Intestinal Carcinoid Tumor Clinical Presentation

  • Author: Hemant Singhal, MD, MBBS, FRCSE, FRCS(C); Chief Editor: Jules E Harris, MD   more...
 
Updated: Jan 27, 2012
 

History

Clinical symptoms can arise from the primary tumor, from the sequelae of metastatic disease, or from the carcinoid syndrome. Many intestinal carcinoids are small and asymptomatic. They are found incidentally or at autopsy.

  • Symptoms of 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. See related CME, An Atypical Cause of Gastrointestinal Bleeding and Gastrointestinal Bleeding in the Elderly.
    • 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 involve 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.

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

LocationNonhormonal SymptomsCarcinoid Syndrome,



%



Metastatic Disease,



%



StomachPain



Pernicious anemia



< 105-10
Small intestinePain



Intestinal obstruction



Up to 905-7
AppendixAppendicitis



Incidental finding



< 5< 5
ColonPain



Bleeding



Weight loss



>66< 5
RectumPain



Constipation



Bleeding



5 (< 1 cm tumors)



>90



< 5
  • 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 have commonly been diagnosed 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 (80% of patients) feature of carcinoid syndrome. 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. Frequency of symptoms in carcinoid syndrome. Frequency of symptoms in carcinoid syndrome.
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Physical

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 aged 61-66 years and experiences flushing when performing a Valsalva maneuver.

  • Skin
    • Facial telangiectasias, usually bimalar
    • Extremity rash, usually in severe, uncontrolled, end-stage disease, thus implying niacin deficiency
  • Lungs - Wheezing
  • Heart - Usually normal but with prolonged, uncontrolled serotonin secretion, tricuspid valve regurgitation, and, less commonly, pulmonic stenosis
  • Abdomen
    • May be distended and nontender
    • Bowel sounds normal or high pitched
    • Hepatomegaly possible
  • Extremities - Bilateral lower extremity edema
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Causes

Risk factors are unknown, and the results of a genetic linkage analysis are inconclusive. Environmental toxins remain unidentified.

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Contributor Information and Disclosures
Author

Hemant Singhal, MD, MBBS, FRCSE, FRCS(C)  Senior Lecturer, Director of Breast Service, Department of Surgery, Imperial College School of Medicine; Consultant Surgeon, Northwick Park and St Marks Hospitals, UK

Hemant Singhal, MD, MBBS, FRCSE, FRCS(C) is a member of the following medical societies: Royal College of Physicians and Surgeons of Canada and Royal College of Surgeons of Edinburgh

Disclosure: Nothing to disclose.

Coauthor(s)

Kanchan Kaur, MBBS, MS (General Surgery), MRCS (Ed)  Consulting Breast and Oncoplastic Surgeon, Medanta, The Medicity, India

Disclosure: Nothing to disclose.

Alan A Saber, MD, MS, FACS, FASMBS  Associate Professor of Surgery, Case Western Reserve University School of Medicine; Director of Metabolic Surgery, Case Medical Center

Alan A Saber, MD, MS, FACS, FASMBS is a member of the following medical societies: American College of Surgeons, American Society for Gastrointestinal Endoscopy, and American Society for Metabolic and Bariatric Surgery

Disclosure: Nothing to disclose.

Charles Zammit, MD  Senior Specialist Registrar, Department of Surgery, Breast Unit Charing Cross Hospital of London, UK

Disclosure: Nothing to disclose.

Michael K McLeod, MD, FACE, FACS  Professor of Surgery and Program Director, Integrated General Surgery Program, Department of Surgery, Michigan State University College of Human Medicine

Michael K McLeod, MD, FACE, FACS is a member of the following medical societies: American Association of Clinical Endocrinologists, American Association of Endocrine Surgeons, American College of Surgeons, American Medical Association, Association for Academic Surgery, Central Surgical Association, International Association of Endocrine Surgeons, Michigan State Medical Society, Midwest Surgical Association, National Medical Association, Society of American Gastrointestinal and Endoscopic Surgeons, and Western Surgical Association

Disclosure: Nothing to disclose.

Specialty Editor Board

Lodovico Balducci, MD  Professor of Oncology and Medicine, University of South Florida College of Medicine; Division Chief, Senior Adult Oncology Program, H Lee Moffitt Cancer Center and Research Institute

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD  Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Benjamin Movsas, MD  Vice-Chairman, Department of Radiation Oncology, Fox Chase Cancer Center

Benjamin Movsas, MD is a member of the following medical societies: American College of Radiology, American Radium Society, and American Society for Therapeutic Radiology and Oncology

Disclosure: Nothing to disclose.

Rajalaxmi McKenna, MD, FACP  Southwest Medical Consultants, SC, Department of Medicine, Good Samaritan Hospital, Advocate Health Systems

Rajalaxmi McKenna, MD, FACP is a member of the following medical societies: American Society of Clinical Oncology, American Society of Hematology, and International Society on Thrombosis and Haemostasis

Disclosure: Nothing to disclose.

Chief Editor

Jules E Harris, MD  Clinical Professor of Medicine, Section of Hematology/Oncology, University of Arizona College of Medicine, Arizona Cancer Center

Jules E Harris, MD is a member of the following medical societies: American Association for Cancer Research, American Association for the Advancement of Science, American Association of Immunologists, American Society of Hematology, and Central Society for Clinical Research

Disclosure: GlobeImmune Salary Consulting

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Distribution of carcinoid tumors.
Frequency of symptoms in carcinoid syndrome.
Table 1. 5-Year Survival Rates by Stage and Primary Site Between 1973 and 1999
Site Localized,



%



Regional,



%



Distant,



%



Stomach683510
Small intestine576740
Appendix918128
Colon745125
Rectum874125
Table 2. Presentation of Intestinal Carcinoids
LocationNonhormonal SymptomsCarcinoid Syndrome,



%



Metastatic Disease,



%



StomachPain



Pernicious anemia



< 105-10
Small intestinePain



Intestinal obstruction



Up to 905-7
AppendixAppendicitis



Incidental finding



< 5< 5
ColonPain



Bleeding



Weight loss



>66< 5
RectumPain



Constipation



Bleeding



5 (< 1 cm tumors)



>90



< 5
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