GITj club cp ns guidelines.

Universitätsklinik für Viszerale Chirurgie und Medizin / www.chirurgiebern.ch
Pancreatic cysts

What type of pancreatic cysts exist ?
Acquired Cysts:
Congenital Cysts:
Cystic Neoplasms:
Post-inflammatory fluid collection
Pseudo-,-Pseudocyst
Postnecrotic sequestrum
Parasitic, Ecchinococcal etc.
True cysts
Enterogenous cysts/ duplication cysts
(Epi)dermoid cysts, Endometriose
Polycystic diseases; Cystic Fibrosis
Cystic Neoplasms:
- IPMN: Intraductal papillary mucinous neoplasm
- MCN: Mucinous cystic neoplasm
- SCN: Serous cystic adenoma/ neoplasm
- SPN: Solid pseudopapillary neoplasm
- CPEN: Cystic pancreatic endocrine neoplasm
Why is this differentiation important ?
Risk Malignancy
Benign

How frequent are neoplastic
pancreatic cystic lesions ?
Average: 2.5%
Age > 70 years: 10-20%*
*: MRI in non-pancreatic disease: 20% of 1444 patients; Zhang XM et al. Radiology 2002

Key features: Serous Cystic Neoplasm
 Malignant potential:
 Location:
 Demographics, rate:
 Morphology: micro-, oligo-, macrocystic
typically: multicystic cluster (each < 2 cm) = honeycumbed
No communication with pancreatic duct
Stroma: (central fibrous and) calcified (stellate scar)
NO
throughout the pancreas
(older) women (80%), 15-20% of PCNs

Key features: IPMN
 Types:
 Location:
 Morphology:
Yes (esp. main/combined duct IPMN)
M: head BD: multifocal !!
Equal m/w, middle-age/old; >25% of PCNs
Main-, branch-duct, mixed type
Cystic dilatation main (> 6 mm) or side
branches; M: Fish-mouth, globules of mucin (= masses)
Stroma: Lack of ovarian stroma (vs. MCN)

Key features: MCN
 Location:
 Morphology:
Yes (but lower than IPMN)
Body/tail (95%), always single lesion!
Middle-aged women (95%), 25% of PCNs
thick-walled single cyst, often septations
Epithelial layer with mucin-producing cells, ovarian-like stroma
No communication with pancreatic duct

Risk of malignancy in pancreatic neoplastic cysts ?
IPMN: BD-:
MD-:
MCN:
SCN:
SPN:
CPEN:
1: Sakorafas GH et al. Surg Oncol. 2011; 2 Sakorafas GH et al. Surg Oncol 2012
++ ̴ 40% (6-46%) Risk of HGD/ malignancy 1
++++ ̴ 65% (57-92%) Risk of HGD/ malignancy in 5 y 1
++ 6-36% Prevalence malignancy 1
(+) VERY low (malignant = serous cystadenocarcinoma)
+ Low malignant potential 2
Variable 2
What factors determine malignant risk in IPMN/MCN?
 Size
 Histopathological type

What are high-risk stigmata for
malignancy in IPMN/MCN?
 Obstructive jaundice (and cystic lesion of the pa-head)
 Enhancing solid component within cyst
 Main pancreatic duct > 10 mm in size
Consequence?
Consider surgery, if clinically appropriate

If no high-risk stigmata in IPMN/MCN:
What are worrisome features ?
Clinical: Pancreatitis
Imaging: Cyst > 3 cm
Thickened/enhancing cyst walls
Main duct size 5-9 mm
Non-enhancing mural nodule
Abrupt change in caliber of pancreatic duct
with distal pancreatic atrophy
Consequence?
Endo-Sonography

What are the advantages of EUS in
diagnostic workup of pancreatic cysts ?
 Superior, higher-resolution imaging of the pancreas
(ductal communication, additional (smaller) cysts, nodules etc.)
 Fine-needle-aspiration (FNA): sampling fluid for
Cytology and tumor markers

 Operator-Dependent Investigation
 Sampling Error
 Contamination (gastric wall)
 Low cellularity -> Low senstivity
e.g. SCN only 30-40% enough cells
diagnostic accuracy: 10-60%
often NON-diagnostic
What are drawbacks of EUS ?
Including high-grade
atypical epithelial cells:
diagnostic in mucinous cysts
diagnostic accuracy: 80%

What are EUS features leading to consider
surgery ?
 Define mural nodule(s): 3-9 fold risk malignancy
 Main duct features suspicious for involvement
 Cytology: suspicious or positive for malignancy

