Table 1.

differential diagnosis of biliary hamartoma

Histological features	Biliary hamartoma	Biliary adenoma	Cholangiocarcinoma	Metastatic adenocarcinomas
Biliary structures architecture	Small, dilated tubules; inter anastomosing pattern of growth; open lumens; inspissated bile is common.	Generally small and round tubules; small or inapparent lumens; no inspissated bile.	Generally larger tumors; infiltrating borders and a destructive growth pattern.	Adenocarcinoma with variable appearance (although it is the well differentiated type that may resemble a biliary hamartoma).
Cytology	Cytologically bland biliary epithelium: no cytological atypia; no mitotic figures.	Bland cuboidal cells; regular nuclei, resembling ductules.	Cytological atypia mitotic figures, atypical mitosis cellular debris in the lumens of biliary structures (dirty luminal necrosis) strongly favors cholangiocarcinoma.	Cytological atypia; mitotic figures, atypical mitosis; 'garland-like' necrosis in cases of metastatic (colorectal adenocarcinomas).
Stroma	Loose and myxoid or densely collagenous; mild lymphocytic inflammation; most hamartomas are located adjacent to, or clearly involve, a portal tract.	Fibrous, shows varying degrees of chronic inflammation and collagenization; portal tracts are often enclosed in the nodule.	Fibrous stroma with marked inflammatory infiltrate; vascular or perineural invasion can be found.	Fibrous stroma with marked inflammatory infiltrate; vascular or perineural invasion can be found.
Immunohistochemistry	Express CK7 and CK19; low proliferative rate (Ki-67).	Express CK7 and CK19, and often MUC6, MUC5AC.	CK7, CK19, ACE: usually positive; CK20: positive in 20%; increased proliferation rate on Ki-67; P53: often strong expression.	Segregate according to CK7/CK20 pattern, then apply markers according to the suspected primary site.