What are the types and definition of Neuroendocrine Tumors (NETs)?

From the Guidelines

Neuroendocrine Tumors (NETs) are a heterogeneous group of neoplasms that arise from the diffuse neuroendocrine cell system and can be classified into well-differentiated NETs and poorly differentiated neuroendocrine carcinomas (NECs).

Types of NETs

• Well-differentiated NETs, which are the most common type, can be further divided into:
  • Carcinoids (about two-thirds of NETs) 1
  • Pancreatic endocrine tumors (PETs) (about one-third of NETs) 1
• Poorly differentiated neuroendocrine carcinomas (NECs), which represent only 10%–20% of all NETs 1

Definition of NETs

NETs are characterized by their ability to produce and secrete hormones, and can be classified according to their site of origin, hormonal activity, and histopathological characteristics 1. The WHO has issued guidance on the classification of NETs according to histopathological characteristics, and the molecular biology of NETs is still poorly understood but emerging data suggest that molecular profiling and identification of common genetic elements may enhance tumour classification and identify potential targets that may be involved in tumour progression 1.

Classification of NETs

NETs can be classified according to their cell characteristics, with low, intermediate, and high malignant potential 1. They can also be classified by site of origin and hormonal activity, with examples including carcinoids, pancreatic endocrine tumors, gastrinomas, insulinomas, and glucagonomas 1. The TNM classification system is also used to classify NETs, with specific criteria for endocrine tumors of the duodenum/ampulla/proximal jejunum 1.

From the Research

Definition of Neuroendocrine Tumors (NETs)

• Neuroendocrine tumors (NETs) are a heterogeneous group of neoplasms that originate from the neuroendocrine cell system, characterized by embryological, biological, and histopathological differences 2.
• NETs are epithelial neoplasms with predominantly neural and endocrine differentiation, having the ability to produce peptide hormones and other biologically active substances 3.

Types of Neuroendocrine Tumors (NETs)

• Well-differentiated, low-proliferating NETs, also called carcinoids, and poorly differentiated, highly proliferating neuroendocrine carcinomas (NECs) are the two fundamentally different groups of NETs 4.
• NETs can be classified based on their embryonic gut derivative, including foregut, midgut, and hindgut, with midgut tumors being the most common 5.
• The most common sites for NETs are the lung, small bowel, pancreas, and appendix 6.
• Specific types of NETs include:
  • Typical carcinoids (TCs)
  • Atypical carcinoids (ACs)
  • Small cell lung cancer (SCLC)
  • Large cell neuroendocrine cancer (LCNEC)

Classification and Grading of NETs

• The World Health Organization (WHO) classification of gastrointestinal NETs uses the Ki67 proliferation index to grade NETs as G1 or G2, and NECs as G3 4.
• The WHO classification of pancreatic NENs introduced a new NET G3 category in 2017, which can be distinguished from NECs by the expression of p53 and rb1 4.
• The classification and grading of NETs are crucial for determining prognosis and treatment 3.