title: Distinction of pulmonary large cell neuroendocrine carcinoma from small cell lung carcinoma: a morphological, immunohistochemical, and molecular analysis.
abstract: The distinction between pulmonary large cell neuroendocrine carcinoma and small cell carcinoma is difficult in some cases. Some propose that these carcinomas should be classified as one high-grade neuroendocrine carcinoma. We examined biological features of small cell carcinoma (n=23), large cell neuroendocrine carcinoma (n=17), and classic large cell carcinoma (n=12). The average ratio of nuclear diameter of the tumor cells to that of lymphocytes for small cell carcinoma was smaller than that for large cell neuroendocrine carcinoma (P<0.0001). The frequencies of the expressions of CD56, mASH1, TTF-1, and p16 were higher and that of NeuroD was lower in small cell carcinoma than in large cell neuroendocrine carcinoma. The frequency of loss of heterozygosity at 3p was higher in high-grade neuroendocrine carcinomas than in classic large cell carcinoma (P=0.0002). Allelic losses at D5S422 (5q33) were more frequent in small cell carcinoma than in large cell neuroendocrine carcinoma (P=0.0091). Mean fractional regional loss indices of the tumors were 0.38, 0.65, and 0.72 for patients with classic large cell carcinoma, large cell neuroendocrine carcinoma, and small cell carcinoma, respectively (P=0.0003). Five-year overall survivals of patients with classic large cell carcinoma, large cell neuroendocrine carcinoma and small cell carcinoma in stage I were 67, 73, 60%, respectively. Patients with NeuroD expression had better survivals, and those with p63 expression had poorer survivals in large cell neuroendocrine carcinoma. Patients with TTF-1 expression had poorer survivals in small cell carcinoma. Our data suggest that large cell neuroendocrine carcinoma and small cell carcinoma are different morphologically, phenotypically, and genetically, although there are some overlapping features. Although further studies are needed to analyze the biological behavior of high-grade neuroendocrine carcinomas including sensitivity to chemotherapy, the pathological distinction of large cell neuroendocrine carcinoma from small cell carcinoma may be necessary to treat the patients with neuroendocrine tumors.
authors.affiliation: Department of Diagnostic Pathology, Graduate School of Medicine, Chiba University, Chiba, Japan. kenzo@faculty.chiba-u.jp
authors.forename: Kenzo
authors.initials: K
authors.lastname: Hiroshima
authors.forename: Akira
authors.initials: A
authors.lastname: Iyoda
authors.forename: Takashi
authors.initials: T
authors.lastname: Shida
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Shibuya
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Iizasa
authors.forename: Hirohisa
authors.initials: H
authors.lastname: Kishi
authors.forename: Tohru
authors.initials: T
authors.lastname: Tanizawa
authors.forename: Takehiko
authors.initials: T
authors.lastname: Fujisawa
authors.forename: Yukio
authors.initials: Y
authors.lastname: Nakatani
mesh_terms: D051792:Basic Helix-Loop-Helix Proteins / Q000032:analysis; D018287:Carcinoma, Large Cell / Q000737:chemistry / Q000235:genetics / Q000473:pathology*; D018278:Carcinoma, Neuroendocrine / Q000737:chemistry / Q000235:genetics / Q000473:pathology*; D018288:Carcinoma, Small Cell / Q000737:chemistry / Q000235:genetics / Q000473:pathology*; D048429:Cell Size; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000032:analysis; D003937:Diagnosis, Differential; D019942:Genes, p16; D006801:Humans; D007150:Immunohistochemistry; D019656:Loss of Heterozygosity; D008175:Lung Neoplasms / Q000737:chemistry / Q000235:genetics / Q000473:pathology*; D018895:Microsatellite Repeats / Q000235:genetics; D016133:Polymerase Chain Reaction; D011379:Prognosis; D012189:Retrospective Studies; D016019:Survival Analysis; D014157:Transcription Factors
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D014157:Transcription Factors; C065500:ASCL1 protein, human; C504003:TTF1 protein, human