Carcinoid tumors: what is it, causes, symptoms, treatment, prognosis

What are carcinoid tumors?

Carcinoid (neuroendocrine) tumors Are slow-growing tumors arising from neuroendocrine cells and capable of secreting various peptides and neuroamines. The usual primary sites are the gastrointestinal tract (60%), followed by the tracheobronchial tree (25%), and other primary sites involving the ovaries or kidneys. The most common location for carcinoids is the small intestine. The term carcinoid is commonly used for highly differentiated and low to moderate neuroendocrine tumors, and the term neuroendocrine carcinoma is used for the least common, poorly differentiated and highly differentiated neuroendocrine tumors. In this article, we will focus on gastrointestinal (GI) carcinoid tumors.

Causes

Carcinoid tumors are of endodermal origin and arise from the enterochromaffin cells of the aerodigestive tract. Carcinoids of the gastrointestinal tract are most often found in the small intestine, then in the rectum,

appendix and stomach. It has been suggested that paracrine agents and growth factors induce cell proliferation and create a fertile ground for mutations of oncogenes and tumor suppressor genes. Carcinoids are also rarely seen in patients with multiple endocrine neoplasia Type 1 (MEN1).

Signs and symptoms

The presentation of carcinoids depends on their location, hormonal activity and tumor aggressiveness. Carcinoid syndrome associated with hypersecretion of vasoactive amines is most common in carcinoids of the small intestine (up to 80%), but can also occur with carcinoids of the foregut in the lungs and ovaries. The most common clinical manifestations are episodic hot flushes (84%), watery diarrhea (70%) and heart diseases (37%). Most episodic hot flashes occur spontaneously, but physical and emotional stress alcohol and tyramine-containing foods such as blue cheese, chocolate, and red wine can provoke him. Hot flushes associated with carcinoids are usually dry hot flashes, as opposed to common causes of hot flashes such as panic attacks and menopause, which are associated with sweating. Over time, due to telangiectasia (persistent dilation of small vessels in the skin) and skin hypertrophy, a facies can develop. Diarrhea is secretory in nature, and the key point in history is its persistence during fasting. Other manifestations may include bronchospasm, arthropathy, neuropathy, and edema. Intestinal ischemia with abdominal pain and bleeding may result from mesenteric fibrosis associated with midgut carcinoids. Local mass impact of the tumor can cause intestinal obstruction.

Chronic exposure to these amines can cause fibrous thickening of the endocardium in the right side of the heart with subsequent regurgitation of the tricuspid valve and pulmonary valve, resulting in right ventricular failure. Left heart disease is rare due to clearance of 5HT by monoamine oxidase present in the lungs.

Patients may also have pellagra as tryptophan switches from niacin synthesis to serotonin synthesis. These patients present with glossitis, angular stomatitis, a characteristic skin rash with rough scaly skin and confusion.

Epidemiology

The estimated annual incidence is 2.5 to 5 cases per 100,000 people per year, and the prevalence is 35 cases per 100,000 people. The highest incidence rate was registered in patients aged 50 to 70 years without a gender predisposition. Thanks to improved methods for detecting tumors, the incidence has increased.

Pathophysiology

Carcinoid tumors are usually classified on the basis of their embryological origin and the vascular supply of the gastrointestinal tract with carcinoids of the anterior, midgut, and hindgut. Functional carcinoids can secrete various vasoactive substances such as serotonin, histamine, tachykinins, and prostaglandins. Carcinoid syndrome usually indicates an underlying metastatic disease to the liver, which indicates a loss of the liver's ability to inactivate these substances, but carcinoids of the anterior intestine can secrete vasoactive amines directly into the systemic circulation and can manifest themselves in carcinoid syndrome without metastases in liver. Hindgut embryonic carcinoids are rarely associated with hormonal syndrome.

