scholarly journals Bilateral primary renal diffuse large B-cell lymphoma: a rare presentation of paediatric renal disease mimicking juvenile nephronophthisis

2020 ◽  
Vol 13 (7) ◽  
pp. e234810
Author(s):  
Gordon Bruce ◽  
Shahzya Chaudhury ◽  
Ben Reynolds

A 12-year-old boy presented with a prolonged history of headache, fatigue and hypertension. Initial investigations were consistent with presumed non-oliguric end-stage renal disease, leading to a provisional diagnosis of juvenile nephronophthisis. Subsequent imaging demonstrated bilaterally enlarged kidneys without cystic change. Mutation analysis was negative for nephronophthisis, causing diagnostic uncertainty which prompted renal biopsy. Histology revealed a primary renal diffuse large B-cell lymphoma which was highly responsive to chemotherapy, including the anti-CD20 monoclonal agent, rituximab. Renal function improved during lymphoma treatment, with residual chronic kidney disease stage 3a once chemotherapy was completed. Atypical diagnostic features should always prompt re-evaluation of a patient. In this case, the delayed malignancy diagnosis did not have an adverse effect on patient survival or morbidity. The outcome for primary renal lymphoma (PRL) has improved markedly following the introduction of rituximab.

Hematology ◽  
2016 ◽  
Vol 2016 (1) ◽  
pp. 366-378 ◽  
Author(s):  
Bertrand Coiffier ◽  
Clémentine Sarkozy

Abstract Although rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) is the standard treatment for patients with diffuse large B-cell lymphoma (DLBCL), ∼30% to 50% of patients are not cured by this treatment, depending on disease stage or prognostic index. Among patients for whom R-CHOP therapy fails, 20% suffer from primary refractory disease (progress during or right after treatment) whereas 30% relapse after achieving complete remission (CR). Currently, there is no good definition enabling us to identify these 2 groups upon diagnosis. Most of the refractory patients exhibit double-hit lymphoma (MYC-BCL2 rearrangement) or double-protein-expression lymphoma (MYC-BCL2 hyperexpression) which have a more aggressive clinical picture. New strategies are currently being explored to obtain better CR rates and fewer relapses. Although young relapsing patients are treated with high-dose therapy followed by autologous transplant, there is an unmet need for better salvage regimens in this setting. To prevent relapse, maintenance therapy with immunomodulatory agents such as lenalidomide is currently undergoing investigation. New drugs will most likely be introduced over the next few years and will probably be different for relapsing and refractory patients.


Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5367-5367
Author(s):  
Aseeb U Rehman ◽  
Tipu Nazeer ◽  
George D. Wilner ◽  
Katsiaryna Laziuk ◽  
Albert N Huho ◽  
...  

Abstract Background: BRG1 is a component of the highly conserved multisubunit, 2.0-MDa mammalian transcriptional coactivator complex SWI/SNF. This chromatin-remodeling complex is critical for the regulation of gene transcription, thereby controlling diverse cellular processes including differentiation, proliferation, tumorigenesis and DNA repair. BRG1 gene is frequently down regulated or conversely, in some cases, up regulated in cancer cell lines and tumors, implicating that BRG1 may regulate cancer proliferation and progression. BRG1 is currently considered a potential selective therapeutic target. BRG1 expression level has been related to cancer cell migration and invasion and studies have suggested that BRG1 may serve as a prognostic marker in certain cancers. Few studies exist on expression of BRG1 in lymphoproliferative disorders and diffuse large B cell lymphoma (DLBCL) in particular. Our study was aimed at determining the immunohistochemical expression of the BRG1 protein in DLBCL and its potential association with clinicopathologic variables. Design: Formalin-fixed, paraffin embedded sections from 49 Diffuse Large B-cell Lymphomas (DLBCL), were immunostained by a manual method (DAKO LSAB+ System-HRP) using rabbit monoclonal BRG1 (Abcam, Cambridge, MA) antibody. Nuclear and cytoplasmic immunoreactivity was semiquantitatively assessed in all cases. Scoring was based on staining intensity (weak, moderate, intense) and percentage of positive tumor cells (focal <= 10%, regional 11-50%, diffuse >50%). Results were correlated with clinicopathologic variables. Results: BRG1 immunoreactivity was predominately nuclear. Intense diffuse nuclear BRG1 overexpression was observed in 22/49 (45%) cases and correlated with tumor stage [73% stage 4 vs 63% stage 3 vs 40% stage 2 vs 13% stage 1, (p=0.005)]. There were no other correlations that reached statistical significance. Conclusion: BRG1 nuclear expression is increased in DLBCL and is associated with advanced tumor stage. This association with an important adverse prognostic indicator warrants further study of BRG1 expression and its potential as a selective therapeutic target in DLBCL. Disclosures No relevant conflicts of interest to declare.


Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 9-10
Author(s):  
Taha Al-Juhaishi ◽  
Ghaith Abu Zeinah ◽  
Sadeer Al-Kindi

Introduction: Cardiac lymphomas are very rare with diffuse large B-cell lymphoma (DLBCL) considered to be the most common histology. These lymphomas can be either local "primary cardiac" disease, or part of dissemination by systemic lymphoma. There is limited data regarding outcomes of patients with this disease. We sought to evaluate the outcomes of cardiac DLBCL in both pre- and rituximab eras using a large retrospective database. Methods: The public Surveillance, Epidemiology and End Results (SEER) database was used to identify all patients diagnosed with DLBCL and heart as the primary disease site. Data cutoff in the database was in 2016. Patients with missing date of diagnosis or survival data were excluded. Patients were divided into two groups based on diagnosis year, with rituximab cohort included all DLBCLs diagnosed in 2006 and later (2006 was FDA approval year of rituximab in untreated DLBCL). Treatment effect (surgery, radiation, chemotherapy) was analyzed when available. survival was estimated using the Kaplan-Meier method, and compared using Log-Rank test. Cox proportional hazards models were used for adjusted survival analyses. Results: Total of 106 patients were included in the final analysis, baseline characteristics are summarized in table 1. Median age at diagnosis was 69.5 years with only about 10% of patients being 50 years or younger. Most patients were white 71 (67%), had local stage I/II disease 68 (64.2%), and belonged to the rituximab era group 71 (67%). Most patients had chemotherapy 82 (77.4%), while only 25 (23.6%) had surgery, and 16 (15.1%) had radiotherapy. Median overall survival (OS) for the entire cohort was 22 months (0-292). Median OS was 16 months (95% CI, 0.55 -31) for the pre-rituximab group, and was 26 months (95% CI, 7.5 - 45) for the rituximab group which were not statistically different (p-value =0.340). Median lymphoma-specific survival (LCS) was 30 months (95% CI, 8.0 -52) for the pre-rituximab group, and was 36 months (95% CI, 16 - 158) for the rituximab group which were not statistically different (p-value =0.295). OS and LCS were also not different between the two era groups when stratified by chemotherapy (figure 1). On univariate analysis, Chemotherapy was associated with better OS [HR = 0.472, 95% CI (0.277-0.806); p-value = 0.006] but not LCS [HR = 0.690, 95% CI (0.341-1.396); p-value = 0.302]. Using a multivariate analysis model, both OS and LCS were associated with lymphoma stage, insurance status and age but not with diagnosis era or chemotherapy (table 2). Conclusion: Cardiac DLBCLs are rare and affecting mostly the elderly. No significant improvement in outcomes were noted in the current rituximab era. Age, disease stage, and having health insurance were associated with better outcomes. The role of chemotherapy needs further evaluation in larger studies. Disclosures No relevant conflicts of interest to declare.


Blood ◽  
2018 ◽  
Vol 131 (24) ◽  
pp. 2670-2681 ◽  
Author(s):  
Weicheng Ren ◽  
Xiaofei Ye ◽  
Hong Su ◽  
Wei Li ◽  
Dongbing Liu ◽  
...  

Hepatitis B virus (HBV) infection is endemic in some parts of Asia, Africa, and South America and remains to be a significant public health problem in these areas. It is known as a leading risk factor for the development of hepatocellular carcinoma, but epidemiological studies have also shown that the infection may increase the incidence of several types of B-cell lymphoma. Here, by characterizing altogether 275 Chinese diffuse large B-cell lymphoma (DLBCL) patients, we showed that patients with concomitant HBV infection (surface antigen positive [HBsAg+]) are characterized by a younger age, a more advanced disease stage at diagnosis, and reduced overall survival. Furthermore, by whole-genome/exome sequencing of 96 tumors and the respective peripheral blood samples and targeted sequencing of 179 tumors from these patients, we observed an enhanced rate of mutagenesis and a distinct set of mutation targets in HBsAg+ DLBCL genomes, which could be partially explained by the activities of APOBEC and activation-induced cytidine deaminase. By transcriptome analysis, we further showed that the HBV-associated gene expression signature is contributed by the enrichment of genes regulated by BCL6, FOXO1, and ZFP36L1. Finally, by analysis of immunoglobulin heavy chain gene sequences, we showed that an antigen-independent mechanism, rather than a chronic antigenic simulation model, is favored in HBV-related lymphomagenesis. Taken together, we present the first comprehensive genomic and transcriptomic study that suggests a link between HBV infection and B-cell malignancy. The genetic alterations identified in this study may also provide opportunities for development of novel therapeutic strategies.


