Carcinoid cancer, a subtype of neuroendocrine tumors (NETs), is a rare and complex disease that arises from specialized hormone-producing cells found throughout the body. These tumors have the unique ability to secrete a variety of biologically active substances, leading to a constellation of symptoms known as carcinoid syndrome. Carcinoid cancer is often indolent in nature, with a slow growth pattern, but it can also exhibit more aggressive behavior, particularly in advanced stages.

The image is taken from the American Society of Clinical Oncology (ASCO)

Causes and Risk Factors of Carcinoid Tumor

1. Genetic Syndromes:
   • Neuroendocrine tumors, including carcinoid tumors, are more common in individuals with inherited genetic conditions such as multiple endocrine neoplasia type 1 (MEN1), neurofibromatosis type 1 (NF1), tuberous sclerosis complex (TSC), and von Hippel-Lindau (VHL) disease.
2. Smoking:
   • Tobacco use is believed to increase the risk of carcinoid tumors in the small intestine, as well as other forms of cancer.
3. Age and Gender:
   • Carcinoid tumors can occur at any age, but they are most commonly diagnosed in individuals between 40 and 60 years old, with a slightly higher incidence in women.
4. Environmental Factors:
   • While the specific environmental factors that contribute to the development of carcinoid tumors are not well-established, some research suggests that exposure to certain toxins or dietary factors may play a role.

It is important to note that the presence of one or more risk factors does not necessarily mean an individual will develop carcinoid cancer, and many people with carcinoid tumors have no known risk factors. However, awareness of these potential risk factors can help healthcare providers and patients be more vigilant in monitoring the development of carcinoid tumors and seeking timely medical attention.

The types of carcinoid tumor

Based on Location

Gastrointestinal Carcinoid Tumors: These are the most common type of carcinoid tumors, occurring within the digestive system. They can be found in the stomach, small intestine, colon, rectum, and appendix. Gastrointestinal carcinoid tumors may produce hormones like serotonin, leading to carcinoid syndrome in some cases.

Lung Carcinoid Tumors: Also known as bronchial carcinoid tumors, these develop in the lungs. They are categorized into typical and atypical carcinoids, with the former being more common and less aggressive than the latter.

Appendiceal Carcinoid Tumors: These tumors start in the appendix and are often discovered incidentally during appendectomies. They are generally slow-growing and less likely to produce symptoms unless they become large.

Based on Biological Behavior

Typical Carcinoids: These tumors are slow-growing and less likely to spread beyond their original site. They are more common and account for about 90% of lung carcinoid tumors. Typical carcinoids rarely produce carcinoid syndrome unless they metastasize to the liver.

Atypical Carcinoids: These grow slightly faster than typical carcinoids and have a higher likelihood of spreading to other organs. Atypical carcinoids are characterized by more cells that are dividing and appear more like a fast-growing tumor. They are less common than typical carcinoids.

Symptoms of Carcinoid Tumor

The clinical presentation of carcinoid cancer can be highly variable, depending on the primary tumor location, the extent of disease, and the specific hormones and bioactive substances secreted by the tumor.

1. Asymptomatic Presentation:
   • Many carcinoid tumors are initially asymptomatic and are discovered incidentally during imaging or surgical procedures performed for other reasons.
2. Carcinoid Syndrome: 
   • Carcinoid syndrome is the most well-known clinical manifestation of carcinoid cancer and occurs in approximately 10-30% of patients with carcinoid tumors.
     

     This image is taken from my.clevelandclinic.org

   • Carcinoid syndrome is caused by the excessive secretion of serotonin and other vasoactive substances, such as histamine, prostaglandins, and tachykinins, by the tumor.
   • The classic symptoms of carcinoid syndrome include:
     • Flushing: Sudden, episodic reddening of the face, neck, and upper body, often triggered by stress, exercise, or certain foods.
     • Diarrhea: Watery, voluminous, and often debilitating diarrhea.
     • Bronchoconstriction: Wheezing, shortness of breath, and bronchial constriction.
     • Cardiac complications: Valvular heart disease, particularly right-sided heart failure due to fibrotic changes in the tricuspid and pulmonary valves.
3. Other Symptoms:
   • Depending on the primary tumor location, patients may experience additional symptoms, such as:
     • Abdominal pain, nausea, and vomiting (for gastrointestinal carcinoid tumors)
     • Cough, chest pain, and hemoptysis (for pulmonary carcinoid tumors)
     • Pelvic pain and menstrual irregularities (for ovarian carcinoid tumors)

