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Japanese Journal of Clinical Oncology Advance Access originally published online on January 20, 2009
Japanese Journal of Clinical Oncology 2009 39(4):267-270; doi:10.1093/jjco/hyn155
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© The Author (2009). Published by Oxford University Press. All rights reserved

Genetic Heterogeneity of EGFR Mutation in Pleomorphic Carcinoma of the Lung: Response to Gefitinib and Clinical Outcome

Atsuhito Ushiki1, Tomonobu Koizumi1, Nobumitsu Kobayashi1, Shintarou Kanda1, Masanori Yasuo1, Hiroshi Yamamoto1, Keishi Kubo1, Daiju Aoyagi2 and Jun Nakayama2

1 First Department of Internal Medicine, Shinshu University School of Medicine, Matsumoto
2 Department of Molecular Pathology, Shinshu University School of Medicine, Matsumoto, Japan

For reprints and all correspondence: Tomonobu Koizumi, the First Department of Internal Medicine, Shinshu University School of Medicine, 3-1-1, Asahi, Matsumoto 390-8621, Japan. E-mail: tomonobu{at}shinshu-u.ac.jp

Received September 16, 2008; accepted December 16, 2008

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.

Key Words: EGFR • T790M • pulmonary pleomorphic carcinoma


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