Comprehensive analysis of mixed neuroendocrine non-neuroendocrine neoplasms (MiNENs): A SEER database analysis of 767 cases

Abstract

BackgroundMixed neuroendocrine non-neuroendocrine neoplasm (MiNEN) is an extremely rare entity, consisting of neuroendocrine and non-neuroendocrine components. It can occur in various organs throughout the body, with a rising incidence. Its clinical management is a rapidly growing field of interest; however, large-scale patient cohorts are still missing to guide clinical practice.Patients and methodsThe demographic, clinicopathological, and survival information of all patients diagnosed with MiNEN in the national Surveillance, Epidemiology, and End Results (SEER) program database (2000–2017) were extracted and further analyzed. The information of the patients before and after 2010 was compared to understand the epidemiological changes of MiNEN. The characteristics of MiNEN originating in different organs were compared. The clinical significance of surgical resection for metastatic MiNENs was also analyzed.ResultsA total of 1081 patients were screened, and after applying the exclusion criteria, 767 patients were finally analyzed. There was no obvious sex preference (49.2% vs 50.8%, p>0.05) and the majority of the patients were Caucasians (n=627, 81.7%). A total of 88.3% of the patients were older than 50 years old, and the median age was 60 years. 79.3% of the tumors are located in the distal digestive tract, and 67.7% were grade 3/4. Distant metastasis was presented in 33.9% of the patients at diagnosis. A total of 88% of the patients underwent surgical treatments. The number of patients increased 10-fold between 2000 and 2017. There was no significant difference in sex, race, stage, or surgical treatments among the patients diagnosed before and after 2010. More patients older than 60 years were diagnosed after 2010 (p=0.009). The median survival was 61.0 ± 9.8 months for the whole cohort. After multivariate analysis, older age (>60 years, p<0.01), more advanced stage (p<0.01), grade 3/4 (p<0.01), and non-surgical treatment (p<0.01) were independent risk factors for poorer survival. The appendiceal MiNENs showed the best prognosis. A total of 260 metastatic MiNENs were further analyzed. Only patients with metastatic MiNENs originating from the appendix had a potential benefit from surgical resection, compared to other sites (p=0.05).ConclusionThis study provides the epidemiological, clinicopathological, and survival information of the largest number of MiNEN patients. Although MiNEN is an extremely rare malignant neoplasm, its incidence increases rapidly. The majority of the patients suffered from advanced-stage disease, which highlights the need for improvement of early detection in the future. The appendix is the most common primary site of MiNEN, and surgical resection for selected metastatic MiNEN originating in the appendix has favorable survival outcomes.

Mixed Adeno-Neuroendocrine Carcinoma of the Appendix Masquerading as Ovarian Cancer: Report of a Case

“…However, the bene t of surgical treatment for MANECs that have metastasised is unclear. A recent retrospective analysis suggests that only patients with metastatic MANECs from the appendix may bene t from surgical resection compared to other sites [23]. In terms of surgical method selection, Zhao, Bochao et al's study showed that for patients with appendiceal MANECs, regardless of lymph node metastasis, hemicolectomy has better survival bene ts than appendectomy (P<0.05) [24].…”

Incidence, survival, and prognostic factors for patients with gastrointestinal mixed neuroendocrine non-neuroendocrine neoplasms: a SEER population-based study

“…The following inclusion criteria were used: (1) tumor histological type: MiNENs (SEER histology code: 8244/3)(Song et al 2022 ), and NETs (SEER histology codes: 8013/3, 8041/3, 8150/3–8157/3, 8240/3, 8241/3, 8242/3, 8243/3, 8246/3, 8249/3) (Cai et al 2022 ; Shah et al 2019 ; Miao et al 2018 ); (2) confirmation of MiNENs and NETs diagnosis histologically or microscopically. The following were the exclusion criteria: (1) survival time was unknown; (2) incomplete clinical and pathological data.…”

Gastric mixed neuroendocrine non-neuroendocrine neoplasms

“…However, the adjuvant therapies for these two components are quite different ( 84 ). In addition, although a number of molecularly targeted drugs and immunotherapies have been initially used to treat MiNENs, evidence of efficacy is limited ( 1 , 85 , 86 ). Given that certain intermediate MiNENs frequently exhibit a significant presence of type 2 somatostatin receptors, it is plausible that patients with such conditions might potentially derive therapeutic benefits from the administration of long-acting somatostatin analogues and peptide-irradiated nucleotide treatment ( 56 ).…”

“…A subgroup of gastric tumours known as g-MiNENs, or gastric mixed neuroendocrine-non-neuroendocrine neoplasms, is morphologically diverse and clinically aggressive. Most individuals with MiNENs are older than 50 years of age, and most MiNENs are discovered at an advanced stage of illness ( 1 ). As awareness of MiNEN increases and diagnostic techniques improve, the number of patients tends to increase ( 2 ).…”