Splenic Diffuse Large B-cell Lymphoma Research Articles

Early-stage splenic diffuse large B-cell lymphoma is highly associated with hepatitis C virus infection

Splenic marginal zone lymphoma (SMZL) and splenic diffuse large B-cell lymphoma (DLBCL) are the most common types of lymphomas involving the spleen. Geographic variation in hepatitis C virus (HCV) seroprevalence is characteristic of splenic lymphomas. In Italy, HCV seroprevalence was higher in patients with SMZL and splenic DLBCL than in patients with all types of lymphoma. In Japan, HCV seroprevalence was higher in patients with splenic DLBCL than in patients with all types of lymphoma; however, HCV seroprevalence in patients with SMZL was similar to that in patients with all types of lymphoma. In this study, clinicopathological data of 74 splenic lymphoma cases between 1988 and 2011 collected from the Department of Pathology at National Taiwan University Hospital were analyzed. Serology for HCV infection was available for 41 cases. Splenic DLBCL and SMZL accounted for 36% (n = 27) and 42% (n = 31) of splenic lymphomas, respectively. Microscopically, most cases of DLBCL (26/27) presented with circumscribed tumor and most cases of SMZL (28/31) presented with white pulp expansion. HCV seroprevalence in patients with DLBCL and SMZL was 44% and 10%, respectively (7/16 vs. 2/20, p = 0.020). The pattern identified in this study is closer to that in Japan than in Italy. HCV seroprevalence in patients with early-stage (I/II) and late-stage (III/IV) DLBCL was 100% and 10%, respectively (6/6 vs. 1/10, p < 0.001). Early-stage DLBCL is clinically considered a form of primary splenic lymphoma rather than a systemic lymphoma with splenic involvement. High HCV seroprevalence in patients with early-stage DLBCL suggests a role of HCV in the pathogenesis of primary DLBCL.

Splenic irradiation-induced gastric variceal bleeding in a primary splenic diffuse large B-cell lymphoma patient: a rare complication successfully treated by splenectomy with short gastric vein ligation

Primary splenic diffuse large B-cell lymphoma (DLBCL) is a rare clinical condition, which is generally treated by six to eight cycles of chemotherapy involving a combination of rituximab and the cyclophosphamide, adriamycin, vincristine, and prednisolone (CHOP) regimen. However, the treatment for chemorefractory primary splenic DLBCL remains controversial. Therapeutic splenic irradiation (SI) might be a reasonable and possibly the only treatment option with curative intention for patients with chemorefractory primary splenic DLBCL. However, the efficacy and safety of therapeutic SI are unclear. Herein, we present the case of a primary splenic DLBCL patient who was refractory to multiple chemotherapy regimens but achieved complete remission after administration of therapeutic SI. However, his condition was complicated with severe gastric variceal bleeding due to splenic venous thrombosis, which was successfully treated via splenectomy and short gastric vein ligation. On the basis of our findings, we concluded that the splenic venous thrombosis-induced gastric variceal bleeding was a rare but life-threatening adverse effect of the therapeutic SI administered for primary splenic DLBCL. Surgical intervention involving splenectomy and short gastric vein ligation is mandatory and should be performed as soon as possible for such patients.

Treatment of Diffuse Large B-Cell Lymphomas

Abstract 2684 Introduction:diffuse Large B-cell lymphoma (DLBCL) are aggressive but potentially curable with multi-agent chemotherapy. The R-CHOP regimen is standard therapy for treatment of DLBCL patients. Whereas attempts to improve outcome with more intensive chemotherapy failed to show additional benefit. Aims:to set the indications to standard or intensive therapy in patients with nodal DLBCL and to evaluate the efficiency of modified protocol NHL-BFM-90 in adult patients. Patients and methods:139 patients with newly diagnosed nodal DLBCL were included in the study since January 2002 till December 2010. The diagnosis was established according to the criteria of the WHO classification. Diagnostic methods include neck, thorax, abdomen and pelvis CT scan, tumor biopsy bilateral bone marrow (BM) biopsy, lumbal puncture, MRT or scintigraphy of bones. Bone marrow involvement was found in 18 cases and confirmed by immunohistochemistry. Bulky disease, direct invasion to adjacent organs, III-IV stage according Ann-Arbor and increased level LDH were considered as the unfavorable prognostic factors. The patients were stratified into 2 groups: the first group with unfavorable prognostic factors (86 patients), the second group without unfavorable prognostic factors (53 patients). Median age in the first group was 53 years. There were 46 men and 40 women. The level of LDH was elevated in the 61 patients. III-IV stage without involvement of BM was diagnosed in the 35 patients, IV stage with BM involvement-in the 18 patients, bulky disease and direct invasion to adjacent organs-in the 33 patients. Median age in the second group was 55 years. There were 28 men and 25 women. All patients in the first group received intensive therapy by modified protocol NHL-BFM-90. The patients in the second group received chemotherapy CHOP-21(n=28) or R-CHOP-21 (n=25). The program NHL-BFM-90 was modified: the dose of methotrexate was 1,5 g/m2 for 12 hours and adriamycin 25 mg/m2 was infused in 1–2 days of course AA. All patients treated with this protocol gave written informed consent. We made spleneectomy to all the patients of splenic DLBCL before chemotherapy (n=20). The estimation of the chemotherapy efficiency was carried out according to the criteria of the International Working Group: rate of complete remissions (CR), overall (OS) and relapse-free (RFS) survival. The data were analyzed with SAS statistical package program. Statistical significance of the difference in the survival curves for two groups was calculated with Log-rank Test. Results:64 patients in the first group (74,4%) and 53 patients (100%) in the second group achieved CR. 5-year OS and RFS were 65% and 86% in the first group 96% and 100% in the second group, accordingly. In the first group the best results were obtained in patients without BM involvement. 5-year OS was 84% in these patients comparing 12% in patients with BM involvement–figure 1 (Log-Rank Test=0,0001). The rate of CR and OS were the same in CHOP-21 group and R-CHOP-21 group–figure 2 (Log-Rank Test=0,8). [Display omitted] [Display omitted] Conclusion:The stated unfavorable prognostic factors allowed to stratify patients into prognostic groups. Modified program NHL-BFM-90 is effective treatment for adult patients with DLBCL with unfavorable prognostic factors. The concordant of BM involvement is the most strict prognostic factor. Disclosures:No relevant conflicts of interest to declare.

Clinical analysis of 3 cases with primary splenic diffuse large B-cell lymphoma

Clinical analysis of 3 cases with primary splenic diffuse large B-cell lymphoma

Histopathological audit of splenectomies received at a cancer hospital

There are few studies in the literature studying the yield of the diagnostic splenectomy in a suspicious lymphoma case. Moreover, their relevance is limited owing to low number of cases, the use of selection criteria, and the lack of modern ancillary studies. We present a histopathological review of splenectomy specimens referred as a case of lymphoma to our center. The medical charts and laboratory data on all patients of all splenectomy specimens between the years 2003 and 2008 were reviewed. Morphological and immunohistochemical features were analyzed and the lymphomas were sub-typed in accordance to 2008 WHO Classification of Hematolymphoid Neoplasms. Flow cytometry immunophenotyping available in few cases was correlated. A total of 46 cases studied included splenic marginal zone lymphoma (SMZL) (19 cases), splenic diffuse large B-cell lymphoma (DLBCL) (14 cases), splenic diffuse red pulp B-cell lymphoma (DRP) (five cases), follicular lymphoma (three cases), hairy cell leukemia (HCL) (two cases), HCL variant (HCLv) (1 case), 1 case of hepatosplenic gamma delta T-cell lymphoma (TCL), and 1 cases of TCL (not otherwise specified). Predominantly splenic lymphoma is a biologically heterogeneous entity, ranging from low-grade SMZL to high-grade DLBCLs. TCLs constituted only 4% of all our cases. DRP, HCL, and HCLv have similar diffuse red pulp patterns of splenic involvement and are differentiated based on flow cytometric immunophenotyping. We had a large number of splenic DLBCL and none of these involved bone marrow (BM), while all other lymphoma subtypes had BM involvement (stage IV disease). Morphological and immunophenotypic (immunohistochemistry and flow cytometry) features of BM and splenectomy specimen need to be correlated to differentiate these rare though similar-looking entities with overlapping features.

