1. Pancreatic Cystic Neoplasms
Bible Class
4th Sept.2013
Zystische Pankreasläsion – wie weiter?
Universitätsklinik für Viszerale Chirurgie und Medizin

2. What type of pancreatic cysts exist ?
Why is this differentiation important ?
Acquired Cysts:
Congenital Cysts:
Cystic Neoplasms:
Post-inflammatory fluid collection Pseudo-,-Pseudocyst Postnecrotic sequestrum Parasitic, Ecchinococcal etc.
Risk Malignancy
Benign
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
True cysts
Enterogenous cysts/ duplication cysts (Epi)dermoid cysts, Endometriose
Polycystic diseases; Cystic Fibrosis
This why it is important to ask about history of pancreatitis!

3. 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

4. Key features: Serous Cystic Neoplasm
micro-, oligo-, macrocystic typically: multicystic cluster (each < 2 cm) = honeycumbed No communication with pancreatic duct
Stroma: (central fibrous and) calcified (stellate scar)
Malignant potential:
Location:
Demographics, rate:
Morphology: NO
throughout the pancreas
(older) women (80%), 15-20% of PCNs
Thin almost translucent wall (vs. Post-inflammatory cysts with fibrous adherence to surrounding)
Single uniform layer of cuboid, glycogen-rich «serous» cells
Contrast to MCN, IPMN: NO!! Atypia or dysplasia
RARELY malignant version = serous cystadeno-Carcinom (only a handful of case reports) = BENIGN
Can grow slowly (the bigger the more likely: Mass General: > 4 cm size then in averag 2cm/year gain in size)
Unclear whether this has impact on malignant potential -> but sure can cause symptomse -> then surgery?
Central scar, up to 30% and if present is pathognomonic for SCN
Macrocystic only up to 10% of cases, often difficult to seperate from MCN
Usually no EUS necessary; and FNA often difficult in microcystic lesions (since volume very low)

5. Key features: IPMN Types: 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)
Types:
Malignant potential:
Location:
Demographics, rate:
Morphology:
Main-, branch-duct, mixed type
Yes (esp. main/combined duct IPMN)
M: head BD: multifocal !!
Risk malignancy: yes all, but particularly main- and so called mixed typ duct BD: all also pre-malignant but depending on size and associated features
Location: M: 2/3 head of pancreas
Gender: M: bit more men
Morphology: M: dilated main duct > 6 mm, 1/3 fish-mouth, bulging mucus from the papilla, most intestinal type
B: dilated side branch: multifocal!! In up to 40% of cases more than 2 cysts! Important for surveillance after resection (later) – since de novo (unmasked) or concomitant PD-AC
Also: in resected BD-IPMN: 25% show main-duct communication so to say = M-IPMN
Equal m/w, middle-age/old; >25% of PCNs

6. Key features: MCN thick-walled single cyst, often septations
Epithelial layer with mucin-producing cells, ovarian-like stroma
No communication with pancreatic duct
Malignant potential:
Location:
Demographics, rate:
Morphology:
Yes (but lower than IPMN)
Body/tail (95%), always single lesion!
Middle-aged women (95%), 25% of PCNs
Risk malignancy: yes, but lower than IPMN, in one series all malignant MCNs were > 4 cm or with nodules
NOT ALL do progress, risk about 15%!!

7. Risk of malignancy in pancreatic neoplastic cysts ?
What factors determine malignant risk in IPMN/MCN?
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
% Prevalence malignancy 1
(+) VERY low (malignant = serous cystadenocarcinoma)
+ Low malignant potential 2
Variable 2
Size
Histopathological type
Also histological type essential: but determined only in resection on pathology:
Gastric, intestinal, pancreaticobiliary and oncocytic SCN: less than 1% malignant, only case reports in literature (Check details)
IPMN: most aggressive form of PCN Main-IPMN basically all are believed to develop into invasive cancer BD-IPMN: more indolent than main-duct IPMN but: surveillance studies: indicate development of cancer in about 2%/year (20%/10 years) in resected cases of BD-IPMN: average rate of cancer 25% problem also of concomitant risk for pancreatic adenocancer
SPN: solid-Pseudo-Papillary: Rare! < 5%
30-40 years
90 % women
Random location in the pancreas
Low-grade malignancy
Calcification

8. 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

9. 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

10. 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

12. What are drawbacks of EUS ?
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
Epithelium very thin, in some cases even epithelial denudation
SCA: if cells or cluster to be seen – as in this smear and cytology work-up: cuboid, small round nuclei, clear cytoplasm
Including high-grade
atypical epithelial cells:
diagnostic in mucinous cysts
diagnostic accuracy: 80%

13. 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
BD-IPMN: resection specimen: low-grade dysplasia: only 3% mural nodules
high-grade dysplasia or carcinoma: 60% have mural nodules
Problem: distinguishing nodules from mucin globules: latter are moving (a feature not possible in CT)

14. EUS-FNA: Fluid Analysis in Cysts
Typ
SCN
MCN
IPMN
SPN
Pseudocyst
Viscosity
Mucin
Amylase
Cytology
Viscosity
Low
High NA
Mucin
Amylase
< 250 U/L
< 250 U/La
Low
High
Cytology
negative or
Glyogen-con-taining cuboid cells
mucin-
containing column cells
papillary clusters of
column cells, atypia
Branching papillae
cuboid or cylindric cells, high cellularity, myxoid stroma
«dirty material»
Macrophages,
Inflammatory cell
Cytology: Pseudocyst: debris, protein-precipitates, inflammatory cells, macrophages = dirty material
Amylase: = connection to duct = exclusion of SCN and MCN, in IPMN some early forms can and do have high levles

15. 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
CEA: differentiation serous from mucinous: <5 basically excludes a mucinous neoplasm cut-off: 192: seperating mucinous from non-mucionous lesions diagnostic accuracy 80%
> 800 indicates strongly a mucinous lesion with PPV 94% and accuracy 80%
exact cut-off however unclear
does not correlate with risk of malignancy

16. 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
CT/MRI yearly (for 2 years) lengthen interval if no change
EUS in 3-6 months
Lengthen interval, alternating EUS and MRI
Consider surgery in young, fit patients (long surveillance)
Close surveillance
alternating MRI with EUS every 3-6 months
Strongly consider surgery (in young, fit patients)

17. Which syndrome associates with multiple/ oligocystic SCN ?
Hippel-Lindau-Syndrome
Due to genetic overexpression of VEGF- thus it may