Year 2017 / Volume 109 / Number 5
Review
Intraductal papillary mucinous neoplasms and mucinous cystadenomas: current status and recommendations

358-367

DOI: 10.17235/reed.2017.4630/2016

Maria Moris, Michael B. Wallace,

Abstract
The real prevalence of pancreatic cystic lesions remains unknown. The malignant potential of some of these lesions remains a cause for significant concern. Thus, it is mandatory to develop a strategy to clearly discriminate those cysts with a potential for malignant transformation from those that do not carry any significant risk. Intraductal papillary mucinous neoplasms and mucinous cystadenomas are mucinous cystic neoplasms with a known malignant potential that have gained greater recognition in recent years. However, despite the numerous studies that have been carried out, their differential diagnosis among other cysts subtypes and their therapeutic approach continue to be a challenge for clinicians. This review contains a critical approach of the current recommendations and management strategies regarding intraductal papillary mucinous neoplasms and mucinous cystadenomas, as well as highlighting the limitations exposed in current guidelines.
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References
1- Kimura W, Nagai H, Kuroda A, et al. Analysis of small cystic lesions of the pancreas. Int J Pancreatol 1995;18:197-206.
2- Zhang XM, Mitchell DG, Dohke M, et al. Pancreatic cysts: depiction on single-shot fast spin-echo MR images. Radiology 2002;223:547-553.
3- Spinelli KS, Fromwiller TE, Daniel RA, et al. Cystic pancreatic neoplasms: observe or operate. Ann Surg 2004;239:651-657.
4- Girometti R, Intini S, Brondani G, et al. Incidental pancreatic cysts on 3D turbo spin echo magnetic resonance cholangiopancreatography: prevalence and relation with clinical and imaging features. Abdom Imaging 2011;36:196-205.
5- Gaujoux S, Brennan MF, Gonen M, et al. Cystic lesions of the pancreas: changes in the presentation and management of 1,424 patients at a single institution over a 15-year time period. J Am Coll Surg 2011;212:590-600.
6- Chung JW, Chung MJ, Park JY, et al. Clinicopathologic features and outcomes of pancreatic cysts during a 12-year period. Pancreas 2013;42:230-238
7- Freeny PC, Saunders MD. Moving beyond morphology: new insights into the characterization and management of cystic pancreatic lesions. Radiology 2014;272:345-363.
8- Moris M, Bridges MD, Pooley RA, et al. Association Between Advances in High-Resolution Cross-Section Imaging Technologies and Increase in Prevalence of Pancreatic Cysts From 2005 to 2014. Clin Gastroenterol Hepatol. 2016;14:585-593.
9- Hoffman RL, Gates JL, Kochman ML, et al. Analysis of cyst size and tumor markers in the management of pancreatic cysts: support for the original Sendai criteria. J Am Coll Surg. 2015;220:1087-1095.
10- Munigala, Gelrud, Agarwal. Risk of pancreatic cancer in patients with pancreatic cyst. Gastrointest Endosc. 2016 Jul;84:81-86
11- Kimura W, Moriya T, Hirai I, Hanada K, Abe H, Yanagisawa A, Fukushima N, Ohike N, Shimizu M, Hatori T, Fujita N, Maguchi H, Shimizu Y, Yamao K, Sasaki T, Naito Y, Tanno S, Tobita K, Tanaka M. Multicenter study of serous cystic neoplasm of the Japan pancreas society. Pancreas 2012;41:380-387.
12- Das A, Wells CD, Nguyen CC. Incidental cystic neoplasms of pancreas: what is the optimal interval of imaging surveillance? Am J Gastroenterol 2008;103:1657-1662.
