Appendiceal Neuroendocrine, Goblet and Signet-Ring Cell Tumors: A Spectrum of Diseases with Different Patterns of Presentation and Outcome

Abstract

PurposeAppendiceal tumors are a heterogeneous group of diseases that include typical neuroendocrine tumors (TNET), goblet cell carcinoids (GCC), and atypical GCC. Atypical GCC are classified into signet-ring cell cancers (SRCC) and poorly differentiated appendiceal adenocarcinoids. The prognosis and management of these diseases is unclear because there are no prospective studies. The aim of this study is to assess the characteristics and outcome of appendiceal TNET, GCC, and SRCC patients.Materials and MethodsAppendiceal TNET, GCC, and SRCC patients diagnosed between 1973 and 2011 were identified in the Surveillance Epidemiology and End Results (SEER) database. Demographics, type of surgery, and clinicopathologic characteristics were collected. Survival functions were estimated by the Kaplan-Meier method, and log-rank test was used to assess the difference in overall survival (OS) among the three histologies.ResultsThe SEER database yielded 1,021 TNET patients, 1,582 with GCC, and 534 SRCC patients. TNET presented at a younger age (p < 0.001). Patients with SRCC presented with advanced stage disease (p < 0.001). The median OS (mOS) for GCC and TNET patients was not reached; mOS for SRCC was 24 months. Multivariate analysis stratified for stage revealed significantly longer survival for TNET and GCC than SRCC (p < 0.001).ConclusionThis is the largest report to date for appendiceal neuroendocrine tumor patients, suggesting a spectrum of diseases with different characteristics and outcomes. In this report, we present a treatment approach for this complex spectrum of disease, based on the experience of Ohio State and Emory Universities investigators.

Appendiceal neuroendocrine neoplasms: diagnosis and management

“…A German multicentre observational study reported aNENs displaying a 5-year OS of 83.1% vs 49.2% for non-carcinoid tumours (Benedix et al 2010). In addition, in a large series from the SEER database stratified by tumour size, the authors did not detect any significant difference in survival between patients who underwent RHC and those who underwent simple appendicectomy (Groth et al 2011), and this was confirmed by a more recent study of the same database (Shaib et al 2015), implying either that RHC does not affect the outcome or that RHC improves the outcome in patients with more severe disease. Another interesting point in this latter study is the fact that specific cancer survival rates could be calculated, as opposed to other databases collecting OS rates (Groth et al 2011) (Supplementary Table 8, see section on supplementary data given at the end of this article).…”

“…Furthermore, among 6824 black patients who underwent an appendicectomy, a similar prevalence (47.6%) of aNENs and benign non-endocrine cell tumours was reported (45.2%) (Coskun et al 2006). In a recent study from SEER, a higher proportion of white patients was observed in aNENs, but the difference was not statistically significant (Shaib et al 2015).…”

“…In terms of patient characteristics, a slightly higher incidence among females (Shaib et al 2015) has been shown in most but not all epidemiological studies (Sandor & Modlin 1998, Hemminki & Li 2001, Prommegger et al 2002, Van Gompel et al 2007, Landry et al 2008, Turaga et al 2012) -a fact that has been attributed to the increased rate of surgical interventions performed in women (Moertel et al 1968, Shapiro et al 2010, Carpenter et al 2012. A possible hormonal influence has not been proven (Graham et al 2009).…”

“…Regarding the type of surgery, in a recent study from the SEER database of 510 patients with localised disease, 7.8% had appendicectomy only, 50.2% RHC and 43% other surgery; of 300 patients with regional disease, 2.6% had simple appendicectomy, 70.7% RHC and 26.7% other surgery; all patients with distant disease had debulking surgery (Shaib et al 2015).…”

“…While previous epidemiological data considered appendiceal NENs (aNENs) to be the most common GI-NENs, the overall percentage has decreased from 17-28% to 2-5% of total NENs, following the overall increase in the relative incidence of other NENs, such as gastric and rectal, reflecting the increasing number of endoscopic procedures performed. However, in absolute terms the incidence of aNENs has increased over the past decade by 70-133% (Hauso et al 2008, Yao et al 2008 attaining in 2011 an incidence as high as 6.7 of 100 000 persons (Shaib et al 2015) possibly due to the increased number of laparoscopies performed, in particular during gynaecological surgery (Giesteira et al 1980, Heller et al 1999, Hauso et al 2008. Observational studies have shown that the natural history of these neoplasms is rather indolent, with only a minority developing extensive disease (Mullen & Savarese 2011).…”