Neuroendocrine, goblet cell and mixed adeno-neuroendocrine tumours of the appendix: updates, clinical applications and the future

Abstract

Appendiceal neuroendocrine neoplasms are rare, clinically challenging tumours that are typically incidentally diagnosed, have a poorly understood biology and have controversy surrounding their management. Most are adequately treated with appendectomy, and although distant metastases are rare, the threat of disease dissemination remains and current guidelines possess poor accuracy in terms of selecting patients requiring more extensive surgery, i.e. oncological right-hemicolectomy. Areas covered: In this article, we discuss the presentation and diagnostic work-up of patients with appendiceal neuroendocrine neoplasms, and also examine the evidence base for existing management strategies. We highlight controversies within the management of these tumours, and anticipate avenues for further progress. Although no longer classified as neuroendocrine neoplasms, we also discuss two related forms of tumours with neuroendocrine features - goblet cell cancers and mixed adeno-neuroendocrine carcinomas. Expert commentary: Existing guidelines for the treatment of appendiceal neuroendocrine neoplasms are derived from a limited evidence base and are unable to accurately predict which patients require extensive attempts at surgical disease control. Future advances in the field of improved patient selection for more extensive surgery may be possible with multi-factorial tumour assessment integrating morphological and molecular analyses.

Neuroendocrine Neoplasms of the Appendix: A Review of the Literature

“…Fewer than 10% of ANENs refer to tumors larger than 2 cm (T2 in UICC/AJCC staging system and T3 in ENETS guidelines). These neoplasms carry a substantially higher risk for systemic dissemination (up to 40%) (63-65) and, therefore, a broader oncological procedure as well as longer follow-up time are warranted (65,66). ANENs of higher stages which have already spread beyond the appendix either invading the peritoneum or other adjacent organs (T4 in all TNM staging systems) or the lymph nodes (stage N1), or tumors that have metastasized to distant locations (stage M1) are considered systemic disease and require a multidisciplinary team approach for adequate treatment (1,34,36).…”

Goblet Cell Carcinoid of Appendix: Report of Two Cases and Review of Controversial Aspects

“…On this way, chromogranin A and synaptophysin are focally positive. Other markers as CEA, CDX-2, CAM5.2 and CK20, CK 7 and CK19 are more evident in immunohistochemistry [4]. Tang reported negativity for MUC1 and preserved staining for MUC2 at groups A and B. Conversely, group C displayed expression of MUC1 and loss of MUC2 [10].…”

“…Some centers recommend right hemicolectomy for all GCCs; however, others highlight that GCC is a peritoneal disease and right hemicolectomy should be performed only in selected cases. Similarly, HIPEC should be considered in some cases, and always in centers of excellence [1,4]. We report two cases of goblet cell carcinoids: group A and B, and review management and controversial points.…”

“…specimens after appendectomy [3][4][5]. They most occurr in caucasians with mean age of 52 years old and no differences in gender have been reported.…”

“…In 2010, WHO determined that GCCs are a subtype of mixed adenoneuroendocrine carcinoma (MANEC) and consequently, they are under neuroendocrine category [6]. In general, it is accepted that their behavior is more aggressive than neuroendocrine and show better prognosis than adenocarcinoma [4]. Their origin is also motive of controversy.…”