Cholangiocarcinoma with intraductal tubular growth pattern versus intraductal papillary growth pattern

Mod Pathol. 2016 Mar;29(3):293-301. doi: 10.1038/modpathol.2015.152. Epub 2016 Jan 15.


Intraductal neoplasms of the bile duct are macroscopically characterized by exophytic or polypoid growth patterns and have a favorable prognosis. Although some tumors with a predominantly tubular microscopic pattern have been reported, they have not been well characterized clinicopathologically. The purpose of the present study was to compare the newly recognized cholangiocarcinoma with an intraductal tubular growth pattern and cholangiocarcinoma with an intraductal papillary growth pattern and to investigate the pathological and prognostic significance of the former. This study analyzed 161 patients with tumors with exophytic or polypoid growth patterns from a large series of 733 cholangiocarcinoma cases surgically resected from January 1998 to May 2013. The study patients were divided into two groups: those whose tumors showed a predominantly tubular growth pattern (n=52) and those whose tumors exhibited a predominantly papillary growth pattern (n=109). Tubular growth pattern was associated with combined vascular resection and the absence of macroscopic mucin. Several histological indexes were significantly higher for the tubular growth pattern than the papillary one, including tubular adenocarcinoma, depth of invasion, microscopic lymphatic invasion, venous invasion, perineural invasion, and necrosis. Although the survival curves overlapped (P=0.693), the rate of liver metastasis was significantly higher for the tubular growth pattern than for the papillary one (P=0.012). Genomic DNA analysis focusing on somatic mutations in codons 12 and 13 of KRAS and codon 600 of BRAF revealed only one (4%) KRAS and no BRAF mutation among the 25 tubular cases examined. In conclusion, the tubular growth pattern exhibited differences in some histologic indexes, in addition to a higher hepatic metastasis rate and a lower KRAS mutation frequency, compared with the papillary growth pattern, but no difference in prognosis was observed. The distinctiveness of this tubular neoplasm should be further examined in the future.

MeSH terms

  • Adenocarcinoma, Papillary / genetics
  • Adenocarcinoma, Papillary / mortality
  • Adenocarcinoma, Papillary / pathology*
  • Aged
  • Bile Duct Neoplasms / genetics
  • Bile Duct Neoplasms / mortality
  • Bile Duct Neoplasms / pathology*
  • Bile Ducts, Intrahepatic / pathology*
  • Cholangiocarcinoma / genetics
  • Cholangiocarcinoma / mortality
  • Cholangiocarcinoma / pathology*
  • DNA Mutational Analysis
  • Female
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Polymerase Chain Reaction
  • Prognosis
  • Proto-Oncogene Proteins B-raf / genetics
  • Proto-Oncogene Proteins p21(ras) / genetics


  • KRAS protein, human
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf
  • Proto-Oncogene Proteins p21(ras)