Year 2017 / Volume 109 / Number 11
Review
Cystic pancreatic neuroendocrine tumors (cPNETs): a systematic review and meta-analysis of case series

778-787

DOI: 10.17235/reed.2017.5044/2017

Luis Hurtado-Pardo, Javier A. Cienfuegos, Miguel Ruiz-Canela, Pablo Panadero, Alberto Benito, José Luis Hernández Lizoain,

Abstract
Cystic pancreatic neuroendocrine tumors represent 13% of all neuroendocrine tumors. The aim of this study is to analyze the phenotype and biologic behavior of resected cystic neuroendocrine tumors. A systematic review and meta-analysis were conducted until September 2016 using a search in Medline, Scopus, and EMBASE with the terms “cystic pancreatic endocrine neoplasm”, “cystic islets tumors” and “cystic islets neoplasms”. From the 795 citations recovered 80 studies reporting on 431 patients were selected. 87.1% (n = 387) were sporadic tumors and 10.3% (n = 40) corresponded to multiple endocrine neoplasia endocrine type 1. Were diagnosed incidentally 44.6% (n = 135). Cytology was found to have a sensitivity of 78.5%. Were non-functional tumors 85% (n = 338), and among the functional tumors, insulinoma was the most frequent. According to the European Neuroendocrine Tumor Society staging, 87.8% were limited to the pancreas (I-IIb), and 12.2% were advanced (III-IV). Disease-free survival at 5 years in stages (I-IIIa) and (IIIb-IV) was 91.5% and 54.2%, respectively; and was significantly lower (p = 0.0001) in functional tumors. In patients with multiple endocrine neoplasia there was a higher incidence of functional (62.5%) and multifocal (28.1%) tumors. Disease-free survival at 5 and 10 years was 60%. Cystic pancreatic neuroendocrine tumors exhibit phenotypical characteristics which are different to those of solid neuroendocrine tumors.
Share Button
New comment
Comments

