**5.1. Mesenchymal tumours**

invasion and accompanied stroma reaction, the term dysplastic ECL-hyperplasia can be used. If the dysplastic ECL-nodules exceed 0.5 mm or invade the submucosa, the correct term is NET [2]. NETs of all types are composed of uniform cuboidal cells with round nuclei with stippled ('salt and pepper-like') chromatin and eosinophilic, granular cytoplasm. Nuclear pleomorphism, nucleoli and mitosis are unusual/infrequent in typical NETs (unlike neuroendocrine carcinoma). Growth pattern of NETs can be quite different and even quite heterogeneous in the same tumour forming nests, trabecular, tubules, rosettes or solid structures of tumour cells. Immunohistochemically, gastric NETs are consistent chromogranin A positive and have

**Type 1 Type 2 Type 3 Indicators of behaviour**

Normal (sporadic tumour)

>1.5 cm, solitary rare < 1.5 cm multiple

Benign <1 cm

mucosa or submucosa no angioinvasion

beyond sumucosa angioinvasion >2 cm any endocrine functioning tumour Ki67 > 2–20%

High-grade malignant smaller or large cell neuroendocrine carcinoma Ki67 > 20%

Hypertrophic with hyperplastic, intense eosinophilic parietal cells due to Zollinger-Ellison syndrome *usually MEN1*

**ECL-hyperplasia** Yes Yes No Low-grade malignant

> 1.5 cm in 20%

**Outcome** Never fatal Rarely fatal 25% mortality *Sources*: Modified from Abraham et al. [13]; Capella et al. [14], and Klöppel et al. [15].

Gastric neuroendocrine carcinomas are very rare (separated into small-cell and large-cell NECs). These poorly differentiated tumours are highly proliferative active (>20 mitosis/10

Rare (atypical), NETs coexist with adenocarcinoma ('adenocarcinoid)—so-called MANEC (mixed adeno-neuroendocrine carcinoma, according to WHO). MANECs have the similar

hpf or Ki67 >20%) and show an aggressive biological behaviour [3, 21].

• NET, type 3: Surgery (e.g. gastrectomy); polypectomy in small tumours [2]

prognosis to that of conventional adenocarcinoma [2].

• NET, type 1: usually endoscopic polypectomy • NET, type 2: usually endoscopic polypectomy

by definition a low Ki67 (up to 2%) [19, 20].

**4.2. Neuroendocrine carcinomas (NECs)**

**Table 6.** Typing of gastric neuroendocrine tumours.

Clinical significance:

**Background mucosa**

278 Gastric Cancer

Chronic atrophic corpus gastritis *usually autoimmune*

**Size** <1.5 cm multiple <1.5 cm multiple
