Carcinoid syndrome pathophysiology

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [2]Associate Editor(s)-in-Chief: Parminder Dhingra, M.D. [3]


Carcinoid syndrome (CS) is a paraneoplastic syndrome caused by the secretion of serotonin (5-hydroxytrptamine) but can be caused by the secretion of histamine, kallikrein, prostaglandins, and tachykinins..Carcinoid syndrome is most commonly caused by neuroendocrine tumors of midgut. In patients with carcinoid syndrome, 70% of tryptophan is converted into serotonin which leads to secondary deficiency of niacin. Serotonin is metabolized into 5-hydroxy indoleacetic acid (5-HIAA) by aldehyde dehydrogenase, which is eliminated into the urine. Deficiency of niacin results in Pellagra which manifests as dermatitis, dementia, and diarrhea. Carcinoid tumors arising in the bronchi reach the systemic circulation before passing through the liver and may be associated with bronchoconstriction and manifestations of carcinoid syndrome without liver metastases. Bronchospasm leading to wheezing is caused by release of histamine. 5-HT2B is the receptor of serotonin in the cardiovascular system that may be involved in fibrogenesis. Fibrosis leads to Tricuspid and pulmonic regurgitation, pulmonary stenosis and cardiac arrhythmias. Serotonin and TGF-beta are secreted by neuroendocrine tumors and appear to play a central role in the development of mesenteric fibrosis. Carcinoid tumors are normally found throughout the gastrointestinal tract from mouth to anus, with the highest concentration of cells in the appendix and small intestine. Lung is the second most common site for neuroendocrine tumours . In the gastric or intestinal wall, carcinoids may occur as firm white, yellow, or gray nodules and may be intramural masses or may protrude into the lumen as polypoid nodules. Neuroendocrine tumors arise from enterochromaffin cells. The name "enterochromaffin" refers to the ability to stain the cell with potassium chromate (chromaffin), a feature of cells that contain serotonin.


  1. Primary pulmonary or ovarian carcinoid
  2. Pelvic or retroperitoneal involvement by metastatic or locally invasive small bowel carcinoid.
  3. Extensive bone metastases

Lung Carcinoid Tumor

Carcinoid Heart Disease

  1. Tricuspid and pulmonic regurgitation.
  2. Pulmonary stenosis.
  3. Cardiac arhythmias.

Mesentric fibrosis




Carcinoid tumors are normally found throughout the gastrointestinal tract from mouth to anus, with the highest concentration of cells in the appendix and small intestine. The pancreas contains a large number of these cells, the biliary tree only a few and the liver normally contains none. Fibrotic lesions are found on endocardium, particularly on the right side of the heart.

Gross Pathology

Gastrointestinal Carcinoid

In the gastric or intestinal wall, carcinoids tumors may occur as firm white, yellow, or gray nodule. The lesions may be intramural masses or may protrude into the lumen as polypoid nodules. The overlying gastric or intestinal mucosa may be intact or have focal ulceration.

Terminal ileal carcinoid gross pathology[17]

Neuroendocrine tumours of the lung

  1. Typical neuroendocrine tumor : well-differentiated, low-grade, slowly growing neoplasms that are localized and rarely metastasize to extrathoracic structures.
  2. Poorly differentiated and high-grade neuroendocrine carcinomas, as typified by small cell lung cancer and large cell carcinomas which behave aggressively, with rapid tumor growth and early distant dissemination.
  3. Atypical neuroendocrine tumor, which are of intermediate grade and differentiation, is intermediate between typical neuroendocrine tumor and small cell lung cancer.
  • Based on the location:

Carcinoid tumor of the lung may be classified based on the location into two subtypes:

  1. Bronchial carcinoid tumors: central lesions
  2. Peripheral pulmonary carcinoid tumors: peripheral lesions
  • Carcinoid syndrome is encountered uncommonly and most often with tumors of the large size (>5 cm).

Left upper lobe": A lung lobe 185x110x55mm with bronchovascular remnants up to 25mm. Arising in the hilum and involving the bronchus is a rubbery tan-pink tumor 21x20x19mm. The tumor is 6mm from the bronchovascular margins and 3mm from the hilar margin. 26mm from the tumor and 1mm from the pleura there is a firm white nodule 6mm. Peripheral to the tumor is an area where the lung shows dilated bronchi up to 12mm in diameter which lie 2mm from the pleura.Source: Radiopedia

Microscopic Pathology

On electron microscopy, the tumor cells are found to contain membrane-bound secretory granules with dense-core granules in the cytoplasm.

Typical carcinoid histopathology-The nuclei of the tumor cells are uniform with a stippled chromatin pattern. There is no mitotic activity or necrosis. source Case courtesy of Dr Yale Rosen, from wikicommons

The most recent nomenclature for neuroendocrine tumors of the digestive system from the World Health Organization (WHO) distinguishes two broad subgroups:[20][21][22]

Neuroendocrine tumor: which are further subdivided according to their proliferative rate:[23]

  1. Well-differentiated :Low grade also known as typical neuroendocrine tumors.
  2. Intermediate grade.(Intermediate-grade neuroendocrine tumor arising in the lung (but not elsewhere) are referred to as atypical carcinoid.


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