Mixed epithelial endocrine neoplasms of the colon and rectum – An evolution over time: A systematic review

Abstract

BACKGROUND Mixed tumors of the colon and rectum, composed of a combination of epithelial and endocrine elements of benign and malignant potential are rare neoplasms. These can occur anywhere in the gastrointestinal tract and are often diagnosed incidentally. Though they have been a well-documented entity in the pancreas, where the exocrine-endocrine mixed tumors have been known for a while, recognition and accurate diagnosis of these tumors in the colon and rectum, to date, remains a challenge. This is further compounded by the different terminologies that have been attributed to these lesions over the years adding to increased confusion and misclassification. Therefore, dedicated literature reviews of these lesions in the colon and rectum are inconsistent and are predominantly limited to case reports and case series of limited case numbers. Though, most of these tumors are high grade and of advanced stage, intermediate and low grade lesions of these mixed tumors are also increasingly been reported. There are no established independent consensus based guidelines for the therapeutic patient management of these unique lesions. AIM To provide a comprehensive targeted literature review of these complex mixed tumors in the colon and rectum that chronicles the evolution over time with summarization of historical perspectives of terminology and to further our understanding regarding their pathogenesis including genomic landscape, clinicoradiological features, pathology, treatment, prognosis, the current status of the management of the primary lesions, their recurrences and metastases. METHODS A comprehensive review of the published English literature was conducted using the search engines PubMed, MEDLINE and GOOGLE scholar. The following search terms [“mixed tumors colon” OR mixed endocrine/neuroendocrine tumor/neoplasm/lesion colon OR adenocarcinoma and endocrine/neuroendocrine tumor colon OR mixed adenocarcinoma and endocrine/neuroendocrine carcinoma colon OR Amphicrine tumors OR Collision tumors] were used. Eligibility criteria were defined and all potential relevant items, including full articles and/or abstracts were independently reviewed, assessed and agreed upon items were selected for in-depth analysis. RESULTS In total 237 full articles/abstracts documents were considered for eligibility of which 45 articles were illegible resulting in a total of 192 articles that were assessed for eligibility of which 139 have been selected for reference in this current review. This seminal manuscript is a one stop article that provides a detailed outlook on the evolution over time with summarization of historical perspectives, nomenclature, clinicoradiological features, pathology, treatment, prognosis and the current status of the management of both the primary lesions, their recurrences and metastases. Gaps in knowledge have also been identified and discussed. An important outcome of this manuscript is the justified prop...

A rare case of poorly differentiated mixed neuroendocrine-nonneuroendocrine tumor of the caecum with long term survival: A case report

“…Colorectal MiNENs belong to the most frequent types of which 85% are poorly differentiated neuroendocrine carcinomas containing a non-endocrine component in 25-40% of cases, usually adenocarcinoma (Li et al 2011;Karkouche et al 2012;La Rosa et al 2012;de Mestier et al 2017). However, the true prevalence of colorectal MiNENs is unknown or underestimated (Komatsubara et al 2016;Watanabe et al 2016;Kanthan et al 2020). The median age at diagnosis is 64-72 years (La Rosa et al 2012;Komatsubara et al 2016;Watanabe et al 2016).…”

“…The median age at diagnosis is 64-72 years (La Rosa et al 2012;Komatsubara et al 2016;Watanabe et al 2016). Reported symptoms in the majority of cases (69%) include abdominal pain and obstructive signs such as nausea, vomiting, abdominal dilatation, malaise, and weight loss (Kanthan et al 2020). Although the patient's symptomatology depends on the primary tumor's size and its ability to secrete neuroamines and peptides, the diagnosis is often delayed because most of these tumors (90%) do not secrete biologically active hormones.…”

Mixed neuroendocrine/Non-neuroendocrine neoplasm (MiNEN) of gastrointestinal lineage arising in an ovarian mature cystic teratoma

“…The other reported cases with a synchronous neuroendocrine tumor include the following: a case of mucinous cystadenocarcinoma and a stromal carcinoid tumor with synchronous cervical cancer Kanthan et al, 2020 , a case of malignant papillary thyroid carcinoma in the setting of struma ovarii and a carcinoid tumor Cagino et al, 2020 , and a case of stromal carcinoid tumor, papillary thyroid carcinoma in the setting of struma ovarii, and mucinous adenocarcinoma Hinshaw et al, 2012 . In these cases, the patients were 48, 62, and 74 years old with MCTs that were 10 cm or greater on pre-operative imaging.…”

“…The patient with the synchronous cervical cancer was treated with exploratory laparotomy, Hartmann’s operation, hysterectomy and bilateral salpingo-oophorectomy. Re-operation for full staging was recommended, but the patient declined, and she was then treated with adjuvant chemotherapy and radiation Kanthan et al, 2020 . The other two patients were treated with surgery alone including hysterectomy with bilateral salpingectomy and either unilateral or bilateral oophorectomy followed by close surveillance Cagino et al, 2020 , Hinshaw et al, 2012 .…”

Collision carcinoma of the rectum involving neuroendocrine carcinoma and adenocarcinoma: A case report

“…Rectal cancer is the most common type of gastrointestinal cancer, and adenocarcinoma is the most common pathological type. Collision tumor refers to a tumor, composed of two components, which are difficult to distinguish from each other[ 1 ]. It represents a tumor, which includes two adjacent tumors but these tumors are histologically distinct.…”