Differential Diagnosis of
Neoplastic Pancreatic Cysts:
The Role of EUS with Guided FNA
E.M.Santo,Y.Ron,O.Barkay,Y.Kopelman,M.Leshno,S.Marmor
Dep. of Gastroenterology & Hepatology,
Dep.of Pathology
Tel-Aviv Sourasky Medical Center 1

Introduction

Cystic lesions constitute about 10 % of pancreatic tumors

Significant increase in detection due to widespread use of US,CT

Most lesions discovered incidentally
2

Clinical Presentation

Asymptomatic

Abdominal pain

Jaundice

Pancreatitis
3

Clinical Presentation
Asymptomatic

Ca in situ / invasive cancer – 17%

Lesion with malignant potential – 42%
Fernandez Del Castillo et al. Arch Surg 2003
4

Classification

Non neoplastic (pseudocysts)

Neoplastic
Non Mucinous
Mucinous
5

Classification
Non Mucinous Cysts
1.
Serous cystadenoma
2.
Cystic endocrine tumors
3.
Other
6

Classification
Mucinous Cysts
1.
Mucinous cystadenoma
2.
Malignant mucinous cystic tumors
3.
Intraductal papillary mucinous neoplasms - IPMN
7

8


CT –
Diagnosis microcystic appearance, central fibrosisSerous
Unilocular, macrocystic, peripheral calcificationMucinous

MRCP – MPD dilatation, mural nodules ductal connection - IPMN
9

Diagnosis

EUS - highly sensitive

FNA – fluid characteristics, tumor markers, cytology

CEA in fluid - most accurate marker
10

EUS – Serous cyst
11

EUS – Mucinous cyst
12

AIM

Evaluation of the various parameters
(clinical,morphological,fluid content, cytology) and their contribution to the ability to distinguish between serous and mucinous cystic tumors
13

AIM

Validation of the current criteria used to distinguish between various cystic tumors (gold standard based on surgical pathology )

Establishing new criteria with higher sensitivity and specificity
14

AIM

Provide an algorithm for the diagnosis and treatment of pancreatic cystic lesions
15

Heuristics used in our Institute for Dx of Serous cysts
-
-
-
-
Clinical
Microcystic morphology
CEA level < 5 ng / ml
Histology- cuboidal, non secreting cells
16

Heuristics used in our Institute for Dx of Mucinous cysts
-
-
-
-
-
Clinical
Morphology – unilocular, thick septa, solid component
High viscosity (mucinous) fluid
CEA - >140 ng/ml
Histology – columnar secreting epithelium
17

18

Methods






Retrospective study
170 patients between 1977-2006
155 patients ,195 EUS exams
40 patients – EUSx2 or more
101 women, 54 men
Mean age – 64.3
± 14 years
19

Methods






Demographic data
Clinical presentation
Imaging – US, CT , EUS
FNA
Surgical findings
Follow up on all patients ( office visits , data from family physicians, gastroenterologists, patient’s families)
20

Methods
EUS



Cyst location, size, morphology
FNA – fluid:
- characteristics
- cytology
- tumor markers – CEA,CA19-9,CA72-4,MCA
Cyst wall sampling (cell block)
21

22

Results
Clinical Presentation
Incidental finding
Abdominal pain
Weight loss
Jaundice
Abdominal pain/weight loss
Dyspepsia
Diarrhea
Diarrhea/weight loss
No.
%
103
29
69.3
19.6
2 1.4
2 1.4
5
2
2
3
3.4
1.4
1.4
2.0
23

Location
Head
Neck
Body
Tail
Other
Results
No.
%
52 33.5
14
9.0
41 26.5
25 16.1
23 14.8
24

– 37 patients had surgery with histological findings.
– 140 patients had FNA but results were available for 80 patients.
25

Results
Surgical Pathology
Non neoplastic
Serous
Mucinous
Mucinous ca.
IPMN
Neuroendocrine
No.
%
6 16.2
4 10.8
13
11
35.1
29.7
2
1
5.4
2.7
26