13- Yamao K, Yanagisawa A, Takahashi K, et al. Clinicopathological features and prognosis of mucinous cystic neoplasm with ovarian-type stroma: a multi-institutional study of the Japan pancreas society. Pancreas 2011;40:67-71.
14- Wu BU, Sampath K, Berberian CE, et al. Prediction of malignancy in cystic neo-plasms of the pancreas: a population-based cohort study. Am J Gastroenterology 2014;109:121–129.
15- Broughton J, Lipschitz J, Cantor M ,et al. Determining the natural history of pancreatic cystic neoplasms: a Manitoban cohort study. HPB (Oxford). 2016;18:383-388
16- Ohashi K, Tajiri H, Gondo M, et al. A case of cystadenocarcinoma of the pancreas forming bilio-pancreatic fistula. Prog Dig Endosc 1980;17:261–264.
17- Kloppel G, Solcia E, Longnecker DS, et al. Histological typing of tumours of the exocrine pancreas, 2nd ed. World Health Organization: international histological classification of tumours. Berlin: Springer-Verlag; 1996.
18- Farrell JJ, Brugge WR. Intraductal papillary mucinous tumor of the pancreas. Gastrointest Endosc. 2002;55:701-714
19- Kang MJ, Lee KB, Jang JY, et al. Disease spectrum of intraductal papillary mucinous neoplasm with an associated invasive carcinoma invasive IPMN versus pancreatic ductal adenocarcinoma-associated IPMN. Pancreas 2013;42:1267-1274.
20- Lafemina J, Katabi N, Klimstra D, et al. Malignant progression in IPMN: a cohortanalysis of patients initially selected for resection or observation. Annals of Surgical Oncology 2013;20:440–447.
21- Ogura T, Masuda D, Kurisu Y, et al. Potential predictors of disease progression formain-duct intraductal papillary mucinous neoplasms of the pancreas. Journal of Gastroenterology and Hepatology 2013;28:1782–1786.
22- Marchegiani G, Mino-Kenudson M, Sahora K, et al. IPMN involving the main pancreatic duct: biology epidemiology, and long-term outcomes following resection. Annals of Surgery 2015;261:976-983.
23- Nagata N, Kawazoe A, Mishima S, et al. Development of Pancreatic Cancer, Disease-specific Mortality, and All-Cause Mortality in Patients with Nonresected IPMNs: A Long-term Cohort Study. Radiology. 2016;278:125-134.
24- Tanaka M, Fernandez-del Castillo C, Adsay V, et al. International consensus guidelines 2012 for the management of IPMN and MCN of the pancreas. Pancreatology 2012;12:183–197.
25- Tanaka M. Intraductal papillary mucinous neoplasms of the pancreas. Pancreas. 2014;43:1136-1140.
26- Sawai Y, Yamao K, Bhatia V, et al. Development of pancreatic cancers during long-term follow-up of side-branch intraductal papillary mucinous neoplasms. Endoscopy 2010;42: 1077-1084.
27- Maguchi H, Tanno S, Mizuno N, et al. Natural history of branch duct intraductal papillary mucinous neoplasms of the pancreas: A multicenter study in japan. Pancreas 2011;40:364-370.
28- Khannoussi W, Vullierme MP, Rebours V, et al. The long term risk of malignancy in patients with branch duct intraductal papillary mucinous neoplasms of the pancreas. Pancreatology 2012;12:198-202.
29- Malleo G, Marchegiani G, Borin A, et al. Observational study of the incidence of pancreatic and extrapancreatic malignancies during surveillance of patients with branch-duct intraductal papillary mucinous neoplasm. Ann Surg 2015;261:984-990.
30- Mino-Kenudson M, Fernández-del Castillo C, Baba Y, et al. Prognosis of invasive intraductal papillary mucinous neoplasm depends on histological and precursor epithelial subtypes. Gut 2011;60:1712–1720.
31- Nakata K, Ohuchida K, Aishima S, et al. Invasive carcinoma derived from intestinal-type intraductal papillary mucinous neoplasm is associated with minimal invasion, colloid carcinoma, and less invasive behavior, leading to a better prognosis. Pancreas 2011;40:581–587.
