Neuroendocrine tumor are a heterogeneous group of epithelial neoplasms originating from cells of the APUD system. Most patients with neuroendocrine tumors develop carcinoid syndrome, including hot flashes, abdominal pain, diarrhea, respiratory disorders, heart valve damage and telangiectasia. Hypoglycemia, hunger, disorders of consciousness, seizures, peptic ulcers, weight loss, diabetes, dermatitis, thrombosis and thromboembolism are also possible. The diagnosis is made taking into account the symptoms, laboratory and instrumental data. Treatment – surgery, chemotherapy, symptomatic therapy.
Meaning
Neuroendocrine tumors (NET) are a group of neoplasms of varying degrees of malignancy originating from cells of the diffuse neuroendocrine system capable of producing peptide hormones and biogenic amines. Neuroendocrine tumors are among the rare oncological diseases. They usually affect the digestive and respiratory systems, but can also be detected in other organs. They occur sporadically or are the result of one of several hereditary syndromes accompanied by the development of multiple neuroendocrine tumors in various organs.
Statistical indicators of morbidity are 2-3 people per 100 thousand population, however, experts point out that during autopsy neuroendocrine tumors are found in 8-9 people per 100 thousand population, which indicates a low level of lifetime diagnosis. Usually detected in adults, men suffer more often than women. Treatment is carried out by specialists in the field of oncology, gastroenterology, pulmonology, endocrinology and other fields of medicine (depending on the localization of the neoplasm).
Classification
Taking into account the peculiarities of embryogenesis, three groups of neuroendocrine tumors are distinguished:
- Neoplasms originating from the upper part of the primary embryonic intestine, giving rise to the lungs, bronchi, esophagus, stomach and upper part of the duodenum.
- Neuroendocrine tumors originating from the middle part of the primary embryonic intestine, which is the precursor of the lower duodenum, jejunum and upper colon, including the appendix, caecum, ileum and ascending colon.
- Neuroendocrine tumors originating from the lower part of the primary embryonic intestine, giving rise to the lower parts of the large intestine and rectum.
Taking into account the localization, bronchopulmonary neuroendocrine tumors and neoplasms of the digestive system are isolated. NET of the bronchi and lungs account for about 3% of all oncological diseases of the respiratory system and about 25% of the total number of neuroendocrine tumors. NET of the digestive system account for about 2% of all oncological processes of this localization and more than 60% of the total number of neuroendocrine tumors. Lesions of the digestive system, in turn, are divided into endocrine carcinomas (obsolete name – carcinoids) and other neoplasms (insulinomas, vipomas, glucagonomas, somatostatinomas, gastrinomas). Endocrine carcinomas are most often found in the appendix and small intestine, other neoplasms – in the pancreas.
In some cases, neuroendocrine tumors are formed from cells derived from the endoderm, neuroectoderm and embryonic neural crest, and are localized in the anterior pituitary gland, thyroid gland, parathyroid glands, adrenal glands, prostate gland, mammary gland, kidneys, skin or ovaries. Neuroendocrine tumors located outside the respiratory system and gastrointestinal tract account for about 15% of the total number of neoplasms in this group.
According to the WHO classification, all neuroendocrine tumors of the digestive system, regardless of their type and localization, are divided into three categories:
- Highly differentiated neoplasms with a benign course or an indefinite degree of malignancy.
- Highly differentiated neuroendocrine tumors with low malignancy potential.
- Low-grade neoplasms with high malignancy potential.
Unlike gastrointestinal neoplasms, neuroendocrine tumors of the respiratory system have retained the old name carcinoid. According to the WHO classification , there are four categories of such neoplasias:
- Carcinoids with low malignancy potential.
- Carcinoids with an average malignancy potential.
- Large-cell neuroendocrine carcinomas.
- Small cell lung cancer.
Along with the listed “generalized” classifications, there are WHO classifications for neuroendocrine tumors of various localization, created taking into account the diameter of the primary neoplasm, the depth of germination of the underlying tissues, the degree of involvement of nerves, lymphatic and blood vessels, the presence or absence of metastases and some other factors affecting the course and prognosis of the disease.
Symptoms
Neuroendocrine tumors of the gastrointestinal tract
Neuroendocrine tumors of the gastrointestinal tract (endocrine carcinomas, carcinoid tumors of the gastrointestinal tract) most often they are detected in the area of the vermiform process. The second place in prevalence is occupied by neoplasia of the small intestine. Neuroendocrine tumors of the colon and rectum account for 1-2% of the total number of oncological processes in this anatomical zone. Neoplasms of the stomach and duodenum are relatively rare. In 10% of patients, a genetic predisposition to the occurrence of multiple neuroendocrine tumors is revealed.
All endocrine carcinomas secrete peptides and biogenic amines, however, the list of biologically active compounds and the level of activity of secretory cells of neoplasms can vary significantly, which causes possible differences in the clinical picture of the disease. The most characteristic feature of neuroendocrine gastrointestinal tumors is carcinoid syndrome, which usually occurs after the appearance of liver metastases, accompanied by hot flashes, diarrhea and abdominal pain. Heart valve lesions, respiratory disorders and telangiectasia are less common with this syndrome.
