J Pathol Transl Med.  2015 Sep;49(5):364-372. 10.4132/jptm.2015.07.19.

Cytology Specimen Management, Triage and Standardized Reporting of Fine Needle Aspiration Biopsies of the Pancreas

• Yoon WJ
• Pitman MB

• KMID: 2381391
• DOI: http://doi.org/10.4132/jptm.2015.07.19

Abstract

The recent advances in pancreas cytology specimen sampling methods have enabled a specific cytologic diagnosis in most cases. Proper triage and processing of the cytologic specimen is pivotal in making a diagnosis due to the need for ancillary testing in addition to cytological evaluation, which is especially true in the diagnosis of pancreatic cysts. Newly proposed terminology for pancreaticobiliary cytology offers a standardized language for reporting that aims to improve communication among patient caregivers and provide for increased flexibility in patient management. This review focuses on these updates in pancreas cytology for the optimal evaluation of solid and cystic lesions of the pancreas.

Keyword

Pancreas; Cytology; Biopsy, fine-needle; Triage; Terminology

MeSH Terms

Biopsy*
Biopsy, Fine-Needle*
Caregivers
Diagnosis
Humans
Pancreas*
Pancreatic Cyst
Pliability
Triage*

Figure

• 

  Fig. 1. Needle casts of blood clot expressed onto a glass slide should be placed in formalin for cellblock processing. Tissue entrapped in blood clot is not evaluable on cytology.

• 

  Fig. 2. Tissue fragments from needle rinsings or clotted tissue worms as illustrated in Fig. 1 should be processed as a cellblock, which provides readily available tissue for ancillary testing. This example of a well-differentiated neuroendocrine tumor resembles a solid-pseudopapillary neoplasm.

• 

  Fig. 3. The example of a well-differentiated neuroendocrine tumor resembling a solid-pseudopapillary neoplasm illustrated in Fig. 2 is tested with an immunohistochemical stain for synaptophysin, which shows diffuse strong staining supporting the diagnosis of a neuroendocrine tumor (peroxidase-anti-peroxidase).

• 

  Fig. 4. Algorithm for PCF triage and ancillary testing at the Massachusetts General Hospital. CEA, carcinoembryonic antigen.

Reference

1. Pitman MB, Centeno BA, Ali SZ, et al. Standardized terminology and nomenclature for pancreatobiliary cytology: the Papanicolaou Society of Cytopathology guidelines. Diagn Cytopathol. 2014; 42:338–50.

2. Mekky MA, Abbas WA. Endoscopic ultrasound in gastroenterology: from diagnosis to therapeutic implications. World J Gastroenterol. 2014; 20:7801–7.

3. Adler D, Max Schmidt C, Al-Haddad M, et al. Clinical evaluation, imaging studies, indications for cytologic study, and preprocedural requirements for duct brushing studies and pancreatic FNA: the Papanicolaou Society of Cytopathology recommendations for pancreatic and biliary cytology. Diagn Cytopathol. 2014; 42:325–32.

4. Brugge W, Dewitt J, Klapman JB, et al. Techniques for cytologic sampling of pancreatic and bile duct lesions. Diagn Cytopathol. 2014; 42:333–7.

5. Volmar KE, Vollmer RT, Jowell PS, Nelson RC, Xie HB. Pancreatic FNA in 1000 cases: a comparison of imaging modalities. Gastrointest Endosc. 2005; 61:854–61.

6. Okasha HH, Naga MI, Esmat S, et al. Endoscopic ultrasound-guided fine needle aspiration versus percutaneous ultrasound-guided fine needle aspiration in diagnosis of focal pancreatic masses. Endosc Ultrasound. 2013; 2:190–3.

7. Dumonceau JM, Polkowski M, Larghi A, et al. Indications, results, and clinical impact of endoscopic ultrasound (EUS)-guided sampling in gastroenterology: European Society of Gastrointestinal Endoscopy (ESGE) Clinical Guideline. Endoscopy. 2011; 43:897–912.

8. Wiersema MJ, Vilmann P, Giovannini M, Chang KJ, Wiersema LM. Endosonography-guided fine-needle aspiration biopsy: diagnostic accuracy and complication assessment. Gastroenterology. 1997; 112:1087–95.

9. Lee JH, Stewart J, Ross WA, Anandasabapathy S, Xiao L, Staerkel G. Blinded prospective comparison of the performance of 22-gauge and 25-gauge needles in endoscopic ultrasound-guided fine needle aspiration of the pancreas and peri-pancreatic lesions. Dig Dis Sci. 2009; 54:2274–81.

10. Madhoun MF, Wani SB, Rastogi A, et al. The diagnostic accuracy of 22-gauge and 25-gauge needles in endoscopic ultrasound-guided fine needle aspiration of solid pancreatic lesions: a meta-analysis. Endoscopy. 2013; 45:86–92.

