This document provides an overview of pancreatic cyst evaluation and management. It discusses the prevalence of incidentally detected pancreatic cysts on imaging and categorizes cysts as benign, pseudocysts, or one of four subtypes of pancreatic cystic neoplasms (PCNs): serous cystic tumors, mucinous cystic neoplasms, intraductal papillary mucinous neoplasms, and solid pseudopapillary neoplasms. For each PCN subtype, it describes characteristics such as patient demographics, location, risk of malignancy, and management guidelines. It also reviews guidelines for managing pseudocysts and outlines the endoscopic, percutaneous, and surgical drainage options with expected outcomes. In summary,

1. Cyst Assist:
Pancreatic Cyst Evaluation & Management
Patricia L. Raymond MD
FACG
Rx For Sanity

2. Dr. Raymond has no relevant relationships with
commercial interest organizations whose products
are related to the program content.
The Society of Gastroenterology Nurses and Associates, Inc. is accredited as a provider of
continuing nursing education by the American Nurses Credentialing Center’s (ANCC)
Commission on Accreditation.
Disclosures

3. Cyst Assist: Pancreatic Cyst Evaluation & Management
Explore the clinical approach to cystic pancreatic lesions, and review
recent guidelines directing observation, endoscopic evaluation, and
surgical referral for patients with pancreatic cystic neoplasms. Much
of our focus will be to understand the natural history and management
of the four subtypes of pancreatic cystic neoplasms (PCNs): Serous
cystic tumors (SCTs), Mucinous cystic neoplasms (MCNs), Intraductal
papillary mucinous neoplasms (IPMNs), and Solid pseudopapillary
neoplasms (SPNs). Pseudocyst management will be included in this
review of these increasingly frequent and often incidental and
asymptomatic CT and MRI findings.

6. • Widespread use of CT/MRI cross-sectional imaging
• Detected in 2.4 to 2.6 %, increases with age
• No difference by sex
Prevalence of unsuspected pancreatic cysts on MDCT.
Laffan TA, Horton KM, Klein AP, et al.AJR Am J Roentgenol. 2008;191(3):802.
High prevalence of pancreatic cysts detected by screening magnetic
resonance imaging examinations. de Jong K, Nio CY, Hermans JJ,et al.
Clin Gastroenterol Hepatol. 2010 Sep;8(9):806-11. Epub 2010 Jun 1.

7. • 9% in EUS for non-pancreatic indications
341 patients (mean age, 59 years; 187 females), 46 incidental pancreatic cysts (median [range], 5 [2-80]mm) in
32 patients (9.4%). Branch duct IPMN was the most common finding. Seven cysts were larger than 1cm and 1
adenocarcinoma was discovered. Association between pancreatic cysts and older age (odds ratio, 1.04 per year;
95% confidence interval, 1.01-1.08) and female sex (odds ratio, 3.08; 95% confidence interval, 1.25-7.45)
Prospective Cross-Sectional Study of the Prevalence of Incidental
Pancreatic Cysts During Routine Outpatient Endoscopic Ultrasound.
Sey MS, Teagarden S, Settles D, et al. Pancreas. 2015 Oct;44(7):1130-3.

8. Categorization of pancreas cysts

9. Benign: Non-neoplastic pancreas cysts
• Typically diagnosed after surgical resection of
a lesion that was thought to be a pancreatic
cystic neoplasm (PCN) preoperatively
• True cysts
• Retention cysts
• dilated pancreatic duct side branches
arising due to obstruction
oops

10. Diseases where cysts expected: von Hippel-Lindau
• Autosomal dominant syndrome, VHL gene, 1: 36,000
• Mean age at initial presentation of 26 y/o
• VHL-associated tumors includes:
• Hemangioblastomas of the brain (cerebellum) and spine
• Accelerated growth within 2 years of pregnancy
• Retinal capillary hemangioblastomas (retinal angiomas)
• Clear cell renal cell carcinomas (RCCs)
• Pheochromocytomas
• Endolymphatic sac tumors of the middle ear
• Papillary cystadenomas of the epididymis and broad ligament
Pancreatic involvement in von Hippel-Lindau disease. The Gro
Francophone d'Etude de la Maladie de von Hippel-Lindau.
Hammel PR, Vilgrain V, Terris B, et al. Gastroenterology. 2000

