Familial Cancer

, Volume 12, Issue 1, pp 89–96

Multiple small “imaging” branch-duct type intraductal papillary mucinous neoplasms (IPMNs) in familial pancreatic cancer: indicator for concomitant high grade pancreatic intraepithelial neoplasia?

  • D. K. Bartsch
  • K. Dietzel
  • M. Bargello
  • E. Matthaei
  • G. Kloeppel
  • I. Esposito
  • J. T. Heverhagen
  • T. M. Gress
  • E. P. Slater
  • P. Langer
Original Article


Most screening programs for familial pancreatic cancer are currently based on endoscopic ultrasonography and/or magnetic resonance imaging (MRI). Cystic lesions, especially those suspicious for small intraductal pancreatic mucinous neoplasms (IPMNs) of the branch ducts, can be visualized in up to 40 % of individuals at risk, but their pathological importance in the setting of FPC is yet not well established. Individuals at risk from a prospective screening program for familial pancreatic cancer with small “imaging” IPMNs of the branch-duct type (BD-IPMN) who underwent pancreatic resection were analysed regarding clinico-pathological data and the locations of pancreatic lesions. Five of 125 individuals at risk who underwent screening had multiple small (size 2–10 mm) unicystic lesions and/or multicystic single lesions in the pancreatic body and tail suspicious for BD-IPMNs upon MRI imaging and decided to undergo surgical resection after interdisciplinary counselling, although none fulfilled the consensus criteria for IPMN resection. Histological examination revealed BD-IPMNs with low or moderate dysplasia of the gastric type in combination with multifocal PanIN2 and PanIN3 lesions in 4 individuals. The remaining patient had only tiny ductectasias in the pancreatic tail with multifocal PanIN 2 lesions in the entire gland and one PanIN3 lesion in the pancreatic head. Intriguingly, the location of the most dysplastic histological lesions (PanIN3) did not correspond to the preoperatively detected lesions and were not visible in preoperative imaging. In the setting of FPC, the presence of multiple small “imaging” BD-IPMNs may indicate the presence of high-grade PanIN lesions elsewhere in the pancreas.


