{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T14:47:42Z","timestamp":1793717262506,"version":"4.6.1"},"reference-count":128,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2024,5,30]],"date-time":"2024-05-30T00:00:00Z","timestamp":1717027200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Pancreatic neuroendocrine tumors (PanNETs) and lung NETs (LNETs) represent a rare but clinically significant subgroup of neoplasms. While the majority is sporadic, approximately 17% of PanNETs and a subset of LNETs develop in the context of monogenic familial tumor syndromes, especially multiple endocrine neoplasia type 1 (MEN1) syndrome. Other inherited syndromes associated with PanNETs include MEN4, von Hippel\u2013Lindau (VHL) syndrome, neurofibromatosis type 1 (NF1), and tuberous sclerosis complex (TSC). These syndromes are highly penetrant and their clinical manifestations may vary even among members of the same family. They are attributed to genetic mutations involving key molecular pathways regulating cell growth, differentiation, and angiogenesis. Pancreatic NETs in hereditary syndromes are often multiple, develop at a younger age compared to sporadic tumors, and are associated with endocrine and nonendocrine tumors derived from multiple organs. Lung NETs are not as common as PanNETs and are mostly encountered in MEN1 syndrome and include typical and atypical lung carcinoids. Early detection of PanNETs and LNETs related to inherited syndromes is crucial, and specific follow-up protocols need to be employed to optimize diagnosis and management. Genetic screening is recommended in childhood, and diagnostic screening starts often in adolescence, even in asymptomatic mutation carriers. Optimal management and therapeutic decisions should be made in the context of a multidisciplinary team in specialized centers, whereas specific biomarkers aiming to identify patients denoted to follow a more aggressive course need to be developed.<\/jats:p>","DOI":"10.3390\/cancers16112075","type":"journal-article","created":{"date-parts":[[2024,5,30]],"date-time":"2024-05-30T06:08:14Z","timestamp":1717049294000},"page":"2075","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Hereditary Syndromes Associated with Pancreatic and Lung Neuroendocrine Tumors"],"prefix":"10.3390","volume":"16","author":[{"given":"Nektaria","family":"Papadopoulou-Marketou","sequence":"first","affiliation":[{"name":"Neuroendocrine Tumor Unit, EURACAN 4 and ENETS Centre of Excellence, 1st Department of Propaedeutic Internal Medicine, Laiko General Hospital, National and Kapodistrian University of Athens, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6013-5893","authenticated-orcid":false,"given":"Marina","family":"Tsoli","sequence":"additional","affiliation":[{"name":"Neuroendocrine Tumor Unit, EURACAN 4 and ENETS Centre of Excellence, 1st Department of Propaedeutic Internal Medicine, Laiko General Hospital, National and Kapodistrian University of Athens, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9173-3271","authenticated-orcid":false,"given":"Eleftherios","family":"Chatzellis","sequence":"additional","affiliation":[{"name":"251 Air Force General Hospital, 11525 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2398-6768","authenticated-orcid":false,"given":"Krystallenia I.","family":"Alexandraki","sequence":"additional","affiliation":[{"name":"2nd Department of Surgery, Aretaieio Hospital Athens, Medical School, 11528 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory","family":"Kaltsas","sequence":"additional","affiliation":[{"name":"Neuroendocrine Tumor Unit, EURACAN 4 and ENETS Centre of Excellence, 1st Department of Propaedeutic Internal Medicine, Laiko General Hospital, National and Kapodistrian University of Athens, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,5,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1335","DOI":"10.1001\/jamaoncol.2017.0589","article-title":"Trends in the Incidence, Prevalence, and Survival Outcomes in Patients with Neuroendocrine Tumors in the United States","volume":"3","author":"Dasari","year":"2017","journal-title":"JAMA Oncol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"559","DOI":"10.21037\/jgo.2020.03.09","article-title":"Inherited syndromes involving pancreatic neuroendocrine tumors","volume":"11","author":"Geurts","year":"2020","journal-title":"J. Gastrointest. Oncol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1038\/nature21063","article-title":"Whole-genome landscape of pancreatic neuroendocrine tumours","volume":"543","author":"Scarpa","year":"2017","journal-title":"Nature"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.mce.2013.08.002","article-title":"Multiple endocrine neoplasia type 1 (MEN1) and type 4 (MEN4)","volume":"386","author":"Thakker","year":"2014","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"T195","DOI":"10.1530\/ERC-17-0243","article-title":"MEN4 and