Podoplanin expression in the cyst wall correlates with the progression of intraductal papillary mucinous neoplasm

A thickened, enhanced cyst wall on imaging examinations is one of the "worrisome features" described in the consensus guidelines for management of intraductal papillary mucinous neoplasm of the pancreas (IPMN). Podoplanin (PDPN) expression by cancer-associated fibroblasts is known to be an indicator of poor prognosis in some types of cancer. We performed immunohistochemical staining for alpha-smooth muscle actin (alpha-SMA) in IPMN lesions and determined the pathological wall thickness by measuring the thinnest and thickest alpha-SMA-positive parts of the wall of the largest cyst in each case, and the mean of these two values was recorded as the wall thickness. The thickness of the pathological wall increased with progression from IPMN with low-grade dysplasia to IPMN with an invasive carcinoma. The pathological wall was thicker in IPMN with main duct involvement, nongastric-type IPMN, and IPMN with mural nodules. We also stained for PDPN and assessed the thickness of cyst wall staining as for alpha-SMA. The thickness of the PDPN-positive cyst wall varied in a pattern similar to the thickness of the alpha-SMA-positive pathological cyst wall. PDPN-positive stromal fibroblasts in the invasive component of IPMN-IC were evaluated as a ratio to alpha-SMA-positive fibroblasts. A high ratio (> 50 %) of PDPN-positive stromal fibroblasts was a predictor of poor outcome. PDPN expression in the cyst wall correlates with the progression of IPMN. PDPN may be a significant prognostic marker of IPMN-IC.