Heterogeneity of Small Intestinal Neuroendocrine Tumors Metastasis: Biologic Patterns of a Series with Virchow’s Node Involvement

SIMPLE SUMMARY: Virchow’s node metastasis (VM) refers to the involvement of the left supraclavicular lymph nodes at the junction of the thoracic duct and the left subclavian vein. Generally, VM is considered by clinicians to be a strong indicator of metastatic abdominal malignancy, and its dismal prognostic significance has previously been described in patients with metastatic gastric and ovarian cancer. To date, comprehensive descriptions of patients with small intestinal neuroendocrine tumors (SI-NETs) and rare metastatic manifestations, including that of VM, are sparse. In the present study from two tertiary referral centers, the prevalence of the VM secondary to SI-NET primaries was found to be 3.9%. VM was more often encountered in patients with higher-grade tumors and established disseminated disease to distant para-aortic lymph nodes. However, the presence of VM did not yield any negative prognostic impact in patient outcomes when compared to age- and sex-matched patients of similar grade with distant metastases confined in the abdomen ABSTRACT: Small intestinal neuroendocrine tumors (SI-NETs) may rarely metastasize to the left supraclavicular lymph nodes, also known as Virchow’s 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 2–15%). Four patients presented with synchronous VM, whereas five developed metachronous VM after a median of twenty-four months (range: 4.8–117.6 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 38.1–175.8]; 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 17.2–260] vs. 109.9 [95% CI 91.7–128] 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’ survival outcomes and treatment responses, when compared to age- and sex-matched SI-NET patients with stage IV disease confined in the abdomen.