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A 75-year-old, nonsmoking white woman was diagnosed with stage IV lung adenocarcinoma. Based on an activating EGFR mutation, she was treated with EGFR tyrosine kinase inhibitors.

After 20 months of treatment, dyspnea worsened, with evidence of increased right pleural effusion. A talc pleurodesis was performed and a pleural biopsy revealed the presence of both adenocarcinoma and small-cell lung cancer (SCLC).

Histologic transformation to SCLC is a known mechanism of TKI resistance in EGFR-mutated lung adenocarcinoma.