Carcinoid Tumors - Symptoms, Causes, and Treatment

Table of contents

• What are carcinoid tumors? - An Introduction

• Causes of Carcinoid Tumors

• Signs and Symptoms of Carcinoid Tumors

• Diagnosis of Carcinoid Tumors

• Treatment for Carcinoid Tumors 

• Take-Home Points

• FAQ on Carcinoid Tumors - Symptoms, Causes, and Treatment

What are carcinoid tumors? - An Introduction

Carcinoid tumors are slow-growing tumors from neuroendocrine cells found in organs throughout the body. Neuroendocrine cells help the body function by sending and receiving messages through hormones.

 Carcinoid tumors secrete a variety of neuroamines and peptides. The paracrine hormones and growth factors provide favorable conditions for mutations in oncogenes and tumor suppressor genes and induce cell proliferation.

Recent data shows common sites for carcinoid tumors are the gastrointestinal (GI) tract, followed by the tracheobronchial tree and ovaries or kidneys. Neuroendocrine tumors are less frequent, poorly differentiated, and high-grade tumors. Carcinoid tumors are rare but more common among adults than in children. The highest incidence is in patients around 50 to 70 years old with no gender predilection. The incidence has increased with improved techniques for tumor detection.

Causes of Carcinoid Tumors

The exact cause of carcinoid tumors is not known. Generally, cancer forms when a cell develops mutations in its DNA, resulting in the abnormal growth and division of the cell. The divided cells accumulate to form the tumor and invade the healthy tissues resulting in the spread of cancer.

In people with or with a family history of MEN 1 (multiple endocrine neoplasia, type 1), there is a risk of developing intestinal and bronchial carcinoid tumors.

Signs and Symptoms of Carcinoid Tumors

The symptoms or clinical presentation of a carcinoid tumor depends on the aggressiveness of cancer, its location, and hormonal activity. The carcinoid tumors secrete certain chemicals into the bloodstream, causing various signs and symptoms known as carcinoid syndromes. The carcinoid syndrome results in skin flushing, facial skin lesions, diarrhea, rapid heartbeat, and difficulty breathing. Carcinoid syndrome from increased secretion of vasoactive amines by tumor cells is typical of small intestinal carcinoids but can also occur in carcinoids in the lung and ovaries. 

The clinical manifestations include:

• Episodic flushing - Most episodes occur spontaneously, but emotional and physical stress, alcohol, and tyramine-containing foods like chocolate, blue cheese, and red wine can provoke it. Flushing seen in carcinoids is characteristically dry flushing and not associated with sweating.

• Watery diarrhea - Diarrhea is secretory, and its persistence with fasting is key in history. The local mass effect of the tumor can cause bowel obstruction.

• Heart diseases - The secretions of cancer cells result in the fibrous endocardial thickening of the right side of the heart. This result in pulmonary valve and tricuspid regurgitation leading to right heart failure.

Patients with a carcinoid tumor in the lungs may experience asthma-like signs and symptoms, like wheezing and shortness of breath. At the same time, the patients may experience skin flushing and cough up blood. Sometimes these symptoms are diagnosed as pneumonia by mistake.

Other presentations include arthropathy, neuropathy, pain in the abdomen, nausea or vomiting, and edema.

Diagnosis of Carcinoid Tumors

Most patients are asymptomatic or present with non-specific symptoms in the initial years, which result in a late diagnosis. By the time of diagnosis, the tumor might have already metastatized in most cases. Diagnosis is usually on clinical suspicion and biochemical evaluation. Imaging technology helps to localize and assess the tumor spread.

1. Biochemical Tests 

Patients with carcinoid tumors should check Chromogranin A, Pancreastatin, and 24-hour urine for 5-HIAA (5-hydroxyindoleacetic acid).

• Chromogranin A is a non-specific neuroendocrine marker. They help in screening and follow-up of functioning and non-functioning carcinoids, like other neuroendocrine tumors. Chromogranin A levels relate to tumor volume, provide prognostic information, and are helpful for monitoring response to therapy.

• Pancreastatin is a post-translational processing product of Chromogranin A. It has the potential to be an alternate biomarker.

• 5-HIAA is a serotonin breakdown product. It helps in the diagnosis and follow-up of carcinoid tumors secreting serotonin. However, patients should avoid foods and medications high in serotonin and tryptophan for three days before the test.

2. Imaging 

CT, MRI, and PET scan help to localize carcinoid tumors and assess metastatic spread. The upper and lower GI endoscopies are helpful for direct visualization and biopsy of accessible lesions in case of intestinal carcinoid tumors.

An octreotide scan or somatostatin receptor scintigraphy helps to detect the neuroendocrine tumor cells. Thus in most cases, an octreotide scan is done as a baseline.

3. Biopsy 

A biopsy is a procedure where pathologists closely examine the sample of tissues taken from the body to detect the presence or extent of the disease. Sometimes a surgical procedure or flexible scope is used to get the tissue samples.