11. Panic N, Larghi A. Techniques for endoscopic ultrasound-guided fine-needle biopsy. Gastrointest Endosc Clin N Am. 2014; 24:83–107.

12. Layfield LJ, Ehya H, Filie AC, et al. Utilization of ancillary studies in the cytologic diagnosis of biliary and pancreatic lesions: the Papanicolaou Society of Cytopathology guidelines for pancreatobiliary cytology. Diagn Cytopathol. 2014; 42:351–62.

13. Pitman M. Pancreas. In : Bibbo M, Wilbur DC, editors. Comprehensive cytopathology. London: Elsevier;2014. p. 751–73.

14. Bang JY, Magee SH, Ramesh J, Trevino JM, Varadarajulu S. Randomized trial comparing fanning with standard technique for endoscopic ultrasound-guided fine-needle aspiration of solid pancreatic mass lesions. Endoscopy. 2013; 45:445–50.

15. Jenssen C, Dietrich CF. Endoscopic ultrasound-guided fine-needle aspiration biopsy and trucut biopsy in gastroenterology: an overview. Best Pract Res Clin Gastroenterol. 2009; 23:743–59.

16. Brugge WR. The role of EUS in the diagnosis of cystic lesions of the pancreas. Gastrointest Endosc. 2000; 52(6 Suppl):S18–22.

17. Lee LS, Saltzman JR, Bounds BC, Poneros JM, Brugge WR, Thompson CC. EUS-guided fine needle aspiration of pancreatic cysts: a retrospective analysis of complications and their predictors. Clin Gastroenterol Hepatol. 2005; 3:231–6.

18. Yoon WJ, Daglilar ES, Fernandez-del Castillo C, Mino-Kenudson M, Pitman MB, Brugge WR. Peritoneal seeding in intraductal papillary mucinous neoplasm of the pancreas patients who underwent endoscopic ultrasound-guided fine-needle aspiration: the PIPE Study. Endoscopy. 2014; 46:382–7.

19. Olson MT, Ali SZ. Cytotechnologist on-site evaluation of pancreas fine needle aspiration adequacy: comparison with cytopathologists and correlation with the final interpretation. Acta Cytol. 2012; 56:340–6.

20. Iglesias-Garcia J, Dominguez-Munoz JE, Abdulkader I, et al. Influence of on-site cytopathology evaluation on the diagnostic accuracy of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) of solid pancreatic masses. Am J Gastroenterol. 2011; 106:1705–10.

21. Collins BT, Murad FM, Wang JF, Bernadt CT. Rapid on-site evaluation for endoscopic ultrasound-guided fine-needle biopsy of the pancreas decreases the incidence of repeat biopsy procedures. Cancer Cytopathol. 2013; 121:518–24.

22. da Cunha Santos G, Ko HM, Saieg MA, Geddie WR. “The petals and thorns” of ROSE (rapid on-site evaluation). Cancer Cytopathol. 2013; 121:4–8.

23. Yoon WJ, Daglilar ES, Pitman MB, Brugge WR. Cystic pancreatic neuroendocrine tumors: endoscopic ultrasound and fine-needle aspiration characteristics. Endoscopy. 2013; 45:189–94.

24. Morales-Oyarvide V, Yoon WJ, Ingkakul T, et al. Cystic pancreatic neuroendocrine tumors: the value of cytology in preoperative diagnosis. Cancer Cytopathol. 2014; 122:435–44.

25. Pitman MB. Pancreatic cyst fluid triage: a critical component of the preoperative evaluation of pancreatic cysts. Cancer Cytopathol. 2013; 121:57–60.

26. Jones M, Zheng Z, Wang J, et al. Impact of next-generation sequencing on the clinical impression of pancreatic cysts. Gastrointest Endosc. 2015; Aug. 5. [Epub]. http://dx.doi.org/10.1016/j.gie.2015.06.047.

27. Cizginer S, Turner BG, Bilge AR, Karaca C, Pitman MB, Brugge WR. Cyst fluid carcinoembryonic antigen is an accurate diagnostic marker of pancreatic mucinous cysts. Pancreas. 2011; 40:1024–8.

28. Brugge WR, Lewandrowski K, Lee-Lewandrowski E, et al. Diagnosis of pancreatic cystic neoplasms: a report of the cooperative pancreatic cyst study. Gastroenterology. 2004; 126:1330–6.

29. van der Waaij LA, van Dullemen HM, Porte RJ. Cyst fluid analysis in the differential diagnosis of pancreatic cystic lesions: a pooled analysis. Gastrointest Endosc. 2005; 62:383–9.

