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

Česká verzia

Authors: Horný I. ¹; Tomáš Hucl ²
Authors place of work: Interní oddělení, Nemocnice Strakonice, a. s. ¹; Klinika hepatogastroenterologie IKEM, Praha ²
Published in the journal: Gastroent Hepatol 2021; 75(5): 417-423
Category: Original Article
doi: https://doi.org/10.48095/ccgh2021417

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:

molecular biology – neoplasia – pancreatic cysts

Zdroje

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 Â 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.