FNA Histology
Non neoplastic
Serous
Mucinous
Carcinoma
Neuroendocrine
Results
No.
%
12 16.0
27 33.8
25
14
2
31.3
17.5
2.5
27

EUS-FNA vs. Surgical biopsy
– 32 patients had both FNA and surgical biopsy.
– The agreement rate was 66% of the cases regarding mucinous vs. non-mucinous with kappa=0.33.
– Sensitivity and specificity of FNA are 59% and 80% respectively.
28





Results
Mean of Ln(CEA) * levels were 2.6 and 5.8 for non mucinous and mucinous cases respectively (p<0.0001)
No statistically significant difference with all the other tumor markers tested
Rate of solid component in cyst – the difference was not statistically significant
(p=0.14)
No difference concerning cyst size or morphology
*CEA is highly skewed distributed and therefore we transformed the CEA level to Ln(CEA)
29

4.00
2.00
0.00
-2.00
12.00
10.00
8.00
6.00
Class
30

Logistic regression results
Variable B S.E.
p-value log
10
CEA 1.818
0.727
0.012
Age -0.041
0.022
0.06
OR
6.2
0.96
95% C.I.for OR
Lower Upper
1.48
25.6
0.92
1.01
Note that CA-19 is highly correlated with CEA, and when CEA levels are unavailable the CA-19 level should play a role in the diagnostic process.
31

ROC of CEA classification of
Mucinous vs. Serous
ROC Curve
1.0
0.8
0.6
0.4
0.2
0.0
0.0
0.2
0.4
0.6
0.8
1 - Specificity
1-specificity
AUC=0.902 (CI=(0.79-1.0))
1.0
A Threshold of CEA=58 ng/ml yields
86.4% and
87.5% sensitivity and specificity respectively
32


Conclusions
EUS is a useful tool but it can not alone distinguish between cystic lesions with variable malignant potential

EUS-FNA alone is also limited in its ability to correctly diagnose a cystic lesion – sensitivity 59% specificity
80%

Combination of parameters – cytology and CEA levels (or CA 19-9 levels) can significantly increase the diagnostic yield
33

A Practical Decision
Algorithm based on the
Threshold Decision Model
Source: NEJM 1980; 302:1109-17
34

For a patient with a pancreatic cyst there are several management options:
• Wait and watch approach with a follow up.
• An initial EUS-FNA is performed and patients with increased cyst fluid CEA or positive cytology undergo a surgical resection.
• Surgical resection of all cysts without prior EUS evaluation.
35

Beside the preferences of the patient, the following parameters are relevant to the decision process:
• Age of the patient
•  60 year
• 61-75 year
•
>
75 year
• Co-morbidity status (CV diseases, diabetes, other neoplastic diseases)
• No co-morbidity
• Co-morbidity
• Test results (CT, EUS)
36

Natural history of mucinous cystic neoplasm
78 years old woman with incidental finding - 1977
90
80
70
60
50
40
30
20
10
0
CEA in cyst
CA19-9 in blood
Cyst size year 1997 1998 1999 2000 2001 2003 2005
10000
9000
8000
7000
6000
5000
4000
3000
2000
1000
0
37

<=60
Co-morbidity
Positive
Cytology or
CEA>60
5< CEA<60
Yes
Yes
No
Complexity of Surgical resection
Compliance
= Surgical Resection
Age
60 - 75 >75
Yes
No
Yes
No
No
Yes
Yes
No
No
Yes No
Yes No
= Wait and Watch = Debate
38

Co-morbidity
Positive
Cytology or
CEA>60
Complexity of Surgical resection
Yes
<=60
No
Age
60 - 75
Yes
Yes
>75
Yes
No
No
No
= Surgical Resection = Wait and Watch = Debate
39

<=60
Co-morbidity
Positive
Cytology or
CEA>60
Yes
Yes
No
Age
60 - 75
Yes
>75
No
No
= Surgical Resection = Wait and Watch = Debate
40

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