title: Multistep and multicentric development of hepatocellular carcinoma: histological analysis of 980 resected nodules.
abstract: OBJECTIVE
  Histological observations support the concept of multistep and multicentric development of hepatocellular carcinoma (HCC) in cases of chronic liver disease. However, the relationship between the incidence of such a modality of development of HCC and the type of background liver disease has not been fully investigated.
  
  
  METHODS
  A total of 980 HCC nodules resected from 664 patients were analyzed. Multistep HCC was defined as well differentiated HCC containing the portal tracts (early HCC), or the presence of early HCC-like areas in the periphery of the nodule. In cases with multiple nodules, if the smaller nodule showed the features of multistep HCC, or if each nodule showed a distinct histology, the case was defined to have multicentric HCC.
  
  
  RESULTS
  Of the 980 nodules, 369 (37.7%) met the criteria of multistep HCC. Of the 664 patients, 177 (26.7%) had multiple nodules that met the criteria of multicentric HCC. Both the incidences of multistep and multicentric HCC were significantly higher in HCV-Ab-positive cases than in HBs-Ag-positive cases (46.0 vs. 19.1%, P<0.001 and 34.1 vs. 16.5%, P=0.005, respectively).
  
  
  CONCLUSIONS
  Multistep and multicentric HCC develops most frequently in patients with HCV infection.
authors.affiliation: Pathology Division, National Cancer Center Research Institute, Tokyo, Japan.
authors.forename: Takuichi
authors.initials: T
authors.lastname: Oikawa
authors.forename: Hidenori
authors.initials: H
authors.lastname: Ojima
authors.forename: Susumu
authors.initials: S
authors.lastname: Yamasaki
authors.forename: Tadatoshi
authors.initials: T
authors.lastname: Takayama
authors.forename: Setsuo
authors.initials: S
authors.lastname: Hirohashi
authors.forename: Michiie
authors.initials: M
authors.lastname: Sakamoto
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000453:epidemiology* / Q000473:pathology*; D006801:Humans; D015994:Incidence; D008107:Liver Diseases / Q000150:complications / Q000473:pathology; D008113:Liver Neoplasms / Q000453:epidemiology* / Q000473:pathology*; D014041:Tokyo / Q000453:epidemiology