Intraductal papillary mucinous neoplasm of the pancreas (IPMN): Evaluation and management
- Sunil G Sheth, MD
Sunil G Sheth, MD
- Assistant Professor of Medicine
- Harvard Medical School
- Douglas A Howell, MD, FASGE, FACG
Douglas A Howell, MD, FASGE, FACG
- Section Editor — EUS/ERCP
- Assistant Clinical Professor of Medicine, Tufts Medical School Director,
- Pancreaticobiliary Center Director, Advanced Interventional Endoscopy Fellowship, Maine Medical Center
- Tara S Kent, MD, FACS
Tara S Kent, MD, FACS
- Assistant Professor of Surgery
- Harvard Medical School
- Beth Israel Deaconess Medical Center
Intraductal papillary mucinous neoplasms (IPMNs) of the pancreas are potentially malignant intraductal epithelial neoplasms that are grossly visible (typically >10 mm) and are composed of mucin-producing columnar cells. The lesions show papillary proliferation, cyst formation, and varying degrees of cellular atypia [1,2].
IPMNs may involve the main pancreatic duct, the branch ducts, or both. Whereas patients with branch-duct lesions are at lower risk for developing malignancy (approximately 20 percent at 10 years), patients with IPMNs involving the main duct are at high risk (approximately 70 percent). As a result, these lesions need to be accurately diagnosed and characterized so that appropriate treatment can be recommended. (See "Intraductal papillary mucinous neoplasm of the pancreas (IPMN): Pathophysiology and clinical manifestations", section on 'Classification' and "Intraductal papillary mucinous neoplasm of the pancreas (IPMN): Pathophysiology and clinical manifestations", section on 'Pancreatic malignancy'.)
This topic will review the evaluation and management of IPMNs. The pathophysiology and clinical manifestations of IPMNs and an overview of the diagnostic approach to pancreatic cystic neoplasms are discussed separately. (See "Intraductal papillary mucinous neoplasm of the pancreas (IPMN): Pathophysiology and clinical manifestations" and "Classification of pancreatic cysts" and "Pancreatic cystic neoplasms: Clinical manifestations, diagnosis, and management".)
The approach to the diagnosis of pancreatic cystic neoplasms typically starts with cross-sectional imaging (magnetic resonance imaging with magnetic resonance cholangiopancreatography or computed tomography). Additional evaluation with endoscopic ultrasound with fine-needle aspiration may be needed to confirm a diagnosis or to assess for malignant features. The diagnostic approach to pancreatic cystic neoplasms is discussed separately. (See "Pancreatic cystic neoplasms: Clinical manifestations, diagnosis, and management".)
EVALUATION FOR MALIGNANCY
The evaluation of a patient with an intraductal papillary mucinous neoplasm (IPMN) aims to determine if the patient has or is at high-risk of developing a malignancy. Resection is typically recommended for IPMNs with high-grade dysplasia (carcinoma in situ), IPMNs that have progressed to invasive carcinoma (also referred to as invasive IPMN or malignant IPMN), and IPMNs with features concerning for malignancy or that are at high risk for developing malignancy. IPMNs not meeting these criteria are typically followed with surveillance imaging. (See 'Management' below.)
- Longnecker DS, Adsay NV, Fernandez-del Castillo C, et al. Histopathological diagnosis of pancreatic intraepithelial neoplasia and intraductal papillary-mucinous neoplasms: interobserver agreement. Pancreas 2005; 31:344.
- Hruban RH, Takaori K, Klimstra DS, et al. An illustrated consensus on the classification of pancreatic intraepithelial neoplasia and intraductal papillary mucinous neoplasms. Am J Surg Pathol 2004; 28:977.
- Irie H, Honda H, Aibe H, et al. MR cholangiopancreatographic differentiation of benign and malignant intraductal mucin-producing tumors of the pancreas. AJR Am J Roentgenol 2000; 174:1403.
- Sahani DV, Kadavigere R, Blake M, et al. Intraductal papillary mucinous neoplasm of pancreas: multi-detector row CT with 2D curved reformations--correlation with MRCP. Radiology 2006; 238:560.
