A 67-year-old man, with a 30-year history of smoking and a five-year history of hypertension, came to Zhongnan Hospital of Wuhan University with a cough on February 1, 2021. Since the nodule of the left lower lobe did not change significantly (), the attending doctor ignored it. The patient’s cough did not abate and he went to another hospital on April 8, 2021. A PET-CT examination revealed a nodule in the basal segment of the left inferior lobe with cavity and increased metabolism. Then, he underwent a lower left lobectomy and lymph node dissection on April 15. The pathological findings of the excised tissue suggested PSC (d=1.3cm) and no lymph node metastasis. In addition, the tumor stage was T1aN0M0. Considering the elevated risk of postoperative recurrence and poor prognosis of PSC, he then received four cycles of postoperative adjuvant chemotherapy (gemcitabine 2200 mg d1, d8 + cisplatin 40 mg d1~d3) from June 3 through August 6 in another hospital, during which severe myelosuppression and anemia occurred, and reexamination showed no tumor recurrence. However, on October 21, 2021, he came to Zhongnan Hospital of Wuhan University again due to fatigue and chest pain, and out-patient CT showed enlarged nodules of left lung and subpleural, enlarged mediastinal lymph nodes and multiple low-density shadows on left ribs (). To clarify the histology of the mass, a lung needle biopsy was performed on November 16 () and an enhanced CT was reviewed (). Microscopically, two morphologies of cells, spindle cells, and epithelial cells were seen (). The immunohistochemical results were as follows: CK7 (+), NapsinA (focal +), TTF-1 (partial +), VIMENTIN (spindle cell +), CK (+), P40 (-), Ki-67 (50%) (), CK5/6 (-), SYN (-), CD56 (-), CgA (-). PD-L1 combined positive score (CPS) of the small amount of tissue taken for biopsy was 0%. The above results support the diagnosis of lung adenocarcinoma poorly differentiated with spindle cell components (). Combined with the pathological diagnosis of the original surgical specimen (), it was consistent with the involvement of PSC. Based on the clinical information, we considered it was a PSC recurrence. Upon next-generation sequencing (NGS) analysis of the biopsy tissue sample, the patient was identified with BRAFV600E mutation (exon 15, 22.7% abundance), KRASG12A mutation (exon 2, 5.71% abundance) (), PIK3CAE707K mutation (exon 14, 1.02% abundance) and TP53H179R mutation (exon 5, 29.65% abundance). To relieve the chest pain, he began to receive radiotherapy (Dt=45Gy/15F) on November 29 for the destruction of the ribs and the surrounding carcinoma tissue (). After radiotherapy, his chest pain eased significantly. He refused targeted therapy for financial reasons. Later, he received one-cycle chemotherapy (albumin-bound paclitaxel 400mg d1 + carboplatin 400mg d1) in combination with tislelizumab (200mg d1) on December 18 and was pleural infused with cisplatin (40mg) on December 20. Unfortunately, he developed severe post-chemotherapy myelosuppression, malnutrition, and pulmonary infection, as well as a large pleural effusion, and the family refused to perform pleurocentesis. After symptomatic treatment, the patient continued to be unable to tolerate chemotherapy, so he was only treated with tislelizumab (200mg d1) on January 22, 2022. However, his condition continued to deteriorate. On February 2, he was re-admitted to the hospital due to fever and dyspnea. CT showed that the left lung was atelectatic due to a tumor and massive pleural effusion (), and the Eastern Cooperative Oncology Group (ECOG) score was up to 3. He could no longer tolerate chemotherapy and immunotherapy, and after adequate communication, he opted for targeted therapy with oral dabrafenib and trametinib. Although he suffered adverse reactions such as pruritus and loss of appetite during the course of the targeted medication, he improved after treatment. Meanwhile, his reexamination results showed that malignant pleural effusion was significantly reduced and the mass significantly retreated (). The tumor response evaluation reached partial response (PR). Nonetheless, he stopped taking dabrafenib and trametinib in July 2022 because of financial pressures and began palliative antitumor therapy with tislelizumab (200mg d1) on August 12. His last imaging examination revealed strict left lung atelectasis, increased malignant pleural effusion, and mass enlargement (). Through follow-up, we learned that he passed away at home on November 7, 2022.