Case report: targeted sequencing improves the diagnosis of multiple synchronous lung cancers.

Background: The ability to distinguish satellite nodules, multiple primary lung cancers (MPLCs), and intrapulmonary metastases (IPM) is crucial for prognosis and treatment. The traditional diagnostic criteria for MPLC/IPM including the Martini and Melamed (MM) criteria and the comprehensive histologic assessment (CHA) criteria, mainly relies on histological comparison between multiple lesions. However, many challenges remain in distinguishing them in clinical practice. Case Description: We herein present a report of 3 lung adenocarcinoma cases who presented with 2 lesions, with improved diagnosis based on targeted sequencing covering driver genes. Based on histopathological features, patient 1 (P1) was classified as MPLC, whereas patients 2 and 3 (P2, P3) were classified as satellite nodules. However, targeted sequencing revealed the clonality status of these lesions and improved their diagnosis. The result of the molecular testing indicated that P1 is IPM and the other two patients (P2, P3) should be diagnosed with MPLC. Conclusions: Different lesions in the same case had different driver mutations, suggesting that the 2 lesions were driven by different molecular events. Therefore, targeted sequencing containing driver genes should be used for the diagnosis of multiple synchronous lung cancers. A limitation of this report is the short follow up period, and long-term outcomes of the patients require further follow up.