Intraductal tubulopapillary neoplasms of the pancreas distinct from pancreatic intraepithelial neoplasia and intraductal papillary mucinous neoplasms

Hiroshi Yamaguchi, Michio Shimizu, Shinichi Ban, Isamu Koyama, Takashi Hatori, Izumi Fujita, Masakazu Yamamoto, Shunji Kawamura, Makio Kobayashi, Kazuyuki Ishida, Takanori Morikawa, Fuyuhiko Motoi, Michiaki Unno, Atsushi Kanno, Kennichi Satoh, Tooru Shimosegawa, Hideki Orikasa, Tomoo Watanabe, Kazuhiko Nishimura, Yoshiro EbiharaNaoto Koike, Toru Furukawa

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157 Citations (Scopus)


We have encountered cases of unusual intraductal pancreatic neoplasms with predominant tubulopapillary growth. We collected data on 10 similar cases of "intraductal tubulopapillary neoplasms (ITPNs)" and analyzed their clinicopathologic and molecular features. Tumor specimens were obtained from 5 men and 5 women with a mean age of 58 years. ITPNs were solid and nodular tumors obstructing dilated pancreatic ducts and did not contain any visible mucin. The tumor cells formed tubulopapillae and contained little cytoplasmic mucin. The tumors exhibited uniform high-grade atypia. Necrotic foci were frequently observed, and invasion was observed in some cases. The ITPNs were immunohistochemically positive for cytokeratin 7 and/or cytokeratin 19 and negative for trypsin, MUC2, MUC5AC, and fascin. Molecular studies revealed abnormal expressions of TP53 and SMAD4 in 1 case, but aberrant expression of β-catenin was not observed. No mutations in KRAS and BRAF were observed in the 8 cases that were examined. Eight patients are alive without recurrence, 1 patient died of liver metastases, and 1 patient is alive but had a recurrence and underwent additional pancreatectomy. The mitotic count and Ki-67 labeling index were significantly associated with invasion. All the features of ITPN were distinct from those of other known intraductal pancreatic neoplasms, including pancreatic intraepithelial neoplasia, intraductal papillary mucinous neoplasm, and the intraductal variant of acinar cell carcinoma. Intraductal tubular carcinomas showed several features that were similar to those of ITPN, except for the tubulopapillary growth pattern. In conclusion, ITPNs can be considered to represent a new disease entity encompassing intraductal tubular carcinoma as a morphologic variant.

Original languageEnglish
Pages (from-to)1164-1172
Number of pages9
JournalAmerican Journal of Surgical Pathology
Issue number8
Publication statusPublished - 2009 Aug


  • IPMN
  • Intraductal tubular neoplasm
  • Intraductal tubulopapillary neoplasm
  • PanIN
  • Pancreatic cancer


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