Splenic Diffuse Large B-cell Lymphoma Research Articles

Primary splenic diffuse large B-cell lymphoma (PS-DLBCL) presenting in an asymptomatic patient after sports trauma

Primary splenic diffuse large cell lymphoma is unusual and accounts for 2% of all splenic lymphomas. The symptoms included left upper abdominal pain, indigestion, loss of appetite, generalized weakness, fever, anemia, and thrombocytopenia or elevated C Reactive Protein. The current case report, to our knowledge the first of its kind, presents unusual clinicopathologic findings, where the patient remained asymptomatic until the time of diagnosis but showed extensive splenic involvement with stage IV disease. Alternatively, the morphologic findings in this case were like to those seen in other Primary Splenic Diffuse Large B Cell Lymphoma reported in the literature. In conclusion, the present report emphasizes the need for additional case studies and research on the biology of this unusual subset of lymphoma.

An Unusual Case of a Central Pontine Myelinolysis Associated with Primary Splenic Diffuse Large B-cell Lymphoma.

A 54-year-old woman with persistent fatigue and a high fever presented with central pontine myelinolysis (CPM) on brain imaging, despite the absence of neurological symptoms. The patient had a slightly low serum sodium concentration. Further investigation led to a diagnosis of primary splenic diffuse large B-cell lymphoma (PS-DLBCL). Brainstem auditory-evoked potentials (BAEP) indicated minor abnormalities. CPM was successfully resolved after splenectomy and immunochemotherapy. This is the first reported case of CPM in a patient with PS-DLBCL confirmed by a pathological diagnosis following splenectomy and BAEP-detected abnormalities that improved with immunochemotherapy.

Primary Splenic Diffuse Large B-Cell Lymphoma: A Case Report.

The differential diagnosis of splenic nodules or infiltrates is vast and challenging, and it includes haematological diseases, systemic infectious diseases but also non-malignant infiltrative diseases.Although some lymphomas frequently present with splenomegaly, this is not the case of DLBCL, with the exception of PS-DLBCL.PS-DLBCL is a very rare pathology, accounting for 1% of all DLBCL and less than 1% of all NHL.

Comparison of survival outcomes of different treatment modalities for patients with primary splenic diffuse large B cell lymphoma.

Primary splenic diffuse large B cell lymphoma (DLBCL) is one of the most common primary tumors in the spleen, while its prevalence is relatively low. Recently, there has been an increase in the incidence rate of primary splenic DLBCL; however, the effectiveness of various treatments for it has not been adequately described previously. The purpose of this study was to compare the effectiveness of various treatments on survival time in primary splenic DLBCL. A total of 347 patients with primary splenic DLBCL were enrolled in The Surveillance, Epidemiology, and End Results (SEER) database. These patients were subsequently divided into four subgroups according to the treatment modalities: non-treatment group (patients who had not received chemotherapy, radiotherapy, or splenectomy, n=19), splenectomy group (patients who had received splenectomy only, n=71), chemotherapy group (patients who had received chemotherapy only, n=95), and the splenectomy combined with chemotherapy group (patients who had received splenectomy and chemotherapy, n=162). The overall survival (OS) and cancer specific survival (CSS) of four treatment groups were evaluated. Compared to the splenectomy group and the non-treatment group, the OS and CSS of the splenectomy combined with chemotherapy group was extremely significantly prolonged (P<0.01). Compared with the chemotherapy group, the OS and CSS of the splenectomy combined with chemotherapy group were longer, but there was no statistical difference (P>0.05). The Cox regression analysis showed that the treatment modality was identified as an independent prognostic factor for primary splenic DLBCL. The landmark analysis shows that the overall cumulative mortality risk was significantly lower in the splenectomy combined with chemotherapy group than in the chemotherapy group within 30 months (P<0.05), and the cancer-specific mortality risk was significantly lower in the splenectomy combined with chemotherapy group than in the chemotherapy group within 19 months (P<0.05). Splenectomy combined with chemotherapy may be the most effective treatment modality for primary splenic DLBCL.

