Skip to main content
SpringerLink
Log in

Pathobiology of Precursors to Pancreatic Cancer

  • Chapter
  • First Online:
Textbook of Pancreatic Cancer

  • 2710 Accesses

Abstract

The identification of noninvasive precursor lesions of pancreatic adenocarcinoma, in particular pancreatic intraepithelial neoplasia (PanIN) and intraductal papillary mucinous neoplasm (IPMN) has led to the proposal of a multi-step progression model of pancreatic cancer. Early and late genetic alterations culminating in invasive cancer have been published. While the majority of pancreatic ductal adenocarcinoma are thought to arise from PanIN, important alternative pathways of carcinogenesis are available through IPMN. In this chapter features of pancreatic intraepithelial neoplasia (PanIN), intraductal papillary mucinous neoplasm (IPMN), intraductal tubulopapillary neoplasm (ITPN), pancreatic intraductal oncocytic papillary neoplasm (IOPN) and mucinous cystic neoplasm (MCN) are discussed.

.

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 129.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 199.99
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

  1. Basturk O, Esposito I, Fukushima N, Furukawa T, Hong SM, Klöppel G, Maitra A, Zamboni G. Pancreatic intraepithelial neoplasia. In: Digestive system tumours. 5th ed. Lyon: International Agency of Research on Cancer. p. 307–9.

    Google Scholar 

  2. Basturk O, Hong S-M, Wood LD, et al. A revised classification system and recommendations from the Baltimore consensus meeting for neoplastic precursor lesions in the pancreas. Am J Surg Pathol. 2015;39:1730–41.

    Article  Google Scholar 

  3. Stamm BH. Incidence and diagnostic significance of minor pathologic changes in the adult pancreas at autopsy: a systematic study of 112 autopsies in patients without known pancreatic disease. Hum Pathol. 1984;15:677–83.

    Article  CAS  Google Scholar 

  4. Lüttges J, Reinecke-Lüthge A, Möllmann B, Menke MA, Clemens A, Klimpfinger M, Sipos B, Klöppel G. Duct changes and K-ras mutations in the disease-free pancreas: analysis of type, age relation and spatial distribution. Virchows Arch Int J Pathol. 1999;435:461–8.

    Article  Google Scholar 

  5. Shi C, Klein AP, Goggins M, Maitra A, Canto M, Ali S, Schulick R, Palmisano E, Hruban RH. Increased prevalence of precursor lesions in familial pancreatic cancer patients. Clin Cancer Res. 2009;15:7737–43.

    Article  CAS  Google Scholar 

  6. Andea A, Sarkar F, Adsay VN. Clinicopathological correlates of pancreatic intraepithelial neoplasia: a comparative analysis of 82 cases with and 152 cases without pancreatic ductal adenocarcinoma. Mod Pathol. 2003;16:996–1006.

    Article  Google Scholar 

  7. Felsenstein M, Hruban RH, Wood LD. New developments in the molecular mechanisms of pancreatic tumorigenesis. Adv Anat Pathol. 2018;25:131–42.

    Article  CAS  Google Scholar 

  8. Furukawa T, Fujisaki R, Yoshida Y, Kanai N, Sunamura M, Abe T, Takeda K, Matsuno S, Horii A. Distinct progression pathways involving the dysfunction of DUSP6/MKP-3 in pancreatic intraepithelial neoplasia and intraductal papillary-mucinous neoplasms of the pancreas. Mod Pathol. 2005;18:1034–42.

    Article  CAS  Google Scholar 

  9. Hosoda W, Chianchiano P, Griffin JF, et al. Genetic analyses of isolated high-grade pancreatic intraepithelial neoplasia (HG-PanIN) reveal paucity of alterations in TP53 and SMAD4. J Pathol. 2017;242:16–23.

    Article  CAS  Google Scholar 

  10. Hata T, Suenaga M, Marchionni L, Macgregor-Das A, Yu J, Shindo K, Tamura K, Hruban RH, Goggins M. Genome-wide somatic copy number alterations and mutations in high-grade pancreatic intraepithelial neoplasia. Am J Pathol. 2018;188:1723–33.

