Skip to main content
SpringerLink
Log in

Histological Subclassification and Its Clinical Significance

  • Chapter
  • First Online:
Intraductal Papillary Mucinous Neoplasm of the Pancreas

  • 916 Accesses

Abstract

Intraductal papillary mucinous neoplasms (IPMNs) show variations in morphological and immunohistochemical features of cells and papillae. Based on the variations, IPMNs are classified into four distinct subtypes, namely, gastric type, intestinal type, pancreatobiliary type, and oncocytic type. These subtypes are well associated with clinicopathological features and known to be an independent prognostic factor. The gastric-type IPMNs show thick fingerlike papillae consisted of low-grade dysplastic cells expressing MUC5AC and occasionally MUC6. Patients with the gastric-type IPMN usually show fair prognosis. However, some of the gastric-type IPMNs are associated with invasive carcinoma that leads to poor prognosis. The intestinal-type IPMNs show villous papillae consisted of high-grade dysplastic cells expressing MUC2 and MUC5AC. They are often associated with mucinous colloid carcinoma. The prognosis is less favorable, around 90 % and 70 % in the 5- and 10-year survivals. The pancreatobiliary-type IPMNs show complex fernlike papillae consisted of high-grade dysplastic cells expressing MUC1 and MUC5AC. They are often associated with tubular adenocarcinoma and, hence, the prognosis is very poor, around 50 % and none in the 5- and 10-year survivals. The oncocytic-type IPMN show fractal-shaped papillae consisted of high-grade oncocytic cells expressing MUC5AC and MUC6. They are occasionally associated with oncocytic carcinoma. Prognosis is less favorable, around 80 % and 70 % in the 5- and 10-year survivals. These subtypes of IPMN can be determined not only on surgical specimen but also on cytology or biopsy specimen; hence, information of the subtypes is available during diagnostic process as well as postoperative follow-up, which is expected to facilitate better clinical management of patients with IPMN.

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

Access this chapter

Log in via an institution
eBook
USD 16.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 159.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Abe M, Kufe D. Characterization of cis-acting elements regulating transcription of the human DF3 breast carcinoma-associated antigen (MUC1) gene. Proc Natl Acad Sci U S A. 1993;90(1):282–6.

    Article  PubMed  CAS  Google Scholar 

  • Adsay NV, Adair CF, Heffess CS, Klimstra DS. Intraductal oncocytic papillary neoplasms of the pancreas. Am J Surg Pathol. 1996;20(8):980–94.

    Article  PubMed  CAS  Google Scholar 

  • Adsay NV, Conlon KC, Zee SY, Brennan MF, Klimstra DS. Intraductal papillary-mucinous neoplasms of the pancreas: an analysis of in situ and invasive carcinomas in 28 patients. Cancer. 2002;94(1):62–77.

    Article  PubMed  Google Scholar 

  • Adsay NV, Merati K, Basturk O, Iacobuzio-Donahue C, Levi E, Cheng JD, et al. Pathologically and biologically distinct types of epithelium in intraductal papillary mucinous neoplasms: delineation of an "intestinal" pathway of carcinogenesis in the pancreas. Am J Surg Pathol. 2004;28(7):839–48.

    Article  PubMed  Google Scholar 

  • Adsay NV, Fukushima N, Furukawa T, Hruban RH, Klimstra DS, Klöppel G, et al. Intraductal neoplasms of the pancreas. In: Bosman FT, Hruban RH, Carneiro F, Theise ND, editors. WHO classification of tumours of the digestive system. WHO classification of tumours. 4th ed. Lyon: IARC; 2010. p. 304–13.

    Google Scholar 

  • Almoguera C, Shibata D, Forrester K, Martin J, Arnheim N, Perucho M. Most human carcinomas of the exocrine pancreas contain mutant c-K-ras genes. Cell. 1988;53(4):549–54.