32- Sohn TA, Yeo CJ, Cameron JL, et al. Intraductal papillary mucinous neoplasmsof the pancreas: an updated experience. Annals of Surgery 2004;239:788–797.
33- Khalid A, Brugge W. ACG practice guidelines for the diagnosis and management of neoplastic pancreatic cysts. American Journal of Gastroenterology 2007;102:2339–2349.
34- Sahani DV, Lin DJ, Venkatesan AM, et al. Multidisciplinary approach to diagnosis and management of intraductal papillary mucinous neoplasms of the pancreas. Clin Gastroenterol Hepatol. 2009;7:259-269.
35- Kitagawa Y, Unger TA, Taylor S, et al. Mucus is a predictor of better prognosis and survival in patients with intraductal papillary mucinous tumor of the pancreas. J Gastrointest Surg 2003;7:12-18.
36- Telford JJ, Carr-Locke DL. The role of ERCP and pancreatoscopy in cystic and intraductal tumors. Gastrointest Endosc Clin N Am 2002;12:747-757.
37- Kanda M, Sadakari Y, Borges M, et al. Mutant TP53 in duodenal samples of pancreatic juice from patients with pancreatic cancer or high-grade dysplasia. Clin Gastroenterol Hepatol 2013;11:719-730.
38- Xiao HD, Yamaguchi H, Dias-Santagata D, et al. Molecular char¬acteristics and biological behaviours of the oncocytic and pancre¬atobiliary subtypes of intraductal papillary mucinous neoplasms. J Pathol 2011;224:508-516.
39- Hong SM, Vincent A, Kanda M, et al. Genome-wide somatic copy number alterations in low-grade PanINs and IPMNs from indi¬viduals with a family history of pancreatic cancer. Clin Cancer Res 2012;18:4303-4312.
40- 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;108:21188-21193.
41- Matthaei H, Norris AL, Tsiatis AC, et al. Clinicopathological characteristics and molecular analyses of multifocal intraductal papillary mucinous neoplasms of the pancreas. Ann Surg 2012;255:326-333.
42- Dal Molin M, Matthaei H, Wu J, et al. Clinicopathological corre¬lates of activating GNAS mutations in intraductal papillary muci¬nous neoplasm (IPMN) of the pancreas. Ann Surg Oncol 2013;20: 3802-3808.
43- Sahora K, Mino-Kenudson M, Brugge W, et al. Branch duct intraductal papillary mucinous neoplasms does cyst size change the tip of the scale? A critical analysis of the revised international consensus guidelines in a large singke-instituttional series. Ann Surg 2013;258:446-475.
44- Lawson RD, Hunt GC, Giap AQ, et al. Pancreatic cysts suspected to be branch duct intraductal papillary mucinous neoplasm without concerning features have low risk for development of pancreatic cancer. Ann Gastroenterol. 2015;28:487-494.
45- Valsangkar NP, Morales-Oyarvide V, Thayer SP, et al. 851 resected cystic tumors of the pancreas: a 33-year experience at the Massachusetts General Hospital. Surgery. 2012;152:S4-12.
46- Baker ML, Seeley ES, Pai R, et al. Invasive mucinous cystic neoplasms of the pancreas. Exp Mol Pathol 2012;93:345-349.
47- Sarr MG, Carpenter HA, Prabhakar LP, et al. Clinical and pathologic correlation of 84 mucinous cystic neoplasms of the pancreas: can one reliably differentiate benign from malignant (or premalignant) neoplasms? Ann Surg. 2000;231:205-212.
48- Barral M, Soyer P, Dohan A, et al. Magnetic resonance imaging of cystic pancreatic lesions in adults: an update in current diagnostic features and management. Abdom Imaging. 2014.39:48–65.
49- Van der Gaag NA, Berkhemer OA, Sprangers MA, et al. Quality of life and functional outcome after resection of pancreatic cystic neoplasm. Pancreas. 2014;43:755-761.
