Frequent use of high-quality cross-sectional imaging has led to a significant rise in diagnosis of pancreatic cystic lesions (PCLs). Despite the fact that enormous effort has been put into the research of PCLs within the last two decades and multiple guidelines have been developed, our clinical decision-making especially in regard to mucinous lesions remains limited. Currently, clinical assessment, cross-sectional imaging and EUS with fluid analysis (if appropriate) belong to the standard care in patients with PCLs. For differentiation of mucinous from nonmucinous cysts, the sensitivity of cytological investigation and CEA in the cyst fluid is 42% and 52-79%, respectively. Due to the limited accuracy, further diagnostic tools are warranted. Two EUS-guided approaches have been introduced recently. Through-the-(19-gauge EUS) needle Moray microforceps have been developed, and several studies have acknowledged their contribution to the correct diagnosis as they help to overcome limited cellularity of the EUS-guided cyst fluid aspiration and traditional cytology. Confocal laser endomicroscopy offers real-time images and seems to be a promising method for the diagnosis and differential diagnosis of pancreatic PCLs. Example images of the needle-based confocal laser endomicroscopy criteria for the diagnosis of PCLs have been suggested recently. Before both, Moray microforceps and confocal laser endomicroscopy can be widely accepted, further studies are necessary to determine the real diagnostic yield and the clinical efficacy.

2nd Department of Internal Medicine Gastroenterology Charles University Faculty of Medicine in Hradec Kralove University Hospital Sokolska 581 Hradec Kralove 500 05 Czech Republic

Hammersmith Hospital Imperial College Healthcare NHS Trust London UK

The Royal Marsden Hospital NHS Foundation Trust Fulham Road Chelsea SW3 6JJ London UK

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Zerboni G., Signoretti M., Crippa S., Falconi M., Arcidiacono P. G., Capurso G. Systematic review and meta-analysis: prevalence of incidentally detected pancreatic cystic lesions in asymptomatic individuals. Pancreatology. 2019;19(1):2–9. doi: 10.1016/j.pan.2018.11.014. PubMed DOI

Farrell J. J. Prevalence, diagnosis and management of pancreatic cystic neoplasms: current status and future directions. Gut Liver. 2015;9(5):571–589. doi: 10.5009/gnl15063. PubMed DOI PMC

Munigala S., Gelrud A., Agarwal B. Risk of pancreatic cancer in patients with pancreatic cyst. Gastrointestinal Endoscopy. 2016;84(1):81–86. doi: 10.1016/j.gie.2015.10.030. PubMed DOI

Matthaei H., Feldmann G., Lingohr P., Kalff J. C. Molecular diagnostics of pancreatic cysts. Langenbeck's Archives of Surgery. 2013;398(8):1021–1027. doi: 10.1007/s00423-013-1116-z. PubMed DOI

de Pretis N., Mukewar S., Aryal-Khanal A., Bi Y., Takahashi N., Chari S. Pancreatic cysts: diagnostic accuracy and risk of inappropriate resections. Pancreatology. 2017;17(2):267–272. doi: 10.1016/j.pan.2017.01.002. PubMed DOI

Li F., Malli A., Cruz-Monserrate Z., Conwell D. L., Krishna S. G. Confocal endomicroscopy and cyst fluid molecular analysis: comprehensive evaluation of pancreatic cysts. World Journal Gastrointestinal Endoscopy. 2018;10(1):1–9. doi: 10.4253/wjge.v10.i1.1. PubMed DOI PMC

Jana T., Shroff J., Bhutani M. S. Pancreatic cystic neoplasms: review of current knowledge, diagnostic challenges, and management options. Journal Carcinogenesis. 2015;14(1):p. 3. doi: 10.4103/1477-3163.153285. PubMed DOI PMC

Moran R., Lennon M. Endoscopic ultrasonography in the evaluation of pancreatic cysts (p 185-192) In: Hawes R., Fockens P., Varadajulu S., editors. Endosonography. 4th Ed. Philadelphia: Elsevier; 2018.

