To Örebro University

Introduction: Small Intestinal Neuroendocrine Neoplasms (SI-NENs) may rarely metastasize to the left supraclavicular lymph nodes, also known as Virchow’s node metastasis (VM).

Aim(s): Data on prevalence, prognostic significance and clinical course of disease for SI-NEN patients with VM is limited.

Materials and methods: In this retrospective analysis of 231 SI-NEN patients treated at two tertiary referal centers we found nine patients with VM. We used a control group of 18 age-and sex-matched SI-NEN patients from the same cohort with stage IV disease, but no extrahepatic metastases.

Results: VM prevalence was 3.9% (9/231; 5 females, median age at VM diagnosis 65 years). Two patients had G1, 5 G2 tumours and 2 of unspecified grade. Four patients presented with synchronous VM, whereas 3 developed metachronous VM after a median of 24 months (range: 4.8–117.6 months). Hepatic metastases were present in 7 patients, extrahepatic metastases (EM) in 8 (6 para-aortic distant lymph node metastases, 1 lung and 1 pancreatic metastasis) and peritoneal carcinomatosis in 2 patients. There was no difference in best-recorded responses to 1st line treatment according to RECIST 1.1 as well as progression-free (PFS) and overall survival rates (PFS) between patients with VM and those in the control group (Chi-square p=0.516; PFS: 71.7 vs. 106.9 months [95%CI 38.1-175.8]; log-rank p=0.855; OS: 138.6 [95%CI 17.2–260] vs. 109.9 [95%CI 91.7–128] months; log-rank p=0.533).

Conclusion: VM is relatively rare in patients with SI-NENs. It is more often encountered in patients withG2 tumors and EM, mainly to distant para-aortic lymph nodes. Its presence does not seem to impact patients’ survival outcomes and treatment responses, when compared to age-and sex-matched patients with stage IV disease.