Neuroendocrine cells are present in various organs, and their function is to secrete hormones. Carcinoid tumors develop in these cells, resulting in increased production of the hormones. These tumors are slow-growing and do not cause symptoms in their early stages.
Carcinoid tumors originate from neuroendocrine cells and are slow-growing tumors. These tumors secrete a variety of hormones and chemical substances. These tumors occur in various organs in the body.
The most common site is the gastrointestinal tract, which constitutes about 60% of all carcinoids. The second most common site is the respiratory tract (tracheobronchial tree), which constitutes about 25% of primary carcinoid cancer cases. Other sites for the occurrence of these tumors include the ovaries and kidneys. The signs and symptoms are due to elevated levels of hormones in the blood.
There is an increasing trend in the development of neuroendocrine tumors. The incidence of neuroendocrine tumors is about 2 per 1,00,000 population and accounts for about 0.5% of all cancers. The incidence of gastrointestinal carcinoid cancer has increased by over ten times during the last 30 years. However, the trend of occurrence is decreasing for some types of carcinoid tumors, such as appendix carcinoid tumors.
Carcinoid tumors are malignant cells that secrete a significant amount of hormones and other substances into the blood. Carcinoid syndrome is characterized by the symptoms that are caused by elevated levels of those substances in the blood.
Almost 10% of people with carcinoid cancer experience carcinoid syndrome. The symptoms of carcinoid syndrome include head and neck flushing (resulting in the change of color from red to purple), excessive intestinal contraction (resulting in diarrhea and abdominal cramping), shortness of breath, wheezing (due to obstruction in the flow of air in the lungs), heart damage (that may cause edema of the legs and feet), low libido, and erectile dysfunction.
Some of the common locations where carcinoid cancers occur include:
The small intestine is the most common site for carcinoid tumor occurrence. Almost 40% of all GIT carcinoid cancers are found in the small intestine. A carcinoid tumor of the small bowel is usually diagnosed in patients aged between 60 and 70 years. The symptoms of small intestinal carcinoid tumors include diarrhea, abdominal pain, and small bowel obstruction. In advanced stages, this disease metastasizes to the liver and lymph nodes.
Most people with appendiceal carcinoid tumors are diagnosed between 40 and 50 years of age. In most cases, the diagnosis is made during the appendix surgery done for other diseases, such as appendicitis. The majority of the patients with this condition do not experience symptoms during the early stages, probably due to the location of these tumors in the distal appendix. At this location, there is a low obstruction risk.
Primary kidney carcinoid tumors are rare. Their clinical presentation, similar to the other renal tumors, makes their diagnosis challenging. These tumors have an uncertain pathology because neuroendocrine cells are absent in the pelvis, ureter, and renal parenchyma.
Carcinoid cancer in the lungs accounts for about 1-2% of all lung cancers. The carcinoids of the lung are divided into typical (low-grade) and atypical (high-grade) tumors. Although typical tumors frequently secrete growth hormones and corticotrophins, only less than 5% of the patients have carcinoid syndrome.
The carcinoid tumors of the ovaries are divided into stromal, trabecular, mucinous, and insular. Of these, carcinoid syndrome occurs with the insular type. A study has reported that most cases of carcinoid tumors of the ovary occur in postmenopausal women.
They have the potential to metastasize and should be diagnosed and treated appropriately.
Pancreatic carcinoid tumors are neuroendocrine tumors that develop from the neuroendocrine cells of the pancreas. These tumors secrete different hormones, such as insulin, glucagon, gastrin, somatostatin, and serotonin. The symptoms of pancreatic carcinoid tumors depend upon the type and amount of hormones secreted by these tumors.
Rectal carcinoid tumors arise from the neuroendocrine cells present in the rectum. Not all rectal carcinoid tumors cause symptoms, and many of them are found incidentally. The symptoms present include abdominal pain, diarrhea, and flushing that are due to the secretion of serotonin by the tumor cells.
