Neuroendocrine Neoplasms of the Appendix

Abstract

Primary neoplasms of the appendix showing neuroendocrine differentiation include neuroendocrine tumors (NETs), neuroendocrine carcinomas (NECs), and mixed adenoneuroendocrine carcinomas (MANECs), including goblet cell carcinoids. NETs comprise 50–77 % of all appendiceal neoplasms and 19 % of all gastrointestinal (GI) NETs. Primary NECs of the appendix are extremely rare and exhibit immunohistopathologic profile similar to NECs at other sites within the GI tract. MANECs arise from a pre-existing goblet cell carcinoid (GCC) and consist of a mixture of exocrine (signet ring type or poorly differentiated) and endocrine carcinoma components, with one component exceeding 30 %. Appendiceal NETs are more frequent in females, and most are diagnosed incidentally in the distal third (75 %) of the appendix. Mean age at presentation is 32–43 years; tubular NETs occur at younger age compared to goblet cell carcinoids. Most appendiceal neoplasms are clinically silent or may simulate acute appendicitis with intermittent abdominal pain or pain localized in the right lower abdomen. Carcinoid syndrome is rare and suggests extensive metastatic disease. Most appendiceal NETs are enterochromaffin cell (EC cell) serotonin-producing neoplasms. Less frequent subtypes include L cell NETs and tubular carcinoids. The latter can be misdiagnosed as metastatic adenocarcinoma as it lacks direct contact with the appendiceal mucosa. GCCs are relatively rare, while primary NECs, or MANECs, are extremely rare, but can pose diagnostic challenges for practicing pathologists and need careful sampling, review, and workup. The vast majority of patients with NETs of the appendix have favorable prognosis, with 88–94 % 5-year survival for localized disease and 25–31 % with distant metastatic disease. Prognosis of GCC is intermediate between carcinoids and appendiceal adenocarcinomas with an overall 5-year survival of 76 %. Since patients with appendiceal NETs are at increased risk for other GI malignancies, follow-up with colonoscopic screening is warranted.