Gastroenterologie
a hepatologie

The role of molecular bio­logy in the differential dia­gnosis of pancreatic cystic neoplasias

Ivo Horný¹, Tomáš Hucl ^{Orcid.org  2}

+ Affiliation
¹ Interní oddělení, gastroenterologie, Nemocnice Strakonice, a. s.
² Klinika hepatogastroenterologie, Transplantcentrum, IKEM, Praha

Summary

Pancreatic cysts have been detected ever more frequently in recent years due to the advanced and wider use of imaging methods. We find them on CT or MR also in asymptomatic patients who do not have a history of any pancreatic disease. Pancreatic cystic lesions represent a wide range of pathological changes from simple cysts through precancerous lesions to malignant cysts. Accurate dia­gnosis remains difficult despite the combination of clinical status evaluation, imaging findings, and bio­chemical and cytological examination. Molecular bio­logical examination of cyst aspirate obtained by endosonographic examination increases the detection rate of mucinous cysts (KRAS/GNAS/VHL) and cysts with a high risk of malignancy (KRAS/GNAS/p53/PIK3CA/PTEN/CDKN2A/SMAD4) and optimizes therapeutic approach. Larger prospective validation studies are necessary to make this costly and limited method a routine part of clinical practice.

Keywords

molekulární biologie, neoplasms, pankreatické cysty

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Literature

1. Lee KS, Sekhar A, Rofsky NM et al. Prevalence of incidental pancreatic cysts in the adult population on MR imaging. Am J Gastroenterol 2010; 105(9): 2079–2084. doi: 10.1038/ajg.2010.122.
2. Faias S, Pereira L, Luís  et al. Genetic testing vs microforceps bio­psy in pancreatic cysts: systematic review and meta-analysis. World J Gastroenterol 2019; 25(26): 3450–3467. doi: 10.3748/wjg.v25.i26.3450.
3. Vege SS, Ziring B, Jain R et al. 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.
4. 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.
5. Plougmann JI, Klausen P, Karstensen JG et al. Molecular bio­markers have the potential to improve the dia­gnostic work-up of pancreatic cystic lesions. Scand J Gastroenterol 2017; 52(9): 932–940. doi: 10.1080/00365521.2017.1333628.
6. Wang K-X, Ben Q-W, Jin Z-D et al. Assessment of morbidity and mortality associated with EUS-guided FNA: a systematic review. Gastrointest Endosc 2011; 73(2): 283–290. doi: 10.1016/j.gie.2010.10.045.
7. ASGE standards of practice committee, Khashab MA, Chithadi KV et al. Antibio­tic prophylaxis for GI endoscopy. Gastrointest Endosc 2015; 81(1): 81–89. doi: 10.1016/j.gie.2014.08. 008.
8. Hawes R, Fockens P, Varadarajulu S. Endosonography. [online]. Dostupné z URL: https: //www.elsevier.com/books/link/link/9780323221511.
9. Barresi L, Tarantino I, Ligresti D et al. A new tissue acquisition technique in pancreatic cystic neoplasm: endoscopic ultrasound-guided through-the-needle forceps bio­psy. Endoscopy 2015; 47 Suppl 1 UCTN: E297–298. doi: 10.1055/s-0034-1392031.
10. Mittal C, Obuch JC, Hammad H, et al. Technical feasibility, dia­gnostic yield, and safety of microforceps bio­psies during EUS evaluation of pancreatic cystic lesions (with video). Gastrointest Endosc. 2018; 87(5): 1263–1269. doi: 10.1016/j.gie.2017.12.025.
11. Basar O, Yuksel O, Yang DJ et al. Feasibility and safety of microforceps bio­psy in the dia­gnosis of pancreatic cysts. Gastrointest Endosc 2018; 88(1): 79–86. doi: 10.1016/j.gie.2018.02.039.
12. Zhang ML, Arpin RN, Brugge WR et al. Moray micro forceps bio­psy improves the dia­gnosis of specific pancreatic cysts. Cancer Cytopathol 2018; 126(6): 414–420. doi: 10.1002/cncy.21988.
13. Walsh RM, Henderson JM, Vogt DP et al. Prospective preoperative determination of mucinous pancreatic cystic neoplasms. Surgery 2002; 132(4): 628–634. doi: 10.1067/msy.2002.127543.
14. Thosani N, Dasari CS, Bhutani MS et al. Molecular pathogenesis of intraductal papillary mucinous neoplasms of the pancreas. Pancreas 2010; 39(8): 1129–1133. doi: 10.1097/MPA.0b013e3181f66cdf.
