Synchronous Multiple Pulmonary Ground-Glass Nodules That Arose from Different Lesions Rather than from Multiple Metastases of a Single Lesion

Abstract

Abstract Purpose This study aimed to investigate the expression of lung cancer driver genes in patients with synchronous multiple ground-glass nodules (SMGGNs), to calculate the relationships of these genes with clinical features, and to probe into the origin of multiple primary pulmonary ground-glass nodules (GGNs) from the perspective of molecular biology. Methods The clinicopathological data of 50 patients with SMGGNs who were admitted to the Department of Thoracic Surgery of the Fourth Hospital of Hebei Medical University from January 2018 to January 2021 were collected for retrospective analysis. All the samples resected were genotyped at 16 lung cancer driver gene loci by next-generation sequencing technology. The relationships between gene mutations and clinical features were analysed, and suspected pulmonary nodules of the same origin were analysed by the whole-exome sequencing. Results Fifty patients were included in the study, 86.0% (43/50) of whom had gene mutations. Some 133 pulmonary nodules were resected, which were pathologically classified into the following types: atypical adenomatous hyperplasia (21 nodules), adenocarcinoma in situ (32), micro-invasive adenocarcinoma (30), and invasive adenocarcinoma (50). Lung cancer driver gene mutations were identified in 73 (54.9%) nodules, 63.0% (46/73) of which were in the epidermal growth factor receptor gene (EGFR). Significant differences were observed in the gene mutation status between nodule types, particularly EGFR mutation, which differed between histological and imaging subtypes. Multiple gene mutations were not discovered in the same tissue. A low-probability mutation (RET fusion) was detected in three nodules of one patient, and further whole-exome sequencing showed that the three nodules had different gene mutations and were not metastatic. Conclusions The driver gene mutations in patients with SMGGNs are quite different and mutually exclusive, and nodules can arise from multiple primary lesions. Surgical resection is considered a superior approach to treating SMGGNs.