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Borzio et al. Hepatoma Res 2019;5:15 Hepatoma Research
DOI: 10.20517/2394-5079.2019.11

Review Open Access

Liver carcinogenesis: diagnostic and clinical
aspects of preneoplastic nodules

Mauro Borzio , Fabio Paladino , Giampiero Francica 3
1
2
1 U.O. Gastroenterologia ed Endoscopia Digestiva, ASST Melegnano-Martesana, Melegnano, Vizzolo Predabissi 20070, MI, Italy.
2 U.O. Chirurgia, ASST Melegnano-Martesana, Melegnano, Vizzolo Predabissi 20070, MI, Italy.
3 U.O. Ecografia ed Econterventistica, Pineta Grande Hospital, Castel Volturno 81030, CE, Italy.

Correspondence to: Dr. Mauro Borzio, Ospedale Uboldo, Cernusco sul Naviglio 20063, MI, Italy. E-mail: mauro.borzio@gmail.com

How to cite this article: Borzio M, Paladino F, Francica G. Liver carcinogenesis: diagnostic and clinical aspects of preneoplastic nodules.
Hepatoma Res 2019;5:15. http://dx.doi.org/10.20517/2394-5079.2019.11

Received: 12 Feb 2019 First Decision: 18 Mar 2019 Revised: 12 Apr 2019 Accepted: 18 Apr 2019 Published: 14 May 2019

Science Editor: Jin-Lin Hou Copy Editor: Cai-Hong Wang Production Editor: Huan-Liang Wu

Abstract
In multistep hepatocarcinogenesis, sizable lesions can precede the development of hepatocellular carcinoma
(HCC). These lesions are currently classified as low grade (LG)- and high grade (HG)-dysplastic nodules.
Following international guidelines recommending the surveillance of cirrhotic patients, a growing number of 1-2 cm
hepatocellular nodules are recognized including early hepatocellular carcinoma (eHCC) and DN the latter accounting
for as many as 70% of nodules < 1 cm. HG-DN are currently considered the most advanced HCC precursors. The
histological diagnosis of low-grade dysplastic nodule (LG-DN), high- grade dysplastic nodule (HG-DN) and eHCC
in small liver biopsies requires a comprehensive stepwise morphological and immunocytochemical approach. By
imaging the differential diagnosis among these lesions is a challenge. According to vascular enhancement at dynamic
computed tomography (CT) or magnetic resonance imaging (MRI) these precursors are classified as hypo-vascular/
indeterminate nodules even though distinction between LG-DN and HG-DN is almost impossible. The introduction
of gadoexetic acid-enhanced MRI has represented an extremely important advance in this field allowing a better
differentiation of dysplastic lesions from eHCC and progressed HCC. Additional MRI features as diffusion-weighted
imaging further improved diagnostic accuracy of imaging. According to Liver Imaging Reporting and Data System (LI-
RADS), either CT/MRI or Contrast-Enhanced Ultrasound LI-RADS, the dysplastic lesions should be categorized as
LR-3 or LR-4. Natural history of these lesions confirmed that HCC can develop from HG-DN but which nodule and
when it will undergo malignant transformation is not predictable. The search and validation of radiological and tissue
markers able to select lesions more prone to HCC development, is currently underway. Whether and how HG-DN
should be ablated or closely followed up is currently debated.

Keywords: Low-grade dysplastic nodule, high-grade dysplastic nodule, early hepatocellular carcinoma, progressed
hepatocellular carcinoma, dynamic imaging, gadoexetic acid-enhanced resonance imaging, hepatobiliary phase

© The Author(s) 2019. Open Access This article is licensed under a Creative Commons Attribution 4.0
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