Absolute Increase in Endocrine Cells in Pediatric Gastric Biopsies Following Long-Term Proton Pump Inhibitor Therapy
DF Schaeffer, E Hassal, T Sturby, DA Owen. The University of British Columbia, Vancouver, BC, Canada
Background: Long term gastric acid inhibition using proton pump inhibitor (PPI) therapy produces a marked increase in plasma gastrin, leading to expansion of the gastric oxyntic mucosa and hyperplasia of enterochromaffin-like (ECL) cells. Whether this leads to neuroendocrine neoplasms is unclear. Endocrine cell proliferative lesions have traditionally been classified as pseudohyperplasia, hyperplasia (diffuse, linear, micronodular, adenomatoid), dysplasia, and neoplasia (intramucosal or invasive carcinoids). This study was aimed at determining the ECL response to long term PPI therapy by measuring the absolute number of endocrine cells in the gastric mucosa pre- and peri- therapy.
Design: 20 pediatric patients (mean age: 8.2yr) received a pretreatment (baseline) gastric body biopsy and a 'treatment' biopsy following PPI therapy for at least 9 month (median: 26.95 months). Immunohistochemical staining for synpathophysin and chromogranin A was performed on all cases. Positive cells were counted in a blinded fashion in at least 5 crypts/biospy and averaged. The Spearman rank-order correlation coefficient (r) was used to assess bivariate association.
Results: 'Treatment' biopsies showed a 72% increase in Synapthophysin positive cells [pre: 649 (range/crypt 2-19); post: 1191(range/crypt 5-25)] and a 100% increase in Chromogranin A positive cells [pre: 563 (range/crypt 1-15); post: 1124 (range/crypt 3-20)]. Three cases showed discordant results by Synaptohysin staining (decrease in ECL cells during treatment), while no discordant cases were identified in the Chromogranin A stained cases. Synapthophysin expression correlated positively with Chromogranin A expression (r=0.07). Histomorphologically, all cases showed simple diffuse hyperplasia, without evidence of nodular changes.
Conclusions: The present study introduces a simple, accurate and reproducible method for counting ECL cells in the gastric mucosa and classifying them accordingly. We demonstrated an increase in endocrine cells in the majority of pediatric patients undergoing long-term PPI treatment. While the ECL increase was predominantly present as simple hyperplasia, the striking increase of ECL cells in this patient cohort, in conjunction with an increase in PPI treatment throughout our society, warrants careful monitoring of ECL hyperplasia and further investigation into the long-term outcomes.
Monday, March 22, 2010 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 110, Monday Morning