Clinicopathological, etiological and molecular characteristics of intrahepatic cholangiocarcinoma subtypes classified by mucin production and immunohistochemical features

Intrahepatic cholangiocarcinoma (ICC) can be divided into two morphological subtypes: large duct type and small duct type ICC. This study aims to verify the feasibility of the classification criteria and clinicopathological characteristics of ICC.ICC patients were divided into the large and small type ICC by morphological and immunohistochemical patterns. Subsequently, clinicopathological data of the two groups was compared and the multivariate COX regression was used to verify the clinical significance of ICC subtypes. In addition, IDH1/2 mutation, KRAS mutation and FGFR2 translocation was also evaluated.Totally, 32, 61 and 13 tumors were defined as large, small and the indeterminate-duct type ICC respectively. Clinicopathologically, the large and small duct type ICC showed distinct morphological features. Compared with the small duct type ICC, the large duct type ICC had higher levels of serum tumor markers, vascular invasion, lymph node metastasis, and postoperative recurrence. Furthermore, positive FGFR2 rearrangement occurred only in small duct type ICC and IDH1/2 was mutated mainly in small duct type ICC.The subclassification system was applicable and the ICC subtypes had distinct clinicopathological characteristics, prognostic outcome, and IDH1/2 mutation pattern.