11. Diseases where cysts expected: von Hippel-Lindau
• 58 consecutive patients with von Hippel-Lindau disease
• 77 % had a pancreatic abnormality
• 70% with cysts
• 9 % serous cystadenomas
• 9 % with neuroendocrine tumors
Screen: Ultrasound and MRI scan of the abdomen with and
without contrast to assess the kidneys, pancreas, and adrenals
at least yearly
Pancreatic involvement in von Hippel-Lindau disease. The Groupe
Francophone d'Etude de la Maladie de von Hippel-Lindau.
Hammel PR, Vilgrain V, Terris B, et al. Gastroenterology. 2000;119(4):1087.

12. Diseases where cysts expected: Polycystic kidney disease
• Autosomal dominant polycystic kidney disease (ADPKD)
• 1 in every 400 -1000 live births
• < half of these cases will be diagnosed; often clinically silent
• 40-59 years old, at least two cysts in each kidney
• Sensitivity, specificity, PPV 90% 100% 100 %
• > 60 years, at least four cysts in each kidney
• 100 % sensitivity and specificity
• Hepatic cysts >half of cases , more common in women, >40 years
• Pancreatic cysts in 7 to 10%
Unified criteria for ultrasonographic diagnosis of ADPKD.
Pei Y, Obaji J, Dupuis A, et al.
J Am Soc Nephrol. 2009;20(1):205. Epub 2008 Oct 22.

13. Pancreatic Pseudocyst

14. Benign inflammatory fluid collections of pancreas
•Not true epithelial cysts
•Local complications of acute pancreatitis or
pancreas trauma
• Acute peri-pancreatic fluid collection
•Within four weeks of the onset of pancreatitis
•Extra-pancreatic, no wall, no solid material, no
pancreatic necrosis
•Pseudocyst
•Mature fluid collections that are usually outside the
pancreas, at least four weeks after acute pancreatitis
Classification of acute pancreatitis--2012: revision of the Atlanta classification and
definitions by international consensus. Banks PA, Bollen TL, Dervenis C,,et al. Acute
Pancreatitis Classification Working Group Gut. 2013;62(1):102.

15. Benign inflammatory fluid collections of pancreas
• Acute necrotic collection
• Hx necrotizing pancreatitis, may be
adjacent to or involve the pancreas, no
definable wall, and may contain both liquid
and solid material
• Walled-off pancreatic necrosis (WOPN)
• Mature encapsulated collection of
pancreatic necrosis that may contain liquid
and solid elements (with or without
loculation), may be intra- or extra-
pancreatic
Classification of acute pancreatitis--2012: revision of the Atlanta classification and
definitions by international consensus. Banks PA, Bollen TL, Dervenis C,,et al. Acute
Pancreatitis Classification Working Group Gut. 2013;62(1):102.

16. Pancreatic Pseudocyst/WOPN management
• Minimal or no symptoms and no evidence of a
pseudo aneurysm
• Clinical observation with follow-up imaging
• N=19 patients with pseudocysts with a mean
diameter size of 9.7 ± 5.3 cm
• 5 patients (26%) had complete resolution
• 11 patients (58%) decrease in pseudocyst
size in one year
• 2 infected pseudocysts IR and Endo/IR
• CT or MR q three to six months
• Repeated sooner for symptoms abdominal
pain, chills, jaundice, early satiety, or fever
Incidence, risk factors and clinical course of pancreatic fluid
collections in acute pancreatitis. Cui ML, Kim KH, Kim HG, et al
Dig Dis Sci. 2014;59(5):1055. Epub 2013 Dec 11.

17. Pancreatic Pseudocyst/WOPN drainage
• Indicated if symptomatic, have rapidly enlargement or
have systemic illness as a result of an infected
pseudocyst that does not improve with medical
management
• Endoscopic, transmural or trans papillary
• Percutaneous drainage
• Rarely surgical
• Criteria:
• Fluid collection has to be mature (ie, well-defined
wall and mostly liquid content)
• Wall of the fluid collection is adherent to the stomach
or duodenum
• Fluid collection has to be 6 cm in size
The role of endoscopy in the diagnosis and treatment of inflammatory pancreatic fluid collections.
ASGE Standards of Practice Committee, Muthusamy VR, Chandrasekhara V, et al.
Gastrointest Endosc. 2016;83(3):481. Epub 2016 Jan 13.