- Carbognin G, Zamboni G, Pinali L, et al. Branch duct IPMTs: value of cross-sectional imaging in the assessment of biological behavior and follow-up. Abdom Imaging 2006; 31:320.
- Kim JH, Eun HW, Kim KW, et al. Intraductal papillary mucinous neoplasms with associated invasive carcinoma of the pancreas: imaging findings and diagnostic performance of MDCT for prediction of prognostic factors. AJR Am J Roentgenol 2013; 201:565.
- Sugiyama M, Atomi Y, Kuroda A. Two types of mucin-producing cystic tumors of the pancreas: diagnosis and treatment. Surgery 1997; 122:617.
- Koito K, Namieno T, Ichimura T, et al. Mucin-producing pancreatic tumors: comparison of MR cholangiopancreatography with endoscopic retrograde cholangiopancreatography. Radiology 1998; 208:231.
- Izuishi K, Nakagohri T, Konishi M, et al. Spatial assessment by magnetic resonance cholangiopancreatography for preoperative imaging in partial pancreatic head resection. Am J Surg 2001; 182:188.
- Albert J, Schilling D, Breer H, et al. Mucinous cystadenomas and intraductal papillary mucinous tumors of the pancreas in magnetic resonance cholangiopancreatography. Endoscopy 2000; 32:472.
- Itai Y, Ohhashi K, Nagai H, et al. "Ductectatic" mucinous cystadenoma and cystadenocarcinoma of the pancreas. Radiology 1986; 161:697.
- 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.
- 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.
- Cellier C, Cuillerier E, Palazzo L, et al. Intraductal papillary and mucinous tumors of the pancreas: accuracy of preoperative computed tomography, endoscopic retrograde pancreatography and endoscopic ultrasonography, and long-term outcome in a large surgical series. Gastrointest Endosc 1998; 47:42.
- Sugiyama M, Atomi Y, Saito M. Intraductal papillary tumors of the pancreas: evaluation with endoscopic ultrasonography. Gastrointest Endosc 1998; 48:164.
- Pais SA, Attasaranya S, Leblanc JK, et al. Role of endoscopic ultrasound in the diagnosis of intraductal papillary mucinous neoplasms: correlation with surgical histopathology. Clin Gastroenterol Hepatol 2007; 5:489.
- Tanno S, Nakano Y, Nishikawa T, et al. Natural history of branch duct intraductal papillary-mucinous neoplasms of the pancreas without mural nodules: long-term follow-up results. Gut 2008; 57:339.
- Kim KW, Park SH, Pyo J, et al. Imaging features to distinguish malignant and benign branch-duct type intraductal papillary mucinous neoplasms of the pancreas: a meta-analysis. Ann Surg 2014; 259:72.
- Grützmann R, Niedergethmann M, Pilarsky C, et al. Intraductal papillary mucinous tumors of the pancreas: biology, diagnosis, and treatment. Oncologist 2010; 15:1294.
- Hirono S, Tani M, Kawai M, et al. The carcinoembryonic antigen level in pancreatic juice and mural nodule size are predictors of malignancy for branch duct type intraductal papillary mucinous neoplasms of the pancreas. Ann Surg 2012; 255:517.
- Sessa F, Solcia E, Capella C, et al. Intraductal papillary-mucinous tumours represent a distinct group of pancreatic neoplasms: an investigation of tumour cell differentiation and K-ras, p53 and c-erbB-2 abnormalities in 26 patients. Virchows Arch 1994; 425:357.
- Kaino M, Kondoh S, Okita S, et al. Detection of K-ras and p53 gene mutations in pancreatic juice for the diagnosis of intraductal papillary mucinous tumors. Pancreas 1999; 18:294.
- Inoue H, Tsuchida A, Kawasaki Y, et al. Preoperative diagnosis of intraductal papillary-mucinous tumors of the pancreas with attention to telomerase activity. Cancer 2001; 91:35.
- Maire F, Voitot H, Aubert A, et al. Intraductal papillary mucinous neoplasms of the pancreas: performance of pancreatic fluid analysis for positive diagnosis and the prediction of malignancy. Am J Gastroenterol 2008; 103:2871.
