Cystic pancreatic neoplasms in a tertiary gastroenterologic referral center: Evaluation of the diagnostic accuracy of endoscopic ultrasound, progression rate and malignancy rate in a large unicentric cohort

Abstract

Introduction Cystic pancreatic neoplasms (CPN) are frequently diagnosed due to better diagnostic techniques and patients becoming older. However, diagnostic accuracy of endoscopic ultrasound (EUS) and value of follow-up are still unclear.

Material and Methods The aim of our retrospective study was to investigate the frequency of different cystic pancreatic neoplasms (intraductal papillary mucinous neoplasm [IPMN], serous and mucinous cystadenoma, solid pseudopapillary neoplasia), diagnostic accuracy, size progression, and rate of malignancy using EUS in a tertiary reference center in Germany. Between January 1, 2012 and December 31, 2018, 455 patients were diagnosed with cystic pancreatic lesions (798 EUS examinations).

Results Endoscopic ultrasound diagnosed 223 patients with cystic pancreatic neoplasms, including 138 (61.9%) patients with branch duct IPMN, 16 (7.2%) with main duct IPMN, and five (2.2%) with mixed-type IPMN. In the largest subgroup of branch duct IPMN, cysts were size progressive in 20 patients (38.5%). Fine needle aspiration (FNA) was performed in 21 patients, and confirmed the suspected diagnosis in 12/21 patients. 28 surgical resections were performed, in 7/28 patients (25%), high-grade dysplasia or cancer was diagnosed. Endoscopic ultrasound diagnosis of serous and mucinous cystic pancreatic neoplasms was correct in 68.4%.

Conclusions Endoscopic ultrasound differential diagnosis of CPNs is challenging. Even in a tertiary expert center, differentiation of serous and mucinous cystic neoplasia is not guaranteed. Relevant size progression of CPN, however, is rare, as is the rate of malignancy. The data of this study suggest that morphologic criteria to assess pancreatic cysts alone are not sufficient to allow a clear diagnosis. Hence, for the improved assessment of pancreatic cysts, EUS should be combined with additional tests and techniques such as MRT/MRCP, contrast-enhanced EUS, and/or FNA/fine needle biopsy including fluid analysis. The combination and correlation of imaging studies with EUS findings is mandatory.

Zusammenfassung

Einleitung Zystische pankreatische Neoplasien (ZPN) werden angesichts besserer diagnostischer Techniken und älter werdender Patienten häufiger diagnostiziert. Nichtsdestotrotz sind diagnostische Präzision und Bedeutung von Verlaufskontrollen des EUS unklar.

Material und Methodik Das Ziel der retrospektiven Studie war die Erhebung der Häufigkeit distinkter ZPNs (intraduktale papilläre muzinöse Neoplasie [IPMN], seröse und muzinöse Zystadenome, solide pseudopapilläre Neoplasie), der diagnostischen Präzision (Feinnadelpunktion, operative Resektion), der Grössenprogression sowie der Rate an maligner Entartung mittels EUS in einem tertiären Referenzzentrum in Deutschland. Hierfür wurden 455 Patienten mit zystischen pankreatischen Läsionen vom 1. Januar 2012 bis zum 31. Dezember 2018 untersucht (798 EUS Untersuchungen).

Ergebnisse 223 Patienten mit ZPN wurden diagnostiziert, davon 138 (61.9%) Patienten mit Seitengang-IPMN, 16 (7.2%) mit Hauptgang-IPMN und 5 (2.2%) mit mixed-type IPMN. In der größten Sub-Gruppe der Seitengang-IPMN waren die Zysten bei 20 Patienten (38.5%) größenprogredient. Feinnadelpunktionen wurden bei 21 Patienten durchgeführt, und bestätigten die vermutete EUS-Diagnose bei 12/21 Patienten. 28 Operationen wurden durchgeführt, dabei wurden bei 7/28 Patienten (25%) high-grade Dysplasien oder Malignome diagnostiziert. Die mittels EUS vorgenommene Einteilung in seröse und muzinöse ZPNs war in 68.4% der Patienten korrekt.