2010 ◽  
Vol 28 (27) ◽  
pp. 4170-4176 ◽  
Author(s):  
Jack Phan ◽  
Ali Mazloom ◽  
L. Jeffrey Medeiros ◽  
Tony G. Zreik ◽  
Christine Wogan ◽  
...  

Purpose The current standard therapy for patients with diffuse large B-cell lymphoma (DLBCL) is rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). The role of consolidative radiation therapy (RT) in the setting of R-CHOP chemotherapy is not well reported. This retrospective analysis is an attempt to clarify this role. Patients and Methods Subjects were 469 patients with histologically confirmed DLBCL treated between January 2001 and December 2007. Variables including age, sex, Ann Arbor disease stage, bulky disease status, standardized uptake values (SUVs) on positron emission tomography (PET), International Prognostic Index (IPI), and Ki67 staining (proliferation). Results Of 469 patients, 190 (40.5%) had stage I or II disease and 279 (59.5%) had stage III or IV disease, 327 (70%) had at least six cycles of R-CHOP, and 142 (30.2%) had involved-field RT (dose, 30 to 39.6 Gy) after complete response to chemotherapy. Median follow-up was 36 months (range, 8 to 85 months). Multivariate analysis showed that RT (P < .0001), IPI score (P = .001), response to therapy (P = .001), use of six to eight cycles of R-CHOP (P < .001), and combined presence (P = .006) or absence (P = .025) of high Ki67, high PET SUV, and bulky disease influenced overall survival (OS) and progression-free survival (PFS). Matched-pair analyses of patients who received six to eight cycles of R-CHOP with stage I or II disease (44 pairs) and all stages (74 pairs) indicated that RT improved OS (hazard ratio [HR], 0.52 and 0.29, respectively) and PFS (HR, 0.45 and 0.24, respectively) compared with no RT. Conclusion This study showed significant improvements in OS and PFS among patients who received consolidation RT after R-CHOP chemotherapy for DLBCL.


2019 ◽  
Vol 08 (01) ◽  
pp. 57-59 ◽  
Author(s):  
Babu Suresh ◽  
Vikas Asati ◽  
K. C. Lakshmaiah ◽  
Govind Babu ◽  
D. Lokanatha ◽  
...  

Abstract Background: Gastrointestinal tract (GIT) is the most common extranodal site for non-Hodgkin's lymphoma (NHL) and constitutes about 10%-15% of all NHL. This was a prospective study to evaluate the epidemiological, clinicopathological characteristics, and treatment outcome of primary GIT diffuse large B-cell lymphoma (PGIL). Materials and Methods: Newly diagnosed patients of PGIL with DLBCL histology were eligible. Lugano staging system was used. All patients were treated with prephase treatment (1 mg vincristine and 100 mg prednisolone) followed by CHOP-based chemotherapy (with or without rituximab) as definitive treatment. Results: A total of 21 patients of PGIL were diagnosed. The median age was 46 years (range: 27–69 years) with male:female ratio of 2:1. Dull aching abdominal pain was the most common presenting complaint. Stomach was the most common site involved (52.4%, n = 11) followed by the colon (23.8%, n = 5). The estimated median survival in patients with Stage IV disease was significantly lower as compared to patients with localized disease (Stage I and II) (6.23 months vs. 23.4 months; P = 0.04). Patients, who did not achieve complete response (CR), had 15.5 times higher risk of death, as compared to those who achieved CR (P = 0.01). Conclusions: Stomach was the most common site for PGIL. Localized disease and CR after first-line chemotherapy were associated with better survival. A higher cost of rituximab was the prohibitive factor for cure in these patients.


Praxis ◽  
2016 ◽  
Vol 105 (1) ◽  
pp. 47-52 ◽  
Author(s):  
Andreas Lohri

Zusammenfassung. Maligne Lymphome unterteilen sich zwar in über 60 Entitäten, das grosszellige B-Zell-Lymphom, das follikuläre Lymphom, der Hodgkin und das Mantelzell-Lymphom machen aber mehr als die Hälfte aller Lymphome aus. Im revidierten Ann Arbor staging system gelten die Suffixe «A» und «B» nur noch für den Hodgkin. «E» erscheint nur noch bei Stadien I und II. Eine Knochenmarksuntersuchung wird beim Hodgkin nicht mehr verlangt, beim DLBCL (Diffuse large B cell lymphoma) nur, falls das PET keinen Knochenmark-Befall zeigt. Der PET-Untersuchung, speziell dem Interim-PET, kommt eine entscheidende Bedeutung zu. PET-gesteuerte Therapien führen zu weniger Toxizität. Gezielt wirkende Medikamente mit eindrücklicher Wirksamkeit wurden neu zugelassen. Deren Kosten sind hoch. Eine strahlen- und chemotherapiefreie Behandlung maligner Lymphome wird in Zukunft möglich sein.


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