title: Large cell neuroendocrine carcinoma of the lung: a clinicopathologic study of eighty-seven cases.
abstract: OBJECTIVE
  Large cell neuroendocrine carcinoma of the lung is a newly recognized clinicopathologic entity. The clinical characteristics and optimal treatment of patients with large cell carcinomas are not yet established. The aim of this study was to define the clinicopathologic characteristics of large cell neuroendocrine carcinoma.
  
  
  METHODS
  The histologic characteristics of the patients receiving an initial diagnosis of poorly differentiated non-small cell lung carcinoma (n = 484), small cell carcinoma (n = 55), carcinoid (n = 31), and large cell neuroendocrine carcinoma (n = 12) were retrospectively reviewed according to World Health Organization criteria. Immunohistochemistry was performed to confirm the neuroendocrine phenotype. The outcomes and other clinical characteristics of those patients with large cell neuroendocrine carcinoma were retrospectively analyzed and compared with those of patients with poorly differentiated carcinoma of other histologic types.
  
  
  RESULTS
  A total of 87 patients were given a diagnosis of large cell neuroendocrine carcinoma after the histologic review. These patients comprised 3.1% of all patients undergoing resection for primary lung cancer during the same period. The overall 5-year survival was 57%. The 5-year survivals of patients with stage I, II, III, and IV disease were 67%, 75%, 45%, and 0%, respectively. There was no statistically significant difference between the overall survival of patients with large cell neuroendocrine carcinoma and those with other non-small cell lung cancers. There was a significant difference between the survival of patients with stage I large cell neuroendocrine carcinoma and that of patients with the same stage of other non-small cell lung carcinomas. The site of the first documented recurrence was locoregional in 12 patients (34%), distant metastases in 20 patients (57%), and both simultaneously in 3 patients. Locoregional lymph node recurrences were observed frequently. More than 80% of recurrences were found within 1 year after the operation.
  
  
  CONCLUSIONS
  In terms of prognosis, large cell neuroendocrine carcinoma is distinctly different from other non-small cell lung cancers. The prognosis of large cell neuroendocrine carcinoma was poor, even for early stage disease; the prognosis of the stage I disease of large cell neuroendocrine carcinoma was poorer than that of the same stage of other non-small cell lung cancers. Because of its aggressive clinical behavior and poor prognosis, large cell neuroendocrine carcinoma should be recognized as one of the poorest prognostic subgroups among primary lung cancers, and therefore novel therapeutic approaches should be established.
authors.affiliation: Clinical Laboratory Division and Thoracic Surgery Division, National Cancer Center Hospital, 1-1 Tsukiji 5 chome, Chuo-ku, Tokyo 104-0045, Japan.
authors.forename: Hidefumi
authors.initials: H
authors.lastname: Takei
authors.forename: Hisao
authors.initials: H
authors.lastname: Asamura
authors.forename: Arafumi
authors.initials: A
authors.lastname: Maeshima
authors.forename: Kenji
authors.initials: K
authors.lastname: Suzuki
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Kondo
authors.forename: Toshiro
authors.initials: T
authors.lastname: Niki
authors.forename: Tesshi
authors.initials: T
authors.lastname: Yamada
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Tsuchiya
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Matsuno
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018287:Carcinoma, Large Cell / Q000401:mortality / Q000473:pathology*; D018278:Carcinoma, Neuroendocrine / Q000401:mortality / Q000473:pathology*; D002289:Carcinoma, Non-Small-Cell Lung / Q000401:mortality / Q000473:pathology*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000401:mortality / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012189:Retrospective Studies; D016019:Survival Analysis