    Article  PubMed  CAS  Google Scholar 

  • Bartman AE, Buisine MP, Aubert JP, Niehans GA, Toribara NW, Kim YS, et al. The MUC6 secretory mucin gene is expressed in a wide variety of epithelial tissues. J Pathol. 1998;186(4):398–405.

    Article  PubMed  CAS  Google Scholar 

  • Biankin AV, Biankin SA, Kench JG, Morey AL, Lee CS, Head DR, et al. Aberrant p16(INK4A) and DPC4/Smad4 expression in intraductal papillary mucinous tumours of the pancreas is associated with invasive ductal adenocarcinoma. Gut. 2002;50(6):861–8.

    Article  PubMed  CAS  Google Scholar 

  • Caldas C, Kern SE. K-ras mutation and pancreatic adenocarcinoma. Int J Pancreatol. 1995;18(1):1–6.

    PubMed  CAS  Google Scholar 

  • Dhanasekaran DN. Transducing the signals: a G protein takes a new identity. Sci STKE. 2006;2006(347):pe31.

    PubMed  Google Scholar 

  • Furukawa T, Takahashi T, Kobari M, Matsuno S. The mucus-hypersecreting tumor of the pancreas. Development and extension visualized by three-dimensional computerized mapping. Cancer. 1992;70(6):1505–13.

    Article  PubMed  CAS  Google Scholar 

  • Furukawa T, Fujisaki R, Yoshida Y, Kanai N, Sunamura M, Abe T, et al. Distinct progression pathways involving the dysfunction of DUSP6/MKP-3 in pancreatic intraepithelial neoplasia and intraductal papillary-mucinous neoplasms of the pancreas. Mod Pathol. 2005a;18(8):1034–42.

    Article  PubMed  CAS  Google Scholar 

  • Furukawa T, Kloppel G, Volkan Adsay N, Albores-Saavedra J, Fukushima N, Horii A, et al. Classification of types of intraductal papillary-mucinous neoplasm of the pancreas: a consensus study. Virchows Arch. 2005b;447(5):794–9.

    Article  PubMed  Google Scholar 

  • Furukawa T, Hatori T, Fujita I, Yamamoto M, Kobayashi M, Ohike N, et al. Prognostic relevance of morphological types of intraductal papillary mucinous neoplasms of the pancreas. Gut. 2011a;60(4):509–16.

    Article  PubMed  Google Scholar 

  • Furukawa T, Kuboki Y, Tanji E, Yoshida S, Hatori T, Yamamoto M, et al. Whole-exome sequencing uncovers frequent GNAS mutations in intraductal papillary mucinous neoplasms of the pancreas. Sci Rep. 2011b;1:161.

    Article  PubMed  Google Scholar 

  • Gerwin BI, Spillare E, Forrester K, Lehman TA, Kispert J, Welsh JA, et al. Mutant p53 can induce tumorigenic conversion of human bronchial epithelial cells and reduce their responsiveness to a negative growth factor, transforming growth factor beta 1. Proc Natl Acad Sci U S A. 1992;89(7):2759–63.

    Article  PubMed  CAS  Google Scholar 

  • Greene FL, Page DL, Fleming ID, Fritz A, Balch CM. AJCC cancer staging handbook. 6th ed. New York: Springer; 2002.

    Book  Google Scholar 

  • Gum JR, Byrd JC, Hicks JW, Toribara NW, Lamport DT, Kim YS. Molecular cloning of human intestinal mucin cDNAs. Sequence analysis and evidence for genetic polymorphism. J Biol Chem. 1989;264(11):6480–7.

    PubMed  CAS  Google Scholar 

  • Hahn SA, Schutte M, Hoque AT, Moskaluk CA, da Costa LT, Rozenblum E, et al. DPC4, a candidate tumor suppressor gene at human chromosome 18q21.1. Science. 1996;271(5247):350–3.

    Article  PubMed  CAS  Google Scholar 

  • Hara T, Ikebe D, Odaka A, Sudo K, Nakamura K, Yamamoto H, Itami M, Hirata T, Kashimura J, Yamaguchi T. Preoperative histological subtype classification of intraductal papillary mucinous neoplasms (IPMN) by pancreatic juice cytology with MUC stain. Ann Surg. 2013. doi: 10.1097/SLA.0b013e318281b824.

