Case 2: A 6-year-old boy was admitted with abdominal pain for two weeks and hematochezia for 2 days. The physical examination, upper gastrointestinal system endoscopy, routine laboratory findings and Meckel　scintigraphy were unremarkable. Colonoscopy revealed polyploid architecture (0.6 cm in diameter) located in the rectum and 5 cm from the anal verge (Fig. 2a). Endoscopic resection was performed and the histopathological examination was consistent with a NET (Fig. 2 b and 2c).　Hematochazia was not observed during the hospitalization period. Due to the low risk of metastatic spread, and as the tumors were small (<1 cm, without muscularis invasion), we planned to perform endoscopic investigation every year.

Fig. 2. (a) Endoscopic view of polyploid architecture (0.6 cm in diameter) located in the rectum (black arrow); (b) Hematoxylin and eosin stain of the colon demonstrating NET; (c), Synaptophysin stain demonstrating NET in the rectum.

There are three situations in which clinicians suspect ECL-cell hyperplasia. The simplest is when a nodule or polyp is identified by the endoscopist. The second situation involves the evaluation of gastric atrophy, and finally in PPI use as a result of iatrogenic hypergastrinemia [5]. Initially, atrophic gastritis was not determined in case 1, although she had nodules in the stomach with history of PPI use.

Neuroendocrine nests are seen on the hematoxylin and eosin-stained sections; there is no need to perform special staining. ECL cells, typically found in the gastric corpus, are rare or absent in other compartments of the stomach [5]. ECL cells were identified in the cardia, corpus and antrum-corpus junction in Case 1. Long-standing hypergastrinemia and, acid suppression exerts a proliferative pressure on ECL cells, especially in the presence of H. pylori infection [6]. The time of ECL hyperplasia regression after H. pylori eradication is not known. In Case 1, there was PPI use together with H. pylori infection. At follow-up, 1 year after diagnosis, H. pylori was negative in the endoscopy examination but ECL had not regressed. Surveillance endoscopic biopsy revealed H. pylori–negative atrophic gastritis.

To date, there have been few published information regarding ECL cell hyperplasia in children [7]. ECL hyperplasia together with autoimmune thyroid disease and autoimmune gastritis has been previously reported [8]. Anti-thyroglobulin antibody was positive in case 1. Colonic and rectal NETs are also very rare in children [9]. Due to the low risk of metastatic spread, tumors that are small and confined to the mucosa or submucosa can be managed with endoscopic resection. Hindgut NETs have a substantial risk of relapse after resection and need to be followed up for at least 7 years [4]. In case 2, a small rectal tumor (<1 cm, without muscularis invasion) was excised, and it was planned to perform endoscopic investigation every year.

Chromogranin A levels correlate positively with ECL cell mass in patients with AMAG [10]. Only a small fraction of hindgut NETs produce and secrete serotonin or other bioactive hormones [3].

In conclusion, gastric NETs are usually solitary and large and have frequently metastasized by the time of presentation. Pediatric gastroenterologists and pathologists must be aware that NETs can begin at a young age, and their immediate precursors such as ECL cell hyperplasia develop in the pediatric age group.

Contributors: TK: management of cases; TK, SD: wrote the manuscript; MC, NK: evaluated the histological preparations; MAK: case management and final　approval　of manuscript.

Funding: None; Competing interest: None stated.

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