title: Genetic heterogeneity of EGFR mutation in pleomorphic carcinoma of the lung: response to gefitinib and clinical outcome.
abstract: Somatic epidermal growth factor receptor (EGFR) mutations in exons 19 and 21 have been found in non-small cell lung cancer (NSCLC) and are associated with the therapeutic response to gefitinib in patients with advanced NSCLC. We report a case of pleomorphic carcinoma of the lung with different EGFR mutations. Prior to gefitinib treatment, an exon 19 deletion of EGFR mutation was positive in the specimens obtained from pleural effusion and left cervical lymph node, histologically proven to be adenocarcinoma. However, the response to gefitinib was poor and the patient died of progressive disease 4 months after the initiation of gefitinib therapy. Postmortem examination revealed the major histological component to be of the sarcomatoid or pleomorphic type with scant mixed adenocarcinoma, resulting in a histological diagnosis of pleomorphic carcinoma of the lung. Although the adenocarcinomatous tissue was still positive for exon 19 deletion of EGFR mutation alone, sarcomatous components had both the exons 19 deletion and 20 T790M mutation concomitantly, thought to be a gefitinib resistance mutation. Pulmonary pleomorphic carcinoma is a rare NSCLC composed of biphasic and heterogeneous malignant cell populations. The present case suggested that expression of different EGFR mutations is related to the biphasic histological appearance in pulmonary pleomorphic carcinoma.
authors.affiliation: First Department of Internal Medicine, Shinshu University School of Medicine, Matsumoto, Japan.
authors.forename: Atsuhito
authors.initials: A
authors.lastname: Ushiki
authors.forename: Tomonobu
authors.initials: T
authors.lastname: Koizumi
authors.forename: Nobumitsu
authors.initials: N
authors.lastname: Kobayashi
authors.forename: Shintarou
authors.initials: S
authors.lastname: Kanda
authors.forename: Masanori
authors.initials: M
authors.lastname: Yasuo
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yamamoto
authors.forename: Keishi
authors.initials: K
authors.lastname: Kubo
authors.forename: Daiju
authors.initials: D
authors.lastname: Aoyagi
authors.forename: Jun
authors.initials: J
authors.lastname: Nakayama
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics / Q000556:secondary; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics* / Q000556:secondary; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D017809:Fatal Outcome; D000077156:Gefitinib; D018773:Genes, erbB-1 / Q000235:genetics*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009378:Neoplasms, Multiple Primary / Q000188:drug therapy* / Q000235:genetics*; D011799:Quinazolines / Q000627:therapeutic use; D017384:Sequence Deletion; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D011799:Quinazolines; D066246:ErbB Receptors; D000077156:Gefitinib