The genomic landscape of mantle cell lymphoma is related to the epigenetically determined chromatin state of normal B cells.

In this study, we define the genetic landscape of mantle cell lymphoma (MCL) through exome sequencing of 56 cases of MCL. We identified recurrent mutations in ATM, CCND1, MLL2, and TP53. We further identified a number of novel genes recurrently mutated in patients with MCL including RB1, WHSC1, POT1, and SMARCA4.

Atypical Epstein-Barr viral genomic structure in lymphoma tissue and lymphoid cell lines.

Epstein-Barr virus (EBV) DNA is found within the malignant cells of some subtypes of lymphoma, and viral presence is being exploited for improved diagnosis, monitoring, and management of affected patients. Recent work suggests that viral genomic polymorphism, such as partial deletion of the viral genome, could interfere with virus detection in tumor tissues. To test for atypical forms of the EBV genome, 98 lymphomas and 6 infected cell lines were studied using a battery of 6 quantitative polymerase chain reaction assays targeting disparate sections of EBV DNA.

Diagnostic and clinical considerations in concomitant bone marrow involvement by plasma cell myeloma and chronic lymphocytic leukemia/monoclonal B-cell lymphocytosis: a series of 15 cases and review of literature.

Context: Plasma cell myeloma and chronic lymphocytic leukemia are both common hematologic malignancies, sharing many epidemiologic features. Concomitant detection of the 2 conditions poses special diagnostic challenges for the pathologist.

Objective: To describe the pathologic findings in cases of concomitant bone marrow involvement by myeloma and CD5(+) monoclonal B cells and to outline the differential diagnostic possibilities, suggest a workup for correct diagnosis, and examine clinical outcome.

Immunosuppressive and immunomodulatory therapy-associated lymphoproliferative disorders.

A variety of therapeutic agents may increase the risk of lymphoproliferative disorders/neoplasms. These include those agents used to treat other malignancies (i.e.

Diagnostic complexities of eosinophilia.

Context: The advent of molecular tools capable of subclassifying eosinophilia has changed the diagnostic and clinical approach to what was classically called hypereosinophilic syndrome.

Objectives: To review the etiologies of eosinophilia and to describe the current diagnostic approach to this abnormality.

Data Sources: Literature review.

Genetic heterogeneity of diffuse large B-cell lymphoma.

Diffuse large B-cell lymphoma (DLBCL) is the most common form of lymphoma in adults. The disease exhibits a striking heterogeneity in gene expression profiles and clinical outcomes, but its genetic causes remain to be fully defined. Through whole genome and exome sequencing, we characterized the genetic diversity of DLBCL.

The genetic landscape of mutations in Burkitt lymphoma.

Burkitt lymphoma is characterized by deregulation of MYC, but the contribution of other genetic mutations to the disease is largely unknown. Here, we describe the first completely sequenced genome from a Burkitt lymphoma tumor and germline DNA from the same affected individual. We further sequenced the exomes of 59 Burkitt lymphoma tumors and compared them to sequenced exomes from 94 diffuse large B-cell lymphoma (DLBCL) tumors.

Composite mantle cell lymphoma and chronic lymphocytic leukemia/small lymphocytic lymphoma: a clinicopathologic and molecular study.

Mantle cell lymphoma (MCL) and chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) share many features and both arise from CD5+ B-cells; their distinction is critical as MCL is a more aggressive neoplasm. Rarely, cases of composite MCL and CLL/SLL have been reported. Little is known about the nature of these cases and, in particular, the clonal relationship of the 2 lymphomas.

Patients with diffuse large B-cell lymphoma of germinal center origin with BCL2 translocations have poor outcome, irrespective of MYC status: a report from an International DLBCL rituximab-CHOP Consortium Program Study.

Diffuse large B-cell lymphoma can be classified by gene expression profiling into germinal center and activated B-cell subtypes with different prognoses after rituximab-CHOP. The importance of previously recognized prognostic markers, such as Bcl-2 protein expression and BCL2 gene abnormalities, has been questioned in the new therapeutic era. We analyzed Bcl-2 protein expression, and BCL2 and MYC gene abnormalities by interphase fluorescence in situ hybridization in 327 patients with de novo disease treated with rituximab-CHOP.