Schlußfolgerungen Die EUS-basierte Differenzialdiagnose zystischer pankreatischer Neoplasien ist ebenso wie die Differenzierung zwischen serösen und muzinösen Zysten auch in einem Referenzzentrum schwierig. Eine relevante Größenprogression der ZPN im Zeitverlauf ist insgesamt jedoch selten zu verzeichnen, die Rate an malignen Entartungen ist niedrig. Die Daten dieser Studie suggerieren, daß morphologische Kritierien allein nicht ausreichen, um eine klare Diagnose zystischer pankreatischer Neoplasien zu stellen. Deshalb sollte der EUS für eine genauere Einteilung von ZPNs mit zusätzlichen Verfahren wie zum Beispiel der MRT/MRCP, dem Kontrastmittel-Ultraschall und/oder der Feinnadelpunktion/ -biopsie inklusive einer Flüssigkeitsanalyse kombiniert werden. Eine Kombination und Korrelation bildgebender Studien mit EUS-Ergebnissen ist unbedingt zu fordern.

Schlüsselwörter

Pankreatische Zysten - Neoplasie - zystisch - muzinös - serös - Bildgebung - Endosonografie - EUS

Keywords

Pancreatic cysts - Neoplasms - Cystic - Mucinous - Serous - Diagnostic Imaging - Endosonography - EUS

