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Differential Diagnosis of Differential Diagnosis of Neoplastic Pancreatic Cysts:Neoplastic Pancreatic Cysts:The Role of EUS with Guided The Role of EUS with Guided

FNAFNA

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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IntroductionIntroduction

Significant increase in detection due Significant increase in detection due to widespread use of US,CTto widespread use of US,CT

Most lesions detected incidentallyMost lesions detected incidentally

The prevalence of pancreatic cyst is The prevalence of pancreatic cyst is ……

Cystic lesions constitute about Cystic lesions constitute about 10 % of pancreatic tumors10 % of pancreatic tumors

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Clinical PresentationClinical Presentation

Most areMost are asymptomaticasymptomatic

Lesion with malignant potentialLesion with malignant potential – – 42%42%

Ca in situ / invasive cancer – 17%Ca in situ / invasive cancer – 17%

Fernandez Del Castillo et al. Arch Surg 2003

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ClassificationClassification

NeoplasticNeoplastic

Mucinous• Mucinous cystadenoma• Malignant mucinous cystic

tumors• Intraductal papillary

mucinous neoplasms - IPMN

Non Mucinous• Serous cystadenomaSerous cystadenoma• Cystic endocrine tumorsCystic endocrine tumors• Others

Non neoplasticNon neoplastic (pseudocysts) (pseudocysts)

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AIMAIM

To describe a single center To describe a single center experience with EUS guided FNA experience with EUS guided FNA in cystic pancreatic lesions in cystic pancreatic lesions

To determine the ability of EUS To determine the ability of EUS guided FNA to differentiate guided FNA to differentiate between between serous serous and and mucinousmucinous cystic tumorscystic tumors

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MethodsMethods

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MethodsMethods

Retrospective study Retrospective study 170 patients between 1997-170 patients between 1997-

20062006 155 patients ,195 EUS exams155 patients ,195 EUS exams 40 patients – EUSx2 40 patients – EUSx2

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MethodsMethods

Demographic dataDemographic data Clinical presentationClinical presentation Imaging – US, CT , EUSImaging – US, CT , EUS FNAFNA Surgical findingsSurgical findings Follow up on all patients (Follow up on all patients (office visits , office visits ,

data from family physicians, data from family physicians, gastroenterologists, patient’s families)gastroenterologists, patient’s families)

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MethodsMethods

EUSEUS Cyst location, size, morphologyCyst location, size, morphology FNA – fluid:FNA – fluid:

- characteristics- characteristics

- cytology- cytology

- tumor markers –- tumor markers –CEA,CA19-9,CA72-4,MCA CEA,CA19-9,CA72-4,MCA

Cyst wall sampling (cell block)Cyst wall sampling (cell block)

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Results

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ResultsResults

Clinical PresentationClinical Presentation No.No. %%

Incidental finding 103103 69.369.3

Abdominal pain 2929 19.619.6

Weight lossWeight loss 2 2 1.41.4

JaundiceJaundice 2 2

1.41.4

Abdominal pain/weight lossAbdominal pain/weight loss 55 3.43.4

DyspepsiaDyspepsia 22 1.4 1.4

DiarrheaDiarrhea 2 2 1.41.4

Diarrhea/weight lossDiarrhea/weight loss 33 2.02.0

101101 women, 54 menwomen, 54 menMean age – 64.3±14 yearsMean age – 64.3±14 years

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ResultsResults

FNA Histology No. %

Non neoplastic 12 16.0Serous 27 33.8 Mucinous 25 31.3Carcinoma 14 17.5Neuroendocrine 2 2.5

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ResultsResults

Surgical Pathology No. %

Non neoplastic 6 16.2Serous 4 10.8 Mucinous 13 35.1Mucinous ca. 11 29.7IPMN 2 5.4Neuroendocrine 1 2.7

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– 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%59% and 80%80% respectively.

EUS-FNA vs. Surgical biopsy

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ResultsResults Mean of Ln(CEA)Mean of Ln(CEA)** levels were 2.6 and levels were 2.6 and

5.8 for non mucinous and mucinous 5.8 for non mucinous and mucinous cases respectively (p<0.0001)cases respectively (p<0.0001)

No statistically significant difference No statistically significant difference with all the other tumor markers with all the other tumor markers testedtested

Rate of solid component in cyst – the Rate of solid component in cyst – the difference was not statistically difference was not statistically significant (p=0.14)significant (p=0.14)

No difference concerning cyst size or No difference concerning cyst size or morphologymorphology*CEA is highly skewed distributed and therefore we *CEA is highly skewed distributed and therefore we transformed the CEA level to Ln(CEA)transformed the CEA level to Ln(CEA)

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10

Class

12.00

10.00

8.00

6.00

4.00

2.00

0.00

-2.00

lnC

EA

Mucinous Ln

(CEA

) BoxPlot

Non-mucinous

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1.00.80.60.40.20.0

1 - Specificity

1.0

0.8

0.6

0.4

0.2

0.0

Sensi

tivi

ty

ROC Curve

ROC of CEA classification of Mucinous vs. Serous

1-specificity

sen

sit

ivit

y

AUC=0.902 (CI=(0.79-1.0))

A Threshold of CEA=58

ng/ml yields 86.4% and

87.5% sensitivity

and specificity

respectively

A Threshold of CEA=58

ng/ml yields 86.4% and

87.5% sensitivity

and specificity

respectively

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ConclusionsConclusions EUS is a useful tool but it can not EUS is a useful tool but it can not

alonealone distinguish between cystic distinguish between cystic lesions with variable malignant lesions with variable malignant potential potential

EUS-FNA EUS-FNA alonealone is also limited in its is also limited in its ability to correctly diagnose a cystic ability to correctly diagnose a cystic lesion – sensitivity 59% specificity lesion – sensitivity 59% specificity 80%80%

CombinationCombination of parameters – of parameters – cytology and CEA levels can cytology and CEA levels can significantly increase the diagnostic significantly increase the diagnostic yieldyield

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Thank You

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Criteria used in our Criteria used in our InstituteInstitute for Dx of for Dx of SerousSerous

cystscysts

- Clinical Clinical - Microcystic morphologyMicrocystic morphology- CEA level CEA level < 5 ng / ml< 5 ng / ml- Histology- cuboidal, non Histology- cuboidal, non

secreting cellssecreting cells

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- ClinicalClinical- Morphology – unilocular, thick Morphology – unilocular, thick

septa, solid componentsepta, solid component- High viscosity (mucinous) High viscosity (mucinous)

fluidfluid- CEA - CEA - >140 ng/ml>140 ng/ml- Histology – columnar Histology – columnar

secreting epitheliumsecreting epithelium

Criteria used in our Criteria used in our InstituteInstitute for Dx of Mucinous for Dx of Mucinous

cystscysts

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TreatmentTreatment

Serous cyst - Serous cyst - follow up only

Mucinous cyst – surgery

Diagnosis indeterminate - surgery