Abstract Multiple primary lung cancer (MPLC) with three distinct pathological subtypes-squamous cell carcinoma (SCC), adenocarcinoma, and small cell lung cancer (SCLC)-is exceedingly rare. We present the first such case with comprehensive large-panel next-generation sequencing (NGS) of three lesions and plasma.A 59-year-old male smoker underwent left upper lobectomy in July 2017 for a solid nodule, diagnosed as stage IIA SCC (Fig.1A). Patient received four cycles of postoperative adjuvant chemotherapy Docetaxel + Nedaplatin. Chest CT at a 3-year follow-up revealed a small solid nodule in the superior lobe of his right lung, which gradually enlarged and was suspected to be lung cancer with intrapulmonary metastasis. In March 2021, the S1a segment of the right upper lobe (RUL) was resected, revealing stage SCLC , T1cN0M0 (stage IA3) (Fig.1B). Six cycles of adjuvant chemotherapy Etoposide+ Nedaplatin and five cycles of immunotherapy Camrelizumab were administered postoperatively. In addition, from the first admission, two micro pure ground-glass opacities (GGOs) existed in the patient’s RUL and middle lobe, respectively. The GGO in the RUL continued to increase during follow-up, and CT-guided percutaneous transthoracic needle biopsy suggested adenocarcinoma (Fig.1C); thus CT-guided percutaneous radiofrequency ablation (PRFA) was performed for the RUL GGO (Fig.1D) in March 2021 after a multidisciplinary team (MDT) discussion to preserve the patient’s lung function as much as possible.The three tumor tissues were retrospectively detected by a panel of genotype detection with 520 somatic genes processed by NGS and presented completely different mutation profiles, whereas Plasma testing at latest follow-up matched the SCC profile (Fig.1E). The patient remains recurrence-free at 3-month follow-up (Fig.1D).Previously, triple primary lung cancer with diverse histological subtypes was documented; however, genetic testing was not performed. There are more MPLC cases with the same histologic type of lung cancer (LC) but with various gene mutations (GMs) of lesions. Notably, no targetable driver variants were detected in in our case, the completely distinct GMs and no germline mutation indicated that the patient’s MPLC might be caused by acquired long-term exposure to smoke rather than congenital causes. Furthermore,Tumor mutational burden was high only in the SCLC lesion (12.96 Muts/Mb), suggesting that this lesion may benefit more from immunotherapy than the other two. Generally, this patient achieved a favorable outcome by regular screening, follow-up, and MDT guidance. Genetic results reveal completely different origins, and potentially treatment options for various lesions. Smoking is a risk factor for MPLC, but additional mechanistic research is required. This abstract is funded by: none
Mu et al. (Fri,) studied this question.