Pathological Characteristics Of Fibrous Mass-forming Chronic Pancreatitis And The Relationship With Immune Competent Cells

Background:Chronic pancreatitis(CP) is a disease that is progressive and characterized by chronic inflammation and fibrsis within pancreas results in irreversible pancreatic dysfunction finally. Fibrous mass-forming chronic pancreatitis(FMCP) is a special type of CP and characterized by local fibrous mass-forming, accounting for15%-30%of CP. FMCP includes autoimmune pancreatitis(AIP) and fibrous mass-forming non-autoimmune pancreatitis(nAIP).Clinical manifestation and imaging changes of FMCP are similar to pancreatic cancer, so FMCP always be treated as surgery strategy used by pancreatic mass, besides, as the rise of incidence of CP, the incidence of FMCP is also ascending, it is not only required to differentiate FMCP with pancreatic cancer, because of FMCP includes AIP and nAIP, accurately distinguish AIP with nAIP has critical clinical significance. As AIP is uniquely steroid-responsive, exact diagnosis can make patient avoid unnecessary surgical pain. Therefore, FMCP has been paid more attention to by clinic and pathology for the past few years.Regulatory T cells(Tregs) and myeloid derived suppressor cells(MDSCs) are two important immune competent cells in human immune system, participating in immunoregulation and pathogenesis and progression of multiple autoimmune diseases and tumors, they may play a role during the disease process of AIP, however, there has no research about the amount of Tregs and MDSCs within pancreas of AIP and their effect on the pathogenesis and progression of AIP.Objective:①To study on FMCP and to investigate the difference of clinical, pathological and immunohistochemical characteristics between AIP and nAIP and provide evidence for pathological diagnosis, differential diagnosis and clinical therapy strategy.②To detect Tregs and MDSCs within local pancreas and to investigate the possible effect that immune competent cells probably have during the disease process of AIP and provide evidence for finding a whole new way for the treatment of AIP. Methods:①Analyzed81cases of FMCP for both histological and clinico-pathological features to investigate the difference of clinical and pathological characteristics between AIP and nAIP.②Immunohistochemical staining was used to detect the amount of infiltrating IgG4+plasmacytes within pancreas of81cases of FMCP and provide evidence for diagnosis of AIP and differential diagnosis with nAIP.③Immnofluorescence staining and Immunohistochemical staining were used to detect the amount of CD11b+CD33+MDSCs and FOXP3+Tregs respectively, to compare the differences of infiltrating CD11b+CD33+MDSCs and FOXP3+Tregs within pancreas between AIP and nAIP and investigate the possible role that CD11b+CD33+MDSCs and FOXP3+Tregs may play during the disease process of AIP further.Results:①Among81cases of FMCP,20cases were diagnosed as AIP, the other61cases were nAIP. AIP were more common in males over50-years old, whereas patients with nAIP were much younger(p=0.001). The amount of inflammatory cells in the stroma of AIPs was much more remarkable than in the nAIPs (p=0.002). The incidence of neuritis in AIPs (100%) was also much higher compared with nAIPs (75.4%)(p=0.017). Storiformed-fibrosis was much more easily to be observed in AIPs (95%,19/20) than in nAIPs (1.6%,1/61)(p=0.000). Pancreatic intraepithelial neoplasia (PanIN) was observed as50.0%(10/20) in AIPs and32.8%(20/61) in nAIPs, with greater severity in AIPs (p=0.031). Tubular complex (TC) was more commonly observed in AIPs (65.0%,13/20) than in nAIPs (26.2%,16/61)(p=0.002).②Among81cases of FMCP,61cases were less than11IgG4+plasmacytes/HPF,7cases within10-30/HPF and13cases over30/HPF.③CD11b+CD33+MDSCs within pancreas of AIP group and nAIP group was12.22±10.87/HPF and4.39±7.29/HPF respectively, the amount of CD11b+CD33+MDSCs in AIP group was much more than nAIP group(p=0.000).④FOXP3+Tregs within pancreas of AIP group and nAIP group was14.91±22.76/HPF and8.12±10.92/HPF respectively, the amount of FOXP3+Tregs between the two group had no statistical significance.Conclusions:①FMCPs include AIP and nAIP, AIP has remarkable pathological features and IgG4+-plasmacytes-counting was one important diagnostic criteria. FMCP is an important precancerous lesion of pancreatic ductal adenocarcinoma as containing PanIN and TC, especially the AIP. Accurate and timely diagnosis of AIP has its critical clinical significance.②CD11b+CD33+MDSCs and FOXP3+Tregs exist in pancreas of both AIP and nAIP, these may be determined by the diseases. However, due to the different entity of AIP and nAIP, compare to nAIP, CDllb+CD33+MDSCs and FOXP3+Tregs may have much more opportunity to facilitate AIP to progress into malignant disease.