2014 and December 2015, 111 consecutive patients underwent PTNB at our hospital, and were pathologically diagnosed with lung adenocarcinoma. Figure 1 shows patients inclusion and exclusion criteria for the study. All patients underwent a subsequent curative surgical resection. Surgical extent was subclassified as segmentectomy, lobectomy, or pneumonectomy; segmentectomies were collectively referred to as limited resection. Patients were excluded from this study if the pathological findings were inconclusive, or if they had a history of a previous lung operation, neoadjuvant therapy, and specific variants of adenocarcinoma such as invasive mucinous adenocarcinoma, fetal or enteric adenocarcinoma, or other specific accompanying components such as squamous, neuroendocrine, or poor differentiation. Clinical parameters, such as patient age, sex, tumor location, and postoperative outcomes, were collected from the medical records. Cao et al. BMC Cancer (2021) 21:913 Page 3 of 8 Evaluation of histologic features Results Pathological examination of the PTNB and surgical specimens was performed using sequential 3-mmthick (...truncated)