CDKN1B mutations: The latest of the MEN syndromes","volume":"24","author":"Alrezk","year":"2017","journal-title":"Endocr. Relat. Cancer"},{"key":"ref_6","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\u2014An International Consensus Statement","volume":"111","author":"Niederle","year":"2021","journal-title":"Neuroendocrinology"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1111\/cen.14727","article-title":"Update on the clinical management of multiple endocrine neoplasia type 1","volume":"97","author":"Pieterman","year":"2022","journal-title":"Clin. Endocrinol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"681013","DOI":"10.3389\/fendo.2021.681013","article-title":"A Direct Comparison of Patients with Hereditary and Sporadic Pancreatic Neuroendocrine Tumors: Evaluation of Clinical Course, Prognostic Factors and Genotype-Phenotype Correlations","volume":"12","author":"Soczomski","year":"2021","journal-title":"Front. Endocrinol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e13318","DOI":"10.1111\/jne.13318","article-title":"European Neuroendocrine Tumor Society 2023 guidance paper for functioning pancreatic neuroendocrine tumour syndromes","volume":"35","author":"Hofland","year":"2023","journal-title":"J. Neuroendocr."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1016\/j.annonc.2021.01.003","article-title":"Lung and thymic carcinoids: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up","volume":"32","author":"Baudin","year":"2021","journal-title":"Ann. Oncol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1007\/s00268-017-4135-z","article-title":"Histologically Proven Bronchial Neuroendocrine Tumors in MEN1: A GTE 51-Case Cohort Study","volume":"42","author":"Lecomte","year":"2018","journal-title":"World J. Surg."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"e1014","DOI":"10.1210\/clinem\/dgaa800","article-title":"The Management of Neuroendocrine Tumors of the Lung in MEN1: Results from the Dutch MEN1 Study Group","volume":"106","author":"Dekkers","year":"2021","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"3325","DOI":"10.1210\/jc.2014-1560","article-title":"Natural course and survival of neuroendocrine tumors of thymus and lung in MEN1 patients","volume":"99","author":"Pieterman","year":"2014","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1807","DOI":"10.1002\/cncr.23648","article-title":"Inherited pancreatic endocrine tumor syndromes: Advances in molecular pathogenesis, diagnosis, management, and controversies","volume":"113","author":"Jensen","year":"2008","journal-title":"Cancer"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1159\/000382138","article-title":"Genetics and Epigenetics of Pancreatic Neuroendocrine Tumors and Pulmonary Carcinoids","volume":"44","author":"Dreijerink","year":"2015","journal-title":"Front. Horm. Res."},{"key":"ref_16","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."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1111\/cen.13264","article-title":"Long-term outcomes in patients with multiple endocrine neoplasia type 1 and pancreaticoduodenal neuroendocrine tumours","volume":"86","author":"Donegan","year":"2017","journal-title":"Clin. Endocrinol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1126\/science.276.5311.404","article-title":"Positional cloning of the gene for multiple endocrine neoplasia-type 1","volume":"276","author":"Chandrasekharappa","year":"1997","journal-title":"Science"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1111\/cen.12714","article-title":"Prevalence of parathyroid carcinoma in 348 patients with multiple endocrine neoplasia type 1\u2014Case report and review of the literature","volume":"84","author":"Sebo","year":"2016","journal-title":"Clin. Endocrinol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1002\/humu.20605","article-title":"Multiple endocrine neoplasia type 1 (MEN1): Analysis of 1336 mutations reported in the first decade following identification of the gene","volume":"29","author":"Lemos","year":"2008","journal-title":"Hum. Mutat."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"6569","DOI":"10.1128\/MCB.24.15.6569-6580.2004","article-title":"Menin missense mutants associated with multiple endocrine neoplasia type 1 are rapidly de-graded via the ubiquitin-proteasome pathway","volume":"24","author":"Yaguchi","year":"2004","journal-title":"Mol. Cell. Biol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1210\/jc.2018-01170","article-title":"UMD-MEN1 Database: An Overview of the 370 MEN1 Variants Present in 1676 Patients from the French Population","volume":"104","author":"Romanet","year":"2019","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1858","DOI":"10.1158\/0008-5472.CAN-08-3662","article-title":"Recapitulation of Pancreatic Neuroendocrine Tumors in Human Multiple Endocrine Neoplasia Type I Syndrome via Pdx1-Directed Inactivation of Men1","volume":"69","author":"Shen","year":"2009","journal-title":"Cancer Res."