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Purpose In 2010, the World Health Organization categorized L-cell type neuroendocrine tumors(NETs) as tumors of uncertain malignancy, while all others were classified as malignant. However, the diagnostic necessity of L-cell immunophenotyping is unclear, as are tumorstage and grade that may guide diagnosis and management. To clarify the predictivemarkers of rectal neuroendocrine neoplasms (NENs), 5- and 10-year overall survival (OS)was analyzed by pathological parameters including L-cell phenotype. Materials and MethodsA total of 2,385 rectal NENs were analyzed from our previous multicenter study and a subsetof 170 rectal NENs was immunophenotyped. ResultsIn univariate survival analysis, tumor grade (p < 0.0001), extent (p < 0.0001), size(p < 0.0001), lymph node metastasis (p=0.0063), and L-cell phenotype (p < 0.0001)showed significant correlation with the prognosis of rectal NENs; however, none of thesemarkers achieved independent significance in multivariate analysis. The 10-year OS oftumors of NET grade 1, < 10 mm, the mucosa/submucosa was 97.58%, 99.47%, and99.03%, respectively. L-Cell marker, glucagon II (GLP-1&2), with a cut off score of > 10, isuseful in defining L-Cell type. In this study, an L-cell immunophenotype was found in 83.5%of all rectal NENs and most, but not all L-cell type tumors were NET G1, small (< 10 mm)and confined to the mucosa/submucosa. ConclusionFrom these results, the biological behavior of rectal NENs does not appear to be determinedby L-cell type alone but instead by a combination of pathological parameters.

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