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neuroendocrine tumors

Monday 28 June 2004



Definition: Neuroendocrine tumors (NETs) are neoplasms that arise from cells of the endocrine (hormonal) and nervous systems. Many are benign, while some are malignant. They most commonly occur in the intestine, but they are also found in the pancreas, lung and the rest of the body.

Benign neuroendocrine tumors (NETs), previously called "carcinoid tumors", are neoplasms of enterochromaffin/neuroendocrine cell origin which display neurosecretory capacity that may result in the carcinoid syndrome.

The annual incidence of patients with NET is 8.4 per 100000; yet many NET remain asymptomatic and clinically undetected. A majority of NET follows a benign course; however, some will display malignant characteristics.


- pulmonary neuroendocrine tumors
- digestive neuroendocrine tumors
- mediastinal neuroendocrine tumors

NET most commonly occur in the gastrointestinal tract (67%) and bronchopulmonary system (25%). Gastrointestinal NET occur within the stomach, small intestine, liver, and rectum.


The key feature of the 2017 classification is a distinction between differentiated neuroendocrine tumors (NETs), also designated carcinoid tumors in some systems, and poorly differentiated neuroendocrine tumors or neuroendocrine carcinomas (NECs), as they both share common expression of neuroendocrine markers.

In many organ systems, NETs are graded as G1, G2, or G3 based on mitotic count and/or Ki-67 labeling index, and/or the presence of necrosis. NECs are considered high grade by definition.

The World Health Organization (WHO) classification scheme places neuroendocrine tumors into three main categories, which emphasize the tumor grade rather than the anatomical origin:
- well-differentiated neuroendocrine tumors, further subdivided into tumors with benign ("typical carcinoid tumor") and those with uncertain behavior ("atypical carcinoid tumor")
- well-differentiated (low grade) neuroendocrine carcinomas with low-grade malignant behavior
- poorly differentiated (high grade) neuroendocrine carcinomas, which are :


- Old WHO 2010 compared to the new WHO 2017 grading of neuroendocrine tumours (NETS) from new WHO blue book.

Digital cases

- JRC:481 : High-grade neuroendocrine carcinoma (possibly anaplastic medullary carcinoma)
- JRC:1591 : Spindle cell carcinoid tumor of the lung


- thyroid medullary carcinoma
- neuroendocrine carcinoma
- paraganglioma
- parathyroid adenoma
- carcinoid tumor


- pancreatic neuroendocrine tumors
- digestive neuroendocrine tumors
- thyroid neuroendocrine tumors
- pulmonary neuroendocrine tumors


- multifocal neuroendocrine tumors


- Grading with Ki-67 (22895268)


- 11q LOH (21%) (15920555)
- 16q (13%) (15920555)
- 18 (30%) (15920555)
- BRAF locus

See also

- neuroendocrine organs
- neuroendocrine markers

Open references

- A common classification framework for neuroendocrine neoplasms: an International Agency for Research on Cancer (IARC) and World Health Organization (WHO) expert consensus proposal. 2018.

Paywall References

- Algorithmic approach to neuroendocrine tumors in targeted biopsies: Practical applications of immunohistochemical markers. 2018. PMID: 27529763 doi : 10.1002/cncy.21765

- Grading of Neuroendocrine Tumors With Ki-67 Requires High-quality Assessment Practices. Remes SM, Tuominen VJ, Helin H, Isola J, Arola J. Am J Surg Pathol. 2012 Sep;36(9):1359-63. PMID: 22895268

- Chung DC. Cyclin D1 in human neuroendocrine tumorigenesis. Ann N Y Acad Sci. 2004 Apr;1014:209-17. PMID: 15153436