Stomach or gastric carcinoid tumors arise from the cells present in the stomach lining that are responsible for secreting hormones. The carcinoid tumor types of the stomach are Type 1, Type 2, and Type 3 tumors, of which Type 2 and Type 3 are aggressive and have the potential to metastasize.
Carcinoid tumors are cancerous and have the potential to metastasize to other organs. However, as compared to typical tumors, carcinoids are slow-growing, and most have a low potential to metastasize. Individuals with well-differentiated carcinoids have a relatively better prognosis, especially when the tumor is diagnosed at an early stage.
The stages of the carcinoid tumor of the stomach are:
At this stage, the tumor is confined to the lining of the internal tissues and has not spread to the deeper tissues.
At this stage of the carcinoid tumor, the malignant cells may invade the deeper tissues but are not spread outside the affected organ.
The tumor has invaded the nearby lymph nodes and tissues but has not spread to other organs.
The tumor, along with the lymph nodes and the nearby tissues, has also invaded the nearby organs.
Stage IV is the most advanced stage. At this stage, the tumor has spread to distant organs.
Carcinoid tumor symptoms do not present in the early stages. Some of the symptoms, if present, may overlap with other conditions. It is essential not to ignore the signs and consult with the doctor. Carcinoid tumor causes include the presence of genetic diseases.
Some of the common signs and symptoms of carcinoid tumors include:
Patients with carcinoid tumors of the stomach usually have abdominal pain as an early carcinoid tumor symptom. In advanced stages, the abdominal pain may be due to gastrointestinal obstruction, infarction or ischemia, and the spread of the tumor to the peritoneum.
Anemia is another important carcinoid tumor symptom. It may be due to bleeding and insufficient production of red blood cells. The severity of anemia depends on the location and stage of the tumor.
Diarrhea is a common carcinoid tumor symptom. Patients with carcinoid tumors have high serotonin levels. Serotonin causes intestinal stimulation, resulting in increased intestinal motility and secretion, resulting in diarrhea.
Diarrhea and anemia in patients with carcinoid tumors result in several symptoms, including fatigue and weakness.
Patients with carcinoid tumors may sometimes have heart complications due to carcinoid heart disease. Serotonin reaches the heart through the blood and may cause structural changes. Some of the heart-related carcinoid tumor complications include heart murmurs, regurgitation, and stenosis.
Jaundice is a carcinoid tumor symptom in patients with advanced disease that has metastasized to the liver. The malignant cells proliferate in the liver, resulting in hepatic complications.
Hypotension is not a direct carcinoid tumor symptom. However, certain other complications related to the disease, such as carcinoid syndrome or heart-related complications, and side effects of medications may cause hypotension.
Nausea and vomiting may be due to a variety of reasons in patients with carcinoid tumors. It may be due to excessive secretion of serotonin or gastrointestinal side effects, especially in patients with advanced disease.
Rectal bleeding is not a common carcinoid tumor symptom, even in rectal carcinoid tumors. However, rectal bleeding may occur in some cases when there is an ulcer or damage to the lining of the rectum.
Shortness of breath may also be a carcinoid tumor symptom, especially in patients with heart and lung involvement. Heart-related complications, such as cardiac dysfunction and heart valve abnormalities, result in shortness of breath.
Patients with carcinoid tumors, especially those with gastrointestinal and liver involvement, have weight loss. It may be due to a loss of appetite, a higher metabolism, or malabsorption.
Wheezing is not an early carcinoid tumor symptom except in patients with primary carcinoid tumors of the lungs. It may be due to the narrowing of the respiratory tract.
Apart from the common carcinoid tumor symptoms, certain symptoms are specific to the location of carcinoid tumors. These include:
The following are the commonly observed lung carcinoid tumor symptoms:
Chest pain may occur when the malignant cells develop and proliferate in the lungs. Chest pain may also be a symptom of carcinoid heart disease.
