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The objective of this study was to evaluate the prognostic impact of genomic regions in a series of human immunodeficiency virus (HIV)-related diffuse large B-cell lymphomas (HIV-DLBCLs) and post-transplant DLBCLs (PT-DLBCLs) analyzed by genome-wide DNA profiling. Minimal common regions (MCRs) were estimated on genomic profiles obtained using Affymetrix Human Mapping 250k Nsp I arrays and tested for their impact on clinical outcome by univariate analysis on 36 PT-DLBCLs, 19 HIV-DLBCLs and, as a control group, 149 DLBCLs arising in immunocompetent individuals (IC-DLBCLs). PT-DLBCL and HIV-DLBCL presented a similar outcome. Immunodeficiency-related DLBCL (ID-DLBCL) had a worse overall survival (OS) than IC-DLBCL. Seven MCRs showed a statistical impact on OS in PT-DLBCL and four in HIV-DLBCL. Among these, the presence of gains at 1q or at 18q defined a group of patients with PT-DLBCL with a very poor outcome ( p < 0.0001). The presence of del(3p14.2) or of ++ 2p23.1 identified a group of HIV-DLBCLs with a very poor outcome ( p == 0.0072). It was concluded that genomic aberrations affecting outcome differ between ID-DLBCL and IC-DLBCL and are also dependent on the type of acquired immunodeficiency. [ABSTRACT FROM AUTHOR]

The article discusses a study which investigated the involvement of CD79A, EZH2, and CD79B gene mutations in immunodeficiency-related non-Hodgkin lymphomas (ID-NHL). Using polymerase chain reaction amplification and direct sequencing, the study identified only EZH2 mutations in 3/116 ID-NHL primary samples. It notes that among the immunocompetent hosts' aggressive NHL, EZH2 mutations are selectively confined to cases of diffuse large B-cell lymphoma (DLBCL) with a germinal centre (GC) phenotype.

Post-transplant lymphoproliferative disorders (PTLD) are complications of solid organ transplantation associated with severe morbidity and mortality. Diffuse large B-cell lymphoma (DLBCL) represents the most common form of monomorphic PTLD. We studied 44 cases of post-transplant DLBCL (PT-DLBCL) with high-density genome wide single nucleotide polymorphism-based arrays, and compared them with 105 cases of immunocompetent DLBCL (IC-DLBCL) and 28 cases of Human Immunodeficiency Virus-associated DLBCL (HIV-DLBCL). PT-DLBCL showed a genomic profile with specific features, although their genomic complexity was overall similar to that observed in IC- and HIV-DLBCL. Among the loci more frequently deleted in PT-DLBCL there were small interstitial deletions targeting known fragile sites, such as FRA1B, FRA2E and FRA3B. Deletions at 2p16.1 (FRA2E) were the most common lesions in PT-DLBCL, occurring at a frequency that was significantly higher than in IC-DLBCL. Genetic lesions that characterized post-germinal center IC-DLBCL were under-represented in our series of PT-DLBCL. Two other differences between IC-DLBCL and PT-DLBCL were the lack of del(13q14.3) ( MIR15/MIR16) and of copy neutral LOH affecting 6p [major histocompatibility complex (MHC) locus] in the latter group. In conclusion, PT-DLBCL presented unique features when compared with IC-DLBCL. Changes in PT-DLBCL were partially different to those in HIV-DLBCL, suggesting different pathogenetic mechanisms in the two conditions linked to immunodeficiency. [ABSTRACT FROM AUTHOR]

We report the case of an Epstein-Barr virus (EBV)- and human immunodeficiency virus-serum negative patient suffering from repeatedly relapsing classical Hodgkin’s Lymphoma (cHL) associated with a histological picture of plasma cell-hyaline vascular (PC-HV) form of Castleman’s disease (CD). The CD30- and CD15- positive, Reed-Sternberg/Hodgkin cells, only occasionally expressed the CD20 molecule, but not leukocyte common antigen and latent membrane protein-1. Single-strand polymerase chain reaction failed to detect human herpesvirus 8 or EBV in the involved tissues. At the time of second relapse in July 2005, the clinical picture was characterized by a palpable right hypogastric mass, disclosed at physical exam, in the absence of other enlarged peripheral lymph nodes, subjective symptoms or laboratory profile alterations. Combined hybrid-(18)F-fluorodeoxyglucose positron emission-computerized tomography (18F-FDG PET/CT) showed increased radionuclide uptake in multiple external iliac lymph nodes [standardized uptake value (SUV) of 7.4] and non-palpable left supraclavicular lymph nodes (SUV of 5.8). Relapsing cHL in the context of mixed PC-HV CD was documented in two of three surgically excised abdominal lymph nodes never previously enlarged or involved by any lymphoproliferative disease. Because of the limited disease extension and failure to induce continuous remission with previous conventional chemoradiotherapy, the patient was treated with six rituximab injections. This immunotherapy induced significant reduction in size of supraclavicular lymph nodes as evident at ultrasound (US) scan (<1 vs. 2.5 cm, post- vs. pretherapy), which was confirmed by the 18F-FDG PET/CT in October 2005, despite no modification in SUV of 4.2. 18F-FDG PET/CT also disclosed no radionuclide uptake by abdominal lymph nodes. Thus, a second course of four additional rituximab injections was given and subsequent 18F-FDG PET/CT indicated persistent, but reduced incorporation of radionuclide compared to the pretherapy value (SUV of 2.7) in the supraclavicular area and confirmed a normal metabolic activity in the iliac external lymph nodes. Because of uncertain persistent disease in the supraclavicular nodal site, involved-field radiotherapy (RT) was delivered in that area as consolidation treatment. After completion of rituximab and RT for 16 and 14 months respectively, US and 18F-FDG PET/CT exams were indicative of complete remission. This case is in concordance with previously published data suggesting that rituximab immunotherapy might be a valid option in the treatment of CD and also have a role in the management of relapsing cHL. [ABSTRACT FROM AUTHOR]