30. Raval JS, Zeh HJ, Moser AJ, et al. Pancreatic lymphoepithelial cysts express CEA and can contain mucous cells: potential pitfalls in the preoperative diagnosis. Mod Pathol. 2010; 23:1467–76.

31. Johnston J, Wheatley GH 3rd, El Sayed HF, Marsh WB, Ellison EC, Bloomston M. Gastric duplication cysts expressing carcinoembryonic antigen mimicking cystic pancreatic neoplasms in two adults. Am Surg. 2008; 74:91–4.

32. Lewandrowski KB, Southern JF, Pins MR, Compton CC, Warshaw AL. Cyst fluid analysis in the differential diagnosis of pancreatic cysts. A comparison of pseudocysts, serous cystadenomas, mucinous cystic neoplasms, and mucinous cystadenocarcinoma. Ann Surg. 1993; 217:41–7.

33. Moparty B, Pitman MB, Brugge WR. Pancreatic cyst fluid amylase is not a marker to differentiate IPMN from MCN. Gastrointest Endosc. 2007; 65:AB303.

34. Khalid A, Zahid M, Finkelstein SD, et al. Pancreatic cyst fluid DNA analysis in evaluating pancreatic cysts: a report of the PANDA study. Gastrointest Endosc. 2009; 69:1095–102.

35. Shen J, Brugge WR, Dimaio CJ, Pitman MB. Molecular analysis of pancreatic cyst fluid: a comparative analysis with current practice of diagnosis. Cancer. 2009; 117:217–27.

36. Wu J, Matthaei H, Maitra A, et al. Recurrent GNAS mutations define an unexpected pathway for pancreatic cyst development. Sci Transl Med. 2011; 3:92ra66.

37. Nikiforova MN, Khalid A, Fasanella KE, et al. Integration of KRAS testing in the diagnosis of pancreatic cystic lesions: a clinical experience of 618 pancreatic cysts. Mod Pathol. 2013; 26:1478–87.

38. Amato E, Molin MD, Mafficini A, et al. Targeted next-generation sequencing of cancer genes dissects the molecular profiles of intraductal papillary neoplasms of the pancreas. J Pathol. 2014; 233:217–27.

39. Hruban RH, Goggins M, Parsons J, Kern SE. Progression model for pancreatic cancer. Clin Cancer Res. 2000; 6:2969–72.

40. Finkelstein SD, Bibbo M, Loren DE, et al. Molecular analysis of centrifugation supernatant fluid from pancreaticobiliary duct samples can improve cancer detection. Acta Cytol. 2012; 56:439–47.

41. Wu J, Jiao Y, Dal Molin M, et al. Whole-exome sequencing of neoplastic cysts of the pancreas reveals recurrent mutations in components of ubiquitin-dependent pathways. Proc Natl Acad Sci U S A. 2011; 108:21188–93.

42. Pitman MB, Centeno BA, Ali SZ, et al. Standardized terminology and nomenclature for pancreatobiliary cytology: The Papanicolaou Society of Cytopathology Guidelines. Cytojournal. 2014; 11(Suppl 1):3.

43. Kuo EJ, Salem RR. Population-level analysis of pancreatic neuroendocrine tumors 2 cm or less in size. Ann Surg Oncol. 2013; 20:2815–21.

44. Klimstra DS. Pathology reporting of neuroendocrine tumors: essential elements for accurate diagnosis, classification, and staging. Semin Oncol. 2013; 40:23–36.

45. Kloppel G, Hruban R, Klimstra D, et al. Solid-pseudopapillary neoplasm of the pancreas. In : Bosman FT, Carneiro F, Hruban RH, Theise ND, editors. WHO classification of tumours of the digestive system. 4th ed. Sterling: Stylus Publishing;2010. p. 327–30.

46. Pitman MB, Centeno BA, Daglilar ES, Brugge WR, Mino-Kenudson M. Cytological criteria of high-grade epithelial atypia in the cyst fluid of pancreatic intraductal papillary mucinous neoplasms. Cancer Cytopathol. 2014; 122:40–7.

47. Pitman MB, Centeno BA, Genevay M, Fonseca R, Mino-Kenudson M. Grading epithelial atypia in endoscopic ultrasound-guided fineneedle aspiration of intraductal papillary mucinous neoplasms: an international interobserver concordance study. Cancer Cytopathol. 2013; 121:729–36.

48. Pitman MB, Genevay M, Yaeger K, et al. High-grade atypical epithelial cells in pancreatic mucinous cysts are a more accurate predictor of malignancy than “positive” cytology. Cancer Cytopathol. 2010; 118:434–40.

49. Pitman MB, Lewandrowski K, Shen J, Sahani D, Brugge W, Fernandez-del Castillo C. Pancreatic cysts: preoperative diagnosis and clinical management. Cancer Cytopathol. 2010; 118:1–13.