# Proposed morphologic classification of prostate cancer with neuroendocrine differentiation

Source: https://onco.cc/key-papers/paper-epstein-neuroendocrine-prostate-morphologic-classification-ajsp-2014/  
OnCo record `paper-epstein-neuroendocrine-prostate-morphologic-classification-ajsp-2014` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

A working committee sorted the confusing family of neuroendocrine prostate cancers into named categories, so that a few scattered stained cells would stop being reported in the same words as a small cell carcinoma.

## Summary

A Prostate Cancer Foundation working committee on the molecular biology and pathologic classification of neuroendocrine differentiation in prostate cancer convened in July 2013, prompted by clinical and molecular data emerging from prostate cancers treated with contemporary androgen deprivation therapies as well as from primary lesions. The resulting classification comprises usual prostate adenocarcinoma with neuroendocrine differentiation; adenocarcinoma with Paneth cell neuroendocrine differentiation; carcinoid tumour; small cell carcinoma; large cell neuroendocrine carcinoma; and mixed neuroendocrine carcinoma with acinar adenocarcinoma. The article also highlights prostate carcinoma with overlapping features of small cell carcinoma and acinar adenocarcinoma, and castration-resistant prostate cancer with a small cell cancer-like clinical presentation.

## Fields

- Kind: Key paper
- Last checked: 2026-09-25
- Journal: American Journal of Surgical Pathology
- Year: 2014
- DOI: 10.1097/PAS.0000000000000208
- Authors: Epstein JI, Amin MB, Beltran H, et al.
- Findings: Six named categories of prostate cancer with neuroendocrine differentiation.; Two further descriptive situations for tumours with overlapping features and for clinically small cell-like castration-resistant disease.; A separation between incidental neuroendocrine staining in ordinary adenocarcinoma and a true neuroendocrine carcinoma.
- What it means: It made the reporting of these tumours mean something. The distinction it draws is the one that changes treatment: a few chromogranin-positive cells in an ordinary adenocarcinoma is not the same event as a small cell carcinoma emerging under hormonal treatment, and only the second leads to platinum and etoposide.
- Caveats: A consensus proposal rather than an outcome study.; The categories were defined before the molecular phenotyping that has since split the androgen receptor-null tumours further.; Interobserver reproducibility of the categories has not been extensively tested.

## Sources

- Epstein et al., Am J Surg Pathol 2014: proposed morphologic classification of prostate cancer with neuroendocrine differentiation (Prostate Cancer Foundation working committee): https://doi.org/10.1097/PAS.0000000000000208
- PubMed: https://pubmed.ncbi.nlm.nih.gov/24705311/

## Connected records

- cancers: [Neuroendocrine and small-cell prostate cancer](https://onco.cc/cancers/prostate-nepc/), [Prostate cancer](https://onco.cc/cancers/prostate/)
- technologies: [Histopathology & immunohistochemistry](https://onco.cc/technologies/histopathology-ihc/)
- targets: [Androgen receptor](https://onco.cc/targets/androgen-receptor/)
- pathways: [Lineage plasticity & neuroendocrine transformation](https://onco.cc/pathways/lineage-plasticity-neuroendocrine/)
- terms: [Castration-resistant prostate cancer (CRPC)](https://onco.cc/terms/castration-resistance/), [Histologic transformation](https://onco.cc/terms/histologic-transformation/), [Immunohistochemistry (IHC)](https://onco.cc/terms/ihc/)
- biomarkers: [Treatment-emergent neuroendocrine transformation (recognising it)](https://onco.cc/biomarkers/nepc-transformation/)

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