title: Large-cell neuroendocrine carcinoma of lung with epidermal growth factor receptor (EGFR) gene mutation and co-expression of adenocarcinoma markers: a case report and review of the literature.
abstract: OBJECTIVE
  A high rate of response to treatment with epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) has been observed in certain patients (women, of East Asian ethnicity, with non-smoking history and adenocarcinoma histology) with mutations in exons 18 to 21 of the tyrosine kinase domain of EGFR. Some cases of high-grade neuroendocrine carcinoma of the lung harboring mutations have been sporadically reported.
  
  
  METHODS
  We describe the case of a 78-year-old woman with large-cell neuroendocrine carcinoma of the lung, with mutation in exon 21 L858R and co-expression of adenocarcinoma markers.
  
  
  RESULTS
  A mass (3.0 cm in diameter) was identified in the inferior lobe of the left lung, accompanied by metastases into ipsilateral mediastinal lymph nodes and elevations of serum pro-gastrin-releasing peptide and carcinoembryonic antigen. Initial transbronchial brushing cytology suggested high-grade neuroendocrine carcinoma favoring small-cell carcinoma in poorly smeared and degenerated preparations, and revealed exon 21 L858R mutation. Re-enlargement of the cancer and bone metastases was observed after chemotherapy, and further testing suggested large-cell neuroendocrine carcinoma with immunoreactivity to markers of primary lung adenocarcinoma and L858R mutation. High-grade neuroendocrine carcinoma with mutations in the tyrosine kinase domain of EGFR may be associated with adenocarcinoma, as reviewed from the literature and may also apply to our case.
  
  
  CONCLUSIONS
  EGFR-TKI could provide better quality of life and survival in patients with advanced or relapsed high-grade neuroendocrine carcinoma with EGFR gene mutations. Further studies in this respect are warranted.
authors.affiliation: Department of Diagnostic Pathology, Kobe University Hospital, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe-shi, Hyogo 650-0017, Japan. sakaiyasuhiro@gaia.eonet.ne.jp.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Sakai
authors.forename: Takashi
authors.initials: T
authors.lastname: Yamasaki
authors.forename: Yoshito
authors.initials: Y
authors.lastname: Kusakabe
authors.forename: Daisuke
authors.initials: D
authors.lastname: Kasai
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Kotani
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Nishimura
authors.forename: Tomoo
authors.initials: T
authors.lastname: Itoh