Skip to main content

Advertisement

SpringerLink
Log in

Current concepts in molecular genetics and management guidelines for pancreatic cystic neoplasms: an essential update for radiologists

  • Pictorial essay
  • Published:
Abdominal Radiology Aims and scope Submit manuscript

Abstract

Cystic neoplasms in the pancreas are encountered frequently on imaging, often detected incidentally during evaluation for other conditions. They can have a variety of clinical and imaging presentations, and similarly, wide-ranging prognostic and treatment implications. In the majority, imaging helps in diagnosis of pancreatic cystic neoplasms (PCNs) and guides management decisions. But, a significant minority of the PCNs remain indeterminate. There have been multiple recent advances in biomarkers and molecular genetics which will likely prove helpful in risk stratification of PCNs. Several prominent national and international societies, as well as consensus groups have put forth recommendations to help guide management of PCNs. The purpose of this article is to discuss the role of imaging in evaluation of PCNs, review the recent advances in molecular genetics and pancreatic cyst fluid analysis, and analyze the pros and cons of major evidence-based and consensus guidelines for management of PCNs.

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

Access this article

Log in via an institution

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
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10
Fig. 11
Fig. 12

Similar content being viewed by others

References

  1. Horton K, Laffan TA, Klein AP, et al. (2008) Prevalence of unsuspected pancreatic cysts on MDCT. Am J Roentgenol 191:802–807

    Article  Google Scholar 

  2. Lee KS, Sekhar A, Rofsky NM, Pedrosa I (2010) Prevalence of incidental pancreatic cysts in the adult population on MR imaging. Am J Gastroenterol 105(9):2079–2084

    Article  PubMed  Google Scholar 

  3. de Jong K, Bruno MJ, Fockens P (2012) Epidemiology, diagnosis, and management of cystic lesions of the pancreas. Gastroenterol Res Pract 2012:147465

    PubMed  Google Scholar 

  4. Kosmahl M, Pauser U, Peters K, et al. (2004) Cystic neoplasms of the pancreas and tumor-like lesions with cystic features: a review of 418 cases and a classification proposal. Virchows Arch 445(2):168–178

    Article  PubMed  CAS  Google Scholar 

  5. Brugge WR, Lewandrowski K, Lee-Lewandrowski E, et al. (2004) Diagnosis of pancreatic cystic neoplasms: a report of the cooperative pancreatic cyst study. Gastroenterology 126(5):1330–1336

    Article  PubMed  Google Scholar 

  6. Centeno BA, Warshaw AL, Mayo-Smith W, Southern JF, Lewandrowski K (1997) Cytologic diagnosis of pancreatic cystic lesions. Acta Cytol 41(4):972–980

    Article  PubMed  CAS  Google Scholar 

  7. Sahani DV, Kambadakone A, Macari M, et al. (2013) Diagnosis and management of cystic pancreatic lesions. Am J Roentgenol 200(2):343–354

    Article  Google Scholar 

  8. Procacci C, Carbognin G, Accordini S, et al. (2001) CT features of malignant mucinous cystic tumors of the pancreas. Eur Radiol 11(9):1626–1630

    Article  PubMed  CAS  Google Scholar 

  9. Sidden CR, Mortele KJ (2007) Cystic tumors of the pancreas: ultrasound, computed tomography, and magnetic resonance imaging features. Sem Ultrasound CT MRI 28:339–356

    Article  Google Scholar 

  10. O’Malley ME, Boland GW, Wood BJ, et al. (1999) Adenocarcinoma of the head of the pancreas: determination of surgical unresectability with thin-section pancreatic-phase helical CT. AJR Am J Roentgenol 173(6):1513–1518

    Article  PubMed  Google Scholar 

  11. Tamm EP, Silverman PM, Charnsangavej C, Evans DB (2003) Diagnosis, staging, and surveillance of pancreatic cancer. AJR Am J Roentgenol 180(5):1311–1323

