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Pancreatic Cystic Neoplasms

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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

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