Resistance to epithelial growth factor receptor tyrosine kinase inhibitors in a patient with transformation from lung adenocarcinoma to small cell lung cancer: A case report.

First-generation epithelial growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have markedly improved the treatment of non-small cell lung cancer (non-SCLC) with EGFR-sensitive mutations. However, acquired resistance to these drugs was inevitable. The transformation of lung adenocarcinoma to SCLC following treatment with EGFR-TKIs is a rare phenomenon that contributes to resistance to EGFR-TKIs. The present case concerns a 74-year-old man previously diagnosed with and treated for pneumonia; however, this was later pathologically confirmed as lung adenocarcinoma by transbronchial lung biopsy. Deletion of exon 19 of EGFR was identified by next-generation sequencing technology. The patient improved markedly when treated with gefitinib, but relapsed after 1 year, with markedly increased serum levels of neuron-specific enolase (NSE). Transformation to SCLC was detected by endobronchial ultrasound transbronchial needle aspiration (EBUS-TBNA) re-biopsy, which was negative for the deletion of exon 19 of EGFR. The patient was positive for vimentin expression and refractory to etoposide and cisplatin chemotherapy, and succumbed to the disease 18 months after diagnosis. Transformation of the disease from adenocarcinoma to SCLC may have been due to cancer heterogeneity. Re-biopsy is therefore important in EGFR-TKI-resistant patients for genetic and histological re-evaluation. NSE serum levels may also be useful for detecting early SCLC transformation.