    Article  PubMed  Google Scholar 

  12. Lee HJ, Kim MJ, Choi JY, et al. (2011) Relative accuracy of CT and MRI in the differentiation of benign from malignant pancreatic cystic lesions. Clin Radiol 66(4):315–321

    Article  PubMed  Google Scholar 

  13. Sahani DV, Sainani NI, Blake MA, et al. (2011) Prospective evaluation of reader performance on MDCT in characterization of cystic pancreatic lesions and prediction of cyst biologic aggressiveness. Am J Roentgenol 197(1):W53–W61

    Article  Google Scholar 

  14. Sahani DV, Kadavigere R, Saokar A, et al. (2005) Cystic pancreatic lesions: a simple imaging-based classification system for guiding management. Radiographics 25:1471–1484

    Article  PubMed  Google Scholar 

  15. Lin X-Z, Wu Z-Y, Li W-X, et al. (2014) Differential diagnosis of pancreatic serous oligocystic adenoma and mucinous cystic neoplasm with spectral CT imaging: Initial results. Clin Radiol 69(10):1004–1010

    Article  PubMed  Google Scholar 

  16. Girometti R, Intini S, Brondani G, et al. (2011) Incidental pancreatic cysts on 3D turbo spin echo magnetic resonance cholangiopancreatography: prevalence and relation with clinical and imaging features. Abdom Imaging 36(2):196–205

    Article  PubMed  Google Scholar 

  17. Visser BC, Yeh BM, Qayyum A, et al. (2007) Characterization of cystic pancreatic masses: relative accuracy of CT and MRI. Am J Roentgenol 189:648–656

    Article  Google Scholar 

  18. Sahani DV, Kambadakone A, Macari M, et al. (2013) Diagnosis and management of cystic pancreatic lesions. Am J Roentgenol 200:343–354

    Article  Google Scholar 

  19. Tirkes T, Aisen AM, Cramer HM, et al. (2014) Cystic neoplasms of the pancreas: findings on magnetic resonance imaging with pathological, surgical, and clinical correlation. Abdom Imaging 39(5):1088–1101

    Article  PubMed  Google Scholar 

  20. Sedlack R, Affi A, Vazquez-Sequeiros E, et al. (2002) Utility of EUS in the evaluation of cystic pancreatic lesions. Gastrointest Endosc 56(4):543–547

    Article  PubMed  Google Scholar 

  21. Kim JH, Eun HW, Park H-J, Hong SS, Kim YJ (2012) Diagnostic performance of MRI and EUS in the differentiation of benign from malignant pancreatic cyst and cyst communication with the main duct. Eur J Radiol 81(11):2927–2935

    Article  PubMed  Google Scholar 

  22. McAuley G, Delaney H, Colville J, et al. (2005) Multimodality preoperative imaging of pancreatic insulinomas. Clin Radiol 60(10):1039–1050

    Article  PubMed  CAS  Google Scholar 

  23. Polkowski M, Larghi A, Weynand B, et al. (2012) Learning, techniques, and complications of endoscopic ultrasound (EUS)-guided sampling in gastroenterology: European Society of Gastrointestinal Endoscopy (ESGE) technical guideline. Endoscopy 44(2):190–206

    Article  PubMed  CAS  Google Scholar 

  24. Kim E, Telford JJ (2009) Endoscopic ultrasound advances, part 1: diagnosis. Can J Gastroenterol 23(9):594–601

    Article  PubMed  PubMed Central  Google Scholar 

  25. Tseng JF, Warshaw AL, Sahani DV, et al. (2005) Serous cystadenoma of the pancreas: tumor growth rates and recommendations for treatment. Ann Surg 242(3):413–419; discussion 419–21

  26. Ketwaroo GA, Mortele KJ, Sawhney MS (2016) Pancreatic cystic neoplasms: an update. Gastroenterol Clin North Am 45(1):67–81

