title: Diagnostic findings of bronchial brush cytology for pulmonary large cell neuroendocrine carcinomas: comparison with poorly differentiated adenocarcinomas, squamous cell carcinomas, and small cell carcinomas.
abstract: BACKGROUND
  Large cell neuroendocrine carcinoma (LCNEC) of the lung has been proposed as a new disease entity. To establish diagnostic features, bronchial brush cytologic findings were evaluated.
  
  
  METHODS
  Bronchial brush cytology material of 20 LCNECs was evaluated by light microscopy and stained immunocytochemically with protein gene product 9.5 (PGP9.5), neuron-specific enolase, and neural cell adhesion molecule antibodies. The findings were compared with those for 19 poorly differentiated adenocarcinomas (ACs), 18 poorly differentiated squamous cell carcinomas (SCCs), and 20 small cell lung carcinomas (SCLCs).
  
  
  RESULTS
  Frequently observed characteristic cytologic findings of LCNECs were necrotic background (90.0%), large tumor cell size (90.0%), naked nuclei (90.0%), and nuclear streaking (90.0%). Nuclei in all LCNECs showed a fine granular chromatin pattern and possessed one or a few nucleoli. Indian-filing and rosette arrangements were observed in less than one-half of the LCNECs. In poorly differentiated ACs and SCCs, these features were less frequent, whereas thick nuclear membranes were observed more often. In SCLCs, tumor cell adhesions and Indian-filing or nuclear molding were observed more frequently than in LCNECs, whereas a necrotic background, tumor cell clusters, large tumor cells, and nucleoli were less prominent. The majority of LCNECs (80.0%) had a positive immunocytochemical reaction for PGP9.5, in contrast to the low positive reactions for ACs (42.1%) and SCCs (30.8%).
  
  
  CONCLUSIONS
  Large cell neuroendocrine carcinomas can be diagnosed preoperatively by bronchial brush cytology using reliable parameters, including tumor cell size, naked nuclei, thin nuclear membranes, nuclear streaking, high PGP9.5 positivity, and a necrotic background.
authors.affiliation: Department of Pathology, Kitasato University Hospital, Sagamihara, Kanagawa, Japan. hi-kaki@kitasato-u.ac.jp
authors.forename: Hirokuni
authors.initials: H
authors.lastname: Kakinuma
authors.forename: Tetuo
authors.initials: T
authors.lastname: Mikami
authors.forename: Keiichi
authors.initials: K
authors.lastname: Iwabuchi
authors.forename: Masaru
authors.initials: M
authors.lastname: Yokoyama
authors.forename: Manabu
authors.initials: M
authors.lastname: Hattori
authors.forename: Eiji
authors.initials: E
authors.lastname: Ohno
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kuramoto
authors.forename: Shi-Xu
authors.initials: SX
authors.lastname: Jiang
authors.forename: Isao
authors.initials: I
authors.lastname: Okayasu
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology*; D000368:Aged; D018278:Carcinoma, Neuroendocrine / Q000473:pathology*; D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology*; D018288:Carcinoma, Small Cell / Q000473:pathology*; D002294:Carcinoma, Squamous Cell / Q000473:pathology*; D003584:Cytological Techniques; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies