case_images: PMC10850318_01
case_images: Radiographic evaluations of main lesions during the disease course. (A) Computed tomography (CT) scan at diagnosis. (B) CT scan showed lesions shrank after 1 month of first-line icotinib; (C) CT scan after resistance to icotinib. (D) CT scan after 3 months of osimertinib treatment; (E) CT scan before the second cycle of nedaplatin-pemetrexed-bevacizumab showing partial response; (F) CT after 6 months of third-line therapy showing disease progression; (G) CT scan after 2 months of immunotherapy. RUL, right upper lobe; RLL, right lower lobe; RML, right middle lobe; PR, partial response.
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case_images: The chest computed tomography (CT) scan showed a suspicious central right lung mass, with hilum of right lung, bilateral lung, and mediastinal lymph node metastasis; right-sided pleural effusion; and a small amount of pericardial effusion and atelectasis of the middle and lower lobes of the right lung ( Figure 1A ). After 1 month, CT showed a partial response (PR;  Figure 1B ). The tumor continued to grow slowly over 3 months ( Figure 1C ), and a lung biopsy was obtained. Figure 1D ), accompanied with increased hemoptysis and cough. From November 2020 to April 2021, he received two cycles of nedaplatin (180 mg)-pemetrexed (900 mg)-bevacizumab (600 mg) therapy, then four cycles of combination therapy with nedaplatin (180 mg) plus pemetrexed (900 mg), and one cycle of pemetrexed (900 mg) monotherapy. Pulmonary CT scans showed PR after first cycle of nedaplatin-pemetrexed-bevacizumab treatment and disease progression in May 2021 [progression-free survival (PFS) 6.5 months,  Figures 1E, F ]. Then, the patient received camrelizumab (anti-PD1, 200 mg) monotherapy (PFS 1 month) and camrelizumab (200 mg, q 3 weeks) plus pemetrexed (900 mg) therapy ( Figure 1G ).
case_images: Hematoxylin and eosin staining and immunohistochemical findings of samples at different disease courses. (A) Circulating tumor cells in pleural fluid on hematoxylin and eosin staining at diagnosis. (B, C) Immunohistochemical staining was positive for NapsinA (B) and TTF-1 (C). (D) Hematoxylin and eosin staining of lung biopsy after resistance to first-line icotinib showed cylindrical morphology and formed glandular tubular structures. (E-H) Immunohistochemical staining was positive for NapsinA (E), TTF-1 (F), CK7 (G), and CK20 (H). (I-L) Immunohistochemical staining was positive for four MMR proteins. Magnification x40 (A-C, E-G, I-L); magnification x200 (D, H). NapsinA, novel aspartic proteinase of the pepsin family A; TTF-1, thyroid transcription factor-1; CK, cytokeratin; CDX2, caudal-type homeobox transcription factor 2; MMR, mismatch repair.
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case_images: Cytological examination of pleural fluid revealed the diagnosis of malignant pleural effusion with the tumor cells positive staining for NapsinA and thyroid transcription factor-1 (TTF-1;  Figures 2A-C ). The lung biopsy showed enteric differentiation components, which exceeded 50% ( Figure 2D ). Immunohistochemical (IHC) assays showed that the tumor was positive for TTF-1, NapsinA, CK7, and CDX2 ( Figures 2D-H ) and negative for programmed death ligand 1 (PD-L1; SP263 antibody), resulting in a diagnosis of an intestinal-type adenocarcinoma of the lung. IHC analysis for DNA mismatch repair proteins (MLH1, PMS2, MSH2, MSH6) revealed that the patient had proficient DNA mismatch repair (pMMR) positive for all microsatellite markers ( Figures 2I-L ).