24/01/2018 23:37:35
THANK YOU


References
1. Singhi AD, Chu LC, Tatsas AD, et al. Cystic Pancreatic Neuroendocrine Tumors. Am J Surg Pathol. 2012;36(11):1666–73.
2. Gaujoux S, Tang L, Klimstra D, et al. The outcome of resected cystic pancreatic endocrine neoplasms: A case-matched analysis. Surgery. 2012;151(4):518–25.
3. Ellison TA, Wolfgang CL, Shi C, et al. A single institution’s 26-year experience with nonfunctional pancreatic neuroendocrine tumors: a validation of current staging systems and a new prognostic nomogram. Ann Surg. 2014;259(2):204–12.
4. Birnbaum DJ, Gaujoux S, Cherif R, et al. Sporadic nonfunctioning pancreatic neuroendocrine tumors: prognostic significance of incidental diagnosis. Surgery. 2014;155(1):13–21.
5. Crippa S, Partelli S, Bassi C, et al. Long-term outcomes and prognostic factors in neuroendocrine carcinomas of the pancreas: Morphology matters. Surgery. 2016;159(3):862–71.
6. Moher D, Liberati A, Tetzlaff J, et al. Preferred reporting items for systematic reviews and meta-analyses: The PRISMA statement. Int J Surg. 2010;8(5):336–41.
7. Gagnier JJ, Kienle G, Altman DG, et al. The CARE guidelines: consensus-based clinical case report guideline development. J Diet Suppl. 2013;10(4):381–90.
8. Klöppel G, Rindi G, Perren A, et al. The ENETS and AJCC/UICC TNM classifications of the neuroendocrine tumors of the gastrointestinal tract and the pancreas: a statement. Virchows Arch. 2010;456(6):595–7.
9. Ricci C, Casadei R, Taffurelli G, et al. Validation of the 2010 WHO classification and a new prognostic proposal: A single centre retrospective study of well-differentiated pancreatic neuroendocrine tumours. Pancreatol Off J. 2016;16(3):403-10.
10. Pergolini I, Iliopoulos O, Ferrone CR, et al. Clinico-pathological features and survival of resected pancreatic neuroendocrine tumors associated with von Hippel Lindau disease and multiple endocrine neoplasia type 1. Gastroenterology. 2016;150(4):S1232–3.
11. Amagai H, Jingu K, Kitabayashi H, et al. A case of nonfunctioning neuroendocrine tumor of the pancreas which had difficulty in differentiation with mucinous cystic tumor. Chiba Med J. 2016;92(2):45–50.
12. Kawai G, Shirota G, Unno T WT. A case of the NET of the pancreas that was difficult to distinguish from SPT. Japanese J Clin Radiol. 2016;61(6):777–81.
13. Tsujino T, Samarasena J CK. Endoscopic ultrasound-guided, needle-based confocal laser endomicroscopy in the diagnosis of cystic pancreatic neuroendocrine tumor: Emerging imaging criteria from surgical pathologic correlation in two cases. Am J Gastroenterol. 2015;110(1):S107–8.
14. Lico V, Milanetto AC, Moletta L, et al. Pancreatic neuroendocrine tumor and ileal carcinoid i nacromegaly. Pluriglandular association in non-MEN1 patient: a case report. Neuroendocrinology. 2015;102(1–2):151.
15. Humphrey PE, Alessandrino F, Bellizzi AM, et al. Non-hyperfunctioning pancreatic endocrine tumors: multimodality imaging features with histopathological correlation. Abdom Imaging. 2015;40(7):2398–410.
16. Apodaca-Torrez FR, Oliveira ML, Triviño T, et al. Tumor neuroendocrino quístico no funcionante del páncreas. Una presentación poco usual. Cir Esp. 2015;93(1):43–54.
17. Welch A, McGarrity T, Mani H MM. Cystic neuroendocrine tumor of the pancreas: a rare type of pancreatic cystic lesion accurately diagnosed and staged by EUS-FNA. Pract Gastroenterol. 2013;37(10):31–4.
18. Bombardieri R, Moavero R, Roberto D, et al. Pancreatic neuroendocrine tumor in a child with a tuberous sclerosis complex 2 (TSC2) mutation. Endocr Pract. 2013;19(5):e124-8.