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Marini, F., Giusti, F., Tonelli, F., and Brandi, M.L. (2021). Pancreatic Neuroendocrine Neoplasms in Multiple Endocrine Neoplasia Type 1. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22084041"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"de Laat, J.M., van der Luijt, R.B., Pieterman, C.R., Oostveen, M.P., Hermus, A.R., Dekkers, O.M., de Herder, W.W., van der Horst-Schrivers, A.N., Drent, M.L., and Bisschop, P.H. (2016). MEN1 redefined, a clinical comparison of mutation-positive and mutation-negative patients. BMC Med., 14.","DOI":"10.1186\/s12916-016-0708-1"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/j.surg.2020.04.067","article-title":"Understanding the clinical course of genotype-negative MEN1 patients can inform management strategies","volume":"169","author":"Pieterman","year":"2021","journal-title":"Surgery"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"T119","DOI":"10.1530\/ERC-17-0199","article-title":"The future: Genetics advances in MEN1 therapeutic approaches and management strategies","volume":"24","author":"Agarwal","year":"2017","journal-title":"Endocr. Relat. Cancer"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1007\/s00268-009-0290-1","article-title":"Risk factors and causes of death in MEN1 disease. A GTE (Groupe d\u2019Etude des Tumeurs Endocrines) cohort study among 758 patients","volume":"34","author":"Goudet","year":"2010","journal-title":"World J. Surg."},{"key":"ref_29","first-page":"3515","article-title":"Initiating Pancreatic Neuroendocrine Tumor (pNET) Screening in Young MEN1 Patients: Results From the DutchMEN Study Group","volume":"106","author":"Pieterman","year":"2021","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"e13343","DOI":"10.1111\/jne.13343","article-title":"European Neuroendocrine Tumour Society (ENETS) 2023 guidance paper for nonfunctioning pancreatic neuroendocrine tumours","volume":"35","author":"Castano","year":"2023","journal-title":"J. Neuroendocr."},{"key":"ref_31","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."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1568","DOI":"10.1210\/jc.2014-3659","article-title":"MEN1 disease occurring before 21 years old: A 160-patient cohort study from the Groupe d\u2019etude des Tumeurs Endocrines","volume":"100","author":"Goudet","year":"2015","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"E89","DOI":"10.1210\/jc.2013-1768","article-title":"Penetrance of functioning and nonfunctioning pancreatic neuroendocrine tumors in multiple endocrine neoplasia type 1 in the second decade of life","volume":"99","author":"Goncalves","year":"2014","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"708","DOI":"10.1111\/cen.14094","article-title":"What is the appropriate management of nonfunctioning pancreatic neuroendocrine tumours disclosed on screening in adult patients with multiple endocrine neoplasia type 1?","volume":"91","author":"Challis","year":"2019","journal-title":"Clin. Endocrinol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1489","DOI":"10.1002\/bjs.11632","article-title":"Surgery for multiple endocrine neoplasia type 1-related insulinoma: Long-term outcomes in a large international cohort","volume":"107","author":"Beek","year":"2020","journal-title":"Br. J. Surg."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"339","DOI":"10.3389\/fendo.2019.00339","article-title":"Multiple Endocrine Neoplasia Type 1 (MEN1): An Update and the Significance of Early Genetic and Clinical Diagnosis","volume":"10","author":"Kamilaris","year":"2019","journal-title":"Front. Endocrinol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1007\/s40618-022-01961-w","article-title":"Sporadic and MEN1-related gastrinoma and Zollinger-Ellison syndrome: Differences in clinical characteristics and survival outcomes","volume":"46","author":"Massironi","year":"2023","journal-title":"J. Endocrinol. Investig."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1097\/01.md.0000112297.72510.32","article-title":"Multiple endocrine neoplasia type 1 and Zollinger-Ellison syndrome: A prospective study of 107 cases and comparison with 1009 cases from the literature","volume":"83","author":"Gibril","year":"2004","journal-title":"Medicine"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1075","DOI":"10.1016\/S0399-8320(04)95184-6","article-title":"Prevalence, characteristics and prognosis of MEN 1-associated glucagonomas, VIPomas, and somatostatinomas: Study from the GTE (Groupe des Tumeurs Endocrines) registry","volume":"28","author":"Merle","year":"2004","journal-title":"Gastroent\u00e9rol. Clin. Biol."},{"key":"ref_40","first-page":"63","article-title":"Management of pancreatic neuroendocrine tumors in patients with MEN 1","volume":"4","author":"Sadowski","year":"2015","journal-title":"Gland Surg."