What is Carcinoid Tumors?
Carcinoid tumors are tumors that grow slowly, originating from cells known as neuroendocrine cells. These types of cells can secrete various peptides and neuroamines, which are types of chemicals that transmit signals in the body. The most common places for these tumors to start are in the gastrointestinal (GI) tract, making up 60% of the cases. This includes parts of the body like the stomach and intestine. Other common places include the tracheobronchial tree, which makes up the airways of the lungs (25%), while other, less common sites can be the ovaries or kidneys.
The most frequent place where carcinoid tumors are found is the small intestine. The term ‘carcinoid’ is generally used to describe tumors that are well-developed and intermediate-grade, which means they aren’t likely to spread rapidly. When the tumors are less developed and more likely to spread quickly, they are typically referred to as neuroendocrine carcinomas.
This explanation mainly focuses on the carcinoid tumors found in the gastrointestinal (GI) tract.
What Causes Carcinoid Tumors?
Carcinoid tumors come from a specific type of cell that originated from the embryo, called enterochromaffin cells, which are located in the digestive and airway systems. These tumors mostly occur in the small bowel, then the rectum, appendix, and stomach.
It is believed that certain substances and agents encouraging cell growth can pave the way for mutations in cancer-promoting and suppressing genes. This creates a favourable environment for these tumors to grow.
Occasionally, these carcinoid tumors can also be seen in people with a family history of a condition called Multiple Endocrine Neoplasia Type 1 (MEN1) syndrome. MEN1 syndrome is a disorder that affects the body’s endocrine system, causing the growth of tumors in various hormone-producing glands.
Risk Factors and Frequency for Carcinoid Tumors
Each year, about 2.5 to 5 out of 100,000 people are diagnosed with this condition. The total number of people currently affected, or the prevalence, is 35 out of 100,000 people. This condition is most commonly seen in people aged 50 to 70, with no difference between men and women. Thanks to better ways of detecting tumors, the number of new cases each year is rising.
Signs and Symptoms of Carcinoid Tumors
Carcinoids are tumors that can present differently based on their location, hormone production, and how aggressive they are. Often, the small intestines are where they originate, making up 80% of cases, but they can also occur in the lungs and ovaries. These tumors can lead to something called carcinoid syndrome, which involves the secretion of substances that affect various bodily functions.
Common symptoms of carcinoid syndrome include:
- Intermittent skin flushing or blushing (84% of cases)
- Watery Diarrhea (70%) which occurs even when fasting
- Heart disease (37%)
Flushing tends to occur spontaneously but can be triggered by things like stress, alcohol, or certain foods like chocolate, blue cheese, and red wine. Unlike most types of flushing, it isn’t associated with sweating. Over time, these episodes of flushing can lead to changes in facial skin (leonine facies). In addition to these symptoms, patients can also experience symptoms like breathlessness due to bronchospasm, joint pain or stiffness, nerve-related symptoms, and swelling. Carcinoids in the intestines can cause fibrous changes in the bowel wall leading to abdominal pain, internal bleeding, and even bowel obstruction.
Long-term exposure to the substances released by these tumors can cause thickening of the inner lining of the right heart, leading to leakage of the tricuspid and pulmonary valves and subsequent right heart failure. However, changes in the left side of the heart are less common because the lung usually breaks down these substances before they reach the left heart. Patients may also develop Pellagra, which is a condition resulting from the diversion of tryptophan from the synthesis of vitamin B3 to serotonin production. Symptoms of Pellagra include inflammation of the mouth and tongue, angular mouth sores, skin rashes with rough, scaly skin, and confusion.
Testing for Carcinoid Tumors
If you have a type of tumor known as a carcinoid tumor, the diagnosis can sometimes take 5 to 7 years. This is because you might not experience any symptoms, or the symptoms might be general and could be caused by many other conditions. Moreover, carcinoid tumors can spread to other parts of the body in 30% of cases by the time they are diagnosed and in up to 70% of a specific type (midgut carcinoid).
Your doctor often diagnoses these tumors based on clinical suspicion and the results of medical tests and scans.
Medical Tests:
If your doctor thinks you might have a carcinoid tumor, they may recommend that you have three key medical tests. They will check the levels of substances in your body known as chromogranin A, pancreastatin and 5-hydroxyindoleacetic acid (5-HIAA) in your urine over a 24-hour period.
