Pancreatic IPMN

Published on 18/07/2015 by admin

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 Well-defined cystic lesion with variable morphology: Unilocular, multicystic, or tubular

image Communication with adjacent main pancreatic duct is key to diagnosis (may be more visible on MR than CT)
image Dilatation of adjacent main pancreatic duct should raise concern for main duct involvement
image Multiplicity is strong clue to diagnosis: Often multiple small cysts scattered throughout pancreas
• Main duct IPMN

image Markedly dilated, tortuous MPD often with bulging ampulla filled with fluid (mucin)
image Dilatation may be segmental or diffuse
image Polypoid nodularity in MPD suspicious for malignancy
image Amorphous calcifications may be seen within duct
image Pancreas often atrophic overlying dilated duct
• Combined IPMN

image Cystic lesion in contiguity with dilated MPD (shares imaging features of main duct and side branch IPMN)

CLINICAL ISSUES

• EUS cyst aspiration: Elevated cyst fluid CEA (> 192 ng/mL)
• Most patients asymptomatic (incidental imaging finding), but can result in repetitive bouts of pancreatitis
• Risk of transformation into invasive carcinoma, with main duct involvement associated with ↑ risk of malignancy
• Management of IPMN based on 2012 IAP guidelines

image Worrisome features: Cyst size ≥ 3 cm, MPD dilatation 5-9 mm, peripheral wall thickening, nonenhancing mural nodularity, abrupt change in main duct caliber with upstream pancreatic atrophy
image High-risk features: MPD dilatation ≥ 1 cm, enhancing solid mural nodularity, or biliary obstruction
image
(Left) Graphic shows combined main and side branch IPMN with gross dilatation of all ducts by mucin, which pours out of a bulging papilla into the duodenum. The parenchyma in the pancreatic head is atrophic.

image
(Right) Coronal MRCP with MIP reconstruction nicely demonstrates 2 discrete side branch IPMNs image and their direct connection with the adjacent normal sized pancreatic duct.
image
(Left) Coronal MRCP with MIP reconstruction demonstrates multiple cysts throughout the pancreas compatible with multiple side branch IPMN. Multifocality is characteristic of IPMN, and multiple discrete cystic lesions are often present in the same patient.

image
(Right) Coronal CECT demonstrates innumerable pancreatic cysts, compatible with multiple side branch IPMN. No suspicious individual cyst or solid mass was seen, but EUS findings were suspicious, and the patient was found to have invasive carcinoma at surgery.

TERMINOLOGY

Abbreviations

• Intraductal papillary mucinous neoplasm (IPMN)

Synonyms

• Intraductal papillary mucinous tumor, intraductal mucin-hypersecreting neoplasm, ductectatic mucinous cystadenoma/carcinoma

Definitions

• Mucin-producing papillary tumor arising from epithelium of main pancreatic duct (MPD) or pancreatic duct side branches

IMAGING

General Features

• Best diagnostic clue

image Side branch type: Cystic lesion with direct communication with adjacent MPD on CECT/MRCP
image MPD type: Dilated MPD with bulging papilla and enhancing soft tissue nodularity within duct lumen
• Location

image Side branch lesion: Predisposition for uncinate process and head, but can occur anywhere in pancreas
image MPD lesion: Either diffuse or segmental involvement of pancreatic duct, but most often involves body and tail
• Size

image Side branch cysts: Variable, but most side branch IPMN measure 5-20 mm
• Morphology

image IPMN: Subdivision of mucin-producing tumors (along with mucinous cystic neoplasm)
image Classified into 3 types

– Side branch pancreatic duct (BPD) type: Focal lobulated “multicystic” dilatation of branch ducts
– Main pancreatic duct (MPD) type: Diffuse dilatation of main pancreatic duct
– Combined type: Dilatation of both BPD and MPD

CT Findings

• Side branch IPMN

image Well-defined cystic lesion with variable morphology: Unilocular, multicystic (with grape-like clusters or tubes and arcs), or tubular
image Communication with adjacent MPD is key to diagnosis, but may not always be possible to demonstrate