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"e1","DOI":"10.1097\/MPA.0000000000000969","article-title":"Simultaneous Glucagon and Vasoactive Intestinal Peptide Producing Pancreatic Neuroendocrine Tumors in a Patient with Multiple Endocrine Neoplasia Type 1: A Case Re-port and Literature","volume":"47","author":"Kim","year":"2018","journal-title":"Pancreas"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"885","DOI":"10.2214\/AJR.19.22542","article-title":"Multiple Endocrine Neoplasia: Spectrum of Abdominal Manifestations","volume":"215","author":"Davila","year":"2020","journal-title":"Am. J. Roentgenol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1677\/ERC-07-0157","article-title":"Somatostatin-producing neuroendocrine tumors of the duodenum and pancreas: Incidence, types, biological behavior, association with inherited syndromes, and functional activity","volume":"15","author":"Garbrecht","year":"2008","journal-title":"Endocr. Relat. Cancer"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"20406223211035288","DOI":"10.1177\/20406223211035288","article-title":"Multiple endocrine neoplasia 1: A broad overview","volume":"12","author":"Thompson","year":"2021","journal-title":"Ther. Adv. Chronic Dis."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"591501","DOI":"10.3389\/fendo.2020.591501","article-title":"Phenotypes Associated with MEN1 Syndrome: A Focus on Genotype-Phenotype Correlations","volume":"11","author":"Mele","year":"2020","journal-title":"Front. Endocrinol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"3795","DOI":"10.1210\/jc.2017-00372","article-title":"Long-Term Natural Course of Small Nonfunctional Pancreatic Neuroendocrine Tumors in MEN1-Results from the Dutch MEN1 Study Group","volume":"102","author":"Pieterman","year":"2017","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1260","DOI":"10.1038\/s41591-019-0493-4","article-title":"Enhancer signatures stratify and predict outcomes of non-functional pancreatic neuroendocrine tumors","volume":"25","author":"Cejas","year":"2019","journal-title":"Nat. Med."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1038\/modpathol.2012.53","article-title":"Loss of ATRX or DAXX expression and concomitant acquisition of the alternative lengthening of telomeres phenotype are late events in a small subset of MEN-1 syndrome pancreatic neuroendocrine tumors","volume":"25","author":"Heaphy","year":"2012","journal-title":"Mod. Pathol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"73","DOI":"10.12688\/f1000research.7230.1","article-title":"Genetics of multiple endocrine neoplasia type 1 syndrome: What\u2019s new and what\u2019s old","volume":"6","author":"Falchetti","year":"2017","journal-title":"F1000Research"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1016\/j.soc.2022.10.008","article-title":"Multiple Endocrine Neoplasia Type 1 Syndrome Pancreatic Neuroendocrine Tumor Genotype\/Phenotype: Is There Any Advance on Predicting or Preventing?","volume":"32","author":"Ramamoorthy","year":"2023","journal-title":"Surg. Oncol. Clin. N. Am."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2650","DOI":"10.1158\/0008-5472.CAN-12-3158","article-title":"Menin Epigenetically Represses Hedgehog Signaling in MEN1 Tumor Syndrome","volume":"73","author":"Gurung","year":"2013","journal-title":"Cancer Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"T147","DOI":"10.1530\/ERC-17-0298","article-title":"Epigenetic regulation by the menin pathway","volume":"24","author":"Feng","year":"2017","journal-title":"Endocr.-Relat. Cancer"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1067","DOI":"10.1210\/js.2018-00087","article-title":"Diagnosing Nonfunctional Pancreatic NETs in MEN1: The Evidence Base","volume":"2","author":"Vriens","year":"2018","journal-title":"J. Endocr. Soc."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"926491","DOI":"10.3389\/fendo.2022.926491","article-title":"Diagnosing pancreatic neuroendocrine tumors in patients with multiple endocrine neo-plasia type 1 in daily practice","volume":"13","author":"Pieterman","year":"2022","journal-title":"Front. Endocrinol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1186\/s13053-017-0084-7","article-title":"Central nervous system gadolinium accumulation in patients undergoing periodical contrast MRI screening for hereditary tumor syndromes","volume":"16","author":"Vergauwen","year":"2018","journal-title":"Hered. Cancer Clin. Pract."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1016\/j.annpat.2020.01.002","article-title":"Inherited tumor syndromes of gastroenteropancreatic and thoracic neuroendocrine neoplasms","volume":"40","author":"Couvelard","year":"2020","journal-title":"Ann. Pathol."