PMC8581303_01
Pathologic findings: (A) the large-sized epithelioid tumor cells were arranged in a nest-like pattern, and they had wide cytoplasm with obvious atypia, large and clear cell nuclear, and nuclear fission. The pathologic diagnosis of the biopsy specimens was poorly differentiated lung adenocarcinoma (H&E, SP x200). (B-F) Immunohistochemical staining showed that tumor cells were positive for CK (B, SP x200), TTF-1 (focal positive, C, SP x100), NapsinA (D, SP x200), and Vimentin (E, SP x200), and Ki-67 was 60% (F, SP x100). SP, streptavidin-peroxidase.
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In July 2020, he underwent CT-guided lung biopsy and was pathologically diagnosed with poorly differentiated LADC ( Figure 1 ).
Next-generation sequencing revealed MET intergenic fusion. Mapping of fusion junction sequence revealed the fusion of random sequences to MET gene. The breakpoints were located on chr7_gl000195_random: 6974 and chr7:116423550 in intron 19 of the MET gene, and the sequence of MET is reversed. (A) DNA sequencing reads indicating fusion region by genomics Viewer software in tissue. (B) DNA sequencing reads indicating fusion region by genomics Viewer software in plasma. (C) The breakpoints detected in the fusion by targeted next-generation sequencing (NGS) and the alterations in gene caused by this fusion.
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Genetic examination by next-generation sequencing further showed an intergenic fusion of MET ( Figure 2 ).
(A) CT image before crizotinib treatment. (B) CT image at 1 month after crizotinib treatment beginning. (C) CT image at 3 months after start of crizotinib treatment. (D) CT image at 3 months after discontinuing treatment. (E) CT image at 5 months after discontinuing treatment. (F) Tumor and lymph node shrink curve. Note that red arrows indicate the tumor. Yellow arrows indicate that the primary tumors almost disappeared. White arrows indicate the lymph nodes.
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Routine CT scans performed after 1 and 3 months of therapy showed partial response (PR) of the lung tumor and lymph metastases ( Figure 3 ). In February 2021, CT scans showed continued PR after 5 months after crizotinib therapy was discontinued ( Figure 3 ). However, the right lower lobe mass progressed in April 2021 ( Figure 3 ), and disease progression was considered.  Figure 4  showed the timeline with relevant data from the episode of care.
Historical and current information from this episode of care organized as timeline. LADC, lung adenocarcinoma; MET, mesenchymal-epithelial transition factor; PR, partial response; PD, progressive disease; ILD, interstitial lung disease; Crizo, crizotinib; Crizo DC, crizotinib was discontinued.
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However, the right lower lobe mass progressed in April 2021 ( Figure 3 ), and disease progression was considered.  Figure 4  showed the timeline with relevant data from the episode of care.