Breathing problems, such as shortness of breath, may occur in patients if the tumor narrows the air passage in the respiratory tract.
Wheezing occurs when the lung carcinoid tumor may cause inflammation and airway obstruction.
Carcinoid syndrome due to advanced lung carcinoid tumors may result in wheezing, diarrhea, and flushing of the skin.
Carcinoid tumors of the lungs may produce several substances, such as ACTH (adrenocorticotropic hormone), that result in weight gain.
Several chemicals are produced by the carcinoid tumors and released in the blood. These chemicals cause skin flushing characterized by warmth in the face and upper chest.
Patients with carcinoid syndrome may have redness on the face or neck due to excessive secretion of hormones and other substances.
Carcinoid tumor symptoms related to the gastrointestinal tract include:
Patients with gastrointestinal tract carcinoid tumors may experience rectal bleeding due to ulcers or damage to the internal lining.
Diarrhea may occur due to hypermotility caused by abnormal levels of hormones released by the tumors. It may also be due to irritation of the gastrointestinal tract because of carcinoid tumors.
Abdominal pain in patients with carcinoid tumors may occur due to obstruction, infarction or ischemia, and compression of healthy tissues by the tumor in the gastrointestinal tract.
It may occur in patients with gastrointestinal carcinoid tumors due to elevated hormone levels or involvement of the liver in the disease.
Patients may have rectal pain due to the excessive growth of carcinoid tumors or damage to the internal lining.
Excessive levels of certain substances may result in carcinoid syndrome. Such patients have flushing and redness on the neck and face.
Many wonder as to what causes carcinoid tumors of the lung. Although we do not know the exact cause, we do know that certain factors increase the risk of carcinoid tumors. Some of the causes of carcinoid tumors are:
It is a genetic condition and is one of the carcinoid tumor causes. The condition is characterized by tumors in pancreatic islet cells, parathyroid glands, or the pituitary gland.
It is also a genetic condition and is one of the carcinoid tumor causes. It involves the development of carcinoid tumors in the parathyroid, thyroid, and adrenal glands.
It is a rare genetic condition and could serve as a carcinoid tumor cause. Patients with this condition may develop cysts or tumors in various organs, such as the spinal cord, brain, eyes, pancreas, and kidneys.
It is also known as von Recklinghausen disease and is one of the carcinoid tumor causes. People with this condition may develop carcinoid tumors.
It is important to consult the oncologist if the individual experiences weight loss, rectal bleeding, chest pain, shortness of breath, diarrhea, abdominal pain, nausea and vomiting, wheezing, redness of the face and neck, a heart murmur, and breathing complications.
Carcinoid tumors are slow-growing and rare neuroendocrine tumors. The clinicians experience diagnostic challenges, as most patients do not have any symptoms in the early stages. If the symptoms do exist, they overlap with other, less serious conditions. A multidisciplinary approach is required for optimal carcinoid tumor treatment, with surgery being the only curative option. Carcinoid syndrome diagnostic tests may also be performed in patients with carcinoid tumors, especially those with advanced stages.
A carcinoid tumor diagnosis begins with a physical examination and a medical history assessment. The doctor will initially try to understand the causes of the symptoms experienced by the patient. If the doctor suspects carcinoid tumors, additional tests will be recommended. The following are the different tests recommended for carcinoid tumor diagnosis:
The carcinoid tumors secrete several hormones and other chemicals. Carcinoid tumor blood tests involve measuring the levels of these chemicals or byproducts of these chemicals in the blood, which may indicate carcinoid tumors.
The chemicals predominantly secreted by carcinoid tumors include 5-hydroxytryptamine, dopamine, histamine, atrial natriuretic peptide, neurotensin, α1-antitrypsin, somatostatin, pancreatic polypeptide, substance P, kallikrein, and prostaglandins. Chromogranin A is probably the most specific carcinoid disease biomarker. As chromogranin testing does not depend on the secretion of serotonin, it is better when compared with the urine 5-HIAA test for non-secreting tumors and atypical carcinoids.