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Ishii, T., Katanuma, A., Toyonaga, H., Chikugo, K., Nasuno, H., Kin, T., Hayashi, T., and Takahashi, K. (2021). Role of Endoscopic Ultrasound in the Diagnosis of Pancreatic Neuroendocrine Neoplasms. Diagnostics, 11.","DOI":"10.3390\/diagnostics11020316"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1055\/a-0931-7005","article-title":"Magnetic Resonance Imaging or Endoscopic Ultrasonography for Detection and Surveillance of Pancreatic Neuroendocrine Neoplasms in Patients with Multiple Endocrine Neoplasia Type 1?","volume":"51","author":"Daskalakis","year":"2019","journal-title":"Horm. Metab. Res."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"bvac001","DOI":"10.1210\/jendso\/bvac001","article-title":"MEN1 Surveillance Guidelines: Time to (Re)Think?","volume":"6","author":"Newey","year":"2022","journal-title":"J. Endocr. Soc."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.ando.2019.11.001","article-title":"Comparison of 68Ga-Dotatate PET\/CT and 18F-FDOPA PET\/CT for the diagnosis of pancreatic neuroendocrine tumors in a MEN1 patient","volume":"81","author":"Jullien","year":"2020","journal-title":"Ann. Endocrinol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1093\/ejendo\/lvad035","article-title":"Pancreatic imaging in MEN1\u2014Comparison of conventional and somatostatin receptor positron emission tomography\/computed tomography imaging in real-life setting","volume":"188","author":"Kostiainen","year":"2023","journal-title":"Eur. J. Endocrinol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"2026","DOI":"10.1007\/s00268-017-3992-9","article-title":"Is Routine Screening of Young Asymptomatic MEN1 Patients Necessary?","volume":"41","author":"Manoharan","year":"2017","journal-title":"World J. Surg."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1007\/BF00353743","article-title":"Surgical management of insulinoma associated with multiple endocrine neoplasia type I","volume":"18","author":"Service","year":"1994","journal-title":"World J. Surg."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1007\/s00259-003-1184-3","article-title":"Concomitant expression of several peptide receptors in neuroendocrine tumours: Molecular basis for in vivo multireceptor tumour targeting","volume":"30","author":"Reubi","year":"2003","journal-title":"Eur. J. Nucl. Med. Mol. Imaging"},{"key":"ref_65","first-page":"27","article-title":"Growth rate of small pancreatic neuroendocrine tumors in multiple endocrine neoplasia type 1: Results from an endoscopic ultrasound-based cohort study","volume":"49","author":"Kappelle","year":"2017","journal-title":"Endoscopy"},{"key":"ref_66","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."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1094","DOI":"10.1097\/SLA.0000000000003162","article-title":"Metastatic Potential and Survival of Duodenal and Pancreatic Tumors in Multiple Endocrine Neoplasia Type 1: A GTE and AFCE Cohort Study (Groupe d\u2019etude des Tumeurs Endocrines and Association Francophone de Chirurgie Endocrinienne)","volume":"272","author":"Vinault","year":"2020","journal-title":"Ann. Surg."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"103648","DOI":"10.1016\/j.critrevonc.2022.103648","article-title":"Pancreatic neuroendocrine neoplasms: Updates on genomic changes in inherited tumour syndromes and sporadic tumours based on WHO classification","volume":"172","author":"Ishida","year":"2022","journal-title":"Crit. Rev. Oncol.\/Hematol."},{"key":"ref_69","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"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"844","DOI":"10.1016\/j.annonc.2020.03.304","article-title":"Gastroenteropancreatic neuroendocrine neoplasms: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up","volume":"31","author":"Pavel","year":"2020","journal-title":"Ann. Oncol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1097\/00000658-200110000-00009","article-title":"Comparison of surgical results in patients with advanced and limited disease with multiple endocrine neoplasia type 1 and Zollinger-Ellison syndrome","volume":"234","author":"Norton","year":"2001","journal-title":"Ann. Surg."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1097\/SLA.0b013e3182536339","article-title":"Partial pancreaticoduodenectomy can provide cure for duodenal gastrinoma associated with multiple endocrine neoplasia type 1","volume":"257","author":"Lopez","year":"2013","journal-title":"Ann. Surg."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"5440","DOI":"10.3748\/wjg.v12.i34.5440","article-title":"Sporadic versus hereditary gastrinomas of the duodenum and pancreas: Distinct clinico-pathological and epidemiological features","volume":"12","author":"Anlauf","year":"2006","journal-title":"World J. Gastroenterol."},{"key":"ref_74","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"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1031","DOI":"10.1007\/s00268-017-4435-3","article-title":"From Initial Description by Wermer to Present-Day MEN1: What have We Learned?","volume":"42","author":"Perrier","year":"2018","journal-title":"World J. Surg."