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Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) mutation has a prevalence of approximately 2% in lung adenocarcinoma. However, cases presenting a PIK3CA mutation alone have rarely been reported, and the clinical significance of a single PIK3CA mutation has not been well discussed. We present 2 similar lung adenocarcinoma cases with a single PIK3CA alteration initially but were found to have a concurrent epidermal growth factor receptor (EGFR) mutation by another genotyping afterward. Both cases experienced an excellent partial response after combination therapy of EGFR tyrosine kinase inhibitor (EGFR-TKI) and angiogenesis inhibitor, which implies that the initial absence of EGFR mutation was a false negative. A single-center retrospective study among 2,214 cases of lung adenocarcinoma regarding their genotyping was conducted. We found that the prevalence of PIK3CA mutation in lung adenocarcinoma was 1.7%, 86.5% of which had other co-existing mutations, with EGFR mutation being the most common. PIK3CA mutation tends to be concurrent with other mutations in lung adenocarcinoma. Physicians should suspect a potential false-negative driver mutation and promptly repeat genotyping when a single PIK3CA mutation is reported in the genotyping of lung adenocarcinoma. Furthermore, physicians should consider agents targeting the driver mutation rather than agents targeting the phosphatidylinositol 3-kinase(PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway for treatment.

Concealed driver in lung adenocarcinoma with single PIK3CA mutation: a case report and single-center genotyping review