What are the subclassifications of DLBCL?

Updated: Jun 12, 2019
  • Author: Shipra Gandhi, MBBS; Chief Editor: Emmanuel C Besa, MD  more...
  • Print
Answer

Under the WHO and/or REAL classification of lymphoid malignancies, the following histological variants are considered clinical and/or pathological distinct subtypes of DLBCL:

  • DLBCL, not otherwise specified

  • T-cell/histiocyte-rich large B-cell lymphoma

  • DLBCL associated with chronic inflammation

  • Epstein-Barr virus (EBV)–positive DLBCL of the elderly

  • Primary mediastinal (thymic) large B-cell lymphoma

  • Intravascular large B-cell lymphoma

  • Primary cutaneous DLBCL, leg type

  • ALK-positive large B-cell lymphoma

  • Plasmablastic lymphoma

  • Primary effusion lymphoma

  • Large B-cell lymphoma arising in human herpes virus type 8–associated multicentric Castleman disease

  • B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and Burkitt lymphoma

Gene expression profiling (GEP) studies provide significant insightful information in the understanding of the DLBCL biology. GEP studies have identified and validated 3 different subtypes of DLBCL, (1) germinal center B-cell (GCB) lymphoma, (1) activated B-cell (ABC) lymphoma, and (3) primary mediastinal lymphoma (PML), each with significant differences in terms of prognosis, PFS, and OS following systemic chemotherapy or, more recently, chemoimmunotherapy. [37, 38, 39]

GCB-DLBCL appears to be derived at the postgerminal state, primarily driven by deregulation of apoptosis by Bcl-6, and has an excellent response to rituximab-based chemoimmunotherapy regimens. ABC-DLBCL is driven by high levels of nuclear factor Kappa-B (NFkB) activity and is associated with a poor outcome, despite chemoimmunotherapy. PML shares GEP signatures similar to those of classic Hodgkin lymphomas (HLs), and, although it has a good prognosis when compared with other DLBCL subtypes, treatment-related toxicities (ie, involved-field radiation) continue to be a significant problem being addressed in clinical trials.

Although GEP studies are the best way to differentiate different subtypes of DLBCL that might be clinically relevant, the use of the GEP studies has not been validated prospectively and widespread use as a routine diagnostic tool is still not practical. Hence, GEP studies are not recommended outside from a clinical trial. Recently, GEP results have been translated into a clinically applicable approaches using immunohistochemistry (IHC). [40, 41, 42]

IHC appears to be an easy and practical method for differentiating DLBCL subgroups. Several attempts to subtype DLBCL cases into GCB and non-GCB have been made, with algorithms using several markers (eg, CD10, Bcl-6, IRF4/MUM1), such as the Hans algorithm and the algorithm proposed by Muris et al. [40, 41, 43] The Hans algorithm reproduces the gene expression-based classification of DLBCL and has a misclassification rate of 20%. [40] Both algorithms have been evaluated as predictors of clinical outcomes in DLBCL patients undergoing front-line therapy with standard chemotherapy or chemoimmunotherapy. [42, 43] On the other hand, the differences in the clinical behavior and therapeutic response of patients with relapsed/refractory GBC and non-GBC DLBCL have been defined in recently completed or ongoing clinical studies. [44, 45, 46]


Did this answer your question?
Additional feedback? (Optional)
Thank you for your feedback!