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carcinoid tumors

Monday 5 April 2004

Digital cases

- JRC:4122 : Pulmonary carcinoid tumor.
- JRC:4124 : Pulmonary carcinoid tumor.
- JRC:4127 : Pulmonary carcinoid tumor.
- JRC:4131 : Pulmonary carcinoid tumor.
- JRC:4135 : Pulmonary carcinoid tumor.
- JRC:6147 : Pulmonary carcinoid tumor.
- JRC:1591 : Spindle cell carcinoid tumor of the lung.
- JRC:6159 : Pulmonary atypical carcinoid tumor.
- JRC:14082 : Lung metastasis of a carcinoid tumor.

Definition: Carcinoid tumors are rare, slow-growing neuroendocrine tumors arising from the enterochromaffin cells disseminated throughout the gastrointestinal and bronchopulmonary systems.

Though they have been traditionally classified based on embryologic site of origin, morphologic pattern, and silver affinity, newer classification systems have been developed to emphasize the considerable clinical and histopathologic variability of carcinoid tumors found within each embryologic site of origin.

These neoplasms pose a diagnostic challenge because they are often innocuous at the time of presentation, emphasizing the need for a multidisciplinary diagnostic approach using biochemical analysis, standard cross-sectional imaging, and newer advances in nuclear medicine.

Similarly, treatment of both primary and disseminated carcinoid disease reflects the need for a multidisciplinary approach, with surgery remaining the only curative modality.

The prognosis for patients with these tumors is generally favorable; however, it can be quite variable and is related to the location of the primary tumor, extent of metastatic disease at initial presentation, and time of diagnosis.


The majority of carcinoids are found within the gastrointestinal tract (55%) and bronchopulmonary system (30%).

Population-based statistics have shown that, within the gastrointestinal tract, the small intestine is the most common site of carcinoids (45%), followed by the rectum (20%), appendix (17%), colon (11%), and stomach (7%).

Far less common anatomic sites have been reported in the literature, including carcinoids of the breast, larynx, thymus, and gall bladder.

Traditionally, the appendix had been identified as the most common site of carcinoid tumors within the gastrointestinal tract; however, recent studies suggest that the incidence of primary appendiceal carcinoid disease is declining while the incidence of gastric and rectal carcinoid disease is on the rise.

This evolution of carcinoid epidemiology presumably stems from improvements in technology and diagnosis over the last several decades, such as better endoscopic recognition of early, presymptomatic carcinoids in these anatomic locations.

- digestive carcinoid tumor

  • intestinal carcinoid tumor
  • appendiceal carcinoid tumor

- bronchial carcinoid tumor
- renal carcinoid tumor


- atypical carcinoid tumor

  • Atypical carcinoid tumor shows either focal necrosis or mitosis numbering between 2-10/2mm2. Atypical carcinoid tumor may exhibit all of the growth patterns and cytologic features of typical carcinoid tumor.

- spindle-cell carcinoid tumor
- goblet cell carcinoid tumor


- typical carcinoid tumor
- atypical carcinoid tumor

  • Atypical carcinoid tumor shows either focal necrosis or mitosis numbering between 2-10/2mm2. Atypical carcinoid tumor may exhibit all of the growth patterns and cytologic features of typical carcinoid tumor.


Carcinoids are rare neuroendocrine tumors (NETs) thought to arise from the enterochromaffin (Kulchitsky) cells found throughout the crypts of Lieberkühn of the gut.

Specifically, the term enterochromaffin refers to the ability to stain with chromium or chrome salts, a common feature of serotonin-containing cells.

Similarly, the granules of carcinoid tumors have a high affinity for silver stains, justifying the use of the nomenclature argentaffinoma, which was used interchangeably with carcinoid tumor years ago.

The diagnosis of carcinoid tumor is initially based on histology with confirmation by positive immunohistochemical staining, defined as positive staining for one or more neuroendocrine markers (such as chromogranin A [CgA]or synaptophysin), or electron microscopy in which the cells in most tumors are found to contain membrane-bound secretory granules with dense-core granules in the cytoplasm. Within these granules are a wide variety of biogenic amines and hormones characteristic of NETs.