  • Hibi Y, Fukushima N, Tsuchida A, Sofuni A, Itoi T, Moriyasu F, et al. Pancreatic juice cytology and subclassification of intraductal papillary mucinous neoplasms of the pancreas. Pancreas. 2007;34(2):197–204.

    Article  PubMed  Google Scholar 

  • Hoshi T, Imai M, Ogawa K. Frequent K-ras mutations and absence of p53 mutations in mucin-producing tumors of the pancreas. J Surg Oncol. 1994;55(2):84–91.

    Article  PubMed  CAS  Google Scholar 

  • House MG, Guo M, Iacobuzio-Donahue C, Herman JG. Molecular progression of promoter methylation in intraductal papillary mucinous neoplasms (IPMN) of the pancreas. Carcinogenesis. 2003;24(2):193–8.

    Article  PubMed  CAS  Google Scholar 

  • Kim GE, Bae HI, Park HU, Kuan SF, Crawley SC, Ho JJ, et al. Aberrant expression of MUC5AC and MUC6 gastric mucins and sialyl Tn antigen in intraepithelial neoplasms of the pancreas. Gastroenterol. 2002;123(4):1052–60.

    Article  CAS  Google Scholar 

  • Kim J, Jang KT, Mo Park S, Lim SW, Kim JH, Lee KH, et al. Prognostic relevance of pathologic subtypes and minimal invasion in intraductal papillary mucinous neoplasms of the pancreas. Tumour Biol. 2011;32(3):535–42. doi:10.1007/s13277-010-0148-z.

    Article  PubMed  Google Scholar 

  • Klöppel G, Solcia E, Longnecker DS, Capella C, Sobin LH. Histological typing of tumours of the exocrine pancreas. International histological classification of tumours. 2nd ed. Berlin: Springer; 1996.

    Book  Google Scholar 

  • Koo BK, Spit M, Jordens I, Low TY, Stange DE, van de Wetering M, et al. Tumour suppressor RNF43 is a stem-cell E3 ligase that induces endocytosis of Wnt receptors. Nature. 2012;488(7413):665–9.

    Article  PubMed  CAS  Google Scholar 

  • Landis CA, Masters SB, Spada A, Pace AM, Bourne HR, Vallar L. GTPase inhibiting mutations activate the alpha chain of Gs and stimulate adenylyl cyclase in human pituitary tumours. Nature. 1989;340(6236):692–6.

    Article  PubMed  CAS  Google Scholar 

  • Mohri D, Asaoka Y, Ijichi H, Miyabayashi K, Kudo Y, Seto M, et al. Different subtypes of intraductal papillary mucinous neoplasm in the pancreas have distinct pathways to pancreatic cancer progression. J Gastroenterol. 2012;47(2):203–13.

    Article  PubMed  CAS  Google Scholar 

  • Morikawa M, Koinuma D, Miyazono K, Heldin CH. Genome-wide mechanisms of Smad binding. Oncogene. 2012. doi: 10.1038/onc.2012.191.

  • Ohhashi K, Murakami Y, Maruyama M, Takekoshi T, Ohta H, Ohhashi I, et al. Four cases of mucous secreting pancreatic cancer. (Jpn. Abstr in English). Prog Digest Endosc. 1982;20:348–51.

    Google Scholar 

  • Samuels Y, Wang Z, Bardelli A, Silliman N, Ptak J, Szabo S, et al. High frequency of mutations of the PIK3CA gene in human cancers. Science. 2004;304(5670):554.

    Article  PubMed  CAS  Google Scholar 

  • Sasaki S, Yamamoto H, Kaneto H, Ozeki I, Adachi Y, Takagi H, et al. Differential roles of alterations of p53, p16, and SMAD4 expression in the progression of intraductal papillary-mucinous tumors of the pancreas. Oncol Rep. 2003;10(1):21–5.

