Participants of the Laennec Liver Pathology Society (Wilson Tsui, Paulette Bioulac-Sage, Charles Balabaud, and Alberto Quaglia) contributed cases for the study and participated in discussion of the results during the performance of the investigation and writing of the article
Ductular reaction is helpful in defining early stromal invasion, small hepatocellular carcinomas, and dysplastic nodules
Article first published online: 5 FEB 2007
Copyright © 2007 American Cancer Society
Volume 109, Issue 5, pages 915–923, 1 March 2007
How to Cite
Park, Y. N., Kojiro, M., Di Tommaso, L., Dhillon, A. P., Kondo, F., Nakano, M., Sakamoto, M., Theise, N. D. and Roncalli, M. (2007), Ductular reaction is helpful in defining early stromal invasion, small hepatocellular carcinomas, and dysplastic nodules. Cancer, 109: 915–923. doi: 10.1002/cncr.22460
- Issue published online: 22 FEB 2007
- Article first published online: 5 FEB 2007
- Manuscript Accepted: 13 NOV 2006
- Manuscript Revised: 7 NOV 2006
- Manuscript Received: 12 SEP 2006
- National Research and Development Program for Cancer Control
- Ministry of Health and Welfare
- Republic of Korea. Grant Number: 0620210
- dysplastic nodule;
- hepatocellular carcinoma;
- ductular reaction;
- stromal invasion;
- cytokeratin 7
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.
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+.
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.
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. Cancer 2007 © 2007 American Cancer Society.