Patients suspected of carcinoid tumors may undergo a 24-hour urine collection to detect levels of 5-hydroxyindoleacetic acid (5-HIAA), a serotonin metabolite. However, this test is highly specific (100%) for carcinoid disease diagnosis but has less specificity (73%). The low specificity of this test is because of non-secreting carcinoid tumors present in several patients.
The levels of 5-HIAA can also be elevated in Whipple's disease, celiac disease, and small bowel obstruction. Certain medications and foods, such as bananas, avocados, and walnuts, may alter the test results and should be avoided before the test.
A colonoscopy is performed to diagnose and manage carcinoid tumors of the rectum and colon. During the colonoscopy, the doctor inserts a flexible tube with a camera at the end into the rectum and guides it to the colon. The camera transmits images of the internal structures that can be clearly seen on the monitor. The abnormal tissues are detected and can be obtained for further analysis.
As gastrointestinal carcinoid tumors are slow-growing and do not cause symptoms at the initial stages, they should be routinely monitored through methods such as colonoscopy, especially in people who are at risk or have a history of carcinoid tumors.
Some carcinoid tumors are slow-growing and non-aggressive and do not present symptoms during the early stages. These are diagnosed by chance while diagnosing or treating other conditions. In some patients, carcinoid tumors are detected when they undergo surgery for appendicitis.
Upper endoscopy, or esophagogastroduodenoscopy, is a technique that involves the insertion of a tube with light and a camera at the end into the mouth and being guided to the esophagus, stomach, and initial section of the small intestine. The technique is used to diagnose carcinoid tumors in the stomach and the small intestine in patients suspected of having the tumors. If carcinoid tumors are detected, the samples can be obtained for further analysis.
Once the patients are suspected of having carcinoid tumors through biochemical tests or urine analysis, the doctor advises them to undergo imaging tests to confirm the exact site of carcinoid tumors. Conventionally, computed tomography is one of the most common tests for carcinoid tumor diagnosis and the extent of metastasis. However, conventional CT has poor sensitivity (44% to 55%). The advanced CT techniques involving multiplanar reconstructions have relatively higher sensitivity.
Abdominal CT assists in diagnosing the liver metastasis of carcinoid tumors. Sometimes, in patients with diarrhea or abdominal pain, small intestine and colon tumors may be detected through barium studies. However, the barium studies are often non-specific and may result in missing tumors.
Radiolabeled receptor-binding peptides and scintigraphy provide valuable information about carcinoid tumor diagnosis. Studies have reported the superiority of the indium-111 (In-111) labeled octreotide (octreoscan) to localize the primary tumor compared with magnetic resonance imaging, or CT. In asymptomatic patients with gastrointestinal carcinoid tumors, the diagnostic sensitivity is between 80% and 90%, and it is greater than 90% in symptomatic patients. Metaiodobenzylguanidine scintigraphy is an alternative method for detecting carcinoid tumors. As carcinoid tumors have low proliferating activity, the FDG-PET scan is not generally useful.
The method involving the removal of the sample tissues for the abnormal site and sending them to the laboratory for carcinoid tumor diagnosis is known as carcinoid tumor biopsy. A biopsy can be performed using different methods. One method is to insert the needle under imaging guidance (image-guided percutaneous biopsy) to obtain the sample from the tumor. In some cases, biopsy may be assisted by endoscopy and colonoscopy. Surgery may also be performed to obtain the tissue samples.
Effective carcinoid tumor treatment involves a multidisciplinary approach that includes surgical resection, debulking, medical therapy, and hepatic chemoembolization. The different options available for carcinoid tumor treatment include:
Surgical resection is the preferred carcinoid tumor treatment. The extent of removal of the malignant tissue is based on the size and location of the tumor. In patients suffering from bronchopulmonary carcinoid tumors and having adequate pulmonary reserve, carcinoid tumor lung surgery is the preferred treatment.
