case_images: PMC10791793_01
case_images: Chest radiological and pathological findings of the 7th station lymph nodes. (A) CT scan images of the primary tumor (red arrow) and (B) CT scan images of the enlarged 7th station lymph nodes (red arrow). (C) EBUS-TBNA for the enlarged 7th station lymph nodes. (D) HE-stained image of the 7th station lymph nodes biopsy specimens (Original magnification, x200). Immunohistochemical features indicate positive expression of TTF-1 (E) and Napsin A (F). (G) PD-L1 assay of the 7th station lymph nodes biopsy specimens by immunohistochemical staining (Original magnification, x200). (H) The presence of KIF5B-RET gene fusion was identified by ARMS RT-PCR. (I)
  RET rearrangement was detected by the break-apart fluorescence in situ hybridization (FISH) assay (Original magnification, x1000). (J) NGS results revealed KIF5B-RET gene fusion in the Integrative Genomics Viewer genome browser. ARMS, Amplification Refractory Mutation System; CT, computed tomography; EBUS-TBNA, endobronchial ultrasound with real-time guided transbronchial needle aspiration; HE, hematoxylin and eosin; PD-L1, programmed cell death-ligand 1; RT-PCR, Reverse Transcription-Polymerase Chain Reaction.
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case_images: Cooperative Oncology Group (ECOG) performance status was 0. Computed tomography (CT) scan revealed a 3.2 cm x 2 cm x 3.2 cm soft tissue mass in the dorsal segment of the lower lobe of the right lung near the hilum ( Figure 1A ) and enlarged mediastinal 2R, 4R, 7th and right hilar lymph nodes ( Figure 1B ). There was no evidence of malignant lesions was observed in the central nervous system ( Supplementary Figure 1 ). Endobronchial ultrasound-transbronchial needle aspiration (EBUS-TBNA) for the mediastinal lymph nodes was performed for enlarged 7th station lymph nodes ( Figure 1C ). Pathological examination showed low-differentiation metastatic lung adenocarcinoma with positive expression of TTF-1 and Napsin A ( Figures 1D-F ). Moreover, programmed cell death-ligand 1 (PD-L1) expression was found to be up to 80% in the tumor cells, as tested by the clone Dako 22C3 pharmDx antibody ( Figure 1G ). The sequencing assay showed that this patient had a RET fusion: KIF5B-RET (K15: R12, abundance: 2.14%) ( Figure 1J ), which was further confirmed by amplification-refractory mutation system-polymerase chain reaction technology (ADx-ARMS RT-PCR kit, Amoy Diagnostics, Xiamen, China) ( Figure 1H ) and in situ hybridization assay analysis with RET break-apart fluorescence (ZytoVision) ( Figure 1I ).
case_images: Images before (red arrow) and after (blue arrow) neoadjuvant camrelizumab plus chemotherapy treatment. (A) showed PET-CT of the primary tumor; (B) showed PET-CT of the 7th station lymph nodes. LN 7, 7th station lymph nodes; PET-CT, positron emission tomography-computed tomography.
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case_images: Posttreatment radiologic evaluation by PET-CT showed that the primary lesion and mediastinal lymph nodes had decreased in size and had slowed their metabolism when compared with the disease status in Nov 2021 ( Figure 2 ).
case_images: Picture of the postoperative pathological HE-staining of the primary lesion of the lower lobe of the right lung. (Original magnification, (A): x40; (B): x100). HE, hematoxylin and eosin.
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case_images: The postoperative pathologic examination demonstrated the absence of any remaining viable tumor cells in both the primary lesion and resected lymph nodes, thereby confirming the patient's attainment of a pCR subsequent to neoadjuvant chemoimmunotherapy ( Figures 3A, B ).
case_images: Timeline of the patient's treatment history. LUAD, lung adenocarcinoma; PD-L1, programmed death-ligand 1; NGS, next-generation sequencing; pCR, pathological complete response; AUC, area under the curve; DFS, disease-free survival.
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case_images: After surgery, the patient was treated with adjuvant immunotherapy using camrelizumab (200 mg/m2) for 13 cycles, and no recurrence or complications were observed during the 12-month follow-up ( Figure 4 ).