Gastric neuroendocrine neoplasias: literature review

Introduction: The gastric neuroendocrine neoplasias (NEN) are being diagnosed more and more often due to the wide spread of endoscopy methods and an increase in the imaging range, despite the rarity of the gastric neuroendocrine tumors (NETs) (which amounts to about 9% of all gastrointestinal neuroendocrine tumors and 0.3% of all gastric tumors). It is extremely important to distinguish in which case clinician and pathologist should suspect a neuroendocrine tumor and to classify it correctly, both at the stage of esophagogastroduodenoscopy and during pathological examination, because all these components affect the choice of the surgery extent, subsequent drug therapy, as well as the possibility of more accurate metastasis prognosis and the patient outcome.

Aim: The aim of this literature review is to systematize, generalize and discuss the recent data on gastric neuroendocrine tumors with a focus on current classifications including their critical analysis, and to show promising ways in the endoscopic and morphological diagnostics of these tumors, which, in turn, will have an effect on patient management. The search was performed among articles in the PubMed database (in English and German) and among Russian articles published on the eLibrary and Cyberleninka platforms using the following keywords: gastric neuroendocrine tumor, gastric carcinoid, gastric NET pathology, gastric NET morphology, gastric NET morphology, gastric NET diagnostics. The papers on surgical treatment methods, adjuvant therapy, as well as drug therapy with somatostatin analogues and other drugs were excluded. A brief retrospective journey into the history of neouroendocrine neoplasias serves to remind the histology and distribution of neuroendocrine cells in the gastric mucosa, followed by chronological review of NEN discovery and theory development up to the present moment. The morphological classification of gastric NET consisting of 4 possible types is highlighted: the correct interpretation of the pathological findings, taking into account not only the histological features of the tumor itself, but also of the adjacent mucosa, allows to suggest the appropriate managment, which fundamentally affects patient survival. The review provides other current classifications of the gastric neuroendocrine neoplasia depending on its location, embryogenesis, functional activity, histological grade (with a focus on the Ki-67 labeling index counting, and ways to improve the interobserver reliability in routine practice). Moreover, the differences in the gastric NET and NEC TNM classification are emphasized. The drawbacks of all classifications are discussed and the possibilities for their further development are considered. An important part of the review is the description of a possible immunohistochemical markers, since immunohistochemistry is widely used to confirm the diagnosis. In addition, INSM1 (insulinomaassociatedprotein 1), the new immunohistochemical and molecular marker for NEN is discussed: according to the literature, it contributes to more accurate assessment of the tumor malignant potential and the metastatic risk. Furthermore, modern methods of endoscopic and PET/CT imaging (68-gallium DOTATATE PET/CT, molecular imaging using SSTR (somatostatin receptor) PET/CT or GLP-1R (Glucagon-like peptide-1 receptor) SPECT (single photon emission computed tomography)/CT), which allows the clinician to suspect a NEN even before morphological analysis of the resected specimen and adequately select the extent of surgical intervention are shown.

Conclusion: We would like to reiterate the importance of further research on the gastric NET subtype pathogenesis and their clinical behavior, also of the correlation of the endoscopic, morphological, and immunohistochemical picture with the patient prognosis to improve managment tactics.