Radical gastrectomy is the mainstay of treatment, irrespective of the tumor size, in patients with type III gastric carcinoid tumors. The surgical management of small intestinal carcinoids depends on the tumor location, size, and extent of metastasis. Small carcinoid tumors of the appendix require a simple appendectomy. However, more extensive surgery is required in cases of tumor size >2 cm, involvement of lymph nodes, and lymphatic invasion of the tumor. It has been reported that 55% of the patients with carcinoid tumors of the colon have nodal or liver metastasis. Thus, formal hemicolectomy with a mesenteric resection is considered the ideal treatment for colon carcinoid tumors.
Patients with carcinoid tumors may also have symptoms due to the secretion of excess hormones by the malignant cells. Oncologists may prescribe medications that block the secretion of hormones, resulting in the management of symptoms and the delay of tumor growth. These drugs have good efficacy in lowering levels of neuroendocrine tumor markers.
Chemotherapy for carcinoid tumors includes the administration of drugs that kill or delay the growth of cancer cells. These drugs are administered systemically, either orally or through injections. These drugs inhibit the synthesis of hormones and proteins in cancer cells, stimulate the immune system, and inhibit angiogenesis. In patients with malignant gastrointestinal neuroendocrine tumors with high proliferation indices, cytotoxic drugs are considered first-line therapy.
Several molecules, such as enzymes and proteins, and various pathways are essential for the growth and proliferation of carcinoid tumor cells. Targeted drug therapy works by targeting these molecules and pathways and killing or delaying the growth of carcinoid tumor cells. As the targeted therapy targets only the processes within the cancer cells, this therapy has relatively fewer side effects compared with conventional chemotherapy.
Drugs that deliver the radiation into the cancer cells are also used for the treatment of carcinoid tumors. Peptide receptor radionuclide therapy (PRRT) involves the combination of the drug with radioactive substances to kill cancer cells. Once the drug is injected into the blood, it travels to the cancer cells, binds with them, and delivers radiation to kill them. It is usually used in patients with advanced carcinoid tumors.
Carcinoid tumors are also treated with a somatostatin analog. Somatostatin is a peptide that occurs naturally and blocks several processes, such as cell growth, hormonal secretion, and smooth muscle contraction. The daily subcutaneous injection of the somatostatin analog may significantly reduce the symptoms; however, the duration of response to standard treatment of the somatostatin analog is 12 months.
Malignant carcinoid tumor cells escape the destructive effects of the immune system through certain processes. Immunotherapy interferes with these processes and makes these carcinoid cancer cells vulnerable to being attacked and killed by the immune system. Immunotherapy drugs also strengthen the patient's immune system and increase their ability to fight against cancer cells.
Carcinoid tumor diagnosis and treatment are challenging, especially in patients who are diagnosed in advanced stages. It requires advanced facilities for diagnosis and treatment, a team to perform complex surgeries, state-of-the-art operating theaters, and experienced paramedical staff to take care before and after the treatment. HCG is one of the highly recommended cancer hospitals in India for carcinoid tumor diagnosis and treatment and is equipped with all facilities that increase the chances of a favorable prognosis and improve the overall quality of life of the patients.
Several factors increase the risk of carcinoid tumors. Identifying these carcinoid tumor risk factors and following the carcinoid tumor prevention measures to reduce those risks helps in the effective management of carcinoid tumors.
Some of the common carcinoid tumor risk factors include:
Although genetic conditions are not directly involved in the development of carcinoid tumors, they do increase the risk of carcinoid tumors and other neuroendocrine tumors. Genetic diseases that increase the risk of carcinoid tumors include MEN1, MEN2, Von Hippel-Lindau syndrome, and neurofibromatosis type 1. It has been reported that the MEN1 gene may cause 5 to 10% of carcinoid tumors, especially in the stomach. Neurofibromatosis type 1 disease may increase the risk of small intestinal carcinoid tumors. Another genetic disease that may increase the risk of carcinoid tumors is the tuberous sclerosis complex.
