Authentic neuroendocrine transdifferentiation from lung adenocarcinoma to small-cell lung cancer: a case report

Reports of small-cell lung cancer (SCLC) transdifferentiation in epidermal growth factor receptor tyrosine (EGFR)‑mutant lung adenocarcinoma (LUAD) often reflect pre‑existing combined SCLC or are limited by sampling bias, obscuring true treatment‑induced lineage transformation. We report a female patient with EGFR‑mutant LUAD who, during EGFR tyrosine kinase inhibitor therapy, developed SCLC transformation confirmed histopathologically. The patient showed limited response to first‑line SCLC chemoimmunotherapy, and a subsequent biopsy revealed mixed SCLC/LUAD histology with neuroendocrine differentiation and shared genetic alterations between components. This case provides strong clinicopathological and molecular evidence supporting neuroendocrine transdifferentiation from LUAD to SCLC, culminating in a mixed phenotypic state. Further research is needed to define optimal therapeutic strategies for this resistant phenotype.