Korean J Gastroenterol.  2022 Feb;79(2):72-76. 10.4166/kjg.2022.020.

Neuroendocrine Tumor with Metachronous Gastrointestinal Stromal Tumor in a Patient: A Case Report

• Heo JH
• Choi EJ
• Yu SJ
• Park YH
• Choi JS

• KMID: 2526786
• DOI: http://doi.org/10.4166/kjg.2022.020

Abstract

Neuroendocrine tumors (NETs) that arise from neuroendocrine cells can develop in most organs; however, it is rarely found in the duodenal papilla. Conversely, gastrointestinal stromal tumors (GISTs), which are mostly asymptomatic and detected incidentally, are usually found in the stomach and very rarely occur metachronously with NETs. A 42-year-old female with no specific underlying disease underwent gastroscopy due to epigastric pain. Biopsy of enlarged major and minor duodenal papilla confirmed the diagnosis of a NET. Endoscopic papillectomy of the major and minor papillae was performed. Multiple duodenal and jejunal submucosal nodules were seen on biliary CT performed at the 30 months follow-up. Pylorus-preserving pancreaticoduodenectomy was performed due to the suspicion of multiple recurrent NETs and muscularis propria involvement on endoscopic ultrasound. Surgical specimen biopsy confirmed the diagnosis of multiple duodenal and jejunal GIST lesions and a metastatic NET in the duodenal lymph node. We report a rare case of a GIST detected in the duodenum during follow-up after the diagnosis and papillectomy of duodenal papilla NET.

Keyword

Neuroendocrine tumors; Gastrointestinal stromal tumors

Figure

• 

  Fig. 1 Endoscopic retrograde choangiopancreatography (ERCP) at the time of initial diagnosis. ERCP reveals (A) major papilla and (B) minor papilla.

• 

  Fig. 2 Biliary computed tomography, endoscopy and endoscopic ultrasound (EUS) findings at follow-up evaluation. (A, B) Submucosal nodules were found in duodenum and jejunum (arrows). (C) Endoscopic image showed polypoid lesions in duodenum. (D) EUS reveals hypoechoic homogenous lesions on the 4th layer (arrow).

• 

  Fig. 3 Histologic features of the (A) neuroendocrine tumor (B) and gastrointestinal stromal tumor. (A) Histopathological evaluation reveals trabecular pattern (hematoxylin and eosin stain [H&E], ×100). Immunohistochemical staining for synaptophysin index is positive (inset). (B) Histopathological evaluation reveals spindle cells proliferation (H&E, ×100). Immunohistochemical staining for C-kit index is positive (inset).

Reference

1. Taal BG, Visser O. 2004; Epidemiology of neuroendocrine tumours. Neuroendocrinology. 80(Suppl 1):3–7. DOI: 10.1159/000080731. PMID: 15477707.

2. Miettinen M, Lasota J. 2001; Gastrointestinal stromal tumors--definition, clinical, histological, immunohistochemical, and molecular genetic features and differential diagnosis. Virchows Arch. 438:1–12. DOI: 10.1007/s004280000338. PMID: 11213830.

3. Miettinen M, Sarlomo-Rikala M, Lasota J. 1999; Gastrointestinal stromal tumors: recent advances in understanding of their biology. Hum Pathol. 30:1213–1220. DOI: 10.1016/S0046-8177(99)90040-0. PMID: 10534170.

4. Raphael MJ, Chan DL, Law C, Singh S. 2017; Principles of diagnosis and management of neuroendocrine tumours. CMAJ. 189:E398–E404. DOI: 10.1503/cmaj.160771. PMID: 28385820. PMCID: PMC5359105.

5. El-Menyar A, Mekkodathil A, Al-Thani H. 2017; Diagnosis and management of gastrointestinal stromal tumors: an up-to-date literature review. J Cancer Res Ther. 13:889–900. DOI: 10.4103/0973-1482.177499. PMID: 29237949.

6. Seo YK, Choi JS. 2018; Endoscopic papillectomy for synchronous major and minor duodenal papilla neuroendocrine tumors. Korean J Gastroenterol. 72:217–221. DOI: 10.4166/kjg.2018.72.4.217. PMID: 30419648.

7. Aluri V, Dillon JS. 2017; Biochemical testing in neuroendocrine tumors. Endocrinol Metab Clin North Am. 46:669–677. DOI: 10.1016/j.ecl.2017.04.004. PMID: 28760232. PMCID: PMC5777173.

8. Wiedenmann B, Franke WW, Kuhn C, Moll R, Gould VE. 1986; Synaptophysin: a marker protein for neuroendocrine cells and neoplasms. Proc Natl Acad Sci U S A. 83:3500–3504. DOI: 10.1073/pnas.83.10.3500. PMID: 3010302. PMCID: PMC323544.

9. Nagtegaal ID, Odze RD, Klimstra D, et al. 2020; The 2019 WHO classification of tumours of the digestive system. Histopathology. 76:182–188. DOI: 10.1111/his.13975. PMID: 31433515. PMCID: PMC7003895.

10. Stueven AK, Kayser A, Wetz C, et al. 2019; Somatostatin analogues in the treatment of neuroendocrine tumors: past, present and future. Int J Mol Sci. 20:3049. DOI: 10.3390/ijms20123049. PMID: 31234481. PMCID: PMC6627451.

