Lymphovascular Invasion Is Associated with Lymph Node Involvement in Small Appendiceal Neuroendocrine Tumors

Background. Appendiceal neuroendocrine tumors (NETs) are incidentally found in up to 1% of appendectomy specimens. The association of lymphovascular invasion (LVI) with risk of regional lymph node involvement is unclear. Methods. From the National Cancer Database, 2004-2015, this study identified patients who had tumors 2 cm or smaller with one or more lymph nodes (LNs) pathologically evaluated. The histology was defined as typical, goblet cell, or composite NETs. Patient demographics, tumor characteristics, and treatment variables were analyzed. Results. The histologies for the 1767 identified patients were typical (n = 921, 52.1%), goblet cell (n = 556, 31.5%), and composite (n = 290, 16.4%). The tumor grades were low (70.4%), moderate (18.6%), and high (11%). The overall LN positivity was 17%. Of 1052 tumors evaluated, 215 (20.4%) had LVI. Overall survival decreased with node involvement (mean 84 vs. 124 months; p < 0.0001, log-rank). In the multivariate logistic regression analysis, LVI was independently associated with node involvement [odds ratio (OR) 5.0; p < 0.0001] after adjustment for patient age and tumor histologic subtype, size, and grade. In the subset analysis of typical NETs, tumor size of 1-2 cm (ref. < 1 cm; OR 5.5; p < 0.001) and presence of LVI (ref. absence of LVI; OR 4.8; p < 0.0001) were the only factors independently associated with LN involvement. Conclusions. Node involvement is associated with worse overall survival in appendiceal NETs. The presence of LVI was strongly associated with lymph node involvement. An appendectomy specimen showing LVI should prompt strong consideration of colectomy with regional lymphadenectomy even for small, typical appendiceal NETs.