},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Kartik, A., Armstrong, V.L., Stucky, C.C., Wasif, N., and Fong, Z.V. (2024). Contemporary Approaches to the Surgical Management of Pancreatic Neuroendocrine Tumors. Cancers, 16.","DOI":"10.3390\/cancers16081501"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"17562848211042171","DOI":"10.1177\/17562848211042171","article-title":"Endoscopic ultrasound-guided ethanol and radiofrequency ablation of pancreatic insulinomas: A systematic literature review","volume":"14","author":"Frim","year":"2021","journal-title":"Ther. Adv. Gastroenterol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"2834","DOI":"10.1016\/j.cgh.2023.02.022","article-title":"Endoscopic Ultrasound-guided Radiofrequency Ablation Versus Surgical Resection for Treatment of Pancreatic Insulinoma","volume":"21","author":"Crino","year":"2023","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1210\/clinem\/dgz007","article-title":"Lanreotide Therapy vs Active Surveillance in MEN1-Related Pancreatic Neuroendocrine Tumors < 2 Centimeters","volume":"105","author":"Faggiano","year":"2020","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"86","DOI":"10.17925\/EE.2022.18.2.86","article-title":"A New Medical Therapy for Multiple Endocrine Neoplasia Type 1?","volume":"18","author":"Boharoon","year":"2022","journal-title":"touchREV. Endocrinol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1155","DOI":"10.1097\/SLA.0000000000002183","article-title":"Management of MEN1 Related Nonfunctioning Pancreatic NETs: A Shifting Paradigm: Results from the DutchMEN1 Study Group","volume":"267","author":"Nell","year":"2018","journal-title":"Ann. Surg."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"966","DOI":"10.1002\/jso.25667","article-title":"Prognostic factors and survival in MEN1 patients with gastrinomas: Results from the DutchMEN study group (DMSG)","volume":"120","author":"Nell","year":"2019","journal-title":"J. Surg. Oncol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"e880","DOI":"10.1210\/clinem\/dgab683","article-title":"Plasma Polyamines as an Additional to Imaging Biomarker in MEN1 Patients with Duodenopancreatic Neuroendocrine Tumors","volume":"107","author":"Kassi","year":"2022","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_84","first-page":"e4969","article-title":"A Blood-based Polyamine Signature Associated with MEN1 Duodenopancreatic Neuroendocrine Tumor Progression","volume":"106","author":"Fahrmann","year":"2021","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1159\/000435921","article-title":"Bronchopulmonary Neuroendocrine Neoplasms and Their Precursor Lesions in Multiple Endocrine Neoplasia Type 1","volume":"103","author":"Bartsch","year":"2016","journal-title":"Neuroendocrinology"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1810","DOI":"10.1016\/j.jtho.2021.07.020","article-title":"Well-Differentiated Bronchopulmonary Neuroendocrine Tumors: More Than One Entity","volume":"16","author":"Dekkers","year":"2021","journal-title":"J. Thorac. Oncol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1007\/s12020-022-03099-4","article-title":"Thymic neuroendocrine tumors in patients with multiple endocrine neoplasia type 1","volume":"77","author":"Yliaska","year":"2022","journal-title":"Endocrine"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1183297","DOI":"10.3389\/fendo.2023.1183297","article-title":"Expressions of Cushing\u2019s syndrome in multiple endocrine neoplasia type 1","volume":"14","author":"Simonds","year":"2023","journal-title":"Front. Endocrinol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1002\/cncr.33978","article-title":"Management recommendations for pancreatic manifestations of von Hippel-Lindau disease","volume":"128","author":"Laks","year":"2022","journal-title":"Cancer"},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"Halperin, R., and Tirosh, A. (2023). Non-Interventional Management of Advanced Pancreatic Neuroendocrine Neoplasms in Patients with von Hippel-Lindau Disease. Cancers, 15.","DOI":"10.3390\/cancers15061739"},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Halperin, R., Arnon, L., Eden-Friedman, Y., and Tirosh, A. (2023). Unique Characteristics of Patients with Von Hippel-Lindau Disease Defined by Various Diagnostic Criteria. Cancers, 15.","DOI":"10.3390\/cancers15061657"},{"key":"ref_92","unstructured":"Adam, M.P., Feldman, J., Mirzaa, G.M., Pagon, R.A., Wallace, S.E., Bean, L.J.H., Gripp, K.W., and Amemiya, A. (1993). GeneReviews\u00ae, University of Washington."