Cystic Neoplasms of the Pancreas https://drdhavalmangukiya.com/ http://www.youtube.com/c/DrDhavalMangukiyaGastrosurgeonSurat https://gastrosurgerysurat.blogspot.com/

1. Cystic Neoplasms of
the Pancreas
Dr Dhaval Mangukiya
SIDS Hospital

2. Introduction
 Increasingly incidentally detected
 Imaging important for determining
prognosis and management
 CT>MR generally preferred for
characterization except for IPMN
 Role of Endoscopic US : increasing

3. Epidemiology
 10% of pancreatic neoplasms are cystic
 Prevalence: varies depending on the study
1) 2004: ~0.7% based on 24,039 CT and MRI reports
(Medical College of Wisconsin)
 290 patients (1.2%) had pancreatic cysts; 0.7% without
previous pancreatitis
 With an average of 16 month follow up, 19% grew, 59% did
not change, 22% shrank
 49 underwent surgery (14 benign, 25 premalignant, 10
malignant)
Spinelli KS, Fromwiller TE, Daniel RA, et al: Cystic pancreatic neoplasms: Observe or
operate. Ann Surg 2004; 239:651‐7.

4. Rising Prevalence
2) 2008: University College Dublin
 2.6% based on 2,832 consecutive 16‐slice MDCT for unrelated
indications
 Cysts were more common in Asians and with older age
3) 2010: Beth Israel Deaconess
 13.5 % based on 616 MRIs excluding symptomatic patients or
history of pancreatic disease
 Prevalence and size increase with age
 Majority of incidental pancreatic cysts were not reported
 40% of patients had more than one cyst
 Laffan TA, Horton KM, Klein AP, Berlanstein B, Siegelman SS, Kawamoto S, Johnson
PT, Fishman EK, Hruban RH. Prevalence of unsuspected pancreatic cysts on MDCT.
AJR Am J Roentgenol. 2008 Sep;191(3):802‐7.
 Lee KS, Sekhar A, Rofsky NM, Pedrosa I. Prevalence of Incidental Pancreatic Cysts in
the Adult Population on MR Imaging. Am J Gastroenterol 2010 Mar 30.

5. WHO Classification (1996)
 Serous Cystic Tumors
 Serous cystadenoma
 Seroud cystadenocarcinoma
 Mucinous Cystic Tumors
 Mucinous cyst adenoma
 Mucinous cystadenocarcinoma (Noninfiltrating or infiltrating)
 IPM Adenoma
 IPMN with moderate dysplasia
 IPM carcinoma (Noninfiltrating or infiltrating)
 Solid Pseudopapillary tumors

6. Kosmahl et al 2004
 Epithelial cystic tumours
 Benign
 Intraducal papillary mucinous adenoma
 Mucinous cystadenoma
 Serous cystadenoma (micro or macro-cystic)
 Benign cystic neuroendocrine tumour
 Acinar cell cystadenoma
 Dermoid cyst
 Cystic hamartoma
 Borderline
 BorderlineIPMT
 Borderline mucinous cystic tumour
 Solid pseudopapillary tumour
 Malignant
 IPM carcinoma
 Mucinous cystadenocarcinoma
 Serous cystadenocarcinoma
 Cystic pancreatoblastoma
 Cystic metastasis
 Malignant cystic neuroendocrine tumour
 Non tumorous epithelial cysts
 Congenital cyst
 Lymphoepithelial cyst
 Non neoplastic mucinous cyst
 Obstructive cyst
 Endométrial cyst
 Non epithelial cystic tumours
 Benign (lymphangiomas…)
 Malignant (sarcomas…)
 Non tumorous non epithelial cysts
 Pseudocysts
 Parasitic cysts

7. Hutchins GF, Draganov PV, Cystic neoplasms of the pancreas: A
diagnostic challenge World J Gastroenterol 2009 January 7; 15(1):
48-54

8. Cystic Pancreatic lesions: A Simple
Imaging-based Classification System for
Guiding Management
Sahani DV, Kadavigere R, Saokar A, Fernandez-del
Castillo C, Brugge WR, Hahn PF.
Radiographics 2005 Nov-Dec;25(6):1471-84.