The article focuses on somatic hypermutation (SHM) in post-transplant lymphoproliferative disorders (PTLD). Monoclonal PTLD include polymorphic PTLD, diffuse large B-cell lymphoma (DLBCL) and Burkitt/Burkitt-like lymphoma. Most PTLD originate from germinal centre experienced B cells that have undergone the physiological SHM process targeting immunoglobulin variable genes. Aberrant SHM is a pathogenetic mechanism implicated in DLBCL of immunocompetent hosts and acquired immuno-deficiency syndrome related lymphomas that target the 5' region, including coding sequences, of multiple proto-oncogenes relevant to lymphomagenesis.

The mutator phenotype caused by defects in the mismatch repair system is observed in a subset of solid neoplasms characterized by widespread microsatellite instability-high (MSl-H). It is known to be very rare in non-Hodgkin lymphomas (NHL), whereas mutator NHL is the most frequent tumor subtype in mismatch repair- deficient mice. By screening a series of 603 human NHL with specific markers of the mutator phenotype, we found here 12 MSI-H cases (12/603, 2%). Of interest we demonstrated that this phenotype was specifically associated with immunodeficiency-related lymphomas (ID-RL), because it was observed in both posttransplant lymphoproliferative disorders (9/111, 8.1%) and HIV infection- related lymphomas (3/128, 2.3%) but not in a large series of NHL arising in the general population (0/364) (P < 0.0001). The M5l pathway is known to lead to the production of hundreds of abnormal protein neoantigens that are generated in MSl-H neoplasms by frameshift mutations of a number of genes containing coding microsatellite sequences. As expected, MSI-H ID-RL were found to harbor such genetic alterations in 12 target genes with a putative role in lymphomagenesis. The observation that the MSl-H phenotype was restricted to HIV infection-related lymphomas and posttransplant lymphoproliferative disorders suggests the existence of the highly immunogenic mutator pathway as a novel oncogenic process in lymphomagenesis whose role is favored when host immunosurveillance is reduced. Because MSl-H-positive cases were found to be either Epstein-Barr virus-positive or -negative, the mutator pathway should act synergistically or not with this other oncogenic factor, playing an important role in ID-RL. [ABSTRACT FROM AUTHOR]

Novel N-glycosylation sites are introduced by somatic mutation into the V genes of the majority of follicular lymphomas. Sites are positively selected and rare in normal memory B cells, indicating a potential role in tumour survival in the germinal centre (GC). The incidence of c. 40% in diffuse large B-cell lymphomas (DLBCL) parallels the known heterogenity of the disease. Immunodeficiency-related non-Hodgkin's lymphomas (NHL) include post-transplant lymphoproliferative disorders (PTLD) and acquired immunodeficiency syndrome-related NHL (AIDS-NHL). Most PTLD derive from B cells that carry mutated VH genes and that have completed the GC reaction. All AIDS-NHL carry mutated VH genes and variable features of GC or post-GC cells. To determine if N-glycosylation is a feature of immunodeficiency-related lymphomas, we analysed the VH genes of 19 PTLD and 36 AIDS-NHL. Novel sites were rare in PTLD (4/19), similar to memory B cells ( P = 0·15). AIDS-NHL, including DLBCL and Burkitt's lymphomas (BL), showed heterogeneity with 16 of 36 (44%) having novel sites. The findings indicate no selection of N-glycosylation sites in PTLD, consistent with post-GC features. The variable incidence of N-glycosylation sites in AIDS-NHL mirrors that in DLBCL and sporadic BL of immunocompetent hosts, supporting the known heterogeneity of these disorders, and possibly pointing to distinct routes of tumour development. [ABSTRACT FROM AUTHOR]

This article presents a letter to the editor concerning the risk of recurrent infections during watch and wait periods of early stage chronic lymphocytic leukemia.