Diffuse Large B‐Cell Lymphoma

Context.—Diffuse large B-cell lymphoma is a heterogenous group of lymphomas. In this review, we present a brief description of the large number of entities recognized in the recently published (2008) World Health Organization classification of tumors of hematopoietic and lymphoid tissues. Objective.—We highlight the unique clinicopathologic and molecular genetic features of these new and previously recognized entities, to illustrate the rational for the development of this classification. To help simplify the understanding of this now large and complex group of diseases, we have attempted to create broader subgroups of related entities. We discuss large B-cell lymphoma that are not otherwise specified, those that are based on anatomic site, those that have unique histology or phenotype or genotype, those that are associated with Epstein-Barr virus or Kaposi sarcoma–associated herpesvirus and herpesvirus 8, and those that are unclassifiable. Data Sources.—World Health Organization classification of tumors of hematopoietic and lymphoid tissues (2008), published literature from PubMed (National Library of Medicine), and primary material from the authors' institution were reviewed. Conclusions.—Recognition of the different subtypes of diffuse large B-cell lymphoma as described in the World Health Organization classification scheme will lead to improved understanding of the unique clinicopathologic and genetic features associated with these subtypes of lymphoma.

Diffuse Large B-Cell Lymphoma—More Than a Diffuse Collection of Large B Cells: An Entity in Search of a Meaningful Classification

Gurbaxani

Anastasi

Hyjek

2009

Expression of p53, c-Myc, or Bcl-6 Suggests a Poor Prognosis in Primary Central Nervous System Diffuse Large B-Cell Lymphoma Among Immunocompetent Individuals

Chang

Kampalath

Schultz

et al. 2003

Context.—Primary central nervous system (CNS) diffuse large B-cell lymphoma (DLBCL) in immunocompetent individuals, although rare, has been rising in incidence. Currently, no reliable prognostic markers are available for these individuals. Objective.—To study the implications of expression of a panel of oncogenic proteins (Bcl-2, Bcl-6, and c-Myc) and p53 for predicting clinical outcome, particularly overall survival, in immunocompetent individuals with primary CNS DLBCL. Design.—Fourteen primary CNS DLBCL cases were retrospectively studied by immunohistochemistry on formalin-fixed, paraffin-embedded sections for the expression of c-Myc, Bcl-2, Bcl-6, and p53. Results.—The overall frequencies of expression for p53, c-Myc, Bcl-2, and Bcl-6 in these cases were 29%, 50%, 71%, and 57%, respectively. Cases with expression of p53, c-Myc, or Bcl-6 had a poorer overall survival than those without (Kaplan-Meier survival analysis: 50% cumulative overall survival, 2 months vs 30–60 months, P = .02, log-rank test; 9–16 months vs 21–60 months, P = .03, log-rank test; and 9–16 months vs 21–60 months, P = .16, log-rank test, respectively). The expression of Bcl-2 or proliferation activity by MIB-1 showed no correlation with overall survival. Likewise, the clinical parameters, including age, location of tumors, multiplicity of tumor lesions, and lactase dehydrogenase levels revealed no impact on overall survival. Conclusion.—Our results suggest that patients with expression of p53, c-Myc, or Bcl-6 have a poorer overall survival than those without. Since traditional prognostic markers in non-CNS DLBCL, such as staging and International Prognostic Index scores, are not applicable to primary CNS DLBCL, evaluation of p53, c-Myc, and Bcl-6 by immunohistochemistry may be warranted as part of prognostic evaluation in immunocompetent patients with primary CNS DLBCL. Further studies are indicated to confirm our observations.

Comparison of Ataxia-Telangiectasia Mutated Protein Expression in Diffuse Large B-Cell Lymphomas of Primary Central Nervous System and Non–Central Nervous System Origin

Kim

Cheong

Park

et al. 2007

Context.—The ataxia-telangiectasia mutated (ATM) gene encodes a nuclear 370-kd phosphoprotein known to be associated with chromosomal regions containing double-strand breaks. The mutations in the ATM gene may be involved in the development of some subtypes of sporadic lymphomas and leukemias. In primary central nervous system diffuse large B-cell lymphomas (PCNS DLBCLs), the pathogenetic role of ATM mutation has not been investigated. Objective.—To investigate ATM protein expression in PCNS DLBCLs, in comparison with that in non–central nervous system (non-CNS) DLBCLs and to study the relationship of ATM protein loss with several clinicopathologic parameters. Design.—This study included 42 cases of PCNS DLBCL and 33 cases of non-CNS DLBCL from immunocompetent patients. The ATM protein loss was analyzed by immunohistochemical staining. For the subclassification of DLBCL and analysis of the relationship between ATM and other prognostic markers, we performed immunohistochemical evaluation to detect the following markers: Bcl-6, CD10, multiple myeloma-1, CD138, Bcl-2, Ki-67, and p53. Results.—The loss of ATM expression was statistically more frequent in PCNS DLBCLs (21/42 cases [50.0%]) than in non-CNS DLBCLs (0/33 cases [0.0%]; P < .001). The loss of ATM expression was not a prognostic marker in PCNS DLBCLs (P = .64). The loss of ATM expression had a strong correlation with the germinal center B-cell–like subtype (P = .01), a low Ki-67 labeling index (P = .03), and low Bcl-2 expression (P = .01) among several clinicopathologic parameters. Conclusions.—Our results suggest that the ATM protein is more strongly correlated with PCNS DLBCL lymphomagenesis than with non-CNS DLBCLs, especially in germinal center B-cell–like subtypes demonstrating low Ki-67 labeling indexes and low Bcl-2 expression.