18. Drainage outcomes with endoscopy
• >90 percent technically successful
• 10 -15% morbidity rate
• 70 - 80 % resolution rate
• 10 - 15 % recurrence rate, 30% for WOPN
Endoscopic drainage of pancreatic-fluid collections in 116 patients:
a comparison of etiologies, drainage techniques, and outcomes.
Hookey LC, Debroux S, Delhaye M, et al. Gastrointest Endosc. 2006;63(4):635.
Single-step EUS-guided transmural drainage of simple and complicated pancreatic
pseudocysts.
Antillon MR, Shah RJ, Stiegmann G, Chen YK Gastrointest Endosc. 2006;63(6):797.
Endoscopic ultrasound drainage of pancreatic pseudocyst: a prospective comparison
with conventional endoscopic drainage. Kahaleh M, Shami VM, Conaway MR, et al.
Endoscopy. 2006;38(4):355.Endoscopic management of pancreatic pseudocysts or
abscesses after an EUS-guided 1-step procedure for initial access.
Krüger M, Schneider AS, Manns MP, Meier PN Gastrointest Endosc.
2006;63(3):409.

21. Four subtypes of PCNs
• Serous cystic tumors (SCTs)
• Mucinous cystic neoplasms (MCNs)
• Intraductal papillary mucinous neoplasms (IPMNs)
• Solid pseudopapillary neoplasms (SPNs)
Each has benign and malignant forms.
• Retrospective series of 851 patients undergoing surgical resection for a cystic neoplasm
of the pancreas between 1978 and 2011
16%
23%
38%
3%
1978-2011
12%
16%
49%
5%
2005-2011
N=376
851 resected cystic tumors of the pancreas: a 33-year experience at the Massachusetts
General Hospital. Valsangkar NP, Morales-Oyarvide V, Thayer SP, et al.
Surgery. 2012;152(3 Suppl 1):S4. Epub 2012 Jul 6.

22. PCNs
•Serous cystic tumors (SCTs)
•Mucinous cystic neoplasms
(MCNs)
•Intraductal papillary mucinous
neoplasms (IPMNs)
•Solid pseudopapillary

23. Serous cystic tumors
• Most are serous cystadenomas
• Benign neoplasms lined by glycogen-rich
cells that originate from pancreatic centro-
acinar cells
• Varieties include microcystic or
oligocystic serous cystadenomas
• Mainly women > 60 years
The spectrum of serous cystadenoma of the pancreas. Clinical, pathologic, and surgical aspects.
Pyke CM, van Heerden JA, Colby TV, Sarr MG, Weaver AL
Ann Surg. 1992;215(2):132.
Image from https://en.wikipedia.org/wiki/Centroacinar_cell
%

26. PCNs
•Serous cystic tumors (SCTs)
•Mucinous cystic neoplasms
(MCNs)
•Intraductal papillary mucinous
neoplasms (IPMNs)
•Solid pseudopapillary

27. Mucinous cystic neoplasms (MCNs)
• Almost exclusively (98%) women, >40 y/o
• Variable cellular atypia
• Secrete mucin similar to IPMNs
• Ovarian-like stroma
• Pancreatic tail/body (93%)
• Doesn’t communicate with pancreatic duct
• Risk of malignancy
• Resection is recommended in appropriate
candidates
%
Mucinous cystic tumors of the pancreas: clinicopathological features, prognosis,
and relationship to other mucinous cystic tumors. Zamboni G, Scarpa A, Bogina G,
et al. Am J Surg Pathol. 1999;23(4):410.
Pancreatic mucinous cystic neoplasm defined by ovarian stroma: demographics,
clinical features, and prevalence of cancer.
Reddy RP, Smyrk TC, Zapiach M, et al. Clin Gastroenterol Hepatol. 2004;2(11):1026.

