Intestinal Carcinoid Tumors and The Carcinoid Syndrome

Epidemiology


Rare

Incidence 2.47 4.48/100,000



Increased incidence in African-Americans

Age of distribution: 2nd to 9th decade



Peak age 50-70

Pathology
 

Arise from enterochromaffin cells of the GI tract Gross specimens are well circumscribed round sub-mucosal lesions

Classification


Classification based on origin of embryonic divisions of the alimentary tract

Foregut Localization
Stomach, duodenum, bronchus Trabecular Argyrophil 5-hydroxytryptophan, histamine, multiple polypeptides Stomach - 20-25 percent

Midgut
Jejunum, ileum, appendix, ascending colon Solid mass of cells Argentaffin Serotonin prostaglandins, polypeptides Small intestine - 35 percent, ascending colon 60 percent, appendix - 2 percent Classical

Hindgut
Transverse, descending, and sigmoid colon, rectum, genitourinary Mixed Variable Variable

Histology Silver staining Secretory products

Metastasis to liver

Rectum - less than 10 percent of tumors larger than 2 cm Rare

Carcinoid syndrome

Atypical + rare

Organ Specific Features



Appendix

Carcinoid is most common neoplasm of appendix Most are asymptomatic Account for 1/3 of small bowel neoplasms Most commonly in ileum within 60cm of ileocecal valve Carcinoid is uncommon Usually present with abdominal pain, anorexia, and weight loss Majority found incidentally on rectal exam or endoscopy Carcinoid syndrome is rare

Small Intestine

Colon

Rectum

Organ Specific Features



Stomach

Type 1: 70 80% of gastric carcinoids



Associated with chronic atrophic gastritis and often pernicious anemia Occur in association with gastrinomas (Zollinger-Ellison Syndrome) or MEN-1 Sporadic Carcinoids Not associated with atrophic gastritis or ZE syndrome or MEN 1

Type 2: < 5% of gastric carcinoids



Type 3: 20% of gastric carcinoids

 

Clinical Features


Foregut: vary with site

Gastric: PUD, abdominal pain, bleeding, occasionally atypical carcinoid syndrome Duodenal: Duodenal or biliary obstruction or duodenal ulcer

Midgut: initial symptom is usually vague abdominal pain

5-7% have carcinoid syndrome When symptoms occur, they are genearlly the same as adenocarcinoma: changes in bowel habits, obstruction, or bleeding.

Hindgut: usually nonsecretory

The Carcinoid Syndrome



Cutaneous Flushing

Occurs in 85% of patients with carcinoid syndrome Involves face, neck, and upper chest Associated with mild burning Mostly spontaneous but can be provoked by eating, drinking, EtOH, or defecation

The Carcinoid Syndrome

 

Venous Telangectasias

Occur late in course Occurs in 80% of patients with carcinoid syndrome Typically watery and nonbloody Can be associated with cramping Usually unrelated to flushing episodes

Diarrhea

Bronchospasm

The Carcinoid Syndrome



Cardiac Valvular Lesions

Plaque-like deposits of fibrous tissue on endocardium of valvular cusps, cardiac chambers, pulmonary artery, or aorta

The Carcinoid Syndrome Pathophysiology



The liver inactivates bioactive products of carcinoid tumors, therefore, patients with GI carcinoid only get carcinoid syndrome with hepatic metastases Many secretory products are involved

Serotonin: increased metabolism of dietary tryptophan to serotonin then to 5-HIAA



Most likely cause of diarrhea

The Carcinoid Syndrome Pathophysiology



Many secretory products are involved

Serotonin
 

increased metabolism of dietary tryptophan to serotonin then to 5-HIAA Most likely cause of diarrhea Seen in gastric carcinoids Leads to flushing Increased bradykinin vasodilitation flushing

Histamine
 

Kallikrein


Prostaglandins


Stimulate intestingal motility and fluid secretion Insulin, ACTH, gastrin, VIP Clinical sequelae are rare

Polypeptides
 

The Carcinoid SyndromeDiagnosis



Biochemical Testing

24 hour urinary excretion of 5-HIAA

   

Sensitivity 75%, specificity up to 100% Errors can be induced by drugs or foods Normal: 2-8 mg/d; Carcinoid: usually > 100 mg/d May not be useful for foregut carcinoids Sensitive but not specific Increased level may be poor prognostic marker

Chromogranin Concentration
 

The Carcinoid SyndromeDiagnosis

 

Blood Serotonin Concentration

Helpful when urinary 5-HIAA is equivocal Epinephrine or Pentagastrin



Provocations Tests

Useful in pateints who have flushing but normal or minimally elevated biomarkers

The Carcinoid SyndromeDiagnosis



Tumor localization

Abdominal CT Pentetreotide imaging

Treatment of Carcinoid Tumors

 

Localized Tumors:

Surgery: Extent of resection depends of site and size of tumor Surgery: Limited role depending on extent of tumor burden Embolization or Chemoembolization
 

Metastatic Tumors:

Prophylactic octreotide is indicated to prevent florid carcinoid crisis Response rate > 50%

RFA or Cryoablation Liver Transplant number of patients is small Chemotherapy

 

Minor activity for 5-FU/Streptozocin combinations Future therapies?: VEGF inhibitors (Bevacizumab) or Tyrosine Kinase Inhibitors (Sunitinib)

Treatment of the Carcinoid Syndrome



Flushing

Octreotide, Prednisone (foregut), Histamine Blockers (gastric), Chlorpromazine (foregut) Mild: Codeine or cholestyramine Severe: Octreotide


Diarrhea

Octreotide may also slow tumor growth

Prognosis


Depends on:
1) 2) 3) 4) 5)

Site of origin Size on discovery Presence and extent of mets on discovery Histology Presence of Carcinoid syndrome
-

worse prognosis

Five Year Survivial

    

Gastric: 51-91% Small Bowel: 52-77% Appendix: 71-100% Colon: 33-75% Rectum: 75-100%