Ductular reaction is helpful in defining early stromal invasion, small hepatocellular carcinomas, and dysplastic nodules

Young Nyun Park, Masamichi Kojiro, Luca Di Tommaso, Amar P. Dhillon, Fukuo Kondo, Masayuki Nakano, Michiie Sakamoto, Neil D. Theise, Massimo Roncalli

Research output: Contribution to journalArticlepeer-review

103 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)915-923
Number of pages9
Issue number5
Publication statusPublished - 2007 Mar 1
Externally publishedYes


  • Cytokeratin 7
  • Ductular reaction
  • Dysplastic nodule
  • Hepatocellular carcinoma
  • Stromal invasion

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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