Carcinoid tumors a rare, potentially malignant neoplasm from the group of neuroendocrine tumors. It is located in the organs of the digestive and respiratory system. Releases large amounts of biologically active substances. Tumor can be asymptomatic for a long time. Subsequently, hot flashes occur, accompanied by redness of the upper half of the body, tachycardia and hypotension. Diarrhea and abdominal pain are possible. In advanced cases, bleeding, intestinal obstruction or lung atelectasis may develop. The diagnosis is established on the basis of symptoms, ultrasound, CT, laboratory tests and other studies. Treatment – surgery, chemotherapy.
General information
Carcinoid tumors is a rare, slow-growing hormone-active tumor originating from cells of the APUD system. According to the clinical course, it resembles benign neoplasms, but is prone to distant metastasis. Pathology is considered as a potentially malignant neoplasia. It affects the stomach and intestines more often, less often occurs in the lungs, pancreas, gallbladder, thymus gland or urogenital tract.
Usually, carcinoid tumors is diagnosed at the age of 50-60 years, although it can also be detected in young patients. It is 0.05-0.2% of the total number of oncological diseases and 5-9% of the total number of neoplasias of the gastrointestinal tract. According to some data, men suffer from carcinoid tumors somewhat more often than women, according to others, the disease equally often affects representatives of both sexes. Treatment is carried out by specialists in the field of oncology, gastroenterology, pulmonology, abdominal surgery, thoracic surgery and endocrinology.
Causes
Neoplasms originating from endocrine cells were described in 1888. A little later, in 1907, Oberndorfer first used the name “carcinoid tumors” to refer to neoplasms resembling bowel cancer, but characterized by a more benign course. Despite the more than a century-old history of studying disease, the causes of their development still remain unknown. Researchers note an indistinctly expressed hereditary predisposition.
Pathogenesis
In 50-60% of cases, disease are located in the appendix, in 30% – in the small intestine. Possible damage to the stomach, large intestine, rectum, pancreas, lungs, ovaries and some other organs. There is a certain correlation between the localization of the carcinoid tumors and the level of serotonin in the patient’s body. The largest amount of serotonin is secreted by carcinoids tumors located in the ileum, jejunum and the right half of the large intestine. Tumors of the bronchi, duodenum, stomach and pancreas are characterized by a lower level of hormonal activity.
Due to the slow growth, small size and long asymptomatic course, disease have long been considered as benign neoplasms. However, later it turned out that tumors of this group often metastasize. With disease of the small intestine, distant metastases are detected in 30-75% of patients, with lesions of the large intestine – in 70%. Secondary oncological processes are usually detected in regional lymph nodes and liver, less often in other organs.
When hollow organs are affected, pathology are localized in the submucosal layer. Tumors grow both in the direction of the outer wall of the intestine and in the direction of the organ cavity. Usually the diameter of the carcinoid does not exceed 3 cm . The neoplasm is dense, yellow or grayish-yellow on the incision. There are three main types of histological structure:
- with the formation of trabeculae and solid nests (type A);
- in the form of narrow ribbons (type B);
- with a pseudo-gelatinous structure (type C).
During the argentaffin and chromafin reactions, serotonin-containing grains are determined in the cytoplasm of the cells of the test sample.
Symptoms
Carcinoid tumors are characterized by a long asymptomatic course. A pathognomonic sign is paroxysmal hot flashes, accompanied by sudden hyperemia of the face, neck, occiput and upper half of the trunk. The prevalence of hyperemia in carcinoid can vary – from local redness of the face to widespread discoloration of the entire upper body. During hot flashes, there is a feeling of heat, numbness or burning in the area of hyperemia. Conjunctival redness, lacrimation, increased salivation and swelling of the face are possible.
Along with the above symptoms, during the period of seizures, patients with carcinoid have an increased pulse rate and a decrease in blood pressure. Less often, hot flashes are accompanied by an increase in blood pressure. Attacks develop for no apparent reason or occur against the background of physical exertion, emotional stress, taking certain medications, drinking alcohol, spicy and fatty foods. The duration of the attack usually ranges from 1-2 to 10 minutes, less often – several hours or days. In the initial stages of the carcinoid, hot flashes are observed 1 time every few weeks or months. Subsequently, the frequency of seizures increases to several times a day.
Taking into account the peculiarities of the flow, there are four types of tides in carcinoid tumors. The duration of seizures of the first type (erythematous) is several minutes. The hyperemia zone is limited to the face and neck. The second type of tides lasts 5-10 minutes. The face of a patient with a carcinoid becomes cyanotic, the nose acquires a red-purple hue. Seizures of the third type are the longest, can last from several hours to several days. They are manifested by increased lacrimation, conjunctival hyperemia, arterial hypotension and diarrhea. With the fourth type of tides, the appearance of bright red spots in the neck and upper extremities is observed.
