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

1. 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

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

3. Clinical Presentation • Asymptomatic • Abdominal pain • Jaundice • Pancreatitis

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

5. Classification • Non neoplastic (pseudocysts) • Neoplastic Non Mucinous Mucinous

6. Classification Non Mucinous Cysts • Serous cystadenoma • Cystic endocrine tumors • Other

7. Classification Mucinous Cysts • Mucinous cystadenoma • Malignant mucinous cystic tumors • Intraductal papillary mucinous neoplasms - IPMN

9. Diagnosis • CT – microcystic appearance, central fibrosis- Serous Unilocular, macrocystic, peripheral calcification- Mucinous • MRCP – MPD dilatation, mural nodules ductal connection - IPMN

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

11. EUS – Serous cyst

12. EUS – Mucinous cyst

13. 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

14. 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

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

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

17. 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

18. Methods

19. 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

20. 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)

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

22. Results

23. Results

24. Results

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

26. Results

27. Results

28. 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.

29. 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)

30. BoxPlot Ln(CEA) Non-mucinous Mucinous

31. Logistic regression results 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.

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

33. 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

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

35. 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.

36. 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)

37. Natural history of mucinous cystic neoplasm 78 years old woman with incidental finding - 1977

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

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

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

41. Thank You