What is a carcinoid tumor?

Carcinoid Tumors: A Comprehensive Overview

Carcinoid tumors are rare neuroendocrine neoplasms that originate primarily in the gastrointestinal tract (two-thirds) and lungs or thymus (one-third), characterized by their ability to secrete hormones and vasoactive peptides that may lead to carcinoid syndrome when metastasized to the liver. 1

Definition and Origin

• Carcinoid tumors are slow-growing neuroendocrine tumors that can arise from different embryonic divisions of the gut: foregut (lungs, bronchi, stomach), midgut (small intestine, appendix, proximal colon), and hindgut (distal colon, rectum) 2
• Within the gastrointestinal tract, they commonly occur in the stomach, small intestine, appendix, and rectum 1
• Approximately one-third arise in the lungs or thymus, while two-thirds originate in the gastrointestinal tract 1

Epidemiology

• Carcinoid tumors affect both sexes equally and can occur in all age groups 3
• The incidence has been steadily increasing in recent years 2
• They are relatively rare with an estimated incidence of 0.2-0.4 per 100,000 per year for pancreatic neuroendocrine tumors 1
• About 10% of carcinoid tumors are associated with Multiple Endocrine Neoplasia type 1 (MEN1) 4
• Another 10% are associated with other non-carcinoid tumors of various histological types 4

Pathophysiology

• Carcinoid tumors may secrete various hormones and vasoactive peptides including serotonin, histamine, and tachykinins 1
• Bronchial carcinoids have been associated with adrenocorticotropic hormone (ACTH) production and can cause Cushing syndrome 1
• Carcinoid tumors arising in the small intestine or appendix are more commonly associated with carcinoid syndrome 1
• The metabolic products released by intestinal carcinoid tumors are normally destroyed by liver enzymes in the portal circulation 1
• Carcinoid syndrome typically occurs when liver metastases or retroperitoneal disease allow these hormones to bypass hepatic metabolism and enter directly into the systemic circulation 1

Clinical Presentation

• Many carcinoid tumors are asymptomatic and found incidentally (e.g., during appendectomy) 5
• Symptoms may be related to:
  • The primary tumor location (obstruction, pain, nausea, vomiting) 1
  • Hormone secretion (carcinoid syndrome) 1
• Carcinoid syndrome occurs in approximately 8% of patients with carcinoid tumors and is characterized by: 1, 3
  • Episodic facial flushing
  • Diarrhea
  • Abdominal pain
  • Wheezing
  • Edema
• Cardiac complications (tricuspid regurgitation and/or pulmonary stenosis) develop in 10-30% of patients with carcinoid syndrome 1

Types of Carcinoid Tumors

• Gastric carcinoids are classified into three types: 1
  • Type 1: Associated with chronic atrophic gastritis
  • Type 2: Associated with Zollinger-Ellison syndrome
  • Type 3: Sporadic
• The NCCN Guidelines address seven major subtypes: 1
  • Jejunal/ileal/colon
  • Duodenal
  • Appendix
  • Rectal
  • Gastric
  • Bronchopulmonary
  • Thymus

Metastatic Potential by Location

• Ileal carcinoids have a 60% rate of nodal metastases and 30% rate of liver metastases 6
• Right colon carcinoids show high metastatic rates (70% nodal, 40% liver metastases) 6
• Appendiceal carcinoids have a low metastatic potential (5% nodal, 2% liver metastases) 6
• Rectal carcinoids have relatively low metastatic rates (15% nodal, 5% liver metastases) 6
• Bronchial carcinoids show a 15% rate of nodal metastases and 5% rate of liver metastases 6

Diagnosis and Evaluation

• Imaging studies are essential to assess disease burden and primary location: 1
  • Multiphase CT or MRI scans for evaluation of liver metastases
  • Radiolabeled somatostatin receptor scintigraphy ([111In-DTPA]-octreotide/Octreoscan)
• Additional site-specific evaluations include: 1
  • Colonoscopy and small bowel imaging for jejunal/ileal/colon carcinoids
  • Endoscopic ultrasound (EUS) and/or esophagogastroduodenoscopy for duodenal and gastric carcinoids
  • Proctoscopic examination for rectal carcinoids
  • Bronchoscopy for bronchopulmonary and thymic carcinoids
• Biochemical diagnosis has improved with the introduction of plasma chromogranin A 4

Treatment

• Surgical resection is the primary treatment approach for most localized carcinoid tumors 1, 6
• Management depends on tumor size, primary site, and the general condition of the patient 1
• For metastatic disease or carcinoid syndrome: 3, 4
  • Somatostatin analogues (lanreotide and octreotide) are the treatment of choice for controlling hormone-mediated symptoms
  • Hepatic-artery embolization and chemo-embolization for liver metastases
  • Radiofrequency ablation
  • Orthotopic liver transplantation in selected patients
• Chemotherapy has limited efficacy in most carcinoid tumors 4, 7

Prognosis

• Prognosis varies according to stage at diagnosis, histologic classification, and primary site of the tumor 1
• Carcinoid tumors are generally slow-growing, and patients have lived for up to 30 years after metastasis diagnosis 3
• The overall five-year survival rate for all neuroendocrine tumors is approximately 67.2% 1

Special Considerations

• A multidisciplinary approach is essential for managing these rare tumors 4, 5, 7
• Genetic testing should be considered in all cases of carcinoid tumors, especially when there is a family history or second endocrine tumor 1
• All patients should be evaluated for second endocrine tumors and possibly for other gut cancers 1