Transformation to Small‐Cell Lung Carcinoma and Then to Sarcomatoid Carcinoma in an EGFR ‐Mutant Lung Adenocarcinoma Patient During Systemic Therapy: A Case Report

ABSTRACT

This case exemplifies stepwise histological transformations of an initially EGFR‐mutant lung adenocarcinoma driven by tumor lineage plasticity under therapeutic pressure. Initial resistance to osimertinib manifested as transformation to combined small‐cell lung carcinoma, associated with concurrent TP53/RB1 co‐inactivation and the acquisition of an epidermal growth factor receptor (EGFR) C797S mutation. Subsequent progression after chemotherapy featured a rare sarcomatoid transformation, with the tumor retaining the original EGFR Exon 19 deletion, supporting clonal evolution. This phenotypic shift, indicative of epithelial‐to‐mesenchymal transition (EMT), may have been associated with PTEN loss and potential activation of the PI3K/AKT/mTOR pathway. The serial emergence of neuroendocrine and sarcomatoid phenotypes underscores the critical need for rebiopsy to guide therapy and highlights the profound adaptability of EGFR‐mutant tumors, which remain a major therapeutic challenge.