The distinctive characteristics of the micro-vasculature and immune cell infiltration in cystic pancreatic neuroendocrine tumors.

Hypervascularity is a main characteristic of pancreatic neuroendocrine tumors (PanNETs), and cystic PanNETs (CPanNETs) are unique type of PanNETs in which the microenvironment remains unknown. We aim to compare the micro-vasculature features and immune cell infiltration between CPanNETs and solid PanNETs (SPanNETs). Data of 301 SPanNET and 36 CPanNET patients from a high-volume institution were evaluated. CD4, CD8, CD11c, CD15, CD20, CD68, CD34 and α-SMA expression levels were assessed by immunohistochemistry and immunofluorescent double staining. The microvessel density (MVD) and microvessel integrity (MVI) were examined. MVD and MVI expression levels in CPanNETs were significantly higher than those in SPanNETs (p = 0.025 and 0.0092, respectively). CPanNETs had higher proportions of T1 (p = 0.023) and G1 (p = 0.052) than SPanNETs. In SPanNETs, higher MVD occurred in stages T1, N0 and G1 than in the T2/T3, N1 and G2 subgroups. In CPanNETs, CD34-MVD was uncorrelated with the T stage or grade. Higher CD34-MVD, but not MVI, was associated with better DFS (HR 0.3209, 95% CI 0.1259–0.8176, p = 0.004). There were significantly more peritumoral infiltrating immune cells than their intratumoral counterparts (p < 0.001 for each) in CPanNETs and SPanNETs. The mean number of peritumoral CD68 + TAM in CPanNETs was significantly lower than that in SPanNETs (p = 0.008). The counts of other peritumoral immune cells did not significantly differ between CPanNETs and SPanNETs. CPanNETs had a microenvironment distinct from that of SPanNETs, including higher CD34-MVD, higher MVI and lower TAM. This specific microenvironment structure may partially help predicting the prognosis of patients with PanNET.