50- Park JW, Jang JY, Kang MJ, et al. Mucinous cystic neoplasm of the pancreas: is surgical resection recommended for all surgically fit patients? Pancreatology. 2014;14:131-136.
51- Xourafas D, Tavakkoli A, Clancy TE, et al.Noninvasive intraductal papillary mucinous neoplasms and mucinous cystic neoplasms: recurrence rates and postoperative imaging follow-up. Surgery. 2015;157:473-483
52- Jimenez RE, Warshaw AL, Z’graggen K, et al. Sequential accu¬mulation of K-ras mutations and p53 overexpression in the pro¬gression of pancreatic mucinous cystic neoplasms to malignancy. Ann Surg 1999;230:501-509.
53- O’Toole D, Palazzo L, Hammel P, et al. Macrocystic pancreatic cystadenoma: the role of EUS and cyst fluid analysis in dis¬tinguishing mucinous and serous lesions. Gastrointest Endosc 2004;59:823-829.
54- Brugge WR, Lewandrowski K, Lee-Lewandrowski E, et al. Diag¬nosis of pancreatic cystic neoplasms: a report of the cooperative pancreatic cyst study. Gastroenterology 2004;126:1330-1336.
55- Correa-Gallego C, Ferrone CR, Thayer SP, et al. Incidental pancreatic cysts: dowe really know what we are watching? Pancreatology 2010;10:144–150.
56- Salvia R, Malleo G, Marchegiani G, et al. Pancreatic resections for cystic neo-plasms: from the surgeon’s presumption to the pathologist’s reality. Surgery2012;152:S135–142.
57- Del Chiaro M, Segersvärd R, Pozzi Mucelli R, et al. Comparison of preoperative conference-based diagnosis with histology of cystic tumors of the pancreas. Ann Surg Oncol. 2014;21:1539–1544.
58- Goh BK, Thng CH, Tan DM, et al. Evaluation of the Sendai and 2012 International Consensus Guidelines based on cross-sectional imaging findings performed for the initial triage of mucinous cystic lesions of the pancreas: a single institution experience with 114 surgically treated patients. Am J Surg. 2014;208:202–209.
59- Curry CA, Eng J, Horton KM, et al. CT of primary cystic pancreatic neoplasms: can CT be used for patient triage and treatment. AJR Am J Roentgenol 2000;175:99–103.
60- Visser BC, Yeh BM, Qayyum A, et al. Characterization of cystic pancreatic masses: relative accuracy of CT and MRI. AJR Am J Roentgenol 2007;189:648–656.
61- Waters JA, Schmidt CM, Pinchot JW, et al. CT vs MRCP: optimal classification of IPMN type and extent. J Gastrointest Surg 2008;12:101–109.
62- Lee HJ, Kim MJ, Choi JY, et al. Relative accuracy of CT and MRI in the differentiation of benign from malignant pancreatic cystic lesions. Clin Radiol 2011;66:315–321.
63- Nougaret S, Reinhold C, Chong J, et al. Incidental pancreatic cysts: natural history and diagnostic accuracy of a limited serial pancreatic cyst MRI protocol. Eur Radiol 2014;24:1020–1029.
64- Muthusamy VR, Chandrasekhara V, Acosta RD, et al. The role of endoscopy in the diagnosis and treatment of cystic pancreatic neoplasms. Gastrointest Endosc. 2016;84:1-9.
65- Suzuki R, Thosani N, Annangi S, et al. Diagnostic yield of endoscopic retrograde cholangiopancreatography-based cytology for distinguishing malignant and benign intraductal papillary mucinous neoplasm: systematic review and meta-analysis. Dig Endosc 2014;26:586-593.
66- Itoi T, Sofuni A, Itokawa F, et al. Initial experience of peroral pancreatoscopy combined with narrow-band imaging in the diagnosis of intraductal papillary mucinous neoplasms of the pancreas. Gastrointest Endosc 2007;66:793-797.
67- Nagayoshi Y, Aso T, Ohtsuka T, et al. Peroral pancreatoscopy using the SpyGlass system for the assessment of intraductal papillary mucinous neoplasm of the pancreas. J Hepatobiliary Pancreat Sci 2014;21:4110-4117.
