cancers Article Predictors of Invasive Adenocarcinomas among Pure Ground-Glass Nodules Less Than 2 cm in Diameter Wen-Chi Hsu 1 , Pei-Ching Huang 1 , Kuang-Tse Pan 1 , Wen-Yu Chuang 2 , Ching-Yang Wu 3 , Ho-Fai Wong 1 , Cheng-Ta Yang 4 and Yung-Liang Wan 1, *   Citation: Hsu, W.-C.; Huang, P.-C.; Pan, K.-T.; Chuang, W.-Y.; Wu, C.-Y.; Wong, H.-F.; Yang, C.-T.; Wan,Y.-L. Predictors of Invasive Adenocarcinomas among Pure Ground-Glass Nodules Less Than 2 cm in Diameter. Cancers 2021, 13, 3945. https://doi.org/10.3390/ cancers13163945 Academic Editors: Giuseppe Broggi and Lucia Salvatorelli Received: 30 June 2021 Accepted: 2 August 2021 Published: 5 August 2021 Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affil- iations. Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). 1 Department of Medical Imaging and Intervention, Linkou Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan; nkuj123321@gmail.com (W.-C.H.); spookie@cgmh.org.tw (P.-C.H.); pan0803@cgmh.org.tw (K.-T.P.); hfwong@adm.cgmh.org.tw (H.-F.W.) 2 Department of Anatomic Pathology, Linkou Chang Gung Memorial Hospital, College of Medicine, Chang GungUniversity, Taoyuan 333, Taiwan; s12126@cgmh.org.tw 3 Division of Thoracic and Cardiovascular Surgery, Linkou Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan; wu.chingyang@gmail.com 4 Department of Thoracic Medicine, Chang Gung Memorial Hospital, Taoyuan 333, Taiwan; yang1946@cgmh.org.tw * Correspondence: ylw0518@cgmh.org.tw; Tel.: +886-3-3281200 (ext. 2575) Simple Summary: Benign lesions, atypical adenomatous hyperplasia, and malignancies such as adenocarcinoma in situ, minimally invasive adenocarcinoma, and invasive adenocarcinoma may feature pure ground-glass nodules on chest CT images, and the prognosis of patients with invasive adenocarcinoma is worse than others. The early detection and adequate management of invasive adenocarcinoma is crucial, but the pathology diagnosis of small nodules is difficult to obtain without surgery. Our study aimed to analyze the CT characteristics of pure ground-glass nodules <2 cm for the identification of invasive adenocarcinomas. A total of 181 nodules in 171 patients were enrolled. The larger size, lobulation, and air cavity were significantly more common in invasive adenocarcinoma. The air cavity is the significant predictor in multivariate analysis. In conclusion, the possibility of invasive adenocarcinoma is higher in a pure ground-glass nodules when it is associated with a larger size, lobulation, and air cavity. Abstract: Benign lesions, atypical adenomatous hyperplasia (AAH), and malignancies such as ade- nocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA), and invasive adenocarcinoma (IA) may feature a pure ground-glass nodule (pGGN) on a thin-slide computed tomography (CT) image. According to the World Health Organization (WHO) classification for lung cancer, the prog- nosis of patients with IA is worse than those with AIS and MIA. It is relatively risky to perform a core needle biopsy of a pGGN less than 2 cm to obtain a reliable pathological diagnosis. The early and adequate management of patients with IA may provide a favorable prognosis. This study aimed to disclose suggestive signs of CT to accurately predict IA among the pGGNs. A total of 181 pGGNs of less than 2 cm, in 171 patients who had preoperative CT-guided localization for surgical excision of a lung nodule between December 2013 and August 2019, were enrolled. All had CT images of 0.625 mm slice thickness during CT-guided intervention to confirm that the nodules were purely ground glass. The clinical data, CT images, and pathological reports of those 171 patients were reviewed. The CT findings of pGGNs including the location, the maximal diameter in the long axis (size-L), the maximal short axis diameter perpendicular to the size-L (size-S), and the mean value of long and short axis diameters (size-M), internal content, shape, interface, margin, lobulation, spiculation, air cavity, vessel relationship, and pleural retraction were recorded and analyzed. The final pathological diagnoses of the 181 pGGNs comprised 29 benign nodules, 14 AAHs, 25 AISs, 55 MIAs, and 58 IAs. Statistical analysis showed that there were significant differences among the aforementioned five groups with respect to size-L, size-S, and size-M (p = 0.029, 0.043, 0.025, respectively). In the univariate analysis, there were significant differences between the invasive adenocarcinomas and the non-invasive adenocarcinomas with respect to the size-L, size-S, size-M, lobulation, and air cavity (p = 0.009, 0.016, 0.008, 0.031, 0.004, respectively) between the invasive Cancers 2021, 13, 3945. https://doi.org/10.3390/cancers13163945 https://www.mdpi.com/journal/cancers