    Article  CAS  Google Scholar 

  11. Hutchings D, Waters KM, Weiss MJ, Wolfgang CL, Makary MA, He J, Cameron JL, Wood LD, Hruban RH. Cancerization of the pancreatic ducts. Am J Surg Pathol. 2018;42:1556–61.

    Article  Google Scholar 

  12. Esposito I, Seiler C, Bergmann F, Kleeff J, Friess H, Schirmacher P. Hypothetical progression model of pancreatic cancer with origin in the centroacinar-acinar compartment. Pancreas. 2007;35:212–7.

    Article  Google Scholar 

  13. Basturk O, Esposito I, Fukushima N, Furukawa T, Hong SM, Klöppel G, Maitra A, Zamboni G. Pancreatic intraductal papillary mucinous neoplasm. In: Digestive system tumours. 5th ed. Lyon: IARC. p. 310–4.

    Google Scholar 

  14. Chang YR, Park JK, Jang J-Y, Kwon W, Yoon JH, Kim S-W. Incidental pancreatic cystic neoplasms in an asymptomatic healthy population of 21,745 individuals. Medicine (Baltimore). 2016;95:e5535. https://doi.org/10.1097/MD.0000000000005535.

    Article  Google Scholar 

  15. Chari ST, Yadav D, Smyrk TC, et al. Study of recurrence after surgical resection of intraductal papillary mucinous neoplasm of the pancreas. Gastroenterology. 2002;123:1500–7.

    Article  Google Scholar 

  16. Shimada K, Sakamoto Y, Sano T, Kosuge T, Hiraoka N. Invasive carcinoma originating in an intraductal papillary mucinous neoplasm of the pancreas: a clinicopathologic comparison with a common type of invasive ductal carcinoma. Pancreas. 2006;32:281–7.

    Article  Google Scholar 

  17. Mino-Kenudson M, Castillo CF, Baba Y, et al. Prognosis of invasive intraductal papillary mucinous neoplasm depends on histological and precursor epithelial subtypes. Gut. 2011;60:1712–20.

    Article  Google Scholar 

  18. Nara S, Shimada K, Kosuge T, Kanai Y, Hiraoka N. Minimally invasive intraductal papillary-mucinous carcinoma of the pancreas: clinicopathologic study of 104 intraductal papillary-mucinous neoplasms. Am J Surg Pathol. 2008;32:243–55.

    Article  Google Scholar 

  19. Baiocchi GL, Portolani N, Missale G, Baronchelli C, Gheza F, Cantù M, Grazioli L, Giulini SM. Intraductal papillary mucinous neoplasm of the pancreas (IPMN): clinico-pathological correlations and surgical indications. World J Surg Oncol. 2010;8:25.

    Article  Google Scholar 

  20. Waters JA, Schmidt CM, Pinchot JW, et al. CT vs MRCP: optimal classification of IPMN type and extent. J Gastrointest Surg. 2008;12:101–9.

    Article  Google Scholar 

  21. Furukawa T, Klöppel G, Volkan Adsay N, et al. Classification of types of intraductal papillary-mucinous neoplasm of the pancreas: a consensus study. Virchows Arch Int J Pathol. 2005;447:794–9.

    Article  Google Scholar 

  22. Yamaguchi H, Kuboki Y, Hatori T, Yamamoto M, Shimizu K, Shiratori K, Shibata N, Shimizu M, Furukawa T. The discrete nature and distinguishing molecular features of pancreatic intraductal tubulopapillary neoplasms and intraductal papillary mucinous neoplasms of the gastric type, pyloric gland variant. J Pathol. 2013;231:335–41.

    Article  CAS  Google Scholar 

  23. Adsay NV, Merati K, Andea A, Sarkar F, Hruban RH, Wilentz RE, Goggins M, Iocobuzio-Donahue C, Longnecker DS, Klimstra DS. The dichotomy in the preinvasive neoplasia to invasive carcinoma sequence in the pancreas: differential expression of MUC1 and MUC2 supports the existence of two separate pathways of carcinogenesis. Mod Pathol. 2002;15:1087–95.

    Article  Google Scholar 

  24. Amato E, dal Molin M, Mafficini A, et al. Targeted next-generation sequencing of cancer genes dissects the molecular profiles of intraductal papillary neoplasms of the pancreas. J Pathol. 2014;233:217–27.