Bone marrow B cell precursor number after allogeneic stem cell transplantation and GVHD development.

Patients without chronic graft-versus-host disease (cGVHD) have robust B cell reconstitution and are able to maintain B cell homeostasis after allogeneic hematopoietic stem cell transplantation (HSCT). To determine whether B lymphopoiesis differs before cGVHD develops, we examined bone marrow (BM) biopsies for terminal deoxynucleotidyl transferase (TdT) and PAX5 immunostaining early post-HSCT at day 30 when all patients have been shown to have high B cell activating factor (BAFF) levels. We found significantly greater numbers of BM B cell precursors in patients who did not develop cGVHD compared with those who developed cGVHD (median = 44 vs 2 cells/high powered field [hpf]; respectively; P < .

Mantle cell lymphoma as a component of composite lymphoma: clinicopathologic parameters and biologic implications.

Composite lymphoma is a rare circumstance in which 2 or more distinct types of lymphoma occur in a single anatomical location. Although composite lymphoma has been increasingly identified with the advent of molecular genetic techniques, this topic has only rarely been a specific focus of the medical scientific literature. In this review, we focus on mantle cell lymphoma occurring as a major pathologic component of composite lymphoma and emphasize the clinicopathologic features of these tumors and associated biologic implications.

Anaplastic large cell lymphoma: an unusual presentation in a 7-year-old girl.

Anaplastic large cell lymphoma (ALCL) accounts for 10% to 30% of all childhood lymphomas and approximately 5% of all non-Hodgkin's lymphoma. ALCL is considered to be a T-cell non-Hodgkin's lymphoma that can be divided into two major groups with distinct genetic, immunophenotypic, and clinical behaviors. The first group consists of a spectrum of CD30+ T-cell lymphoproliferative disorders that include primary cutaneous ALCL (C-ALCL) and lymphomatoid papulosis.

miRNA expression in diffuse large B-cell lymphoma treated with chemoimmunotherapy.

Diffuse large B-cell lymphoma (DLBCL) prognostication requires additional biologic markers. miRNAs may constitute markers for cancer diagnosis, outcome, or therapy response. In the present study, we analyzed the miRNA expression profile in a retrospective multicenter series of 258 DLBCL patients uniformly treated with chemoimmunotherapy.

Comparative analysis of detecting monocytic cells and their aberrancy.

Background And Study Purpose: Detection of monocytic cells (MCs) and their aberrancy is important in the diagnoses of monocytic leukemias [chronic myelomonocytic leukemia (CMML), acute MML (AMML), and acute monocytic/monoblastic leukemia (AMoL)]. MCs may be identified by cytomorphology (CM), enzyme cytochemical staining with nonspecific esterases, flow cytometric analysis (FCA), and immunohistochemical analysis (IHCA); their aberrancy, by FCA or IHCA. As aberrant antigen expression on MCs is not detected by CM or enzyme cytochemical staining and as there may be instances of "dry tap" or a fresh bone marrow aspirate is not available for further analysis, the primary and specific purpose of this study is to globally compare the detection of MCs and their aberrancy by the 2 methods of FCA and IHCA.

Deep sequencing of the small RNA transcriptome of normal and malignant human B cells identifies hundreds of novel microRNAs.

A role for microRNA (miRNA) has been recognized in nearly every biologic system examined thus far. A complete delineation of their role must be preceded by the identification of all miRNAs present in any system. We elucidated the complete small RNA transcriptome of normal and malignant B cells through deep sequencing of 31 normal and malignant human B-cell samples that comprise the spectrum of B-cell differentiation and common malignant phenotypes.

A case-control study of tobacco use and other non-occupational risk factors for lymphoma subtypes defined by t(14; 18) translocations and bcl-2 expression.

Objective: We re-evaluated reported associations between tobacco use and other factors and non-Hodgkin lymphoma (NHL) t(14; 18)-subtypes based on fluorescence in situ hybridization (FISH) assays believed to be more sensitive than polymerase chain reaction (PCR), previously used for detecting t(14; 18).