EUS-FNA: Fluid Analysis in Cysts
Typ SCN MCN IPMN SPN Pseudocyst
Viscosity
Mucin
Amylase
CytologyCytology negative
or
Glyogen-con-
taining cuboid
cells
mucin-
containing
column cells
papillary
clusters of
mucin-
column cells,
atypia
Branching
papillae
cuboid or
cylindric cells,
high cellularity,
myxoid stroma
«dirty
material»
Macrophages,
Inflammatory cell
Viscosity Low High High NA Low
Mucin Low High High NA Low
Amylase < 250 U/L < 250 U/L < 250 U/La Low High

CEA in Cyst-Fluid: What for ? Useful ?
 Mucinous vs. Non-mucinous (serous)
 Cut-off unclear: e.g. > 800 ng/mL
 No correlation with risk of malignancy

How to perform surveillance for
BD-IPMN and MCN?
< 1 cm:
1-2 cm:
2-3 cm:
> 3 cm:
CT/MRI in 2-3 years
Close surveillance
alternating MRI with EUS every 3-6 months
Strongly consider surgery (in young, fit patients)
EUS in 3-6 months
Lengthen interval, alternating EUS and MRI
Consider surgery in young, fit patients (long surveillance)
CT/MRI yearly (for 2 years)
lengthen interval if no change

Which syndrome associates with multiple/
oligocystic SCN ?
Hippel-Lindau-Syndrome

The role of endoscopy in the diagnosis and
treatment of cystic pancreatic neoplasms
Volume 84, No. 1 : 2016 GASTROINTESTINAL
ENDOSCOPY

Cyst fluid collection:
Often present a diagnostic / therapeutic challenge.
They range from pseudocysts &pancreatic necrosis to
benign & malignant neoplasms.
May be encountered during the evaluation of pancreatitis or
abdominal pain&found incidentally in 2.5% of abdominal
imaging performed for unrelated reasons, increases 10% in
70 ys.
Can be misclassified as pseudocysts.

EUS Findings:
• Diagnostic accuracy 40-96%.
• Sensitivity 56%, specifi city 45% for differentiating
mucinous cysts (mucinous cystic neoplasms/IPMNs) from
nonmucinous cysts were low, resulting in poor overall
accuracy 51%.
• The agreement of whether a cyst was neoplastic versus
nonneoplastic was fair with moderate agreement for
serous cystic neoplasms&for solid components.
• Small cyst size alone does not exclude malignancy.
• 20% of lesions 2 cm or smaller were malignant&an
additional 45% of lesions had malignant potential.
• Only 3.5% asymptomatic lesions < 2 cm was malignant.

EUS Findings:
• Certain EUS features are more predictive of particular
types:
• Multiple small (< 3 mm) compartments within a cystic
lesion (microcystic lesion), suggest a serous cystic
neoplasm with an accuracy of 92-96% not seen in
mucinous cystic neoplasms.
• Cysts without septations or solid components within a
pancreas having parenchymal features of pancreatitis
(calcifications, atrophy, change in echo texture) indicates a
pseudocyst with sen of 94% &spec of 85%.
• EUS imaging cannot reliably distinguish benign from
malignant IPMNs.

EUS Findings:
• A mural nodule, MPD dilation, thickened septal walls,
• cyst size > 3 cm on radiologic or EUS imaging were
independent predictors of malignant branch-duct IPMN.
• A MPD 10 mm or the presence of an enhancing solid
component on radiologic imaging as high-risk stigmata.
• Lower risk findings, categorized as worrisome features,
included a cyst size of 3 cm, thickened enhancing cyst
walls, nonenhancing mural nodules, MPD size of 5 to 9
mm, an abrupt change in the MPD caliber with upstream
pancreatic atrophy, or the presence of peripancreatic LAP.
• Distinguishing cyst wall nodules that are epithelial
(neoplastic) from those that are mucinous (nonneoplastic)
is critical to properly risk stratify PCNs.

EUS Findings:
• EUS imaging of intracystic mucus appears as a smooth,
well-defined hyperechoic rim with a hypoechoic center
compared with the surrounding parenchyma serves to
distinguish mucus from true epithelial nodules, which
have ill-defined borders &hyperechoic center.
• Intraductal US may identify malignant IPMN by the
presence of protruding lesions 4 mm.
• Contrast-enhanced EUS, may aid in distinguishing infl
ammatory cysts from cystic pancreatic neoplasms &
vascular epithelial mural nodules from nonvascular
mucous in IPMNs.

EUS -FNA:
Analyzed for cytologic, chemical/or molecular studies.
Any solid component or regional LNs aspirated for cytology
or histology.
A higher diagnostic yield when a solid component on EUS
A dilated PD can be safely targeted for FNA when IPMN is
suspected.
FNA of the cyst wall may provide additional cyto material&
increase the diagnostic yield for mucinous lesions by 37%.
EUS-FNA + CT /MRI increased the overall accuracy for
diagnosing cystic pancreatic neoplasms by 36% & 54%,
respectively.
FNA greatest in cysts containing imaging features most
associated with malignancy, namely an epithelial nodule or
mass lesion, cyst size > 3 cm, or MPD dilation.