– May be more apparent on multiplanar reformations
– Dilatation of adjacent main pancreatic duct should raise concern for main duct involvement
image Multiplicity is strong clue to diagnosis: Often multiple small cysts scattered throughout pancreas
image Calcifications in 20%, but no correlation with malignancy
• Main duct IPMN

image Markedly dilated, tortuous MPD without evidence of distal obstructing mass and often with “bulging” ampulla filled with fluid (mucin) at duodenal sweep

– Dilatation may be segmental or diffuse
– Possibility of main duct IPMN should be considered when duct measures ≥ 5 mm
image Presence of polypoid enhancing nodularity within MPD lumen is very suspicious for malignancy
image Amorphous calcifications may be seen within duct
image Pancreas often atrophic overlying dilated duct
• Combined IPMN

image Cystic lesion in contiguity with dilated MPD (shares imaging features of main duct and side branch IPMN)
• Concerning imaging features based on 2012 International Association of Pancreatology (IAP) guidelines

image Worrisome features: Cyst size ≥ 3 cm in any dimension, MPD dilatation between 5-9 mm, peripheral wall thickening or enhancement, nonenhancing mural nodularity, abrupt change in main duct caliber with distal pancreatic atrophy, lymphadenopathy
image High-risk features: MPD dilatation ≥ 1 cm, enhancing solid mural nodularity, or biliary obstruction

MR Findings

• Little data directly comparing CT and MR, but MR likely superior for identifying small cysts and multifocal disease, visualizing communication between cyst and main duct, and assessing main duct involvement

image Superior soft tissue resolution of MR may allow better assessment of subtle mural nodularity
• Side branch IPMN typically hyperintense on T2WI and low signal on T1WI, and can appear unilocular, multicystic, tubular, or as grape-like cluster of cysts

image Presence of dilated adjacent main pancreatic duct concerning for main duct involvement

– MRCP may be more accurate than CT for assessing main duct size and internal mural nodularity
• Direct communication with main pancreatic duct easier to identify on thin-section 3D MRCP images

image Enlargement of cyst following administration of secretin may be secondary sign of communication with main duct
• Malignant IPMN may have lower ADC values on DWI compared to benign IPMN, but not widely clinically utilized (due to overlap in ADC values)

Ultrasonographic Findings

• Conventional ultrasound lacks spatial resolution to identify high-risk or worrisome imaging features
• Endoscopic ultrasound (EUS): Now considered important part of evaluation of pancreatic cysts in specialized centers

image Spatial resolution of EUS may help identify suspicious morphologic features (e.g., mural nodularity) not visible on CT/MR, and can help guide FNA and cyst aspiration

– May identify communication between cyst and MPD
image 2012 IAP guidelines recommend EUS with cyst aspiration for cysts with worrisome imaging features 

– Cyst size ≥ 3 cm, MPD dilatation 5-9 mm, peripheral wall thickening, nonenhancing mural nodularity, etc.

Radiographic Findings

• ERCP

image Direct visualization of patulous, bulging, “fish-mouth” ampulla with mucin extruding through ampulla (due to mucin hypersection) in main duct IPMN
image Can directly demonstrate dilatation of MPD (in main duct IPMN) or communication of side branch IPMN with MPD
image Filling defects within duct (either nodular or band-like) may represent mucin or papillary tumors

Imaging Recommendations

• Best imaging tool

image MR or CECT are best initial noninvasive modalities
image EUS utilized for lesions with suspicious imaging features

DIFFERENTIAL DIAGNOSIS

Chronic Pancreatitis

• Dilated, beaded, irregular main pancreatic duct with intraductal calculi and parenchymal atrophy/calcifications
• Significant imaging/clinical overlap with main duct IPMN

Pancreatic Ductal Carcinoma

• Hypodense mass with abrupt cutoff of pancreatic duct and upstream MPD dilatation/parenchymal atrophy
• Small occult lesion obstructing MPD may appear identical to main duct IPMN

Pancreatic Pseudocyst

• Cystic lesions that may communicate with MPD and can mimic side branch IPMN
• Usually known clinical history of pancreatitis (or risk factors) and inflammatory changes surrounding cyst

