Small Neuroendocrine Tumors of the Whole Gastrointestinal Tract Performed Endoscopic or Surgical Resections Also Show Positive for Lymphovascular Invasion

Background and aims: In gastrointestinal neuroendocrine tumors (GI-NETs), tumor size and grading based on cellular proliferative ability indicate biological malignancy but not necessarily clinically efficient prognostic stratification. We analyzed tumor size- and grading-based prevalence of lymphovascular invasion in GI-NETs to establish whether these are true biological malignancy indicators.

Methods: We included 155 cases (165 lesions), diagnosed histologically with GI-NETs, that had undergone endoscopic or surgical resection. Patient age, sex, method of treatment, tumor size, invasion depth, lymphovascular invasion positivity according to Ki-67 index-based neuroendocrine tumor grading, distant metastases, and outcome were evaluated. The primary endpoints were the prevalence of lymphovascular invasion according to tumor size and grading.

Results: Overall, 24.8% were positive for lymphovascular invasion. There was a high rate of lymphovascular invasion positivity even among grade 1 cases (22.8%). The rate of lymphovascular invasion was 3.4% for grade 1 cases <5 mm, with a lymphovascular invasion rate of 8.7% for those 5-10 mm. Lymphovascular invasion ≤10% required a tumor size ≤8 mm, and lymphovascular invasion ≤5% required a tumor size ≤6 mm. A cutoff of 6 mm was identified, which yielded a sensitivity of 79% and a specificity of 63%. Even small GI-NETs grade 1 of the whole GI tract also showed positive for lymphovascular invasion.

Conclusions: GI-NETs ≤10 mm had a lymphovascular invasion prevalence exceeding 10%. The lymphovascular invasion impact in GI-NET development is incompletely understood, but careful follow-up, including consideration of additional surgical resection, is crucial in cases with lymphovascular invasion.