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"2381","DOI":"10.1002\/ajmg.a.38324","article-title":"von Hippel-Lindau development in children and adolescents","volume":"173","author":"Launbjerg","year":"2017","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1159\/000335587","article-title":"ENETS Consensus Guidelines for the management of patients with digestive neuroendocrine neoplasms of the digestive system: Well-differentiated pancreatic non-functioning tumors","volume":"95","author":"Falconi","year":"2012","journal-title":"Neuroendocrinology"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1530\/ERC-18-0100","article-title":"Preventive medicine of von Hippel-Lindau disease-associated pancreatic neuroendocrine tumors","volume":"25","author":"Krauss","year":"2018","journal-title":"Endocr. Relat. Cancer"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1001\/jamaoncol.2017.3428","article-title":"Association of VHL Genotype with Pancreatic Neuroendocrine Tumor Phenotype in Patients With von Hippel-Lindau Disease","volume":"4","author":"Tirosh","year":"2018","journal-title":"JAMA Oncol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1351","DOI":"10.1016\/S1470-2045(18)30487-X","article-title":"Pazopanib in patients with von Hippel-Lindau disease: A single-arm, single-centre, phase 2 trial","volume":"19","author":"Jonasch","year":"2018","journal-title":"Lancet Oncol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"2036","DOI":"10.1056\/NEJMoa2103425","article-title":"Belzutifan for Renal Cell Carcinoma in von Hippel-Lindau Disease","volume":"385","author":"Jonasch","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"ref_99","first-page":"1285","article-title":"Belzutifan in a Patient with VHL-Associated Metastatic Pancreatic Neuroendocrine Tumor","volume":"20","author":"Pelle","year":"2022","journal-title":"J. Natl. Compr. Cancer Netw."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1111\/j.1749-6632.2009.05117.x","article-title":"The tuberous sclerosis complex","volume":"1184","author":"Orlova","year":"2010","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"627672","DOI":"10.3389\/fneur.2021.627672","article-title":"Frequency, Progression, and Current Management: Report of 16 New Cases of Nonfunctional Pancreatic Neuroendocrine Tumors in Tuberous Sclerosis Complex and Comparison with Previous Reports","volume":"12","author":"Mowrey","year":"2021","journal-title":"Front. Neurol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.pediatrneurol.2021.07.011","article-title":"Updated International Tuberous Sclerosis Complex Diagnostic Criteria and Surveillance and Management Recommendations","volume":"123","author":"Northrup","year":"2021","journal-title":"Pediatr. Neurol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"2666","DOI":"10.1002\/ajmg.a.62850","article-title":"Tuberous sclerosis complex-associated nonfunctional pancreatic neuroendocrine tumors: Management and surgical outcomes","volume":"188","author":"Evans","year":"2022","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"1065","DOI":"10.1136\/bmj.2.5159.1065","article-title":"Tuberous sclerosis associated with spontaneous hypoglycaemia","volume":"2","author":"Gutman","year":"1959","journal-title":"Br. Med. J."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"1209","DOI":"10.1136\/jnnp.55.12.1209","article-title":"Insulinoma complicating tuberous sclerosis","volume":"55","author":"Davoren","year":"1992","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_106","first-page":"477","article-title":"Metastasierendes Gastrinom und der Tuber\u00f6se-Sklerose-Komplex. Assoziation oder Koinzidenz? [Metastasizing gastrinoma and tuberous sclerosis complex. Association or coincidence?]","volume":"139","author":"Schwarzkopf","year":"1994","journal-title":"Zentralbl. Pathol."},{"key":"ref_107","first-page":"1543","article-title":"The association between tuberous sclerosis and insulinoma","volume":"16","author":"Kim","year":"1995","journal-title":"AJNR Am. J. Neuroradiol."},{"key":"ref_108","unstructured":"Boubaddi, N.E., Imbert, Y., Tissot, B., Chapus, J.J., Dupont, E., Gallouin, D., Masson, B., and De Mascarel, A. (1997). Insulinome s\u00e9cr\u00e9tant et scl\u00e9rose tub\u00e9reuse de Bourneville [Secreting insulinoma and Bourneville\u2019s tuberous sclerosis]. Gastroenterol. Clin. Biol., 21."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1007\/s004310051073","article-title":"Malignant pancreatic tumour within the spectrum of tuberous sclerosis complex in childhood","volume":"158","author":"Verhoef","year":"1999","journal-title":"Eur. J. Pediatr."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"109","DOI":"10.4158\/EP.8.2.109","article-title":"Insulinoma in a patient with tuberous sclerosis: Is there an association?","volume":"8","author":"Eledrisi","year":"2002","journal-title":"Endocr. Pract."