Journal Article
. 2007 Dec; 2:51.
doi: 10.1186/1746-1596-2-51.

Analysis of morphological variables and arterialization in the differential diagnosis of hepatic nodules in explanted cirrhotic livers

Cristina Nascimento 1 Adriana Bottino  Cristiane Nogueira  Vera Pannain  
  • PMID: 18154665
  •     19 References
  •     5 citations


Background: Many terminologies have been given to dysplastic hepatocellular nodules, which are preneoplastic lesions. In 1995, the International Working Party meeting established the nomenclature and morphological criteria for hepatocellular nodular lesions. Nevertheless, an unequivocal differential diagnosis is sometimes difficult, particularly among large regenerative nodules, dysplastic nodules and hepatocellular carcinoma. Angiogenesis is observed during hepatocarcinogenesis and the presence of the isolated arteries may help to discriminate these nodules. The relevance of the International Working Party histological variables and presence of the isolated arteries were analyzed with regard to the diagnosis of large regenerative nodules, low and high grade dysplastic nodules and hepatocellular carcinoma, in order to evaluate which have a real contribution in such diagnoses.

Methods: One hundred and seven nodular hepatocellular lesions over 5 mm (or smaller nodules with a different color) from explanted cirrhotic livers were analyzed and classified following the criteria of the International Working Party. Classifications were as follows: large regenerative nodules, low grade dysplastic nodules, high grade dysplastic nodules and hepatocellular carcinoma. The presence of isolated arteries (not related to the portal tracts or fibrosis) was verified for the nodules.

Results: Among the 107 nodular lesions studied, 17 were classified as large regenerative nodules, 38 as low grade dysplastic nodules, 28 as high grade dysplastic nodules and 24 as hepatocellular carcinoma. The most relevant International Working Party variables in the differential diagnosis of the nodules were cellularity, trabeculae thickness, cytoplasmic staining, nuclear atypia, pseudoacinar pattern, portal tracts, nucleocytoplasmic ratio and mitosis. The isolated arteries, identified by hematoxylin and eosin staining, were important discriminating between two groups: low grade lesions (large regenerative nodules/low grade dysplastic nodules) and high grade lesions (high grade dysplastic nodules/hepatocellular carcinoma) (P < 0.001).

Conclusion: The International Working Party criteria allow for the classification of the majority of hepatocellular nodules. However, other features such as cytoplasmatic tintorial affinity and pseudoacinar pattern may contribute to these diagnoses. The finding of isolated arteries in a nodular lesion should be investigated carefully, since the nodule could be a dysplastic lesion or hepatocellular carcinoma.

