Aberrant activation of NOTCH signaling and gain-of-function mutations in the genes encoding isocitrate dehydrogenases (IDH1 and IDH2) are required for ICC development, and thus are significantly more common in ICC than in HCC (Sekiya and Suzuki, 2012; Moeini et al., 2016). Here, IDH2 is linked to intrahepatic cholangiocarcinoma.