Surgical management and pathology of gastric neuroendocrine tumours – Medical News Asia

ONCOLOGY

Endocrine/neuroendocrine tumours: Surgical management and pathology of gastric neuroendocrine tumours

Medical writer: Christy Leung | Last updated: 16 May 2025 | In: Oncology, Neuroendocrine Tumours, Endocrine Therapy

Article Keywords

gastric neuroendocrine tumours, histological features, surgical management, types of gastric neuroendocrine tumours, treatment algorithm

In February 2025, Dr Shirley Liu (Department of Surgery, The Chinese University of Hong Kong) and Dr Shelly Ni (Department of Anatomical & Cellular Pathology, The Chinese University of Hong Kong) shared their experience and expertise on gastric neuroendocrine tumours (NETs).

Gastric NETs are a rare type of neoplasm in Hong Kong, with fewer than five clinically confirmed cases reported at the Prince of Wales Hospital (PWH) in 2024. There is, in fact, no territory-wide or hospital-specific registry for gastric NETs at present locally. Gastric NETs are categorised into three types, each carrying a different prognosis (Table 1) and possessing particular endoscopic features (Figure 1).

Table 1. Types of gastric NETs^1-3

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Note: The abovementioned endoscopic features represent common findings. There may be exceptions in the clinical setting.

gNET, gastric neuroendocrine tumours; OGD, oesophagogastroduodenoscopy; SOB, shortness of breath; sx, symptoms; WLI, white light imaging

Figure 1. Features of gastric NET types^4-6

The basics of gastric NETs

Clinical presentation

Gastric NETs are often clinically silent, and most cases at PWH were diagnosed as incidental findings during oesophagogastroduodenoscopy.

Histological diagnosis and grading

While the gross appearance of NETs and other tumours of the stomach are comparable, gastric NETs exhibit some specific histopathological features. NET cells are arranged in nests, trabeculae, and organoid patterns. They are rounder in shape, with typical salt-and-pepper chromatin. The stroma is more vascular, and granular eosinophilic cytoplasm may be present, likely reflecting neuroendocrine substance secretion. The typical histological features of gastric NET cells under haematoxylin and eosin (H&E), synaptophysin, and chromogranin A stains are shown in Figure 2.

Slide (a), processed with H&E stain, shows vascularised stroma and cells with round nuclei. These cells are arranged in nests and focal rosette pattern. Gastric NET specimens are stained positively with the markers synaptophysin and chromogranin A, as seen in (b) and (c).

H&E, haematoxylin and eosin

Images courtesy of Dr Shelly Ni.

Figure 2. Histological features of gastric NET specimens

Once the features are identified as compatible with gastric NET, the specimen receives a histological diagnosis and tumour cells are graded. Mitotic index (number of cells in mitosis per 2 mm²) and Ki-67 proliferation index are the parameters positively associated with tumour grading (Table 2). Low-grade tumours generally present as small polypoid or nodular growths of tissue, whereas high-grade tumours exhibit greater cytological pleomorphism and cellular atypia, although these are not among the defining parameters. Examples of low-grade versus high-grade gastric NET specimens can be seen in Figure 3.

Note: If any discrepancy exists between the two parameters in determining the grading, the tumour is labelled as the higher grade.

Table 2. Grading of gastric NETs⁷

Histological slides (a) and (b) are from grade 1 well differentiated neuroendocrine tumour in the stomach, while specimen (c) can be found in a poorly differentiated neuroendocrine tumour. In slide (c), the tumour cells are monotonous with ovoid-shaped nuclei, stippled chromatin, and eosinophilic granular cytoplasm, with a background of intestinal metaplasia. Mitosis is inconspicuous.

Images courtesy of Dr Shelly Ni.

Figure 3. Histological specimens of low-grade (well-differentiated) versus high-grade (poorly differentiated) gastric NET

Biomarkers for gastric NETs

Pathologists use a combination of biomarkers to confirm the diagnosis, including insulinoma-associated protein 1 (INSM-1), synaptophysin, and chromogranin A. Synaptophysin has a higher sensitivity and lower specificity, while chromogranin A is more specific but less sensitive; these two biomarkers are thus complementary and used together in clinical practice, as recommended by the European Neuroendocrine Tumour Society (ENETS).⁸

Contrary to local clinical practice, which supports biomarkers mainly for NET diagnosis, the role of chromogranin A for other purposes remains controversial. Some researchers suggest using chromogranin A for treatment monitoring purposes⁹, while the Commonwealth Neuroendocrine Tumour Collaboration (CommNETS) working group questions its significance for detecting recurrence.¹⁰

Mode of treatment: endoscopy, laparoscopic surgery, or open surgery?

Gastric NETs may be resected via endoscopy or surgery, depending on the tumour type, size, depth of local invasion, and extent of disease. Currently, there is no standardised management algorithm for gastric NETs in international guidelines. The standard of practice at PWH is illustrated in Figure 4.

Type 3 gastric NETs, which have the poorest prognosis, require surgical resection. Laparoscopic surgery is feasible for small lesions confined to the stomach, whereas larger lesions that have invaded surrounding structures are managed via open surgery. Although an Italian consensus suggests endoscopic resection for type 3 lesions if the tumours are of small size, have low Ki-67 proliferation index, and have no radiological evidence of invasion or metastasis¹¹, this approach is not yet practiced locally due to insufficient evidence on survival outcomes.

Cases of type 1 tumour measuring <1 cm are suitable for endoscopic resection with a subsequent pathological assessment to confirm clear resection margins. Type 1 tumour lesions ≥ 1cm, or those with regional lymph node involvement or suspicion of deep tumour invasion (to the muscularis propria level) may warrant surgical removal (gastrectomy) instead of endoscopic resection. Imaging investigations such as endoscopic ultrasound, computed tomography (CT), and Positron Emission Tomography (PET)-CT are first carried out to detect lymph node involvement; radical gastrectomy is indicated if such involvement is confirmed. In cases where type 1 lesions are widespread across the stomach, gastrectomy may be considered. 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Treatment algorithm of gastric NETs at PWH

Follow-up monitoring

Patients receive individualised follow-up plans post-treatment based on tumour type, grading, and staging. For example, patients who have undergone endoscopic resection up to 3 years prior are suggested to be monitored and receive further endoscopic surveillance every 6 to 12 months.

As a tertiary care hospital, PWH is equipped with robust radiological, surgical, and pathological support, altogether facilitating a streamlined approach for disease management. Accurate classification of the tumour type, prompt referral to endocrine surgeons, and timely investigations will optimise the prognosis for patients with gastric NETs.

References

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Kim Y, et al. Gut Liver. 2023;17(6):863–73.

Sok C, et al. Ann Surg Oncol. 2024;31(3):1509–18.

Köseoğlu H, et al. World J Clin Cases. 2021;9(27):7973–85.

Bethineedi LD, et al. Int J Surg Case Rep. 2023;106:108238.

Sato Y. World J Gastrointest Endosc. 2015;7(4):346–53.

Nagtegaal ID, et al. Histopathology. 2020;76(2):182–8.

Shamiyeh A & Gabriel M. World J Gastroenterol. 2014;20(42):15608–15.

Tsai HJ, et al. Front Oncol. 2021;11:741096.

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This article is not medical advice. Patients should seek personal assessment by a licenced specialist. Physicians are recommended to read the full publication(s) as cited in the article before making medical decisions. This article does not supersede nor replace the published article(s).