    Article  PubMed  Google Scholar 

  27. Sarr MG, Murr M, Smyrk TC, et al. (2003) Primary cystic neoplasms of the pancreas. Neoplastic disorders of emerging importance-current state-of-the-art and unanswered questions. J Gastrointest Surg 7(3):417–428

    Article  PubMed  Google Scholar 

  28. Hamilton SR, Aaltonen LA (2000) Pathology and genetics of tumours of the digestive system. Lyon, Oxford: IARC Press, Oxford University Press [distributor]

    Google Scholar 

  29. Singhi AD, Nikiforova MN, Fasanella KE, et al. (2014) Preoperative GNAS and KRAS testing in the diagnosis of pancreatic mucinous cysts. Clin Cancer Res 20(16):4381–4389

    Article  PubMed  CAS  Google Scholar 

  30. Singhi AD, Zeh HJ, Brand RE, et al. (2016) American Gastroenterological Association guidelines are inaccurate in detecting pancreatic cysts with advanced neoplasia: a clinicopathologic study of 225 patients with supporting molecular data. Gastrointestinal endoscopy 83(6):1107.e2–1117.e2

    Google Scholar 

  31. Wu J, Jiao Y, Dal Molin M, et al. (2011) Whole-exome sequencing of neoplastic cysts of the pancreas reveals recurrent mutations in components of ubiquitin-dependent pathways. Proc Natl Acad Sci USA 108(52):21188–21193

    Article  PubMed  Google Scholar 

  32. Springer S, Wang Y, Dal Molin M, et al. (2015) A combination of molecular markers and clinical features improve the classification of pancreatic cysts. Gastroenterology 149(6):1501–1510

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  33. Theisen BK, Wald AI, Singhi AD (2016) Molecular diagnostics in the evaluation of pancreatic cysts. Surg Pathol Clin 9(3):441–456

    Article  PubMed  Google Scholar 

  34. Stark A, Donahue TR, Reber HA, Hines OJ (2016) Pancreatic cyst disease: a review. JAMA 315(17):1882–1893

    Article  PubMed  CAS  Google Scholar 

  35. Park JW, Jang JY, Kang MJ, et al. (2014) Mucinous cystic neoplasm of the pancreas: is surgical resection recommended for all surgically fit patients? Pancreatology 14(2):131–136

    Article  PubMed  Google Scholar 

  36. Goh BK, Tan YM, Chung YF, et al. (2006) A review of mucinous cystic neoplasms of the pancreas defined by ovarian-type stroma: clinicopathological features of 344 patients. World J Surg 30(12):2236–2245

    Article  PubMed  Google Scholar 

  37. Sakorafas GH, Smyrniotis V, Reid-Lombardo KM, Sarr MG (2011) Primary pancreatic cystic neoplasms revisited: Part II. Mucinous cystic neoplasms. Surg Oncol 20(2):e93–e101

    Article  PubMed  Google Scholar 

  38. Kalb B, Sarmiento JM, Kooby DA, Adsay NV, Martin DR (2009) MR imaging of cystic lesions of the pancreas. Radiographics 29(6):1749–1765

    Article  PubMed  Google Scholar 

  39. Lv P, Mahyoub R, Lin X, et al. (2011) Differentiating pancreatic ductal adenocarcinoma from pancreatic serous cystadenoma, mucinous cystadenoma, and a pseudocyst with detailed analysis of cystic features on CT scans: a preliminary study. Korean J Radiol 12(2):187–195

    Article  PubMed  PubMed Central  Google Scholar 

  40. Rockacy M, Khalid A (2013) Update on pancreatic cyst fluid analysis. Ann Gastroenterol 26:122–127

    PubMed  PubMed Central  Google Scholar 

  41. Nikiforova MN, Khalid A, Fasanella KE, et al. (2013) Integration of KRAS testing in the diagnosis of pancreatic cystic lesions: a clinical experience of 618 pancreatic cysts. Mod Pathol 26(11):1478–1487