Primary splenic diffuse large B-cell lymphoma presenting as a splenic abscess.

Diffuse large B-cell lymphoma (DLBCL) arising in the spleen, also known as primary splenic DLBCL (PS-DLBCL), is a rare form of malignant lymphoma. It is defined as a lymphoma confined to the spleen or involving splenic hilar lymph nodes. Here we report a case of PS-DLBCL with CD30. The patient was a 62-year-old who presented with 2 weeks of left flank pain, chills, and abdominal distension. Computed tomography identified an 8-cm splenic mass with central necrosis interpreted as an abscess. A drain was placed, yielding purulent necrotic material; cytologically, only neutrophils were identified. However, purulent drainage continued for 28 days without resolution, prompting splenectomy. Pathological dissection revealed a multinodular mass with central necrosis. Microscopic examination revealed extensive karyorrhexis, abundant ghosts of large cells, and scattered large cells with pleomorphic, multilobated, and vesicular nuclei with moderately abundant cytoplasm. Immunohistochemical staining revealed large, atypical cells positive for CD20, CD30, CD45, PAX5, MYC (>40%), MUM1 (>30%), and p53 (focally). The large cells were negative for CD3 (polyclonal), CD4, CD5, CD8, CD10, CD15, CD34, BCL2, BCL6, AE1/AE3, S100, HHV8, and ALK. The Ki-67 proliferation rate was approximately 80% in large cells. Notably, this PS-DLBCL was positive for CD30, an unusual finding among non-Hodgkin B-cell lymphomas, which, coupled with the Reed-Sternberg-like morphology, raised the possibility of classic Hodgkin lymphoma. Therefore, we reviewed the literature to confirm the unique features of this large B-cell lymphoma, its abscess-like appearance, and its expression of CD30.

Splenic Lymphomas: A Tertiary Care Center Experience and Review of Literature.

Primary splenic lymphomas are rare with the majority of lymphomas in spleen being secondary to an extra-splenic lymphoma. We aimed to analyze the epidemiological profile of the splenic lymphoma and review the literature. This was a retrospective study including all splenectomies and splenic biopsies from 2015 to September 2021. All the cases were retrieved from Department of Pathology. Detailed histopathological, clinical and demographic evaluation was done. All the lymphomas were classified according to WHO 2016 classification. A total of 714 splenectomies were performed for a variety of benign causes, as part of tumor resections and for the diagnosis of lymphoma. Few core biopsies were also included. A total of 33 lymphomasdiagnosed in the spleen, primary splenic lymphomas constituted 84.84% (n = 28) of the cohort with 5 (15.15%) having the primary site elsewhere. The primary splenic lymphomas constituted 0.28% of all the lymphomas arising at various sites. Adult population (19-65years) formed the bulk (78.78%) with a slight male preponderance. Splenic marginal zone lymphomas (n = 15, 45.45%) comprised of major proportion of cases followed by primary splenic diffuse large B-cell lymphoma (n = 4, 12.12%). Splenectomy was the main course of treatment for SMZL with a good overall outcome, with chemotherapy ± radiotherapy forming the mainstay in other lymphomas. Lymphomas in spleen can be infiltrative or a primary, hence proper clinic-radiological and pathological evaluation is required. Appropriate management is guided by the precise and detailed evaluation by the pathologist, requiring understanding of the same.

Unusual Rapid Growth of Primary Splenic Diffuse Large B-Cell Lymphoma with Extensive Necrosis.

The primary splenic lymphoma is extremely uncommon with an incidence rate of <1% of all the lymphomas under the strict criteria for diagnosis expounded by Das Gupta et al. Clinical presentations of nonspecific symptoms are weight loss, weakness, fever, and left upper quadrant pain or discomfort due to enlarged spleen. Abdominal ultrasound and CT are the most widely used imaging modality for the assessment of lymphoma. The imaged features of splenic lymphoma are nonspecific; typical lymphoma presents as a diffusely enlarged spleen. The abdominal CT scan in our case showed a large cystic splenic mass measuring 14 cm without enhancement after contrast medium. Lymphoma is often described as an aggressive tumor because its rapid doubling time can quickly increase the size of a tumor. In our case, the tumor grew to more than 100 times its original size in 4 months. So, we present this unusual rapid growth of primary splenic lymphoma.