Methods: Commercial FISH assays and bcl-2 immunostaining were performed on paraffin sections to determine t(14; 18) and bcl-2 case-subtypes. Polytomous logistic regression models estimated associations between NHL case-subtypes (versus 1,245 population-based controls) and tobacco use as well as other factors.

The implication of identifying JAK2 ( V617F ) in myeloproliferative neoplasms and myelodysplastic syndromes with bone marrow fibrosis.

The myeloproliferative neoplasms (MPN) and myelodysplastic syndromes (MDS) occasionally demonstrate overlapping morphological features including hypercellularity, mild/nonspecific dysplastic changes and variable bone marrow fibrosis. Thus, when the associated bone marrow fibrosis results in a suboptimal specimen for morphological evaluation, the descriptive diagnosis "fibrotic marrow with features indeterminate for MDS versus MPN" is often applied. The JAK2 ( V617F ) mutation was recently shown to be frequently identified in MPN, but it is rarely present in other myeloid disorders.

Primary mediastinal B-cell lymphoma: detection of BCL2 gene rearrangements by PCR analysis and FISH.

Primary mediastinal large B-cell lymphoma (PMBCL) has a characteristic clinical presentation, morphology, and immunophenotype, representing a clinically favorable subgroup of diffuse large B-cell lymphoma (DLBCL). By gene expression profiling (GEP), PMBCL shares features with classical Hodgkin lymphoma (cHL). Of further interest, BCL6 gene mutations and BCL6 and/or MUM1 expression in a number of PMBCLs have supported an activated B-cell (ABC) origin.

Glut1 and Glut3 expression in lymphoma and their association with tumor intensity on 18F-fluorodeoxyglucose positron emission tomography.

Objective: To evaluate the expression of glucose transporters (Gluts) 1 and 3 in Hodgkin and nonHodgkin lymphoma and to assess the association between their expression and the tumor intensity on 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET).

Methods: All 31 lymphoma patients in whom the histologic diagnosis was made and who had also undergone a prechemotherapy PET scan at our institution between June 2001 and December 2005 were included in this retrospective study. The percentage of tumor cells in the various lymphoma subtypes was estimated by comparison of hematoxylin and eosin stain with a lineage-associated immunohistochemical stain on the same block of tissue.

Non-Hodgkin lymphoma (NHL) subtypes defined by common translocations: utility of fluorescence in situ hybridization (FISH) in a case-control study.

We used fluorescence in situ hybridization (FISH) assays to identify t(14;18) translocations in archival paraffin-embedded tumor sections from non-Hodgkin lymphoma (NHL) cases enrolled in a population-based study. t(14;18) was identified in 54% of 152 cases, including 39% of diffuse large cell lymphomas (26 of 66 cases) and 84% of follicular lymphomas (36 of 43 cases). Eighty-seven percent of t(14;18)-positive cases and 57% of t(14;18)-negative cases expressed bcl-2.

Mast cell burden and reticulin fibrosis in the myeloproliferative neoplasms: a computer-assisted image analysis study.

The mast cell has been associated with fibrosis in many different tissues, organs, and different disease processes including hematopoietic malignancies. Mast cells are often increased in the bone marrow of patients with primary bone marrow disorders, and patients with systemic mastocytosis often have a second concomitant neoplastic disease of the bone marrow. The goals of the current study were to determine the role the mast cell has in the pathogenesis of myeloproliferative neoplasms (MPN) and to correlate the mast cell burden with the degree of reticulin fibrosis.

p38 mitogen-activated protein kinase has different degrees of activation in myeloproliferative disorders and myelodysplastic syndromes.

The goal of the present study was to evaluate the activation patterns of p38 mitogen-activated protein kinase (MAPK) in myeloproliferative disorders (MPDs) and myelodysplastic syndromes (MDSs). Phosphorylated (activated) p38 MAPK was analyzed immunohistochemically in formalin-fixed decalcified bone marrow core biopsy specimens from 32 MPD, 33 MDS, and 11 control cases. Moderate p38 activation was commonly seen in MDS, whereas weak p38 activation was seen in all MPD cases and all control cases but 1 in the erythroid lineage.