PMC10403232_01
CT-guided needle biopsy, and its pathological staining and NGS analysis. (A) CT-guided needle biopsy. (B) HE staining, spindle cells, scale bars: 100mum. (C) CK7 (+). (D) NapsinA (focal +). (E) TTF-1 (partial +). (F) VIMENTIN (spindle cell +). (G) CK (+). (H) P40 (-). (I) Ki-67 (50%). (J) NGS revealed the presence of the BRAFV600E mutation (exon 15, 22.7% abundance) and KRASG12A mutation (exon 2, 5.71% abundance). Technical details are provided in the 
Supplementary Material S5
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Since the nodule of the left lower lobe did not change significantly ( Figure S1 ), the attending doctor ignored it. To clarify the histology of the mass, a lung needle biopsy was performed on November 16 ( Figure 1A ) and an enhanced CT was reviewed ( Figure 2A ). Microscopically, two morphologies of cells, spindle cells, and epithelial cells were seen ( Figure 1B ). P40 (-), Ki-67 (50%) ( Figures 1C-I ), CK5/6 (-), SYN (-), CD56 (-), CgA (-). PD-L1 combined positive score (CPS) of the small amount of tissue taken for biopsy was 0%. 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) ( Figure 1J ), PIK3CAE707K mutation (exon 14, 1.02% abundance) and TP53H179R mutation (exon 5, 29.65% abundance).
Disease status after chemoradiotherapy and two-cycle immunotherapy. (A) CT images before treatment. (B) After chemoradiotherapy and two-cycle immunotherapy, there was a marked increase in the size of the mass and a massive encapsulated malignant pleural effusion leading to left atelectasis. The tumor response evaluation is a progressive disease (PD). Red arrows indicate tumor or lymph node lesions.
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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 ( Figure S2 ). To clarify the histology of the mass, a lung needle biopsy was performed on November 16 ( Figure 1A ) and an enhanced CT was reviewed ( Figure 2A ). CT showed that the left lung was atelectatic due to a tumor and massive pleural effusion ( Figure 2B ), and the Eastern Cooperative Oncology Group (ECOG) score was up to 3.
Disease status after targeted therapy and palliative immunotherapy. (A-C) During nearly six months of targeted therapy, the malignant pleural effusion continued to decrease and the mass continued to shrink. The tumor response evaluation of the three times respectively was SD, PR, and SD. (D) After discontinuation of targeted therapy and palliation with immunotherapy, the disease progressed. SD, stable disease; PR, partial response.
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Combined with the pathological diagnosis of the original surgical specimen ( Figure S3 ), it was consistent with the involvement of PSC. Meanwhile, his reexamination results showed that malignant pleural effusion was significantly reduced and the mass significantly retreated ( Figures 3A-C ). His last imaging examination revealed strict left lung atelectasis, increased malignant pleural effusion, and mass enlargement ( Figure 3D ).
Complete diagnosis and treatment of this PSC patient. This patient with PSC had a rapid relapse following surgery and adjuvant chemotherapy in the early stages of the disease. NGS suggested that he had a BRAFV600E mutation, but he refused targeted therapy for financial reasons, so chemotherapy combined with immunotherapy was used. However, the disease progressed rapidly, and the patient's general condition deteriorated sharply. Desperate, the patient tried targeted therapy, achieved remission and six months of PFS. But he stopped taking targeted drugs for financial reasons, the disease progressed and eventually died. Due to the need for text editing, the time axis in the image is not proportional to the length of time.
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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 ( Figure S4 ).