Intestinal Carcinoid Tumor Clinical Presentation

Updated: Mar 02, 2017
  • Author: Hemant Singhal, MD, MBBS, MBA, FRCS(Edin), FRCS, FRCSC; Chief Editor: N Joseph Espat, MD, MS, FACS  more...
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Presentation

History

Clinical manifestations can arise from the primary tumor, from the sequelae of metastatic disease, or from the carcinoid syndrome. Nonhormonal manifestations vary according to the location of the primary tumor (see the Table below). Many intestinal carcinoids are small and asymptomatic, and are found incidentally or at autopsy.

Table 2. Presentation of Intestinal Carcinoids (Open Table in a new window)

Location Nonhormonal Symptoms Carcinoid Syndrome,



%



Metastatic Disease,



%



Stomach



 



Pain



Pernicious anemia



< 10 5-10



 



Small intestine



 



Pain



Intestinal obstruction



Up to 90 5-7
Appendix



 



Appendicitis



Incidental finding



 



< 5 < 5
Colon



 



Pain



Bleeding



Weight loss



>66 < 5
Rectum



 



Pain



Constipation



Bleeding



5 (< 1 cm tumors)



>90



< 5

Partial intestinal obstruction can be the result of an intense desmoplastic reaction characteristic of carcinoid tumors. Lower gastrointestinal bleeding can result from ulceration of the mucosa overlaying the tumor. Intestinal ischemia or infarction can occur secondary to mesenteric angiopathy characterized by a desmoplastic mesenteric reaction.

Constitutional symptoms are common to the clinical presentation. They include anorexia, weight loss, and fatigue. This is usually related to disease metastasis to regional lymph nodes or the liver, which is present in up to 90% of patients at the time of diagnosis.

Malignant carcinoid syndrome develops with carcinoid of the small bowel only with massive hepatic replacement by metastatic tumor. Serotonin and other vasoactive substances secreted by the hepatic metastases escape hepatic degradation and enter the systemic circulation directly, with resultant symptoms.

Approximately 10% of patients with an intestinal carcinoid tumor develop carcinoid syndrome.

Metastatic carcinoid neoplasm can be difficult to diagnose early in its natural history because the patient generally reports vague abdominal symptoms or flushing. The disease is typically estimated to have been present for more than 8 years before diagnosis.

Patients with carcinoid tumors are often misdiagnosed with irritable bowel syndrome or idiopathic flushing. The syndrome is characterized by hepatomegaly, diarrhea, and flushing in 80% of patients; right heart valvular disease in 50%; and asthma in 25%. Malabsorption and pellagra (ie, dementia, dermatitis, and diarrhea) are occasionally present and are thought to be caused by the excessive diversion of dietary tryptophan to serotonin.

Cutaneous flushing is a common manifestation (80% of patients) and is often the earliest sign of the syndrome. Flushing can occur spontaneously, typically in the head and neck. It may be triggered by excitement, exercise, some types of food, or alcohol. Flushing is mediated by the vasoactive peptides secreted by the tumor.

Diarrhea is the most common feature of carcinoid syndrome, affecting 80% of patients. It is usually episodic, often occurring after meals. The elevated circulating levels of serotonin stimulate the secretion of small bowel fluid and electrolytes and increase intestinal motility, resulting in diarrhea.

Carcinoid abdominal crisis is a rare acute abdominal syndrome characterized by severe abdominal cramping without a mechanical bowel obstruction. The mechanism of the crisis is believed to be intestinal ischemia caused by vasoactive substances elaborated by the carcinoid tumor, combined with a decreased mesenteric blood supply due to a perivascular fibrosis. The large-scale and continuous release of bioactive substances may also cause severe hypotension and watery diarrhea. Edema of the face, rapid pulse, and pruritus may also be present.

Right-sided cardiac valvular disease usually develops only after many years of the syndrome and manifests in approximately half the patients with long-standing carcinoid syndrome. Serotonin stimulation induces irreversible endocardial fibrosis of the tricuspid and pulmonary valves, resulting in valvular dysfunction (stenosis or incompetence). The lungs metabolize serotonin and protect the left heart from fibrosis. Carcinoid heart disease may ultimately result in cardiac insufficiency, usually with right-sided heart failure.

Asthma (25% of patients) is due to bronchoconstriction, which may be attributed to serotonin, bradykinin, or substance P elaborated by the carcinoid tumor. The treatment of asthma associated with carcinoid syndrome must be conducted very carefully because adrenergic drugs may cause the release of humoral agents from the tumor that may cause status asthmaticus.

The frequency of the various symptoms in carcinoid syndrome are depicted in the image below.

Frequency of symptoms in carcinoid syndrome. Frequency of symptoms in carcinoid syndrome.
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Causes

A prospective study by Cross et al identified the following risk factors for malignant small-intestine carcinoids [9] :

  • Age - Hazard ratio (HR) for ≥ 65 vs. 50-55 years = 3.31
  • Male sex - HR = 1.44
  • Obesity - HR for body mass index ≥ 35 vs. 18.5 to < 25 kg/m 2 = 1.95
  • Current menopausal hormone therapy use - HR = 1.94

Genetic syndromes associated with increased risk for carcinoid include multiple endocrine neoplasia type 1 (MEN1), neurofibromatosis type 1, tuberous sclerosis complex, and von Hippel-Lindau disease. MEN1 may be responsible for approximately 10% of carcinoid tumors. [5]

A population-based study from Sweden and Finland by Kharazmi et al found a high incidence of small intestine carcinoid tumors in first-degree relatives of patients with the disease; because of the rareness of small intestine carcinoid, however, the absolute risk remains moderate even within affected families. [10]

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Physical Examination

Physical examination findings may be normal, and the patient may appear to be healthy. Patients in carcinoid crises can have face, neck, and upper chest flushing lasting for hours to days. They can have hypotension, increased lacrimation, and fever and can be in moderate to severe distress. The typical patient is 61-66 years old and experiences flushing when performing a Valsalva maneuver.

Skin findings include facial telangiectasias, usually bimalar. Extremity rash is usually a finding in severe, uncontrolled, end-stage disease, thus implying niacin deficiency.

Examination of the lungs may reveal wheezing. Cardiac examination usually yields normal results, but with prolonged, uncontrolled serotonin secretion, patients may have evidence of tricuspid valve regurgitation and, less commonly, pulmonic stenosis.

The abdomen may be distended and nontender. Bowel sounds may be normal or high pitched. Hepatomegaly is possible.

Examination of the extremities may demonstrate bilateral lower extremity edema.

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