Splenic diffuse large B-cell lymphoma. Case report

Splenic diffuse large B-cell lymphoma. Case report

Primary Splenic Lymphoma with Splenic Hilar Lymphadenopathy

Splenic lymphoma can occur as a primary or secondary malignancy, but the latter form is more common. Primary splenic lymphoma is defined as lymphomatous involvement of the spleen with or without splenic hilar lymphadenopathy. It can present as splenomegaly with homogenous echogenicity without a focal lesion, a diffuse infiltrative lesion with miliary lesions, multiple focal nodular lesions, or as a large solitary mass. A 71-year-old woman presented with mild upper abdominal pain and a splenic mass. We visualized a hypoechoic splenic mass with splenic hilar lymphadenopathy on abdominal ultrasound. The patient underwent surgery and was diagnosed with splenic diffuse large B-cell lymphoma.

Primary splenic diffuse large B-cell lymphoma with multinucleated giant cells in a horse

A diagnosis of a diffuse splenic large B-cell lymphoma with multinucleated giant cells in a 5-year-old mare was made based upon the clinical, pathological, and immunohistochemical findings. The enormous primary splenic mass weighed 51.75 kg. To the best of our knowledge, this is the biggest reported splenic mass and the first case of an equine diffuse large B-cell lymphoma with multinucleated giant cells.

B-cell neoplasms and Hodgkin lymphoma in the spleen

B-cell lymphoma of spleen may be primary (most commonly splenic diffuse large B-cell lymphoma) or secondary (typically low-grade non-Hodgkin lymphoma). Depending on the specific lymphoma subtype, there may be a predominantly white pulp pattern of involvement, a predominantly red pulp pattern or a focal nodular pattern. Splenectomy is the ideal specimen for a multiparametric integrative diagnosis of splenic lymphoma, as it allows for a combined study of morphology, immunohistology, flow cytometry, cytogenetics, and molecular genetic techniques. This review article describes the clinicopathologic characteristics of all the relevant B-cell neoplasms that may be encountered in a splenic biopsy or a splenectomy specimen.

Massive Splenomegaly as Initial Presentation of Diffuse Large B-Cell Lymphoma

Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin's lymphoma in western countries and is characterized by aggressive clinical behavior. Primary splenic DLBCL is an extremely rare clinical condition. We present a case of successfully treated HCV who presented with acute abdominal pain and was found to have massive splenmogaly secondary to DLBCL. A 65-y.o. female presented with 1-week history of marked sharp left upper quadrant, non-radiating abdominal pain. She had poor appetite, nausea and 3 episodes of coffee-ground emesis over one day. She denied fever and review of systems was otherwise negative. Her history is significant for recently treated hepatitis C with sofosbuvir/velpatasvir a few months prior to this presentation. Physical exam was only positive for tender splenomegaly. CT abdomen showed massive splenomegaly with multiple new splenic infarcts (image 1). She was noted to have a 3-gram drop in hemoglobin in one month, so EGD was done (image 2,3). Her HCV RNA was undetectable by PCR. BCR/ABL and JAK2 mutations, as well as EBV and CMV serology were all negative. Peripheral blood showed mature B-cells. Lymph node biopsy and bone marrow biopsy were diagnostic for DLBCL. Patient was started on chemotherapy with RCHOP regimen with good response. Tumors of the spleen are rare and are classified into benign and malignant. Primary malignancies are extremely rare, with lymphoma being the most common splenic malignancy. Splenic lymphomas are heterogeneous. They may be primary, arising from the spleen, or secondary, involving the spleen as part of systemic dissemination of a lymphoma that arises elsewhere. As a general rule, isolated presentation with splenomegaly is more common in indolent lymphoma than in aggressive lymphoma. The association between hepatitis C virus (HCV) infection and malignant lymphoma is well documented. For patients with hepatitis C, who subsequently develop splenomegaly, it is important for clinicians to be suspicious for splenic DLBCL and not blame HCV as the only cause of splenomegaly especially if it develops after treating HCV. This case is unique as it presents a very rare initial presentation of DLBCL, which is splenomegaly due to splenic involvement without having any other symptoms or signs of systemic involvement. Physicians should be made aware of this rare presentation to avoid delay in diagnosis that can adversely affect patient morbidity and mortality.1925_A Figure 1. CT abdomen shows massive splenomegaly, with multiple infarcts1925_B Figure 2. EGD shows gastric polyp1925_C Figure 3. EGD shows non-bleeding angioectasia

