Pancreatic-polypeptide cell hyperplasia associated with pancreatic or duodenal gastrinomas

An immunohistochemical investigation of pancreatic-polypeptide (PP) cells in the PP-rich region of the pancreas, of ventral embryological origin, was performed in three female patients affected by or previously operated on for functioning duodenal or pancreatic gastrinomas not associated with multiple endocrine neoplasia syndrome. A pronounced PP-cell hyperplasia showing histological patterns of endocrine cell dysplasia and focal adenomatosis as defined by Jaffe et al was found in all cases. Morphometric analysis showed that in these patients the fraction of ventral-type pancreatic lobules occupied by PP-immunoreactive cells was 14.77 +/- 5.73%, 8.94 +/- 2.92%, and 10.83 +/- 5.64%, respectively. These values were three to five times higher than the upper values found in controls (mean, 2.20%; range, 1.54 to 2.93%; P < .0001). PP-cell hyperplasia may contribute for the increased circulating levels of PP found in gastrinoma patients. In this regard, elevation of fasting blood PP was found in one of four determinations done in one patient, indicating that PP-cell hyperplasia may be responsible for, at least, transient PP hypersecretion. In one of our patients, PP-cell hyperplasia was found 15 years after normalization of gastrin levels by removal of a single pancreatic gastrinoma. This finding is against a trophic role for hypergastrinemia in the development of PP-cell hyperplasia. In one of two patients in whom the pancreatic regions of dorsal embryological origin (ie, body and tail of the gland) were examined, ventral-type, PP-rich islets were frequently encountered, a finding at variance with their exceptional detection in control cases. This finding suggests that PP cell hyperplasia of the PP-rich pancreatic region may be a feature of a more diffuse disorder of PP cell development in the pancreas of gastrinoma patients.