The histological classification of diffuse large B-cell lymphomas

Abstract

Diffuse large B-cell lymphomas (DLBCLs) are aggressive B-cell neoplasms with considerable clinical, biologic, and pathologic diversity, in part reflecting the functional diversity of the B-cell system and multiple pathways of transformation. In recent years, the advent of new high-throughput genomic technologies has provided new insights into the biology of DLBCL, leading to the identification of distinct molecular identities and novel pathogenetic pathways. This increasing complexity had led to an expanding number of entities in the World Health Organization classification. Using a multi-modality approach, the updated 2008 classification delineated some new subgroups, including DLBCLs associated with particular age groups or specific anatomic sites, as well as two borderline categories (tumors at the interface between classical Hodgkin lymphoma and DLBCL as well as between Burkitt lymphoma and DLBCL). This article reviews the histopathologic features of the various aggressive B-cell lymphoma subtypes included in the 2008 classification, with emphasis on some of the new entities as well as areas of diagnostic challenge.

Figure 1

DLBCL subtypes. (A) DLBCL, centroblastic variant. The cells have vesicular chromatin and often membrane-bound nucleoli. Polylobated centroblasts may be common, as in this case. (B) DLBCL, immunoblastic variant. The cells are round with prominent central nucleoli. (C) PMBL. The cells have clear cytoplasm and fine compartmentalizing fibrosis. (D) B-UNC/BL/DLBCL is composed of monomorphic medium-sized cells without a starry sky pattern. This case had translocations involving both MYC and BCL2, so-called double hit.

Figure 2

DLBCLs associated with virus infection. (A) Plasmablastic lymphoma involving the oral cavity. There is sheet-like growth of tumor beneath the mucosa. The tumor cells are positive for EBV by EBER in situ hybridization (B). (C) PEL, pleural fluid containing large, atypical cells with a plasmacytoid appearance. The nuclei are strongly positive for the HHV8-associated latent protein, LANA (D).