title: Tumorlets, multicentric carcinoids, lymph-nodal metastases, and long-term behavior in bronchial carcinoids.
abstract: BACKGROUND
  The clinical significance of lymph-node metastases, multicentric forms, and tumorlets in bronchial carcinoids is still a matter of debate. Aim of this study was to analyze their prevalence and clinical significance in a series of 123 bronchial carcinoids.
  
  
  METHODS
  Nodal dissection and serial sections of resected lung parenchima for research of multicentric forms and tumorlets were performed in most patients. Survival curve was produced using the Kaplan-Meyer method and multivariate analysis by the Cox proportional hazard model.
  
  
  RESULTS
  Lymph-node involvement was present in 14% of typical (14 of 100) and 13.04% of atypical carcinoids (3 of 23). Multicentric forms (syncronous carcinoids or tumorlets) were found in 11.3% of the total with a negative impact on survival (p = 0.021). Multiple tumorlets were found in 7.3% of all cases at the standard pathologic examination, but whenever accurate palpation and serial sections of the surgical specimen were performed, the percentage reached 24% of the cases. Overall survival was 98.2%, 95.8%, and 83.9% for typical and 71.6%, 57.3%, and 24% for atypical carcinoid respectively at 5, 10, and 15 years. Time from surgery was significantly directly correlated with recurrences (p < 0.0001) and disease related death (p = 0.0002).
  
  
  CONCLUSIONS
  A high prevalence of tumorlets, multiple carcinoids, and lymph-nodal involvement was found in our series. On the basis of these observations bronchial carcinoids always require major surgical procedures with systematic nodal dissection, and a careful search for multifocal lesions should always be performed. Follow-up should always be accurate and protracted, due to the frequency of very long-term relapses (often more than 10 years after surgery).
authors.affiliation: Department of Internal Medicine and Endocrine Sciences, University of Perugia, Perugia, Italy. pferolla@tin.it
authors.forename: Piero
authors.initials: P
authors.lastname: Ferolla
authors.forename: Niccolò
authors.initials: N
authors.lastname: Daddi
authors.forename: Moira
authors.initials: M
authors.lastname: Urbani
authors.forename: Antonia
authors.initials: A
authors.lastname: Semeraro
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Ribacchi
authors.forename: Paolo
authors.initials: P
authors.lastname: Giovenali
authors.forename: Stefano
authors.initials: S
authors.lastname: Ascani
authors.forename: Verena
authors.initials: V
authors.lastname: De Angelis
authors.forename: Lucio
authors.initials: L
authors.lastname: Crinò
authors.forename: Francesco
authors.initials: F
authors.lastname: Puma
authors.forename: Giuliano
authors.initials: G
authors.lastname: Daddi
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D001707:Biopsy, Needle; D001984:Bronchial Neoplasms / Q000401:mortality* / Q000473:pathology* / Q000601:surgery; D002276:Carcinoid Tumor / Q000401:mortality* / Q000556:secondary* / Q000601:surgery; D016009:Chi-Square Distribution; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008198:Lymph Nodes / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D009360:Neoplastic Cells, Circulating / Q000473:pathology*; D011336:Probability; D011379:Prognosis; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D018570:Risk Assessment; D012737:Sex Factors; D018709:Statistics, Nonparametric; D016019:Survival Analysis