- Saito M, Ishihara T, Tada M, et al. Use of F-18 fluorodeoxyglucose positron emission tomography with dual-phase imaging to identify intraductal papillary mucinous neoplasm. Clin Gastroenterol Hepatol 2013; 11:181.
- Maker AV, Katabi N, Gonen M, et al. Pancreatic cyst fluid and serum mucin levels predict dysplasia in intraductal papillary mucinous neoplasms of the pancreas. Ann Surg Oncol 2011; 18:199.
- Farrell JJ, Toste P, Wu N, et al. Endoscopically acquired pancreatic cyst fluid microRNA 21 and 221 are associated with invasive cancer. Am J Gastroenterol 2013; 108:1352.
- Siddiqui AA, Shahid H, Shah A, et al. High risk of acute pancreatitis after endoscopic ultrasound-guided fine needle aspiration of side branch intraductal papillary mucinous neoplasms. Endosc Ultrasound 2015; 4:109.
- Sai JK, Nobukawa B, Matsumura Y, Watanabe S. Pancreatic duct lavage cytology with the cell block method for discriminating benign and malignant branch-duct type intraductal papillary mucinous neoplasms. Gastrointest Endosc 2013; 77:726.
- Yamaguchi T, Hara T, Tsuyuguchi T, et al. Peroral pancreatoscopy in the diagnosis of mucin-producing tumors of the pancreas. Gastrointest Endosc 2000; 52:67.
- Kaneko T, Nakao A, Nomoto S, et al. Intraoperative pancreatoscopy with the ultrathin pancreatoscope for mucin-producing tumors of the pancreas. Arch Surg 1998; 133:263.
- Yamao K, Ohashi K, Nakamura T, et al. Efficacy of peroral pancreatoscopy in the diagnosis of pancreatic diseases. Gastrointest Endosc 2003; 57:205.
- Hara T, Yamaguchi T, Ishihara T, et al. Diagnosis and patient management of intraductal papillary-mucinous tumor of the pancreas by using peroral pancreatoscopy and intraductal ultrasonography. Gastroenterology 2002; 122:34.
- Shah RJ. Innovations in Intraductal Endoscopy: Cholangioscopy and Pancreatoscopy. Gastrointest Endosc Clin N Am 2015; 25:779.
- Furukawa T, Tsukamoto Y, Naitoh Y, et al. Differential diagnosis between benign and malignant localized stenosis of the main pancreatic duct by intraductal ultrasound of the pancreas. Am J Gastroenterol 1994; 89:2038.
- Sperti C, Pasquali C, Chierichetti F, et al. Value of 18-fluorodeoxyglucose positron emission tomography in the management of patients with cystic tumors of the pancreas. Ann Surg 2001; 234:675.
- Baiocchi GL, Portolani N, Bertagna F, et al. Possible additional value of 18FDG-PET in managing pancreas intraductal papillary mucinous neoplasms: preliminary results. J Exp Clin Cancer Res 2008; 27:10.
- Pedrazzoli S, Sperti C, Pasquali C, et al. Comparison of International Consensus Guidelines versus 18-FDG PET in detecting malignancy of intraductal papillary mucinous neoplasms of the pancreas. Ann Surg 2011; 254:971.
- Fritz S, Hackert T, Hinz U, et al. Role of serum carbohydrate antigen 19-9 and carcinoembryonic antigen in distinguishing between benign and invasive intraductal papillary mucinous neoplasm of the pancreas. Br J Surg 2011; 98:104.
- Wakabayashi T, Kawaura Y, Morimoto H, et al. Clinical management of intraductal papillary mucinous tumors of the pancreas based on imaging findings. Pancreas 2001; 22:370.
- Myung SJ, Kim MH, Lee SK. Pancreatoscopy and magnetic resonance pancreatography may decrease the margin-positive cases and recurrence rate in surgical therapy of mucinous ductal ectasia. Gastrointest Endosc 1998; 48:556.
- Bassi C, Procacci C, Zamboni G, et al. Intraductal papillary mucinous tumors of the pancreas. Verona University Pancreatic Team. Int J Pancreatol 2000; 27:181.
