Splenic Diffuse Red Pulp Small B-Cell Lymphoma Descriptors and Clinicopathologic Determinants of Clinical Outcomes: Analysis of a Pooled Database

Abstract

Introduction: Splenic Diffuse Red Pulp Small B-Cell Lymphoma (SDRPL) is a rare clinical entity representing <1% of B-Cell Lymphomas. Previously identified as a variant of SMZL, the WHO has recognized it as a provisional entity since its 2008 classification updates. The diagnosis can be challenging as it shares multiple clinical and laboratory features with Splenic Marginal Zone Lymphoma (SMZL), Hairy Cell Leukemia (HCL) and HCL variant (HCL-v). It is characterized by diffuse involvement of the splenic red pulp by small monomorphic B-cells. Due to our limited understanding of this disease, we conducted this pooled database analysis of all cases of SDRPL to delineate key clinicopathological characteristics, prognostic indicators and treatment modalities that affect outcomes in this rare lymphoma subtype. Methods: In order to study the demographic characteristics, molecular and immunohistochemical signatures, therapeutic interventions, survival, and prognostic factors, we compiled a pooled database of 80 cases. Kaplan-Meier survival curves were constructed. Cox proportional hazards model and Log-rank tests were used to assess the influence of demographic and clinicopathologic factors on overall (OS) and disease-free survival (DFS) survival. Results: A total of 80 patients with confirmed SDRPL were identified. The median age was 66.5 years, with a peak incidence between 69 and 70. There was a male preponderance with M:F ratio of 1.7. Splenomegaly, hepatomegaly (HM), lymphadenopathy (LN), constitutional symptoms (CS), ECOG0-1, and bone marrow (BM) involvement were present in 91%, 33%, 21%, 44%, 95%, and 95%, respectively. The median splenic weight was 2450g. While splenic red pulp was solely involved in 69% of the cases, 31% had mixed red and white pulp involvement. Three patients had active HBV, one had EBV, 4 had skin involvement, and 1 transformed into B-PLL. SDRPL Immunophenotype consisted of: TRAP(37%), Annexin A1(5%), CD5(14%), CD11c(63%), CD19(97%), CD20&22(100%), CD25(11%), CD27(60%), CD79(100%), CD103(26%), Bcl2(80%), CyclinD1(10%). CyclinD3(55%), and BRAF(16%). The median OS and DFS of the whole group were not reached (mean 138 mo) and 86mo, respectively. Age > 60 adversely impacted DFS (84mo vs. NR, p=0.03). The same trend was noted for age and OS. Compared to no treatment, splenectomy alone and the addition of combination chemotherapy were superior, with a median DFS of 36, 105, and 100 months respectively (p=0.06). HM, BM involvement, WBC>20K, absolute lymphocyte count>5K, and platelets<100K tended to adversely impact DFS, while only BM involvement and platelets<100K tended to impact OS adversely. CD25+ status was detrimental to DFS (36 vs. 105mo, p=0.049) whereas CD103+ status was advantageous to DFS (NR vs. 42mo, p=0.06). When chemotherapy was used, purine analogues tended to have better DFS and OS (76 vs. 26mo, p=0.09) compared to CHOP-like regimens. Neither DFS nor OS was impacted by sex, CS, LN, splenic weight, or splenic white pulp involvement. Conclusions: This study presents an updated clinicopathologic data from a pooled cohort of patients with SDRPL. It identifies the clinical, immunohistochemical, and treatment modalities that are major determinants of DFS and OS in this rare and distinct B-cell lymphoma entity.