Race and ethnicity affect the risk of carcinoid tumors. It has been found that African Americans are at an increased risk of developing carcinoid tumors compared to white people. Further, the prognosis of carcinoid tumors is relatively less favorable in African Americans compared with whites.
Gender (male or female) also affects the incidence, clinical characteristics, and prognosis of carcinoid tumors. It has been found that females are slightly at a higher risk of developing carcinoid tumors compared to males. It is reported that women have better outcomes for carcinoid tumors, possibly due to a better response to medical treatment. In addition, the disease also affects the patient's quality of life differently and has different social and psychological consequences.
Carcinoid tumors may occur at any age. However, the disease is slow-growing, so the symptoms are not presented until age 55 to 65 in most cases. Thus, there is a considerable difference in the time between the onset of the disease and the diagnosis.
Several underlying medical conditions are also carcinoid tumor risk factors. The location of tumor development depends upon the type of disease. Stomach diseases, such as Zollinger-Ellison syndrome or atrophic gastritis, can also serve as carcinoid tumor risk factors. However, the presence of these stomach conditions does not affect the risk of carcinoid tumors in other organs.
Another genetic disease that may increase the risk of carcinoid tumors is the tuberous sclerosis complex. The condition may increase the risk of both non-cancerous and cancerous tumors. The site of non-cancerous tumors in patients with tuberous sclerosis complex includes the brain, skin, heart, kidneys, and lungs.
Other factors that increase the risk of carcinoid tumors include smoking, excessive alcohol consumption, and a family history of carcinoid tumors.
Although 100% carcinoid tumor prevention is not possible, following certain measures can help one reduce their carcinoid tumor formation risk. Some of the carcinoid tumor prevention measures are:
A protein diet not only helps reduce the risk of the disease but also helps manage carcinoid tumor symptoms. Protein strengthens the immune system and assists the body in fighting against abnormal cells. Further, a diet rich in protein helps maintain optimal health in patients with carcinoid tumors.
Excessive consumption of alcohol for prolonged periods increases the risk of various cancers, including carcinoid cancer. Limiting alcohol consumption lowers the risk of carcinoid tumors. In patients with carcinoid tumors, certain foods trigger the symptoms.
Patients with carcinoid tumors should avoid the consumption of alcohol, vinegar, yeast, soybean products, smoked and salted fish, and aged cheese.
Smoking increases the risk of carcinoid tumors, as the smoke contains several harmful carcinogens that cause genetic mutations, which in turn can lead to tumor formation. Thus, quitting or not initiating smoking reduces the risk of carcinoid tumors.
Stress may not increase the risk of carcinoid tumors. However, it may worsen the symptoms in patients with carcinoid tumors. The patients should manage their stress effectively through various techniques.
Patients with carcinoid tumors should provide detailed information about their medical history and the medications they are taking. Certain medications may worsen the symptoms of carcinoid tumors. These include asthma inhalers, decongestants, and antidepressants.
Certain mind-body exercises, such as meditation and yoga, help reduce stress and the severity of symptoms. Further, these techniques and other measures enhance immunity and reduce the risk of various cancers.
Emotional stress worsens carcinoid tumor symptoms. Patients should consider managing their emotional stress through music therapy, guided imagery, and meditation.
The carcinoid tumor risk factors include the presence of genetic disease, race and ethnicity, gender, age, smoking, alcohol consumption, and diseases such as Zollinger-Ellis syndrome, atrophic gastritis, and the tuberous sclerosis complex. Effective carcinoid tumor prevention measures include a high-protein diet, limiting alcohol consumption, stress management, meditation, yoga, music therapy, and avoiding certain medications such as decongestants and antidepressants (as these medications worsen carcinoid tumor symptoms).