Distler M., Aust D., Weitz J., Pilarsky C., Grützmann R. Precursor lesions for sporadic pancreatic cancer: PanIN, IPMN, and MCN. BioMed Research International. 2014;2014:11. doi: 10.1155/2014/474905.474905 PubMed DOI PMC

European Study Group on Cystic Tumours of the Pancreas. European evidence-based guidelines on pancreatic cystic neoplasms. Gut. 2018;67(5):789–804. doi: 10.1136/gutjnl-2018-316027. PubMed DOI PMC

Repák R., Rejchrt S., Bártová J., Malírová E., Tycová V., Bures J. Endoscopic ultrasonography (EUS) and EUS-guided fine-needle aspiration with cyst fluid analysis in pancreatic cystic neoplasms. Hepato-Gastroenterology. 2009;56(91-92):629–635. PubMed

Dumonceau J. M., 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(10):897–912. doi: 10.1055/s-0030-1256754. PubMed DOI

Polkowski M., Jenssen C., Kaye P., et al. Technical aspects of endoscopic ultrasound (EUS)-guided sampling in gastroenterology: European Society of Gastrointestinal Endoscopy (ESGE) Technical Guideline - March 2017. Endoscopy. 2017;49(10):989–1006. doi: 10.1055/s-0043-119219. PubMed DOI

Gillis A., Cipollone I., Cousins G., Conlon K. Does EUS-FNA molecular analysis carry additional value when compared to cytology in the diagnosis of pancreatic cystic neoplasm? A systematic review. HPB: The Official Journal of the International Hepato Pancreato Biliary Association. 2015;17(5):377–386. doi: 10.1111/hpb.12364. PubMed DOI PMC

Brugge W. R., Lewandrowski K., Lee-Lewandrowski E., et al. Diagnosis of pancreatic cystic neoplasms: a report of the cooperative pancreatic cyst study. Gastroenterology. 2004;126(5):1330–1336. doi: 10.1053/j.gastro.2004.02.013. PubMed DOI

Guarner-Argente C., Shah P., Buchner A., Ahmad N. A., Kochman M. L., Ginsberg G. G. Use of antimicrobials for EUS-guided FNA of pancreatic cysts: a retrospective, comparative analysis. Gastrointestinal Endoscopy. 2011;74(1):81–86. doi: 10.1016/j.gie.2011.03.1244. PubMed DOI

Facciorusso A., Buccino V. R., Turco A., Antonino M., Muscatiello N. Antibiotics do not decrease the rate of infection after endoscopic ultrasound fine-needle aspiration of pancreatic cysts. Digestive Diseases and Sciences. 2019;64(8):2308–2315. doi: 10.1007/s10620-019-05655-x. PubMed DOI

Castellano-Megías V. M., Andrés C. I., López-Alonso G., Colina-Ruizdelgado F. Pathological features and diagnosis of intraductal papillary mucinous neoplasm of the pancreas. World Journal Gastrointestinal Oncology. 2014;6(9):311–324. doi: 10.4251/wjgo.v6.i9.311. PubMed DOI PMC

Grützmann R., Niedergethmann M., Pilarsky C., Klöppel G., Saeger H. D. Intraductal papillary mucinous tumors of the pancreas: biology, diagnosis, and treatment. The Oncologist. 2010;15(12):1294–1309. doi: 10.1634/theoncologist.2010-0151. PubMed DOI PMC

Furukawa T., Klöppel G., Volkan Adsay N., et al. Classification of types of intraductal papillary-mucinous neoplasm of the pancreas: a consensus study. Virchows Archiv. 2005;447(5):794–799. doi: 10.1007/s00428-005-0039-7. PubMed DOI

Furukawa T., Hatori T., Fujita I., et al. Prognostic relevance of morphological types of intraductal papillary mucinous neoplasms of the pancreas. Gut. 2011;60(4):509–516. doi: 10.1136/gut.2010.210567. PubMed DOI

Tanaka M., Fernández-del Castillo C., Adsay V., et al. International consensus guidelines 2012 for the management of IPMN and MCN of the pancreas. Pancreatology. 2012;12(3):183–197. doi: 10.1016/j.pan.2012.04.004. PubMed DOI

Adsay N. V., Merati K., Basturk O., et al. Pathologically and biologically distinct types of epithelium in intraductal papillary mucinous neoplasms: delineation of an “intestinal” pathway of carcinogenesis in the pancreas. The American Journal of Surgical Pathology. 2004;28(7):839–848. doi: 10.1097/00000478-200407000-00001. PubMed DOI

Adsay N. V., Pierson C., Sarkar F., et al. Colloid (mucinous noncystic) carcinoma of the pancreas. The American Journal of Surgical Pathology. 2001;25(1):26–42. doi: 10.1097/00000478-200101000-00003. PubMed DOI

Allen P. J. The diagnosis and management of cystic lesions of the pancreas. Chinese Clinical Oncology. 2017;6(6):p. 60. doi: 10.21037/cco.2017.12.05. PubMed DOI

Sahani D. V., Kadavigere R., Saokar A., Fernandez-del Castillo C., Brugge W. R., Hahn P. F. Cystic pancreatic lesions: a simple imaging-based classification system for guiding management. Radiographics. 2005;25(6):1471–1484. doi: 10.1148/rg.256045161. PubMed DOI

