Stomach
Neuroendocrine tumors
Neuroendocrine-classification
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PubMed Search: Stomach neuroendocrine neoplasms
Table of Contents
Definition / general | Major updates | WHO (2019) | Diagrams / tables | Microscopic (histologic) images | Additional references | Practice question #1 | Practice answer #1 | Practice question #2 | Practice answer #2Cite this page: Mahjabin F, Assarzadegan N. Neuroendocrine-classification. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/stomachneuroendocrineclassification.html. Accessed September 18th, 2025.
Definition / general
- New WHO classification of tumors of the stomach (5th edition), published in 2019
- Classification of neuroendocrine neoplasms (NENs) is one of the most important updates covered in this edition (Arch Pathol Lab Med 2021;145:664)
- Mixed neuroendocrine nonneuroendocrine neoplasm (MiNEN) is defined as a tumor with neuroendocrine and nonneuroendocrine components, each comprising at least 30% of the neoplasm based on morphology and immunohistochemistry
Major updates
- Grading
- G3 category
- Older classifications equated G3 with poor differentiation (neuroendocrine carcinoma / NEC)
- Current classification acknowledges that well differentiated neuroendocrine tumors (NET) in various organs can be high grade (G3) (Am J Surg Pathol 2015;39:683, Clin Cancer Res 2016;22:1011)
- Poorly differentiated NECs are considered high grade by default; new proposal removes the assignment of a grade to NECs to avoid confusion with G3 NETs (Arch Pathol Lab Med 2021;145:664)
- Ki67 proliferation index
- Cannot be solely used to distinguish NETs from NECs, as some NETs can have high Ki67 values
- G3 category
- Terminology changes
- Well differentiated NETs were previously called carcinoid tumors when in the gastrointestinal tract
- The term NEC is now only used for poorly differentiated neoplasms, although formerly it was also used for well differentiated NETs with signs of malignant activity such as metastasis (Clin Colon Rectal Surg 2006;19:45)
WHO (2019)
-
Terminology ICD-O code
- Neuroendocrine tumor (NET) 8240/3
- Neuroendocrine carcinoma (NEC) 8246/3
- Mixed neuroendocrine nonneuroendocrine neoplasm (MiNEN) 8154/3
Diagrams / tables
Grading criteria of NENs
| Terminology | Differentiation | Grade | Mitotic count (mitoses/2 mm2) | Ki67 index |
| NET, G1 | Well differentiated | Low | < 2 | < 3% |
| NET, G2 | Intermediate | 2 - 20 | 3 - 20% | |
| NET, G3 | High | > 20 | > 20% | |
| NEC, small cell type (SCNEC) | Poorly differentiated | High | > 20 | > 20% |
| NEC, large cell type (LCNEC) | > 20 | > 20% | ||
| MiNEN | Well or poorly differentiated | Variable | Variable | Variable |
Microscopic (histologic) images
Contributed by FNU Mahjabin, M.B.B.S.
Well differentiated neuroendocrine tumor
Small cell neuroendocrine carcinoma
Large cell neuroendocrine carcinoma
Mixed neuroendocrine nonneuroendocrine neoplasm
Synaptophysin immunostain
Chromogranin immunostain
Ki67 immunostain
Additional references
Practice question #1
The tumor morphology shown in the image above is most consistent with which of the following neuroendocrine neoplasms?
- Large cell neuroendocrine carcinoma (NEC)
- Mixed neuroendocrine nonneuroendocrine neoplasm (MiNEN)
- Small cell neuroendocrine carcinoma (NEC)
- Well differentiated neuroendocrine tumor (NET)
Practice answer #1
A. Large cell neuroendocrine carcinoma (NEC). Large cell NEC is characterized by large round vesicular nuclei, with prominent nucleoli, moderate to abundant eosinophilic cytoplasm and numerous mitotic figures.
Answer D is incorrect because well differentiated NET is usually composed of nests of monotonous tumor cells, which have oval nuclei with salt and pepper chromatin and absent or a very few mitotic figures.
Answer C is incorrect because the tumor cells of small cell NEC are characterized by pleomorphic, hyperchromatic nuclei with high N:C ratio and nuclear molding.
Answer B is incorrect because MiNEN is a mixed tumor of neuroendocrine and nonneuroendocrine components, each comprising ≥ 30% of the neoplasm both morphologically and by immunohistochemistry.
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Reference: Stomach - Neuroendocrine-classification
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Reference: Stomach - Neuroendocrine-classification
Practice question #2
What is the minimum percentage of each tumor component required by WHO criteria to qualify as a mixed neuroendocrine nonneuroendocrine neoplasm (MiNEN)?
- 10%
- 20%
- 30%
- 40%
Practice answer #2
C. 30%. The WHO classification of mixed neuroendocrine nonneuroendocrine neoplasms (MiNENs) requires that each component (neuroendocrine and nonneuroendocrine) comprises at least 30% of the tumor. Answers A, B and D are incorrect because according to WHO, these are the essential diagnostic criteria to be classified as MiNEN: a mixed tumor composed of at least 2 components, ≥ 30% of the neoplasm should be composed of each type and the neuroendocrine component must be substantiated by immunohistochemistry.
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Reference: Stomach - Neuroendocrine-classification
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Reference: Stomach - Neuroendocrine-classification
