Mixed neuroendocrine non-neuroendocrine neoplasms in gastroenteropancreatic tract

Table 1 Classification of neuroendocrine component according to morphology, mitoses, and differentiation

Neuroendocrine component	Mitotic index	Ki-67
NET G1	Mitotic index < 2 per 10 high-power field	Ki-67 < 3%
NET G2	Mitotic index 2-20 high-power field	Ki-67 3%-20%
NET G3	Mitotic index > 20 high-power field	Ki-67 > 20%
Poorly differentiated neuroendocrine cancers	Mitotic index > 20 high-power field	Ki-67 > 20%

NET: Neuroendocrine tumours; G: Grade.

Table 2 Types of mixed neuroendocrine non-neuroendocrine neoplasm according to morphology

Types	Description
Collision	The juxtaposition of two populations of coexisting malignant cells that generally do not have a common precursor and are separated with no transition zone between the two
Composite	Two morphologically distinct components that coexist in an intermixed population or with a predominant component and a focal area of another minority component
Amphicrine	A population of single cells that display the phenotypes of at least two neoplasms

Table 3 Adjuvant treatment in mixed neuroendocrine non-neuroendocrine neoplasms

Ref.	Number	Location	Chemotherapy scheme	Result
Wen et al[68], 2020	n = 67	Biliary tract	Adjuvant CT-RT after R0 (n = 22) vs only surgery (n = 29); platinum and fluoropyrimidine regimens	OS, P = 0.076
Nießen et al[69], 2021	n = 13	Pancreatic	Adjuvant after surgery (n = 11); gemcitabine = 9; platinum-etoposide = 2	At 17-month follow-up, 2 patients were alive with no evidence of disease, 2 were alive with disease and 9 had died from the disease. 2 patients who had received NE regimens were alive
Zheng et al[70], 2021	n = 777	Gastric	Adjuvant after surgery (n = 198); unspecified regimen	DFS, P = 0.051
Watanabe et al[43], 2016	-	CCR	Adjuvant after surgery (MANEC n = 15 vs ADC n = 23); platinum and fluoropyrimidine regimens	DFS, P = 0.268; there were no differences between them
Wang et al[40], 2021	-	Gallbladder	Adjuvant after surgery (n = 15) vs only surgery (n = 15); capecitabine	DFS, P = 0.916

CT-RT: Chemotherapy and radiotherapy; R0: Adequate margins free of neoplasia; OS: Overall survival; NE: Neuroendocrine; DFS: Disease free survival; CCR: Colorectal cancer; MANEC: Mixed adeno-neuroendocrine carcinomas; ADC: Adenocarcinoma.