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

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.

Feasibility and safety of endoscopic resection for the jejunoileal lesions

“…Endoscopic resection cannot be performed in such cases, and conventional surgery or adjuvant therapy can only be considered. The 5‐year OS and RFS of small bowel malignant tumors reported in previous studies after surgery and adjuvant treatment are much lower than our corresponding results 30,31 . A major reason for these differences may be that some of our patients had benign lesions or some of our patients had earlier tumor stages.…”

“…The 5-year OS and RFS of small bowel malignant tumors reported in previous studies after surgery and adjuvant treatment are much lower than our corresponding results. 30,31 A major reason for these differences may be that some of our patients had benign lesions or some of our patients had earlier tumor stages. Limited data are available on ER of JILs, so such procedures' recurrence and overall survival rates are not well explored.…”

Prevalence of metastases outside the liver and abdominal lymph nodes on 68Ga‐DOTATOC‐PET/CT in patients with small intestinal and pancreatic neuroendocrine tumours

“…11 To date, comprehensive descriptive and survival analyses in patients with rare metastases are sparse. 3,7,8,13,20,24 Of note, earlier studies have reported significantly shorter OS for patients with bone metastases, as compared to patients with other types of distant metastases. 3,10 The prevalence of Virchow's lymph node metastasis among patients with abdominal and thoracic malignancies has previously been estimated to be up to 2.8%.…”

“…22,23 In two previous studies, the prevalence of Virchow's lymph node metastasis was 3%-4% in Si-NET and Pan-NET patients, but it was not associated with worse prognosis. 7,8 Finally, the presence of synchronous tumour deposits in both the small intestine and pancreas has been reported. In about one-third of the patients, two different primary tumours were identified according to the histopathological report after surgical resection.…”

“…1,2 Other, less common metastatic sites are bone, orbita, breast, heart, Virchow's lymph node, and, in Si-NET patients, pancreas. [3][4][5][6][7][8] Somatostatin receptor imaging (SRI) is well established as part of tumour staging at the time of NET diagnosis, as well as for restaging and to determine the tumour somatostatin receptor status when peptide receptor radionuclide therapy (PRRT) is considered. 1,9 Most Si-NET and Pan-NET of grade 1 (G1) and grade 2 (G2), express an abundance of somatostatin receptors (SST).…”