29. PCNs
•Serous cystic tumors (SCTs)
•Mucinous cystic neoplasms
(MCNs)
•Intraductal papillary mucinous
neoplasms (IPMNs)
•Solid pseudopapillary

30. Intraductal papillary mucinous neoplasms (IPMNs)
• Mucin-producing papillary neoplasms of the pancreatic
ductal system of variable cellular atypia
• Cause dilation of the pancreatic ducts
• Equal sex distribution, incidence peaks > 50 years
• Main pancreatic duct (main duct IPMN)
• Side branch of pancreas duct (branch duct IPMN)
• Mixed-type IPMN
Intraductal papillary mucinous neoplasms of the pancreas: an analysis
of clinicopathologic features and outcome.
D'Angelica M, Brennan MF, Suriawinata AA, Klimstra D, Conlon KC
Ann Surg. 2004;239(3):400. Image from UpToDate.com

33. IPMN surgical outcomes
• 1987 to 2003, 136 pancreatic resections were performed for patients with IPMNs
• Mean age of the patients was 66.8 +/- 1.1 years, with 57% male and 89% white
• IPMNs without evidence of invasive cancer were identified in 62% (n = 84)
• 17% adenoma, 28% borderline, or 55% CIS
• IPMNs with associated invasive cancer 38% (n = 52)
• 60% tubular, 27% colloid, 7% mixed, and 6% anaplastic
• Five-year survival for those patients following resection of IPMNs with invasive cancer
43%
• vs pancreatic ductal adenocarcinoma in the absence of IPMN 15%-25%
• Five-year survival post resection of IPMNs without invasive cancer (regardless of degree
of dyplasia) 77%
• Recurrent disease may occur in the residual pancreas
• Long-term surveillance is critical
• 5-year lag time from IPMN adenoma (63.2 years) to invasive cancer (68.1 years)
• Based on the age at resection data
Intraductal papillary mucinous neoplasms of the pancreas: an updated experience.
Sohn TA, Yeo CJ, Cameron JL, Hruban RH, Fukushima N, Campbell KA, Lillemoe KD
Ann Surg. 2004;239(6):788
%

34. PCNs
•Serous cystic tumors (SCTs)
•Mucinous cystic neoplasms
(MCNs)
•Intraductal papillary mucinous
neoplasms (IPMNs)
•Solid pseudopapillary

35. Solid pseudopapillary neoplasms (SPNs)
• Typically occur in young women < 35 years of age
• Body or tail of the pancreas, rare
• Contain both solid and cystic components and occasional calcifications
• Various nomenclature
• Solid and papillary epithelial neoplasms of the pancreas
• Papillary cystic tumors of the pancreas
%
Diagnosis of solid-pseudopapillary neoplasm of the pancreas by EUS-guided FNA.
Master SS, Savides TJ
Gastrointest Endosc. 2003;57(7):965.

39. Management of cysts

40. Risk of malignancy
• Estimated risk of malignancy at the time of diagnosis is at most 0.01%
• 0.21% for cysts >2 cm
• If cyst was surgically resected, risk of malignancy was 15%
• Selection bias in the surgical series in which cysts were resected
• Increased risk of malignancy
• Cyst size >3 cm (43% versus 22% if the cyst was <3 cm, odds ratio [OR] 3.0)
• Solid component within the cyst (73% versus 23% no solid component, OR 7.7)American gastroenterological association technical review on the diagnosis
and management of asymptomatic neoplastic pancreatic cysts.
Scheiman JM, Hwang JH, Moayyedi P
Gastroenterology. 2015 Apr;148(4):824-48.e22.

41. Risk of malignancy
• The malignant potential of a cyst also depends on the cyst type
• Serous cystic tumors: very low risk for developing malignancy
• Risk is moderate to high:
• Mucinous cystic neoplasms
• Solid pseudopapillary neoplasms
• Some intraductal papillary mucinous neoplasms (IPMNs)
American gastroenterological association technical review on the diagnosis
and management of asymptomatic neoplastic pancreatic cysts.
Scheiman JM, Hwang JH, Moayyedi P
Gastroenterology. 2015 Apr;148(4):824-48.e22.

43. Cyst symptoms
• Most asymptomatic, if symptoms present they are nonspecific
• Serous cystic tumors – cyst enlargement and resultant space occupation
• Cysts > 4 cm in size are more likely to cause symptoms or findings on
physical examination
• Abdominal discomfort, a palpable mass, and bile duct and/or gastric
outlet obstruction
• Mucinous cystic neoplasms
• Abdominal pain, recurrent pancreatitis, gastric outlet
obstruction, and/or a palpable mass
• Jaundice and/or weight loss are more common with malignant
lesions.