9. Classification of Cystic Pancreatic
Lesions
 Pseudocyst
 Common cystic pancreatic neoplasms
 Serous cystadenoma
 Mucinous cystic neoplasm
 IPMN
 Rare cystic pancreatic neoplasms
 Solid pseudopapillary tumor
 Acinar cell cystadenocarcinoma
 Lymphangioma
 Hemangioma
 Paraganglioma

10. Classification of Cystic Pancreatic
Lesions (cont)
 Solid pancreatic lesions with cystic degeneration
 Pancreatic adenocarcinoma
 Cystic islet cell tumor (insulinoma, glucagonoma,
gastrinoma)
 Metastasis
 Cystic teratoma
 Sarcoma
 True epithelial cysts*
*Associated with von Hippel–Lindau disease, autosomal
-dominant polycystic kidney disease, and cystic
fibrosis)

11. Four Morphologic Types of Cystic
Lesions of the Pancreas

12. Unilocular Cyst
 Pseudocyst
 IPMN occasionally
 Unilocular serous cystadenoma
 Lymphoepithelial cyst
 Multiple
 von Hippel-Lindau
 Pseudocysts

13. Pseudocyst
 Generally symptomatic (i.e. pain)
 History of acute or chronic pancreatitis
 Look for associated findings
 Pancreatic inflammation, parenchymal calcifications,
atrophy, typical intraductal calcifications
 Can communicate with pancreatic duct
 Wall can calcify
 No mural nodules

14. Side-branch IPMN manifesting as a
unilocular cyst

15. Multiple unilocular cysts in a patient with
von Hippel–Lindau disease

16. Microcystic Lesions
 Serous cystadenoma
 Only lesion included in this category
 Benign tumor
 May grow up to approx 4 mm/year
 70% cases demonstrate:
 Polycystic/microcystic pattern
 Collection of cysts (>6)
 Range: few mm – 2 cm
 External lobulations
 Enhancing septa, walls
 30% demonstrate fibrous central scar +/- stellate calcifcation
 Other variants (macrocystic + oligocystic)

17. Serous Cystadenoma
 Formerly known as microcystic
adenoma
 Second most common pancreatic
cystic tumor
 75% are women
 Mean age 62
 50‐70% in body or tail
 Association with Von Hippel‐Lindau

18. SCN Appearance
 Macroscopic: well circumscribed, numerous thin
cysts with delicate fibrous septa “honeycomb”
appearance
 Honeycomb may be best seen on EUS
 Cysts are often arranged around a central stellate scar
that may be calcified
 (classic “sunburst”‐ calcification only seen in 10% of
patients)
 Clear watery (low viscosity) fluid‐ low CEA, negative
cytology
 Histology: cuboidal epithelium containing glycogen

19. Serous cystadenoma

20. Gross appearance of serous cystadenoma. Note
central stellate scar

21. SCN When to Resect
 Only case reports of serous
cystadenocarcinoma
 Symptomatic
 Risk of observation
 Hemorrhage
 Jaundice
 Gastric outlet obstruction
 Some group recommends 4cm at
presentation as cut‐off for deciding when to
resect in asymptomatic patients

22. Macrocystic Lesions
 Mucinous cystic neoplasms
 Intraductal Papillary Mucinous Neoplasm
(IPMN)

23. Mucinous cystic neoplasms
 Mucinous cystadenomas & cystadenocarcinomas
 Multilocular with complex internal architecture
 May contain internal hemorrhage or debris
 Peripheral eggshell Calcification predictive of
malignancy
 Body & tail of pancreas
 Asymptomatic in 75% cases
 If symptoms, usually due to mass effect
 High potential for malignancy

24. IPMN -definition
 Hruban et al, Am J Surg Pathol 2004

25. MCN vs. IPMN
 The International Association of
Pancreatology put forward guidelines
to accurately differentiate an MCN from
IPMN
 Guidelines require the histologic
presence of ovarian‐type stroma within
the tumor to establish the diagnosis of
MCN

26. IPMN Further Classified
 Main Duct IPMN
 Can involve the entire duct
 Dilation of duct >1cm strongly suggests
main duct IPMN
Branch duct IPMN appear as small blebs on EUS
 Pancreatic mucinous cyst communicating
with main duct without dilation
Tanaka M et al; International Association of Pancreatology. International consensus
guidelines for management of intraductal papillary mucinousneoplasms and mucinous
cystic neoplasms of the pancreas. Pancreatology. 2006;6(1‐2):17‐32.