The most common biologically active substance secreted from carcinoid tumors is serotonin, a vasoactive peptide whose biosynthesis is accomplished nearly exclusively by the enterochromaffin cells.

Synthesized from the amino acid tryptophan, the release of serotonin into the systemic circulation can cause the classic symptoms of carcinoid syndrome, which include diarrhea, episodic flushing, bronchoconstriction, and eventual right-sided valvular heart disease.


Traditionally, the biochemical diagnosis of carcinoid tumors has been based on the measurement of serotonin metabolites in a 24-hour urine collection.

Elevation of the pharmacologically inactive metabolite of serotonin, 5-hydroxyindoleacetic acid (5-HIAA), in a 24-hour sample has been found to be highly specific (100%) for the diagnosis of carcinoid disease but lacks sensitivity (73%).

The low sensitivity is not surprising, given that a negative urine 5-HIAA is expected for any patient who has a carcinoid tumor that does not secrete serotonin.

Likewise, 5-HIAA levels may not be elevated in atypical carcinoid disease and may be falsely elevated in other conditions such as celiac sprue, Whipple’s disease, and SBO.

Importantly, urine 5-HIAA must be performed on a 24-hour urine specimen because of fluctuations in serotonin over the course of a day.

Also, there are medications and foods (i.e., avocados, bananas, walnuts, etc.) that can affect the results of the urine 5-HIAA level and should be avoided during the collection.

Like 5-HIAA, platelet and urinary serotonin levels are highly specific for carcinoid and may be useful in patients with tumors that produce low levels of serotonin.

In fact, recent data suggest that the combination of urinary 5-HIAA levels with platelet and urinary serotonin levels results in accurate carcinoid identification in at least 84% of patients.

Serum analysis of CgA, the major member of the granin family of acidic secretory glycoproteins that are expressed in neuroendocrine cells and are cosecreted with bioactive hormones, is perhaps the most specific serum biomarker for carcinoid disease.

In a recent series of 238 patients with carcinoid tumors, CgA levels were found to be much higher in patients with neuroendocrine disease when compared with healthy control patients (p @<@ .001).

Likewise, when comparing all patients without reported neoplasia and patients with NETs, the specificity of CgA serum analysis for diagnosis was 84%–95% whereas the sensitivity was in the range of 75%–85%.

Unlike a urine 5-HIAA test, serum CgA testing does not rely on serotonin secretion by the tumor, and therefore it can be a better test for atypical carcinoids and nonsecreting tumors.

False-positive results may be seen with hepatic or renal failure, inflammatory bowel disease, atrophic gastritis, or chronic proton pump inhibitor use. Likewise, a 40% false-positive rate has been demonstrated in patients with multiple myeloma.


Effective treatment of carcinoid tumors requires a multidisciplinary approach in which combined modalities are used, including surgical resection of the primary tumor and debulking, hepatic chemoembolization, and medical therapy.

Though specific treatment decisions are complex and related to the location of the primary carcinoid disease and the presence of distal metastases, the preferred initial treatment for carcinoid tumors remains surgical resection.

Traditionally, the extent of surgical resection was dependent on the size of the primary tumor and its location, while a location-specific prognosis was commonly based on the extent of carcinoid disease, tumor histology, depth of tumor invasion, and gender.

In a more recent SEER database review of >35,618 patients with neuroendocrine disease, multivariate analysis revealed that, in patients with well-differentiated to moderately differentiated NETs, disease stage, primary tumor site, histologic grade, sex, race, age, and year of diagnosis were predictors of outcome (p @<@ .001)


- Carcinoid tumors. Pinchot SN, Holen K, Sippel RS, Chen H. Oncologist. 2008 Dec;13(12):1255-69. PMID: 19091780

- Carcinoid tumors. Barham M. N Engl J Med. 1999 Aug 5;341(6):454-5. PMID: 10438272

- Carcinoid Tumors: Current Concepts in Diagnosis and Treatment.
Öberg K. Oncologist. 1998;3(5):339-345. PMID: 10388123