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Review
. 2024 Apr 15;16(4):1166-1179.
doi: 10.4251/wjgo.v16.i4.1166.

Mixed neuroendocrine non-neuroendocrine neoplasms in gastroenteropancreatic tract

Sebastián Díaz-López  1 , Jerónimo Jiménez-Castro  2 , Carlos Enrique Robles-Barraza  1 , Carlos Ayala-de Miguel  1 , Manuel Chaves-Conde  1
Affiliations
Review

Mixed neuroendocrine non-neuroendocrine neoplasms in gastroenteropancreatic tract

Sebastián Díaz-López et al. World J Gastrointest Oncol. .

Abstract

Mixed neuroendocrine non-neuroendocrine neoplasms (MiNENs) are a heterogeneous group of malignant neoplasms that can settle in the gastroenteropancreatic tract. They are composed of a neuroendocrine (NE) and a non-NE component in at least 30% of each tumour. The non-NE component can include different histological combinations of glandular, squamous, mucinous and sarcomatoid phenotypes, and one or both of the components can be low-or high grade malignant. Recent changes in the nomenclature of these neoplasms might lead to great deal of confusion, and the lack of specific clinical trials is the main reason why their management is difficult. The review aims to clarify the definition of MiNEN and analyze available evidence about their diagnosis and treatment options according to their location and extension through careful analysis of the available data. It would be important to reach a general consensus on their diagnosis in order to construct a classification that remains stable over time and facilitates the design of clinical trials that, due to their low incidence, will require long recruitment periods.

Keywords: Diagnosis; Etiology; Gastroenteropancreatic; Mixed adeno-neuroendocrine carcinomas; Mixed neuroendocrine non-neuroendocrine neoplasms; Mixed tumours; Treatment.

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Conflict of interest statement

Conflict-of-interest statement: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: S. Díaz-López: Travel expenses/Congress Support: Merck, Pfizer, LEO Pharma, IPSEN Pharma; J. Jiménez-Castro: Honoraria: Servier, Merck. Travel expenses/Congress Support: Amgen; CE Robles-Barraza: Honoraria: GSK, Aztra, Pharmamar, Roche. Travel expenses/Congress support: GSK, Aztra; C. Ayala-de Miguel: Honoraria: LEO Pharma. Travel expenses/Congress Support: Pfizer, Novartis; M. Chaves-Conde: Honoraria: Merck. Travel expenses/Congress Support: Pfizer, MSD, Merck.

Figures

Figure 1
Figure 1
Evolution of the current concept over the years. MANECs: Mixed adeno-neuroendocrine carcinomas; MiNEN: Mixed neuroendocrine non-neuroendocrine neoplasms; WHO: World Health Organization.
Figure 2
Figure 2
Origin according to the theory of a common pluripotent stem cell progenitor. Non-NE: Non-neuroendocrine; NE: Neuroendocrine.
Figure 3
Figure 3
Origin according to the theory of a common monoclonal origin with a gradual process, neuroendocrine trans/dedifferentiation. Non-NE: Non-neuroendocrine; NE: Neuroendocrine.
Figure 4
Figure 4
Origin according to the theory of an epithelial and endocrine components that arise differently from precursor cells in a synchronous or metachronous manner. Non-NE: Non-neuroendocrine; NE: Neuroendocrine.
Figure 5
Figure 5
Adjuvant treatment recommendations. NET: Neuroendocrine tumours; NEC: Poorly differentiated neuroendocrine cancers; Non-NE: Non-neuroendocrine; MiNEN: Mixed neuroendocrine non-neuroendocrine neoplasms.
Figure 6
Figure 6
Metastatic treatments recommendations. NET: Neuroendocrine tumours; NEC: Poorly differentiated neuroendocrine cancers; Non-NE: Non-neuroendocrine; M: Month; 1L: First line treatment; 2L: Second line treatment; FOLFIRI: Irinotecan plus 5-fluorouracil; CAPTEM: Capecitabine plus temozolamide; BV: Bevacizumab; STZ: Streptozocin; MMR: Mismatch repair; SSTR-5: Expression of somatostatin receptor type 5; PRRT: Radiotherapy with radionuclides; AS: Somatostatin anologues; FOLFOX: Oxaliplatin plus 5-fluorouracil.
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