Multi-Database Description of Primary Splenic Diffuse Large B-Cell Lymphoma.

Stage I splenic diffuse large B-cell lymphoma (DLBCL) is rare and there are few data to guide management. We sought to further define prognosis and outcomes. We utilized the Surveillance, Epidemiology, and End Results registry to identify patients with stage I splenic DLBCL diagnosed 1973-2013. Patients were divided into two cohorts based on the year of diagnosis (1983-2005; 2006-2013) as rituximab was approved by the U.S. Food and Drug Administration in 2006 for first-line treatment of DLBCL. Utilization of splenectomy decreased after the approval of rituximab (82% pre- versus 72% rituximab-era). Disease-specific and overall survival were greater with splenectomy [hazard ratio (HR)=0.57, p=0.04; and HR=0.66, p=0.03, respectively], but this benefit was only seen in the pre-rituximab cohort, not in the rituximab-era cohort. There was a trend toward improved overall survival with the introduction of rituximab (HR=0.75, p=0.054). Utilization of splenectomy for stage I splenic DLBCL has decreased with the introduction of rituximab without compromising outcomes.

Clinicopathological analysis of primary splenic diffuse large B-cell lymphoma.

Splenic infiltration is often seen in diffuse large B-cell lymphoma (DLBCL). However, primary splenic DLBCL is rare and studies on its clinicopathological features are limited. We assessed 66 cases of primary splenic DLBCL and 309 control DLBCL, not otherwise specified. Hepatitis C virus antibody prevalence, B symptoms, poor performance status and CD5 positivity differed significantly between the primary splenic DLBCL and control DLBCL groups. Primary splenic DLBCL cases were classified histopathologically into two groups [white pulp pattern (n=46), red pulp pattern (n=20)]. Survival analysis showed no difference in overall survival between the primary splenic DLBCL and the control group, but the former had a more favourable progression-free survival. In the examination of primary splenic DLBCL, the white pulp pattern was statistically associated with a lower performance status (2-4), and a lower CD5 positivity than the red pulp pattern. In the survival analysis, the red pulp pattern demonstrated poorer overall survival. Multivariate analysis of overall survival in primary splenic DLBCL cases identified CD5 positivity as an indicator of poor prognosis. Classifying primary splenic DLBCL into white and red pulp patterns was useful in terms of clinicopathological features and overall survival.

