An Immunohistochemical and Ultrastructural Study of Pancreatic Microcystic Serous Cyst Adenoma with Special Reference to Tumor-Associated Microvasculature and Vascular Endothelial Growth Factor in Tumor Cells

Abstract

Pancreatic microcystic serous cyst adenomas are rare exocrine tumors composed of small cysts lined by glycogen-rich cells. The disease may be sporadic or present as part of von Hippel-Lindau (VHL) syndrome. Four sporadic cases of pancreatic serous cyst adenoma were examined by conventional histological, immunohistochemical, and ultrastructural methods. In the present study, new findings include the immunohistochemical identification of vascular endothelial growth factor (VEGF) and the lack of PDX-1 (putative master transcriptional factor in pancreatic stem cells) in the epithelial tumor cells. Ultrastructurally, many small blood vessels were intimately associated with epithelial tumor cells and adjacent fibroblastic cells. The observations suggest the possibility that VEGF-containing tumor cells act in a paracrine fashion to stimulate neovascularization; that peripheral blood in the vascular lumen might be filtered or processed by the endothelial and epithelial tumor cells; and that filtrates might therefore be stored as serous inclusions. It is hypothesized that pancreatic serous cyst adenomas might be under the abnormal regulation of the VHL gene, just like VHL disease itself and certain types of renal cell carcinoma, showing the distinctive histology of a rich vascularity intimately related to epithelial lining cells of cysts accompanied by stromal fibroblasts/myofibroblasts and collagenous stroma.