PMC9643274_01
Chest computed tomography at initial diagnosis, during and after treatment. (A). At initial diagnosis. (B). After treatment of EP combined with radiotherapy. (C). At the first relapse. (D). After treatment with chemotherapy plus icotinib. (E). After icotinib resistance. (F). After treatment of osimertinib.
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Chest computed tomography (CT) revealed a left hilar mass with obstructive pneumonia of the left upper lobe ( Figure 1A ). Tumors version 1.1 ( Figure 1B ,  3 ). The patient showed good tolerance to chemoradiotherapy with a transient gastrointestinal response. A CT scan revealed a new lesion at the same site of the primary tumor ( Figure 1C ). After six cycles of chemotherapy plus icotinib followed by icotinib maintenance, the patient achieved a near-complete radiological response ( Figure 1D ,  3 ). After 19 months of stable disease, a chest CT disclosed a mass occupying the left upper hilar portion with obstructive pneumonia ( Figure 1E ). T790M was detected in blood plasma by the NGS CGP assay. The patient began to take osimertinib (80mg, q.d., p.o.) and achieved a partial response ( Figures 1F ,  3 ).
Histopathologic analysis at initial diagnosis, during and after treatment. (A-D) H&E staining and IHC analysis of Napsin-A at initial diagnosis (A, B), at the first relapse (C, D). (E) H&E staining after icotinib resistance.
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Hematoxylin-eosin (H&E) staining of the bronchoscopic specimens showed small round and poorly differentiated cells without non-small cells ( Figure 2A ). Immunohistochemistry (IHC) staining showed that the biopsy was negative for Napsin-A, a marker for LUAD ( Figure 2B ). H&E staining of the bronchoscopic re-biopsy displayed adenoid structure ( Figure 2C ). Napsin-A was positive in the IHC analysis ( Figure 2D ). Histopathological analysis of the bronchoscopic re-biopsy reported LUAD structure ( Figure 2E ).
Treatment timeline of our case. SCLC, small-cell lung cancer; LUAD, lung adenocarcinoma; EP, etoposide plus cisplatin; TRT, thoracic radiation therapy; RT, radiation therapy; AP, cisplatin plus pemetrexed; PR, partial response; CR, complete response, PD, progressive disease; EGFR, epidermal growth factor receptor; 19Del, exon 19 deletion.
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American Joint Commission on Cancer classification criteria) ( Figure 3 ). A targeted comprehensive genomic profiling (CGP), which contains 654 cancer-related genes, was performed on the tumor tissue by next-generation sequencing (NGS). Tumors version 1.1 ( Figure 1B ,  3 ). The patient showed good tolerance to chemoradiotherapy with a transient gastrointestinal response. Based on the diagnosis, he was given the first-generation EGFR-TKI icotinib plus chemotherapy (pemetrexed: 500 mg/m2, days 1; cisplatin: 75 mg/m2, days 1-3; icotinib: 125 mg, t.i.d., p.o.) ( Figure 3 ). After six cycles of chemotherapy plus icotinib followed by icotinib maintenance, the patient achieved a near-complete radiological response ( Figure 1D ,  3 ). Taken together, the diagnosis of left central LUAD was confirmed (T4NXM1, stage IVA) ( Figure 3 ). T790M was detected in blood plasma by the NGS CGP assay. The patient began to take osimertinib (80mg, q.d., p.o.) and achieved a partial response ( Figures 1F ,  3 ).