Multi-Database Description of Primary Splenic Diffuse Large B-Cell Lymphoma

Introduction:Although the spleen is involved in about a third of patients with Diffuse Large B-cell Lymphoma (DLBCL), stage I splenic DLBCL is rare and there is little data to guide management. Potential treatment modalities include combinations of splenectomy, radiation and immuno-chemotherapy, but there is no consensus on the optimal approach. Using multiple publically available and propriety databases, we sought to further define the prognosis and outcomes for stage I splenic DLBCL.Methods:We utilized the Surveillance Epidemiology and End Results (SEER) 18 registry to identify patients with stage I splenic DLBCL diagnosed during the years 1973-2013. Appropriate cases were identified using a combination of International Classification of Diseases for Oncology, 3rd edition code DLBCL (9680/3) and location code for spleen (C42.2). These patients were divided into two cohorts based on the year of diagnosis (1983-2005; 2006-2013) as rituximab (R) was approved by the FDA in 2006 for use in the first line treatment of DLBCL. Patient characteristics and survival outcomes were analyzed by GraphPad Prism 6 and Microsoft Excel. Disease specific survival (DSS) and Overall survival (OS) comparisons were made using the Gehan-Breslow-Wilcoxon test. All p-values were 2-sided and results ≤0.05 were considered significant.We queried the Mitelman Database of Chromosome Aberrations and Gene Fusions in Cancer to identify patients with stage I splenic lymphoma during the years 1973-2013. We also searched the Caris Life Sciences database for patients profiled by Caris Molecular Intelligence using the keywords "splenic lymphoma " in the clinical history and diagnosis fields for cases of stage I splenic DLBCL from 2007-2015. All database searches were conducted with IRB approval.Results:107,550 patients with known stage and histologically confirmed DLBCL were identified within the SEER database. 30,455 patients had stage I disease with 470 of them diagnosed as stage I splenic DLBCL. The mean age was 66 years (range, 17-93 years) and the majority were Caucasian (89%). There was equal distribution of patients in the pre-rituximab (pre-R) era and post rituximab (R) era (53% vs 47%). 42% (470/1116) of splenic DLBCL were diagnosed as stage I compared to 28% (29,985/106,434) of all other types of DLBCL (p<0.01). Stage I splenic DLBCL treated in the R-era has better OS than all other stage I DLBCLs treated during the same period (HR = 0.62, 95% CI 0.53-0.86, p<0.01)The rate of splenectomy was lower after the approval of rituximab (82% in pre-R vs 72% in R era, p=0.03). Splenectomy was associated with an improvement in DSS (HR = 0.57, 0.28 - 0.96, p=0.04), but when stratified by pre-R and R era, improved DSS with splenectomy was only seen in the pre-R (HR = 0.51, 0.17-1.08, p =0.04), but not in the R-era (HR =0.62, 0.25 - 1.38 p=0.53). OS advantage with splenectomy was also seen only in the pre-R era (HR = 0.66, 0.32 - 1.14, 106m vs 137m, p=0.03) but splenectomy had no impact on OS in the R-era (HR = 0.74, 0.37 - 1.43, p=0.45). There was a trend toward improved OS with the introduction of rituximab (HR = 0.75, 0.48 - 1.14, p=0.054). There was no difference in the utilization of radiation between these cohorts (6% in pre-R vs 3% in R era, p=0.13).Our search of the Mitelman database found 1413 patients with DLBCL, but none of them had stage I splenic DLBCL. We also identified 20 patients with Non-Hodgkin lymphoma profiled by Caris Life Sciences, of which only one had primary splenic DLBCL. This patient was a 35 year old male who on immunohistochemistry was found to be positive for MGMT, MRP1, PTEN, TOP2A, TOPO1, and TS.Conclusion:The utilization of splenectomy for stage I splenic DLBCL has decreased with the introduction of rituximab without compromise of outcomes. Radiation is rarely used and does not appear to influence outcomes. Splenic DLBCL is more likely to present as stage I disease compared to other types of DLBCLs and Stage I splenic DLBCL appears to have a favorable prognosis relative to other stage I DLBCLs. Alternative databases added little to the understanding of the biology of stage I splenic DLBCL. DisclosuresNo relevant conflicts of interest to declare.

Magnetic resonance image guided radiation therapy for primary splenic diffuse large B-cell lymphoma: A teaching case

Magnetic resonance image guided radiation therapy for primary splenic diffuse large B-cell lymphoma: A teaching case

Primary splenic diffuse large B-cell lymphoma: one case report and literature review

目的 探讨原发性脾弥漫大B细胞淋巴瘤(DLBCL)的临床病理学特征及治疗策略。 方法 回顾性分析1例原发性脾DLBCL患者的临床资料及病理切片，并复习相关文献。 结果 ，无发热及浅表淋巴结肿大，CT证实脾多发占位性病变伴脾门多发肿大淋巴结。行脾、胰尾切除术，病理确诊为DLBCL，免疫分型为生发中心B细胞型。外周血和骨髓检查结果正常。脾切除术后给予联合化疗，随访1年处于完全缓解期。 结论 原发性脾DLBCL罕见，患者早期无明显症状，手术探查是早期诊断的首选方法，病理学检查是诊断金标准。治疗首选脾切除术，术后辅助化疗及放疗可以提高患者生存率。