- Traverso LW, Peralta EA, Ryan JA Jr, Kozarek RA. Intraductal neoplasms of the pancreas. Am J Surg 1998; 175:426.
- Sohn TA, Yeo CJ, Cameron JL, et al. Intraductal papillary mucinous neoplasms of the pancreas: an updated experience. Ann Surg 2004; 239:788.
- Sohn TA, Yeo CJ, Cameron JL, et al. Intraductal papillary mucinous neoplasms of the pancreas: an increasingly recognized clinicopathologic entity. Ann Surg 2001; 234:313.
- Gigot JF, Deprez P, Sempoux C, et al. Surgical management of intraductal papillary mucinous tumors of the pancreas: the role of routine frozen section of the surgical margin, intraoperative endoscopic staged biopsies of the Wirsung duct, and pancreaticogastric anastomosis. Arch Surg 2001; 136:1256.
- 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.
- Tanaka M, Chari S, Adsay V, et al. International consensus guidelines for management of intraductal papillary mucinous neoplasms and mucinous cystic neoplasms of the pancreas. Pancreatology 2006; 6:17.
- Raman SP, Kawamoto S, Blackford A, et al. Histopathologic findings of multifocal pancreatic intraductal papillary mucinous neoplasms on CT. AJR Am J Roentgenol 2013; 200:563.
- Paye F, Sauvanet A, Terris B, et al. Intraductal papillary mucinous tumors of the pancreas: pancreatic resections guided by preoperative morphological assessment and intraoperative frozen section examination. Surgery 2000; 127:536.
- McMillan MT, Lewis RS, Drebin JA, et al. The efficacy of adjuvant therapy for pancreatic invasive intraductal papillary mucinous neoplasm (IPMN). Cancer 2016; 122:521.
- Swartz MJ, Hsu CC, Pawlik TM, et al. Adjuvant chemoradiotherapy after pancreatic resection for invasive carcinoma associated with intraductal papillary mucinous neoplasm of the pancreas. Int J Radiat Oncol Biol Phys 2010; 76:839.
- Tanaka M, Fernández-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.
- Sugiyama M, Izumisato Y, Abe N, et al. Predictive factors for malignancy in intraductal papillary-mucinous tumours of the pancreas. Br J Surg 2003; 90:1244.
- Hackert T, Fritz S, Klauss M, et al. Main-duct Intraductal Papillary Mucinous Neoplasm: High Cancer Risk in Duct Diameter of 5 to 9 mm. Ann Surg 2015; 262:875.
- Goh BK, Tan DM, Thng CH, et al. Are the Sendai and Fukuoka consensus guidelines for cystic mucinous neoplasms of the pancreas useful in the initial triage of all suspected pancreatic cystic neoplasms? A single-institution experience with 317 surgically-treated patients. Ann Surg Oncol 2014; 21:1919.
- Anand N, Sampath K, Wu BU. Cyst features and risk of malignancy in intraductal papillary mucinous neoplasms of the pancreas: a meta-analysis. Clin Gastroenterol Hepatol 2013; 11:913.
- Salvia R, Fernández-del Castillo C, Bassi C, et al. Main-duct intraductal papillary mucinous neoplasms of the pancreas: clinical predictors of malignancy and long-term survival following resection. Ann Surg 2004; 239:678.
- Kang MJ, Jang JY, Lee KB, et al. Long-term prospective cohort study of patients undergoing pancreatectomy for intraductal papillary mucinous neoplasm of the pancreas: implications for postoperative surveillance. Ann Surg 2014; 260:356.
- Terris B, Ponsot P, Paye F, et al. Intraductal papillary mucinous tumors of the pancreas confined to secondary ducts show less aggressive pathologic features as compared with those involving the main pancreatic duct. Am J Surg Pathol 2000; 24:1372.
- Sho M, Nakajima Y, Kanehiro H, et al. Pattern of recurrence after resection for intraductal papillary mucinous tumors of the pancreas. World J Surg 1998; 22:874.