15. Frossard JL, Amouyal P, Amouyal G et al. Performance of endosonography-guided fine needle aspiration and bio­psy in the dia­gnosis of pancreatic cystic lesions. Am J Gastroenterol 2003; 98(7): 1516–1524. doi: 10.1111/j.1572- 0241.2003.07530.x.
16. Nakai Y, Iwashita T, Shinoura S et al. Role of serial EUS-guided FNA on pancreatic cystic neoplasms: a retrospective analysis of repeat carcinoembryonic antigen measurements. Gastrointest Endosc 2016; 84(5): 780–784. doi: 10.1016/j.gie.2016.03.1500.
17. Al-Rashdan A, Schmidt CM, Al-Haddad M et al. Fluid analysis prior to surgical resection of suspected mucinous pancreatic cysts. A single centre experience. J Gastrointest Oncol 2011; 2(4): 208–214. doi: 10.3978/j.issn.2078-6891. 2011.020.
18. Gaddam S, Ge PS, Keach JW et al. Suboptimal accuracy of carcinoembryonic antigen in differentiation of mucinous and nonmucinous pancreatic cysts: results of a large multicenter study. Gastrointest Endosc 2015; 82(6): 1060–1069. doi: 10.1016/j.gie.2015.04.040.
19. de Pretis N, Mukewar S, Aryal-Khanal A et al. Pancreatic cysts: dia­gnostic accuracy and risk of inappropriate resections. Pancreatology 2017; 17(2): 267–272. doi: 10.1016/j.pan.2017.01.002.
20. Khalid A, McGrath KM, Zahid M et al. The role of pancreatic cyst fluid molecular analysis in predicting cyst pathology. Clin Gastroenterol Hepatol 2005; 3(10): 967–973. doi: 10.1016/s1542-3565 (05) 00409-x.
21. Theisen BK, Wald AI, Singhi AD. Molecular dia­gnostics in the evaluation of pancreatic cysts. Surg Pathol Clin 2016; 9(3): 441–456. doi: 10.1016/j.path.2016.04.008.
22. Reid MD, Choi H, Balci S et al. Serous cystic neoplasms of the pancreas: clinicopathologic and molecular characteristics. Semin Dia­gn Pathol 2014; 31(6): 475–483. doi: 10.1053/j.semdp.2014.08.009.
23. Singhi AD, McGrath K, Brand RE et al. Preoperative next-generation sequencing of pancreatic cyst fluid is highly accurate in cyst classification and detection of advanced neoplasia. Gut 2018; 67(12): 2131–2141. doi: 10.1136/gutjnl- 2016-313586.
24. Wu J, Jiao Y, Molin MD et al. Whole-exome sequencing of neoplastic cysts of the pancreas reveals recurrent mutations in components of ubiquitin-dependent pathways. Proc Natl Acad Sci 2011; 108(52): 21188–21193. doi: 10.1073/pnas.1118046108.
25. Biankin AV, Biankin SA, Kench JG et al. Aberrant p16 (INK4A) and DPC4/Smad4 expression in intraductal papillary mucinous tumours of the pancreas is associated with invasive ductal adenocarcinoma. Gut 2002; 50(6): 861–868. doi: 10.1136/gut.50.6.861.
26. Farrell JJ, Toste P, Wu N et al. Endoscopically acquired pancreatic cyst fluid microRNA 21 and 221 are associated with invasive cancer. Am J Gastroenterol 2013; 108(8): 1352–1359. doi: 10.1038/ajg.2013.167.
27. Matthaei H, Wylie D, Lloyd MB et al. miRNA bio­markers in cyst fluid augment the dia­gnosis and management of pancreatic cysts. Clin Cancer Res 2012; 18(17): 4713–4724. doi: 10.1158/1078-0432.CCR-12-0035.
28. Utomo WK, Looijenga LH, Bruno MJ et al. A microRNA panel in pancreatic cyst fluid for the risk stratification of pancreatic cysts in a prospective cohort. Mol Ther Nucleic Acids 2016; 5(8): e350. doi: 10.1038/mtna.2016.61.
29. Faias S, Duarte M, Albuquerque C et al. Clinical impact of KRAS and GNAS analysis added to CEA and cytology in pancreatic cystic fluid obtained by EUS-FNA. Dig Dis Sci 2018; 63(9): 2351–2361. doi: 10.1007/s10620-018- 5128-y.
30. Haeberle L, Schramm M, Goering W et al. Molecular analysis of cyst fluids improves the dia­gnostic accuracy of pre-operative assessment of pancreatic cystic lesions. Sci Rep 2021; 11(1): 2901. doi: 10.1038/s41598-021-81065-2.
31. Zhang ML, Pitman MB. Practical applications of molecular testing in the cytologic diagnosis of pancreatic cysts. J Mol Pathol 2021; 2(1): 11–22. doi: https: //doi.org/10.3390/jmp2010002.