Characteristics of primary splenic diffuse large B‐cell lymphoma and role of splenectomy in improving survival

Primary splenic diffuse large B-cell lymphoma (PS-DLBCL), an uncommon type of non-Hodgkin lymphoma, has been investigated only in small patient series before the rituximab era. The therapeutic role of splenectomy in addition to immunochemotherapy is unknown. The databases of 7 medical centers in Israel were searched for patients diagnosed with PS-DLBCL in 1982-2013, and clinical, treatment, and outcome data were collected for 87 patients. The mean patient age was 59.6 years; 57.5% were male. Patients presented with abdominal pain (81%), B symptoms (59%), splenomegaly (84%), splenic masses (97%), and high lactate dehydrogenase (LDH) levels (84%); 61% had stage I or II disease. The diagnosis was made with core-needle biopsy in 46 patients and with diagnostic splenectomy in 39 patients. Eighty patients (92%) were treated with cyclophosphamide, doxorubicin, vincristine, and prednisone; 68 (78%) received rituximab. A complete response was achieved in 67 patients (77%), and a partial response was achieved in 8 (9%). At 5 years, the overall survival (OS) rate was 77%, and the progression-free survival (PFS) rate was 67%. When patients were stratified by splenectomy at diagnosis, the OS rates were 91% for splenectomized patients and 68% for nonsplenectomized patients (P = .08), and the PFS rates were 85% and 55%, respectively (P = .02). The respective values for the subgroup with early-stage disease were 96% and 63% for OS (P = .009) and 90% and 51% for PFS (P = .01). In a multivariate analysis, a low Eastern Cooperative Oncology Group performance status and splenectomy independently predicted better PFS (P < .03). Patients with PS-DLBCL usually present with abdominal pain, high LDH levels, and a splenic mass. This study shows for the first time that splenectomy at diagnosis improves survival, specifically in patients with early-stage disease.

Primary Splenic Diffuse Large B-Cell Lymphoma (PS-DLBCL): Splenectomy Improves Survival