19. Addeo A, Bini R, Viora T, et al. Von Hippel-Lindau and myotonic dystrophy of Steinert along with pancreatic neuroendocrine tumor and renal clear cell carcinomal neoplasm: Case report and review of the literature. Int J Surg Case Rep. 2013;4(8):648–50.
20. Deshmukh SD, Gulati HK, Gaopande V, et al. Incidental cystic endocrine tumor of the pancreas: a case report with immunohistochemical study. J Cancer Res Ther. 2012;8(2):289–91.
21. Hu K-C, Chang W-H, Chu C-H, et al. Pancreatic head well-differentiated endocrine tumor. Am J Surg. 2011;201(3):e26–8.
22. Potru R, Collins C S V. Rare presentation of cystic nonfunctioning pancreatic neuroendocrine tumor: a case-series. Am J Gastroenterol. 2011;106(2):S219–20.
23. Baig M, Chin U, Wilhite D CH. Cystic pancreatic neuroendocrine tumors. Am J Gastroenterol. 2011;106(2):S213.
24. Higashi T, Kawaguchi Y, Tsukune Y, et al. A case report of glucagon-producing multiple pancreatic neuroendocrine tumors that involved pancreatic cystic lesions. Pancreatology. 2010;10(1):70.
25. Diehl DL, Blansfield J, Li J. Cystic pancreatic neuroendocrine tumor. Gastrointest Endosc. 2010;71(6):1064–5; discussion 1065.
26. Colović RB, Matić S V, Micev MT, et al. Two synchronous somatostatinomas of the duodenum and pancreatic head in one patient. World J Gastroenterol. 2009;15(46):5859–63.
27. Kobayashi Y, Yamao K, Sawaki A, et al. A case of pancreatic neuroendocrine tumor (NET) with atypical looking which diagnosed by EUS-FNA. Pancreas. 2009;38(8):1018.
28. Basu A, Sistla SC IK. Image of the month. Arch Surg. 2009;144(1):89.
29. Kamei K, Yasuda T, Shinzaki W, et al. Cystic nonfunctioning pancreatic endocrine neoplasm presenting communication with main pancreatic duct. Dig Surg. 2009;26(1):25–6.
30. Charfi S, Marcy M, Bories E, et al. Cystic pancreatic endocrine tumors: an endoscopic ultrasound-guided fine-needle aspiration biopsy study with histologic correlation. Cancer. 2009;117(3):203–10.
31. Chetty R, El-Shinnawy I. Intraductal pancreatic neuroendocrine tumor. Endocr Pathol. 2009;20(4):262–6.
32. Kongkam P, Al-Haddad M, Attasaranya S, et al. EUS and clinical characteristics of cystic pancreatic neuroendocrine tumors. Endoscopy. 2008;40(7):602–5.
33. Ballarin R, Masetti M, Losi L, et al. Cystic pancreatic neuroendocrine neoplasms with uncertain malignant potential: report of two cases. Surg Today. 2009;39(2):162–7.
34. Sumarac-Dumanovic M, Micic D, Krstic M, et al. Pitfalls in diagnosing a small cystic insulinoma: a case report. J Med Case Rep. 2007;1(1):181.
35. Kajiwara M, Gotohda N, Konishi M, et al. Cystic endocrine tumor of the pancreas with an atypical multilocular appearance. J Hepatobiliary Pancreat Surg. 2007;14(6):586–9.
36. Li Destri G, Reggio E, Veroux M, et al. A rare cystic non-functioning neuroendocrine pancreatic tumor with an unusual presentation. Tumori. 92(3):260–3.
37. Goh BKP, Ooi LLPJ, Tan YM, et al. Clinico-pathological features of cystic pancreatic endocrine neoplasms and a comparison with their solid counterparts. Eur J Surg Oncol. 2006;32(5):553–6.
38. Tamagno G, Maffei P, Pasquali C, et al. Clinical and diagnostic aspects of cystic insulinoma. Scand J Gastroenterol. 2005;40(12):1497–501.
39. Imaoka H, Yamao K, Salem AAS, et al. Pancreatic endocrine neoplasm can mimic serous cystadenoma. Int J Gastrointest Cancer. 2005;35(3):217–20.
40. Gerke H, Byrne MF, Xie HB, et al. A wolf in sheep’s clothing: a non-functioning islet cell tumor of the pancreas masquerading as a microcystic (serous cystic) adenoma. JOP. 2004;5(4):225–30.
41. Christein JD MK. Pancreatic somatostitoma associated with obstructive jaundice, pancreatic and biliary Kaposi´s sarcoma in a man with neurofibromatosis. HPB. 2003;5(1):49–53.
