Transcript Differential Diagnosis of Neoplastic Pancreatic Cysts - Tel

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
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Introduction



Cystic lesions constitute about 10 %
of pancreatic tumors
Significant increase in detection due
to widespread use of US,CT
Most lesions discovered incidentally
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Clinical Presentation

Asymptomatic

Abdominal pain

Jaundice

Pancreatitis
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Clinical Presentation
Asymptomatic

Ca in situ / invasive cancer – 17%

Lesion with malignant potential – 42%
Fernandez Del Castillo et al. Arch Surg 2003
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Classification

Non neoplastic (pseudocysts)
Non Mucinous

Neoplastic
Mucinous
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Classification
Non Mucinous Cysts
1.
Serous cystadenoma
2.
Cystic endocrine tumors
3.
Other
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Classification
Mucinous Cysts
1.
Mucinous cystadenoma
2.
Malignant mucinous cystic tumors
3.
Intraductal papillary mucinous
neoplasms - IPMN
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Diagnosis

CT –
microcystic appearance, central
fibrosis- Serous
Unilocular, macrocystic, peripheral
calcification- Mucinous

MRCP – MPD dilatation, mural nodules
ductal connection - IPMN
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Diagnosis
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EUS - highly sensitive
FNA – fluid characteristics, tumor
markers, cytology
CEA in fluid - most accurate marker
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EUS – Serous cyst
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EUS – Mucinous cyst
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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
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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
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AIM
 Provide
an algorithm for the diagnosis
and treatment of pancreatic cystic
lesions
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Heuristics used in our Institute
for Dx of Serous cysts
-
-
Clinical
Microcystic morphology
CEA level < 5 ng / ml
Histology- cuboidal, non secreting
cells
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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
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Methods
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Methods
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
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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
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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)
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Methods
EUS


Cyst location, size, morphology
FNA – fluid:
- characteristics
- cytology
- tumor markers –CEA,CA19-9,CA72-4,MCA

Cyst wall sampling (cell block)
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Results
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Results
Clinical Presentation
No.
%
Incidental finding
103
69.3
29
19.6
Weight loss
2
1.4
Jaundice
2
1.4
Abdominal pain/weight loss
5
3.4
Dyspepsia
2
1.4
Diarrhea
2
1.4
Diarrhea/weight loss
3
2.0
Abdominal pain
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Results
Location
No.
Head
52
Neck
14
%
33.5
9.0
Body
41
26.5
Tail
25
16.1
Other
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14.8
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Results
– 37 patients had surgery with histological
findings.
– 140 patients had FNA but results were
available for 80 patients.
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Results
Surgical Pathology
No.
%
Non neoplastic
6
4
13
11
2
1
16.2
10.8
35.1
29.7
5.4
2.7
Serous
Mucinous
Mucinous ca.
IPMN
Neuroendocrine
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Results
FNA Histology
No.
%
Non neoplastic
12
27
25
14
2
16.0
33.8
31.3
17.5
2.5
Serous
Mucinous
Carcinoma
Neuroendocrine
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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.
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Results
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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)
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BoxPlot
12.00
10.00
Ln(CEA)lnCEA
8.00
6.00
4.00
2.00
0.00
-2.00
Non-mucinous
0
Mucinous
1
Class
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Logistic regression results
95% C.I.for OR
Variable
B
S.E.
p-value
OR
Lower
Upper
log10CEA
1.818
0.727
0.012
6.2
1.48
25.6
-0.041
0.022
0.06
0.96
0.92
1.01
Age
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.
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ROC of CEA classification of
Mucinous vs. Serous
ROC Curve
A Threshold
of CEA=58
ng/ml yields
86.4% and
87.5%
sensitivity and
specificity
respectively
0.8
Sensitivity
sensitivity
1.0
0.6
0.4
0.2
0.0
0.0
0.2
0.4
0.6
0.8
1.0
1 - Specificity
1-specificity
AUC=0.902 (CI=(0.79-1.0))
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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
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A Practical Decision
Algorithm based on the
Threshold Decision Model
Source: NEJM 1980; 302:1109-17
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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.
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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)
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Natural history of mucinous cystic neoplasm
78 years old woman with incidental finding - 1977
CEA in cyst
90
CA19-9 in blood
Cyst size (mm)
Cyst size
10000
80
9000
70
8000
7000
60
6000
50
5000
40
4000
30
3000
20
2000
10
1000
0
0
year
1997 1998 1999 2000 2001 2003 2005
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Age
<=60
Yes
Co-morbidity
Positive
Cytology or
CEA>60
60 - 75
Yes
Yes
Complexity
of Surgical
resection
Compliance
= Surgical Resection
Yes
Yes
Yes
No
Yes
5< CEA<60
No
Yes
No
No
>75
No
No
No
No
= Wait and Watch
= Debate
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Age
<=60
Co-morbidity
Yes
60 - 75
No
>75
No
Yes
Positive
Cytology or
CEA>60
Yes
Yes
Complexity
of Surgical
resection
= Surgical Resection
= Wait and Watch
No
No
= Debate
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Age
<=60
>75
No
Yes
Co-morbidity
Positive
Cytology or
CEA>60
60 - 75
Yes
No
= Surgical Resection
Yes
= Wait and Watch
No
= Debate
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