Introduction: Neuroendocrine tumors of the appendix are a relatively frequent type of neuroendocrine tumor, usually detected incidentally after appendectomy. Almost all small slow-growing G1 tumors with no risk factors are cured with appendectomy while the rare and aggressive G3 carcinomas may represent a challenge in terms of management and often lead to a poor outcome. In the middle of the spectrum, a number of tumors present with in-between features and sometimes no clear-cut guidance emerges from the literature for directing the management and follow-up of these patients.
Evidence acquisition: A meticulous review of the literature on neuroendocrine tumors of the appendix, including the recommendations published by the relevant international societies.
Evidence synthesis: The literature on the neuroendocrine tumors of the appendix appears to be inhomogeneous. Likely this occurs as a consequence of a number of factors, including the mostly retrospective nature of the available data, the heterogeneous records of the same, and some peculiar aspects of the appendiceal neuroendocrine tumors, with evidence of considerable biological and clinical differences in terms of epidemiology, management, and prognosis from the less aggressive tumors to the most aggressive cancers. In particular, some situations concerning tumors in the middle of the biological and clinical spectrum are still poorly defined.
Conclusions: There are some persisting "grey areas" with regard to the characterization and the clinical management of neuroendocrine tumors of the appendix. An increasing awareness of the biological and clinical aspects of this disease and new, ideally prospective, focused studies might help and clarify some relevant issues that are not fully elucidated yet and could increase the solidity of the guidance for the management and the follow-up of the patients.