PMC10126330_01
Timeline of the treatment and disease course (A). Computed tomography scans corresponding to the timeline (B).
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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 ).
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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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.
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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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).