Hot flashes are part of the carcinoid syndrome and develop in 90% of patients suffering from carcinoids. Along with hot flashes, 75% of patients have diarrhea caused by increased motor function of the intestine under the influence of serotonin. The severity of diarrhea in carcinoid can vary significantly, with repeated liquid stools, hypovolemia, hypoproteinemia, hypocalcemia, hypokalemia and hypochloremia may occur. Bronchospasm is also possible, accompanied by expiratory shortness of breath, buzzing and whistling dry wheezes.
Over time, half of patients with carcinoid endocardial fibrosis occurs due to the influence of peak serotonin emissions. There is a predominant lesion of the right parts of the heart with the formation of tricuspid valve insufficiency. Along with the above symptoms, carcinoids can reveal pellagra-like skin changes, fibrosing urethral stenosis, fibrous changes and vasoconstriction of the mesentery. Sometimes patients with carcinoid have the formation of adhesions in the abdominal cavity with the development of intestinal obstruction.
During surgical intervention or an invasive procedure, carcinoid crises may develop that threaten the patient’s life. The crisis is manifested by a rush, a sudden drop in blood pressure (vascular collapse is possible), a pronounced increase in heart rate, an increase in body temperature, profuse sweating and a sharp bronchospasm. In some cases, carcinoid crises occur spontaneously or against a background of stress.
Complications
With metastasis, the liver is most often affected. With common secondary foci, there is an increase in the liver, jaundice and an increase in the activity of transaminases. With carcinoid metastases in the peritoneum, ascites is possible. Some patients have metastases in the bones, pancreas, brain, skin, ovaries or chest. When the skeleton is affected, patients with carcinoid have bone pain, with metastases to the pancreas – pain in the epigastric region with irradiation to the back, with brain damage – neurological disorders, with metastases to the chest – shortness of breath and cough. In some cases, small metastatic foci in carcinoid occur without clinical manifestations and are detected only during instrumental studies.
Diagnostics
Due to the possible asymptomatic course, slow progression and the small size of the primary focus, the diagnosis of a carcinoid can be associated with certain difficulties. Specific laboratory tests that confirm the presence of a neuroendocrine tumor are the determination of the level of serotonin in blood plasma and the level of 5-hydroxyindolacetic acid in urine. Scintigraphy with octreotide is used to determine the localization of primary neoplasia and metastatic foci.
In some cases, the carcinoid can be detected during an endoscopic examination. If a stomach lesion is suspected, gastroscopy is prescribed, colonoscopy is prescribed for the large intestine, rectum is prescribed for rectoromanoscopy, bronchoscopy is prescribed for the bronchi, etc. During endoscopy, a biopsy is performed followed by a histological examination of the tissue sample. Along with scintigraphy, in the process of detecting carcinoid and metastatic foci, MRI and CT of abdominal organs, chest x-ray, selective angiography, scintigraphy of the entire skeleton and other studies can be used.
Laboratory methods can also be used to assess the prevalence of carcinoid, in particular, to determine the level of chromatogranin A in the blood. An increase in the concentration of chromatogranin A over 5000 mg/ml indicates the presence of multiple carcinoid metastases. In the presence of carcinoid syndrome, differential diagnosis with other neuroendocrine tumors, medullary thyroid tumor and small cell lung cancer may be required. In the absence of hot flashes, appendix carcinoid sometimes has to be differentiated with chronic appendicitis, colon cancer with colon cancer, liver metastases with other liver diseases accompanied by jaundice and hepatomegaly.
Treatment
The main method of treating a carcinoid is surgical intervention. With neoplasia of the appendix, appendectomy is performed, with tumors of the jejunum and ileum, resection of the affected area is performed in combination with removal of the mesentery and regional lymph nodes. With carcinoids of the large intestine, hemicolectomy is performed. With single metastases in the liver, segmental resection of the organ is possible. With multiple metastases, embolization of the hepatic arteries, cryodestruction or radiofrequency destruction are sometimes used, but the effectiveness of these methods of treatment, as well as the likelihood of complications, have not been sufficiently studied due to the small number of observations.
Chemotherapy for carcinoid is ineffective. A slight increase in life expectancy was noted with the appointment of fluorouracil with streptozocin, however, the use of these drugs is limited due to nausea, vomiting, negative effects on the kidneys and the hematopoiesis system. Drug therapy of a carcinoid usually consists in the use of somatostatin analogues (octreotide, lanreotide), possibly in combination with interferon. The use of this combination of drugs makes it possible to eliminate the manifestations of the disease and reduce the rate of tumor growth.
Forecast
The prognosis for carcinoids is relatively favorable. With early detection of neoplasms, the absence of distant metastases and successful radical surgery, recovery is possible. The average life expectancy is 10-15 years. The cause of death of patients with common forms of carcinoid is usually heart failure due to damage to the tricuspid valve, intestinal obstruction during the adhesive process in the abdominal cavity, cancerous cachexia or dysfunction of various organs (usually the liver) due to distant metastasis.