{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T13:33:41Z","timestamp":1767965621723,"version":"3.49.0"},"reference-count":35,"publisher":"The Endocrine Society","issue":"10","funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["1ZIABC011789"],"award-info":[{"award-number":["1ZIABC011789"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) may occur in 30% to 90% of patients with multiple endocrine neoplasia type 1 (MEN1). However, only 1% of GEP-NETs are grade 3 (G3). Given the rarity of these aggressive tumors, treatment of advanced G3 GEP-NETs in MEN1 is based on the treatment guidelines for sporadic GEP-NETs. We report a 43-year-old male with germline MEN1 followed at our institution, with clinical features including hyperparathyroidism, a nonfunctional pancreatic NET, and Zollinger\u2013Ellison syndrome. On routine surveillance imaging at age 40, computed tomography\/positron emission tomography imaging showed 2 arterially enhancing intraluminal masses on the medial aspect of the gastric wall. Anatomical imaging confirmed 2 enhancing masses within the pancreas and a rounded mass-like thickening along the lesser curvature of the stomach. The gastric mass was resected, and pathology reported a well-differentiated G3 NET with a Ki-67 &amp;gt;20%. The patient continued active surveillance. Eighteen months later cross-sectional imaging studies showed findings consistent with metastatic disease within the right hepatic lobe and bland embolization was done. On follow-up scans, including 68Ga-DOTATATE (68Ga-DOTA(0)-Tyr(3)-octreotate) imaging, interval increase in number and avidity of metastatic lesions were compatible with disease progression. Given a paucity of treatment recommendations for G3 tumors in MEN1, the patient was counseled based on standard NET treatment guidelines and recommended 177Lu-DOTATATE treatment. PRRT (peptide receptor radionuclide therapy) with 177Lu-DOTATATE (177Lu-tetraazacyclododecanetetraacetic acid-octreotide) is an important therapeutic modality for patients with somatostatin receptor\u2013positive NETs. However, prospective studies are needed to understand the role of PRRT in G3 NETs.<\/jats:p>","DOI":"10.1210\/jendso\/bvac122","type":"journal-article","created":{"date-parts":[[2022,8,13]],"date-time":"2022-08-13T14:37:02Z","timestamp":1660401422000},"source":"Crossref","is-referenced-by-count":4,"title":["Metastatic Grade 3 Neuroendocrine Tumor in Multiple Endocrine Neoplasia Type 1 Expressing Somatostatin Receptors"],"prefix":"10.1210","volume":"6","author":[{"given":"Akua","family":"Graf","sequence":"first","affiliation":[{"name":"Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Health , Bethesda, MD 20892 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James","family":"Welch","sequence":"additional","affiliation":[{"name":"Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Health , Bethesda, MD 20892 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rashika","family":"Bansal","sequence":"additional","affiliation":[{"name":"Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Health , Bethesda, MD 20892 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adel","family":"Mandl","sequence":"additional","affiliation":[{"name":"Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Health , Bethesda, MD 20892 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vaishali I","family":"Parekh","sequence":"additional","affiliation":[{"name":"Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Health , Bethesda, MD 20892 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Craig","family":"Cochran","sequence":"additional","affiliation":[{"name":"Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Health , Bethesda, MD 20892 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elliot","family":"Levy","sequence":"additional","affiliation":[{"name":"Radiology and Imaging Sciences, Center for Cancer Research, National Cancer Institute, National Institutes of Health , Bethesda, MD 20892 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naris","family":"Nilubol","sequence":"additional","affiliation":[{"name":"Endocrine Surgery Section, Surgical Oncology Program, National Cancer Institute , Bethesda 20892, MD , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dhaval","family":"Patel","sequence":"additional","affiliation":[{"name":"Endocrine Surgery Section, Surgical Oncology Program, National Cancer Institute , Bethesda 20892, MD , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samira","family":"Sadowski","sequence":"additional","affiliation":[{"name":"Endocrine Surgery Section, Surgical Oncology Program, National Cancer Institute , Bethesda 20892, MD , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9201-3340","authenticated-orcid":false,"given":"Smita","family":"Jha","sequence":"additional","affiliation":[{"name":"Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Health , Bethesda, MD 20892 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sunita