Evaluation of Pancreatic Cystic Lesions

1
Evaluation of Pancreatic Cystic Lesions
Peter Darwin, MD Director,
Therapeutic Endoscopy University of Maryland
Hospital Division of Gastroenterology
2
Cystic Lesions of the Pancreas

• Case Presentations
• Differential
• EUS evaluation
• Management
• Complications

3
Case 1

• 27 year old woman referred for evaluation of
  recurrent pancreatitis with a cystic lesion
• Initially admitted 1/03 with acute pancreatitis
  and a 3 cm cyst of pancreatic body. MRCP -
• EUS/FNA 11/05 of a 4 cm cystic collection.
  Histology showed histiocytes, inflammatory cells
  and debris. Mucin stain negative. CEA 390 ng/ml,
  amylase 91,700 U/l.
• What is the most likely diagnosis?

4
(No Transcript)
5
Case 2

• 77 year old woman with virtual colonoscopy that
  demonstrated a 1.5 cm cystic lesion of the
  pancreatic head
• EUS/FNA showed a multi-septated cyst with
  clear/thin fluid. Mucin stain was positive and
  CEA in the fluid 546 ng/ml
• What is the appropriate next step?

6
Differential

• Simple (Congenital) Cyst
• Cystic Neoplasm
• Serous
• Mucinous
• Cystic degeneration
• IPMT
• Inflammatory
• Pseudocyst

7
Simple Cyst (Retention cyst)

• Asymptomatic
• Thin walled, no septations
• Thin clear fluid
• Collapses with FNA
• No malignant potential

8
Simple Cyst
9
Serous Cystadenoma

• Usually found incidentally
• Microcystic with a honeycomb appearance rarely
  has a macrocystic component central
  calcification
• Thin, clear fluid
• Cuboidal epithelium that stains positive for
  glycogen
• Little to no malignant potential

10
(No Transcript)
11
(No Transcript)
12
Mucinous Cystadenoma

• Usually found incidentally but can cause
  abdominal pain and a palpable mass
• Macrocystic, occasionally septated peripheral
  calcifications, solid components
• Fluid Viscous or stringy, clear
• Cytology Mucinous columnar cells with variable
  atypia fluid stains positive for mucin
• Malignant potential 30 lifetime risk

13
(No Transcript)
14
(No Transcript)
15
Cyst Adenocarcinoma

• Presents with painless jaundice, abdominal/back
  pain or rarely pancreatitis
• Primarily solid mass with cystic spaces
• Bloody debris
• Malignant adenocarcinoma may be seen, but varying
  degrees of atypia may be present in the specimen

16
(No Transcript)
17
Inflammatory

• Pseudocyst
• History of moderate to severe pancreatitis
• Anechoic, thick-walled, rare septations
• Fibrous lining of cyst (no epithelium)
• FNA-gt Thin, muddy-brown fluid
• Cytology-gt Neutrophils, macrophages, histiocytes
  negative staining for mucin
• Malignant potential None

18
Pseudocyst
19
(No Transcript)
20
Intraductal Papillary Mucinous Neoplasm (IPMN)

• 3 types main duct, branch type and mixed
• History of pancreatitis, abdominal pain, or found
  incidentally
• Imaging Dilated main pancreatic duct or side
  branches
• Fluid Viscous or stringy, clear
• Cytology Mucinous columnar cells with variable
  atypia fluid stains positive for mucin
• Malignant potential 20 to 30 lifetime risk

21
IPMN main duct
22
IPMN side branch
23
Solid Pseudopapillary Neoplasm

• Usually found incidentally rarely causes
  abdominal discomfort
• Solid and cystic components
• Bloody necrotic debris
• Monomorphic cells with round nuclei and
  eosinophilic or foamy cytoplasm immunostaining
• Locally invasive (similar to Desmoids)

24
Pseudo
25
7.5 / 12 MHz.
UM-130
7.5 MHz.
UC-30P
26
Can EUS alone Differentiate Between Malignant and
Benign Cystic Lesions ?

• 48 patients with surgical/pathologic correlation
• EUS images reviewed 2 blinded endosonographers
• Assessed for wall, solid component, septae,
  lymphadenopathy and of cysts
• EUS features cannot reliably differentiate

Ahmad N, Kochman M, Lewis J, Ginsberg G. Am J
Gastro 2001963229-30.
27
EUS-Guided FNA

• Results for FNA cytology are variable
• Mucinous vs nonmucinous epithelium
• Tumor Markers
• CEA, CA 72-4, CA 125,
• CA 19-9, CA 15-3
• Molecular analysis

28
Cyst Fluid Analysis in the Differential Diagnosis
of Pancreatic Cystic Lesions a Pooled Analysis

• Pub Med review of articles with cyst fluid
  analysis
• At least 7 patients
• Diagnosis of cystadenoma made by pathology
• Pseudocyst diagnosed by history and follow up

van der Waaij L, van Dullemen H, Porte R. Gastro
Endo 200562383-389.
29
(No Transcript)
30
(No Transcript)
31
(No Transcript)
32
(No Transcript)
33
(No Transcript)
34
(No Transcript)
35
(No Transcript)
36

• DNA QUANTITY QUALITY REFLECT LINING CELL
  PROLIFERATION

Pancreatic Cyst Fluid

• KRAS GNAS POINT MUTATION (ONCOGENE)

