gastric carcinoid tumor
Originating from the histamine-containing enterochromaffin-like (ECL) cells of the embryologic foregut, gastric carcinoid tumors represent approximately 1.8% of all gastric neoplasms and approximately 7% of all carcinoids.
Because they are most often discovered incidentally during endoscopy, the incidence of gastric carcinoid tumors has increased in recent years as endoscopic technology continues to improve both technologically and diagnostically.
Carcinoids of the stomach are generally divided into three distinct groups based on their clinical and histological characteristics: carcinoid tumors associated with CAG-A, carcinoid tumors associated with Zollinger-Ellison syndrome (ZES) or MEN-1, and carcinoid tumors that occur sporadically.
Type I gastric carcinoids
Type I gastric carcinoids account for 70%–80% of all gastric carcinoids. These tumors are small, benign tumors associated with chronic atrophic gastritis and chronic hypergastrinemia. The relative importance of gastrin in the development of type I gastric carcinoids is lent support by animal studies in which lifelong inhibition of acid secretion in rats induced by potent inhibitors of acid secretion or subtotal fundectomy was found to be associated with the development of carcinoid tumors of ECL cells in the gastric corpus.
To date, however, no cases of carcinoid tumor have been attributed to the use of proton pump inhibitor therapy in humans, suggesting the importance of other factors in the development of type I gastric carcinoids. These tumors often exhibit an indolent disease course and tend to be nonfunctional and asymptomatic.
Likewise, metastases are rare, occurring in <10% of tumors <2 cm in greatest dimension.
Type II gastric carcinoids
Accounting for approximately 5% of gastric carcinoids, type II tumors arise in the setting of MEN-1 and ZES. Like type I gastric carcinoids, they are thought to arise from ECL cells under the influence of hypergastrinemia, resulting in low-grade malignant behavior and associated hyperplasia of surrounding ECL cells.
Allelic loss of the MEN1 gene locus, a tumor-suppressor gene located on chromosome 11q13, is thought to be involved in the pathogenesis of many of these tumors.
Though type II gastric carcinoids are generally indolent and behave similar to type I lesions, these tumors may be large and polypoid, unlike most small type I carcinoids.
Type III gastric carcinoids
Type III gastric carcinoids account for nearly 15%–25% of tumors. They are usually large, solitary, sporadic tumors unassociated with hypergastrinemic states. Sporadic carcinoid tumors may be aggressive, with a high incidence of metastases and a 5-year survival rate <75%.
Unlike type I and II lesions, which produce serotonin, these tumors are prone to the development of atypical carcinoid syndrome related to the production of 5-hydroxytryptophan (5-HTP), characterized by flushing, hypotension, excessive lacrimation, edema, and bronchoconstriction.
Excessive production of 5-HTP is thought to be related to the absence of the enzyme aromatic acid decarboxylase, which converts 5-HTP to serotonin.
Treatment
Recent evidence suggests that type I gastric carcinoids have been overtreated. In a recent multi-institutional study of 65 patients with gastric carcinoid tumors, Borch and colleagues demonstrated that a majority of type I carcinoids were asymptomatic and were often detected incidentally at the time of upper endoscopy for other nonrelated symptoms.
As such, tumors <1–2 cm in greatest dimension may be clinically observed or removed endoscopically.
Antrectomy, by eliminating the trophic effect of gastrin, can be useful for large, multiple, or recurrent type I carcinoids.
The treatment of type II gastric carcinoids is more complex, largely because of the presence of multicentric disease and the relative frequency of distant metastases.
Currently, the treatment of type II carcinoids associated with ZES is similar to that of type I tumors; however, when tumors become >2 cm, gastrectomy should be considered.
Treatment recommendations for type III tumors are universal, given the much poorer prognosis and aggressive nature of these tumors. As such, radical gastrectomy, regardless of tumor size, is the mainstay of current therapy for these lesions.