# Epithelial Neuroendocrine Neoplasms: Grading Based on the New WHO 2022 Guidelines

**Authors:** Rizwana Shaik, Inuganti Venkata Renuka, Bakkamanthala S K Kanth, Leela Lahari Arikathota

PMC · DOI: 10.7759/cureus.102857 · 2026-02-02

## TL;DR

This paper discusses the grading of epithelial neuroendocrine tumors based on new 2022 WHO guidelines.

## Contribution

The paper introduces updated grading criteria for epithelial neuroendocrine neoplasms per the new WHO 2022 guidelines.

## Key findings

- Epithelial neuroendocrine tumors are typically slow-growing and can arise in various body sites.
- Grading these tumors helps distinguish them from carcinomas based on proliferative activity.
- The incidence of these tumors has increased, possibly due to better awareness and diagnostics.

## Abstract

Neuroendocrine tumors (NETs) are rare. Epithelial NETs are generally considered slow-growing tumors. Arising from neuroendocrine cells, NETs can develop at various primary sites in the body.

Gastrointestinal NETs are the most common of all NETs. The ileum, appendix, and rectum are among the most common sites, followed by the colon, stomach, and duodenum; some series report a female preponderance.

Bronchopulmonary NETs are relatively rare and are often indolent in nature.

In recent decades, the incidence has been rising. This may be due to greater awareness, improved diagnostic tools, or changes in definitions/classification. Grading of epithelial neuroendocrine neoplasms is beneficial, as it allows tumors to be graded by proliferative activity and distinguished from neuroendocrine carcinomas.

## Full-text entities

- **Genes:** MIB1 (MIB E3 ubiquitin protein ligase 1) [NCBI Gene 57534] {aka DIP-1, DIP1, LVNC7, MIB, ZZANK2, ZZZ6}, SYP (synaptophysin) [NCBI Gene 6855] {aka MRX96, MRXSYP, XLID96}, INSM1 (INSM transcriptional repressor 1) [NCBI Gene 3642] {aka IA-1, IA1}, CHGA (chromogranin A) [NCBI Gene 1113] {aka CGA, PHE5, PHES}
- **Diseases:** Pituitary adenomas (MESH:D010911), lung NENs (MESH:D008175), Lung NET (MESH:D008171), Tumors (MESH:D009369), MTC (MESH:C536911), intestinal, colonic, rectal, appendiceal, and pancreatic NETs (MESH:D007414), small cell carcinoma (MESH:D018288), SCLC (MESH:D055752), PD-NECs (MESH:D010300), GEP NET (MESH:C535650), MCT (MESH:C536914), Lung NETs (MESH:D018358), WD-NENs (MESH:D006527), Endocrine Tumors (MESH:D004701), NECs (MESH:D018278), Epithelial Neuroendocrine Neoplasms (MESH:D009375), necrosis (MESH:D009336), thymic (MESH:D013953), carcinoids (MESH:D002276)
- **Chemicals:** paraffin (MESH:D010232), Abdulfattah (-), H&amp;E (MESH:D006371), hematoxylin (MESH:D006416), alcohol (MESH:D000438), serotonin (MESH:D012701), formalin (MESH:D005557)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Figures

7 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12960784/full.md

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Source: https://tomesphere.com/paper/PMC12960784