Abstract

Objective: To describe histologic transformation after targeted therapy in non-small cell lung cancer (NSCLC). Methods: We reported a case series at the National Lung Hospital and reviewed the literature regarding clinical features, histopathology, immunohistochemistry, molecular findings, and treatment. Results: Three female never-smokers with advanced lung adenocarcinoma harboring ALK or EGFR alterations were included. After 12 - 14 months of tyrosine kinase inhibitor treatment, re-biopsy revealed transformation into high-grade neuroendocrine carcinoma (large-cell/small-cell type). Immunohistochemistry supported the diagnosis, showing high Ki67 expression, while the original driver mutations were retained. Subsequent treatment with regimens for transformed carcinoma achieved clinical response. Conclusion: Histologic transformation is an important mechanism of acquired resistance in NSCLC after targeted therapy. Re-biopsy plays an essential role in diagnosis and treatment guidance.