27. IPMN (cont.)
 60% of IPMNs are already malignant
 Others are considered premalignant
 Histology‐ ranges from hyperplasia to
carcinoma within a single tumor
􀁺 Benign (adenoma)
􀁺 Borderline
􀁺 Malignant (carcinoma in situ vs. invasive‐
extension beyond basement membrane)

28. IPMN: Clinical Presentation
 Men = Women
 Median age ~ 65 years
 75% symptomatic
􀁺 weight loss, abdominal pain
􀁺 Acute pancreatitis (25%)
􀁺 Recurrent pancreatitis (20%)
 Predictors of malignant IPMN: older age,
jaundice or newonset DM at presentation

29. IPMN

30. IPMN: Radiography &
Endoscopy
 Often find a dilated pancreatic
duct
 Extruding mucus from ampulla
“Fish mouth”
 Filling defect in ducts (viscous
mucus or tumor nodules)
McGrath K and Slivka A (2005) Diagnosis and
management of intraductal papillary
mucinousneoplasia
Nat ClinPractGastroenterolHepatol2:316– 322
doi:10.1038/ncpgasthep0213

31. Prevalence of cancer
 Main duct IPMN -- 57 to 92%
 Branch duct IPMN -- 6 to 46%
 MCN – 6 to 36%

32. Predictors of Malignant
Transformation
 Age >70
 New symptoms
 Cyst growth on serial imaging

33. SIGNS OF MALIGNANCY
•Macrocystic lesions with internal septations
•Calcifications
•Nodular components (Mural Nodules)
•Dilation of the pancreatic duct or side branches

34. IPMN Treatment
 Resection with intaoperative frozen
section to confirm negative resection
margins

35. IPMN Prognosis
 Prognosis following resection: >75% 5 year survival
 Predictors of worse outcome:
 Elevated bilirubin
 Invasive IPMN (12‐65% recurrence at 3 years)
 Lymph node metastases
 Vascular invasion
 *Surveillance is important if invasion present*
 May benefit from completion pancreatectomy if
localized recurrence

36. MCN

37. Cysts with a solid component
 Unilocular or multilocular
 True cystic tumors or solid pancreatic neoplasms with
cystic component/degeneration
 Wide DDx
 Mucinous cystic neoplasms
 IPMNs
 Islet cell tumor
 Solid pseudopapillary tumor (SPEN)
 Adenocarcinoma
 Metastasis
 All malignant or have a high malignant potential
 Surgical management

38. Solid Pseudopapillary Tumor
(SPT)
 Rare (<10% of cystic pancreatic
neoplasms)
 Classically young women in their 30s
 Women > Men (10:1)
 95% are <50 years of age
 20% of cases occur in children (age
<19 years)

39. SPT Clinical Presentation
 Abdominal pain (50%)
 Large abdominal mass (35%)
 34% are >10cm in diameter

40. SPT
 Slow‐growing
 60% body or tail
 Small tumors: solid
 Large tumors: some have cystic degeneration
 Histology
 Mixture of solid, pseudopapillary, and hemorrhagic
pseudocystic areas
 Uniform neoplastic tumor cells separated by vascular
hyalinizedstroma
 Abnormal (or loss of) expression of E‐Cadherin protein
 Related to abnormal expression of β‐catenin and p120

41. SPT ‐> malignancy
 Uncertain malignant potential
 20% frequency of solid pseudopapillary
carcinoma
 Criteria to be Malignant:
 Perineural invasion
 Angioinvasion
 Adjacent tissue invasion
 Metastases (5‐10% of patients at
presentation)

42. SPT Treatment
 Complete resection
 5 year survival 95%
 Resection of synchronous metastases
 Prolonged survival has been described

