Exocrine tumors / carcinomas
Intraductal papillary mucinous neoplasm (IPMN)

Author: Deepali Jain, M.D. (see Authors page)

Revised: 14 December 2017, last major update December 2012

Copyright: (c) 2002-2017,, Inc.

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

Cite this page: Jain, D. Intraductal papillary mucinous neoplasm (IPMN). website. Accessed May 27th, 2018.
Definition / general
  • Proposed definition: intraductal grossly visible (1 cm or more) epithelial neoplasm of mucin producing cells, arising in main pancreatic duct or its branches; neoplastic epithelium is usually papillary; variable mucin secretion, duct dilatation (cyst formation) and dysplasia; classify based on highest degree of cytoarchitectural atypia and invasiveness as:
  • One of three precursor lesions of pancreatic adenocarcinoma (also PanIN, mucinous cystic neoplasm)
Diagrams / tables

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Proposed neoplastic pathways

Clinical features
  • More common in men age 60+ at head of pancreas
  • Signs and symptoms include epigastric pain, weight loss, jaundice, diabetes, pancreatitis (Arch Pathol Lab Med 1996;120:981)
  • Associated with Peutz-Jeghers syndrome
  • IPMN component may be favorable prognostic factor in invasive disease (Hum Pathol 2001;32:834)
  • Resection often requires frozen sections, since most lesions are contiguous
  • Patients with branch duct involvement only: associated with mild dilation of main duct; much lower risk of invasive carcinoma; management uncertain but less aggressive (Dig Liver Dis 2012;44:257, Am J Surg Pathol 2000;24:1372)
  • Clinical subtypes include main duct, which is symptomatic, branch duct, which is typically asymptomatic, and mixed
  • Assess dysplasia (none, low / intermediate grade dysplasia, high grade dysplasia)
  • 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)
  • Minimal invasion does not affect survival (Am J Surg Pathol 2008;32:243)
Patterns of papillae
Gastric foveolar type papillae:
Intestinal type papillae:
  • More common, occurs in main duct, usually intermediate to high grade dysplasia
  • Resembles colonic villous adenoma, may exhibit pale apical mucin reminiscent of gastric foveolar cells, MUC1-, MUC2+, CDX2+
  • Also claudin4+ (Mod Pathol 2011;24:533)
  • When invasive, associated with colloid carcinoma (also MUC1-, MUC2+)

Pancreaticobiliary type papillae:
  • Complex arborizing papillae with 2 - 5 cell layers and cuboidal cells with prominent nucleoli, less mucinous, more cytologic atypia
  • MUC1+, MUC2- / focal, MUC6+ (Am J Surg Pathol 2010;34:364)
  • When invasive, associated with usual ductal adenocarcinoma (also MUC1+, MUC2-)
  • Associated with invasive carcinoma more often than intestinal type

Oncocytic type papillae (intraductal oncocytic papillary neoplasm, IOPN):
  • See IOPN topic
  • MUC1+, MUC2+, MUC6+

Intraductal tubulopapillary neoplasm
  • Recently recognized subtype (Am J Surg Pathol 2009;33:1164)
  • See ITPN topic
  • Potential origin from peribiliary cysts; tubulopapillary architecture, necrotic foci, more solid growth without visible mucin, scanty cytoplasmic mucin, no KRAS2 gene mutations
  • MUC1+, MUC2-, MUC6+

  • Benign and nonneoplastic pancreas is MUC1-
  • PanIN and invasive ductal NOS are usually MUC2-
Case reports
  • Resect entire tumor if > 3 cm, symptomatic with positive cytology, dilated main duct and mural nodules
  • Sample extensively (> 50 blocks) to rule out invasion or atypia
Gross description
  • Main duct involvement: usually diffusely dilated, tortuous and irregular, filled with mucin; usually arises in head and progresses along path of main duct, may involve entire pancreas; may involve major or minor papillae leading to mucin extrusion from ampulla; associated with higher risk of high grade dysplasia and invasive carcinoma than branch duct involvement; uninvoled pancreas is often pale and firm, reflecting extensive chronic obstructive pancreatitis
  • Branch duct involvement: often in uncinate process; forms multicystic, grape-like structures; cystically dilated ducts are 1 to 10 cm, filled with tenacious mucin; cyst walls are usually thin with flat or papillary lining; cysts separated by normal pancreas, suggesting that cysts are separate on cut sections (WHO)
Gross images

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Main duct involvement: left sided pancreatectomy specimen

Sticky mucin

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Branch duct involvement
(arrows in figure on right
are main pancreatic duct)

Main duct involvement

Microscopic (histologic) description
  • Multicentric
  • Complex papillary fronds of mucin producing epithelial cells with variable atypia
  • Various types of papillae described above and below
  • Ductal fibrosis, acinar atrophy but well preserved islets
  • Associated with PanIN (Am J Surg Pathol 2004;28:1184), chronic pancreatitis
  • No ovarian type stroma
Microscopic (histologic) images

Images hosted on PathOut server:

Branch duct

Epithelial papillary proliferations

Low grade dysplasia

Intermediate grade dysplasia:
lining epithelium of papillae is
characterized by nuclear enlargement,
stratification and crowding

High grade dysplasia and invasion (left)

High grade dysplasia: cells have varying sized nuclei, some show thick nucleoli and mitoses (arrow)

High grade dysplasia: severely atypical epithelium forms irregular projections without any tissue stalk

High grade dysplasia: the atypical epithelium shows branching and bridging

Tall columnar mucin producing epithelium



Images hosted on other servers:

Gastric papillae

Gastric papillae - top: low grade (blue arrows) and intermediate grade dysplasia (black arrows); bottom: high grade dysplasia (black arrows) with cribriform formation and marked nuclear atypia

Comparison of subtypes:
gastric, intestinal,

Intestinal papillae

Intestinal papillae (H&E and CDX2+)

Intestinal papillae: intermediate grade dysplasia (top) and high grade dysplasia (bottom)

Invasive (colloid carcinoma, figure 9)

Noninvasive (figure 4)

Pancreaticobiliary papillae: intermediate grade dysplasia (top) and high grade dysplasia (bottom)

Patient with both gastric and intestinal papillae

With loss of mismatch repair in patient with Lynch syndrome

Positive stains
Molecular / cytogenetics description
Differential diagnosis: mucinous cystic neoplasm (MCN)

F > M M > F
Age: 40 - 50 60 - 70 years
Tail Head
Grossly cystic Grossly cystic with papillae > 1 cm
Not in duct In duct
Ovarian type stroma No ovarian type stroma

  • See also MCN topic
Differential diagnosis: other