Background: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are recommended for patients with non-small cell lung cancer with EGFR mutations. However, acquired resistance to EGFR-TKIs seems inevitable and the mechanism of drug resistance has not been fully defined. There is no effective treatment for patients with advanced lung adenocarcinoma who are resistant to TKIs owing to pathologic type conversion. Case presentation: We report a patient who was initially diagnosed with lung adenocarcinoma. At first, she was sensitive to the first-generation TKI icotinib. After 17 months of treatment, the patient acquired resistance to icotinib. Moreover, after tumor resection, immunohistochemical analysis showed pathologic change from adenocarcinoma to adenosquamous carcinoma, and next-generation sequencing technology discovered EGFR exon19 p.745-750 del, exon20 p.T790M, and KMT2C exon 18 p.R973G mutations. After video-assisted tumor resection, the patient is receiving osimertinib (AZD 9291). Current overall survival is 60 months. Conclusions: Surgical intervention may prolong survival time in patients with acquired TKI resistance, especially when there is no evidence of metastasis.

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