Histologic evolution from adenocarcinoma to squamous cell carcinoma after gefitinib treatment

We report two cases of lung cancer with histologic transformation from adenocarcinoma to squamous cell carcinoma after gefitinib treatment. Both cases involved advanced lung cancers, initially confirmed as adenocarcinomas with sensitive epidermal growth factor gene mutations. After gefitinib treatment, the second pathologic examination in each case revealed squamous cell carcinoma retaining identical mutations without newly acquired resistance mutations. The underlying mechanism may have been pluripotent tumor cells with divergent differentiation or mixed lung cancer including both adenocarcinomatous and squamous cell carcinomatous components. This report widens the spectrum of histologic evolution as a mechanism underlying the acquisition of drug resistance.