It is important to note that not all carcinoid tumors are associated with the classic carcinoid syndrome, and some patients may present with non-specific symptoms or even be asymptomatic, particularly in the early stages of the disease

Diagnosis of Carcinoid Tumor

The diagnosis of carcinoid cancer involves a comprehensive approach that includes various tests and procedures to confirm the presence of the tumor and determine its characteristics. Common diagnostic methods for carcinoid cancer include:

1. Blood Tests:
   • Blood tests can detect high levels of hormones secreted by carcinoid tumors or byproducts created when those hormones are broken down by the body.
   • Elevated levels of specific biomarkers, such as chromogranin A (CgA), may indicate the presence of a carcinoid tumor.
2. Urine Tests:
   • Urine tests can identify excess levels of chemicals produced when the body breaks down hormones secreted by carcinoid tumors.
   • A 24-hour urine collection to measure 5-hydroxy-indole-acetic acid (5-HIAA) is often used to diagnose functional neuroendocrine tumors, including carcinoid tumors.
3. Imaging Tests:
   • Imaging tests, such as computed tomography (CT) scans, magnetic resonance imaging (MRI), positron emission tomography (PET), X-rays, and nuclear medicine scans, help pinpoint the location of the carcinoid tumor.
   • Endoscopic procedures, including endoscopy, bronchoscopy, and colonoscopy, allow visualization of the tumor and collection of tissue samples for biopsy.
     

     MRI scans of a patient with metastatic carcinoid tumor. A T1-weighted image that shows low signal density (arrow), which contrasts with the T2-weighted image of the same tumor. b | T2-weighted image that exhibits high signal density (arrow).                                            This image is taken from Researchgate.net

4. Biopsy:
   • Tissue samples from the tumor are collected through biopsy procedures to confirm the diagnosis of carcinoid cancer and determine the type and aggressiveness of the tumor.
   • Biopsy samples are sent to a laboratory for histopathological analysis to identify the types of cells in the tumor and assess their aggressiveness.

In summary, the diagnosis of carcinoid cancer involves a combination of blood tests, urine tests, imaging studies, endoscopic procedures, and biopsy to confirm the presence of the tumor, determine its location, and guide treatment decisions. Early and accurate diagnosis is essential for initiating appropriate management and improving patient outcomes.

Treatment of Carcinoid Tumor

Management Strategies

1. Surgery:
   • Surgery is a primary treatment option for carcinoid tumors, especially when detected early. Complete surgical removal of the tumor can be curative.
   • Surgeons may attempt to remove as much of the tumor as possible in advanced cases to help control signs and symptoms.
2. Medications:
   • Medications like octreotide and lanreotide are used to control excess hormones secreted by the tumor, reducing the signs and symptoms of carcinoid syndrome and slowing tumor growth.
   • Telotristat may be used in combination with octreotide or lanreotide to further improve symptoms of carcinoid syndrome.
3. Chemotherapy:
   • Chemotherapy, which uses strong drugs to kill tumor cells, is recommended for treating advanced carcinoid tumors that cannot be removed with surgery.
4. Targeted Drug Therapy:
   • Targeted drug treatments focus on specific abnormalities within tumor cells, causing them to die. This therapy is usually combined with chemotherapy for advanced carcinoid tumors.
5. Peptide Receptor Radionuclide Therapy (PRRT):
   • PRRT combines a drug that seeks out cancer cells with a radioactive substance that kills them. It delivers radiation directly to cancer cells and may be an option for people with advanced carcinoid tumors.
6. Liver-Directed Therapies:
   • Treatments for carcinoid tumors that spread to the liver may include surgery to remove part of the liver, hepatic artery embolization, radiofrequency ablation, and cryoablation.

These management strategies aim to control symptoms, slow tumor growth, and improve the quality of life for individuals with carcinoid tumors. The choice of treatment depends on factors such as tumor location, stage, hormone secretion, overall health, and patient preferences.

After Treatment

Follow-up Care