Neuroendocrine neoplasms of gastrointestinal tract and secondary primary synchronous tumors: A systematic review of case reports. Casualty or causality?

Abstract

Background Neuroendocrine neoplasms (NENs) can arise in most of the epithelial organs of the body and are not a rare condition in the gastrointestinal tract (GIT). The presence of NENs in GIT associated with other secondary primary malignancies (SPM) has been considered an exotic event. This study aims to describe the case reports of NENs accompanied by synchronous primary tumors. Methods and findings We performed a systematic literature search of the databases Scopus, PubMed, Scielo and LILACS to identify case reports that described the presence of NENs in GIT with SPM. 78 case reports were included. The mean of age of the cases was 60.2 years. 60% were male. 95.4% were NENs G1. 17 cases of NENs had metastasis. 80% of SPM were recognized in the GIT (36% in stomach, 27% in large intestine, 11.2% in small intestine, and 5.6% in esophagus). The most common type of SPM was adenocarcinoma (49.4%), followed by GIST (13.5%), other NENs in different GIT segment (7.9%), lymphoma (6.8%), and squamous cell carcinoma (4.5%). The most common tumor in GIT was adenocarcinoma (97.6%) and the presence of adenocarcinoma in the same segment of GIT was found in 68.4% of the cases. Association between adenocarcinomas and NENs in GIT (p:<0.0001) and adenocarcinoma and tumor in the same segment of GIT location were observed (p<0.001). Conclusion These results demonstrate that NENs with SPM are not a rare condition. Several theories have been proposed to explain this association; one of these is the ability of NENs to generate synchronous tumors by autocrine and paracrine effect. We observed an association between adenocarcinomas and NENs in the same segment of GIT.

Multiple liver metastases originating from synchronous double cancer of neuroendocrine tumor and rectal cancer: a case report

“…However, SPMs have been reported to occur in only 6% of patients with rectal NETs in Japan [19], and the frequency of SPMs with NETs differs between Japan and Western nations. A total of 80% of SPMs are recognized in the gastrointestinal tract, and the most common type of SPM is adenocarcinoma (49.4%) [20]. The pathogenesis of NETs associated with SPMs remains unclear but may be rooted in the tumorigenic properties of the various neuroendocrine peptides expressed and secreted by neuroendocrine cells.…”

“…The pathogenesis of NETs associated with SPMs remains unclear but may be rooted in the tumorigenic properties of the various neuroendocrine peptides expressed and secreted by neuroendocrine cells. Peptides such as secretin, gastrin, bombesin, cholecystokinin, and vasoactive intestinal peptide are believed to promote the proliferation of tumor cells [3,20]. Prognosis is affected by the progression of SPMs and the exacerbation of NET metastatic lesions rather than the primary lesion of NETs [21].…”

Ampullary Adenocarcinoma with Incidental Pancreatic Neuroendocrine Tumor: Report of an Extremely Rare Case and Review of Literature

“…Five-year survival rates are about 30% in non-functioning PanNETs and up to 97% in surgical resectable functioning PanNETs. The synchronous presence of a second primitive tumor in patients affected by GEP-NENs is reported in the literature; incidence is variable from 12% to 46%, and the most common site is the GI tract [3,14-16]. This setting may be explained by “field-effect theory,” whereby a single carcinogenic agent could stimulate the development of both tumors [17-18].…”

“…Moreover, NETs produce several neuropeptides/non-neuropeptides comparable to a growth factor and could promote the development of a synchronous primitive tumor within target organs [19]. Therefore, investigating the presence of a synchronous primitive tumor in patients affected by NET is recommended [3].…”

“…Neuroendocrine neoplasms (NENs) can arise throughout the entire body from neuroendocrine cells; they are often found in the lungs and gastroenteropancreatic (GEP) system, less frequently in the skin, breast, and genitourinary tract [2]. A relationship exists between the presence of GEP-NENs and the simultaneous presence of primitive neoplasms in other body regions [3-4].…”