44. Cyst symptoms- vary by subtype
• Intraductal papillary mucinous neoplasms (IPMNs)
• Intermittent obstruction of the pancreatic duct with mucus plugs
• History of recurrent acute pancreatitis or symptoms suggestive of chronic
pancreatitis
• Back pain, jaundice, weight loss, anorexia, steatorrhea, and diabetes
suggest malignancy
• Solid pseudopapillary neoplasms (SPNs)
• Incidental detection of SPNs with imaging studies up to 50 percent of cases
• Abdominal pain, nausea, vomiting, and weight loss
• Gastrointestinal obstruction, anemia, jaundice, pancreatitis, palpable mass

45. Differentiate cyst types: MRI
• Magnetic resonance imaging (MRI) with MRCP is first step
• Findings that increase the risk of malignancy (large cyst >3 cm, a solid
component within the cyst, main pancreatic duct dilation)
• Serous cystic tumors – Well-demarcated multicystic lesion
• A central scar or "sunburst" calcification (in 20%, considered diagnostic)
• Mucinous cystic neoplasms – septated cystic lesion, may be unilocular
• May contain eccentric calcifications (seen in up to 15 %)
• Findings associated with malignancy include:
• Larger size (5 cm or larger in one series)
• Thickened or irregular cyst wall
• Internal solid component or mass
• Calcification of the cyst wall
Pancreatic mucinous cystic neoplasm defined by ovarian stroma: demographics,
clinical features, and prevalence of cancer.Reddy RP, Smyrk TC, Zapiach M, et al,
Clin Gastroenterol Hepatol. 2004;2(11):1026.

46. Differentiate: MRI
• Intraductal papillary mucinous neoplasms
• IPMNs may involve the main pancreatic duct, the
branch ducts, or both
• Main duct involvement is characterized by a diffusely
or partially dilated main pancreatic duct filled with
mucin
• Predominantly found in the pancreatic head, but
can involve any part of the pancreas
Mucinous cystadenomas and intraductal papillary mucinous tumors of the pancreas in
magnetic resonance cholangiopancreatography.
Albert J, Schilling D, Breer H, Jungius KP, Riemann JF, Adamek HE

47. Differentiate: MRI
• Intraductal papillary mucinous neoplasms
• Branch-duct (BD) IPMN is characterized by dilation of side branches of the pancreatic
duct
• . Often in the pancreatic head or the uncinate process.
• MRCP VS ERCP
• MRCP is more sensitive for differentiating mural nodules from mucin globs
• Mucin has the same signal intensity as pancreatic fluid
• MRCP is also superior for demonstrating the internal architecture of the main
duct and the extent of IPMN.
• However, MRCP < ERCP in demonstrating peripheral ductal
abnormalities
• Solid pseudopapillary neoplasms
• Lesions may appear as well-demarcated solid tumors.
Mucinous cystadenomas and intraductal papillary mucinous tumors of the pancreas in
magnetic resonance cholangiopancreatography.
Albert J, Schilling D, Breer H, Jungius KP, Riemann JF, Adamek HE

49. • AGA 2015 guidelines:
• Further evaluation only if the cyst has two or more worrisome features
• Size ≥3 cm
• Solid component
• Dilated main pancreatic duct
• Evidence is low quality; it is reasonable to pursue additional evaluation if only one
worrisome feature is present
• ASGE 2016 guidelines:
• EUS-FNA of cysts with any one of the following features:
Then what? Controversial
American gastroenterological association institute guideline on the diagnosis and management of asymptomatic neoplastic pancreatic cysts.
Vege SS, Ziring B, Jain R, Moayyedi P, Clinical Guidelines Committee, American Gastroenterology Association
Gastroenterology. 2015;148(4):819.
The role of endoscopy in the diagnosis and treatment of cystic pancreatic neoplasms.
ASGE Standards of Practice Committee, Muthusamy VR, Chandrasekhara V, Acosta RD, et al

50. • 2018 ACG guidelines:
• EUS-FNA for high risk features
• Main duct diameter >5 mm
• Cyst ≥3 cm
• Change in main duct caliber with upstream atrophy
• If an associated solid mass is present, referral to a multidisciplinary group with
consideration for EUS-FNA is advised.
• For cysts 2 to 3 cm in size, if not clearly an IPMN or MCN based on cross-sectional
imaging, EUS-FNA is recommended.
• If the cyst is determined to be a mucinous lesion by EUS-FNA, MRI or EUS is
Then what? Controversial & Confusing
ACG Clinical Guideline: Diagnosis and Management of Pancreatic Cysts.
Elta GH, Enestvedt BK, Sauer BG, Lennon AM
Am J Gastroenterol. 2018;113(4):464. Epub 2018 Feb 27.

