title: Ductular reaction is helpful in defining early stromal invasion, small hepatocellular carcinomas, and dysplastic nodules.
abstract: BACKGROUND
  Stromal invasion is 1 of the main features used to distinguish high-grade dysplastic nodules (DNs) from well-differentiated hepatocellular carcinomas (HCCs). The authors hypothesized that ductular reaction (DR) takes place around noninvasive hepatocellular nodules but not within the stroma contiguous to invasive HCC.
  
  
  METHODS
  DR/cytokeratin 7 (CK7)-positive patterns were evaluated in 105 resected small hepatic nodules according to the level of invasion. The nodules were classified histologically prior to immunostaining as noninvasive (large regenerative nodules, low-grade DNs, and high-grade DNs), minimally invasive (early HCCs with a vaguely nodular type), and overtly invasive (typical HCCs with a distinctly nodular type) in a review by expert pathologists, the current gold standard. Intranodular DR (inner DR) and DR around the nodule periphery (outer DR) were assessed separately on a semiquantitative scale from 0 to 4+.
  
  
  RESULTS
  DR was 3 or 4+ in the majority of noninvasive nodules (inner DR, 81%; outer DR, 91%), whereas DR was 0 or 1+ in overtly invasive HCCs (inner DR, 96%; outer DR, 81%). Minimally invasive HCCs showed an intermediate DR pattern (2 or 3+ inner DR, 75%; 2+ outer DR, 67%). DR characteristically was absent at the stromal-invasive, leading edge of tumor cells in both minimally invasive HCCs (focal loss of DR/CK7) and overtly invasive HCCs (diffuse loss of DR/CK7). The DR patterns in 41 needle-biopsy samples were similar to the patterns observed in resected nodules.
  
  
  CONCLUSIONS
  DR/CK7 immunostaining may help to identify small foci of invasion and to distinguish noninvasive, high-grade DNs from both minimally invasive and overtly invasive HCCs.
authors.affiliation: Department of Pathology and Institute of Gastroenterology, Center for Chronic Metabolic Disease, Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Young Nyun
authors.initials: YN
authors.lastname: Park
authors.forename: Masamichi
authors.initials: M
authors.lastname: Kojiro
authors.forename: Luca
authors.initials: L
authors.lastname: Di Tommaso
authors.forename: Amar P
authors.initials: AP
authors.lastname: Dhillon
authors.forename: Fukuo
authors.initials: F
authors.lastname: Kondo
authors.forename: Masayuki
authors.initials: M
authors.lastname: Nakano
authors.forename: Michiie
authors.initials: M
authors.lastname: Sakamoto
authors.forename: Neil D
authors.initials: ND
authors.lastname: Theise
authors.forename: Massimo
authors.initials: M
authors.lastname: Roncalli
mesh_terms: D015415:Biomarkers / Q000032:analysis; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D053552:Keratin-7 / Q000378:metabolism; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology*; D009362:Neoplasm Metastasis / Q000473:pathology*; D011230:Precancerous Conditions / Q000378:metabolism / Q000473:pathology*
chemical_list: D015415:Biomarkers; D053552:Keratin-7