Ductular reaction is helpful in defining early stromal invasion, small hepatocellular carcinomas, and dysplastic nodules.
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.
Park
Young Nyun
YN
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.
Kojiro
Masamichi
M
Di Tommaso
Luca
L
Dhillon
Amar P
AP
Kondo
Fukuo
F
Nakano
Masayuki
M
Sakamoto
Michiie
M
Theise
Neil D
ND
Roncalli
Massimo
M
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*
D015415:Biomarkers; D053552:Keratin-7