Neuroendocrine Tumors: Origin, Examination and Therapy

Neuroendocrine tumors are tumors that originate from neuroendocrine cells. Neuroendocrine cells are a large group of cells in the body with neuroendocrine phenotypes that can produce various hormones. Neuroendocrine cells are distributed throughout the body, so neuroendocrine tumors can occur in any part of the body, but the most common are neuroendocrine tumors in the digestive system such as the stomach, intestines, and pancreas, accounting for about 2/3 of all neuroendocrine tumors. The incidence rate of neuroendocrine tumors in European and American populations is also very high. The incidence rate has increased more in the past 30 years. Compared with other tumors, the incidence rate of neuroendocrine tumors has increased more rapidly.

Figure 1. Neuroendocrine Tumors.

Origin and Definition: Neuroendocrine System

When neuroendocrine cells undergo genetic mutations leading to uncontrolled proliferation, NETs will develop. They can occur anywhere these cells are present, but the most common primary site is:

• Gastrointestinal tract (67%): commonly referred to as carcinoid, especially found in the appendix, small intestine, rectum, and stomach.
• Lungs (27%): the second most common site, ranging from typical carcinoid (low-grade) to atypical carcinoid (high-grade).
• Pancreas: an important subgroup that includes functional tumors such as insulinomas or gastrinomas.
• Rare sites: including thymus, adrenal gland, thyroid (medullary carcinoma), and skin (Merkel cell carcinoma).

Clinical Manifestations

Neuroendocrine tumors are classified into two categories: non functional (about 80%) and functional (about 20%) based on whether the tumor has hormone secretion function and whether there are clinical symptoms caused by hormones. Non functional gastrointestinal pancreatic neuroendocrine tumors are mainly characterized by non-specific gastrointestinal symptoms or local tumor occupying symptoms, such as progressive swallowing difficulties, abdominal pain, bloating, diarrhea, abdominal masses, jaundice, or black stools; Functional gastrointestinal and pancreatic neuroendocrine tumors are mainly characterized by clinical symptoms caused by the secretion of biologically active hormones, such as skin flushing, sweating, asthma, diarrhea, hypoglycemia, refractory gastrointestinal ulcer, diabetes, etc. Functional gastrointestinal and pancreatic neuroendocrine tumors are mainly pancreatic neuroendocrine tumors, including insulinoma, somatostatin tumor, glucagon tumor, gastrinoma, etc.

Diagnosis

Diagnosis of neuroendocrine tumors is based on corresponding clinical manifestations, tumor marker detection, imaging examination, and pathological examination. The complete diagnostic content includes tumor location, grading, staging, and functional status.

Conclusions

Neuroendocrine tumors were once considered obscure and untreatable, but now they are at the forefront of oncology innovation. In the past two decades, significant progress has been made in diagnostic accuracy, the development of effective biological therapies (SSA), and the emergence of targeted radiation therapy (PRRT). These developments have transformed NETs into chronic, manageable diseases for many patients, significantly improving their quality of life and overall survival rates. However, challenges still exist, particularly in early detection and management of treatment resistance. The ongoing research continues to uncover the complex genetics of NETs, paving the way for more personalized and effective treatments.

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