• Literature

• 1 Zerboni G, Signoretti M, Crippa S. et al. Systematic review and meta-analysis: Prevalence of incidentally detected pancreatic cystic lesions in asymptomatic individuals. Pancreatology 2019; 19: 2-9
• 2 de Jong K, Nio CY, Hermans JJ. et al. High prevalence of pancreatic cysts detected by screening magnetic resonance imaging examinations. Clin Gastroenterol Hepatol 2010; 08: 806-811
• 3 Kromrey ML, Bülow R, Hübner J. et al. Prospective study on the incidence, prevalence and 5-year pancreatic-related mortality of pancreatic cysts in a population-based study. Gut 2018; 67: 138-145
• 4 Moris M, Bridges MD, Pooley RA. et al. Association between advances in high-resolution cross-section imaging technologies and increase in prevalence of pancreatic cysts from 2005 to 2014. Clin Gastroenterol Hepatol 2016; 14: 585-593
• 5 Abdelkader A, Hunt B, Hartley CP. et al. Cystic Lesions of the Pancreas: Differential Diagnosis and Cytologic-histologic correlation. Arch Pathol Lab Med 2020; 144: 47-61
• 6 Basturk O, Coban I, Adsay NV. Pancreatic cysts: pathologic classification, differential diagnosis, and clinical implications. Arch Pathol Lab Med 2009; 133: 423-438
• 7 Furukawa T, Hatori T, Fujita I. et al. Prognostic relevance of morphological types of intraductal papillary mucinous neoplasms of the pancreas. Gut 2011; 60: 509-516
• 8 Ooka K, Rustagi T, Evans A. et al. Surveillance and Outcomes of nonresected presumed branch-duct intraductal papillary mucinous neoplasms: A meta-analysis. Pancreas 2017; 46: 927-935
• 9 Stark A, Donahue TR, Reber HA. et al. Pancreatic cyst disease a review. J Am Med Assoc 2016; 315: 1882-1893
• 10 Park JW, Jang JY, Kang MJ. et al. Mucinous cystic neoplasm of the pancreas: Is surgical resection recommended for all surgically fit patients?. Pancreatology 2014; 14: 131-136
• 11 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: 305-312
• 12 Law JK, Ahmed A, Singh VK. et al. A systematic review of solid-pseudopapillary neoplasms: Are these rare lesions?. Pancreas 2014; 43: 331-337
• 13 Sakorafas GH, Smyrniotis V, Reid-Lombardo KM. et al. Primary pancreatic cystic neoplasms of the pancreas revisited. Part IV: Rare cystic neoplasms. Surg Oncol 2012; 21: 153-163
• 14 Scholten L, Van Huijgevoort NCM, Van Hooft JE. et al. Pancreatic cystic neoplasms: Different types, different management, new guidelines. Visc Med 2018; 34: 173-177
• 15 Elta GH, Enestvedt BK, Sauer BG. et al. ACG Clinical Guideline: Diagnosis and Management of Pancreatic Cysts. Am J Gastroenterol 2018; 113: 464-479
• 16 Pezzilli R, Buscarini E, Pollini T. et al. Epidemiology, clinical features and diagnostic work-up of cystic neoplasms of the pancreas: interim analysis of the prospective PANCY survey. Digestive and liver disease 2020; 52: 547-554
• 17 Sahora K, Castillo CFD, Dong F. et al. Not all mixed-type intraductal papillary mucinous neoplasms behave like main-duct lesions: Implications of minimal involvement of the main pancreatic duct. Surg [United States] 2014; 156: 611-621
• 18 Del Chiaro M, Besselink MG, Scholten L. et al. European evidence-based guidelines on pancreatic cystic neoplasms. Gut 2018; 67: 789-804
• 19 Crippa S, Salvia R, Warshaw AL. et al. Mucinous Cystic Neoplasm of the Pancreas is Not an Aggressive Entity. Ann Surg 2008; 247: 571-579
• 20 Winner M, Sethi A, Poneros JM. et al. The role of molecular analysis in the diagnosis and surveillance of pancreatic cystic neoplasms. J Pancreas 2015; 16: 143-149
• 21 Kwong WT, Lawson RD, Hunt G. et al. Rapid Growth Rates of Suspected Pancreatic Cyst Branch Duct Intraductal Papillary Mucinous Neoplasms Predict Malignancy. Dig Dis Sci 2015; 60: 2800-2806
• 22 Kayal M, Luk L, Hecht EM. et al. Long-term surveillance and timeline of progression of presumed low-risk intraductal papillary mucinous neoplasms. Am J Roentgenol 2017; 209: 320-326
• 23 El Chafic A, El II Hajj, DeWitt J. et al. Does cyst growth predict malignancy in branch duct intraductal papillary mucinous neoplasms? Results of a large multicenter experience. Dig Liver Dis 2018; 50: 961-968
• 24 Akahoshi K, Ono H, Akasu M. et al. Rapid growth speed of cysts can predict malignant intraductal mucinous papillary neoplasms. J Surg Res 2018; 231: 195-200
• 25 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: 1095-1102
• 26 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: 1330-1336
• 27 Bilge AR, Brugge WR, Karaca C. et al. Cyst fluid carcinoembryonic antigen is an accurate diagnostic marker of pancreatic mucinous cysts. Pancreas 2011; 40: 1024-1028
• 28 Jin DX, Small AJ, Vollmer CM. et al. A lower cyst fluid CEA cut-off increases diagnostic accuracy in identifying mucinous pancreatic cystic lesions. J Pancreas 2015; 16: 271-277
• 29 Hackert T, Fritz S, Klauss M. et al. Main-duct Intraductal Papillary Mucinous Neoplasm. Ann Surg 2015; 262: 875-881
• 30 Liu M, Liu J, Hu Q. et al. Management of solid pseudopapillary neoplasms of pancreas: A single center experience of 243 consecutive patients. Pancreatology 2019; 19: 681-685
• 31 Yu PF, Hu ZH, Wang XB. et al. Solid pseudopapillary tumor of the pancreas: a review of 553 cases in Chinese literature. World J Gastroenterol 2010; 16: 1209-1214
• 32 Tjaden C, Hassenpflug M, Hinz U. et al. Outcome and prognosis after pancreatectomy in patients with solid pseudopapillary neoplasms. Pancreatology 2019; 19: 699-709
• 33 Le Borgne J, de Calan L, Partensky C. Cystadenomas and cystadenocarcinomas of the pancreas. Ann Surg 1999; 230: 152-161