68- Ahmad NA, Kochman ML, Brensinger C, et al. Interobserver agreement among endosonographers for the diagnosis of neoplastic versus non-neoplastic pancreatic cystic lesions. Gastrointest Endosc 2003;58:59-64.
69- Lim LG, Lakhtakia S, Ang TL, et al. Factors determining diagnostic yield of endoscopic ultrasound guided fine-needle aspiration for pancreatic cystic lesions: a multicentre Asian study. Dig Dis Sci 2013; 58:1751-1757.
70- Rogart JN, Loren DE, Singu BS, et al. Cyst wall puncture and aspiration during EUS-guided fine needle aspiration may increase the diagnostic yield of mucinous cysts of the pancreas. J Clin Gastroenterol 2011;45:164-169.
71- Khashab MA, Kim K, Lennon AM, et al. Should we do EUS/FNA on patients with pancreatic cysts? The incremental diagnostic yield of EUS over CT/MRI for prediction of cystic neoplasms. Pancreas 2013;42: 717-721.
72- Zhong N, Zhang L, Takahashi N, et al. Histologic and imaging features of mural nodules in mucinous pancreatic cysts. Clin Gastroenterol Hepatol 2012;10:192-198.
75- Thornton GD, McPhail MJ, Nayagam S, et al. Endoscopic ultrasound guided fine needle aspiration for the diagnosis of pancreatic cystic neoplasms: a meta-analysis. Pancreatology 2013;13:48-57.
76- Pitman MB, Genevay M, Yaeger K, et al. High-grade atypical epithelial cells in pancreatic mucinous cysts are a more accurate predictor of malignancy than “positive” cytology. Cancer Cytopa¬thol 2010;118:434-440.
77- Genevay M, Mino-Kenudson M, Yaeger K, et al. Cytology adds value to imaging studies for risk assessment of malignancy in pancreatic mucinous cysts. Ann Surg. 2011;254:977–983.
78- Cizginer S, Turner B, Bilge AR, et al. Cyst fluid carcinoembryonic antigen is an accurate diagnostic marker of pancreatic mucinous cysts. Pancreas. 2011;40:1024–1028.
79- Van der Waaij LA, van Dullemen HM, Porte RJ. Cyst fluid analy¬sis in the differential diagnosis of pancreatic cystic lesions: a pooled analysis. Gastrointest Endosc 2005;62:383-389.
80- Park WG, Mascarenhas R, Palaez-Luna M, et al. Diagnostic performance of cyst fluid carcinoembryonic antigen and amylase in histologically confirmed pancreatic cysts. Pancreas. 2011;40:42–45.
81- Nakai Y, Iwashita T, Shinoura S, et al. Role of serial EUS-guided FNA on pancreatic cystic neoplasms: a retrospective analysis of repeat carcinoembryonic antigen measurements. Gastrointest Endosc. 2016 Apr. Epub.
82- Khalid A, Zahid M, Finkelstein SD, et al. Pancreatic cyst fluid DNA analysis in evaluating pancreatic cysts: a report of the PANDA study. Gastrointest Endosc 2009;69:1095-1102.
83- Siddiqui AA, Kowalski TE, Kedika R, et al. EUS-guided pancreatic fluid aspiration for DNA analysis of KRAS and GNAS mutations for the evaluation of pancreatic cystic neoplasia: a pilot study. Gastrointest Endosc 2013;77:669-670.
84- Al-Haddad M, DeWitt J, Sherman S, et al. Performance character¬istics of molecular (DNA) analysis for the diagnosis of mucinous pancreatic cysts. Gastrointest Endosc 2014;79:79-87.
85- Al-Haddad MA, Kowalski T, Siddiqui A, et al. Integrated molecular pathology accurately determines the malignant potential of pancreatic cysts. Endoscopy 2015;47:136-146.
86- Kanda M, Knight S, Topazian M, et al. Mutant GNAS detected in duodenal collections of secretin-stimulated pancreatic juice indicates the presence or emergence of pancreatic cysts. Gut 2013;62:1024-1033.
87- Tanaka M, Chari S, Adsay V, et al. International consensus guidelines for man-agement of intraductal papillary mucinous neoplasms and mucinous cysticneoplasms of the pancreas. Pancreatology 2006;6:17–32.