    Article  PubMed  CAS  Google Scholar 

  42. Jimenez RE, Warshaw AL, Z’graggen K, et al. (1999) Sequential accumulation of K-ras mutations and p53 overexpression in the progression of pancreatic mucinous cystic neoplasms to malignancy, Ann Surg 230(4):501–509; discussion 509–11

  43. Reid SB, Saka B, Balci M (2014) Molecular genetics of pancreatic neoplasms and their morphologic correlates: an update on recent advances and potential diagnostic applications. Am J Clin Pathol 141(2):168–180

    Article  PubMed  CAS  Google Scholar 

  44. Farrell JJ (2015) Prevalence, diagnosis and management of pancreatic cystic neoplasms: current status and future directions. Gut Liver 9(5):571–589

    Article  PubMed  PubMed Central  Google Scholar 

  45. Rezaee N, Barbon C, Zaki A, et al. (2016) Intraductal papillary mucinous neoplasm (IPMN) with high-grade dysplasia is a risk factor for the subsequent development of pancreatic ductal adenocarcinoma. HPB 18(3):236–246

    Article  PubMed  Google Scholar 

  46. Kawamoto S, Horton KM, Lawler LP, et al. (2005) Intraductal papillary mucinous neoplasm of the pancreas: can benign lesions be differentiated from malignant lesions with multidetector CT? Radiographics 25(6):1451–1468; discussion 1468–70

  47. Waters JA, Schmidt CM, Pinchot JW, et al. (2008) CT vs MRCP: optimal classification of IPMN type and extent. J Gastrointest Surg 12(1):101–109

    Article  PubMed  Google Scholar 

  48. Salvia R, Crippa S, Partelli S, et al. (2010) Differences between main-duct and branch-duct intraductal papillary mucinous neoplasms of the pancreas. World J Gastrointest Surg 2(10):342–346

    Article  PubMed  PubMed Central  Google Scholar 

  49. Tanaka M, Fernández-del Castillo C, Kamisawa T, et al. (2017) Revisions of international consensus Fukuoka guidelines for the management of IPMN of the pancreas. Pancreatology 17(5):738–753

    Article  PubMed  Google Scholar 

  50. Remotti HE, Winner M, Saif MW (2012) Intraductal papillary mucinous neoplasms of the pancreas: clinical surveillance and malignant progression, multifocality and implications of a field-defect. JOP J Pancreas 13(2):135–138

    Google Scholar 

  51. Khalid A, Zahid M, Finkelstein SD, et al. (2009) Pancreatic cyst fluid DNA analysis in evaluating pancreatic cysts: a report of the PANDA study. Gastrointest Endosc 69(6):1095–1102

    Article  PubMed  Google Scholar 

  52. Brugge WR, Lewandrowski K, Lee-Lewandrowski E, et al. (2004) Diagnosis of pancreatic cystic neoplasms: a report of the cooperative pancreatic cyst study. Gastroenterology 126(5):1330–1336

    Article  PubMed  Google Scholar 

  53. Distler M, Kersting S, Niedergethmann M, et al. (2013) Pathohistological subtype predicts survival in patients with intraductal papillary mucinous neoplasm (IPMN) of the pancreas. Ann Surg 258(2):324–330

    Article  PubMed  Google Scholar 

  54. Wu J, Matthaei H, Maitra A, et al. (2011) Recurrent GNAS mutations define an unexpected pathway for pancreatic cyst development. Sci Transl Med 3(92):92ra66

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  55. Paini M, Crippa S, Partelli S, et al. (2014) Molecular pathology of intraductal papillary mucinous neoplasms of the pancreas. World J Gastroenterol 20(29):10008–10023

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  56. Kanda M, Sadakari Y, Borges M, et al. (2013) Mutant TP53 in duodenal samples of pancreatic juice from patients with pancreatic cancer or high-grade dysplasia. Clin Gastroenterol Hepatol 11(6):719.e5–730.e5

