Intralobular Distribution of Ovarian-like Stroma in Pancreatic Mucinous Cystic Neoplasms: Hypothesis on Its Tumorigenesis

Abstract

Pancreatic mucinous cystic neoplasm (MCN) harbors two histological components, tumor epithelia and ovarian-like stroma (OLS). To examine the tumorigenesis of pancreatic MCNs, this study analyzed the distribution, amount, immunohistochemical phenotype, presence of theca cells of the OLS, and the alteration of tumor epithelium of 29 surgically resected MCN cases and compared them with tumor sizes. Non-mucinous type epithelium was present in all low-grade MCNs but its ratio decreased with tumor size (p < 0.05), suggesting that epithelial mucinous changes are a progression phenomenon. The intralobular distribution of OLS was observed in 27.6 % of MCN cases and its existence related to a smaller size (p< 0.05), suggesting intralobular generation of MCNs. Nuclear expression of β-catenin was observed for OLS of everywhere, suggesting consistent activation of the Wnt pathway for OLS. Three MCN cases (10.3%) contained a-smooth muscle actin (SMA)-negative OLS, where OLS surrounding dilated pancreatic ducts or MCN cysts were a-SMA-positive and otherwise negative, suggesting that a-SMA-positivity is an acquired phenomenon of OLS. With this study, we could hypothesize that pancreatic MCNs may generate intralobularly. Epithelial mucinous change and a-SMA-positivity of OLS may be progression phenomena. This is the first study to show the intralobular distribution of OLS.