Nestin may be a candidate marker for differential diagnosis between small duct type and large duct type intrahepatic cholangiocarcinomas

Intrahepatic cholangiocarcinoma (iCCA) is subclassified into small and large duct types. These two subtypes show distinct differences in various clinicopathological features and possible cell origin and pathways of carcinogenesis, however, a differential diagnosis may be sometimes difficult. Given the type IV intermediate filament, Nestin, may be a candidate diagnostic marker for combined hepatocellular-cholangiocarcinoma (cHCC-CCA) and small duct type iCCAs, the significance of nestin as a differential diagnostic marker between small and large duct types of iCCAs was addressed in the present study. Nestin expression was immunohistochemically assessed in the sections from 36 patients with small duct-type iCCA, 30 with large duct-type iCCA, and 27 with extrahepatic cholangiocarcinoma (CCA). Nestin expression and its relationship with clinicopathological features and genetic alterations were investigated in small duct type iCCAs. Nestin expression was detected in 17 small duct type iCCAs (47.2%), one large duct type iCCA (3.8%) and zero extrahepatic CCA. Nestin expression was significantly more frequent in the patients with small duct type iCCAs than in those with large duct type iCCA and extrahepatic CCA (p<0.01). In 10 liver biopsies, all samples with nestin expression were small duct type iCCAs. Nestin-positive small duct type iCCAs were characterized by a higher histological grade, compared to Nestin-negative small duct type iCCAs (p<0.01). Nestin-positive small duct type iCCAs tended to have 2 or more genetic alterations, but there was no statistic difference (p>0.05). Different nestin expression may reflect differences between small duct type iCCA and large duct type/extrahepatic CCA and may be a useful diagnostic marker for small duct type iCCAs.