Morphological studies of the pancreas in persistent hyperinsulinemic hypoglycemia of infancy (PHHI) have focused on the diagnosis of focal vs. diffuse forms, a distinction that determines the optimal surgical management. ABCC8 or KCNJ11 genomic mutations are present in most of them.Aim:
Our aim was to report a new form of PHHI with peculiar morphological and clinical characteristics.Research Design and Methods:
Histopathological review of 217 pancreatic PHHI specimens revealed 16 cases morphologically different from diffuse and focal forms. They were analyzed by conventional microscopy, quantitative morphometry, immunohistochemistry, and in situ hybridization.Results:
Their morphological peculiarity was the coexistence of two types of islet: large islets with cytoplasm-rich β-cells and occasional enlarged nuclei and shrunken islets with β-cells exhibiting little cytoplasm and small nuclei. In small islets, β-cells had abundant insulin content but limited amount of Golgi proinsulin. Large islets had low insulin storage and high proinsulin production and were mostly confined to a few lobules. No evidence for KATP channels involvement or 11p15 deletion was found. Genomic mutations for ABCC8, KCNJ11, and GCK were absent. Patients had normal birth weight and late hypoglycemia onset and improved with diazoxide. Ten were cured by limited pancreatectomy. Six recurred after surgery and were medically controlled.Conclusion:
This new form of PHHI is characterized by a morphological mosaicism. Pathologists should recognize this mosaicism on intraoperative frozen sections because it is often curable by partial pancreatectomy. The currently unknown genetic background does not involve the classical genomic mutations responsible for diffuse and focal PHHI.