**3.2. Type 2 GNETs**

described as slowly growing, they all have malignant potential. Therefore, surgical resection

Gastric NETs (GNETs) are rare tumours, but their incidence is growing. The proportion of GNETs amongst all gastrointestinal NETs also increases. The current incidence is 1–2 per 100,000 persons per year which accounts for 8.7% of all gastrointestinal NETs. This increase of incidence is at least partly related to more widespread use of gastrointestinal endoscopy [18, 19]. There are three to four types of GNETs which differ significantly in terms of biologic behaviour, malignancy, prognosis and optimal treatment [18–20]. Some discrepancy in literature regarding classification of GNETs is noted. Although the latest European Neuroendocrine Tumour Society (ENETS) guidelines still divide GNETs in three types, a further subclassification of type 3 tumours is considered appropriate [20]. A comparison of different GNET types

**Tumour characteristics Type 1 GNET Type 2 GNET Type 3 GNET**

Proportion of GNETs (%) 70–80 5–6 10–15 Associated diseases/syndromes Chronic atrophic gastritis MEN1-ZES Sporadic Typical tumour size (cm) <1–2 cm <1–2 cm >2 cm Tumour number Multiple Multiple Solitary Location Fundus, corpus Fundus, corpus Any Serum gastrin ↑ ↑ N Histology (most common) NET G1 NET G1/G2 NEC G3 Invasion Mucosa, submucosa Mucosa, submucosa Any Frequency of metastasis (%) 2–5 10–30 >50 Prognosis Excellent Good Poor

This is the most common type of GNETs (70–80%) and is more frequently seen in female patients. Type 1 GNETs develop from enterochromaffin-like (ECL) cells and are associated with chronic gastric mucosal atrophy caused by *H. pylori* or autoimmune gastritis. These tumours are well differentiated, usually small (<1 cm), multiple, located in the fundus or corpus, limited to mucosa or submucosa and have an excellent prognosis [18–20]. They have a very low mitotic rate and metastatic potential (2–5%) [18, 19]. Pathophysiological mechanism of type 1 GNET development is achlorhydria caused by atrophic gastritis, which stimulates

GNET, gastric neuroendocrine tumour; MEN1-ZES, multiple endocrine neoplasia type 1 and Zollinger-Ellison syndrome;

These tumours are best treated with conservative approach, with surgery reserved for selected cases. In ENETS guidelines, endoscopic surveillance every 1–2 years is recommended

gastrin production, which in turn evokes ECL cell hyperplasia [19].

N, normal; NET, neuroendocrine tumour; G, grade; NEC, neuroendocrine carcinoma.

is the only definitive treatment [18].

is depicted in **Table 2**.

212 Gastric Cancer

**3.1. Type 1 GNETs**

**Table 2.** Features of different gastric NETs.

These tumours are less frequently encountered (5–6%) and are associated with multiple endocrine neoplasia type 1 and Zollinger-Ellison syndrome (MEN1-ZES). Just like type 1 GNETs, they are gastrin-dependent, consist of ECL cells, are small, multiple and relatively benign. These are equally distributed amongst genders and in 10–30% of cases are metastatic at presentation. Although type 2 GNETs are asymptomatic per se, they can present with peptic ulcer disease due to hypersecretion of gastric acid caused by ZES [18–20].

According to the National Comprehensive Cancer Network (NCCN) guidelines, the treatment of type 2 GNETs is similar to type 1 tumours. In ENETS guidelines, however, only local surgical excision is recommended. The fact that the patient has multiple tumours does not alter surgical treatment by itself. Local or limited resection of the coexisting gastrinoma is recommended, but decision has to be made in a multidisciplinary setting in high-volume centres [18, 20].
