Appendiceal Goblet Cell Carcinoids: Management Considerations from a Reference Peritoneal Tumour Service Centre and ENETS Centre of Excellence

Abstract

Background: Appendix goblet cell carcinoids are known to share histological features of adenocarcinoma and neuroendocrine tumours. Due to their low incidence, quality evidence is lacking for the management of these patients. Methods: We performed a single-centre retrospective study of patients with a confirmed diagnosis of appendiceal goblet cell carcinoid (GCC; 1996-2014). Patients were divided into curative intent (CI) and palliative intent (PI) cohorts. Our primary end point was overall survival (OS). Results: Seventy-four patients were eligible; 76% were treated with CI [surgery only (36%), cytoreductive surgery (CRS) and hyperthermic intra-peritoneal chemotherapy (HIPEC; 36%), adjuvant chemotherapy (20%) and a combination of CRS and HIPEC followed by adjuvant chemotherapy (9%)], and 23% had advanced-stage disease amenable to palliative treatment (chemotherapy or supportive care) only. Completion right hemicolectomy, performed in 64% of the CI cohort, did not impact on the relapse rate or disease-free survival. FOLFOX chemotherapy was used in both the adjuvant and palliative settings; safety was as expected, and we observed a high rate (60%) of disease control in the palliative cohort. The estimated median OS (all patients), disease-free survival (CI patients) and progression-free survival (PI patients) were 52.1 (95% CI 29.4-90.3), 75.9 (26.6-not reached) and 5.3 (0.6-5.7) months, respectively. Age and stage were independent factors associated with OS in the multivariable analysis. Tang classification showed a trend for impact on OS. No benefit from specific adjuvant approach was identified; however, selection bias for treatment approach was observed. Conclusion: Prospective trials are needed to define optimal approaches in GCC. All GCC patients should be managed by specialized centres due to their esoteric behaviour; we provide management considerations based on our experience and conclusions.

ENETS Consensus Guidelines for Neuroendocrine Neoplasms of the Appendix (Excluding Goblet Cell Carcinomas)

“…Neither is considered a NET, and thus beyond the scope of these guidelines. The management of these neoplasms should be tailored to the respective adenocarcinomas [46,56,66]. …”

Goblet cell carcinoids of the appendix: Tumor biology, mutations and management strategies

“…They are most often diagnosed incidentally during appendectomy or ileocecal resection and confirmed by the pathologist in post-surgical specimens. About 27% of patients may present with perforated appendicitis[9]. Patients may also present sub-acutely in advanced stages with vague abdominal pain and mass[7,8].…”

“…Solid organ metastases to liver, lung, bones are uncommon[8]. A previous study reports the rate of metastases to lymph nodes increases with the T stage of the tumor T2 (0%), T3 (13%), T4 (60%)[9]. …”

“…The significance remains unknown as some groups have shown worsening survival rates with rising Ki67 index[19,27] while other have shown no correlation[9,28,29]. Positive staining for p53 and MUC1 with loss of MUC2 expression is suggestive of transformation to adenocarcinoma phenotype similar to colorectal adenocarcinoma[8].…”

Peritoneal Metastases from Gastroenteropancreatic Neuroendocrine Tumors

“…adjuvant chemotherapy. 10 Such tumors display neuroendocrine features but must be clearly distinguished from the far more indolent ANET with rigorous immunohistopathological examination; however, this has not been widely recognized until relatively recently. Of note, the European Neuroendocrine Tumor Society no longer includes discussion of GCC in their current guidelines for ANET, 11 which was present in the previous iteration published in 2012.…”