Transformation to Small-Cell Lung Carcinoma and Then to Sarcomatoid Carcinoma in an EGFR-Mutant Lung Adenocarcinoma Patient During Systemic Therapy: A Case Report.
Bingyu Huang, Tao Lu, Ruping Hong et al.
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Case in brief
A patient with EGFR-mutant lung adenocarcinoma developed resistance to osimertinib with transformation to combined small-cell lung carcinoma. This change was associated with TP53/RB1 co-inactivation and an acquired EGFR C797S mutation. After chemotherapy, the tumor progressed with sarcomatoid transformation while retaining the original EGFR exon 19 deletion, supporting clonal evolution. The authors suggest that the sarcomatoid phenotype may reflect epithelial-to-mesenchymal transition and may have been associated with PTEN loss and potential PI3K/AKT/mTOR pathway activation.
What made this case unusual
The tumor underwent sequential transformation to both small-cell and sarcomatoid phenotypes during systemic therapy, while retaining the original EGFR exon 19 deletion at the sarcomatoid stage.
Diagnostic / clinical pearl
When an EGFR-mutant lung cancer progresses on therapy, rebiopsy can identify histological transformation and provide information relevant to subsequent treatment decisions.