Management of Gastric Polyps

An Endoscopy-Based Approach

Yasser H. Shaib; Massimo Rugge; David Y. Graham; Robert M. Genta


Clin Gastroenterol Hepatol. 2013;11(11):1374-1384. 

In This Article

Gastric Neuroendocrine Tumors (Carcinoids)

Carcinoids are neuroendocrine tumors derived from enterochromaffin-like (ECL) cells.[70] The term carcinoid was discarded in the most recent (2010) World Health Organization classification of tumors in favor of neuroendocrine tumor.[71] In 2 large studies (Germany in 1994 and the United States in 2008) gastric neuroendocrine tumors comprised less than 2% of gastric polypoid lesions.[1,46]

Gastric neuroendocrine tumors are classified in 3 distinct types. Type I tumors represent 70% to 80% of all gastric endocrine tumors. They are associated with hypergastrinemia resulting from autoimmune (corpus-restricted) atrophic gastritis and, therefore, are found more commonly in elderly patients, particularly women, with atrophic gastritis and often are associated with pernicious anemia.[72,73,74] These tumors (Figure 7) are small (<1 cm), confined to the oxyntic mucosa, and tend to be multiple and usually co-exist with multifocal ECL cell hyperplasia. Gastric neuroendocrine tumors tend to be found incidentally, often in patients undergoing EGD as part of an evaluation for anemia. Histologically, they consist of nests or ribbons of endocrine cells (small polygonal cells with round nuclei featuring salt-and-pepper chromatin) with a very low proliferation index.

Figure 7.

Gastric neuroendocrine tumor. (A) A small gastric carcinoid with surface ulceration seen on retroflexion in the distal body. (B) Merging nests of ECL cells arranged in cords in the deeper part of carcinoids are characteristic of carcinoid tumors. (C) The neuroendocrine origin of their cells can be confirmed by a positive synaptophysin immunohistochemical stain.

Type II gastric neuroendocrine tumors are associated with hypergastrinemia resulting from a gastrin-secreting tumor. They frequently are detected as part of the work-up for MEN-1 syndrome or for Zollinger–Ellison syndrome.[75] In both instances the tumors are usually small (<1 cm) and show neither infiltrating nor pleomorphic features. In patients with MEN-1 syndrome the gastric mucosa is normal or mildly inflamed, but not atrophic. The fundic mucosa of patients with Zollinger–Ellison syndrome often is hypertrophic, with long densely packed oxyntic glands and no significant inflammation. This type of neuroendocrine tumor is the most uncommon, representing only 5% to 8% of gastric neuroendocrine tumors.[76,77] Type III (sporadic) neuroendocrine tumors are not associated with hypergastrinemia, are generally solitary, arise in otherwise healthy gastric mucosa, and are not accompanied by ECL cell hyperplasia. These tumors, which represent approximately 20% of all gastric neuroendocrine tumors, usually are detected when they become symptomatic, either secondary to mucosal erosion and blood loss or metastasis. Because these events tend to occur only after the tumors reach a certain size, these tumors are usually larger than 1.5 cm, display infiltrating growth patterns with areas of necrosis, and show various degrees of pleomorphism. Their proliferation index is high (mitotic count >20 per high-power field or a Ki-67 index > 20%). Type III neuroendocrine tumors have a generally poor prognosis with a mean survival of 28 months.[73,78]

Clinical Approach

Type I and II tumors often can be removed endoscopically. In select patient with numerous and recurrent type I neuroendocrine tumors, antral resection could be a reasonable option. Antrectomy works by reducing the gastrin-producing cell mass in the stomach, thus removing the stimulus (ie, hypergastrinemia) for ECL cell proliferation.[79] Newer treatments such as the gastrin receptor antagonist netazepide are being investigated and could represent an alternative new medical treatment for type I gastric carcinoids.[80] Patients with sporadic carcinoids (type III) may present with anemia, epigastric pain, or signs and symptoms caused by metastases, including the rare carcinoid syndrome (characterized by cutaneous flushing, diarrhea, bronchospasm, and cardiac valvular lesions). Surgery followed with chemotherapy is the treatment of choice.

Histopathologic Diagnostic Tips: Special Stains, Immunohistochemistry, and Molecular Studies

Neuroendocrine tumors are best diagnosed with the help of an immunohistochemical stain (synaptophysin, chromogranin A, or CD56). These 3 stains are essentially equivalent in their ability to highlight neuroendocrine markers: their specific use is mostly a matter of preference for each pathologist. In addition, a Ki-67 stain should be performed to count the percentage of proliferating cells and to determine the grade of the tumor (Figure 8).

Figure 8.

Ki-67 for carcinoids. When stained with Ki-67 (an immunohistochemical stain that selectively highlights proliferating cells), the indolent carcinoids (type I neuroendocrine tumors) found in patients with atrophic gastritis show that less than 2% of the neuroendocrine cells are in a proliferative status (A). In contrast, the usually malignant sporadic carcinoids (type III) show a proliferation index of a 20% or higher (B).