Chromogranin A is a physical sign that can present itself in your body if you have a neuroendocrine tumor, of which carcinoid tumors are a type. It can be used to monitor how you’re responding to therapy, but levels can be normal if the tumor is small. Also, it can appear due to other medical conditions, making it less specific to carcinoid tumors. It’s vital that you fast and avoid exercising before taking these tests for accurate results.
Pancreastatin and 5-HIAA are also markers that can indicate the presence of carcinoid tumors in your body. The 5-HIAA test is useful in keeping tabs on carcinoid tumors that secrete a hormone called serotonin, mainly midgut carcinoids. before and during the urine collection, you should steer clear of certain foods and medications that may falsely elevate the 5-HIAA levels.
Scans:
As part of the diagnosis, your doctor may conduct various scans such as Computerized Tomography (CT), Magnetic Resonance Imaging (MRI), Octreoscan (used to locate tumors), and Positron Emission Tomography (PET) scanning using a substance called DOTATOC. Each scan has its strengths in detecting the carcinoid tumors and their spread.
The MRI scan is often more efficient at identifying small liver metastases – carcinoid tumors that have spread to the liver. There’s a type of PET scan called FDG-PET, but it usually isn’t effective in the detection of carcinoid tumors because of their low cell growth rate. A pill-cam endoscopy that utilizes a swallowable camera to capture images of the small intestine can sometimes be used but isn’t recommended for routine use because the pill can get stuck at the site of the tumor.
An Echocardiogram (a type of heart scan) can be used to detect any tumors that might be affecting your heart valves and is advised before any major surgery. Octreotide scanning, on the other hand, can be helpful in predicting how well you might respond to the treatment with a medication of the same name.
Treatment Options for Carcinoid Tumors
Patients with carcinoids often experience vague symptoms that doesn’t directly point to the disease. As a result, the diagnosis often comes late and the disease may have spread to other parts of the body. The goal of treatment is to surgically remove the original (primary) tumor and the nearby lymph nodes, and control the symptoms of carcinoid syndrome if present.
Surgery can cure the disease if it’s only localized to one area. However, finding the small primary tumor can be difficult. In cases of midgut carcinoids, surgery aims for the complete removal of the primary tumor and nearby lymph nodes. A special substance known as methylene blue is used in surgery to mark the areas of surgery for carcinoids in the midgut, the part of the small intestine that includes the distal part of the ileum and the jejunum.
Carcinoids of the small intestine can create some complex problems where they can lead to a reaction causing new, fibrous tissue to form, and can deeply invade the lymph nodes near major blood vessels. As a result, it is typically not possible to surgically remove the entire tumor. However, surgery can remove a significant part (90%) of the tumor, which can help manage symptoms.
Doctors recommend not to wait until symptoms appear to perform surgery, as this only makes it more difficult to remove as much of the tumor as possible. Most patients with midgut carcinoids need treatment with drugs called somatostatin analogs at some point. These drugs can cause problems with bile flow and gallstones, so doctors usually remove the gallbladder during the first surgery. If the disease results in a blockage of the small intestine, surgery can remove the affected parts.
Patients with carcinoids that have spread should be considered for a combined approach that involves surgery, medication, and radiation therapy. Surgery can also be helpful if the disease has spread to just one or a few sites, as well as for reducing the size of tumors to ease symptoms.
Somatostatin analogs, drugs that act like the hormone somatostatin, are the main treatment for carcinoid syndrome. These help manage symptoms in a majority of patients. There’s a possibility of patients developing a resistance to these drugs over time, which would necessitate increased doses. Diarrhea that doesn’t respond to somatostatin analogs may be treated with the drug loperamide. Medications known as mTOR inhibitors are being studied for their usefulness in treating carcinoids.
As carcinoids are typically slow-growing, standard chemotherapy regimes are not effective. An emerging treatment involves using radiation therapy directed at the somatostatin receptors on the tumor. Further studies are needed to fully understand and confirm these treatment options.
What else can Carcinoid Tumors be?
When trying to diagnose carcinoid tumors, doctors might also consider other conditions that could cause similar symptoms. These can include:
- Acute Urticaria (a type of skin rash)
- Anaphylaxis (a severe allergic reaction)
- Angioedema (swelling beneath the skin)
- Celiac disease, also known as sprue (a disorder that damages the small intestine)
- Intestinal motility disorders (issues with the movement of food through the digestive tract)
- Irritable bowel syndrome (a common disorder that affects the large intestine)
- Ogilvie syndrome (a disorder that leads to a large colon, also known as mega colon)
- Tumor lysis syndrome (a group of problems that can happen after cancer treatment)