Pancreas
Exocrine tumors / carcinomas
Intraductal papillary mucinous neoplasm (IPMN)

Author: Diana Agostini-Vulaj D.O.
Editorial Board Member Review: Raul S. Gonzalez, M.D.
Editor-in-Chief Review: Debra Zynger, M.D.

Revised: 19 November 2018, last major update July 2018

Copyright: (c) 2002-2018, PathologyOutlines.com, Inc.

PubMed Search: Intraductal papillary mucinous neoplasm[TI] pancreas[TI] free full text[sb]

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Cite this page: Agostini-Vulaj, D. Intraductal papillary mucinous neoplasm (IPMN). PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/pancreasipmn.html. Accessed December 18th, 2018.
Definition / general
Essential features
  • Grossly visible (> 1 cm) cystic pancreatic neoplasm usually in head of pancreas
  • > 90% 5 year survival with complete resection
  • Roughly 1/3 of cases have an associated invasive carcinoma
  • Further subtyped into gastric, intestinal and pancreaticobiliary types based on epithelium (note: intraductal oncocytic papillary neoplasm (IOPN) is now considered a distinct and separate entity)
Terminology
  • Low grade to intermediate grade dysplasia previously termed: intraductal papillary mucinous adenoma
  • High grade dysplasia previously termed: intraductal papillary mucinous carcinoma, noninvasive
  • With an associated invasive carcinoma previously termed: intraductal papillary mucinous carcinoma, invasive
  • Other previous terms include: mucin producing tumor, mucinous duct ectasia, ductectatic mucinous cystadenoma / cystadenocarcinoma, villous adenoma or papillary adenoma / carcinoma (Bosman: WHO Classification of Tumours of the Digestive System, 4th Edition, 2010)
ICD coding
  • D13.6: benign neoplasm of pancreas
Epidemiology
Sites
  • Main duct IPMN mostly involves head of pancreas, 1/3 in body and tail (Hum Pathol 2012;43:1)
  • Branch duct IPMN mostly involves head of pancreas or uncinate process, with multiple distinct lesions seen in ~1/3 of cases (Hum Pathol 2012;43:1)
Etiology
Diagrams / tables

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Clinical management

Clinical features
Diagnosis
  • Radiographic / endoscopic findings
  • Surgical specimen
Laboratory
Radiology description
  • CT:
    • Main duct IPMN causes distention of main pancreatic duct
    • Branch duct IPMN produces multilocular grape-like cystic appearance
  • ERCP (endoscopic retrograde cholangiopancreatography): pancreatic ductal filling defects may be seen / ductal dilation
  • MRCP (magnetic resonance cholangiopancreatography): additional imaging option which does not produce radiation
  • EUS (endoscopic ultrasound):: can also allow FNA and cyst fluid analysis
Radiology images

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MRCP

MRCP

Enhanced CT

Cysts in isthmus


IPMN and MCN

MRCP

CT and MRCP

MRCP

Prognostic factors
  • Without an invasive carcinoma has > 90% 5 year survival; those associated with an invasive carcinoma carry a worse prognosis (about half die of disease) (Ann Surg 2016;263:162)
  • Main duct IPMN: 60% have high grade dysplasia and 45% are associated with an invasive carcinoma (Hum Pathol 2012;43:1)
  • Branch duct IPMN: most are low grade, 25% have high grade dysplasia and 20% are associated with an invasive carcinoma (Hum Pathol 2012;43:1)
  • Invasive carcinoma associated with IPMN includes:
    • Tubular (ductal) adenocarcinoma: seen in about half of cases, with slightly better prognosis than non IPMN associated pancreatic ductal adenocarcinoma
    • Colloid carcinoma: seen in half of cases, with much better prognosis than pancreatic ductal adenocarcinoma (Ann Surg 2016;263:162)
Case reports
Treatment
  • Main duct IPMN: surgical resection for all cases
  • Branch duct IPMN: indications for resection include symptomatic, association with mural nodule, dilated main duct and positive cytology (if size > 3 cm without any of the prior characteristics, can be observed with close interval surveillance imaging) (Pancreatology 2012;12:183)
Gross description
Gross images

Images hosted on PathOut server:

Contributed by Dennis R. Dening, PA (ASCP)

