Skip to main content

Advertisement

Log in

Clinicopathological features of intraductal papillary neoplasms of the bile duct: a comparison with intraductal papillary mucinous neoplasm of the pancreas with reference to subtypes

Virchows Archiv Aims and scope Submit manuscript

Abstract

Intraductal papillary epithelial neoplasms of the pancreatobiliary system (intraductal papillary neoplasm of the bile duct (IPNB) and intraductal papillary mucinous neoplasm (IPMN)) seem to share many clinicopathological features; however, IPNB has not been fully characterized. In order to understand the clinicopathological/immunohistochemical features of IPNB better, we compared 52 cases of IPNB with 42 cases of IPMNs with mural nodules. The IPNB cases were divided into two groups according to their histological similarity and according to five key histological findings. All IPNB and IPMN cases mainly affected middle-aged to elderly people, predominantly men. Mucin hypersecretion was less frequent in IPNB compared to IPMN. Group 2 IPNB more frequently had a higher histopathological grade and more extensive stromal invasion than IPMN. Group 1 IPNB and IPMN were further classified into four subtypes (gastric, intestinal, pancreatobiliary, and oncocytic). Although each subtype of IPNB and IPMN showed similar histology, the immunohistochemical results were different. The gastric type of IPNB was less frequently positive for CDX2, and intestinal IPNB was more frequently positive for MUC1 and less frequently positive for MUC2, MUC5AC, and CDX2 compared to each subtype of IPMN, respectively. In conclusion, IPNB and IPMN have some clinicopathological features in common, but mucin hypersecretion was less frequent both in IPNBs than in IPMN. Group 2 IPNB differed from IPMN in several parameters of tumor aggressiveness. Additional clinicopathological and molecular studies should be performed with respect to the subtypes of IPNB and IPMN.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Nakanuma Y, Curado M-P, Franceschi S, Gores G, Paradis V, Sripa B (2010) Intrahepatic cholangiocarcinoma. In: Bosman F, Carmeiro F, Hruban RH, Theise ND (eds) WHO classification of tumours of the digestive system, 4th edn. International Agency for Research on Cancer, Lyon, pp 217–224

    Google Scholar 

  2. Klöppel G, Kosmahl M (2006) Is the intraductal papillary mucinous neoplasia of the biliary tract a counterpart of pancreatic papillary mucinous neoplasm? J Hepatol 44:249–250

    Article  PubMed  Google Scholar 

  3. Chen TC, Nakanuma Y, Zen Y, Chen MF, Jan YY, Yeh TS, Chiu CT, Kuo TT, Kamiya J, Oda K, Hamaguchi M, Ohno Y, Hsieh LL, Nimura Y (2001) Intraductal papillary neoplasia of the liver associated with hepatolithiasis. Hepatology 34:651–658

    Article  CAS  PubMed  Google Scholar 

  4. Shibahara H, Tamada S, Goto M, Oda K, Nagino M, Nagasaka T, Batra SK, Hollingsworth MA, Imai K, Nimura Y, Yonezawa S (2004) Pathologic features of mucin-producing bile duct tumors. Two histopathologic categories as counterparts of pancreatic intraductal papillary-mucinous neoplasms. Am J Surg Pathol 28:327–338

    Article  PubMed  Google Scholar 

  5. Ohtsuka M, Shimizu H, Kato A, Yoshitomi H, Furukawa K, Tsuyuguchi T, Sakai Y, Yokosuka O, Miyazaki M (2014) Intraductal papillary neoplasms of the bile duct. Int J Hepatol. doi:10.1155/2014/45909

  6. Hruban RH, Pitman MB, Klimstra DS (2007) Intraductal neoplasms. In: AFIP ATLAS OF TUMOR PATHOLOGY Series 4. Tumors of the pancreas. American Registry of Pathology and Armed Forces Institute of Pathology, Washington, DC, pp 75–110

    Google Scholar 

  7. Minagawa N, Sato N, Mori Y, Tamura T, Higure A, Yamaguchi K (2013) A comparison between intraductal papillary neoplasms of the biliary tract (BT-IPMNs) and intraductal papillary mucinous neoplasms of the pancreas (P-IPMNs) reveals distinct clinical manifestations and outcomes. Eur J Surg Oncol 39:554–558

