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

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Abstract

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.

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References

  1. Bartsch DK (2003) Familial pancreatic cancer. Br J Surg 90:386–387

    Article  PubMed  CAS  Google Scholar 

  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 1:510–516

    Article  PubMed  CAS  Google Scholar 

  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 95:214–221

    Article  PubMed  CAS  Google Scholar 

  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 62:3789–3793

    PubMed  CAS  Google Scholar 

  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 324:217–220

    Article  PubMed  CAS  Google Scholar 

  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 78:490–494

    Article  PubMed  CAS  Google Scholar 

  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 2:41–46

    Article  PubMed  Google Scholar 

  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 56:1460–1469

    Article  PubMed  Google Scholar 

  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 22

  10. Bartsch DK, Gress TM, Langer P (2012) Familial pancreatic cancer-current knowledge. Nat Rev Gastroenenterol Hepatol, ahead of print

  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):796–804

    Article  PubMed  Google Scholar 

  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 20:348–351

    Google Scholar 

  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 6:17–32

    Article  PubMed  Google Scholar 

  14. Bussom S, Saif MW (2010) Intraductal papillary mucinous neoplasia (IPMN). JOP 11:131–134

    PubMed  Google Scholar 

  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 57:1561–1565

    Article  PubMed  CAS  Google Scholar 

  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 251:70–75

    Article  PubMed  Google Scholar 

  17. Sipos B, Frank S, Gress T, Hahn SA, Klöppel G (2009) Pancreatic intraepithelial neoplaia revisited and updated. Pancreatology 9:45–54

    Article  PubMed  CAS  Google Scholar 

  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 1:510–516

    Article  PubMed  CAS  Google Scholar 

  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 59:1006–1007

    Article  Google Scholar 

  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 256:313–320

    Article  PubMed  Google Scholar 

  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 226:723–734

    Article  PubMed  CAS  Google Scholar 

  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 10:323–330

    Article  PubMed  Google Scholar 

  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 30:1067–1076

    PubMed  Google Scholar 

  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 12:358–363

    PubMed  Google Scholar 

  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):7737–7743

    Article  PubMed  CAS  Google Scholar 

  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 2:342–346

    Article  PubMed  Google Scholar 

  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 4:766–781

    Article  PubMed  Google Scholar 

  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 104:2175–2181

    Article  PubMed  CAS  Google Scholar 

  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 16:5028–5037

    Article  PubMed  Google Scholar 

  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]

  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 140:850–856

    Article  PubMed  CAS  Google Scholar 

  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 467:1114–1147

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

We would like to thank all individuals who participated in the study. Supported by the Deutsche Krebshilfe (107259 to D.K.B and P.L).

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Authors and Affiliations

  1. Department of Visceral, Thoracic and Vascular Surgery, Philipps University Marburg, Baldingerstrasse, 35033, Marburg, Germany

    D. K. Bartsch, K. Dietzel, M. Bargello, E. Matthaei, E. P. Slater & P. Langer

  2. Institute of Pathology, Technische Universität München, Munich, Germany

    G. Kloeppel & I. Esposito

  3. Department of Radiology, Philipps University Marburg, Marburg, Germany

    J. T. Heverhagen

  4. Department of Gastroenterology, Endocrinology and Infectology, Philipps University, Marburg, Germany

    T. M. Gress

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  1. D. K. Bartsch
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Correspondence to D. K. Bartsch.

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Bartsch, D.K., Dietzel, K., Bargello, M. et al. Multiple small “imaging” branch-duct type intraductal papillary mucinous neoplasms (IPMNs) in familial pancreatic cancer: indicator for concomitant high grade pancreatic intraepithelial neoplasia?. Familial Cancer 12, 89–96 (2013). https://doi.org/10.1007/s10689-012-9582-y

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