From: The biology of Hepatocellular carcinoma: implications for genomic and immune therapies
Tumor type | Pathologic features | Molecular signatures |
---|---|---|
Focal nodular hyperplasia (FNH) | Well-differentiated hepatocytes [88] | IHC staining positive for CK19, NCAM in proliferating ductules [88] |
Intervening fibrous bands radiating from a central scar, Â Abundant, proliferating bile ductules | GS staining pattern: map-like pattern [89] | |
Hepatocellular Adenoma (HCA) | Well differentiated proliferating hepatocytes in cords one to two cells thick and lacking portal tracts [88] | IHC staining positive for CK7 [88] |
Rare bile ductules | GS staining pattern: diffuse pattern (beta-catenin activating pattern) or absent/irregular pattern (beta-catenin normal pattern) [88] | |
Naked arterioles | Loss/mutation of TCF1 gene that encodes HNF1 (35–40% of HCA) [93, 94] | |
Overexpressed SAA, CRP, and gp130 in inflammatory subtype (50% of HCA) [95] | ||
Dysplastic nodules (DN) | Vaguely (low-grade DN) or distinctly (high-grade DN) nodular with peripheral fibrous scar [96] | TERT promoter mutation in 6% of low-grade DN; 19% of high-grade DN [97] |
Mild increase in cell density with monotonous pattern, with no cytologic atypia (low-grade DN) or increased cellularity in irregular trabecular pattern with moderate atypia (high-grade DN) | ||
No pseudoglands or markedly thickened trabeculae | ||
Unpaired arteries sometimes present | ||
No stromal invasion | ||
Early HCC | Increased cell density with an elevated nuclear/cytoplasm ratio and irregular thin-trabecular pattern [98] | Increased mRNA expression of GPC3 and survivin and down regulation of LYVE1 [99,100,101,102,103] |
Varying numbers of portal tracts inside the nodule | Positive IHC staining for GS, HSP70, and GPC3 [104,105,106,107] | |
Pseudo-glandular pattern | ||
Diffuse fatty change | TERT promoter mutations in 61% of early HCC [97] | |
Varying numbers of unpaired arteries | ||
Stromal invasion present | ||
Fibrolamellar HCC | Arising in non-cirrhotic liver [11] | Fusion gene--DNAJB1-PRKACA [10] |
Nests of well-differentiated oncocytic cells in a background of acellular but dense collagen bundles arranged in parallel lamellae | Overexpression of EGFR [11]. | |
Advanced HCC | Unifocal, multifocal, or diffusely infiltrative soft tumor [98] | |
Polygonal cells with distinct cell membranes, abundant granular eosinophilic cytoplasm, round nuclei with course chromatin, and higher nucleus/cytoplasm ratio, | ||
Tumor capsule present | Activating mutations of CTNNB1 [108] | |
Invasion and minute intrahepatic metastasis | Other alterations listed in Table 2 | |
Unpaired arteries | ||
Absent portal tracts |