Gastric neuroendocrine tumors associated with acid suppressant drugs are frequently associated with very prolonged drug use and may show unconventional morphologies.

BACKGROUND

Gastric well-differentiated neuroendocrine tumors (gNETs) arising in association with prolonged acid suppressant drug use, including proton pump inhibitors (PPIs) and/or histamine type 2 receptor antagonists (H2RAs), are an emerging subtype of gNET presumably arising from drug-related chronic hypergastrinemia. The clinicopathologic features of these gNETs were examined in an institutional cohort.

DESIGN

23 patients with 39 gNETs were included. gNETs were considered acid suppressant-associated in patients with documented PPI and/or H2RA use for >1 year or ≥2 features of drug effect (parietal and/or enterochromaffin-like (ECL)-cell hyperplasia and/or elevated serum gastrin) in those with limited clinical information. Histomorphologic features were assessed.

RESULTS

The median patient age was 65 years (range: 37-84) with a female predominance (female:male 1.6:1). Hypergastrinemia was present in 69 % (11/16) of tested patients (median: 232 pg/mL, range 130-407). In patients with documented drug use (n = 16), 50 % used for ≥10 years. Most gNETs were ≤1 cm and were restricted to the mucosa. Regional lymph node metastasis was rare (2/21; 9 %). Unconventional morphology included 15 % with secretory cribriform morphology and 3 % with mixed pseudopapillary and conventional morphology. 30 % of patients had multiple tumors diagnosed over spans ranging from 0.75 to 9 years, though none developed distant disease (median follow-up: 3 years, range 0-15), including 2 patients with lymph node metastasis (10- and 13-year follow-up).

CONCLUSIONS

Acid suppressant-associated gNETs have an indolent course, are often multiple, and are frequently associated with very prolonged PPI/H2RA use. Unconventional morphologies like those described in type 1 gNETs may be observed.