INTRODUCTION: Biomarker status is one of the key factors in the management of patients with advanced non-small cell lung cancer. Programmed death-ligand 1 (PD-L1) expression in tumor cells is routinely assessed in all patients, while patients with non-squamous lung cancer also undergo molecular profiling. However, in never-smokers, some molecular abnormalities may be found regardless of tumor histology. CASE PRESENTATION: We present the case of a 72-year-old woman with no history of active tobacco use who was incidentally diagnosed with a right lung mass during the workup for deep vein thrombosis. Imaging revealed a tumor in the apex of the right lung with suspected metastatic lesions. Histopathological examination confirmed squamous cell carcinoma with high PD-L1 expression (TPS 60%). The patient was initially treated with cemiplimab, achieving temporary disease stabilization followed by systemic progression after six months. Given the atypical clinical course and the absence of active smoking history, comprehensive molecular profiling using next-generation sequencing was performed and revealed an activating EGFR exon 19 deletion. Due to the presence of this mutation, treatment with the EGFR tyrosine kinase inhibitor gefitinib was initiated. After three months of therapy, follow-up imaging demonstrated a partial response, with regression of the primary tumor and metastatic lesions. CONCLUSIONS: This case highlights the clinical importance of molecular testing in selected patients with squamous NSCLC, particularly never-smokers or those with atypical clinical presentations. The identification of activating EGFR mutations can significantly influence the treatment strategy, as EGFR tyrosine kinase inhibitors remain the treatment of choice in this molecular subgroup.
Kalman et al. (Fri,) studied this question.