Update on Histological Reporting Changes in Neuroendocrine Neoplasms

Area of Science:

• Oncology
• Pathology
• Genetics

Background:

• Neuroendocrine neoplasms (NEN) classification and nomenclature have undergone frequent revisions.
• These changes stem from advancements in scientific understanding and global standardization efforts.

Purpose of the Study:

• To review recent changes in NEN classification, particularly within the Gastro-Entero-Pancreatic (GEP) system.
• To discuss the heterogeneity of NEN, including well-differentiated neuroendocrine tumors (NET) with high proliferation rates (NET G3) and pulmonary NEN nomenclature.
• To highlight the molecular heterogeneity observed in both well-differentiated NET and poorly differentiated neuroendocrine carcinomas (NEC).

Main Methods:

• Review of recent literature and international guidelines on NEN classification.
• Analysis of nomenclature changes and their impact on understanding NEN heterogeneity.
• Examination of molecular data to assess heterogeneity within different NEN subtypes.

Main Results:

• Recent GEP system changes introduced the concept of NET G3, partially explaining G3 NEN heterogeneity.
• Pulmonary NEN nomenclature, while distinct, shows overlap between 'carcinoid'/'atypical carcinoid' and NET G1/G2.
• Molecular data reveals significant heterogeneity in well-differentiated NET and poorly differentiated NEC, though clinical utility is yet to be demonstrated.

Conclusions:

• NEN exhibit considerable heterogeneity based on organ of origin, differentiation, and molecular subtypes.
• This heterogeneity presents challenges for developing personalized therapies.
• Further international collaboration, interdisciplinary efforts, and clinical trials are needed for NEN stratification based on biological subgroups.