88- Goh BK, Tan DM, Ho MM, et al. Utility of the Sendai consensus guidelines forbranch-duct intraductal papillary mucinous neoplasms: a systematic review. Journal of Gastrointestinal Surgery 2014;18:1350–1357.
89- Yamada S, Fujii T, Murotani K, et al. Comparison of the internationalconsensus guidelines for predicting malignancy in intraductal papillary mucinous neoplasms. Surgery 2016;159:878-884.
90- Anand N, Sampath K, Wu BU. Cyst features and risk of malignancy in intra-ductal papillary mucinous neoplasms of the pancreas: a meta-analysis. ClinicalGastroenterology and Hepatology 2013;11:913–921.
91- Kim KW, Park SH, Pyo J, et al. Imaging features to distinguish malignant andbenign branch-duct type intraductal papillary mucinous neoplasms of the pan-creas: a meta-analysis. Annals of Surgery 2014;259:72–81.
92- Jang JY, Park T, Lee S, et al. Validation of international consensus guidelines forthe resection of branch duct-type intraductal papillary mucinous neoplasms.British Journal of Surgery 2014;101:686–692.
93- Sadakari Y, Ienaga J, Kobayashi K, et al. Cyst size indicates malignant transfor-mation in branch duct intraductal papillary mucinous neoplasm of the pancreaswithout mural nodules. Pancreas 2010;39:232–236.
94- Vege SS, Ziring B, Jain R, et al. American Gastroenterological Association Institute guideline on the diagnosis and management of asymptomatic neoplastic pancreatic cysts. Gastroenterology 2015;148:819-822.
95- Singhi AD, Zeh HJ, Brand RE, et al. American Gastroenterological Association guidelines are inaccurate in detecting pancreatic cysts with advanced neoplasia: a clinicopathologic study of 225 patients with supporting molecular data. Gastrointest Endosc. 2016;83:1107-1117
96- Tanno S, Nakano Y, Koizumi K, et al. Pancreatic ductal adenocarcinomas in long-term follow-up patients with branch duct intraductal papillary mucinous neoplasms. Pancreas 2010;39:36-40.
97- Rautou PE, Levy P, Vullierme MP, et al. Morphologic changes in branch duct intraductal papillary mucinous neoplasms of the pancreas: a midterm follow-up study. Clin Gastroenterol Hepatol 2008;6:807-814.
98- Crippa S, Bassil C, Salvia R, et al. Low progression of intraductal papillary mucinous neoplasms with worrisome features and high-risk stigmata undergoing non-operative management: a mid-term follow-up analysis. Gut. Epub 2016 Jan 7.
99- Kwong WT, Hunt GC, Fehmi SM, et al. Low Rates of Malignancy and Mortality in Asymptomatic Patients With Suspected Neoplastic Pancreatic Cysts Beyond 5 Years of Surveillance. Clin Gastroenterol Hepatol. 2016;14:865-871
100- Mukewar S,de Pretis N, Aryal-Khanal A, et al. Fukuoka criteria accurately predict risk for adverse outcomes during follow-up of pancreatic cysts presumed to be intraductal papillary mucinous neoplasms. Gut Published Online First: 7 July, 2016
73- Hocke M, Cui XW, Domagk D, et al. Pancreatic cystic lesions: the value of contrast-enhanced endoscopic ultrasound to influence the clinical pathway. Endosc Ultrasound 2014;3:123-130.
74- Nakai Y, Iwashita T, Park DH, et al. Diagnosis of pancreatic cysts: EUS-guided, through-the-needle confocal laser-induced endomicroscopy and cystoscopy trial: DETECT study. Gastrointest Endosc. 2015;81:1204-14.
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Publication history

Received: 21/09/2016

Accepted: 04/11/2016

Online First: 23/01/2017

Published: 03/05/2017

Article revision time: 34 days

Article Online First time: 124 days

Article editing time: 224 days


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