Cytology:
Has pooled sensitivity of 63%/specificity of 88% & in other
study were 54%/93%.
Cytologic findings suggestive of a pseudocyst include
macrophages, histiocytes, neutrophils.
The presence of mucin is suggestive of a mucinous
neoplasm&seen in 35% or more of cases.
Glycogen-rich cuboidal cells indicate a serous cystic
neoplasm but are present only in 10% of cases.
The diagnostic accuracy of cytology from EUS-FNA for cystic
lesions ranges from 54-97%&may be lower in smaller cysts.
Malignancy within a cystic neoplasm can be identified by
cytology with 83-99% specificity, sensitivities 25- 88%.
A Cytology brush limited benefit over standard EUS-FNA &
potential increased risk of adverse events.

Chemistry & markers:
• Amylase, lipase, CEA.
• Amylase < 250 U/L virtually excluded (specificity 98%) the
• lesion as a pseudocyst.
• CEA cutoff of 192 ng/mL for differentiating mucinous from
nonmucinous cysts, sensitivity of 75% /specificity 84%.
When morphologic criteria (associated
• Higher CEA levels increase specificity for the diagnosis of
a mucinous cyst but do not correlate with malignancy.
Conversely, a CEA < 5 ng/mL was seen in only 7% of
mucinous cystic neoplasms & all serous cystic
neoplasms. CEA to have a sensitivity of 63% & specificity
of 88% for the identification of mucinous cystic tumors.
• Other tumor markers CA 19-9, CA 125, CA 72-4,CA 15-3,
but none of these appear accurate enough to provide a
definitive diagnosis.

DNA & Molecular analysis:
• Improve the limitations of cytology, chemical/or markers.
An K-ras mutation strongly associated with mucinous
cysts & K-ras/allelic loss showed a specificity of 96% for
malignancy.
• The CEA&DNA molecular analysis improved diagnostic
accuracy compared to either test alone.
• Integrated molecular analysis of cyst fluid (ie,molecular
analysis with imaging&clinical features) was able to better
characterize the malignant potential of pancreatic cysts.
• Acquisition of cyst fluid via EUSFNA, duodenal collection
of pancreatic juice for DNA analysis via an echoendoscope
after secretin stimulation found GNAS mutations in 64.1%.
• Molecular analysis (requires only 200 m L of fluid) may be
most useful in small cysts with nondiagnostic cytology,
equivocal cyst fluid CEA results, or when insufficient fluid
is present for CEA testing.

Emerging techniques:
Direct optical & endomicroscopic exam
of pancreatic cysts has become feasible.
Intracystic visualization &biopsy through a 19-gauge needle
can be obtained with either a reusable 0.9-mm fiberoptic
probe or via a dedicated system primarily indicated for
single-operator cholangioscopy/pancreatography
Real-time in vivo microscopic imaging via needle-based
confocal laser endomicroscopy after IV fluorescein with
presence of epithelial villous structures had a sensitivity of
59% &specificity of 100% for IPMN, MCN, or adenocarcinoma.
A superficial vascular network seen only in serous cystic
neoplasms with accuracy of 87%
The combined findings of mucin (by transneedle
cystoscopy), papillary projections& dark rings on
confocal laser endomicroscopy improved diagnostic
accuracy compared with either technique alone.

EUS Complications:
• Abdominal pain
• Pancreatitis
• Intracystic hemorrhage
• ASGE suggest antibiotics for 3 -5 days after EUSFNA of a
pancreatic cystic lesion.

EUS intervention:
• EUS-guided cyst ablation with ethanol alone or + paclitaxel
for suspected pancreatic cystic neoplasms is performed
only at select centers &might be considered for patients
who refuse or are not candidates for surgery.

ASGE recommendations:
1. EUS-FNA of any pancreatic cystic lesion > 3 cm in
diameter or when cross-sectional or EUS imaging confirms
an epithelial nodule, dilated MPD, or suspicious mass lesion.
2. EUS-FNA is optional in asymptomatics in whom cross-
sectional imaging demonstrates a cyst < 3 cm without either
a mass and/or epithelial nodule or associated dilated MPD.
3. We recommend initial testing of aspirated pancreatic
cyst fluid for CEA, amylase&cytology.
4. We suggest that molecular testing of the cyst be
considered when initial ancillary testing of cytology & CEA is
inconclusive &when test results may alter management.
5. Prophylactic antibiotics for patients undergoing EUS-FNA
for the evaluation of cystic pancreatic neoplasms.
6. ERCP, pancreatoscopy& intraductal US may be helpful in
the diagnosis and characterization of suspected MD IPMNs.

GITj club cp ns guidelines.

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