58. Overall plan for pancreas cyst neoplasm
• CT
• MRI
• EUS/FNA
• Resect or surveillance MRI

59. EUS/FNA
• Test FNA fluid for
• Cytology and CEA level
• Diagnostic molecular markers (KRAS, GNAS, VHL, CTNNB1)
• Prognostic molecular markers (TP53, PIK3CA, PTEN)
• Cytology
• Glycogen-rich cells (SCTs)
• Mucin-containing cells (MCNs and IPMNs)
• Low sensitivity
• N= 341 patients undergoing EUS-FNA of pancreatic cysts, with 112 to surgery
• Cytology for detecting mucinous lesions (MCNs and IPMNs) only 35% sensitivity,
83% specificity
• Cytology brushings may improve the yield for diagnosing mucinous lesions.
• N=37 >2 cm diameter
• Cytobrushings were significantly more likely to detect intracellular mucin than
was FNA (62 % vs 23 %)
Diagnosis of pancreatic cystic neoplasms: a report of the cooperative pancreatic cyst study.
Brugge WR, Lewandrowski K, Lee-Lewandrowski E,et al.
Gastroenterology. 2004;126(5):1330.

60. CEA for mucinous PCN
• Best studied and most accurate tumor marker for diagnosing a mucinous PCN
• Accuracy and the cutoff level vary among laboratories
• Approximately 0.2 to 1 mL of cyst fluid is required to run the test
• Studies have attempted to determine the optimal cutoff for CEA predicting a
mucinous cyst
• N= 112 Cutoff of 192 ng/mL had a sensitivity of 73% , specificity of 83%
• N=198 Cutoff of 110 ng/mL had a sensitivity of 81%, specificity of 98%
• N=226 Cutoff of 105 ng/mL had a sensitivity of 70%, specificity of 63%
• Higher CEA level yields a higher likelihood that a cyst is mucinous
• No direct correlation of CEA concentration with malignancy
Cyst fluid carcinoembryonic antigen is an accurate diagnostic marker of pancreatic mucinous cysts.
Cizginer S, Turner BG, Bilge AR, Karaca C, Pitman MB, Brugge WR
Pancreas. 2011;40(7):1024.

62. Ready for your song?
The IPMN Song

63. You only have a side branch IPMN
A low malignant side branch IPMN
It is not a close call, your main duct is small
You'll survive for the whole long haul
You only have a side branch IPMN
A low malignant side branch IPMN
You can take a deep breath, you likely won't die,
We will follow with MRI...
CT, for abdominal pain
And then MR, your doc fails to explain
"Abnormal pancreas", blood runs cold in your
veins
Anyone would be unhappy.
Woman, there's a place you should go
See your GI, what comes next we will know
Have a consult, and I'm sure you will find
You may regain your peace of mind
CT MR, 2.4 percent cysts
EUS, 9 percent preexist
Panc cysts are common, so be a pancreas queen
But you got to know these four things!
SCT, older women, benign
MPN, younger, surgery assign
SPN, body tail in young girls
And scary main duct IPMN.
Not good to have a main duct IPMN
We're bummed about your main duct IPMN
Send to surgery, cause I can't calm your fears
Cyst to cancer in five short years
Not good to have a main duct IPMN
We're bummed about your main duct IPMN
Get your pancreas clean, your Whipple surgery will heal,
You may need enzymes to eat a meal...
You want to have a side branch IPMN
We're hoping for a side branch IPMN.
It is not a close call, if your main duct is small
You'll survive for the whole long haul
You only have a side branch IPMN
A low malignant side branch IPMN
You can take a deep breath, you likely won't die,
We will follow with MRI...

65. Questions?
plraymond@rxforsanity.com
Slide deck available for viewing on
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