title: A study of moderately differentiated neuroendocrine carcinomas of the larynx and an examination of non-neoplastic larynx tissue for neuroendocrine cells.
abstract: OBJECTIVE
  To determine the most appropriate terminology for neuroendocrine carcinomas (NEC) of the larynx, successive clinicopathologic studies are encouraged. The typical location and immunophenotype of laryngeal NEC raise a question of whether any precursor cells exist.
  
  
  METHODS
  Six patients with laryngeal NEC were analyzed. Another 20 laryngectomy specimens were examined for the presence of non-neoplastic neuroendocrine cells.
  
  
  METHODS
  Tumor morphology and patient outcome were determined, and tumor tissue underwent immunohistochemical examination to identify cytokeratin, neuroendocrine markers (chromogranin, synaptophysin, CD56, calcitonin), S-100 protein, and p53 protein. A neuroendocrine marker study was also performed on non-neoplastic regions of another 20 laryngectomy specimens to identify any neuroendocrine cells.
  
  
  RESULTS
  Laryngeal NEC, all submucosal, exhibited various morphology with or without histologic evidences of neuroendocrine differentiation. The tumors showed frequent (67%) calcitonin expression, calcitonin secretion in one case, and common (50%) p53 over-expression. Three patients died within 3 years. In the non-neoplastic larynx specimens, Kulchitsky cell-like bipolar neuroendocrine cells were identified in the basal and middle layer of the respiratory epithelium of the ventricle and subglottis but none in the submucosal layer of the supraglottic region. The neuroendocrine cells did not express calcitonin.
  
  
  CONCLUSIONS
  Moderately differentiated or large-cell NEC is a more favored term than atypical carcinoid until more refined classifications for upper respiratory tract NEC are agreed on. Despite the confirmed presence of neuroendocrine cells in the respiratory epithelium of the larynx, the origin of laryngeal NEC remains unknown. p53 mutation might be one of the major molecular steps in the pathogenesis of laryngeal NEC.
authors.affiliation: Department of Pathology, Korea Cancer Center Hospital, Seoul, South Korea.
authors.forename: Jin-Haeng
authors.initials: JH
authors.lastname: Chung
authors.forename: Seung-Sook
authors.initials: SS
authors.lastname: Lee
authors.forename: Yoon-Sang
authors.initials: YS
authors.lastname: Shim
authors.forename: Sang-Yoon
authors.initials: SY
authors.lastname: Kim
authors.forename: Soon-Yuhl
authors.initials: SY
authors.lastname: Nam
authors.forename: Dong-Hoon
authors.initials: DH
authors.lastname: Kim
authors.forename: Kyung-Ja
authors.initials: KJ
authors.lastname: Cho
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism; D018278:Carcinoma, Neuroendocrine / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D007822:Laryngeal Neoplasms / Q000473:pathology*; D007830:Larynx / Q000473:pathology*; D008297:Male; D008875:Middle Aged
chemical_list: D014408:Biomarkers, Tumor