FREE DNA

• LOSS OF HETEROZYGOSITY (LOH) MUTATIONS (25)
  (TUMOR SUPPRESSOR GENES)

CEA
DETACHED LINING CELLS
Second line molecular analysis targets both
cellular and free DNA designed to complement
cytology and other first line information.
Multiple molecular parameters reflects multiple
pathways of neoplasia development and progression
37
PFTG Pancreatic Cysts
Diagnostic category Molecular criteriaa Co-existing concerning clinical featuresb
Benign DNA lacks molecular criteria Not required for diagnosis
Statistically indolent (SI) DNA meets at least 1 molecular criterion Patient lacks concerning clinical features
Statistically higher risk (SHR) DNA meets at least 1 molecular criterion Patient may have 1 or more concerning clinical features
Aggressive DNA meets at least 2 molecular criteria Not required for diagnosis
aMolecular criteria that have been correlated with malignant or high-grade disease are a single high-clonality mutation elevated level of high-quality DNA multiple low-clonality mutations and a single low-clonality oncogene mutation. bIncludes cyst size gt3 cm, growth rate gt3 mm/year, main or side branch duct dilation gt1 cm, carcinoembryonic antigen level gt1000 ng/mL and/or cytologic evidence of high-grade dysplasia. aMolecular criteria that have been correlated with malignant or high-grade disease are a single high-clonality mutation elevated level of high-quality DNA multiple low-clonality mutations and a single low-clonality oncogene mutation. bIncludes cyst size gt3 cm, growth rate gt3 mm/year, main or side branch duct dilation gt1 cm, carcinoembryonic antigen level gt1000 ng/mL and/or cytologic evidence of high-grade dysplasia. aMolecular criteria that have been correlated with malignant or high-grade disease are a single high-clonality mutation elevated level of high-quality DNA multiple low-clonality mutations and a single low-clonality oncogene mutation. bIncludes cyst size gt3 cm, growth rate gt3 mm/year, main or side branch duct dilation gt1 cm, carcinoembryonic antigen level gt1000 ng/mL and/or cytologic evidence of high-grade dysplasia.
38
Performance of PFTG (n492) in Diagnosing
Malignant Outcome
The National Pancreatic Cyst Registry
www.npcnregistry.com
39
Complications of EUS

• Pancreatitis (2-3)
• Hemorrhage within the cyst (lt1)
• Infection (lt1)
• The prevailing opinion is to administer an
  antibiotic, e.g., a fluoroquinolone, prior to
  aspiration and possibly several days post.

40
Serous Cystadenoma

• Management determined by symptoms, progression,
  and lesion location.
• Symptomatic or enlarging serous cystadenomas
  should be resected.
• Small, asymptomatic, and nonenlarging serous
  cystadenomas can be observed

41
Mucinous Cystadenoma

• Consider for resection
• Potential for malignant change (30 lifetime)
• Distal pancreatectomy should be performed for
  lesions in the body or tail of the pancreas
• Pancreaticoduodenectomy for lesions in the
  pancreatic head.

42
Ethanol Lavage Initial Pilot Study

• Background lavage ablates liver cysts
• Methods post evacuation, lavaged with ethanol
  (5 to 80)
• Observations 25 patients no symptoms
  resolution in 8 patients (35)
• Conclusions subset had long-term resolution.
  Further studies needed.

Gan S, Thompson C, Bounds B, Brugge W. Gastro
Endo 200561746-752.
43
Prospective multicenter randomized double blinded
study
EUS lavage
Baseline SA
Post procedure SA
Complete ablation
Complications
Saline N15
1.7 cm2 1.4 cm2 0/15
0
Ethanol (1) N36
1.5 cm2 1.1 cm2 2/37
1
Ethanol (2) N23
1.4 cm2 1.0 cm2 10/23
1
P.002 P.0001 ETOH vs saline

Brugge W, et al. Am J of Gastro 2007106S192
44
Revised International Consensus Guidelines for
the Management of Patients With Mucinous Cysts
Tanaka M, et al. Panceatology 12(2012) 183-197
45
Solid Pseudopapillary Neoplasm

• Solid pseudopapillary neoplasms are locally
  aggressive lesions, which should be resected
  surgically if possible.
• The type of resection is determined by the
  location of the tumor

46
Endoscopic Management of Pseudocysts

• Can be considered for mature pseudocysts,
  infected pseudocysts, and in selected cases of
  organized necrosis.
• Symptomatic lesions (abdominal pain, gastric
  outlet obstruction, early satiety, weight loss,
  or jaundice)
• 82-84 success rate
• Complication rates occurring in 5 to 16
• Recurrence rates ranging from 4 to 18

47
Endoscopic Management

• Prophylactic antibiotics
• Special care must be taken to avoid drainage of
  cystic neoplasms, pseudoaneurysms, duplication
  cysts, and other noninflammatory fluid
  collections.
• Pseudocyst size is not an indication for
  drainage
• ERCP prior

48
(No Transcript)
49
(No Transcript)
50
(No Transcript)
51
(No Transcript)
52
(No Transcript)
53
(No Transcript)
54
(No Transcript)
55
(No Transcript)
56
(No Transcript)
57
(No Transcript)
58
(No Transcript)
59
(No Transcript)
60
(No Transcript)
61
Hookey L, et. al. Gastro Endo 200663635-43.
62
Complications of Drainage

• Bleeding
• Infection
• Perforation
• Pancreatitis
• Aspiration
• Stent migration
• Death