Springer S., Wang Y., Dal Molin M., et al. A combination of molecular markers and clinical features improve the classification of pancreatic cysts. Gastroenterology. 2015;149(6):1501–1510. doi: 10.1053/j.gastro.2015.07.041. PubMed DOI PMC

Moore P. S., Zamboni G., Brighenti A., et al. Molecular characterization of pancreatic serous microcystic adenomas: evidence for a tumor suppressor gene on chromosome 10q. The American Journal of Pathology. 2001;158(1):317–321. doi: 10.1016/S0002-9440(10)63971-5. PubMed DOI PMC

Jais B., Rebours V., Malleo G., et al. Serous cystic neoplasm of the pancreas: a multinational study of 2622 patients under the auspices of the International Association of Pancreatology and European Pancreatic Club (European Study Group on Cystic Tumors of the Pancreas) Gut. 2016;65(2):305–312. doi: 10.1136/gutjnl-2015-309638. PubMed DOI

van der Waaij L. A., van Dullemen H. M., Porte R. J. Cyst fluid analysis in the differential diagnosis of pancreatic cystic lesions: a pooled analysis. Gastrointestinal Endoscopy. 2005;62(3):383–389. doi: 10.1016/S0016-5107(05)01581-6. PubMed DOI

Klimstra D. S., Wenig B. M., Heffess C. S. Solid-pseudopapillary tumor of the pancreas: a typically cystic carcinoma of low malignant potential. Seminars in Diagnostic Pathology. 2000;17(1):66–80. PubMed

Tanaka M., Chari S., Adsay V., et al. International consensus guidelines for management of intraductal papillary mucinous neoplasms and mucinous cystic neoplasms of the pancreas. Pancreatology. 2006;6(1-2):17–32. doi: 10.1159/000090023. PubMed DOI

Tanaka M., Fernández-Del Castillo C., Kamisawa T., et al. Revisions of international consensus Fukuoka guidelines for the management of IPMN of the pancreas. Pancreatology. 2017;17(5):738–753. doi: 10.1016/j.pan.2017.07.007. PubMed DOI

Vege S. S., Ziring B., Jain R., Moayyedi P. American gastroenterological association institute guideline on the diagnosis and management of asymptomatic neoplastic pancreatic cysts. Gastroenterology. 2015;148(4):819–822. doi: 10.1053/j.gastro.2015.01.015. quize12-3. PubMed DOI

Aparicio J. R., Martínez J., Niveiro M., et al. Direct intracystic biopsy and pancreatic cystoscopy through a 19-gauge needle EUS (with videos) Gastrointestinal Endoscopy. 2010;72(6):1285–1288. doi: 10.1016/j.gie.2010.08.036. PubMed DOI

Barresi L., Tarantino I., Ligresti D., Curcio G., Granata A., Traina M. A new tissue acquisition technique in pancreatic cystic neoplasm: endoscopic ultrasound-guided through-the-needle forceps biopsy. Endoscopy. 2015;47(S 01):E297–E298. doi: 10.1055/s-0034-1392031. PubMed DOI

Pham K. D., Engjom T., Gjelberg Kollesete H., Helgeland L. Diagnosis of a mucinous pancreatic cyst and resection of an intracystic nodule using a novel through-the-needle micro forceps. Endoscopy. 2016;48(S 01):E125–E126. doi: 10.1055/s-0042-105437. PubMed DOI

Shakhatreh M. H., Naini S. R., Brijbassie A. A., Grider D. J., Shen P., Yeaton P. Use of a novel through-the-needle biopsy forceps in endoscopic ultrasound. Endoscopy International Open. 2016;04(04):E439–E442. doi: 10.1055/s-0042-101941. PubMed DOI PMC

Attili F., Pagliari D., Rimbaș M., et al. Endoscopic ultrasound-guided histological diagnosis of a mucinous non-neoplastic pancreatic cyst using a specially designed through-the-needle microforceps. Endoscopy. 2016;48(S 01):E188–E189. doi: 10.1055/s-0042-108194. PubMed DOI

Huelsen A., Cooper C., Saad N., Gupta S. Endoscopic ultrasound-guided, through-the-needle forceps biopsy in the assessment of an incidental large pancreatic cystic lesion with prior inconclusive fine-needle aspiration. Endoscopy. 2017;49(S 01):E109–E110. doi: 10.1055/s-0043-100217. PubMed DOI

Chen A. L., Misdraji J., Brugge W. R., Ferrone C. R., Pitman M. B. Acinar cell cystadenoma: a challenging cytology diagnosis, facilitated by moray® micro-forceps biopsy. Diagnostic Cytopathology. 2017;45(6):557–560. doi: 10.1002/dc.23693. PubMed DOI