    Article  CAS  Google Scholar 

  25. Kuboki Y, Shimizu K, Hatori T, Yamamoto M, Shibata N, Shiratori K, Furukawa T. Molecular biomarkers for progression of intraductal papillary mucinous neoplasm of the pancreas. Pancreas. 2015;44:227–35.

    Article  CAS  Google Scholar 

  26. Fischer CG, Beleva Guthrie V, Braxton AM, et al. Intraductal papillary mucinous neoplasms arise from multiple independent clones, each with distinct mutations. Gastroenterology. 2019;157:1123–37.e22.

    Article  CAS  Google Scholar 

  27. Kuboki Y, Fischer CG, Guthrie VB, et al. Single-cell sequencing defines genetic heterogeneity in pancreatic cancer precursor lesions. J Pathol. 2019;247:347–56.

    Article  CAS  Google Scholar 

  28. Majumder S, Taylor WR, Yab TC, et al. Novel methylated DNA markers discriminate advanced neoplasia in pancreatic cysts: marker discovery, tissue validation, and cyst fluid testing. Am J Gastroenterol. 2019;114:1539–49.

    Article  Google Scholar 

  29. Basturk O, Chung SM, Hruban RH, et al. Distinct pathways of pathogenesis of intraductal oncocytic papillary neoplasms and intraductal papillary mucinous neoplasms of the pancreas. Virchows Arch Int J Pathol. 2016;469:523–32.

    Article  CAS  Google Scholar 

  30. Basturk O, Tan M, Bhanot U, et al. The oncocytic subtype is genetically distinct from other pancreatic intraductal papillary mucinous neoplasm subtypes. Mod Pathol. 2016;29:1058–69.

    Article  CAS  Google Scholar 

  31. Singhi AD, Wood LD, Parks E, et al. Recurrent rearrangements in PRKACA and PRKACB in intraductal oncocytic papillary neoplasms of the pancreas and bile duct. Gastroenterology. 2020;158:573–82.e2.

    Article  CAS  Google Scholar 

  32. Simon EP, Freije CA, Farber BA, et al. Transcriptomic characterization of fibrolamellar hepatocellular carcinoma. Proc Natl Acad Sci U S A. 2015;112:E5916–25.

    Article  CAS  Google Scholar 

  33. Yamaguchi H, Shimizu M, Ban S, et al. Intraductal tubulopapillary neoplasms of the pancreas distinct from pancreatic intraepithelial neoplasia and intraductal papillary mucinous neoplasms. Am J Surg Pathol. 2009;33:1164–72.

    Article  Google Scholar 

  34. Basturk O, Adsay V, Askan G, et al. Intraductal tubulopapillary neoplasm of the pancreas: a clinicopathoological and immunohistochemicaol analysis of 33 cases. Am J Surg Pathol. 2017;41:313–25.

    Article  Google Scholar 

  35. Basturk O, Berger MF, Yamaguchi H, et al. Pancreatic intraductal tubulopapillary neoplasm is genetically distinct from intraductal papillary mucinous neoplasm and ductal adenocarcinoma. Mod Pathol. 2017;30:1760–72.

    Article  Google Scholar 

  36. Wu J, Jiao Y, Dal Molin M, 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. 2011;108:21188–93.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. INNPATH, Institute of Pathology, University Clinic Innsbruck, Innsbruck, Austria

    Georg Oberhuber

Authors
  1. Georg Oberhuber
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Georg Oberhuber .

Editor information

Editors and Affiliations

  1. Stavanger University Hospital, The University of Bergen, Bergen, Norway

    Kjetil Søreide

  2. Chirurgie (VTT), Innsbruck Medical University, Innsbruck, Tirol, Austria

    Stefan Stättner

Rights and permissions

Reprints and permissions

Copyright information

© 2021 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Oberhuber, G. (2021). Pathobiology of Precursors to Pancreatic Cancer. In: Søreide, K., Stättner, S. (eds) Textbook of Pancreatic Cancer. Springer, Cham. https://doi.org/10.1007/978-3-030-53786-9_15

Download citation

  • DOI: https://doi.org/10.1007/978-3-030-53786-9_15

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-53785-2

  • Online ISBN: 978-3-030-53786-9

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation