The diversity of diffuse large B-cell lymphoma in extranodal sites: overview and update

Abstract

Extranodal lymphomas are a diverse group of low and high grade neoplasms of B-, T-, and NK-cell lineage, each with characteristic sites of origin, morphology, immunophenotype, genetic features, patterns of spread, and prognosis. The diversity is sometimes seen even within a single histologic type of lymphoma. This phenomenon is especially striking in the category of diffuse large B-cell lymphoma (DLBCL). DLBCLs as classified in the WHO Classification are clinically and pathologically heterogeneous . Since the publication of the most recent edition of the WHO Classification of tumours of haematopoietic and lymphoid tissues ), a number of advances in the understanding of these lymphomas have been made. This review provides an overview of extranodal DLBCLs and describes recent updates regarding these lymphomas.

Diagnosis and management of primary central nervous system lymphoma

“…Gene expression profiles also demonstrate that PCNSL is characterized by the differential expression of genes related to adhesion and extracellular matrix pathways, including MUM1 , CXCL13 , and CHI3L1 . Alterations in TP53 , CDKN2A/p16 , BCL‐6 , MYC , and PAX5 genes are also commonly observed in PCNSL …”

“…Mutations leading to the activation of the nuclear factor jB signaling pathway, such as activating mutations of MYD88, CARD11, and CD79 and deletions of TNFAIP3 and TBL1XR1, are observed in almost all PCNSL cases, and this suggests that nuclear factor jB activation may play a role in the pathogenesis of PCNS DLBCL and may represent a potential therapeutic target. 8,9 Gene expression profiles also demonstrate that PCNSL is characterized by the differential expression of genes related to adhesion and extracellular matrix pathways, including MUM1, CXCL13, and CHI3L1. Alterations in TP53, CDKN2A/p16, BCL-6, MYC, and PAX5 genes are also commonly observed in PCNSL.…”

Primary central nervous system lymphoma

“…Mutations leading to activation of the nuclear factor κB (NF-κB) signaling pathway, such as activating mutations of MYD88, CARD11 and CD79 and deletions of TNFAIP3 and TBL1XR1 , are observed in almost all PCNSL cases, suggesting that NF-κB activation may play a role in the pathogenesis of PCNS DLBCL and may represent a potential therapeutic target. 11 , 13 , 14 Gene expression profiles also demonstrate that PCNSL is characterized by differential expression of genes related to adhesion and extracellular matrix pathways, including MUM1, CXCL13 and CHI3L1. Alterations in TP53, CDKN2A/p16, BCL-6, MYC and PAX5 genes are also commonly observed in PCNSL.…”

“… 10 Inactivation of CDKN2A is also commonly observed in PCNSL and systemic DLBCL. 11 PCNS DLBCL more often have loss of human leukocyte antigen (HLA) class I or HLA class II expression compared with primary nodal DLBCL. This could result in the evasion of neoplastic B cells from immune surveillance by T cells which, in turn, may explain the poorer prognosis of PCNS DLBCL.…”

Thomas Hodgkin and Hodgkin lymphoma

“…The term "primary mediastinal gray-zone lymphoma" is used for cases of B cell lymphoma, unclassifiable, with features intermediate between diffuse large B cell lymphoma (in particular, primary mediastinal large B cell lymphoma) and CHL arising in the mediastinum [64]. As can be concluded by this designation, subclassification of these cases is often problematic [11,63,65]. Tumor cells are usually abundant, often growing in sheets.…”