• Clinical science

Carcinoid tumor

Abstract

Carcinoids are small, slow-growing neuroendocrine tumors. They are most commonly located in the gastrointestinal tract and can synthesize a variety of hormones (especially serotonin). Most carcinoids are asymptomatic because most of the hormones they produce are metabolized by the first-pass effect in the liver. Carcinoid syndrome – characterized by diarrhea, flushing, dyspnea, and wheezing may occur if a serotonin-producing tumor has metastasized to the liver, bypassing first-pass metabolism. Elevated 5-HIAA in the urine helps to establish the diagnosis. Imaging techniques such as CT, MRI, and somatostatin receptor scintigraphy are used to detect the primary tumor as well as its metastases. Surgical resection is the first-line treatment. In inoperable cases, somatostatin analogs can be given.

Epidemiology

  • Incidence: 1.5/100,000 per year
  • Bimodal distribution: 15–25 years and 65–75 years (but can occur at any age)
  • Sex: > approx. (5:4.5)

References:[1][2]

Epidemiological data refers to the US, unless otherwise specified.

Pathophysiology

The rule of thirds for carcinoid tumors: ⅓ are multiple, ⅓ have a second malignancy, ⅓ metastasize.

References:[3][4][5][1][6][7]

Clinical features

In a patient presenting with secretory diarrhea, episodic flushing, wheezing, and cardiac valvular abnormalities, consider a carcinoid tumor!References:[1][7][8][4][9][6]

Subtypes and variants

Diagnostics

Biochemistry tests should be performed first if a carcinoid tumor is suspected. Imaging tests are then used to localize and stage the tumor.

  • Biochemistry tests
    • ↑ 5-hydroxyindoleacetic acid (5-HIAA) in 24-hour urine
      • Beginning 3 days prior to urine collection, serotonin-rich foods should be avoided (e.g., bananas, walnuts, avocados, and pineapples).
    • Fasting plasma 5-HIAA concentration
    • Chromogranin A (tumor markers) serum levels
    • Serotonin serum levels
  • Imaging
    • CT scans of the abdomen and pelvis
    • Somatostatin-receptor scintigraphy
    • MRI
    • Transabdominal ultrasound: although not part of the workup, sometimes detects a mass if routinely conducted
    • Endosonography may be considered
  • Biopsy (with histology and immunohistochemistry)
  • Further diagnostics, depending on tumor location

References:[10][1][11]

Differential diagnoses

References:[12][8]

The differential diagnoses listed here are not exhaustive.

Treatment

  • Operable disease
    • Surgical resection is the treatment of choice. The exact procedure depends on the location of the tumor:
      • In the small intestine → resection of the affected segment and mesentery
      • In the appendixappendectomy
      • In the rectum → resection via endoscopy may be possible
      • In the liver → ligation of the hepatic artery
  • Inoperable disease
    • Somatostatin analogs (e.g., octreotide) relieve symptoms
      • 5-HIAA levels in the urine
      • High-dose treatment in metastatic carcinoid tumors: slows progression/increases survival time
    • Radiotherapy with radioactively-marked somatostatin analogs: indicated for neuroendocrine tumors expressing somatostatin receptors
    • Palliative chemotherapy (not very efficient): to reduce rapid tumor progression

References:[1]

Prognosis

5-year survival rate: 70–80%

  • Best survival rates in the case of localized disease, esp. appendiceal or lung carcinoids (93%)
  • Poor survival rates in metastatic disease (20%–30%)

Carcinoid heart disease (CHD) → late complication in 20%–70% of metastatic carcinoids. CHD may be the direct cause of death.