Familial pancreatic cancer IPMN PanIN Screening 


  1. 1.
    Bartsch DK (2003) Familial pancreatic cancer. Br J Surg 90:386–387PubMedCrossRefGoogle Scholar
  2. 2.
    Bartsch DK, Sina-Frey M, Ziegler A, Hahn SA, Pryzpadlo E, Kress R, Gerdes B, Rieder H (2001) Update of familial pancreatic cancer in Germany. Pancreatology 1:510–516PubMedCrossRefGoogle Scholar
  3. 3.
    Hahn SA, Greenhalf B, Ellis I, Sina-Frey M, Rieder H, Korte B, Gerdes B, Kress R, Ziegler A, Raeburn JA, Campra D, Grützmann R, Rehder H, Rothmund M, Schmiegel W, Nepoptolemus JP, Bartsch DK (2003) BRCA2 germline mutations in familial pancreatic carcinoma. J Natl Cancer Inst 95:214–221PubMedCrossRefGoogle Scholar
  4. 4.
    Murphy KM, Brune KA, Griffin C, Sollenberger JE, Petersen GM, Bansal R, Hruban RA, Kern SE (2002) Evaluation of candidate genes MAP2K4, MADH4, ACVR1B, and BRCA2 in familial pancreatic cancer: deleterious BRCA2 mutations in 117 %. Cancer Res 62:3789–3793PubMedGoogle Scholar
  5. 5.
    Jones S, Hruban RH, Kamiyama M, Borges M, Zhang X, Parsons DW, Lin JC, Palmisano E, Brune K, Jaffee EM, Iacobuzio-Donahue CA, Maitra A, Parmigiani G, Kern SE, Velculescu VE, Kinzler KW, Vogelstein B, Eshleman JR, Goggins M, Klein AP (2009) Exomic sequencing identifies PALB2 as a pancreatic cancer susceptibility gene. Science 324:217–220PubMedCrossRefGoogle Scholar
  6. 6.
    Slater EP, Langer P, Niemczyk E, Strauch K, Butler J, Habbe N, Neoplotemos JP, Greenhalf W, Bartsch DK (2010) PALB2 mutations in European familial pancreatic cancer families. Clin Genet 78:490–494PubMedCrossRefGoogle Scholar
  7. 7.
    Roberts NJ, Jiao Y, Yu J, Kopelovich L, Petersen GM, Bondy ML, Gallinger S, Schwartz AG, Syngal S, Cote ML, Axilbund J, Schulick R, Ali SZ, Eshleman JR, Velculescu VE, Goggins M, Vogelstein B, Papadopoulos N, Hruban RH, Kinzler KW, Klein AP (2011) ATM mutations in patients with hereditary pancreatic cancer. Cancer Discov 2:41–46PubMedCrossRefGoogle Scholar
  8. 8.
    Brand RE, Lerch MM, Rubinstein WS, Neoptolemos JP, Whitcomb DC, Hruban RH, Brentnall TA, Lynch HT, Canto MI (2007) Advances in counselling and surveillance of patients at risk for pancreatic cancer. Gut 56:1460–1469PubMedCrossRefGoogle Scholar
  9. 9.
    Canto MI, Harink F, Hruban RH, Offerhaus J, Poley J-W, Fockens P, Kamel IR, Nio CY, Schulick RD, Basel C, Kluijt I, Goggins MG, Bruno MJ (2012) On behalf of the International CAPS Consortium. International consensus recommendations on the management of patients with increased risk for familial pancreatic cancer (Cancer of the Pancreas Screening Consortium (CAPS) 2011 Summit), to be presented at the Digestive Disease Week (DDW), San Diego, California, USA, May 19–May 22Google Scholar
  10. 10.
    Bartsch DK, Gress TM, Langer P (2012) Familial pancreatic cancer-current knowledge. Nat Rev Gastroenenterol Hepatol, ahead of printGoogle Scholar
  11. 11.
    Canto MI, Hruban RH, Fishman EK, Kamel IR, Schulick R, Zhang Z, Topazian M, Takahashi N, Fletcher J, Petersen G, Klein AP, Axilbund J, Griffin C, Syngal S, Saltzman JR, Mortele KJ, Lee J, Tamm E, Vikram R, Bhosale P, Margolis D, Farrell J, Goggins M (2012) American cancer of the pancreas screening (CAPS) consortium. Frequent detection of pancreatic lesions in asymptomatic high-risk individuals. Gastroenterology 142(4):796–804PubMedCrossRefGoogle Scholar
  12. 12.
    Ohashi K, Murakami Y, Takekoshi T (1982) Four cases of mucin-producing cancer of the pancreas on specific findings of the papilla of Vater. Progn Diagn Endosc 20:348–351Google Scholar
  13. 13.
    Tanaka M, Chari S, Adsay V, Fernandez-del Castillo C, Falconi M, Shimizu M, Yamaguchi K, Yamao K, Matsuno S (2006) International consensus guidelines for management of intraductal papillary mucinous neoplas and mucinous cystic neoplasms of the pancreas. Pancreatology 6:17–32PubMedCrossRefGoogle Scholar
  14. 14.
    Bussom S, Saif MW (2010) Intraductal papillary mucinous neoplasia (IPMN). JOP 11:131–134PubMedGoogle Scholar
  15. 15.
    Uehara H, Nakaizumi A, Ishikawa O, Iishi H, Tatsumi K, Takakura R, Ishida T, Takano Y, Tanaka S, Takenaka A (2008) Development of ductal carcinoma of the pancreas during follow-up of branch duct intraductal papillary mucinous neoplasm of the pancreas. Gut 57:1561–1565PubMedCrossRefGoogle Scholar
  16. 16.
    Ingkakul T, Sadakari Y, Ienaga J, Satoh N, Takahata S, Tanaka M (2010) Predictors of the presence of concomitant invasive ductal carcinoma in intraductal. Ann Surg 251:70–75PubMedCrossRefGoogle Scholar
  17. 17.
    Sipos B, Frank S, Gress T, Hahn SA, Klöppel G (2009) Pancreatic intraepithelial neoplaia revisited and updated. Pancreatology 9:45–54PubMedCrossRefGoogle Scholar
  18. 18.
    Bartsch DK, Sina-Frey M, Ziegler A, Hahn SA, Przypadlo E, Kress R, Gerdes B, Rieder H (2001) Update of familial pancreatic cancer in Germany. Pancreatology 1:510–516PubMedCrossRefGoogle Scholar