- Niedergethmann M, Grützmann R, Hildenbrand R, et al. Outcome of invasive and noninvasive intraductal papillary-mucinous neoplasms of the pancreas (IPMN): a 10-year experience. World J Surg 2008; 32:2253.
- Uehara H, Nakaizumi A, Ishikawa O, et al. Development of ductal carcinoma of the pancreas during follow-up of branch duct intraductal papillary mucinous neoplasm of the pancreas. Gut 2008; 57:1561.
- Lafemina J, Katabi N, Klimstra D, et al. Malignant progression in IPMN: a cohort analysis of patients initially selected for resection or observation. Ann Surg Oncol 2013; 20:440.
- Baiocchi GL, Portolani N, Grazioli L, et al. Management of pancreatic intraductal papillary mucinous neoplasm in an academic hospital (2005-2010): what follow-up for unoperated patients? Pancreas 2013; 42:696.
- Kobari M, Egawa S, Shibuya K, et al. Intraductal papillary mucinous tumors of the pancreas comprise 2 clinical subtypes: differences in clinical characteristics and surgical management. Arch Surg 1999; 134:1131.
- Rivera JA, Fernández-del Castillo C, Pins M, et al. Pancreatic mucinous ductal ectasia and intraductal papillary neoplasms. A single malignant clinicopathologic entity. Ann Surg 1997; 225:637.
- Loftus EV Jr, Olivares-Pakzad BA, Batts KP, et al. Intraductal papillary-mucinous tumors of the pancreas: clinicopathologic features, outcome, and nomenclature. Members of the Pancreas Clinic, and Pancreatic Surgeons of Mayo Clinic. Gastroenterology 1996; 110:1909.
- Partelli S, Fernandez-Del Castillo C, Bassi C, et al. Invasive intraductal papillary mucinous carcinomas of the pancreas: predictors of survival and the role of lymph node ratio. Ann Surg 2010; 251:477.
- Murakami Y, Uemura K, Sudo T, et al. Invasive intraductal papillary-mucinous neoplasm of the pancreas: comparison with pancreatic ductal adenocarcinoma. J Surg Oncol 2009; 100:13.
- Maire F, Hammel P, Terris B, et al. Prognosis of malignant intraductal papillary mucinous tumours of the pancreas after surgical resection. Comparison with pancreatic ductal adenocarcinoma. Gut 2002; 51:717.
- Shimada K, Sakamoto Y, Sano T, et al. 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.
- Woo SM, Ryu JK, Lee SH, et al. Survival and prognosis of invasive intraductal papillary mucinous neoplasms of the pancreas: comparison with pancreatic ductal adenocarcinoma. Pancreas 2008; 36:50.
- Poultsides GA, Reddy S, Cameron JL, et al. Histopathologic basis for the favorable survival after resection of intraductal papillary mucinous neoplasm-associated invasive adenocarcinoma of the pancreas. Ann Surg 2010; 251:470.
- Waters JA, Schnelldorfer T, Aguilar-Saavedra JR, et al. Survival after resection for invasive intraductal papillary mucinous neoplasm and for pancreatic adenocarcinoma: a multi-institutional comparison according to American Joint Committee on Cancer Stage. J Am Coll Surg 2011; 213:275.
- Wasif N, Bentrem DJ, Farrell JJ, et al. Invasive intraductal papillary mucinous neoplasm versus sporadic pancreatic adenocarcinoma: a stage-matched comparison of outcomes. Cancer 2010; 116:3369.
- EVALUATION FOR MALIGNANCY
- Cross-sectional imaging
- Indications for additional evaluation
- Endoscopic ultrasound with fine-needle aspiration
- - Sonographic findings
- - Pancreatic and cyst fluid analysis
- Other tests
- High-grade dysplasia or invasive cancer
- - Surgical therapy
- - Adjuvant therapy
- IPMN without confirmed malignancy or high-grade dysplasia
- - Main-duct IPMN
- - Branch-duct IPMN
- - Combined main-duct and branch-duct IPMN
- Surveillance following surgery
- Surveillance for extrapancreatic malignancies
- Patients who do not undergo surgery
- Prognosis following surgery
- SUMMARY AND RECOMMENDATIONS