{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T13:52:18Z","timestamp":1768485138044,"version":"3.49.0"},"reference-count":28,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2022,2,12]],"date-time":"2022-02-12T00:00:00Z","timestamp":1644624000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001725","name":"Royal Swedish Academy of Sciences","doi-asserted-by":"publisher","award":["ME2019-0060"],"award-info":[{"award-number":["ME2019-0060"]}],"id":[{"id":"10.13039\/501100001725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Small intestinal neuroendocrine tumors (SI-NETs) may rarely metastasize to the left supraclavicular lymph nodes, also known as Virchow\u2019s node metastasis (VM). Data on prevalence, prognostic significance, and clinical course of disease for SI-NET patients with VM is limited. In this retrospective analysis of 230 SI-NET patients treated at two tertiary referral centers, we found nine patients with VM (prevalence 3.9%). Among those, there were 5 females and median age at SI-NET and VM diagnosis was 61 and 65 years, respectively. Two patients had G1 tumors and five G2, while two tumors were of unspecified grade (median Ki67: 7%, range 2\u201315%). Four patients presented with synchronous VM, whereas five developed metachronous VM after a median of twenty-four months (range: 4.8\u2013117.6 months). Hepatic metastases were present in seven patients, extrahepatic metastases (EM) in eight (six para-aortic distant lymph node metastases, one lung and one pancreatic metastasis), whereas peritoneal carcinomatosis (PC) in two patients. We used a control group of 18 age- and sex-matched SI-NET patients from the same cohort with stage IV disease but no extra-abdominal metastases. There was no difference in best-recorded response to first line treatment according to RECIST 1.1 as well as progression-free survival (PFS) between patients with VM and those in the control group (Chi-square test p = 0.516; PFS 71.7 vs. 106.9 months [95% CI 38.1\u2013175.8]; log-rank p = 0.855). In addition, median overall survival (OS) of SI-NET patients with VM did not differ from those in the control group (138.6 [95% CI 17.2\u2013260] vs. 109.9 [95% CI 91.7\u2013128] months; log-rank p = 0.533). In conclusion, VM, although relatively rare in patients with SI-NETs, is more often encountered in patients with G2 tumors and established distant para-aortic lymph node metastases. The presence of VM in SI-NET patients does not seem to impact patients\u2019 survival outcomes and treatment responses, when compared to age- and sex-matched SI-NET patients with stage IV disease confined in the abdomen.<\/jats:p>","DOI":"10.3390\/cancers14040913","type":"journal-article","created":{"date-parts":[[2022,2,13]],"date-time":"2022-02-13T20:32:30Z","timestamp":1644784350000},"page":"913","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Heterogeneity of Small Intestinal Neuroendocrine Tumors Metastasis: Biologic Patterns of a Series with Virchow\u2019s Node Involvement"],"prefix":"10.3390","volume":"14","author":[{"given":"Maria","family":"Wedin","sequence":"first","affiliation":[{"name":"Department of Surgery, Faculty of Medicine and Health, \u00d6rebro University, 70185 \u00d6rebro, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6013-5893","authenticated-orcid":false,"given":"Marina","family":"Tsoli","sequence":"additional","affiliation":[{"name":"1st Department of Propaedeutic Internal Medicine, National and Kapodistrian, University of Athens, 11527 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G\u00f6ran","family":"Wallin","sequence":"additional","affiliation":[{"name":"Department of Surgery, Faculty of Medicine and Health, \u00d6rebro University, 70185 \u00d6rebro, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eva Tiensuu","family":"Janson","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences, Uppsala University, 75185 Uppsala, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4159-2511","authenticated-orcid":false,"given":"Anna","family":"Koumarianou","sequence":"additional","affiliation":[{"name":"Hematology-Oncology Unit, Fourth Department of Internal Medicine, Attikon Hospital, Medical School, National and Kapodistrian University of Athens, 12462 