43. Solid pseudopapillary tumor
manifesting as a cyst with a solid
component

44. Islet cell tumor manifesting as a
cyst with a solid component

45. Metastases manifesting as cysts with
solid components
Pancreatic Adenocarcinoma Malignant IPMN

46. Diagnostic Imaging for cystic
tumors
 CT/MRI
 Traditional cross sectional imaging cannot always
provide diagnostic images
 EUS is ideal
 Detailed images of wall, septations, adjacent masses
 Still not always adequate for deciding malignant vs. benign
 Pancreatoscopy/MPD - Sonography
 Secretin stimulated MRCP for branch duct IPMN
 PET
 Metabolic activity correlates with malignancy
 Not frequently used
 Role in the nonsurgical follow‐up

47. Endoscopic US
 Can provide detailed morphologic evaluation of cystic
lesions
 For detecting malignant tumors:
 Sensitivity: 40%
 Specificity: 100%
 Accuracy: 50%
 Advantage of aspiration of contents, sampling of cyst
wall, septa or mural nodule
 Less potential for tumor seeding than percutaneous sampling
 Highly viscous contents (mucin) consistent with mucinous
neoplasm
 Tumor markers, cytologic analysis, biochemical markers, fluid
amylase

48. Cyst Fluid Analysis

49. Brugge Study
 Purpose: to determine the most accurate test for
differentiating mucinous from nonmucinous cystic
lesions
 Method: EUS imaging, cyst fluid cytology, and cyst
fluid tumor markers
 CEA Cutoff of 192 ng/ml optimal cutoff for mucinous
vs. nonmucinous
Brugge WR et al. Diagnosis of Pancreatic Cystic Neoplasms: A Report of
the Cooperative Pancreatic Cyst Study. Gastroenterology. 2004
May;126(5):1330‐6.

50. ASGE Guidelines for
Antibiotics
 “Prophylaxis with an antibiotic such as a fluoroquinolone
administered before the procedure is recommended before an
EUS‐FNA of cystic lesions along the GI tract. Antibiotics may
be continued for 3 to 5 days after the procedure (Grade 1C).”
2008 ASGE Guideline “Antibiotic Prophylaxis for GI Endoscopy”

51. PANDA Study: DNA analysis
of pancreatic cysts
 K‐ras mutation is indicative of a
mucinous cyst
 High‐amplitude mutations, specific
mutation sequences also indicators of
malignancy
Khalid A et al. Pancreatic cyst fluid DNA analysis in evaluating pancreatic
cysts: a report of the PANDA study. GastrointestEndosc. 2009
May;69(6):1095‐102.

52. TREATMENT
Leave alone:
 Asymptomatic pseudocysts
 Serous cystadenomas
Resect:
 Adenocarcinomas
 Islet cell tumors when feasible
Debatable:
 MCN & IPMN
 Must weigh risk of lesion with conservative management vs. risk of surgery
 Difficult to weigh given our inadequate natural history data
Chak A. Pancreatic cysts: Clin Gastroenterol Hepatol. 2005 Oct;3(10):964‐6.

53. Management

54. Resection is indicated if one or more of the following
are present:
 Symptoms attributable to the cyst
 Dilation of the main pancreatic duct (≥10 mm)
 Cyst size ≥30 mm
 Presence of intramural nodules
 Cyst fluid cytology suspicious or positive for
malignancy
Tanaka M, Chari S, Adsay V, Fernandez‐del Castillo C, Falconi M, Shimizu M, Yamaguchi
K, Yamao K, Matsuno S; International Association of Pancreatology. International
consensus guidelines for management of intraductal papillary mucinousneoplasms
and mucinous cystic neoplasms of the pancreas. Pancreatology. 2006;6(1‐2):17‐32.

55. Cyst Ablation
 Ethanol has been used in hepatic, renal cysts as well as
thryoid, parathyroid, and adrenal adenomas
 Ethanol and paclitaxel may be alternative treatment modalities
for :
 poor surgical candidates
 unilocular cysts <3cm; growing cysts
 without associated mass or mural nodule
 Promising but still experimental
“Ho KY, Brugge WR. EUS 2008 Working Group document: evaluation of
EUS‐guided pancreatic‐cyst ablation. GastrointestEndosc. 2009 Feb;69(2
Suppl):S22‐7.”

56. Follow-up
 No consensus
 6 month intervals for 1st year
 Annual imaging for 3 years

57. THANK YOU