    Article  CAS  PubMed  Google Scholar 

  8. Kloek JJ, van der Gaag NA, Erdogan D, Rauws EA, Busch OR, Gouma DJ, ten Kate FJ, van Gulik TM (2011) A comparative study of intraductal papillary neoplasia of the biliary tract and pancreas. Hum Pathol 42:824–832

    Article  CAS  PubMed  Google Scholar 

  9. Kubota K, Nakanuma Y, Kondo F, Hachiya H, Miyazaki M, Nagino M, Yamamoto M, Isayama H, Tabata M, Kinoshita H, Kamisawa T, Inui K (2014) Clinicopathological features and prognosis of mucin-producing bile duct tumor and mucinous cystic tumor of the liver: a multi-institutional study by the Japan Biliary Association. J Hepatobiliary Pancreat Sci 21:176–185

    Article  PubMed  Google Scholar 

  10. Nakanuma Y (2010) A novel approach to biliary tract pathology based on similarities to pancreatic counterparts: is the biliary tract an incomplete pancreas? Pathol Int 60:419–429

    Article  PubMed  Google Scholar 

  11. Wang M, Deng BY, Wen TF, Peng W, Li C, Trishul NM (2016) An observational and comparative study on intraductal papillary mucinous neoplasm of the biliary tract and the cohort. Clin Res Hepatol Gastroenterol 40:161–168

  12. Adsay NV, Fukushima N, Furukawa T, Hruban RH, Klimstra DS, Klöppel G, Offerhaus GJA, Pitman MB, Shimizu M, Zamboni G (2010) Intraductal neoplasms of the pancreas. In: Bosman F, Carmeiro F, Hruban RH, Theise ND (eds) WHO classification of tumours of the digestive system, 4th edn. International Agency for Research on Cancer, Lyon, pp 304–313

    Google Scholar 

  13. Zen Y, Fujii T, Itatsu K, Nakamura K, Minato H, Kasashima S, Kurumaya H, Katayanagi K, Kawashima A, Masuda S, Niwa H, Mitsui T, Asada Y, Miura S, Ohta T, Nakanuma Y (2006) Biliary papillary tumors share pathological features with intraductal papillary mucinous neoplasm of the pancreas. Hepatology 44:1333–1343

    Article  CAS  PubMed  Google Scholar 

  14. Schlitter AM, Jang KT, Klöppel G, Saka B, Hong SM, Choi H, Offerhaus GJ, Hruban RH, Zen Y, Konukiewitz B, Regel I, Allgauer M, Balci S, Basturk O, Reid MD, Esposito I, Adsay V (2015) Intraductal tubulopapillary neoplasms of the bile ducts: clinicopathologic, immunohistochemical, and molecular analysis of 20 cases. Modern Pathol 28:1249–1264

    Article  CAS  Google Scholar 

  15. Schlitter AM, Born D, Bettstetter M, Specht K, Kim-Fuchs C, Riener MO, Jeliazkova P, Sipos B, Siveke JT, Terris B, Zen Y, Schuster T, Hofler H, Perren A, Kloppel G, Esposito I (2014) Intraductal papillary neoplasms of the bile duct: stepwise progression to carcinoma involves common molecular pathways. Modern Pathol 27:73–86

    Article  CAS  Google Scholar 

  16. Tsai JH, Yuan RH, Chen YL, Liau JY, Jeng YM (2013) GNAS is frequently mutated in a specific subgroup of intraductal papillary neoplasms of the bile duct. Am J Surg Pathol 37:1862–1870

    Article  PubMed  Google Scholar 

  17. Sasaki M, Matsubara T, Nitta T, Sato Y, Nakanuma Y (2013) GNAS and KRAS mutations are common in intraductal papillary neoplasms of the bile duct. PLoS One 8:e81706