Mucinous Cystic Pancreatic Tumor

• Cyst (± thick wall) most often occurring in pancreatic body/tail in middle-aged female
• Unilocular or oligocystic with no MPD communication

Pancreatic Serous Cystadenoma

• Classic microcystic lesions appear sponge-like and are composed of multiple tiny cysts (± central calcification)
• No demonstrable communication with MPD

PATHOLOGY

General Features

• Etiology

image Pathogenesis: Follows adenoma-carcinoma sequence  

– Hyperplasia of columnar epithelial cells lining ducts → dysplasia and proliferation to form papillary projections → papillary projections protrude into and expand branch ducts (BPD) and MPD → excessive mucin production, obstruction, and dilatation of BPD/MPD
• Genetics

image Several known associated gene mutations including KRAS (∼ 50% of cases)

Staging, Grading, & Classification

• IPMN can be divided into 3 types

image Side branch IPMN: Mucin-producing neoplasm centered in pancreatic duct side branch with normal MPD

– Variable risk of malignancy: ∼ 25% contain high-grade dysplasia and ∼ 17% contain invasive carcinoma
image Main duct IPMN: Mucin-producing neoplasm centered in main pancreatic duct

– High risk of malignancy: ∼ 62% contain high-grade dysplasia and ∼ 58% contain invasive carcinoma
image Combined IPMN: Involves both main duct and side branch with malignancy risk similar to main duct IPMN
• WHO classification separates IPMN into 4 categories

image IPMN with low-grade dysplasia (previously adenoma)
image IPMN with intermediate-grade dysplasia (previously borderline)
image IPMN with high-grade dysplasia (previously carcinoma in situ)
image IPMN with invasive carcinoma
image High-grade dysplasia or invasive carcinoma considered true malignancy

Gross Pathologic & Surgical Features

• Side branch type

image Single or multiple dilated branch ducts
image Cluster of grapes appearance often within head or uncinate process
image Cysts communicate with MPD

– Communication to MPD best seen with MRCP
• MPD type

image Dilated MPD > 5 mm filled with mucin
image Bulging ampulla with mucin streaming form papilla on ERCP

Microscopic Features

• Histologic subtypes based on mucosal lining: Gastric, intestinal, pancreatobiliary, oncocytic, and tubular subtypes

CLINICAL ISSUES

Presentation

• Most common signs/symptoms

image Majority of patients asymptomatic (incidental finding)
image Usually nonspecific symptoms: Abdominal pain, weight loss, nausea, vomiting
image Obstruction of MPD with mucin can result in repetitive bouts of pancreatitis or exocrine/endocrine insufficiency
• Lab data

image EUS-guided cyst aspiration: Elevated cyst fluid CEA (> 192 ng/mL), positive mucin stain
image Amylase/lipase may be elevated due to pancreatitis
image Elevated CEA and CA 19-9 concerning for malignancy

Demographics

• Age

image Presentation usually between 50-70 years
• Gender

image Possible slight male predominance
• Epidemiology

image Most often incidentally discovered asymptomatic pancreatic cystic neoplasm
image True incidence unclear, as lesions are usually (and increasingly) identified incidentally on CT or MR

– IPMN accounts for 20-50% of all pancreatic cysts
image More common in familial pancreatic cancer, Peutz-Jeghers, and familial adenomatous polyposis

Natural History & Prognosis

• Most lesions are asymptomatic, incidental findings, but can result in recurrent attacks of acute and chronic pancreatitis
• Risk of transformation into invasive carcinoma

image ↑ risk of invasive carcinoma distant from primary lesion suggests entire ductal epithelium may be predisposed to development of atypia (field defect theory)
image Presence of multiple IPMN may also be associated with ↑ risk of invasive carcinoma

Treatment

• Management of IPMN based on 2012 IAP guidelines

image High-risk features (MPD ≥ 1 cm, enhancing mural nodularity, or biliary obstruction) warrant resection
image Lesions with worrisome features (cyst size ≥ 3 cm, MPD dilatation between 5-9 mm, nonenhancing mural nodularity, abrupt change in main duct caliber with distal pancreatic atrophy) should undergo EUS

