Classification, diagnosis, treatment of neuroendocrine tumors, and recommendation for genetic testing!

Author: Ihebari Chi, Chief Physician, Cancer Hospital, Chinese Academy of Medical Sciences

Reviewer: Ge Yuping, deputy chief physician, Peking Union Medical College Hospital

Neuroendocrine tumors are a group of tumors that originate from peptidergic neuronal cells.

Figure 1 Original copyright image, no permission to reprint

Neuroendocrine cells have both endocrine functions and the functions of nerve receptors. Depending on whether there are hormone-related symptoms, they are divided into functional and non-functional neuroendocrine tumors.

1. What are functional and non-functional neuroendocrine tumors?

Neuroendocrine cells are a large group of cells that produce a variety of peptide hormones and are widely distributed throughout the body. Therefore, neuroendocrine tumors can develop in any area of ​​the body. When the hormones secreted by these tumor cells enter the blood circulation, they may cause a series of functional symptoms, such as diarrhea or facial flushing.

Specifically, neuroendocrine tumors that originate in the stomach, duodenum, or pancreas may cause difficult-to-heal peptic ulcers, while those that originate in the lungs or thymus may cause hypokalemia or other symptoms of endocrine imbalance. Therefore, these tumors that present with specific symptoms are called functional neuroendocrine tumors.

However, not all neuroendocrine tumors cause clinically significant symptoms. Tumors that do not produce hormones that cause symptoms are classified as non-functioning neuroendocrine tumors. In fact, the majority of neuroendocrine tumors fall into this category.

2. How are neuroendocrine tumors diagnosed?

When patients have clinical symptoms or physical examinations suggest space-occupying lesions, a series of imaging examinations such as CT and MRI are used for preliminary diagnosis, and the sensitivity of these examinations is about 60%. If a neuroendocrine tumor is suspected, high-level imaging examinations such as whole-body octreotide imaging scan, 68Ga-PET/CT or 18F-FDG PET/CT are further recommended to obtain more accurate diagnostic information.

Figure 2 Original copyright image, no permission to reprint

In terms of tumor marker detection, chromaffin cell A (CgA) in serum, 5-hydroxyindoleacetic acid in urine, carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA199), neuron-specific enolase (NSE), alpha-fetoprotein (AFP) and pro-gastrin-releasing peptide (ProGRP) are all important detection items. Among them, NSE is regarded as a specific marker for neuroendocrine cancer, and alpha-fetoprotein (AFP) will also increase in some patients. For small cell neuroendocrine tumors, the increase of ProGRP is indicative. The detection of these tumor markers is often used as an auxiliary imaging examination during the treatment process. Monitoring indicators for efficacy evaluation.

However, the gold standard for diagnosing neuroendocrine tumors is still the pathological examination results obtained through biopsy, which can not only clarify the pathological type, but also determine the pathological grade, including well-differentiated typical carcinoid, atypical carcinoid, and poorly differentiated small cell neuroendocrine carcinoma and large cell neuroendocrine carcinoma, providing a solid foundation for the formulation of treatment plans.

3. How to treat neuroendocrine tumors?

Treatments for neuroendocrine tumors mainly include surgery, chemoradiotherapy, somatostatin analogs (SSA), targeted therapy, and other methods. If surgery can achieve a radical cure, it is considered the preferred treatment method. After surgery, the risk of recurrence will be comprehensively assessed based on pathological results, such as the tumor's malignancy, size, presence of lymph node or nerve invasion, and presence of small lymphatic or vascular tumor thrombi, to determine whether adjuvant chemotherapy or radiotherapy is needed.

For some functional neuroendocrine tumors, if radical resection is not feasible, a palliative surgical strategy can be adopted, that is, to remove most of the tumor tissue to significantly reduce the level of hormone secretion, thereby effectively controlling symptoms. When there are no surgical conditions, local radiofrequency ablation or interventional therapy can also be used to reduce the tumor burden, regulate hormone levels, and thus alleviate clinical symptoms.

For advanced neuroendocrine tumors, the main treatment method before 2009 was to control hormone-related symptoms, such as long-acting octreotide. However, since 2009, a number of rigorous studies have confirmed the effectiveness of SSA drugs, targeted drugs, chemotherapy, and radionuclide-mediated octreotide therapy (PRRT).

Neuroendocrine tumors can be cured with early surgical treatment and, in a few cases, with combined treatment options. However, given the potential risk of tumor recurrence, continued close monitoring is essential.

4. Do patients with neuroendocrine tumors need to undergo genetic testing?

Neuroendocrine tumors may be inherited in the family, and patients with neuroendocrine tumors are generally recommended to go to the pathology department for saliva or blood tumor susceptibility gene testing.

If you have the MEN1 gene, you may develop neuroendocrine tumors in the thyroid, thymus, or pancreas at any time in your life, and you may develop multiple neuroendocrine tumors in the same organ, such as the pancreas. Of course, there are some very rare gene mutations that are also closely related to the occurrence of neuroendocrine tumors.

There is currently no definite preventive measure for neuroendocrine tumors caused by this inherited gene or gene mutation.