  19. 19.
    Langer P, Gress TM, Bartsch DK (2010) Pancreatic cancer screening in individuals at risk- too early for a general implementation on a health care basis. Gut 59:1006–1007CrossRefGoogle Scholar
  20. 20.
    Fritz S, Klauss M, Bergmann F, Hackert T, Hartwig W, Strobel O, Bundy BD, Büchler MW, Werner J (2012) Small (Sendai negative) branch-duct IPMNs: not harmless. Ann Surg 256:313–320PubMedCrossRefGoogle Scholar
  21. 21.
    Aichler M, Seiler C, Tost M, Siveke J, Mazur PK, Da Silva-Buttkus P, Bartsch DK, Langer P, Chiblak S, Dürr A, Höfler H, Klöppel G, Müller-Decker K, Brielmeier M, Esposito I (2012) Origin of pancreatic ductal adenocarcinoma from atypical flat lesions: a comparative study in transgenic mice and human tissues. J Pathol 226:723–734PubMedCrossRefGoogle Scholar
  22. 22.
    Schneider R, Slater EP, Sina M, Habbe N, Fendrich V, Matthäi E, Langer P, Bartsch DK (2011) German national case collection for familial pancreatic cancer (FaPaCa) ten years experience. Fam Cancer 10:323–330PubMedCrossRefGoogle Scholar
  23. 23.
    Brune K, Abe T, Canto M, O’Malley L, Klein AP, Maitra A, Volkan Adsay N, Fishman EK, Cameron JL, Yeo CJ, Kern SE, Goggins M, Hruban RH (2006) Multifocal neoplastic precursor lesions associated with lobular atrophy of the pancreas in patients having a strong family history of pancreatic cancer. Am J Surg Path 30:1067–1076PubMedGoogle Scholar
  24. 24.
    Nehra D, Ovaride VM, Mino-Kenudson M, Thayer SP, Ferrone CR, Wargo JA, Muzikansky A, Finkelstein D, Warshaw AL, Castillo F (2012) Intraductal papillary mucinous neoplasms: does a family history of pancreatic cancer matter? Pancreatology 12:358–363PubMedGoogle Scholar
  25. 25.
    Shi C, Goggins M, Maitra A, Canto M, Ali S, Schulick R, Palmisano E, Hruban RH (2009) Increased prevalence of precursor lesions in familial pancreatic cancer patients. Clin Cancer Res 15(24):7737–7743PubMedCrossRefGoogle Scholar
  26. 26.
    Salvia R, Crippa S, Partelli S, Armatura G, Malleo G, Paini M, Pea A, Bassi C (2010) Differences between main-duct and branch-duct intraductal papillary mucinous neoplasms of the pancreas. World J Gastrointest Surg 2:342–346PubMedCrossRefGoogle Scholar
  27. 27.
    Canto MI, Goggins M, Hruban RH, Petersen GM, Giardiello FM, Yeo C, Fishman EK, Brune K, Axilbund J, Griffin C, Ali S, Richman J, Jagannath S, Kantsevoy SV, Kalloo AN (2006) Screening for early pancreatic neoplasia in high-risk individuals: a prospective controlled study. Clin Gastroenterol Hepatol 4:766–781PubMedCrossRefGoogle Scholar
  28. 28.
    Poley JW, Kluijt I, Gouma DJ, Harinck F, Wagner A, Aalfs C, van Eijck CH, Cats A, Kuipers EJ, Nio Y, Fockens P, Bruno MJ (2009) The yield of first-time endoscopic ultrasonography in screening individuals at a high risk of developing pancreatic cancer. Am J Gastroenterol 104:2175–2181PubMedCrossRefGoogle Scholar
  29. 29.
    Verna EC, Hwang C, Stevens PD, Rotterdam H, Stavropoulos SN, Sy CD, Prince MA, Chung WK, Fine RL, Chabot JA, Frucht H (2010) Pancreatic cancer screening in a prospective cohort of high-risk patients: a comprehensive strategy of imaging and genetics. Clin Cancer Res 16:5028–5037PubMedCrossRefGoogle Scholar
  30. 30.
    Al-Sukhni W, Borgida A, Rothenmund H, Holter S, Semotiuk K, Grant R, Wilson S, Moore M, Narod S, Jhaveri K, Haider MA, Gallinger S (2011) Screening for pancreatic cancer in a high-risk cohort: an eight-year experience. J Gastrointest Surg 30 [Epub ahead of print]Google Scholar
  31. 31.
    Vasen HF, Wasser M, van Mil A, Tollenaar RA, Konstantinovski M, Gruis NA, Bergman W, Hes FJ, Hommes DW, Offerhaus GJ, Morreau H, Bonsing BA, de Vos tot Nederveen Cappel WH (2011) Magnetic resonance imaging surveillance detects early-stage pancreatic cancer in carriers of a p16-Leiden mutation. Gastroenterology 140:850–856PubMedCrossRefGoogle Scholar
  32. 32.
    Yachida S, Jones S, Bozic I, Antal T, Leary R, Fu B, Kamiyama M, Hruban RH, Eshleman JR, Nowak MA, Velculescu VE, Kinzler KW, Vogelstein B, Iacobuzio-Donahue CA (2010) Distant metastasis occurs late during the genetic evolution of pancreatic cancer. Nature 467:1114–1147PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2012

Authors and Affiliations

  • D. K. Bartsch
    • 1
  • K. Dietzel
    • 1
  • M. Bargello
    • 1
  • E. Matthaei
    • 1
  • G. Kloeppel
    • 2
  • I. Esposito
    • 2
  • J. T. Heverhagen
    • 3
  • T. M. Gress
    • 4
  • E. P. Slater
    • 1
  • P. Langer
    • 1
  1. 1.Department of Visceral, Thoracic and Vascular SurgeryPhilipps University MarburgMarburgGermany
  2. 2.Institute of PathologyTechnische Universität MünchenMunichGermany
  3. 3.Department of RadiologyPhilipps University MarburgMarburgGermany
  4. 4.Department of Gastroenterology, Endocrinology and InfectologyPhilipps UniversityMarburgGermany

Personalised recommendations