K","family":"Agarwal","sequence":"additional","affiliation":[{"name":"Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Health , Bethesda, MD 20892 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Corina","family":"Millo","sequence":"additional","affiliation":[{"name":"Radiology and Imaging Sciences, Center for Cancer Research, National Cancer Institute, National Institutes of Health , Bethesda, MD 20892 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jenny E","family":"Blau","sequence":"additional","affiliation":[{"name":"Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Health , Bethesda, MD 20892 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William F","family":"Simonds","sequence":"additional","affiliation":[{"name":"Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Health , Bethesda, MD 20892 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lee S","family":"Weinstein","sequence":"additional","affiliation":[{"name":"Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Health , Bethesda, MD 20892 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9710-4030","authenticated-orcid":false,"given":"Jaydira","family":"Del Rivero","sequence":"additional","affiliation":[{"name":"Center for Cancer Research, National Cancer Institute, National Institutes of Health , Bethesda, MD 20892 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"80","published-online":{"date-parts":[[2022,8,13]]},"reference":[{"issue":"2","key":"2022091316573119300_CIT0001","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1210\/endrev\/bnaa031","article-title":"Multiple endocrine neoplasia type 1: latest insights","volume":"42","author":"Brandi","year":"2021","journal-title":"Endocr Rev."},{"issue":"4","key":"2022091316573119300_CIT0002","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1046\/j.1523-1747.1998.00140.x","article-title":"Cutaneous tumors in patients with multiple endocrine neoplasia type 1 show allelic deletion of the MEN1 gene","volume":"110","author":"Pack","year":"1998","journal-title":"J Invest Dermatol."},{"issue":"7","key":"2022091316573119300_CIT0003","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1159\/000511791","article-title":"Multiple endocrine neoplasia type 1 and the pancreas: diagnosis and treatment of functioning and non-functioning pancreatic and duodenal neuroendocrine neoplasia within the MEN1 syndrome - an international consensus statement","volume":"111","author":"Niederle","year":"2021","journal-title":"Neuroendocrinology."},{"issue":"5","key":"2022091316573119300_CIT0004","doi-asserted-by":"crossref","first-page":"766","DOI":"10.1016\/j.pan.2017.07.196","article-title":"Prognostic value of WHO grade in pancreatic neuro-endocrine tumors in multiple endocrine neoplasia type 1: results from the DutchMEN1 Study Group","volume":"17","author":"Conemans","year":"2017","journal-title":"Pancreatology."},{"issue":"9","key":"2022091316573119300_CIT0005","doi-asserted-by":"crossref","first-page":"2990","DOI":"10.1210\/jc.2012-1230","article-title":"Clinical practice guidelines for multiple endocrine neoplasia type 1 (MEN1)","volume":"97","author":"Thakker","year":"2012","journal-title":"J Clin Endocrinol Metab."},{"issue":"12","key":"2022091316573119300_CIT0006","doi-asserted-by":"crossref","first-page":"1248","DOI":"10.1007\/s00268-004-7609-8","article-title":"Surgery of resectable nonfunctioning neuroendocrine pancreatic tumors","volume":"28","author":"Dralle","year":"2004","journal-title":"World J Surg."},{"issue":"5","key":"2022091316573119300_CIT0007","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1097\/01.pas.0000194044.01104.25","article-title":"Microadenomatosis of the endocrine pancreas in patients with and without the multiple endocrine neoplasia type 1 syndrome","volume":"30","author":"Anlauf","year":"2006","journal-title":"Am J Surg Pathol."},{"issue":"1","key":"2022091316573119300_CIT0008","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.beem.2006.12.004","article-title":"Surgery on neuroendocrine tumours","volume":"21","author":"Akerstr\u00f6m","year":"2007","journal-title":"Best Pract Res Clin Endocrinol Metab."},{"issue":"3","key":"2022091316573119300_CIT0009","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1097\/MD.0b013e3182954af1","article-title":"Causes of death and prognostic factors in multiple endocrine neoplasia type 1: a prospective study: comparison of 106 MEN1\/Zollinger-Ellison syndrome patients with 1613 literature MEN1 patients with or without pancreatic endocrine tumors","volume":"92","author":"Ito","year":"2013","journal-title":"Medicine (Baltimore)."},{"issue":"2","key":"2022091316573119300_CIT0010","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1159\/000443171","article-title":"ENETS consensus guidelines update for the management of patients with functional pancreatic neuroendocrine tumors and non-functional pancreatic neuroendocrine tumors","volume":"103","author":"Falconi","year":"2016","journal-title":"Neuroendocrinology."