    Article  CAS  Google Scholar 

  57. Hackeng WM, Hruban RH, Offerhaus GJ, Brosens LA (2016) Surgical and molecular pathology of pancreatic neoplasms. Diagn Pathol 11(1):47

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  58. Law JK, Ahmed A, Singh VK, et al. (2014) A systematic review of solid-pseudopapillary neoplasms: are these rare lesions? Pancreas 43(3):331–337

    Article  PubMed  PubMed Central  Google Scholar 

  59. Park MJ, Lee JH, Kim JK, et al. (2014) Multidetector CT imaging features of solid pseudopapillary tumours of the pancreas in male patients: distinctive imaging features with female patients. Br J Radiol 87(1035):20130513

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  60. Sur YK, Lee JH, Kim JK, et al. (2015) Comparison of MR imaging features of solid pseudopapillary neoplasm of pancreas between male and female patients. Eur J Radiol 84(11):2065–2070

    Article  PubMed  Google Scholar 

  61. Ventriglia A, Manfredi R, Mehrabi S, et al. (2014) MRI features of solid pseudopapillary neoplasm of the pancreas. Abdom Imaging 39(6):1213–1220

    Article  PubMed  Google Scholar 

  62. Singhi AD, Nikiforova MN, McGrath K (2017) DNA testing of pancreatic cyst fluid: is it ready for prime time? Lancet Gastroenterol Hepatol 2(1):63–72

    Article  PubMed  Google Scholar 

  63. Singhi AD, Chu LC, Tatsas AD, et al. (2012) Cystic pancreatic neuroendocrine tumors: a clinicopathologic study. Am J Surg Pathol 36(11):1666–1673

    Article  PubMed  Google Scholar 

  64. Baker MS, Knuth JL, DeWitt J, et al. (2008) Pancreatic cystic neuroendocrine tumors: preoperative diagnosis with endoscopic ultrasound and fine-needle immunocytology. J Gastrointest Surg 12(3):450–456

    Article  PubMed  Google Scholar 

  65. Kawamoto S, Johnson PT, Shi C, et al. (2013) Pancreatic neuroendocrine tumor with cystlike changes: evaluation with MDCT. AJR Am J Roentgenol 200(3):W283–W290

    Article  PubMed  PubMed Central  Google Scholar 

  66. Singhi AD, Liu T-C, Roncaioli JL, et al. (2017) Alternative lengthening of telomeres and loss of DAXX/ATRX expression predicts metastatic disease and poor survival in patients with pancreatic neuroendocrine tumors. Clin Cancer Res 23(2):600–609

    Article  PubMed  CAS  Google Scholar 

  67. Thoeni RF (2012) The revised Atlanta classification of acute pancreatitis: its importance for the radiologist and its effect on treatment. Radiology 262(3):751–764

    Article  PubMed  Google Scholar 

  68. Banks PA, Bollen TL, Dervenis C, et al. (2013) Classification of acute pancreatitis—2012: revision of the Atlanta classification and definitions by international consensus. Gut 62(1):102–111

    Article  PubMed  Google Scholar 

  69. Correa-Gallego C, Ferrone CR, Thayer SP, et al. (2010) Castillo, incidental pancreatic cysts: do we really know what we are watching? Pancreatology 10(2–3):144–150

    Article  PubMed  PubMed Central  Google Scholar 

  70. Garcia-Carracedo D, Chen ZM, Qiu W, et al. (2014) PIK3CA mutations in mucinous cystic neoplasms of the pancreas. Pancreas 43(2):245–249

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  71. Garcia-Carracedo D, Turk AT, Fine SA, et al. (2013) Loss of PTEN expression is associated with poor prognosis in patients with intraductal papillary mucinous neoplasms of the pancreas. Clin Cancer Res 19(24):6830–6841

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  72. Rachagani S, Macha MA, Heimann N, et al. (2015) Clinical implications of miRNAs in the pathogenesis, diagnosis and therapy of pancreatic cancer. Adv Drug Deliv Rev 81:16–33