Main duct IPMN



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Main duct IPMN

Microscopic (histologic) description
  • Mucin producing epithelial cells with varied degrees of dysplasia (low, intermediate and high) and varied architecture ranging from flat to papillae that may be simple, complex or branching (Bosman: WHO Classification of Tumours of the Digestive System, 4th Edition, 2010)
    • Low grade dysplasia is characterized by a flat epithelial lining with basal located nuclei without significant pleomorphism, while intermediate dysplasia has features between those of low and high grade dysplasia; note low and intermediate dysplasia are now both grouped as low grade dysplasia (Am J Surg Pathol 2015;39:1730)
    • High grade dysplasia is characterized by complex architectural features (ie. irregular branching, cribiforming) with loss of nuclear polarity along with increased nuclear hyperchromasia and nuclear irregularities (Am J Surg Pathol 2015;39:1730)
  • Epithelial cells show variable differentiation and can be subclassified into: intestinal, gastric and pancreaticobiliary subtypes (oncocytic lining suggests intraductal oncocytic papillary neoplasm (IOPN)) (Bosman: WHO Classification of Tumours of the Digestive System, 4th Edition, 2010)
  • Associated with pancreatic intraepithelial neoplasia (PanIN), chronic pancreatitis (Am J Surg Pathol 2004;28:1184)
  • No ovarian type stroma
  • Assess presence or absence of invasive carcinoma (most important prognostic factor) (Hum Pathol 2012;43:1)
  • Type of invasion is associated with MUC1 / MUC2 pattern, see below (Mod Pathol 2002;15:1087)
  • Gastric type IPMN: cells resemble gastric foveolae, intestinal metaplasia may be seen, usually with low grade dysplasia and branch duct IPMN; if associated invasive carcinoma present, typically ductal (tubular) adenocarcinoma (Ann Surg 2016;263:162, Virchows Arch 2005;447:794, Bosman: WHO Classification of Tumours of the Digestive System, 4th Edition, 2010)
  • Intestinal type IPMN: cells with tall columnar epithelium (resembling intestinal villous adenomas), usually low or high grade dysplasia and main duct IPMN ; if associated invasive carcinoma present, typically mucinous (colloid) carcinoma
  • Pancreaticobiliary type IPMN: complex, thin branching papillae resembling cholangiopapillary neoplasms, cuboidal cells with prominent nucleoli, usually high grade dysplasia and main duct IPMN; if associated invasive carcinoma present, typically ductal (tubular) adenocarcinoma
Microscopic (histologic) images

Images hosted on PathOut server:

Contributed by Diana Agostini-Vulaj D.O.

IPMN intestinal subtype with low grade dysplasia

IPMN gastric subtype with low grade dysplasia

MUC1

MUC2



AFIP

Low grade dysplasia

Intermediate grade dysplasia

High grade dysplasia



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Comparison of subtypes

Intestinal papillae (H&E and CDX2+)

Intermediate (top) and high (bottom) grade dysplasia

Intermediate (top) and high (bottom) grade dysplasia

Loss of mismatch repair in Lynch syndrome

Positive stains
Negative stains
Molecular / cytogenetics description
  • KRAS, GNAS and RNF43 mutations seen in decreasing frequency in noninvasive IPMNs as well as IPMNs with an associated invasive carcinoma (J Am Coll Surg 2015;220:845)
  • GNAS mutations more commonly associated with IPMNs which harbor an invasive colloid carcinoma
  • KRAS mutations more commonly associated with IPMNs which harbor an invasive tubular (ductal) adenocarcinoma
  • With increasing grades of dysplasia, increased mutations in KRAS, TP53, CDKN2A (p16); also hypermethylation and reduced BRG1 protein (Hum Pathol 2012;43:585)
  • Loss of programmed cell death 4 (PDCD4) and CD24 expression associated with tumor progression and proliferation (Hum Pathol 2010;41:1507, Hum Pathol 2010;41:1466)
  • Cyst fluid shows mutations in KRAS2 and GNAS
Differential diagnosis
Board review question #1
Which subtype of intraductal papillary mucinous neoplasm (IPMN) is more likely to arise from a branched pancreatic duct?

  1. Gastric
  2. Intestinal
  3. Pancreaticobiliary
  4. Invasive
Board review answer #1
A. Gastric
Board review question #2
Based on the below clinical scenario which would most likely represent an intraductal papillary mucinous neoplasm (IPMN)?

  1. 29 year old woman with 8 cm solid and cystic pancreatic tail mass
  2. 45 year old woman with 3 cm cystic pancreatic tail mass
  3. 58 year old man with 3 cm solid pancreatic head mass
  4. 66 year old man with 2 cm cystic pancreatic head mass
  5. None of the above
Board review answer #2
D. 66 year old man with 2 cm cystic pancreatic head mass