},{"issue":"8","key":"2022091316573119300_CIT0011","doi-asserted-by":"crossref","first-page":"1187","DOI":"10.1007\/s00423-011-0828-1","article-title":"Long-term results of surgery for pancreatic neuroendocrine neoplasms in patients with MEN1","volume":"396","author":"Lopez","year":"2011","journal-title":"Langenbecks Arch Surg."},{"issue":"6","key":"2022091316573119300_CIT0012","doi-asserted-by":"crossref","first-page":"R145","DOI":"10.1530\/ERC-19-0372","article-title":"Prognostic factors for the outcome of nonfunctioning pancreatic neuroendocrine tumors in MEN1: a systematic review of literature","volume":"27","author":"Sadowski","year":"2020","journal-title":"Endocr Relat Cancer."},{"issue":"1","key":"2022091316573119300_CIT0013","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1097\/SLA.0000000000002191","article-title":"Long-term follow-up of MEN1 patients who do not have initial surgery for small \u22642 cm nonfunctioning pancreatic neuroendocrine tumors, an AFCE and GTE study: Association Francophone de Chirurgie Endocrinienne & Groupe d\u2019Etude des Tumeurs Endocrines","volume":"268","author":"Triponez","year":"2018","journal-title":"Ann Surg."},{"issue":"2","key":"2022091316573119300_CIT0014","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1097\/01.sla.0000197715.96762.68","article-title":"Epidemiology data on 108 MEN 1 patients from the GTE with isolated nonfunctioning tumors of the pancreas","volume":"243","author":"Triponez","year":"2006","journal-title":"Ann Surg."},{"issue":"6","key":"2022091316573119300_CIT0015","doi-asserted-by":"crossref","first-page":"641","DOI":"10.4158\/EP161639.OR","article-title":"Prognostic factors for survival of MEN1 patients with duodenopancreatic tumors metastatic to the liver: results from the DMSG","volume":"23","author":"Conemans","year":"2017","journal-title":"Endocr Pract."},{"issue":"5","key":"2022091316573119300_CIT0016","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1007\/s00268-005-0354-9","article-title":"Is surgery beneficial for MEN1 patients with small (&lt; or = 2 cm), nonfunctioning pancreaticoduodenal endocrine tumor? An analysis of 65 patients from the GTE","volume":"30","author":"Triponez","year":"2006","journal-title":"World J Surg"},{"issue":"2","key":"2022091316573119300_CIT0017","doi-asserted-by":"crossref","first-page":"R1","DOI":"10.1530\/JME-20-0020","article-title":"c-MET inhibition: novel treatment for sporadic and MEN1-associated GEP NETs","volume":"65","author":"Lee","year":"2020","journal-title":"J Mol Endocrinol."},{"issue":"2","key":"2022091316573119300_CIT0018","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1111\/his.13975","article-title":"The 2019 WHO classification of tumours of the digestive system","volume":"76","author":"Nagtegaal","year":"2020","journal-title":"Histopathology."},{"issue":"6","key":"2022091316573119300_CIT0019","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1016\/j.annpat.2017.10.003","article-title":"Classification des tumeurs neuroendocrines pancr\u00e9atiques: nouveaut\u00e9s introduites par la classification OMS 2017 des tumeurs des organes endocrines et perspectives [Classification of pancreatic neuroendocrine tumours: Changes made in the 2017 WHO classification of tumours of endocrine organs and perspectives for the future]","volume":"37","author":"Scoazec","year":"2017","journal-title":"Ann Pathol."},{"issue":"10","key":"2022091316573119300_CIT0020","doi-asserted-by":"crossref","first-page":"1191","DOI":"10.1634\/theoncologist.2015-0476","article-title":"Gastroenteropancreatic well-differentiated grade 3 neuroendocrine tumors: review and position statement","volume":"21","author":"Coriat","year":"2016","journal-title":"Oncologist."},{"issue":"6","key":"2022091316573119300_CIT0021","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1016\/j.surg.2012.08.038","article-title":"Small, nonfunctioning, asymptomatic pancreatic neuroendocrine tumors (PNETs): role for nonoperative management","volume":"152","author":"Lee","year":"2012","journal-title":"Surgery."},{"issue":"16","key":"2022091316573119300_CIT0022","doi-asserted-by":"crossref","first-page":"4464","DOI":"10.1073\/pnas.1600007113","article-title":"Identification of tumorigenic cells and therapeutic targets in pancreatic neuroendocrine tumors","volume":"113","author":"Krampitz","year":"2016","journal-title":"Proc Natl Acad Sci USA."},{"issue":"2","key":"2022091316573119300_CIT0023","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1530\/ERC-18-0424","article-title":"Peptide receptor radionuclide therapy in gastroenteropancreatic NEN G3: a multicenter cohort study","volume":"26","author":"Carlsen","year":"2019","journal-title":"Endocr Relat Cancer."},{"issue":"2","key":"2022091316573119300_CIT0024","doi-asserted-by":"crossref","first-page":"278","DOI":"10.2214\/AJR.18.19953","article-title":"Neuroendocrine tumor therapy: 177Lu-DOTATATE","volume":"211","author":"Mittra","year":"2018","journal-title":"AJR Am J Roentgenol."