Hot flashes are observed in 90% of patients with neuroendocrine tumors. The release of a large amount of serotonin, prostaglandins and tachykinins into the blood is considered as the main cause of the development of seizures. Hot flashes develop spontaneously, against the background of alcohol consumption, emotional stress or physical exertion and last from several minutes to several hours. During hot flashes in patients with neuroendocrine tumors, hyperemia of the face or upper half of the trunk is detected in combination with hypotension (rarely hypertension), tachycardia and dizziness.
Diarrhea can occur both against the background of seizures and in their absence and is detected in 75% of patients with neuroendocrine tumors. Heart valve damage develops gradually, occurs in 45% of patients. Pathology is caused by cardiac fibrosis resulting from prolonged exposure to serotonin. In 5% of patients with carcinoid syndrome, pellagra is observed, manifested by weakness, sleep disorders, increased aggressiveness, neuritis, dermatitis, glossitis, photodermatosis, cardiomyopathy and cognitive disorders.
5% of patients with neuroendocrine tumors have an atypical course of carcinoid syndrome caused by the release of histamine and 5-hydroxytryptophan into the blood. Usually this variant is detected with NET of the stomach and upper part of the duodenum. Atypical carcinoid syndrome in neuroendocrine tumors is manifested by headache, hot flashes, bronchospasm and lacrimation. During hot flashes, a short hyperemia of the face and upper half of the trunk is detected, accompanied by fever, sweating and itching of the skin. At the end of the tides, numerous telangiectasias form in the area of redness.
A dangerous complication of neuroendocrine tumors is a carcinoid crisis. Usually, such a crisis develops against the background of surgery, an invasive procedure (for example, a biopsy) or severe stress, but it can occur without apparent external causes. The condition is accompanied by a sharp drop in blood pressure, pronounced tachycardia and severe bronchospasm. It is life-threatening and requires urgent medical measures.
Other neuroendocrine tumors
Insulinomas are neuroendocrine tumors that occur in 99% of cases in the tissues of the pancreas, in 1% of cases – in the duodenum. As a rule, they proceed benign, usually they are single, less often they are multiple. Women suffer more often than men. In 5% of patients, neuroendocrine tumors develop against the background of genetic disorders. They are manifested by hypoglycemia, hunger, visual impairment, confusion, hyperhidrosis and trembling of the limbs. Seizures are possible.
Gastrinomas are neuroendocrine tumors, in 70% of cases localized in the duodenum, in 25% – in the pancreas, in other cases – in the stomach or small intestine. They usually proceed malignantly. They are more common in men. 25% of patients have a genetic predisposition. At the time of diagnosis, 75-80% of patients with neuroendocrine tumors have liver metastases, and 12% have bone metastases. The main manifestation is single or multiple peptic ulcers. Severe diarrhea is often observed. The causes of death may be bleeding, perforation or dysfunction of organs affected by distant metastases.
Vipomas are neuroendocrine tumors that usually occur in the pancreas, less often in the lungs, adrenal glands, small intestine or mediastinum. Pancreatic neuroendocrine tumors, as a rule, are malignant, extra-pancreatic – benign. Hereditary predisposition is detected in 6% of patients. The main symptom of a neuroendocrine tumor is life-threatening, debilitating chronic diarrhea, causing disturbances in the water-electrolyte balance with the development of seizures and cardiovascular disorders. Other manifestations of the disease include hyperemia of the upper half of the body and hyperglycemia.
Glucagonoma are neuroendocrine tumors that are always localized in the pancreas. In 80% of cases, they are malignant, usually metastasize to the liver, less often to the lymph nodes, ovaries and spine. Possible dissemination of the peritoneum. The average size of a neuroendocrine tumor at the time of diagnosis is 5-10 cm, 80% of patients with primary treatment have liver metastases. Glucagonomies are manifested by weight loss, diabetes, stool disorders, stomatitis and dermatitis. Thrombosis, thromboembolism and mental disorders are possible.
Diagnosis and treatment
The diagnosis is established on the basis of clinical symptoms, results of laboratory and instrumental studies. In endocrine carcinomas, the level of serotonin in the blood and 5-GIUK in the urine is determined. With insulomas, a blood test is performed for glucose, insulin, proinsulin and C-peptide. With glucagonoma, a blood test is performed for a glucogen, with vipomas – for a vasoactive intestinal peptide, with gastrinomas – for gastrin. In addition, the examination plan for patients with suspected neuroendocrine tumor includes ultrasound of the abdominal organs, CT and MRI of the abdominal organs, PET, scintigraphy and endoscopic examinations. If the malignant nature of the tumor is suspected, a biopsy is performed.
A radical method of treating a neuroendocrine tumor is its surgical excision within healthy tissues. Due to the multiplicity of neoplasms, difficulties in determining the location of small nodes and the high frequency of metastasis, complete removal of neuroendocrine tumors in a significant part of patients is not possible. To reduce the clinical manifestations of the disease, symptomatic treatment is prescribed using octreotide and other somatostatin analogues. With a rapid growth of malignant neoplasms, chemotherapy is indicated.
Forecast
The prognosis depends on the type, degree of malignancy and prevalence of neoplasia. The average five-year survival rate of patients with endocrine carcinoma is 50%. In patients with carcinoid syndrome, this indicator decreases to 30-47%. With gastrinoma without metastases, 51% of patients manage to survive up to five years from the moment of diagnosis. In the presence of metastases, the five-year survival rate of patients with such a neuroendocrine tumor is reduced to 30%. The prognosis for glucagonoma is unfavorable, but the average survival rates are not precisely established due to the rare occurrence of this type of neuroendocrine tumor.