Islet-cell hyperplasia in genetic deficiency of alpha-1-proteinase inhibitor

By light microscopy and immunoperoxidase methods, morphology and distribution of alpha-1-proteinase inhibitor (Api) cells in the pancreatic islets were studied in seven patients with and in 17 patients without periodic acid-Schiff-positive, diastase-resistant globules in the liver. Five of the seven patients with liver globules had cirrhosis and emphysema, suggesting genetic deficiency of Api, which was confirmed in four by pi phenotyping (blood from one patient was not available). The two remaining patients had only a mild degree of liver fibrosis and mild emphysema and showed a normal MM phenotype. Islet cell hyperplasia and an increased population of Api cells were observed in all five patients with genetic deficiency, compared with the 17 patients without Api deficiency. These morphologic changes were more pronounced in the one homozygous patient than in the heterozygous patients. Nesidioblastosis, ductular proliferation, and atypia of insular cells were seen only in patients with an abnormal phenotype. The increased amount of Api in the islets in the genetic deficiency state may be due to hyperplasia and hypertrophy of Api cells or due to storage of abnormal Api in the preexisting Api cells. The exact stimulus for islet cell hyperplasia and proliferation of Api cells is still unknown.