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"1386","DOI":"10.1097\/00000478-200310000-00012","article-title":"Malignant pancreatic endocrine tumor in a child with tuberous sclerosis","volume":"27","author":"Francalanci","year":"2003","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"1669","DOI":"10.1002\/ajmg.a.31351","article-title":"Extensive acrochordons and pancreatic islet-cell tumors in tuberous sclerosis associated with TSC2 mutations","volume":"140","author":"Merritt","year":"2006","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1097\/PAS.0b013e31823d0560","article-title":"Well-differentiated pancreatic neuroendocrine carcinoma in tuberous sclerosis\u2014Case report and review of the literature","volume":"36","author":"Arva","year":"2012","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1007\/s00247-016-3701-0","article-title":"Pancreatic tumors in children and young adults with tuberous sclerosis complex","volume":"47","author":"Koc","year":"2017","journal-title":"Pediatr. Radiol."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"e124","DOI":"10.4158\/EP13010.CR","article-title":"Pancreatic neuroendocrine tumor in a child with a tuberous sclerosis complex 2 (TSC2) mutation","volume":"19","author":"Bombardieri","year":"2013","journal-title":"Endocr. Pract."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1007\/s10689-017-0029-3","article-title":"Pancreatic neuroendocrine tumor in a patient with a TSC1 variant: Case report and review of the literature","volume":"17","author":"Mortaji","year":"2018","journal-title":"Fam. Cancer"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"1201","DOI":"10.1210\/js.2019-00051","article-title":"Pancreatic Neuroendocrine Tumor in a Young Child With Tuberous Sclerosis Complex 1","volume":"3","author":"Mehta","year":"2019","journal-title":"J. Endocr. Soc."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"1035","DOI":"10.1016\/j.mcna.2019.07.004","article-title":"The Diagnosis and Management of Neurofibromatosis Type 1","volume":"103","author":"Ly","year":"2019","journal-title":"Med. Clin. N. Am."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1097\/GIM.0b013e3181bf15e3","article-title":"Clinical and genetic aspects of neurofibromatosis 1","volume":"12","author":"Jett","year":"2010","journal-title":"Genet. Med."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1002\/jso.2930590116","article-title":"Von Recklinghausen\u2019s disease associated with duodenal somatostatinoma: Contrast of duodenal versus pancreatic somatostatinomas","volume":"59","author":"Mao","year":"1995","journal-title":"J. Surg. Oncol."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1097\/MPA.0000000000002068","article-title":"Neurofibromatosis Type 1: A Rare Predisposition for Gastrinomas and Other Neuroendocrine Tumors","volume":"51","author":"Gauci","year":"2022","journal-title":"Pancreas"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"e220411","DOI":"10.1530\/EC-22-0411","article-title":"Multiple endocrine neoplasia type 4: A new member of the MEN family","volume":"12","author":"Singeisen","year":"2023","journal-title":"Endocr. Connect."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"e4154","DOI":"10.1210\/clinem\/dgac454","article-title":"Early Detection of Relapse by ctDNA Sequencing in a Patient with Metastatic Thymic Tumor and MEN1 Mosaicism","volume":"107","author":"Lagarde","year":"2022","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"3363","DOI":"10.1111\/cas.14972","article-title":"Detection of von Hippel-Lindau gene mutation in circulating cell-free DNA for clear cell renal cell carcinoma","volume":"112","author":"Sumiyoshi","year":"2021","journal-title":"Cancer Sci."},{"key":"ref_125","first-page":"e220146","article-title":"NETest: Serial liquid biopsies in gastroenteropancreatic NET surveillance","volume":"11","author":"Korse","year":"2022","journal-title":"Endocr. Connect."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/j.surg.2017.04.030","article-title":"Health-related quality of life in MEN1 patients compared with other chronic conditions and the United States general population","volume":"163","author":"Peipert","year":"2018","journal-title":"Surgery"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1159\/000508374","article-title":"Health-Related Quality of Life in Patients with Multiple En-docrine Neoplasia Type 1","volume":"111","author":"Pieterman","year":"2021","journal-title":"Neuroendocrinology"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1186\/s13023-020-01650-y","article-title":"Quality of life in Italian patients with Multiple endocrine neoplasia type 1 (MEN 1): Results of an extensive survey","volume":"16","author":"Giusti","year":"2021","journal-title":"Orphanet J. Rare Dis."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/16\/11\/2075\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:50:56Z","timestamp":1760107856000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/16\/11\/2075"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,30]]},"references-count":128,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2024,6]]}},"alternative-id":["cancers16112075"],"URL":"https:\/\/doi.org\/10.3390\/cancers16112075","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,5,30]]}}}