11. Yao JC, Shah MH, Ito T, et al. 2011; Everolimus for advanced pancreatic neuroendocrine tumors. N Engl J Med. 364:514–523. DOI: 10.1056/NEJMoa1009290. PMID: 21306238. PMCID: PMC4208619.

12. Raymond E, Dahan L, Raoul JL, et al. 2011; Sunitinib malate for the treatment of pancreatic neuroendocrine tumors. N Engl J Med. 364:501–513. DOI: 10.1056/NEJMoa1003825. PMID: 21306237.

13. Hirota S, Isozaki K, Moriyama Y, et al. 1998; Gain-of-function mutations of c-kit in human gastrointestinal stromal tumors. Science. 279:577–580. DOI: 10.1126/science.279.5350.577. PMID: 9438854.

14. Heinrich MC, Corless CL, Duensing A, et al. 2003; PDGFRA activating mutations in gastrointestinal stromal tumors. Science. 299:708–710. DOI: 10.1126/science.1079666. PMID: 12522257.

15. Postow MA, Robson ME. 2012; Inherited gastrointestinal stromal tumor syndromes: mutations, clinical features, and therapeutic implications. Clin Sarcoma Res. 2:16. DOI: 10.1186/2045-3329-2-16. PMID: 23036227. PMCID: PMC3496697.

16. Huda T, Singh MP. 2019; Gastrointestinal stromal tumors of small intestine. Surg J (N Y). 5:e92–e95. DOI: 10.1055/s-0039-1694704. PMID: 31475241. PMCID: PMC6713571.

17. Gasparotto D, Rossi S, Bearzi I, et al. 2008; Multiple primary sporadic gastrointestinal stromal tumors in the adult: an underestimated entity. Clin Cancer Res. 14:5715–5721. DOI: 10.1158/1078-0432.CCR-08-0622. PMID: 18779314.

18. Demetri GD, van Oosterom AT, Garrett CR, et al. 2006; Efficacy and safety of sunitinib in patients with advanced gastrointestinal stromal tumour after failure of imatinib: a randomised controlled trial. Lancet. 368:1329–1338. DOI: 10.1016/S0140-6736(06)69446-4. PMID: 17046465.

19. Raut CP, Posner M, Desai J, et al. 2006; Surgical management of advanced gastrointestinal stromal tumors after treatment with targeted systemic therapy using kinase inhibitors. J Clin Oncol. 24:2325–2331. DOI: 10.1200/JCO.2005.05.3439. PMID: 16710031.

20. Sym SJ, Ryu MH, Lee JL, et al. 2008; Surgical intervention following imatinib treatment in patients with advanced gastrointestinal stromal tumors (GISTs). J Surg Oncol. 98:27–33. DOI: 10.1002/jso.21065. PMID: 18452195.

21. Park SJ, Ryu MH, Ryoo BY, et al. 2014; The role of surgical resection following imatinib treatment in patients with recurrent or metastatic gastrointestinal stromal tumors: results of propensity score analyses. Ann Surg Oncol. 21:4211–4217. DOI: 10.1245/s10434-014-3866-4. PMID: 24980089.

22. Blay JY, Bonvalot S, Casali P, et al. 2005; Consensus meeting for the management of gastrointestinal stromal tumors. Report of the GIST Consensus Conference of 20-21 March 2004, under the auspices of ESMO. Ann Oncol. 16:566–578. DOI: 10.1093/annonc/mdi127. PMID: 15781488.

23. Tavares AB, Viveiros FA, Cidade CN, Maciel J. 2012; Gastric GIST with synchronous neuroendocrine tumour of the pancreas in a patient without neurofibromatosis type 1. BMJ Case Rep. 2012:bcr0220125895. DOI: 10.1136/bcr.02.2012.5895. PMID: 22675144. PMCID: PMC4543145.

24. Poredska K, Kunovsky L, Prochazka V, et al. 2019; Triple malignancy (NET, GIST and pheochromocytoma) as a first manifestation of neurofibromatosis type-1 in an adult patient. Diagn Pathol. 14:77. DOI: 10.1186/s13000-019-0848-7. PMID: 31301733. PMCID: PMC6626625.

25. Lin YL, Wei CK, Chiang JK, Chou AL, Chen CW, Tseng CE. 2008; Concomitant gastric carcinoid and gastrointestinal stromal tumors: a case report. World J Gastroenterol. 14:6100–6103. DOI: 10.3748/wjg.14.6100. PMID: 18932294. PMCID: PMC2760185.

26. Hung CY, Chen MJ, Shih SC, et al. 2008; Gastric carcinoid tumor in a patient with a past history of gastrointestinal stromal tumor of the stomach. World J Gastroenterol. 14:6884–6887. DOI: 10.3748/wjg.14.6884. PMID: 19058321. PMCID: PMC2773889.

27. Samaras VD, Foukas PG, Triantafyllou K, et al. 2011; Synchronous well differentiated neuroendocrine tumour and gastrointestinal stromal tumour of the stomach: a case report. BMC Gastroenterol. 11:27. DOI: 10.1186/1471-230X-11-27. PMID: 21435225. PMCID: PMC3070680.

28. Wu E, Son SY, Gariwala V, O'Neill C. 2021; Gastric gastrointestinal stromal tumor (GIST) with co-occurrence of pancreatic neuroendocrine tumor. Radiol Case Rep. 16:1391–1394. DOI: 10.1016/j.radcr.2021.03.014. PMID: 33912253. PMCID: PMC8063710.