From the Guidelines
A neuroendocrine tumor is a rare and heterogeneous tumor that arises from neuroendocrine cells, which possess characteristics of both nerve and hormone-producing cells, and can be classified into different categories based on the WHO 2022 classification, including neuroendocrine tumors (NET) G1, NET G2, NET G3, and neuroendocrine carcinomas (NEC). According to the study published in 2025 1, these tumors can exhibit various biological characteristics that significantly affect patient prognosis. The WHO 2022 classification serves as the cornerstone for most therapeutic decisions, dividing neuroendocrine neoplasms into four main categories: NET G1 (well-differentiated, with Ki67 < 3 %), NET G2 (well-differentiated, with Ki67 3–20 %), NET G3 (well-differentiated, with Ki67 > 20 %), and neuroendocrine carcinomas (NEC or poorly differentiated, with Ki67 always > 20 %). Some key characteristics of neuroendocrine tumors include:
- They are rare, with an incidence of approximately 0.3–0.8 new cases per 100,000 individuals per year 1
- They can occur in various parts of the body, including the pancreas, lungs, and thymus
- They may be functioning or non-functioning, with functioning tumors producing excess hormones that cause symptoms
- Treatment options depend on the tumor's location, size, and whether it has spread, and may include surgery, radiation therapy, chemotherapy, targeted therapy, and hormone therapy. The exact trigger for the genetic mutations that lead to neuroendocrine tumors remains unknown in most cases, but the classification and treatment of these tumors continue to evolve based on the latest research and guidelines 1.
From the Research
Definition of Neuroendocrine Tumors
- Neuroendocrine tumors (NETs) are a heterogeneous group of malignancies that arise from neuroendocrine cells throughout the body, most commonly originating from the lungs and gastrointestinal tract 2.
- They comprise a family of neoplasms with a wide range of morphologic, functional, and behavioral characteristics 3.
- NETs can be grouped into epithelial and neural subtypes on the basis of the presence of cytokeratins or neurofilaments, respectively 3.
Characteristics of Neuroendocrine Tumors
- NETs display variable malignant potential, hormone-related syndromes (functionality), localization, and genetic background 4.
- They may manifest as noninfiltrative, slow-growing tumors, locally invasive masses, or even swiftly metastasizing cancers 5.
- The biologic behavior of NETs is defined by the grade and stage of the tumor 5.
Diagnosis and Classification of Neuroendocrine Tumors
- The diagnosis of NETs depends on the recognition of characteristic morphologic features and on the presence of markers indicative of neuroendocrine differentiation 3.
- NETs can be classified as well-differentiated (low-grade) or poorly differentiated (high-grade) 2.
- The classification and diagnosis of NETs are complicated by several factors, including a variable natural history and nonspecific symptoms 2.
Treatment of Neuroendocrine Tumors
- Surgery is the only curative treatment for NETs and represents the first therapeutic choice for any localized tumor 5, 4.
- Alternative therapeutic approaches, including chemotherapy, radiofrequency ablation, and biotherapy, have failed to demonstrate a long-term survival benefit 4.
- Recent evidence suggests that patients with small, nonfunctioning G1 tumors can be safely observed, and that an aggressive surgical approach towards liver metastases is recommended in selected cases 5.