Foregut NET

Also known as carcinoid tumours

See separate topic under 'small bowel' - 'midgut NETs'

Epidemiology

• Increasing incidence in stomach - thought to be due to increasing surveillance and widespread use of PPIs

Pathophysiology

• Arise from neuroendocrine precursor cells (enterochromaffin cells)
• Can manifest at any site in the body
• GIT sites:
  • Stomach (8% of all NETs)
  • Small intestine
  • Rectum
  • Appendix
• Typically non-functioning in the stomach and rarely cause carcinoid syndrome
• Classification:
  • Classification based on morphology alone is not very useful, because it does not accurately predict clinical course. Need to use mitotic rate and Ki67 index. The distinction between a G3 NET and a carcinoma can be difficult.

Classification

• Three distinct subtypes of gastric NETs

	Type 1 - complication of atrophic gastritis	Type 2 -  complication of ZES	Type 3 - sporadic	Type 4 (Neuroendocrine carcinoma)
Proportion of gastric NETs	70-80%	5-10%	10-15%
NET characteristics	Usually non-functioning	Usually non-functioning
Associated pathology	ECL cells transform into NETs in setting of chronic achlorhydria and subsequent high gastrin levels.  Can occur with atrophic gastritis, pernicious anaemia, prolonged PPI use.	ECL cells transform into NETs in setting of hypergastrinaemia, but this time it is caused by gastrinomas in pancreas or duodenum. Often seen with ZES and MEN1.	None - sporadic tumours. Absence of atrophic gastritis, ZES or MEN1.
Location	Multiple small tumours (<1cm) confined to mucosa or submucosa in fundus or body. Tumours usually appear as polypoid lesions with a small central ulceration.	Multiple small tumours in fundus, antrum and body	Large solitary lesions in fundus or antrum
Gastric acid level	Low	High	Normal
Serum gastrin level	High (because of atrophic gastritis)	High (because of ZES)	Normal
Treatment	EMR if <1-2cm Partial gastrectomy or wedge if larger Antrectomy sometimes performed - can lead to regression after fixing high gastrin levels.	EMR if <1-2cm Partial gastrectomy or wedge if larger Treat gastrinoma	Partial or total gastrectomy with local lymph node resection	Aim for curative resection, but rarely possible Palliative approaches
Prognosis	Excellent	Good (long-term survival 70-90%, but can metastasise to regional nodes)	Poor (5 year survival 25-30%)	Poor - most patients present with widespread mets. Very aggressive.

Staging

• See 'pancreatic NETs' topic

Staging duodenal/ampulla of Vater NENs

Primary tumor (T)
T category	T criteria
TX	Primary tumor cannot be assessed
T1	Tumor invades the mucosa or submucosa only and is ≤1 cm (duodenal tumors). Tumor ≤1 cm and confined within the sphincter of Oddi (ampullary tumors).
T2	Tumor invades the muscularis propria or is >1 cm (duodenal). Tumor invades through sphincter into duodenal submucosa or muscularis propria, or is >1 cm (ampullary).
T3	Tumor invades the pancreas or peripancreatic adipose tissue
T4	Tumor invades the visceral peritoneum (serosa) or other organs
NOTE: Multiple tumors should be designated as such (and the largest tumor should be used to assign the T category): If the number of tumors is known, use T(#); eg, pT3(4) N0 M0. If the number of tumors is unavailable or too numerous, use the m suffix, T(m); eg, pT3(m) N0 M0.
Regional lymph nodes (N)
N category	N criteria
NX	Regional lymph nodes cannot be assessed
N0	No regional lymph node involvement
N1	Regional lymph node involvement
Distant metastasis (M)
M category	M criteria
M0	No distant metastasis
M1	Distant metastases
M1a	Metastasis confined to liver
M1b	Metastases in at least one extrahepatic site (eg, lung, ovary, nonregional lymph node, peritoneum, bone)
M1c	Both hepatic and extrahepatic metastases
Prognostic stage groups
When T is...	And N is...	And M is...	Then the stage group is...
T1	N0	M0	I
T2	N0	M0	II
T3	N0	M0	II
T4	N0	M0	III
Any T	N1	M0	III
Any T	Any N	M1	IV

Workup

• Gastroscopy
  • EUS can help establish depth of lesion
• CT
  • Bright enhancement on CT on arterial phase, mets will also be hyperenhancing
• PET
  • Avid on DOTATATE-PET or octreotide scan
• Chromogranin A is often elevated - useful as biomarker