42. Vandecaveye V, Verswijvel G, Colla P, et al. Cystic insulinoma of the pancreas in a patient with myotonic dystrophy: correlation of imaging and pathologic findings. JBR-BTR. 86(5):268–71.
43. Ahrendt SA, Komorowski RA, Demeure MJ, et al. Cystic pancreatic neuroendocrine tumors: is preoperative diagnosis possible? J Gastrointest Surg. 6(1):66–74.
44. Oberg KC, Wells K, Seraj IM, et al. ACTH-secreting islet cell tumor of the pancreas presenting as bilateral ovarian tumors and Cushing’s syndrome. Int J Gynecol Pathol. 2002;21(3):276–80.
45. Kato K, Kondo S, Ambo Y, et al. Nonfunctioning endocrine tumor of the pancreas with extrapancreatic growth and cyst formation: report of a case. Surg Today. 2000;30(7):651–4.
46. Brown K, Kristopaitis T, Yong S, et al. Cystic glucagonoma: A rare variant of an uncommon neuroendocrine pancreas tumor. J Gastrointest Surg. 2(6):533–6.
47. Kotoulas C, Panayiotides J, Antiochos C, et al. Huge non-functioning pancreatic cystic neuroendocrine tumour: a case report. Eur J Surg Oncol. 1998;24(1):74–6.
48. Sohaib SA, Reznek RH, Healy JC, et al. Cystic islet cell tumors of the pancreas. AJR Am J Roentgenol. 1998;170(1):217.
49. Sarui H, Yoshimoto K, Okumura S, et al. Cystic glucagonoma with loss of heterozygosity on chromosome 11 in multiple endocrine neoplasia type 1. Clin Endocrinol (Oxf). 1997;46(4):511–6.
50. Zanow J, Gellert K, Benhidjeb T MJ. Cystische tumoren des pankreas. Chirurg. 1996;67:719–24.
51. Goto M, Nakano I, Sumi K, et al. Cystic insulinoma and nonfunctioning islet cell tumor in multiple endocrine neoplasia type 1. Pancreas. 1994;9(3):393–5.
52. Weissmann D, Lewandrowski K, Godine J, et al. Pancreatic cystic islet-cell tumors. Clinical and pathologic features in two cases with cyst fluid analysis. Int J Pancreatol. 1994;15(1):75–9.
53. Iacono C, Serio G, Fugazzola C, et al. Cystic islet cell tumors of the pancreas. A clinico-pathological report of two nonfunctioning cases and review of the literature. Int J Pancreatol. 1992;11(3):199–208.
54. Yagihashi S, Yagihashi N, Nagai K. Cystic Pancreatic Glucagonoma in Contact with Insulinoma Found in a Hypoglycemic Patient. Pathol - Res Pract. 1992;188(6):751–6.
55. Nojima T, Kojima T, Kato H, et al. Cystic endocrine tumor of the pancreas. Int J Pancreatol. 1991;10(1):65–72.
56. Azoulay D, Sauvanet A, Bonnichon P, et al. [Non-functioning tumors of the endocrine pancreas. Concept, diagnosis, treatment]. J Chir (Paris). 1990;127(4):185–90.
57. Warshaw AL, Compton CC, Lewandrowski K, et al. Cystic tumors of the pancreas. New clinical, radiologic, and pathologic observations in 67 patients. Ann Surg. 1990;212(4):432-43-5.
58. von Herbay A, Sieg B, Otto HF. Solid-cystic tumour of the pancreas. An endocrine neoplasm? Virchows Arch A Pathol Anat Histopathol. 1990;416(6):535–8.
59. Davtyan H, Nieberg R, Reber HA. Pancreatic cystic endocrine neoplasms. Pancreas. 1990;5(2):230–3.
60. Lapeyrie H, Loizon P, Chapuis H, et al. [Non-functional or silent endocrine tumors of the pancreas. Apropos of a case of cystic form]. Ann Chir. 1989;43(4):302–5.
61. Yagihashi S, Sato I, Kaimori M, et al. Papillary and cystic tumor of the pancreas. Two cases indistinguishable from islet cell tumor. Cancer. 1988;61(6):1241–7.
62. Kamisawa T, Fukayama M, Koike M, et al. A case of malignant cystic endocrine tumor of the pancreas. Am J Gastroenterol. 1987;82(1):86–9.
63. Stair JM, Schaefer RF, McCowan TC, et al. Cystic islet cell tumor of the pancreas. J Surg Oncol. 1986;32(1):46–9.
64. Loiterman DA, Schwartz IS, Aufses AH. Cystic islet cell tumor: diagnosis and surgical management. Mt Sinai J Med. 1985;52(3):212–5.
