Pathological, molecular, and clinical characteristics of cholangiocarcinoma: A comprehensive review

Table 3 Clinicopathologic, immunohistochemical, and molecular characteristics

	Large duct type	Small duct type
Location	Proximal to hepatic hilum	Peripheral
Risk factors	PSC, Liver fluke infection, Hepatolithiasis	Chronic liver disease, viral hepatitis
Gross features	Periductal infiltrating, Mixed pattern	Mass forming
Precursor lesion	BilIN, IPNB, ITPN	Unknown
Pathology	Large, widely spaced glands, Columnar with mucin production, desmoplastic stroma	Small tubules, fused or anastomosing glands, cuboidal to low columnar, central scarring, minimal to no mucin
Perinerual invasion	Common	Rare
Lymphovascular invasion/lymph node metastases	Common	Rare
Tumour border	Infiltrative	Expansile or pushing, rarelyinfiltrative
Immunohistochemical features	S100P and TFF1	CD56, N-cadherin, CRP
Molecular alterations	KRAS and GNAS mutationsCOX2 upregulations	IDH1/IDH2 and BRAF mutations, FGFR2 fusion

BilIN: Biliary intraepithelial neoplasia; CRP: C-reactive protein; IPNB: Intraductal papillary neoplasm of the bile duct; ITPN: Intraductal tubulopapillary neoplasms; PSC: Primary sclerosing cholangitis.