Table 2.
| Characteristics | NEC | NET |
|---|---|---|
| Proportion of GEP-NENs | 10% | 90% |
| Proportion of all extrapulmonary NECs | One-third | - |
| Incidence trend | Increasing | Increasing |
| Association with smoking history | Weak | Weak |
| Sex | Male > female | Male = female |
| Median age | 60–70 years | 60 years |
| Location of primary tumor | Colorectum, pancreas, and esophagus-stomach | Rectum, pancreas, and stomach in Asia, and small intestine and appendix in Europe |
| Diagnosis at a metastatic stage | 60 to 85% | 20% |
| Most common sites of metastases | Lymph node, liver, and peritoneum | Liver |
| Brain metastases | Rare | Rare |
| Prognostic outcomes | Poor (5–8 months) | Good (20–53 months), 18–40 months for G3 NET |
| Survival trend | Improving | Stable |
| Neuroendocrine differentiation markers | Diffuse positive (INSM1 and Syn) and focal/faint positive (CgA) | Strong positive (INSM1, Syn, and CgA) |
| SSTRs expression | Weak to absent | Strong |
| Hormone | Weak to absent | Strong |
| Ki-67 index | High (typically ≥ 55%) | Low (typically < 55%) |
| Mitosis | High | Low |
| Morphology | Sheet-like architecture, abundant necrosis, and high nuclear/cytoplasm ratio | Organoid or nested architecture, including trabecular, glandular, or solid patterns; minimal necrosis; round nuclei; and finely granular cytoplasm |
| Morphology of SCNEC | Similar to SCLC, which is composed of relatively small cells with a high nuclear/cytoplasmic ratio, tightly packed fusiform nuclei, hyperchromatic and finely granular chromatin, and inconspicuous nucleoli | - |
| Morphology of LCNEC | Round to polygonal large cells with moderate amounts of cytoplasm, more rounded nuclei, vesicular chromatin, and prominent nucleoli | - |
| Proportion of small cell versus large cell morphology | 40% vs. 60% | - |
| Predominant small cell morphology | Esophagus, anal, and gallbladder | - |
| Predominant large cell morphology | Small intestine, colorectum, stomach, liver, biliary tract, and pancreas | - |
Abbreviations: GEP, gastro-entero-pancreatic; NEN, neuroendocrine neoplasm; NET, neuroendocrine tumor; NEC, neuroendocrine carcinoma; SCNEC, small cell neuroendocrine carcinoma; LCNEC, large cell neuroendocrine carcinoma; CgA, chromogranin A; Syn: synaptophysin; INSM1, insulinoma-associated protein 1; SSTR, somatostatin receptor