65. Heidrich W, Kubale R, Seitz G, et al. [Endocrine tumor of the pancreas--a case report on the differential diagnosis of cystic epigastric tumors]. Ultraschall Med. 1986;7(3):138–40.
66. Pogany AC, Kerlan RK, Karam JH, et al. Cystic insulinoma. AJR Am J Roentgenol. 1984;142(5):951–2.
67. Ho PW, Moore GW, Hoge AF. Glucagonoma occurring as a large cystic abdominal mass. South Med J. 1984;77(5):666.
68. Thompson NW, Eckhauser FE, Vinik AI, et al. Cystic neuroendocrine neoplasms of the pancreas and liver. Ann Surg. 1984;199(2):158–64.
69. Grosdidier J, Duprez J, Delfosse J, et al. [Nonfunctional benign Langerhans tumor of the cystic type]. Sem Hop. 1983;59(23):1773–6.
70. Frija J, Schmit P, Vadrot D, et al. Non-secreting islet cell adenoma of the pancreas evaluated by computed tomography and sonography. Report of a case. Eur J Radiol. 1982;2(2):160–1.
71. Caplan RH, Koob L, Abellera RM, et al. Cure of acromegaly by operative removal of an islet cell tumor of the pancreas. Am J Med. 1978;64(5):874–82.
72. Riddle MC, Golper TA, Fletcher WS, et al. Glucagonoma syndrome in a 19-year-old woman. West J Med. 1978;129(1):68–72.
73. Deltz VE PM. Zystisches Insulom. Zbl Chir. 10975;100:1521–4.
74. Winston JH. Malignant islet cell adenoma in a pancreatic cyst. Report of a case. J Natl Med Assoc. 1965;57(3):203–4.
75. Leger L, Canivet J, Mizon JP, et al. [Cyst-like tumors of the islands of Langerhans. Apropos of 2 cases]. J Chir (Paris). 94(1):7–20.
76. Joshi RA, Probstein JG. Benign cystic islet-cell tumor of the head of the pancreas; report of a case probably of delta-cell origin. AMA Arch Surg. 1955;71(1):74–7.
77. Cloyd JM, Kopecky KE, Norton JA, et al. Neuroendocrine tumors of the pancreas: Degree of cystic component predicts prognosis. Surgery. 2016;160(3):708–13.
78. Mitra V, Nayar MK, Leeds JS, et al. Diagnostic performance of endoscopic ultrasound (EUS)/endoscopic ultrasound--fine needle aspiration (EUS-FNA) cytology in solid and cystic pancreatic neuroendocrine tumours. J Gastrointestin Liver Dis. 2015;24(1):69–75.
79. Chen L, Nassar A, Kommineni VT, et al. Endoscopic ultrasonography-guided fine-needle aspiration cytology of surgically confirmed cystic pancreatic neuroendocrine tumors: a Mayo Clinic experience. J Am Soc Cytopathol. 2015;4(6):335–43.
80. Komminemi VT, Chen L, Zhang J, et al. Cystic pancreatic neuroendocrine tumors: Clinical and endoscopic ultrasound characteristics and accuracy of EUS-FNA. Am J Gastroenterol. 2014;109(2):S92.
81. Morales-Oyarvide V, Yoon WJ, Ingkakul T, et al. Cystic pancreatic neuroendocrine tumors: The value of cytology in preoperative diagnosis. Cancer Cytopathol. 2014;122(6):435–44.
82. Ho HC, Eloubeidi MA, Siddiqui UD, et al. Endosonographic and cyst fluid characteristics of cystic pancreatic neuroendocrine tumours: a multicentre case series. Dig Liver Dis. 2013;45(9):750–3.
83. Konukiewitz B, Enosawa T, Klöppel G. Glucagon expression in cystic pancreatic neuroendocrine neoplasms: an immunohistochemical analysis. Virchows Arch. 2011;458(1):47–53.
84. Boninsegna L, Partelli S, D’Innocenzio MM, et al. Pancreatic Cystic Endocrine Tumors: A Different Morphological Entity Associated with a Less Aggressive Behavior. Neuroendocrinology. 2010;92(4):246–51.
85. Baker MS, Knuth JL, DeWitt J, et al. Pancreatic cystic neuroendocrine tumors: preoperative diagnosis with endoscopic ultrasound and fine-needle immunocytology. J Gastrointest Surg. 2008;12(3):450–6.
86. Ligneau B, Lombard-Bohas C, Partensky C, et al. Cystic endocrine tumors of the pancreas: clinical, radiologic, and histopathologic features in 13 cases. Am J Surg Pathol. 2001;25(6):752–60.