    PubMed  CAS  Google Scholar 

  • Satoh K, Shimosegawa T, Moriizumi S, Koizumi M, Toyota T. K-ras mutation and p53 protein accumulation in intraductal mucin-hypersecreting neoplasms of the pancreas. Pancreas. 1996;12(4):362–8.

    Article  PubMed  CAS  Google Scholar 

  • Schönleben F, Qiu W, Ciau NT, Ho DJ, Li X, Allendorf JD, et al. PIK3CA mutations in intraductal papillary mucinous neoplasm/carcinoma of the pancreas. Clin Cancer Res. 2006;12(12):3851–5.

    Article  PubMed  Google Scholar 

  • Serrano M, Hannon GJ, Beach D. A new regulatory motif in cell-cycle control causing specific inhibition of cyclin D/CDK4. Nature. 1993;366(6456):704–7.

    Article  PubMed  CAS  Google Scholar 

  • Tanaka M, Fernandez-del Castillo C, Adsay V, Chari S, Falconi M, Jang JY, et al. International consensus guidelines 2012 for the management of IPMN and MCN of the pancreas. Pancreatol. 2012;12(3):183–97.

    Article  Google Scholar 

  • Thatcher JD. The Ras-MAPK signal transduction pathway. Sci Signal. 2010;3(119):tr1.

    Article  PubMed  Google Scholar 

  • Wu J, Jiao Y, Dal Molin M, Maitra A, de Wilde RF, Wood LD, et al. Whole-exome sequencing of neoplastic cysts of the pancreas reveals recurrent mutations in components of ubiquitin-dependent pathways. Proc Natl Acad Sci U S A. 2011a;108(52):21188–93.

    Article  PubMed  CAS  Google Scholar 

  • Wu J, Matthaei H, Maitra A, Dal Molin M, Wood LD, Eshleman JR, et al. Recurrent GNAS mutations define an unexpected pathway for pancreatic cyst development. Sci Transl Med. 2011b;3(92):92ra66.

    Article  PubMed  CAS  Google Scholar 

  • Xiao HD, Yamaguchi H, Dias-Santagata D, Kuboki Y, Akhavanfard S, Hatori T, et al. Molecular characteristics and biological behaviours of the oncocytic and pancreatobiliary subtypes of intraductal papillary mucinous neoplasms. J Pathol. 2011;224(4):508–16.

    Article  PubMed  CAS  Google Scholar 

  • Yamaguchi H, Kuboki Y, Hatori T, Yamamoto M, Shiratori K, Kawamura S, et al. Somatic mutations in PIK3CA and activation of AKT in intraductal tubulopapillary neoplasms of the pancreas. Am J Surg Pathol. 2011;35(12):1812–7.

    Article  PubMed  Google Scholar 

  • Yonezawa S, Horinouchi M, Osako M, Kubo M, Takao S, Arimura Y, et al. Gene expression of gastric type mucin (MUC5AC) in pancreatic tumors: its relationship with the biological behavior of the tumor. Pathol Int. 1999;49(1):45–54.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institute for Integrated Medical Sciences, Tokyo Women’s Medical University, Tokyo, Japan

    Toru Furukawa

Authors
  1. Toru Furukawa
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Toru Furukawa .

Editor information

Editors and Affiliations

  1. Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Fukuoka, Japan

    Masao Tanaka

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer Japan

About this chapter

Cite this chapter

Furukawa, T. (2014). Histological Subclassification and Its Clinical Significance. In: Tanaka, M. (eds) Intraductal Papillary Mucinous Neoplasm of the Pancreas. Springer, Tokyo. https://doi.org/10.1007/978-4-431-54472-2_4

Download citation

  • DOI: https://doi.org/10.1007/978-4-431-54472-2_4

  • Published:

  • Publisher Name: Springer, Tokyo

  • Print ISBN: 978-4-431-54471-5

  • Online ISBN: 978-4-431-54472-2

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation