Transformation to “high grade” neuroendocrine carcinoma as an acquired drug resistance mechanism in EGFR-mutant lung adenocarcinoma

• Published in: Lung cancer (Amsterdam, Netherlands) Netherlands), 2013-04, Vol.80 (1), p.1-4
• Main Authors: Popat, S, Wotherspoon, A, Nutting, C.M, Gonzalez, D, Nicholson, A.G, O’Brien, M
• Format: Article
• Language: English
• Subjects: Adenocarcinoma; Adenocarcinoma - genetics; Adenocarcinoma - metabolism; Adenocarcinoma - pathology; Biological and medical sciences; Carcinoma, Neuroendocrine - genetics; Carcinoma, Neuroendocrine - metabolism; Carcinoma, Neuroendocrine - pathology; Cell Transformation, Neoplastic - drug effects; Cell Transformation, Neoplastic - genetics; Drug Resistance, Neoplasm - drug effects; Drug Resistance, Neoplasm - genetics; EGFR; Erlotinib Hydrochloride; Female; Hematology, Oncology and Palliative Medicine; Humans; Immunohistochemistry; Lung Neoplasms - genetics; Lung Neoplasms - metabolism; Lung Neoplasms - pathology; Medical sciences; Middle Aged; Mutation; Neoplasm Grading; Neuroendocrine; NSCLC; Pneumology; Protein Kinase Inhibitors - therapeutic use; Pulmonary/Respiratory; Quinazolines - therapeutic use; Receptor, Epidermal Growth Factor - antagonists & inhibitors; Receptor, Epidermal Growth Factor - genetics; Receptor, Epidermal Growth Factor - metabolism; SCLC; Small Cell Lung Carcinoma - genetics; Small Cell Lung Carcinoma - metabolism; Small Cell Lung Carcinoma - pathology; Tumors; Tumors of the respiratory system and mediastinum
• ISSN: 0169-5002; 1872-8332
• DOI: 10.1016/j.lungcan.2012.12.019

Abstract Several different acquired resistance mechanisms of EGFR mutant lung adenocarcinoma to EGFR-tyrosine kinase inhibitor (TKI) therapy have been described, most recently transformation to small cell lung carcinoma (SCLC). We describe the case of a 46-year-old female with relapsed EGFR exon 19 deletion lung adenocarcinoma treated with erlotinib, and on resistance, cisplatin-pemetrexed. Liver rebiopsy identified an afatinib-resistant combined SCLC and non-small cell carcinoma with neuroendocrine morphology, retaining the EGFR exon 19 deletion. This case highlights acquired EGFR-TKI resistance through transformation to the high-grade neuroendocrine carcinoma spectrum and that that such transformation may not be evident at time of progression on TKI therapy.