Histopathology

Tumors are usually small, polypoid and hard, grow slowly, often penetrate transmurally, and spread to the lymphatic vessels and the adjacent mesentery. Tumor cells are located in nests or trabeculae and are characterized by slightly eosinophilic cytoplasm, varying nuclear grade, and round or oval fine-grained nuclei. Immunostaining for common markers of neuroendocrine tumors, such as chromogranin A and synaptophysin, is often done for diagnostic confirmation. WHO (2010) classified all neuroendocrine tumors, including carcinoids, into three classes based on the mitotic coefficient, or Ki-67 index:

1. Low-grade, well-differentiated endocrine tumors with benign or indeterminate behavior at the time of diagnosis with a mitosis rate of less than 2 and a Ki-67 index of less than 3% (from 10% up to 30%)
2. Well-differentiated endocrine carcinomas with low-grade malignant behavior with a mitosis rate of 2 to 20 and a Ki-67 index of 3 to 20% (50 to 80%)
3. Poorly differentiated high grade endocrine carcinomas with high grade malignant behavior with a mitotic rate of more than 20 and a Ki-67 index of more than 20% (from 1% to 3%).

Diagnostics

If a symptom suggests a carcinoid tumor, the diagnosis is often confirmed by measuring the amount 5-Hydroxyindoleacetic acid (5-HIAA) - one of the chemical byproducts of serotonin - in the patient's urine, which is collected in within 24 hours. For at least 3 days before the analysis, the patient should refrain from eating food foods high in serotonin - bananas, tomatoes, plums, avocados, pineapples, eggplants, and walnuts nuts.

Several drugs also affect test results, including guaifenesin (which is found in many cough syrups), methocarbamol (a muscle relaxant), and phenothiazines (antipsychotics). Patients taking any drug, especially one of these, should see a doctor before collecting a urine sample for this test.

If a diagnosis is not made, doctors give the patient a drug in an attempt to induce hot flashes (provocative test). Nowadays, provocative tests by injecting drugs are rarely performed, but doctors always ask the patient what foods, substances or other factors can cause hot flashes.

- Localization of the tumor.

Various diagnostic tests are performed to localize carcinoid tumors. These tests include computed tomography (CT), magnetic resonance imaging (MRI) and x-rays. which is performed after a radiopaque contrast agent visible on the images is injected into the patient's artery (angiography). Sometimes a diagnostic surgical intervention is required to localize the tumor.

Another useful test is a scintigraphic examination or radioisotope scan. During this test, a radioactive tracer is injected into the patient's vein, which accumulates in a specific organ. Most carcinoid tumors have receptors for the hormone somatostatin. Doctors can inject a radioactive form of somatostatin into the blood and use scintigraphic examination to localize the carcinoid tumor and determine if it has spread. This method can detect approximately 90% of tumors. MRI or CT scans can help confirm that the tumor has spread to liver.

Other causes of hot flashes, such as menopause or alcohol consumption, should be ruled out. This can usually be done by asking questions (for example, about age and about alcohol use), but sometimes testing is required.

Treatment

- Surgical intervention.

If the carcinoid tumor is confined to a specific area, such as the appendix, small intestine, rectum, or lungs, the disease can be treated with surgery. If the tumor has spread to the liver, surgery rarely cures the disease, but may help relieve symptoms. Tumors grow so slowly that even patients with large tumors can live 10-15 years.

- Reducing the severity of symptoms.

Radiation or chemical therapy is ineffective in treating carcinoid tumors. However, a combination of certain chemotherapy drugs (streptozocin with fluorouracil and sometimes doxorubicin) can relieve symptoms.

A drug called octreotide can relieve the symptoms of hot flashes. Other treatments for hot flashes include phenothiazines (such as prochlorperazine) and histamine blocking drugs such as famotidine. Rarely, tamoxifen, interferon alfa, and phentolamine are used to control hot flashes in patients with carcinoid syndrome. Prednisone is sometimes prescribed for patients with carcinoid tumors of the lung who have episodes of severe hot flushes.

Diarrhea can be controlled with loperamide, codeine, opium tincture, diphenoxylate, or cyproheptadine.

Pellagra prevention includes proper protein intake and niacin intake. Also, for the prevention of pellagra, drugs are used that suppress the production of serotonin, for example, methyldopa.

Forecast

5-year relative survival rate for GI carcinoid tumors (based on people diagnosed with carcinoid tumors gastrointestinal tract 1 or 2 degrees [stomach, small intestine, large intestine, appendix, cecum and rectum] during the period from 2010 to 2016.)

SEER* stages	5-year relative survival
Localized	97%
Regional	95%
Far	67%
All SEER stages are combined	94%

* SEER - National Cancer Institute Surveillance, Epidemiology and Outcomes Program is a source of epidemiological information on cancer incidence and survival in the United States.