87. Buetow PC, Parrino T V, Buck JL, et al. Islet cell tumors of the pancreas: pathologic-imaging correlation among size, necrosis and cysts, calcification, malignant behavior, and functional status. AJR Am J Roentgenol. 1995;165(5):1175–9.
88. Bordeianou L, Vagefi PA, Sahani D, et al. Cystic Pancreatic Endocrine Neoplasms: A Distinct Tumor Type? J Am Coll Surg. 2008;206(6):1154–8.
89. Yang M, Ke NW, Zeng L, et al. Survival Analyses for Patients With Surgically Resected Pancreatic Neuroendocrine Tumors by World Health Organization 2010 Grading Classifications and American Joint Committee on Cancer 2010 Staging Systems. Medicine (Baltimore). 2015;94(48):e2156.
90. Muthusamy VR, Chandrasekhara V, Acosta RD, et al. The role of endoscopy in the diagnosis and treatment of cystic pancreatic neoplasms. Gastrointest Endosc. 2016;84(1):1–9.
91. Iacono C, Verlato G, Ruzzenente A, et al. Systematic review of central pancreatectomy and meta-analysis of central versus distal pancreatectomy. Br J Surg. 2013;100(7):873–85.
92. Koh YX, Chok AY, Zheng HL, et al. A systematic review and meta-analysis of the clinicopathologic characteristics of cystic versus solid pancreatic neuroendocrine neoplasms. Surgery. 2014;156(1):83–96.e2.
93. Cienfuegos JA, Rotellar F, Salguero J, et al. A single institutions 21-year experience with surgically resected pancreatic neuroendocrine tumors: an analysis of survival and prognostic factors. Rev Española Enfermedades Dig. 2016;108(11):689–96.
94. Thakker R V, Newey PJ, Walls G V, et al. Clinical practice guidelines for multiple endocrine neoplasia type 1 (MEN1). J Clin Endocrinol Metab. 2012;97(9):2990–3011.
95. Kouvaraki MA, Shapiro SE, Cote GJ, et al. Management of pancreatic endocrine tumors in multiple endocrine neoplasia type 1. World J Surg. 2006;30(5):643–53.
96. Vandenbroucke JP. In defense of case reports. Ann Intern Med. 2001;134(2 Pt 2):330–4.
97. Agha RA, Fowler AJ, Lee S-Y, et al. Systematic review of the methodological and reporting quality of case series in surgery. Br J Surg. 2016;103(10):1253–8.
98.- Barkin J A, Barkin J S. Pancreatic cysts. Controversies, advances, diagnoses, and therapies. Pancreas. 2017,46(6).735-741
99.- Moris M, Wallace MB. Intraductal papillary mucinous neoplasms and mucinous cystadenomas: current status and recommendations. Rev. Esp. Enferm. Digest. 2017 (5): 358-367
Citation tools
Hurtado-Pardo L, A. Cienfuegos J, Ruiz-Canela M, Panadero P, Benito A, Hernández Lizoain J, et all. Cystic pancreatic neuroendocrine tumors (cPNETs): a systematic review and meta-analysis of case series. 5044/2017


Download to a citation manager

Download the citation for this article by clicking on one of the following citation managers:

Metrics
This article has received 1504 visits.
This article has been downloaded 971 times.

Statistics from Dimensions


Statistics from Plum Analytics

Publication history

Received: 03/05/2017

Accepted: 07/08/2017

Online First: 26/10/2017

Published: 02/11/2017

Article revision time: 91 days

Article Online First time: 176 days

Article editing time: 183 days


Share
This article has been rated by 6 readers.
Reader rating:
Valora este artículo:




Asociación Española de Ecografía Digestiva Sociedad Española de Endoscopia Digestiva Sociedad Española de Patología Digestiva
The Spanish Journal of Gastroenterology is the official organ of the Sociedad Española de Patología Digestiva, the Sociedad Española de Endoscopia Digestiva and the Asociación Española de Ecografía Digestiva
Cookie policy Privacy Policy Legal Notice © Copyright 2023 y Creative Commons. The Spanish Journal of Gastroenterology