gastric carcinoid tumor

Definition: Neuroendocrine neoplasms arising from enterochromaffin-like (ECL) cells measuring more than 0.5 mm of diameter in size or invading submucosa

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.

Etiology

 Autoimmune Gastritis

• Related to type 1 carcinoid (75% of cases)
• Gastrin hypersecretion causes hyperplasia and neoplastic transformation of gastric ECL cells

 Zollinger-Ellison Syndrome Associated with MEN1

• Related to type 2 carcinoid (5-10% of cases)
• Gastrin hypersecretion by gastrin-secreting tumor causes hyperplasia and neoplastic transformation of gastric ECL cells

 Sporadic

• Related to solitary and larger type 3 carcinoids

 Defect of Acid Secretion by Parietal Cells

• Related to type 4 carcinoids
• Hypergastrinemia is secondary to achlorhydria

Clinical synopsis

 Gastric carcinoids represent 5% of all gastrointestinal carcinoids
 Most carcinoids (type 1, 2, and 4) are fundic
 Type 3 can arise anywhere in gastric mucosa
 Majority of gastric carcinoids are slowly growing, locally infiltrative, and generally of low-grade malignancy
 Endoscopic resection advocated for small tumors limited in numbers
 Antrectomy that removes hypergastrinemic drive advocated for type 1 carcinoid
 Metastases do not preclude long-term survival

Macroscopy

 Commonly multiple
 Small, smooth, firm, circumscribed, polypoid elevations of mucosa and submucosa

Microscopy

 Small cuboidal cells with round nuclei with evenly dispersed chromatin
 Solid, trabecular, and ribbon-like arrangement
 Commonly infiltrate submucosa but seldom deeper
 High-grade sporadic carcinoid tumor may resemble small cell carcinoma
 Immunocytochemistry positive for chromogranin-A, synaptophysin, Leu-7 and PGP9.5, and CEA-M
 Background corpus mucosa of type 1, 2, and 4 carcinoids shows various patterns of ECL-cell hyperplasia

Types

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,
 carcinoid tumors that occur sporadically.

 Type 1 gastric carcinoid tumors

• Type 1 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 2 gastric carcinoids

• Accounting for approximately 5% of gastric carcinoids, type II tumors arise in the setting of MEN-1 and ZES.
• Like type 1 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 2 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 3 gastric carcinoids

• Type 3 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 1 and 2 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

 type 1 gastric carcinoids

• Recent evidence suggests that type 1 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.

 type 2 gastric carcinoids

• The treatment of type 2 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 2carcinoids associated with ZES is similar to that of type I tumors; however, when tumors become >2 cm, gastrectomy should be considered.

 type 3 gastric carcinoids

• Treatment recommendations for type 3 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.