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5876-7883","authenticated-orcid":false,"given":"Gregory","family":"Kaltsas","sequence":"additional","affiliation":[{"name":"1st Department of Propaedeutic Internal Medicine, National and Kapodistrian, University of Athens, 11527 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4224-8912","authenticated-orcid":false,"given":"Kosmas","family":"Daskalakis","sequence":"additional","affiliation":[{"name":"Department of Surgery, Faculty of Medicine and Health, \u00d6rebro University, 70185 \u00d6rebro, Sweden"},{"name":"2nd Department of Surgery, \u201cKorgialenio-Benakio\u201d, Red Cross General Hospital, 11526 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,2,12]]},"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":"1419","DOI":"10.1007\/s00268-011-1296-z","article-title":"Long-term results of surgery for small intestinal neuroendocrine tumors at a tertiary referral center","volume":"36","author":"Norlen","year":"2012","journal-title":"World J. Surg."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1002\/bjs.10333","article-title":"Clinical signs of fibrosis in small intestinal neuroendocrine tumours","volume":"104","author":"Daskalakis","year":"2017","journal-title":"Br. J. Surg."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Koumarianou, A., Alexandraki, K.I., Wallin, G., Kaltsas, G., and Daskalakis, K. (2020). Pathogenesis and Clinical Management of Mesenteric Fibrosis in Small Intestinal Neuroendocine Neoplasms: A Systematic Review. J. Clin. Med., 9.","DOI":"10.3390\/jcm9061777"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1159\/000497183","article-title":"Lung Metastases in Patients with Well-Differentiated Gastroenteropancreatic Neuroendocrine Neoplasms: An Appraisal of the Validity of Thoracic Imaging Surveillance","volume":"108","author":"Daskalakis","year":"2019","journal-title":"Neuroendocrinology"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"690","DOI":"10.1007\/s12020-019-01838-8","article-title":"The prognosis and management of neuroendocrine neoplasms-related metastatic bone disease: Lessons from clinical practice","volume":"64","author":"Alexandraki","year":"2019","journal-title":"Endocrine"},{"key":"ref_7","first-page":"727","article-title":"Virchow\u2019s node revisited. Analysis with clinicopathologic correlation of 152 fine-needle aspiration biopsies of supraclavicular lymph nodes","volume":"119","author":"Cervin","year":"1995","journal-title":"Arch. Pathol. Lab. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"742","DOI":"10.1177\/000313489906500809","article-title":"Supraclavicular lymphadenopathy: The spectrum of pathology and evaluation by fine-needle aspiration biopsy","volume":"65","author":"McHenry","year":"1999","journal-title":"Am. Surg."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1007\/s12094-012-0938-4","article-title":"Advanced or metastatic gastric cancer in elderly patients: Clinicopathological, prognostic factors and treatments","volume":"15","author":"Lu","year":"2013","journal-title":"Clin. Transl. Oncol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1377","DOI":"10.1136\/ijgc-2019-000829","article-title":"Prognostic significance of supraclavicular lymphadenopathy in patients with high-grade serous ovarian cancer","volume":"29","author":"Cybulska","year":"2019","journal-title":"Int. J. Gynecol. Cancer"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1016\/j.jclinepi.2007.11.008","article-title":"The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: Guidelines for reporting observational studies","volume":"61","author":"Altman","year":"2008","journal-title":"J. Clin. Epidemiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1159\/000443170","article-title":"ENETS Consensus Guidelines Update for Neuroendocrine Neoplasms of the Jejunum and Ileum","volume":"103","author":"Niederle","year":"2016","journal-title":"Neuroendocrinology"},{"key":"ref_13","unstructured":"Lloyd, R.V., Osamura, R.Y., Kl\u00f6ppel, G., and Rosai, J. (2017). Who Classification of Tumours of Endocrine Organs, IARC. [4th ed.]."},{"key":"ref_14","unstructured":"Amin, M.B., Edge, S.B., Greene, F.L., Byrd, D.R., Brookland, R.K., Washington, M.K., Gershenwald, J.E., Compton, C.C., Hess, K.R., and Sullivan, D.C. (2017). Principles of Cancer Staging. AJCC Cancer Staging Manual, Springer. [8th ed.]