A 30-Year Long-Term Experience in Appendix Neuroendocrine Neoplasms-Granting a Positive Outcome

Abstract

Neuroendocrine neoplasms (NENs) are the most common tumor of the appendix and have an excellent prognosis. Appendiceal tumors diagnosed between 1989 and 2019 were reviewed, and clinical data were collected from patient files. Part of the series was immuno-profiled for markers related to cell cycle proliferation and/or senescence-type, apoptotic, and metastatic potential. Appendix NENs were detected in 74 patients, with 0.47% of incidence per appendectomy. The median age of the patients was 21.5 years, with two age peaks of incidence at 17.0 and 55.2 years. The median tumors size was 5.8 mm, and most were smaller than 10 mm. Lymphovascular and perineural invasion, as well as necrosis, was associated with larger tumor size. G1 tumors composed 96.0% of the cohort. The presence of moderate/strong p16 and the absent/low Bcl-2 expression was frequently observed and associated with a smaller size. This study represents one of the largest cohorts and with a long follow-up. For tumors smaller than 10 mm appendicectomy was sufficient as a curative procedure, as revealed by the good outcome. This series presented a 100% disease-free survival. The indolent phenotype of appendix NENs is supported by the expression of markers that point towards a strong inhibition of cell replication and growth inhibition.

Keywords: appendix neuroendocrine neoplasm; carcinoid; cell cycle; indolent.

Figure 1

Graphical representation of (A) Age distribution of the appendiceal neuroendocrine neoplasms (NENs), median with interquartile range (IQR); (B) Bimodal distribution of age according to appendiceal NENs incidence; (C) Size distribution, median with IQR; (D) Patient staging (frequencies) according to European Neuroendocrine Tumour Society (ENETS) and the American Joint Committee on Cancer (AJCC) recommendations; and (E) Follow-up time distribution for ENETS and AJCC stage, median with IQR.

Figure 2

Representation of the final score estimation in the immunoexpression profiling: (A) Results of the immunoexpression profiling classified in absent or low staining and moderate or strong staining categories for p16, p21, Bcl-2, Raf kinase inhibitor protein (RKIP), and cyclin-dependent kinase D1 (Cyclin D1); and (B) Median size of the appendiceal NENs according to the molecular markers’ staining score, (bars with s.e.m., * p < 0.05).