    Article  PubMed  CAS  Google Scholar 

  73. Berland LL, Silverman SG, Megibow AJ, Mayo-Smith WW (2014) ACR members’ response to JACR white paper on the management of incidental abdominal CT findings. J Am Coll Radiol 11(1):30–35

    Article  PubMed  Google Scholar 

  74. Megibow AJ, Baker ME, Morgan DE, et al. (2017) Management of incidental pancreatic cysts: a white paper of the ACR Incidental Findings Committee. J Am Coll Radiol 14(7):911–923

    Article  PubMed  Google Scholar 

  75. Berland LL, Silverman SG (2010) Managing incidental findings on abdominal CT: white paper of the ACR Incidental Findings Committee. J Am Coll Radiol 7:754–773

    Article  PubMed  Google Scholar 

  76. Vege SS, Ziring B, Jain R (2015) American Gastroenterological Association Institute guidelines for management of asymptomatic neoplastic pancreatic cysts. Gastroenterology 148(4):819–822

    Article  PubMed  Google Scholar 

  77. Brook OR, Beddy P (2016) Delayed growth in incidental pancreatic cysts: are the current american college of radiology recommendations for follow-up appropriate? Radiology 278(3):752–761

    Article  PubMed  Google Scholar 

  78. Fernández-del Castillo C, Tanaka M, Adsay V, et al. (2012) International Consensus Guidelines 2012 for the management of IPMN and MCN of the pancreas. Pancreatology 12:183–197

    Article  Google Scholar 

  79. Goh BK, Lin Z, Tan DM, et al. (2015) Evaluation of the Fukuoka Consensus Guidelines for intraductal papillary mucinous neoplasms of the pancreas: results from a systematic review of 1,382 surgically resected patients. Surgery 158(5):1192–1202

    Article  PubMed  Google Scholar 

  80. Taffurelli G, Ricci C, Pacilio CA, et al. (2015) Branch duct intraductal papillary mucinous neoplasm: validation of Fukuoka 2012 guidelines using a systematic review and meta-analysis. Pancreatology 3(15):S39

    Article  Google Scholar 

  81. Miyasaka Y, Ohtsuka T, Tamura K, et al. (2016) Predictive factors for the metachronous development of high-risk lesions in the remnant pancreas after partial pancreatectomy for intraductal papillary mucinous neoplasm. Ann Surg 263(6):1180–1187

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Radiology, University of Pittsburgh Medical Center, Radiology Suite 200 East Wing E2051B, 200 Lothrop Street, Pittsburgh, PA, 15213, USA

    Matthew Kulzer, Alessandro Furlan, Matthew T. Heller & Anil K. Dasyam

  2. Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA

    Aatur D. Singhi

  3. Department of Radiology, University of Texas at San Antonio, San Antonio, TX, USA

    Venkata S. Katabathina

  4. Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA, USA

    Kevin M. Mcgrath

  5. Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA, USA

    Herbert J. Zeh & Amer Zureikat

Authors
  1. Matthew Kulzer
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Aatur D. Singhi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Alessandro Furlan
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Matthew T. Heller
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Venkata S. Katabathina
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Kevin M. Mcgrath
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Herbert J. Zeh
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Amer Zureikat
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Anil K. Dasyam
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Anil K. Dasyam.

Ethics declarations

Funding

No funding was received for this study.

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

This review article does not contain any studies with human participants or animals performed by any of the authors.

Informed consent

Statement of informed consent was not applicable to this review article since the manuscript does not contain any patient data.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kulzer, M., Singhi, A.D., Furlan, A. et al. Current concepts in molecular genetics and management guidelines for pancreatic cystic neoplasms: an essential update for radiologists. Abdom Radiol 43, 2351–2368 (2018). https://doi.org/10.1007/s00261-017-1452-5

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00261-017-1452-5

Keywords

Search

Navigation