Intraductal papillary mucinous neoplasms or tumors (IPMNs or IMPTs) are epithelial cystic pancreatic tumors of mucin-producing cells that arise from the pancreatic ducts. They are most commonly seen in elderly patients. On imaging, particularly MRCP, they are characterized by single or multiple unilocular or septated pancreatic cystic lesions communicating with the pancreatic ducts. 

Epidemiology

These tumors are most frequently identified in older patients, 50-60 years of age ⁶, and thus are sometimes colloquially referred to as the "grandfather lesion". The main duct type appears to present around a decade earlier than branch duct type ⁵. The sex distribution is roughly balanced with a possible slight male predominance ¹⁵.

Clinical presentation

Clinical presentation can be difficult to distinguish from chronic pancreatitis with repeated acute exacerbations. Patients can present with abdominal pain, weight loss, obstructive jaundice, pancreatitis and new-onset diabetes mellitus ^5,9. 

Pathology

Intraductal papillary mucinous neoplasms are one of several mucinous tumors of the pancreas and can be further divided both histologically and with respect to their macroscopic appearance ⁵.

Location

Reported locations of IPMN include ¹⁵:

• head ~50%

• tail ~7%

• uncinate process ~4%

• elsewhere throughout the pancreas ~40%

Macroscopic appearance

Divided macroscopically:

• main duct type

  • reminiscent of chronic pancreatitis

  • segmental or diffuse distribution

  • highest malignant potential ⁶

    • ~60% are malignant ¹⁰

• branch duct type

  • mostly seen in the head and uncinate process

  • more localized and mass-like

  • may be multifocal ¹³

  • may be macro- or microcystic in appearance ⁵

  • typically indolent behavior ⁶

    • ~5% (range 2-10%) are malignant ^11,12

• mixed type

  • similar to the main duct type in terms of prognosis and overall survival

Solid components, as well as bile duct dilatation ¹⁴, are suspicious of malignant transformation.

Microscopic appearance

They are histologically divided into:

• adenoma

• borderline-malignant

• intraductal papillary mucinous adenocarcinoma

Markers

In patients without pancreatitis, abnormal (either elevated or depressed) pancreatic enzyme markers (amylase/lipase) are associated with malignant IPMN, with the elevation of these a marker of invasiveness ⁸. 

Radiographic features

The characteristic feature is that these tumors communicate with the main pancreatic duct or its branches, which helps distinguish them from mucinous cystadenoma/cystadenocarcinoma, which do not.

Calcifications have been reported in retrospective imaging analyzes of resected IPMN at an incidence of ~13% (range 5-20%) ^17-21, however, the overall incidence of calcifications in all IPMNs (i.e. resected and unresected) is not known (c.2023) and, interestingly, calcifications are not a criterion in the Kyoto guidelines to help guide whether surgical treatment is appropriate and are much more common in other pancreatic cystic lesions (e.g. serous cystadenomas).

Fluoroscopy

ERCP

Direct imaging of the pancreatic duct demonstrates variable dilatation (segmental, diffuse, or branch) depending on the type. Polypoid mural tumor or amorphous mucinous luminal filling defects may be identified ⁵.

Mucinous material may be seen protruding from the ampulla of Vater ⁶.

Ultrasound

Ultrasound may demonstrate small thin-walled pancreatic cysts or dilated hypoechoic ducts (main pancreatic duct over 5 mm in caliber). Diffuse main duct type appears essentially indistinguishable from chronic pancreatitis, with duct dilatation and parenchymal atrophy ⁵.

Mural nodules and mucin globules may appear hyperechoic and difficult to separate from adjacent pancreatic parenchyma ⁶.

CT

They present as single or multiple pancreatic cystic hypodense lesions. Dilatation of the main duct over 5 mm concerns the main duct type IPMN. The communication with the pancreatic ducts, particularly the side branch lesions, may be difficult to demonstrate on CT. They do not calcify. 

Both a dedicated pancreatic CT protocol and pancreatic MRI/MRCP have been reported as having similar accuracy in the characterization of the pancreatic cystic lesions ¹⁶, but guidelines recommend MRI as the modality of choice for IPMN follow-up.  

MRI

MRI, particularly MRCP, is considered the most sensitivity modality to characterize IPMNs ²³.

• main duct type

  • segmental or diffuse main pancreatic duct dilatation >5 mm without stricture ^22,23

  • pancreatic parenchymal atrophy is common ²³

  • bulging duodenal papilla: due to mucinous distension of the ampulla of Vater; a less common but highly specific (>97%) finding ²²

  • solid mural nodules are concerning for malignant transformation, particularly if enhancing following administration of contrast ^ref

    • the absence of mural nodules does not exclude malignancy ²²

  • mucin globules do not enhance and lie dependently within the duct

• branch duct type

  • the majority of the gland is normal in appearance, except for a single or multifocal cystic lesions that communicate with the main pancreatic duct ²³

  • these can measure between a few millimeters to a few centimeters ²³

  • cystic mass-like appearance, which has been has been termed a bunch of grapes although uncommonly can be unilocular ²²

• mixed type

  • appears like an advanced branch duct IPMN with main pancreatic duct dilatation over 5 mm ²³

See the Kyoto guidelines for further details.

Treatment and prognosis

Although generally indolent, malignant degeneration does occur, with direct invasion into adjacent organs or, more frequently, dissemination in the peritoneal cavity (pseudomyxoma peritonei).

Consensus criteria recommend resection for main duct type IPMNs and varying treatment of branch duct type IPMNs, ranging from resection to surveillance, depending on high-risk stigmata and worrisome features (see Kyoto guidelines). Patient co-morbidities and wishes clearly have a major impact on the decision to operate.

If the lesion is proximal (either segmental main duct type or branch type), a Whipple procedure may be performed. If distal, a partial pancreatectomy suffices. Complete resection is curative.

Differential diagnosis

Main duct IPMN

• chronic pancreatitis: can be difficult to distinguish from main duct type on account of dilated duct ⁵ but main duct strictures and pancreatic stones are far more common in chronic pancreatits ²²

Branch-type IPMN

• mucinous cystadenoma/cystadenocarcinoma: should not appear to communicate with the main pancreatic duct ²³

• serous cystadenoma

  • should not appear to communicate with the main pancreatic duct ²³

  • appear similar to microcystic branch type IPMN ²³

  • central stellate scar +/- calcification ²³

• pancreatic pseudocyst

  • should not appear to communicate with the main pancreatic duct ²³

  • more commonly unilocular ²²

Practical points 

The radiological report has to be clear regarding imaging worrisome features of these lesions that may guide further surgical intervention:

• main duct type

  • main pancreatic duct over 5 mm

  • presence of contrast-enhancing components

• branch duct type

  • main pancreatic duct over 5 mm

  • cyst diameter ≥3 cm

  • presence of a contrast-enhancing mural nodule ≥5 mm ¹⁶

  • presence of solid mass ¹⁶

  • thickened and enhancing cyst wall

  • growth rate ≥5 mm/year

Clinical features to guide surgery may also include:

• increased serum CA 19-9 level

• endoscopic ultrasound (EUS) with FNA sampling 

  • CEA

  • cytology: differentiate between benign and lesions with either high-grade dysplasia or cancer

  • KRAS/GNAS mutation analyzes ¹⁶

• new onset of ¹⁶

  • jaundice

  • diabetes mellitus

  • acute pancreatitis