Objective:Diffuse Large B Cell Lymphoma(DLBCL)is a heterogeneous group of tumors with different biological and clinical characteristics that have diverse clinical outcomes and response to therapy.Stromal-1 signature of tumor microenvironment of DLBCL represents extracellular matrix deposition and histiocytic infiltrate,whereas stromal-2 represents angiogenesis that could affect tumor progression.Methods:The aim of the present study is to assess the significance of stromal-1 signature using SPARC-1 and stromal-2 signature using CD31 expression and then finally to construct biologic prognostic model(BPM)in 60 cases of DLBCL via immunohistochemistry.Results:Microvessel density(P<0.05)and SPARC percentage of expression(P<0.001)were higher in DLBCL,including germinal and nongerminal cases,compared with reactive follicular hyperplasia.High microvessel density was significantly associated with splenic involvement(P=0.008),high mitotic count(P=0.045),and presence of capsular invasion(P=0.035).Percentage of SPARC expression was significantly associated with splenic involvement(P=0.03).Constructing BPM showed that 42 cases(70%)were of low biologic score(0–1)and 18 cases(30%)were of high biologic score(2–3).Low BPM cases showed less probability for splenic involvement(P=0.04)and a higher rate of complete response to therapy compared with high score cases(P=0.08).Conclusions:The DLBCL microenvironment could modulate tumor progression behavior since angiogenesis and SPARC positive stromal cells promote dissemination by association with spleen involvement and capsular invasion.Biologic prognostic models,including modified BPM,which considered cell origin of DLBCL and stromal signature pathways,could determine DLBCL progression and response to therapy. Objective: Diffuse Large B Cell Lymphoma (DLBCL) is a heterogeneous group of tumors with different biological and clinical characteristics that have diverse clinical outcomes and response to therapy. Stromal-1 signature of tumor microenvironment of DLBCL represents extracellular matrix deposition and histiocytic infiltrate, whereas stromal-2 represents angiogenesis that could affect tumor progression. Methods: The aim of the present study is to assess the significance of stromal-1 signature using SPARC-1 and stromal-2 signature using CD31 expression and then finally to construct biologic prognostic model ( BPM) in 60 cases of DLBCL via immunohistochemistry. Results: Microvessel density (P <0.05) and SPARC percentage of expression (P <0.001) were higher in DLBCL, including germinal and nongerminal cases, compared with reactive follicular hyperplasia. High microvessel density was Significantly associated with splenic involvement (P = 0.008), high mitotic count (P = 0.045), and presence of capsular invasion (P = 0.035). Percentage of SPARC expression was significantly associated with splenic involvement (P = 0.03) .Constructing BPM showed that 42 cases (70%) were of low biologic score (0-1) and 18 cases (30%) were of high biologic score -3). Low BPM cases showed less probability for splenic involvement (P = 0.04) and a higher rate of complete response to therapy compared with high score cases (P = 0.08) .Conclusions: The DLBCL microenvironment could modulate tumor progression behavior since angiogenesis and SPARC positive stromal cells promote dissemination by association with spleen involvement and capsular invasion. Biologic prognostic models, including modified BPM, which considered cell origin of DLBCL and stromal signature pathways, could determine DLBCL progression and response to therapy.