The vascular profile of regenerative and dysplastic nodules of the cirrhotic liver: implications for diagnosis and classification.
M Roncalli, E Roz, +5 authors, M Borzio.
Hepatology, 1999 Oct 26; 30(5). PMID: 10534338
Increased expression of vascular endothelial growth factor and angiogenesis in the early stage of multistep hepatocarcinogenesis.
Y N Park, Y B Kim, K M Yang, C Park.
Arch Pathol Lab Med, 2000 Jul 11; 124(7). PMID: 10888784
Endothelial cell marker expression in dysplastic lesions of the liver: an immunohistochemical study.
S Frachon, G Gouysse, +7 authors, J Y Scoazec.
J Hepatol, 2001 Jul 14; 34(6). PMID: 11451168
Cytology and cytogenesis of neoplastic (hyperplastic) hepatic nodules.
P Bannasch.
Cancer Res, 1976 Jul 01; 36(7 PT 2). PMID: 1277165
Adenomatous hyperplasia in the vicinity of small hepatocellular carcinoma.
A Eguchi, O Nakashima, +2 authors, M Kojiro.
Hepatology, 1992 May 01; 15(5). PMID: 1314770
Aberrant CpG island hypermethylation along multistep hepatocarcinogenesis.
Sun Lee, Hyeon Joo Lee, +3 authors, Gyeong Hoon Kang.
Am J Pathol, 2003 Sep 26; 163(4). PMID: 14507645    Free PMC article.
Preneoplastic lesions in human hepatocarcinogenesis.
Louis Libbrecht, Valeer Desmet, Tania Roskams.
Liver Int, 2005 Feb 09; 25(1). PMID: 15698394
Hepatocellular carcinoma: incidental finding in cirrhotic explanted livers.
A Caroli-Bottino, C M Nascimento, +6 authors, V L Pannain.
Transplant Proc, 2005 Sep 27; 37(6). PMID: 16182811
Classification tool for the systematic histological assessment of hepatocellular carcinoma, macroregenerative nodules, and dysplastic nodules in cirrhotic liver.
A Quaglia, M A Jutand, +6 authors, A P Dhillon.
World J Gastroenterol, 2006 Jan 19; 11(40). PMID: 16419153    Free PMC article.
Grid technology in tissue-based diagnosis: fundamentals and potential developments.
Jürgen Görtler, Martin Berghoff, Gian Kayser, Klaus Kayser.
Diagn Pathol, 2006 Aug 26; 1. PMID: 16930477    Free PMC article.
Molecular diagnostic approach to liver tissue as an ancillary tool for liver histopathology.
Louis Libbrecht, Tania Roskams.
Semin Liver Dis, 2006 Oct 20; 26(4). PMID: 17051447
Macroregenerative nodule of the liver. A clinicopathologic study of 345 autopsy cases of chronic liver disease.
K Furuya, M Nakamura, +2 authors, H Otsuka.
Cancer, 1988 Jan 01; 61(1). PMID: 2825960
Hepatocellular pseudotumor in the cirrhotic liver. Report of three cases.
N Nagasue, H Akamizu, H Yukaya, I Yuuki.
Cancer, 1984 Dec 01; 54(11). PMID: 6093981
Adenomatous hyperplasia in cirrhotic livers: histological evaluation, cellular density, and proliferative activity of 35 macronodular lesions in the cirrhotic explants of 10 adult French patients.
B Le Bail, G Belleannée, +3 authors, P Bioulac-Sage.
Hum Pathol, 1995 Aug 01; 26(8). PMID: 7635452
Terminology of nodular hepatocellular lesions.
International Working Party.
Hepatology, 1995 Sep 01; 22(3). PMID: 7657307
Highly Cited. Review.
Proposal for standardized criteria for the diagnosis of benign, borderline, and malignant hepatocellular lesions arising in chronic advanced liver disease.
L D Ferrell, J M Crawford, +2 authors, Y Nakanuma.
Am J Surg Pathol, 1993 Nov 01; 17(11). PMID: 8214256
Macroregenerative (dysplastic) nodules and hepatocarcinogenesis: theoretical and clinical considerations.
N D Theise.
Semin Liver Dis, 1995 Nov 01; 15(4). PMID: 8578320
Arterial elements and perisinusoidal cells in borderline hepatocellular nodules and small hepatocellular carcinomas.
T Terada, Y Nakanuma.
Histopathology, 1995 Oct 01; 27(4). PMID: 8847063
Neoangiogenesis and sinusoidal "capillarization" in dysplastic nodules of the liver.
Y N Park, C P Yang, +3 authors, N D Theise.
Am J Surg Pathol, 1998 Jun 18; 22(6). PMID: 9630172
Small interfering RNAs induce target-independent inhibition of tumor growth and vasculature remodeling in a mouse model of hepatocellular carcinoma.
Mathieu Bergé, Philippe Bonnin, +7 authors, Tatyana Merkulova-Rainon.
Am J Pathol, 2010 Oct 26; 177(6). PMID: 20971743    Free PMC article.
The intrahepatic expression and distribution of BTLA and its ligand HVEM in patients with HBV-related acute-on-chronic liver failure.
Huan Xu, Dayan Cao, +3 authors, Yongwen Chen.
Diagn Pathol, 2012 Oct 17; 7. PMID: 23067542    Free PMC article.
Latest developments in precancerous lesions of hepatocellular carcinoma.
Zhao-Shan Niu, Xiao-Jun Niu, Wen-Hong Wang, Jing Zhao.
World J Gastroenterol, 2016 Mar 30; 22(12). PMID: 27022212    Free PMC article.
Multiparametric imaging for detection and characterization of hepatocellular carcinoma using gadoxetic acid-enhanced MRI and perfusion-CT: which parameters work best?
Mustafa Kurucay, Christopher Kloth, +4 authors, Wolfgang M Thaiss.
Cancer Imaging, 2017 Jul 01; 17(1). PMID: 28659180    Free PMC article.
Abnormal expression of HNRNPA3 in multistep hepatocarcinogenesis.
Xinlu Ren, Yi Dong, +2 authors, Peng Gao.
Oncol Lett, 2020 Dec 08; 21(1). PMID: 33281957    Free PMC article.