Introduction: Although the spleen is involved in about a third of patients with non-Hodgkin’s lymphoma (NHL), primary splenic diffuse large B-cell lymphoma (PS-DLBCL) is rare having a reported incidence of less than 1% of all NHL. Most of the described series include small numbers of patients before the rituximab era and the role of splenectomy treatment in addition to immuno-chemotherapy is unknown.Methods: Data were retrospectively collected for 87 patients (pts) with PS-DLBCL treated in 7 medical centers in Israel during the years 1982-2013. Patients presenting with systemic disease with splenic involvement or those having a diagnostic biopsy from other nodal or extranodal disease were excluded.Results: The mean age was 59.6 years (range, 24-89 years); 57.5% were male. Abdominal pain was reported in 61 pts (81%), B symptoms in 49 pts (59%), ECOG performance status 0 - 1 in 85%. Stage I disease was recorded in 28%, II in 33%, III in 18%, and IV in 21%. Thrombocytopenia (<100,000/µl) was recorded in only 6 pts. Lactic dehydrogenase levels (LDH) were elevated in 69 pts (84%). Favorable International Prognostic Index (IPI) 0-2 was recorded in 62 pts (72%). The mean splenic length was 17.34±6 cm (range 7- 37 cm) and the mean splenic weight was 1216 gm±1243 gm (range 180-6000 gm). A splenic mass was found in 97% of pts, and its mean size was 9.26 cm (range 3-18 cm). The diagnostic procedure was core needle biopsy in 46 pts and splenectomy in 39 pts: 27 underwent open splenectomy and 12 laparoscopic splenectomy. Splenectomized pts had lower IPI (p<0.05) and lower stage (p<0.05) compared to non-splenectomized pts. Treatment: The CHOP regimen was given to 80 pts (92%), DA-EPOCH was given to 2 pts (2%) and 5 pts (6%) received other regimens. Rituximab was given to 68 pts (78%). Complete response was achieved in 67 pts (80%) and partial response in 8 (9%). Relapse occurred in 17 pts (22%).Survival: The median follow-up time was 7 years (range 0-19.4 years). During this period 24 pts died (27.5%). The 5-year overall survival (OS) was 76.6±4.9% and 5-year event-free survival (EFS) 67.2±5.5%. Splenectomy at diagnosis improved survival: the 5-year EFS was 85.4±6% and 54.7±8% for splenectomized and non-splenectomized pts respectively (p=0.02) and the 5-year OS was 91.2±5% and 67.9±7% respectively (p=0.08). For the 53 pts with stage I-II disease, both 5-year EFS and OS were better in the splenectomized pts (p<0.02, Fig 1). The 5-year EFS and OS in pts with stage I and II disease that were splenectomized at diagnosis was 89.6±6% and 96.4±3.5% as compared with 50.5±11% and 63.2±11% in pts who were not splenectomized (p=0.012 and 0.009). The EFS and OS were not influenced by the stage of the disease. Overall survival was associated with B symptoms (p=0.02), weight loss (p=0.04) and ECOG performance status (p=0.03). In a multivariate model, low ECOG PS and splenectomy independently predicted a better EFS (p=0.03 and 0.02 respectively), however for OS, low ECOG PS independently predicted better OS (p=0.03), while splenectomy had only marginal effect on the OS (p=0.056).Conclusions: In our group of pts, PS-DLBCL generally presented with abdominal pain, high LDH and a splenic mass. We demonstrate for the first time that splenectomy at diagnosis improves survival in early stages of PS-DLBCL. Our study is a retrospective one. Therefore, until prospective studies prove that early splenectomy in PS-DLBCL is beneficial in terms of overall survival, the risk and benefit of performing splenectomy should be weighed for each patient. [Display omitted] [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Abstract 81: Deregulated expression of HDAC9 in B cells leads to the development of lymphoproliferative disease and lymphoma

Abstract Aberrant epigenetics leading to changes in chromatin structure and patterns of gene expression is an important factor in cancer pathogenesis. Histone Deacetylase 9 (HDAC9) is a class IIa chromatin-modifying enzyme that, within the haematopoietic system, is preferentially expressed in the B-cell lineage. Furthermore, HDAC9 expression is deregulated in B-lymphoid malignancies. To examine the role of HDAC9 in malignant B-cell transformation, we generated an in vivo mouse model that constitutively expresses human HDAC9 from early stages of B-cell development under the control of the immunoglobulin heavy chain (IgH) enhancer (Eµ). In this study, we demonstrate that from an average of six months of age, Eµ-HDAC9 transgenic mice displayed splenomegaly and immunophenotypic features that resemble lymphoproliferative disease (LPD) in spleen. Later on in life, up to twenty-three months of age, 24% (19 out of 78) of Eµ-HDAC9 mice developed mature B-cell neoplasms such as splenic marginal zone lymphoma (SMZL) and aggressive diffuse large B-cell lymphoma (DLBCL) that could represent a progression stage of the observed lymphoproliferative disease (LPD) and monoclonal B-cell lymphocytosis (MBL). In contrast, a low background incidence of these malignancies was observed in control mice, 2% (1 out of 46) (p = 0.0008). The molecular pathogenesis of the Eµ-HDAC9 B-cell tumors seems to involve activation-deactivation of the BCL6-p53 axis by HDAC9 influenced deacetylation thus affecting DNA repair and cell cyle progression in germinal centre (GC) during immune response. Consistently, ZFN-mediated HDAC9-knockout results in cell cycle changes leading to strong inhibition of cell growth in vitro. In summary, aberrant expression of HDAC9 leads to the development of lymphoproliferative disorders, including GC and post-GC lymphomas, demonstrating an oncogenic role for HDAC9 in B-cells and highlighting its importance as a therapeutic target. Citation Format: Veronica S. Gil. Deregulated expression of HDAC9 in B cells leads to the development of lymphoproliferative disease and lymphoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 81. doi:10.1158/1538-7445.AM2014-81