Basar O., Brugge W. R. My treatment approach: pancreatic cysts. Mayo Clinic Proceedings. 2017;92(10):1519–1531. doi: 10.1016/j.mayocp.2017.06.017. PubMed DOI

Vilas-Boas F., Macedo G. Pancreatic cystic lesions: new endoscopic trends in diagnosis. Journal of Clinical Gastroenterology. 2018;52(1):13–19. doi: 10.1097/MCG.0000000000000945. PubMed DOI

Basar O. Pancreatic cyst biopsy: improvement in diagnosis with micro forceps biopsy. Cancer Cytopathology. 2018;126(4):227–228. doi: 10.1002/cncy.21975. PubMed DOI

Mittal C., Obuch J. C., Hammad H., et al. Technical feasibility, diagnostic yield, and safety of microforceps biopsies during EUS evaluation of pancreatic cystic lesions (with video) Gastrointestinal Endoscopy. 2018;87(5):1263–1269. doi: 10.1016/j.gie.2017.12.025. PubMed DOI

Basar O., Yuksel O., Yang D. J., et al. Feasibility and safety of microforceps biopsy in the diagnosis of pancreatic cysts. Gastrointestinal Endoscopy. 2018;88(1):79–86. doi: 10.1016/j.gie.2018.02.039. PubMed DOI

Zhang M. L., Arpin R. N., Brugge W. R., Forcione D. G., Basar O., Pitman M. B. Moray micro forceps biopsy improves the diagnosis of specific pancreatic cysts. Cancer Cytopathology. 2018;126(6):414–420. doi: 10.1002/cncy.21988. PubMed DOI

Kovacevic B., Karstensen J. G., Havre R. F., et al. Initial experience with EUS-guided microbiopsy forceps in diagnosing pancreatic cystic lesions: a multicenter feasibility study (with video) Endoscopic Ultrasound. 2018;7(6):383–388. doi: 10.4103/eus.eus_16_18. PubMed DOI PMC

Minsky M. Memoir on inventing the confocal scanning microscope. Scanning. 1988;10(4):138. doi: 10.1002/sca.4950100403. DOI

Savidge T. C., Walker-Smith J. A., Phillips A. D. Novel insights into human intestinal epithelial cell proliferation in health and disease using confocal microscopy. Gut. 1995;36(3):369–374. doi: 10.1136/gut.36.3.369. PubMed DOI PMC

ASGE Technology Committee. Confocal laser endomicroscopy. Gastrointestinal Endoscopy. 2014;80(6):928–938. PubMed

Hoffman A., Goetz M., Vieth M., Galle P. R., Neurath M. F., Kiesslich R. Confocal laser endomicroscopy: technical status and current indications. Endoscopy. 2006;38(12):1275–1283. doi: 10.1055/s-2006-944813. PubMed DOI

Kunes M., Kvetina J., Malakova J., Bures J., Kopacova M., Rejchrt S. Pharmacokinetics and organ distribution of fluorescein in experimental pigs: an input study for confocal laser endomicroscopy of the gastrointestinal tract. Neuro Endocrinology Letters. 2010;31(Suppl 2):57–61. PubMed

Tringali A., Lemmers A., Meves V., et al. Intraductal biliopancreatic imaging: European Society of Gastrointestinal Endoscopy (ESGE) technology review. Endoscopy. 2015;47(08):739–753. doi: 10.1055/s-0034-1392584. PubMed DOI

Li F., El-Dika S., Modi R. M., Chen W., Krishna S. G. Poorly differentiated pancreatic carcinoma with sarcomatoid differentiation: confocal endomicroscopy of an uncommon pancreatic cystic lesion. Endoscopy. 2016;48(S 01):E363–E364. doi: 10.1055/s-0042-118457. PubMed DOI

Napoleon B., Palazzo M., Lemaistre A. I., et al. Needle-based confocal laser endomicroscopy of pancreatic cystic lesions: a prospective multicenter validation study in patients with definite diagnosis. Endoscopy. 2018 doi: 10.1055/a-0732-5356. PubMed DOI

Salom F., Prat F. Current indications and yield of endoscopic ultrasound and ancillary techniques in pancreatic cystic neoplasms. Clinical Journal of Gastroenterology. 2019;12(2):93–101. doi: 10.1007/s12328-018-00930-2. PubMed DOI

Okuno N., Hara K., Obata M. Novel method of diagnosing solid pseudopapillary neoplasms of the pancreas: needle-based confocal laser endomicroscopy. Digestive Endoscopy. 2019 doi: 10.1111/den.13396. PubMed DOI

