case_images: PMC10126330_01
case_images: Timeline of the treatment and disease course (A). Computed tomography scans corresponding to the timeline (B).
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case_images: Chest computed tomography (CT) revealed a mass with a diameter of 77 mm in the lower lobe of the right lung with left atrial invasion ( Figure 1B  CT1), enlarged mediastinal lymph nodes (#2R, 4R, #7, and # 2L), right hilar lymph nodes, and right pleural effusion ( Figure 1A ). The tumor size decreased two months after the initiation of alectinib therapy ( Figure 1B  CT2), and he continued its intake as prescribed without any adverse events. Additionally, the CT scan showed left atrial invasion progression ( Figure 1B  CT3). The left atrial invasion was significantly decreased two months after pembrolizumab therapy was initiated ( Figure 1B  CT4). The patient continued pembrolizumab therapy for a year with no adverse events, and continued tumor shrinkage ( Figure 1B  CT5). Heparin was switched to Apixaban, which the patient continues to use ( Figure 1A ).
case_images: Transbronchiallung biopsy before treatment. (A, B) Atypical cell infiltration and lymphocyte infiltration were observed. (100x, 400x) (C) Tumor cells positive by immunohistochemistry (IHC) for TTF-1. (100x) (D) Tumor cells were negative by IHC for p40. (100x) (E) Tumor cells positive for ALK IHC (Roche-Ventana, D5F3). (100x) (F) PD-L1 IHC (Dako, 22C3), giving a tumor proportion score of 100. (100).
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case_images: Transbronchial lung biopsy histopathological immunohistochemistry (IHC) revealed TTF-1 positive adenocarcinoma ( Figures 2A-D ). Target Test Multi-CDx System (Life Technologies corporation, Frederic and Pleasanton facility, USA) and Oncomine Comprehensive Assay v3 (OCA v3; Thermo Fisher Scientific) using fresh-frozen tissues, which was performed in a lung cancer genomic screening project for individualized medicine in Japan (LC-SCRUM)revealed an EML4-ALK fusion V1 (E13:A20). The IHC analysis using programmed death-ligand 1 (PD-L1) IHC 22C3 pharmDx assay showed high PD-L1 expression with a tumor proportion score (TPS) of 100%. ( Figure 2F ) Additionally, analysis by electrophoresis of the PCR products revealed that the case was MSI-high. The tumor size decreased two months after the initiation of alectinib therapy ( Figure 1B  CT2), and he continued its intake as prescribed without any adverse events.
case_images: Immunohistochemistry for MMR proteins MLH1, MSH2, PSM2, and MSH6. The nuclei of tumor cell were clearly positive for MLH1 and PMS2 staining together with the surrounding non-neoplastic cell nuclei, largely of infiltrating lymphocytes. In contrast. MSH2 and MSH6 were negative in tumor cells with positive staining for non-neoplastic cell nuclei, serving as internal positive control for staining. The bars in the lower left corner indicate 100mm.
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case_images: The nuclei of the tumor cells were positive for MLH1 and PMS2 but negative for MSH2 and MSH6 indicating MSI status with MSH2 gene disruption ( Figure 3 ). Additionally, the CT scan showed left atrial invasion progression ( Figure 1B  CT3).