Background: Germline epidermal growth factor receptor (EGFR) mutations have been increasingly recognized as genetic risk factors for non-small cell lung cancer (NSCLC), with T790M, V843I, and R776H constituting the mostly reported variants. The germline EGFR p848L mutation (c.2543C>T, p.Pro848Leu), initially identified by de Gunst et al as a rare germline polymorphism suppressor, presents unsolved clinical challenge due to its ambiguous association with familial NSCLC risk and lack of established therapeutic guidelines. Case presentation: We presented a case of a 57-year-old male with a family history of lung cancer. Diagnostic workup revealed squamous cell carcinoma in the right upper lobe. Genetic profiling identified a germline EGFR P848L mutation (c.2543C>T, p.Pro848Leu) through next-generation sequencing. First-line chemotherapy with nab-paclitaxel/carboplatin failed to achieve disease control. According to the RECIST 1.1 guidelines, the therapeutic effect after immunotherapy was determined to be stable disease. Conclusions: This case highlights the clinical challenges and therapeutic implications of germline EGFR P848L mutation in lung squamous cell carcinoma. Immunotherapy demonstrated promising efficacy, suggesting potential value in this rare genetic subset. Further studies are warranted to elucidate the oncogenic role of P848L and optimize treatment strategies for patients with this germline alteration.
Xu et al. (Thu,) studied this question.