Intraductal Papillary Mucinous Neoplasm (IPMN)

Intraductal papillary mucinous adenoma

Intraductal papillary mucinous carcinoma

Mucin-producing tumour

Mucinous duct ectasia

Ductectatic mucinous cystadenoma/cystadenoacarcinoma

Villous adenoma

Papillary adenoma/carcinoma

Epidemiology:

• M > F
• Common
• Elderly
• Peutz-Jeghers
• FAP

Common sites:

• head > tail of pancreas
• may extend to the ampulla of Vater and common bile duct

Gross features:

• arise in main pancreatic ducts or its branches
• macroscopically identifiable by definition (at least 1 cm arbitrarily) (distinguish from PanIN)
• relatively large size
• significant luminal accumulation of mucin (one feature that distinguishes it from ITPN)
• mucin extrusion from the ampulla of Vater (characteristic but not always)
• multicentricity (up to 40%)
• heterogeneous thickening, fibrotic foci, or gelatinous stromal masses characteristic for invasive carcinoma
• thorough histologic sampling is needed to rule out invasion
• fistulization to other organs (controversial as to whether this constitutes invasion)

Histologic features:

• predominantly papillary histological growth pattern (most) (one feature that distingusihsed it from ITPN)
• may be flat or form tubules as well
• simple and villous like, or complex and branching
• columnar mucin-producing cells characteristically
• can show a variety of directions of differentiation (4 types / subclassifications):
• gastric

• innocuous, tall columnar cells with basally oriented nuclei and abundant pale mucinous cytoplasm reminiscent of gastric foveolar epithelium
• pyloric-like glands at periphery often
• low or intermediate-grade dysplasia generally
• scattered goblet cells maybe

• intestinal

• columnar cells with pseudostratified, cigar-shaped nuclei and basophilic cytoplasm with variable amount of apical mucin
• reminiscent of colonic villous adenomas
• predominant goblet-like cells in some cases
• micropapillary features in some
• intermediate or high-grade dysplasia usually

• pancreatobiliary

• thin, branching papillae with high-grade dysplasia
• cuboidal with round, hyperchromatic nuclei, prominent nucleoli, moderately amphophilic cytoplasm, and less mucinous appearance
• may overlap features wiith intraductal oncoctic papillary neoplasms, or intraductal tubulopapillary neoplasms

• oncocytic

• complex and arborizing papillae with delicate stroma usually
• two to five layers of cuboidal to columnar cells with abundant eosinophilic granular cytoplasm
• nuclei round, large, and fairly uniform and typically contain single, prominent eccentrically located nucleoli
• goblet cells interspersed maybe
• intraepithelial lumina often

• cribriform pattern maybe
• solid pattern maybe

• high-grade dysplasia (most)

• ill-defined leading edge often (often extends microscopically beyond grossly visible lesion
• necrosis / comedonecrosis generally ABSENT (one feature that distinguishes it from ITPN)
• lack of dense “ovarian” stroma
• degree of dysplasia and presence of invasion variable
• noninvasive:
• low-grade dysplasia
1. single layer
2. well-polarized
3. small and uniform nuclei
4. mild pleomorphism
5. rare mitoses
• intermediate dysplasia
1. nuclear stratification
2. crowding
3. loss of polarity
4. enlarged nuclei
5. moderately hyperchromatic
6. identifiable stromal cores maintained
• high-grade dysplasia (Tis stage)
1. severe architectural and cytological atypia
2. irregular branching papillae
3. cribriform growth sometimes
4. lack of polarity
5. stratified, hyperchromatic, pleomorphic nuclei
6. mitoses frequent, even near luminal surface
• “IPMN with an associated invasive carcinoma” (~30%)
• Invasive colloid carcinoma (usually arises in association with intestinal-type IPMN)
• Tubular (conventional, ductal) adenocarcinoma (usually arises in association with pancreatobiliary-type or intestinal0-type IPMN)
• Specify type, grade, size, and stage of the invasive component, and all other parameters typically documented for invasive carcinomas
• Perineural invasion often

Immunophenotype:

Marker:	Sensitivity:	Specificity:
MUC5AC	Common Gastric type Intestinal type Pancreatobiliary type Oncocytic type (focal)	Negative in vast majority of ITPN
CK7	Most
CK19	Most
CA19-9	Most
B72.3	Most
CEA	Most
MUC1	Not gastric type Not intestinal type Pancreatobiliary type
MUC2	Not gastric type Intestinal type Not pancreatobiliary type Not oncocytic type
Intestinal differentiation markers	Intestinal type consistently
CDX2	Intestinal type Not pancreatobiliary type Not oncocytic type
111.3	Oncocytic type
MUC6	Oncocytic type Pyloric components
EGFR	Relatively frequently especially in those with HG dysplasia
ERBB2	Commonly
SMAD4	Most	Loss of expression in high-grade pancreatic intraepithelial neoplasia and in infiltrating ductal adenocarcinoma

Molecular features:

• PIK3CA mutation (?restricted to IPMN and not ductal adenocarcinoma or PanIN)

Other features:

• Epigastric pain
• Chronic pancreatitis
• Weight loss
• DM
• jaundice

References:

• Robbins 2005
• Bosman FT, Carneiro F, Hruban RH, Theise ND (eds). WHO Classification of Tumours of the Digestive Tract, 4^th ed. (2010)