The American Journal of Gastroenterology · 2 authors, 2 centres
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Gastrointestinal neuroendocrine tumors (NETs) are increasingly common and often found incidentally during routine endoscopy. Accurate staging using Tumor-Node-Metastasis classification and grading via the WHO mitotic/Ki-67 index is critical for prognosis and management. Many small, low-grade NETs can be managed endoscopically, but higher-risk lesions (G2/G3, >2 cm, or midgut NETs) require surgical referral and multidisciplinary care.
**Background:** Gastrointestinal neuroendocrine tumors (GI NETs) are increasing in incidence, with rectal and small bowel NETs being the most common. They are frequently diagnosed incidentally on endoscopy or cross-sectional imaging. Because all NETs have malignant potential, accurate diagnosis, staging, and grading are essential for appropriate management. This narrative review provides gastroenterologists with practical guidance on recognizing, diagnosing, staging, and treating GI NETs.
**Methods:** This is a narrative review summarizing current evidence and consensus guidelines on GI NETs. The authors discuss epidemiology, diagnostic markers, endoscopic characteristics, staging modalities, grading classification, and management strategies for gastric, duodenal, small intestinal, and rectal NETs. Key data are drawn from published studies and consensus guidelines.
**Key Results:** Chromogranin A (CgA) is the most common serum marker but has limited sensitivity and specificity; it is not a screening test and is frequently falsely elevated by proton pump inhibitor use. Endoscopically, GI NETs appear as firm, nonmobile, polypoid or round lesions with smooth mucosa or central erosion, often with a red or yellow hue. Endoscopic ultrasound (EUS) shows hypoechoic, well-defined lesions in deep mucosal/submucosal layers. The WHO grading classification uses mitotic index and Ki-67 proliferation index to stratify tumors into G1, G2, and G3, with higher grades associated with worse prognosis. For staging, Gallium-68 Dotatate PET scans have 91% sensitivity and 94% specificity for initial NET diagnosis. For gastric NETs: Type I has 5- and 10-year survival equivalent to the general population; Type II lesions >2 cm have 10%–30% lymph node (LN) metastases and 5-year survival of 60%–75%; Type III has overall 5-year survival <50%. For duodenal NETs: tumors <1 cm have 2% risk of LN involvement, 1–2 cm tumors have 4.7% risk, and >2 cm tumors have 20% risk. R0 resection rates for duodenal NETs are estimated at 50%–60%. For midgut (jejunal/ileal) NETs, surgical resection is recommended regardless of size due to high metastatic potential; they are multicentric in 20% of cases, and carcinoid syndrome is the initial presentation in 35% of midgut NETs in population-based studies and >60% at tertiary centers. For rectal NETs: subcentimeter tumors without muscularis propria invasion, LVI, or nodal disease can be endoscopically resected with 98.9%–100% 5-year survival. Conventional polypectomy is not recommended due to high likelihood of incomplete resection.
**Clinical Implications:** Gastroenterologists play a critical role in the early detection and management of GI NETs. Accurate staging and grading are essential for prognosis and treatment decisions. Small, low-grade NETs (especially Type I gastric, small duodenal, and subcentimeter rectal NETs) can often be managed endoscopically. However, G2/G3 tumors, lesions >2 cm, and all midgut NETs should be referred to specialty centers with multidisciplinary tumor board discussion. Endoscopic resection should achieve negative margins; if margins are positive or worrisome features (LVI, G2/3) are present, further management is warranted. Genetic testing for MEN1, VHL, and NF1 may be relevant in appropriate cases.