Pleomorphic Carcinoma With EGFR and Concomitant Mutations Transformed From Lung Adenocarcinoma: A Case Report

Background Transformation to small cell carcinoma, squamous cell carcinoma, and rarely, pleomorphic carcinoma (PC) has been reported to be found in EGFR ‐mutated lung cancer with acquired resistance to EGFR tyrosine kinase inhibitors (TKIs). However, evidence for underlying factors including genomic profiles associated with PC transformation has been lacking. Case We report a case of EGFR ‐mutated lung adenocarcinoma that transformed to PC confirmed by an autopsy after stereotactic radiotherapy and treatment with EGFR‐TKIs. Comprehensive genomic profiling of the autopsy tissue revealed BRAF G466A, KRAS L19F, and NF1 Q2324* mutations in addition to EGFR E746_A750del. Anti‐cancer treatments with radiation and EGFR‐TKIs accompanying these gene alterations might induce the histological transformation and resistance to EGFR‐TKIs. Conclusion This report adds an insight into the involvement of genetic events in histological transformation in EGFR ‐mutated lung cancer.