East J. E., Vleugels J. L., Roelandt P., et al. Advanced endoscopic imaging: European Society of Gastrointestinal Endoscopy (ESGE) Technology Review. Endoscopy. 2016;48(11):1029–1045. doi: 10.1055/s-0042-118087. PubMed DOI

Fugazza A., Gaiani F., Carra M. C., et al. Confocal laser endomicroscopy in gastrointestinal and pancreatobiliary diseases: a systematic review and meta-analysis. Biomed Research International. 2016;2016:31. doi: 10.1155/2016/4638683.4638683 PubMed DOI PMC

Konda V. J. A., Aslanian H. R., Wallace M. B., Siddiqui U. D., Hart J., Waxman I. First assessment of needle-based confocal laser endomicroscopy during EUS-FNA procedures of the pancreas (with videos) Gastrointestinal Endoscopy. 2011;74(5):1049–1060. doi: 10.1016/j.gie.2011.07.018. PubMed DOI

Konda V. J., Meining A., Jamil L. H., et al. A pilot study of in vivo identification of pancreatic cystic neoplasms with needle-based confocal laser endomicroscopy under endosonographic guidance. Endoscopy. 2013;45(12):1006–1013. doi: 10.1055/s-0033-1344714. PubMed DOI

Kahaleh M., Turner B. G., Bezak K., et al. Probe-based confocal laser endomicroscopy in the pancreatic duct provides direct visualization of ductal structures and aids in clinical management. Digestive and Liver Disease. 2015;47(3):202–204. doi: 10.1016/j.dld.2014.11.006. PubMed DOI

Nakai Y., Iwashita T., Park D. H., Samarasena J. B., Lee J. G., Chang K. J. Diagnosis of pancreatic cysts: EUS-guided, through-the-needle confocal laser-induced endomicroscopy and cystoscopy trial: DETECT study. Gastrointestinal Endoscopy. 2015;81(5):1204–1214. doi: 10.1016/j.gie.2014.10.025. PubMed DOI

Napoleon B., Lemaistre A. I., Pujol B., et al. A novel approach to the diagnosis of pancreatic serous cystadenoma: needle-based confocal laser endomicroscopy. Endoscopy. 2015;47(01):26–32. doi: 10.1055/s-0034-1390693. PubMed DOI

Kadayifci A., Atar M., Basar O., Forcione D. G., Brugge W. R. Needle-based confocal laser endomicroscopy for evaluation of cystic neoplasms of the pancreas. Digestive Diseases and Sciences. 2017;62(5):1346–1353. doi: 10.1007/s10620-017-4521-2. PubMed DOI

Kadayifci A., Atar M., Yang M., Fernandez-Del Castillo C., Mino-Kenudson M., Brugge W. R. Imaging of pancreatic cystic lesions with confocal laser endomicroscopy: an ex vivo pilot study. Surgical Endoscopy. 2017;31(12):5119–5126. doi: 10.1007/s00464-017-5577-y. PubMed DOI

Krishna S. G., Modi R. M., Kamboj A. K., et al. In vivo and ex vivo confocal endomicroscopy of pancreatic cystic lesions: a prospective study. World Journal of Gastroenterology. 2017;23(18):3338–3348. doi: 10.3748/wjg.v23.i18.3338. PubMed DOI PMC

Karia K., Waxman I., Konda V. J., et al. Needle-based confocal endomicroscopy for pancreatic cysts: the current agreement in interpretation. Gastrointestinal Endoscopy. 2016;83(5):924–927. doi: 10.1016/j.gie.2015.08.080. PubMed DOI

Krishna S. G., Brugge W. R., Dewitt J. M., et al. Needle-based confocal laser endomicroscopy for the diagnosis of pancreatic cystic lesions: an international external interobserver and intraobserver study (with videos) Gastrointestinal Endoscopy. 2017;86(4):644–654.e2. doi: 10.1016/j.gie.2017.03.002. PubMed DOI

Wallace M. B., Meining A., Canto M. I., et al. The safety of intravenous fluorescein for confocal laser endomicroscopy in the gastrointestinal tract. Alimentary Pharmacology & Therapeutics. 2010;31(5):548–552. doi: 10.1111/j.1365-2036.2009.04207.x. PubMed DOI

Le Pen C., Palazzo L., Napoleon B. A health economic evaluation of needle-based confocal laser endomicroscopy for the diagnosis of pancreatic cysts. Endoscopy International Open. 2017;05(10):E987–E995. doi: 10.1055/s-0043-117947. PubMed DOI PMC

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