Table 1.
Classifications of GEP-NENs
| NEN classification according to embryological origin37 | |
|---|---|
| Foregut | NEN originating from the thymus, respiratory tract, esophagus, stomach, pancreas, duodenum, and ovaries |
| Midgut | NEN originating from the jejunum, ileum, appendix, cecum, ascending colon, and Meckel’s diverticulum |
| Hindgut | NEN originating from the transverse, descending, and sigmoid colon |
| GEP-NEN classification according to grade of differentiation38,a | |
| Well-differentiated tumors (“carcinoid”) | Mild or no atypia, restricted to the mucosa or submucosa, absence of angioinvasion, tumor size <1 cm, and proliferation rate <2 mitoses/10 HPFs or Ki-67 <2% |
| Well-differentiated carcinomas (“malignant carcinoid”) | Malignant endocrine tumor cells, moderate atypia, deep invasion of the gut wall, often metastases to regional lymph nodes or liver, tumor size >1 cm, and proliferation rates >2 mitoses/10 HPFs or Ki-67 index >2% |
| Poorly differentiated carcinomas (“small cell carcinoma”) | Highly atypical, small- to intermediate-sized tumor cells, deep invasion or destruction of the gut wall, often necrosis and angio- and perineural invasion, local and distant metastases, size >1 cm, and proliferation rates of >10 mitoses/10 HPFs or Ki-67 index of >15% |
| Mixed exocrine–endocrine tumors | Unusual bimorphous tumors. Prominent exocrine cells (acinar or ductal) admixed with at least 30% endocrine component. Biological behavior of the exocrine component |
| Tumor-like lesion | |
| WHO 2010 classification35
| |||
|---|---|---|---|
| Neuroendocrine neoplasm typeb | Grade | Ki-67 indexc | Mitotic count (per 10 HPFs)d |
| Neuroendocrine tumor | G1 | ≤2% | <2 |
| Neuroendocrine tumor | G2 | 3%–20% | 2–20 |
| Neuroendocrine carcinoma | G3 | >20% | >20 |
| Mixed adenoneuroendocrine carcinoma | G1–G3 (mostly G3 component) | All ranges | All ranges |
Notes:
a
In the WHO 2000 classification of GEP-NENs, large cell carcinomas were mentioned under the stomach, colon, and rectum sections, but no other classification criteria were described.
b
The WHO recommends the use of the term “neuroendocrine neoplasm” to indicate low- to high-grade lesions. However, the term “neuroendocrine tumor” is still widely used. The term “neuroendocrine carcinoma” indicates high-grade lesions.
c
Ki-67 index: % of 500–2,000 cells in “hot spot areas” stained positive for MIB-1 antibody.
d
10 HPFs =2 mm2, based on measurement in at least 50 HPFs in hot spot areas.
Abbreviations: GEP, gastroenteropancreatic; HPFs, high-power fields; NENs, neuroendocrine neoplasms; WHO, World Health Organization.