},{"issue":"2","key":"2022091316573119300_CIT0025","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1056\/NEJMoa1607427","article-title":"Phase 3 trial of 177Lu-Dotatate for midgut neuroendocrine tumors","volume":"376","author":"Strosberg","year":"2017","journal-title":"N Engl J Med."},{"issue":"4","key":"2022091316573119300_CIT0026","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1038\/nrendo.2018.3","article-title":"Current and emerging therapies for PNETs in patients with or without MEN1","volume":"14","author":"Frost","year":"2018","journal-title":"Nat Rev Endocrinol."},{"issue":"2","key":"2022091316573119300_CIT0027","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1007\/s00259-017-3821-2","article-title":"Peptide receptor radionuclide therapy (PRRT) in European Neuroendocrine Tumour Society (ENETS) grade 3 (G3) neuroendocrine neoplasia (NEN) \u2013 a single-institution retrospective analysis","volume":"45","author":"Thang","year":"2018","journal-title":"Eur J Nucl Med Mol Imaging."},{"issue":"6","key":"2022091316573119300_CIT0028","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1007\/s00259-017-3925-8","article-title":"Investigation of receptor radionuclide therapy with 177Lu-DOTATATE in patients with GEP-NEN and a high Ki-67 proliferation index","volume":"45","author":"Nicolini","year":"2018","journal-title":"Eur J Nucl Med Mol Imaging."},{"issue":"3","key":"2022091316573119300_CIT0029","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1159\/000475526","article-title":"ENETS consensus guidelines for the standards of care in neuroendocrine neoplasia: peptide receptor radionuclide therapy with radiolabeled somatostatin analogues","volume":"105","author":"Hicks","year":"2017","journal-title":"Neuroendocrinology."},{"issue":"5","key":"2022091316573119300_CIT0030","doi-asserted-by":"crossref","first-page":"704","DOI":"10.2967\/jnumed.109.069765","article-title":"Functional imaging of neuroendocrine tumors: a head-to-head comparison of somatostatin receptor scintigraphy, 123I-MIBG scintigraphy, and 18F-FDG PET","volume":"51","author":"Binderup","year":"2010","journal-title":"J Nucl Med."},{"issue":"4","key":"2022091316573119300_CIT0031","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1530\/ERC-15-0119","article-title":"Characteristics and treatment of patients with G3 gastroenteropancreatic neuroendocrine neoplasms","volume":"22","author":"Heetfeld","year":"2015","journal-title":"Endocr Relat Cancer."},{"issue":"1","key":"2022091316573119300_CIT0032","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1093\/annonc\/mds276","article-title":"Predictive and prognostic factors for treatment and survival in 305 patients with advanced gastrointestinal neuroendocrine carcinoma (WHO G3): the NORDIC NEC study","volume":"24","author":"Sorbye","year":"2013","journal-title":"Ann Oncol."},{"issue":"3","key":"2022091316573119300_CIT0033","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1097\/MPA.0000000000000735","article-title":"Treatment response and outcomes of grade 3 pancreatic neuroendocrine neoplasms based on morphology: well differentiated versus poorly differentiated","volume":"46","author":"Raj","year":"2017","journal-title":"Pancreas."},{"issue":"5","key":"2022091316573119300_CIT0034","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1530\/ERC-13-0027","article-title":"Are G3 ENETS neuroendocrine neoplasms heterogeneous?","volume":"20","author":"V\u00e9layoudom-C\u00e9phise","year":"2013","journal-title":"Endocr Relat Cancer."},{"issue":"4","key":"2022091316573119300_CIT0035","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1038\/modpathol.2016.217","article-title":"Somatostatin receptor expression related to TP53 and RB1 alterations in pancreatic and extrapancreatic neuroendocrine neoplasms with a Ki67-index above 20","volume":"30","author":"Konukiewitz","year":"2017","journal-title":"Mod Pathol."}],"container-title":["Journal of the Endocrine Society"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jes\/advance-article-pdf\/doi\/10.1210\/jendso\/bvac122\/45415318\/bvac122.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jes\/article-pdf\/6\/10\/bvac122\/45813434\/bvac122.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jes\/article-pdf\/6\/10\/bvac122\/45813434\/bvac122.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,9,13]],"date-time":"2022-09-13T16:59:32Z","timestamp":1663088372000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jes\/article\/doi\/10.1210\/jendso\/bvac122\/6665666"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,8,13]]},"references-count":35,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2022,10,1]]}},"URL":"https:\/\/doi.org\/10.1210\/jendso\/bvac122","relation":{},"ISSN":["2472-1972"],"issn-type":[{"value":"2472-1972","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2022,10,1]]},"published":{"date-parts":[[2022,8,13]]},"article-number":"bvac122"}}