– Presence of suspicious cytology or mural nodularity/main duct involvement on EUS in this subgroup warrants consideration of surgery
– If EUS is negative, follow up with CT/MR based on size (2-3 years for cysts < 1 cm, yearly × 2 years for 1-2 cm, and 3-6 months for > 2 cm)
image For lesions without worrisome imaging features, follow up based on size as above (surgery often considered for cysts measuring ≥ 3 cm in young patients)
image Cysts may be resected regardless of worrisome features or size if patient is symptomatic
image Surgery depends on cyst location and extent of MPD involvement: Whipple, distal pancreatectomy, or total pancreatectomy

– If multiple cysts, most suspicious often resected and other lesions observed

DIAGNOSTIC CHECKLIST

Image Interpretation Pearls

• Consider IPMN when confronted by pancreatic cyst that communicates with adjacent pancreatic duct
• Differentiate main duct IPMN from other causes of dilated pancreatic duct (e.g., obstructing pancreatic mass, chronic pancreatitis)
image
(Left) Axial CECT demonstrates a cystic lesion image in the pancreatic head. Note the soft tissue image around the margins of the cyst, as well as its communication with a dilated pancreatic duct image. This was found to be an IPMN with invasive carcinoma and main duct involvement at surgery.

image
(Right) Coronal volume-rendered CECT demonstrates a complex cystic mass image in the pancreatic head with multiple septations, mural nodularity, and obstruction of the CBD. This was found to be an IPMN with invasive carcinoma.
image
(Left) Axial T2 FS MR demonstrates diffuse severe dilatation of the MPD, with associated pancreatic parenchymal atrophy.

image
(Right) Coronal MRCP with MIP reconstruction better demonstrates the severe dilatation of the entire MPD as well as marked cystic dilatation of innumerable side branches. Frank mucin was seen extruding from the duct on ERCP, and this was found to represent a main duct IPMN with invasive carcinoma.
image
(Left) Axial CECT demonstrates a profoundly dilated MPD with amorphous calcifications image in the center of the duct and clear enhancing intraductal soft tissue image. The pancreatic parenchyma is severely atrophic.

image
(Right) Axial CECT in the same patient shows a large cystic mass inferior to the pancreas directly contiguous with the dilated pancreatic duct. Note the large amount of enhancing soft tissue image within the mass. This was found to represent a mixed-type IPMN with invasive colloid carcinoma at surgery.
image
(Left) Coronal CECT demonstrates a diffusely dilated MPD image. Note the presence of subtle enhancing soft tissue image within the duct.

image
(Right) Axial CECT from the same patient demonstrates multiple discrete enhancing nodules image within the downstream duct, a highly suspicious feature for malignancy. This was found to be a main duct IPMN with invasive carcinoma at surgery.
image
(Left) Axial CECT shows multiple calcifications within a markedly dilated pancreatic duct image.

image
(Right) Axial volume-rendered CECT in the same patient shows that the calcifications are associated with soft tissue masses image within the massively dilated pancreatic duct. At surgery the calcifications were due to invasive mucinous adenocarcinoma from a main duct IPMN.
image
(Left) Axial CECT shows focal dilatation of the MPD in the tail of the pancreas image.

image
(Right) Axial CECT at a more caudal level in the same patient shows extensive mucinous material filling the lesser sac image. At surgery a ruptured IPMN was found with mucinous debris in the lesser sac.
image
(Left) Axial CECT with curved planar reformation shows a diffusely dilated MPD image with a bulging ampulla image, a characteristic feature of main duct IPMN.

image
(Right) Axial CECT demonstrates a markedly dilated MPD image that contains intraductal solid tissue image characteristic of a malignant main duct IPMN.
image
(Left) Axial minimum-intensity projection image (MinIP) from a CECT shows a cystic lesion image connected by a side branch image to the MPD image. These findings are diagnostic of a side branch IPMN.