Treatment for Carcinoid Tumors 

The focus of carcinoid tumor management is symptom control, biochemical control, tumor control, and improving the quality of life. 

Management of carcinoid tumors uses various approaches.

1. Cytoreductive Surgery

Cytoreductive surgery is the cornerstone in the management of carcinoid tumors. The surgery aims to improve survival and control symptoms by destroying or removing the tumor. It includes tumor resection, fulguration, and cryotherapy. Local excision may be successful for smaller tumors, but more radical surgery might be required in patients with larger tumors.

Surgery can reduce tumor bulk and prevents other local or systemic effects. Thus, surgery improves the quality of life and hormone-related symptoms and can prolong survival in some patients.

2. Systemic treatment

Systemic treatment includes therapy with somatostatin analogs, cytotoxic agents, and interferon alfa. Other agents are administered as required, for example, loperamide or diphenoxylate for diarrhea and H1 or H2 blockers (or both) for histamine-secreting tumors.

• Somatostatin analogs relieve symptoms and decrease hormone levels. Somatostatin analogs help to treat or prevent carcinoid crises before, during, and after procedures such as surgery in asymptomatic patients with progressive disease.

• Cytotoxic therapy is usually utilized for tumors with a high proliferative capacity and significant tumor burden, like bronchial carcinoids. Cytotoxic drugs prevent the replication or growth of cancer cells.

• Interferon alfa inhibits hormone and protein synthesis in cancer cells, hinders angiogenesis, and stimulates the immune system. Combining interferon alfa with somatostatin analogs has synergistic effects in treating carcinoids.

3. Radiotherapy

• Tumor-targeted treatment with radioactive octreotide derivatives is associated with tumor shrinkage in some tumors. Recent evidence suggests that combining radioisotope with concurrent systemic therapy might be more effective.

Take-Home Points

• Carcinoid tumors are slow-growing tumors from neuroendocrine cells found in organs throughout the body. Common carcinoid tumor sites are the gastrointestinal (GI) tract, followed by the tracheobronchial tree and ovaries or kidneys. 

• The exact cause of carcinoid tumors is not known. Carcinoid tumors are rare but more common among adults aged 50 to 70 with no gender predilection. 

• The symptoms of a carcinoid tumor depend on the aggressiveness of cancer, its location, and hormonal activity. The carcinoid tumors secrete certain chemicals into the bloodstream, producing carcinoid syndromes. The carcinoid syndrome results in skin flushing, facial skin lesions, diarrhea, rapid heartbeat, and difficulty breathing.

• Most patients are asymptomatic or present with non-specific symptoms in the initial years, which result in a late diagnosis. In most cases, the tumor might have already metastatized at the time of diagnosis. Biochemical tests help identify the tumor's presence and imaging technology helps to localize carcinoid tumors and assess metastatic spread. 

• The focus of carcinoid tumor management is symptom control, biochemical control, tumor control, and improving the quality of life. Management of carcinoid tumors uses approaches like cytoreductive surgeries, systemic treatment, and radiotherapy.

FAQ on Carcinoid Tumors - Symptoms, Causes, and Treatment

1. What is a carcinoid tumor?

Ans. Carcinoid tumors are rare and slow-growing neuroendocrine tumors that can occur in different places of the body.

2. What are neuroendocrine tumors?

Ans. Neuroendocrine tumors arise from neuroendocrine cells. These cells are found throughout the body and help the body function by sending and receiving messages through hormones. Carcinoid tumors are a rare type of neuroendocrine tumor.

3. What is carcinoid syndrome?

Ans. Carcinoid syndrome is the group of symptoms that develop in patients with carcinoid tumors. The carcinoid tumors secrete certain chemicals into the bloodstream, causing carcinoid syndrome. The carcinoid syndrome results in skin flushing, facial skin lesions, diarrhea, rapid heartbeat, and difficulty breathing.

4. How is a carcinoid tumor diagnosed?

Ans. In most cases, patients are asymptomatic or present with non-specific symptoms in the initial years, which result in a late diagnosis. Diagnosis is usually on clinical suspicion and biochemical evaluation. Imaging technology helps to localize and assess the tumor spread.

5. Do carcinoid tumors run in families?

Ans. Carcinoid tumor does not appear to run in families. However, people with a familial genetic condition, like  MEN 1 (multiple endocrine neoplasia - type 1), have a higher risk of getting intestinal and bronchial carcinoid tumors.

6. How is carcinoid tumor treated?

Ans. The treatment focuses on symptom control, biochemical control, tumor control, and improving quality of life. Cytoreductive surgeries, systemic therapy, and radiotherapy help manage carcinoid tumors.

7. What is the prognosis for carcinoid tumors?

Ans. Prognosis refers to the possible outcome or the course of the disease; the chance of recovery or recurrence. 

The prognosis depends on various factors like the tumor's location, metastasis, and treatment plans.

References

• Carcinoid Tumors

• Guidelines for the diagnosis and management of carcinoid tumors

• Neuroendocrine tumors and carcinoid syndrome