."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1016\/0021-9681(87)90171-8","article-title":"A new method of classifying prognostic comorbidity in longitudinal studies: Development and validation","volume":"40","author":"Charlson","year":"1987","journal-title":"J. Chronic Dis."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1159\/000510444","article-title":"Cardiac Metastases in Patients with Neuroendocrine Tumours: Clinical Features, Therapy Outcomes, and Prognostic Implications","volume":"111","author":"Liu","year":"2021","journal-title":"Neuroendocrinology"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1701","DOI":"10.1007\/s00268-013-2037-2","article-title":"Metastases from neuroendocrine tumors to the breast are more common than previously thought. A diagnostic pitfall?","volume":"37","author":"Crona","year":"2013","journal-title":"World J. Surg."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1007\/s12020-019-02130-5","article-title":"Orbital metastases from neuroendocrine neoplasms: Clinical implications and outcomes","volume":"67","author":"Kamieniarz","year":"2020","journal-title":"Endocrine"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1001\/archotol.1988.01860170108030","article-title":"Virchow\u2019s node revisited","volume":"114","author":"Shetty","year":"1988","journal-title":"Arch. Otolaryngol. Head Neck Surg."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"850","DOI":"10.1097\/SLA.0b013e3181fd37e8","article-title":"The impact of 68Ga-DOTATOC positron emission tomography\/computed tomography on the multimodal management of patients with neuroendocrine tumors","volume":"252","author":"Frilling","year":"2010","journal-title":"Ann. Surg."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Alevroudis, E., Spei, M.E., Chatziioannou, S.N., Tsoli, M., Wallin, G., Kaltsas, G., and Daskalakis, K. (2021). Clinical Utility of 18F-FDG PET in Neuroendocrine Tumors Prior to Peptide Receptor Radionuclide Therapy: A Systematic Review and Meta-Analysis. Cancers, 13.","DOI":"10.3390\/cancers13081813"},{"key":"ref_22","unstructured":"Aghedo, B.O., and Kasi, A. (2021). Virchow Node. StatPearls, StatPearls Publishing."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"724","DOI":"10.1002\/ca.22271","article-title":"Thoracic outlet syndrome: A neurological and vascular disorder","volume":"27","author":"Klaassen","year":"2014","journal-title":"Clin. Anat."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1016\/j.amjmed.2005.07.067","article-title":"Virchow\u2019s node and Horner\u2019s syndrome","volume":"119","author":"Maslovsky","year":"2006","journal-title":"Am. J. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1505","DOI":"10.1002\/bjs.9262","article-title":"Outcome after resection and radiofrequency ablation of liver metastases from small intestinal neuroendocrine tumours","volume":"100","author":"Norlen","year":"2013","journal-title":"Br. J. Surg."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1159\/000443167","article-title":"ENETS Consensus Guidelines Update for the Management of Distant Metastatic Disease of Intestinal, Pancreatic, Bronchial Neuroendocrine Neoplasms (NEN) and NEN of Unknown Primary Site","volume":"103","author":"Pavel","year":"2016","journal-title":"Neuroendocrinology"},{"key":"ref_27","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_28","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1159\/000471880","article-title":"ENETS Consensus Guidelines for the Standards of Care in Neuroendocrine Neoplasms: Systemic Therapy\u2014Biotherapy and Novel Targeted Agents","volume":"105","author":"Pavel","year":"2017","journal-title":"Neuroendocrinology"}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/14\/4\/913\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:18:16Z","timestamp":1760134696000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/14\/4\/913"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,2,12]]},"references-count":28,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2022,2]]}},"alternative-id":["cancers14040913"],"URL":"https:\/\/doi.org\/10.3390\/cancers14040913","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,2,12]]}}}