Pathologic and molecular features of hepatocellular carcinoma: An update

Table 1 Hepatocellular carcinoma distinct subtypes with pathological and molecular features

Distinct subtypes	Pathological features	Molecular features
Macrotrabecular massive	Macrotrabeculae > 50% of the tumor, staellite nodules, vascular invasion	TP53 mutations and FGF19 amplifications
Steatohepatitic	Steatohepatitis in the tumor	IL6/JAK/STAT pathway activation
Scirrhous	Dense fibrosis in > 50% of the tumor	Activation of (TGF-β) pathway, with overexpression of VIM, SNAIL (SNAI1), SMAD4 and TWIST
Fibrolamellar	Large polygonal tumor cells with abundant eosinophilic granular cytoplasm and dense bands of intratumoral fibrosis	Recurrent chimeric DNAJB1-PRKACA gene fusion
Lymphoepithelioma-like	Neoplastic epithelial cells with a prominent lymphoid infiltrate	Marked focal amplification of chromosome 11q13.3
Progenitor	Immunohistochemical expression of biliary marker CK19 in > 5% of tumor cells	TP53 mutations
Combined hepatocellular-cholangiocarcinoma	Unequivocal presence of both hepatocytic and cholangiocytic differentiation	TP53, TERT, IDH mutations

DNAJB1-PRKACA: DnaJ heat shock protein family member B1 (DNAJB1) and protein kinase 3'-5'-cyclic adenosine monophosphate-activated catalytic subunit alpha; IL6: Interleukin-6; JAK: Janus kinas; STAT: Signal transducer and activator of transcription; FGF19: Fibroblast growth factor 19; TERT: Telomerase reverse transcriptase; IDH: Isocitrate dehydrogenase; SNAIL (SNAI1): SNAIL family transcriptional repressor 1; SMAD4: SMAD family member 4; TWIST: Twist-related protein; TGF-β: Transforming growth factor beta.