Nesidioblastosis and Pancreatic Non-functioning Islet Cell Tumor in an Adult with Type 2 Diabetes Mellitus
A 43-year-old woman was hospitalized due to fever and right flank pain with a 2-year history of type 2 DM treated with oral hypoglycemic agents. Physical examination indicated right flank knocking tenderness. All laboratory findings were within normal limits, except for an increased white blood cell count in blood and urine, and elevated blood sugar level (201 mg/dL). Abdominal computed tomography showed a right ureteral stone with pyelonephritis. A 3.6 cm-sized cystic lesion in the pancreatic head was found incidentally (). After treating the pyelonephritis, the patient underwent a pylorus-preserving pancreatico-duodenectomy and double Roux-en-Y reconstruction based on a pancreatic cystic tumor, such as a solid pseudopapillary neoplasm or serous cystadenoma. Grossly, the cut surface of the pancreas head revealed a well-demarcated, solitary cystic mass that measured 5.6×3.7 cm and was dark red in color, with a soft cut surface and extensive hemorrhage (). On serial-sectioning, adjacent non-tumor pancreatic tissue appeared normal in gross examination. Histologically, the pancreatic mass was surrounded by a fibrous capsule consisting of nests or trabecular cords of neoplastic cells with extensive hemorrhage and coagulation necrosis (). The neoplastic cells were relatively uniform, with round or irregular nuclei and abundant eosinophilic cytoplasm, and revealed a centrally located round to oval nucleus. The chromatin pattern was characteristically coarsely clumped. Mitoses were very difficult to find. Lymphovascular invasion of the tumor cells was not observed. The neoplastic cells stained diffusely positive for synaptophysin and chromogranin (), but were negative for insulin and glucagon. The proliferation index was very low on the Ki-67 immunohistochemistry stain. Based on the histological and immunohistochemical findings, the tumor was diagnosed as a non-functioning pancreatic neuroendocrine tumor. There were a number of irregularly distributed hyperplastic islets throughout the uninvolved pancreatic parenchyma, and their contour and size were markedly variable (). Many islets were closely associated with pancreatic duct structures (). Hyperplastic islets were characterized by the presence of islet cells showing enlarged hyperchromatic nuclei with pleomorphism (). The majority of these dysplastic islet cells were positive for insulin, but negative for glucagon (). The histology of the non-tumoral pancreatic tissue was compatible with diffuse nesidioblastosis. She remained free of any sign of recurrent tumor and her diabetic symptoms were controlled with oral hypoglycemic drugs for 40 months after surgery.