title: Transformation to "high grade" neuroendocrine carcinoma as an acquired drug resistance mechanism in EGFR-mutant lung adenocarcinoma.
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.
authors: Royal Marsden Hospital NHS Foundation Trust, London, and Surrey, UK. sanjay.popat@rmh.nhs.uk
authors: S
authors: S
authors: Popat
authors: A
authors: A
authors: Wotherspoon
authors: C M
authors: CM
authors: Nutting
authors: D
authors: D
authors: Gonzalez
authors: A G
authors: AG
authors: Nicholson
authors: M
authors: M
authors: O'Brien
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D018278:Carcinoma, Neuroendocrine / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002471:Cell Transformation, Neoplastic / Q000187:drug effects / Q000235:genetics; D019008:Drug Resistance, Neoplasm / Q000187:drug effects / Q000235:genetics; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000069347:Erlotinib Hydrochloride; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008875:Middle Aged; D009154:Mutation; D060787:Neoplasm Grading; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011799:Quinazolines / Q000627:therapeutic use; D055752:Small Cell Lung Carcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
chemical_list: D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D000069347:Erlotinib Hydrochloride; D066246:ErbB Receptors