image
(Right) ERCP in the same patient demonstrates the side branch IPMN image and confirms its communication with the adjacent main pancreatic duct image.
image
(Left) Axial CECT demonstrates gross dilation of the entire pancreatic duct image, with diffuse atrophy of the pancreatic parenchyma, a characteristic constellation of findings for a main duct IPMN.

image
(Right) Endoscopic photograph in the same patient shows a gaping ampulla image with clear mucin pouring from the orifice, a classic finding in main duct IPMN due to mucin hypersecretion by the tumor.
image
Axial CECT shows combined main- and branch-type IPMN, with dilatation of all pancreatic ducts and pancreatic parenchymal atrophy.

image
Axial CECT shows combined branch pancreatic duct (BPD) and main pancreatic duct (MPD) IPMN. Note the dilated main pancreatic duct and glandular atrophy. No mass is present.
image
Axial CECT shows combined branch pancreatic duct (BPD) and main pancreatic duct (MPD) IPMN. Note the cystic dilatation of the branch ducts in the pancreatic head and uncinate.
image
Coronal MRCP with MIP reconstruction demonstrates a cystic lesion image with a cluster of “grapes” morphology directly communicating with the normal-sized main pancreatic duct, compatible with a side branch IPMN.
image
Axial CECT in a patient with combined main and branch IPMN types shows dilation of the pancreatic duct image throughout its length. In addition, a discrete cystic mass image is present in the pancreatic head, in direct communication with the duct. The pancreatic parenchyma is atrophic.
image
Coronal MRCP in the same patient nicely demonstrates numerous cyst-like focal dilations of the side branches image. MRCP is an excellent noninvasive method to evaluate suspected pancreatic IPMNs.
image
Coronal MRCP in the same patient confirms the dilation of the main pancreatic duct image, as well as the side branches. Note the cyst-like focal dilations of side branches image.
image
Coronal volume-rendered image shows a hypodense mass image obstructing the pancreatic image and common bile duct image.
image
Axial CECT in the same patient shows dilation of multiple pancreatic duct side branches image and a hypodense intraductal solid mass image within the pancreatic duct image. Whipple resection confirmed invasive carcinoma and IPMN.
image
Curved planar reformation CECT shows markedly dilated main pancreatic duct image. Note enhancing soft tissue mass within the duct image.
image
Coronal scan in the same patient shows punctate calcifications image within the intraductal soft tissue mass. Whipple resection showed a malignant IPMN with invasive carcinoma. Main duct IPMNs have a much higher malignant potential than side branch lesions. A soft tissue mass within the pancreatic duct strongly suggests carcinoma.
image
Gross pathologic specimen shows a main duct IPMN within a markedly dilated main duct image. Note nodular mucosa with abundant mucin (stained with yellow dye). (Courtesy M. Mino-Kenudson, MD.)
image
Gross pathologic specimen shows an IPMN branch duct type. Note the small cyst with a smooth lining image connected to the main pancreatic duct image through a dilated branch duct image. (Courtesy M. Mino-Kenudson, MD.)
image
Coronal curved planar CECT demonstrates a diffusely dilated pancreatic duct image. Note the subtle soft tissue mural nodularity image within the duct lumen downstream, a highly suspicious feature for malignancy. This was found to be a main duct IPMN with invasive carcinoma.
image
Coronal MRCP in a patient with combined main and side branch IPMN shows the dilated pancreatic duct image and common bile duct image. A cluster of dilated, mucin-filled branch ducts image in the pancreatic head are seen, simulating a multicystic pancreatic head mass such as serous cystadenoma.
image
Endoscopic view shows mucin pouring out of a patulous papilla in a patient with main duct IPMN.
image
Axial T2 HASTE MR demonstrates a complex multilocular cystic lesion image in the pancreatic uncinate process.
image
Coronal MRCP with MIP reconstruction in the same patient demonstrates that the cystic lesion image communicates with the adjacent normal sized pancreatic duct, compatible with a side branch IPMN. There is an additional smaller IPMN in the pancreatic tail image.
image
Coronal MRCP with MIP reconstruction demonstrates a side branch IPMN image with a “bunch of grapes” appearance.

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