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Intraductal papillary mucinous neoplasm


Editorial Board Member: Monika Vyas, M.D.
Deputy Editor-in-Chief: Catherine E. Hagen, M.D.
Diana Agostini-Vulaj, D.O.

Last author update: 14 September 2021
Last staff update: 14 September 2021

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PubMed Search: Intraductal papillary mucinous neoplasm[title] pancreas[title] review[ptyp]

Diana Agostini-Vulaj, D.O.
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Table of Contents
Definition / general | Essential features | Terminology | ICD coding | Epidemiology | Sites | Pathophysiology | Etiology | Diagrams / tables | Clinical features | Diagnosis | Laboratory | Radiology description | Radiology images | Prognostic factors | Case reports | Treatment | Clinical images | Gross description | Gross images | Frozen section description | Frozen section images | Microscopic (histologic) description | Microscopic (histologic) images | Virtual slides | Cytology description | Cytology images | Positive stains | Negative stains | Molecular / cytogenetics description | Sample pathology report | Differential diagnosis | Additional references | Board review style question #1 | Board review style answer #1 | Board review style question #2 | Board review style answer #2
Cite this page: Agostini-Vulaj D. Intraductal papillary mucinous neoplasm. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/pancreasipmn.html. Accessed July 6th, 2022.
Definition / general
Essential features
  • Grossly visible (> 5 mm) cystic pancreatic neoplasm, usually in head of pancreas
  • > 90% 5 year survival with complete resection
  • Roughly 33% 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
ICD coding
  • ICD-10: D13.6 - benign neoplasm of pancreas
Epidemiology
Sites
  • Main duct intraductal papillary mucinous neoplasm (IPMN) mostly involves head of pancreas, 33% 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 ~33% of cases (Hum Pathol 2012;43:1)
Etiology
Diagrams / tables

Images hosted on other servers:

Indications for surgery

Clinical features
Diagnosis
  • Radiographic / endoscopic findings
  • Fine needle aspiration
  • 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
  • References: Diagn Interv Imaging 2016;97:1275, World J Gastroenterol 2016;22:9562
Radiology images

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MRCP demonstrating various types of IPMN

MRCP demonstrating side branch IPMNs

Differing radiologic
modalities demonstrating
various types of
IPMN and MCN

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 the 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 indicated if main pancreatic duct > 10 mm, jaundice or presence of mural nodules (Pancreatology 2017;17:738)
    • Branch duct IPMN: surgical resection indicated if symptomatic, presence of mural nodule ≥ 5 mm, suspicious / positive cytology, obstructive jaundice or main pancreatic duct ≥ 10 mm (Pancreatology 2017;17:738)
    • See Diagrams / tables
Clinical images

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Mucin extrusion from duodenal papilla

Gross description
  • Main duct involvement:
    • Usually diffusely dilated, tortuous and irregular, filled with mucin
    • Typically 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
    • Uninvolved 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, 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
  • Multicentricity seen in up to 40% of cases (Am J Gastroenterol 2007;102:1759)
  • Extensive sampling / complete submission of cyst for microscopic evaluation important to rule out an associated invasive carcinoma (Am J Surg Pathol 2014;38:480, Ann Surg 2016;263:162)
  • Greater than 5 mm in diameter
    • Incipient IPMN is a term that can be used for lesions 0.5 - 1.0 cm in size
Gross images

Contributed by Dennis R. Dening, PA (ASCP)

Main duct IPMN

Frozen section description
Frozen section images

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Normal pancreatic duct

Pancreatic duct with low grade dysplasia

Microscopic (histologic) description
  • Mucin producing epithelial cells with varied degrees of dysplasia (Am J Surg Pathol 2015;39:1730)
    • 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 (i.e. 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)
  • 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)
  • 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

Contributed by Diana Agostini-Vulaj, D.O.
 

IPMN intestinal subtype with low grade dysplasia

 

IPMN gastric subtype with low grade dysplasia


 

IPMN with high grade dysplasia

MUC1

MUC2

Virtual slides

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IPMN, low grade, intestinal type

Cytology description
  • Cannot distinguish IPMN from mucinous cystic neoplasm on cytology (neoplastic mucinous cyst)
  • Disordered mucinous epithelial clusters with nuclear overlap and variable cytologic atypia
  • Distinguishing a low grade mucinous neoplasm from gastrointestinal tract contaminant (particularly gastric mucosa) can be challenging
Cytology images

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Low grade epithelial atypia

High grade epithelial atypia with necrotic debris

Positive stains
Negative stains
Molecular / cytogenetics description
  • KRAS, GNAS and RNF43 mutations seen in decreasing frequency in noninvasive IPMNs and 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
Sample pathology report
  • Pancreas, small bowel and stomach, pancreaticoduodenectomy (Whipple resection):
    • Intraductal papillary mucinous neoplasm (IPMN), low grade, gastric phenotype, branch duct type, 3.0 cm (see comment)
    • Negative for high grade dysplasia or malignancy.
    • Margins are negative for IPMN.
    • 23 lymph nodes with no significant histologic abnormality.
    • Comment: The entire cyst is submitted for histologic examination.
Differential diagnosis
Board review style question #1


Which morphologic type of intraductal papillary mucinous neoplasm is depicted in the above photo, seen arising from a branch of the main pancreatic duct?

  1. Gastric
  2. Intestinal
  3. Invasive
  4. Oncocytic
  5. Pancreaticobiliary
Board review style answer #1
A. Gastric. The histologic features are typical of the gastric type of IPMN, no features of intestinal or pancreatobiliary differentiation are seen (choices B and E); choice D is not a morphologic type of IPMN; rather, intraductal oncocytic papillary neoplams are a distinct separate entity.

Comment Here

Reference: Intraductal papillary mucinous neoplasm
Board review style question #2
Which of the following clinical scenarios 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
Board review style answer #2
D. 66 year old man with 2 cm cystic pancreatic head mass. IPMNs are more often seen in older men and are cystic; thus choices A - C are incorrect (choice A would be more typical of a solid pseudopapillary neoplasm; choice B would more typical of a mucinous cystic neoplasm; choice C would be more typical of pancreatic ductal adenocarcinoma or a pancreatic neuroendocrine tumor).

Comment Here

Reference: Intraductal papillary mucinous neoplasm
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