NEWSLETTER
Carcinoid Tumors
Dr. Syed Khurram Shahid
Carcinoid tumors are rare, slow-growing tumors that originate in the cells of the neuroendocrine system. There are three main areas of origin for carcinoid tumors:
a). Foregut carcinoid tumors start in the lungs, bronchi, or stomach.
b). Midgut carcinoid tumors start in the smali intestine, appendix, or proximal large bowel.
c). Hindgut carcinoid tumors start in the distal colon or rectum.
The appendix is the most common site of Carcinoid tumors.
| Characteristics of Carcinoid Tumors by Location | |||||
| Location | Percent | Age at presentation | Symptoms | Metastasis at diagnosis | Carcinoid Syndrome (%) |
| Rectum | 26 | 60 | Rectal bleeding, pain and constipation | Tumor size < 1cm; 5%. Tumor size > 2cm; majority | < 5 |
| Small Intestine | 25 | 60 to 70 | Abdominal Pain, small bowel obstruction | Majority present with metastasis, usually to lymph nodes or liver | 5 to 7 |
| Lungs, bronchi and trachea | 23 | 50 | Recurrent Pneumonia, cough, hemoptysis, chest pain, wheeze | < 15% | < 5 |
| Appendix | 12 | 40 to 50 | Appendicitis, incidental finding during other pelvic operations | < 5% | < 5 |
| Stomach | 7 | 60 to 70 | Anemia, abdominal pain | < 10% | 5 to 10. also Zollinger-Ellison syndrome |
| Colon | 7 | 70 | Pain, anorexia, weight loss, anemia | > 66% | < 5 |
Carcinoid tumors pose a diagnostic challenge because they often are asymptomatic. Prognosis varies widely depending on the location and stage of tumor.
Clinical Presentation
Many carcinoid tumors are found during surgery for other reasons, usually at appendectomy or surgery for acute pancreatitis. If there are symptoms, they usually are vague, nonspecific, and organ-related.. The average time from symptom onset to diagnosis is more than nine years. A carcinoid tumor can be the lead point for an intermittent intestinal intussuception. These tumors characteristically present at age 50 to 60.
CARCINOID SYNDROME
Carcinoid syndrome typically does not occur until the tumor has metastasized to the lungs or liver. The symptoms of carcinoid syndrome include flushing (pale, purplish, or red), diarrhea (watery and explosive), tachycardia or hypotension, bronchospasm, telangicectasia, and right-sided heart disease of failure. Symptoms often are precipitated by exertion or by eating or drinking (especially items high in tyramine like blue cheeses, choclate and ethanol.
Carcinoid tumors contain many neurosecretory granules that are capable of the synthesis, storage, and release of substances, including serotonin, histamine, prostaglandins, kallikrein, bradykinins, substance P, gastrin corticotrophin, and neuron-specific enolase. The most prominent of these substances is serotonin. Degradation of 5-hydroxytryptamine results in 5-hydroxyindoleacetic acid (5-HIAA), which is excreted in the urine. 5-hydroxytryptamine can result in the symptoms of carcinoid syndrome.
Carcinoid syndrome occurs in only 10 percent of all patients with carcinoid tumors, and it is most often asscociated with midgut tumors.
| Differential diagnosis of Carcinoid Syndrome |
| FLUSHING Menopausal symptoms; pheochromocytoma; mastocytosis; benign cutaneous flushing; medullary carcinoms of thyroid; ingestants (e.g., food, drugs) |
| WHEEZING Asthma; anaphylaxis; pulmonary edema; bronchial foreign body |
DIARRHEA |
| HEART VALVE SYMPTOMS Rheumatic heart disease; subacute bacterial endocarditis; dilated cardiomyopathy; ischemic heart disease with papillary muscle dysfunction |
The diarrhea seems to be largely caused by excessive serotonin in the system. Bronchospasm may be mediated by serotonin and bradykinin. Patients with carcinoid heart disease demonstrate higher levels of serum serotonin and urine 5-HIAA than other patients with carcinoid syndrome. Left-side heart valves usually are less affected because of the metabolism of serotonin in the lungs.
Diagnosis
In patients with vasoactive symptoms, measuring the urinary excretion of 5-HIAA and serum chromogranin A level is recommended. Those with symptoms of bowel dysmotility syndromes, computed tomography (CT) and magnetic resonance imaging (MRI) may be helpful.
Urinalysis: HIAA may not be elevated in atypical carcinoids and can be elevated in other conditions such as tropical sprue, celiac disease, Whipple's disease, and small bowel obstruction.
Serum Analysis: 20glycoprotein that is secreted with other hormones by neuroendocrine tumors, appears to be the most promising, with specificity approaching 95 percent and sensitivity for carcinoid tumors approaching 80 percent.
Nuclear Medicine: (MIBG) is a structural analogue to norepinephrine, and I-labeled MIBG can be used for the detection of neuroendocrine tumors. PET may be useful in the diagnosis of neuroendocrine tumors as well. Somatostatin receptor scintigraphy with indium-111 labeled octreotide is superior to CT scans for localizing the primary tumor site and to MIBG scans in the diagnosis of carcinoid tumors.
TREATMENT
Treatment options include surgery, chemotherapy, and radiation with somatostatin analogues such as octreotide (Sandostatin) or alpha-interferon. Patients with carcinoid tumors should be referred to subspecialists who have expertise in its diagnosis, staging, and treatment.
| General Treatment options for the Malignant Carcinoid Tumors |
Carcinoid Tumor Hepatic metastases dominant: Long-acting somatostatin analogues; hepatic artery embolization or ligation with or without interferon, with or without chemotherapy. Systemic spread: Chemotherapy or interferon or long-acting somatostatin analogues |
Carcinoid Syndrome Systematic progression through treatment options: Heart disease |
Heart Disease Diuretics, long-acting somatostatin analogues, occasional valvular replacement. |
Flushing Avoid precipitating food and alcohol; 5-HT3-receptor antagonist; long-acting somatostatin analogues; interferon; hepatic artery embolization or ligation with or without interferon, with or without chemotherapy. |
Diarrhea Antidiarrheal agents; 5-HT3-receptor antagonist; long-acting somatostatin analogues; interferon; hepatic artery embolization or ligation with or without interferon, with or without chemotherapy. |
Wheezing >Selective bronchodilators; long-acting somatostatin analogues; interferon; hepatic artery embolization or ligation with or without interferon, with or without chemotherapy. |
PROGNOSIS
The prognosis for patients with these tumors is variable and related to the site of the primary tumor. Importantly, the most common cause of carcinoid syndrome is metastatic liver disease arising from a smali bowel carcinoid tumor. For these patients, the prognosis is uniformly poor.