Mast Cells in the Diffuse Large B-Cell Lymphoma; Their Role for Fibrosis.

Mast cells (MCs) play an important role in tissue remodeling in inflammation. According to content of tryptase and chymase, MC is divided into two phenotypes; MC_TC phenotype contains tryptase and chymase, while MC_T phenotype contains only tryptase. Recent studies have revealed that interleukin-4 (IL-4) promotes the maturation of MCs and the development of MC_TC phenotype from MC_T phenotype. Although MCs infiltration into diffuse large B-cell lymphoma (DLBCL) has been reported, MC phenotypes infiltrating into lymphomas remain unknown. We examined MC phenotype infiltrating into lymph nodes in 50 DLBCL and 20 reactive lymph nodes, and evaluated their association with fibrosis. We also evaluated IL-4-expressing cells in DLBCL. Reviewing hematoxylin-eosin stain and Azan-Mallory stain, 50 cases with DLBCL were divided into 3 groups; no fibrosis type in 32, reticular type in 8, showing fine reticular fibrosis in focal areas, and bundle type in 10, showing thick collagenous bundle through the parenchyma. Using these formalin-fixed and paraffin-embedded specimens, immunohistochemistry for tryptase and chymase was performed. Furthermore, immunodouble staining methods were performed to detect the MC phenotypes and the cells that express IL-4 in DLBCL, using frozen sections. Tryptase-positive, and chymase-positive MCs were found in all groups of DLBCL and density of tryptase-positive MCs were higher than that of chymase-positive MCs. Densities of trytase-positive, and chymase-positive MCs in fibrotic areas were significantly higher than those in the areas without fibrosis (reticular type; 12.681 ± 11.307 / mm² vs. 2.082 ± 2.260 / mm², p = 0.018, bundle type; 22.407 ± 11.989 / mm² vs. 1.319 ± 1.937 /mm², p = 0.005, in tryptase-positive MCs, reticular type; 4.758 ± 5.468 / mm² vs. 0.440 ± 1.164 / mm², p = 0.028, bundle type; 4.114 ± 5.216 / mm² vs. 0.220 ± 0.374 / mm², p = 0.008; in chymase-positive MCs). Numbers of tryptase-positive MCs in reactive lymph nodes were not different from those in no fibrosis type of DLBCL. There were few chymase-positive MCs in reactive lymph nodes. Immunodouble staining revealed that MCs in DLBCL comprised MC_T and MC_TC phenotypes. Chymase-positive MCs and T-lymphocytes expressed IL-4. These findings suggest that T-lymphcytes play a role in the development of MCTC phenotype from MCT phenotype in DLBCL and that tryptase-positive MCs and chymase-positive MCs are associated with the development of fibrosis in DLBCL.