Primary splenic diffuse large B-cell lymphoma manifesting in red pulp

We evaluated six cases of diffuse large B-cell lymphoma (DLBCL) involving the red pulp of the spleen. All had B symptoms and an aggressive clinical course. The lymphoma cells proliferated diffusely and non-cohesively in the cords of the red pulp. The lymphoma involved the bone marrow in four of the five patients and the liver in all four of the patients examined. However, lymph node (LN) involvement was rare at presentation, and systemic LN involvement was not observed even in the terminal phase. The lymphoma cells infiltrated the intrasinusoidal/intravascular and interstitial spaces of the involved tissues and were detected in the peripheral blood in two of the six patients. CD5-expressing lymphoma cells were detected in four of the five patients examined. Because these cases had some unique clinical features and occurred in distinct splenic sites, we proposed that primary splenic DLBCL manifesting in red pulp is a distinct clinicopathological entity.

Splenic diffuse large B-cell lymphoma in a patient with type 1 Gaucher disease: diagnostic and therapeutic challenges

Splenic diffuse large B-cell lymphoma in a patient with type 1 Gaucher disease: diagnostic and therapeutic challenges

Prevalence of hepatitis C virus infection in cases of B‐cell lymphoma in Japan

To determine the prevalence of hepatitis C virus (HCV) infection in B-cell lymphoma in Japan. HCV infection and type II (monoclonal IgM) cryoglobulinaemia (CG) may be involved in the pathogenesis of low-grade B-cell lymphoma (ML) in southern Europe. Forty-five (11.3%) of 400 B-cell ML cases were HCV antibody (Ab) positive, which was significantly (P < 0.01) higher than the blood donors (2.5%). Among them, 28 diffuse large B-cell lymphoma (DLBCL) cases were included. In the primary sites, 10 (47.6%) of 21 splenic DLBCL and seven (23.3%) of 30 gastric DLBCL were HCV Ab positive, which were significantly (P < 0.05) higher than the myeloma cases (4.9%). HCV infection was rarely (4.2%) detected in 24 lymphoplasmacytic and salivary gland low-grade B-cell ML cases. Type II CG was detected in one myeloma case (3.5%) of 29 HCV+ B-cell ML. By real-time polymerase chain reaction, HCV RNA was detected in fresh tumour tissues of all 11 B-cell ML cases examined. Lymphoma cells were positive for the envelope HCV non-structural (NS)3 and envelope (E2) proteins in six of eight examined B-cell ML cases. The rare incidence of type II CG is characteristic of Japanese HCV+ ML patients and may influence the low incidence of low-grade B-cell ML. HCV infection may play a role in lymphomagenesis of splenic and gastric DLBCL.

Splenic large B-cell lymphoma in patients with hepatitis C virus infection

Hepatitis virus infection, especially type C (hepatitis C virus [HCV]), has been suggested to be one of the important pathogenetic factors for low- and high-grade B-cell lymphoma, including splenic marginal zone lymphoma (SMZL), in southern Europe. Here, we analyzed the incidences of HCV and hepatitis B virus (HBV) infections, and the clinicopathologic features in 29 cases of splenic diffuse large B-cell lymphoma (DLBCL), 10 SMZL, 3 splenic mantle cell lymphoma, 1 hairy cell leukemia, 13 B-chronic lymphocytic leukemia, and 12 hepatosplenic T-cell and natural killer cell lymphoma. Fifteen (51.7%) splenic DLBCL cases were HCV antibody-positive, and another 6 (20.7%) had the HBsAg. The incidence of each was significantly (P < .01) higher than those of HCV (9.3%) and HBV (1.9%) infections in 54 node-based DLBCL cases. Four examined HCV-positive DLBCL cases showed no type II cryoglobulinemia. HCV RNA was detected in fresh tumor tissues from 6 of 7 examined DLBCL cases, and HBV DNA was present in another 2, as evaluated by real-time polymerase chain reaction. Immunohistologically, tumor cells in 5 of 7 examined DLBCL cases showed intracytoplasmic reactions for HCV NS3 and E2 proteins and the viral receptor CD81. Of 6 cases, 2 showed an intranuclear reaction for the HBV surface protein. By Southern blot analysis, no rearrangement of the Bcl2 gene was detected in the tumor tissue of 7 HCV-positive DLBCL cases. For the other types of malignant lymphoma, 1 case each of SMZL (10%) and hepatosplenic T-cell and natural killer cell lymphoma (8.3%) showed HCV infection. In conclusion, persistent human hepatitis virus infections, especially HCV, may play an important role in the tumorigenesis of splenic DLBCL in Japan.