Transformation From Adenocarcinoma to Pleomorphic Carcinoma as an Acquired Resistance to Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors

Pulmonary pleomorphic carcinoma is a very rare histological type of primary lung cancer, and usually provides aggressive clinical courses. A 65-year-old Japanese woman was diagnosed by transbronchial biopsy of the primary tumor as c-stage IV (cT4N3M1b) of adenocarcinoma harboring L858R point mutation in the exon 21 of epidermal growth factor receptor (EGFR). She received EGFR tyrosine kinase inhibitors (TKIs) (gefitinib and erlotinib) and subsequently cytotoxic chemotherapies. Gefitinib achieved partial response, but was switched to erlotinib due to elevated serum aspartate transaminase. After resistance to EGFR-TKIs, the second transbronchial re-biopsy revealed pulmonary pleomorphic carcinoma. Both carcinomatous and sarcomatous components retained the L858R mutation, but did not acquire T790M mutation. This case suggested that the histological transformation to pulmonary pleomorphic carcinoma may be one of mechanisms of drug resistance to EGFR-TKIs.