    Article  PubMed  PubMed Central  Google Scholar 

  18. Matthaei H, Wu J, Dal Molin M, Debeljak M, Lingohr P, Katabi N, Klimstra DS, Adsay NV, Eshleman JR, Schulick RD, Kinzler KW, Vogelstein B, Hruban RH, Maitra A (2012) GNAS codon 201 mutations are uncommon in intraductal papillary neoplasms of the bile duct. HPB 14:677–683

    Article  PubMed  PubMed Central  Google Scholar 

  19. Ajioka Y, Watanabe H, Jass JR (1997) MUC1 and MUC2 mucins in flat and polypoid colorectal adenomas. Clin Pathol 50:417–421

    Article  CAS  Google Scholar 

  20. Yonezawa S, Higashi M, Yamada N, Yokoyama S, Kitamoto S, Kitajima S, Goto M (2011) Mucins in human neoplasms: clinical pathology, gene expression and diagnostic application. Pathol Int 61:697–716

    Article  CAS  PubMed  Google Scholar 

  21. Drummond F, Putt W, Fox M, Edwards YH (1997) Cloning and chromosome assignment of the human CDX2 gene. Ann Hum Genet 61:393–400

    Article  CAS  PubMed  Google Scholar 

  22. Werling RW, Yaziji H, Bacchi CE, Gown AM (2003) CDX2, a highly sensitive and specific marker of adenocarcinomas of intestinal origin. An immunohistochemical survey of 476 primary and metastatic carcinomas. Am J Surg Pathol 27:303–310

    Article  PubMed  Google Scholar 

  23. Reid MD, Stallworth CR, Lewis MM, Akkas G, Memis B, Bastrurk O, Adsay NV (2016) Cytopathologic diagnosis of oncocytic type intraductal papillary mucinous neoplasm: criteria and clinical implications of accurate diagnosis. Cancer Cytopathol 124:122–134

    Article  CAS  PubMed  Google Scholar 

  24. Adsay NV, Adair DF, Heffess CS, Klimstra DS (1996) Intraductal oncocytic papillary neoplasms of the pancreas. Am J Surg Pathol 20:980–994

    Article  CAS  PubMed  Google Scholar 

  25. Marchegiani G, Mino-Kenudson M, Ferrone CR, Warshaw AL, Lillemore KD, Fernandez-del Castillo C (2015) Oncocytic-type intraductal papillary mucinous neoplasms: a unique malignant pancreatic tumor with good long-term prognosis. J Am Coll Surg 220:839–844

    Article  PubMed  Google Scholar 

  26. Basturk O, Khayyata S, Klimstra DS, Hruban RH, Zamboni G, Coban I, Adsay NV (2010) Preferential expression of MUC6 in oncocytic and pancreatobiliary types of intraductal papillary neoplasms highlights a pyloropancreatic pathway, in pancreatic carcinogenesis. Am J Surg Pathol 34:364–370

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

The authors thank Dr. Katsuhiko Uesaka, Director of the Department of Hepatobiliary Surgery in Shizuoka Cancer Center, for his support on the clinicopathological analysis of biliary tract carcinoma cases in Shizuoka Cancer Center, and also Dr. Jo Matsuoka, Research Support Center, Juntendo University Graduate School of Medicine, Tokyo, Japan, for his advice on statistical methods. The authors also thank Dr. R Wada, Professor of Juntendo Shizuoka Hospital, Department of Clinical Pathology; Dr. N. Tomita, Professor of Juntendo Urayasu Hospital, Department of Clinical Pathology; and Dr. T. Matsumoto, Professor of Juntendo Nerima Hospital, Department of Clinical Pathology, for providing us the opportunity to analyze IPMN cases resected at their hospitals.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Yuki Fukumura.

Ethics declarations

Institutional review board approval was obtained from Shizuoka Cancer Center.

Conflict of interest

The authors declare that they have no conflict of interest.

Funding

None.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Fukumura, Y., Nakanuma, Y., Kakuda, Y. et al. Clinicopathological features of intraductal papillary neoplasms of the bile duct: a comparison with intraductal papillary mucinous neoplasm of the pancreas with reference to subtypes. Virchows Arch 471, 65–76 (2017). https://doi.org/10.1007/s00428-017-2144-9

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00428-017-2144-9

Keywords

Navigation