Latest developments in precancerous lesions of hepatocellular carcinoma

Table 1 Summary of the main pathological, molecular genetic and radiological features of distinction between low- and high-grade dysplastic nodules

	LGDNs	HGDNs	e/WD-HCC	Quoted literature examples
Cytologic features
Small cell change	-	+	+	Roncalli et al[30]
Large cell change	±	±	-	Roncalli et al[30]
Architectural features
Nuclear/cyto-plasmic ratio	±	+	+	Chang et al[2]
Increased cell density compared with surroundings	-	1.3 to 2 times	> 2 times or more	Park et al[4]
Pseudoglands	-	±	+	Nascimento et al[31]
Unpaired arteries	±	±	+	Park et al[4]
Portal tract	-	+	+	Kojiro et al[32]
Hyperchromasia/nuclear atypia	-	+	+	Nascimento et al[31]
Radiological features
Hepatobiliary phase images	No hypointensity	Hypointensity (70%)	Hypointensity (97.5%)	Gatto et al[40]
Arterial phase	Iso/hyperintensity (100%)	Iso/hypointense (96.7%)	Iso/hypointense (27.5%)	Gatto et al[40]
Washout and arterial enhancement	No washout or arterial enhancement on CT or MRI	6 (6/6 )showed arterial enhancement on CT, 4 (4/6) were hypervascular on MRI; 5 (5/6) on CT and 4 (4/6) on MRI	51 (51/74) were hypervascular on CT, 57 (57/74) were hypervascular on MRI; washout was not showed	Serste et al[25]
Molecular genetic biomarkers
Overall FAL index	0.16 ± 0.07	0.33 ± 0.21	0.40 ± 0.23	Lee et al[27]
Chromosomal changes	Deletions and gains were not found	Deletions of 8p and gains of 1q	Deletions of 8p and gains of 1q	Tornillo et al[45]
TERT promoter mutations	6%	19%	61%	Nault et al[50]
TRF length	7.2 ± 1.97	4.0 ± 0.89	4.5 ± 0.85	Oh et al[53]
Telomerase activity	0.9 ± 0.56	1.7 ± 0.75	2.3 ± 1.39	Oh et al[53]
miRNAs (miR-224)	-	+ (50%)	+ (100%)	Gao et al[57]
DNA methylation Nuclear expression of Dnmt3a	-	+ (29.2%)	+ (53.8%)	Choi et al[62]
Immunohistological biomarkers
VEGF	± (100%)	+ (100%)	+ (100%)	Park et al[67]
GPC3	± (5.48%)	+ (50%)	+ (57.1%)	Gong et al[1]
MN index (number of micronuclei per 3000 hepatocytes)	0.9 ± 0.16	3.1 ± 0.38	4.0 ± 0.58	Lee et al[77]

-: absent; ±: may be present; +: usually present. CT: Computed tomography; MRI: Magnetic resonance imaging; FAL: Fractional allelic loss; TERT: Telomerase reverse-transcriptase; TRF: Terminal restriction fragment; Dnmt3a: DNA methyltransferases 3a; VEGF: Vascular endothelial growth factor; GPC3: Glypican-3; MN: Micronucleus; LGDNs: Low-grade dysplastic nodules; HGDNs: High-grade dysplastic nodules; e/WD-HCC: Early/well-differentiated hepatocellular carcinoma.