Diffuse Large B-Cell Lymphoma (DLBCL)


Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma (NHL), comprising approximately 35% to 40% of all cases of NHL.1 Patients usually present clinically with rapidly enlarging lymph nodes or extranodal tumor masses. These extranodal sites, which are affected in approximately 40% of cases, commonly include the gastrointestinal tract, skin, central nervous system, mediastinum, and bones, although any organ may be affected. Involvement of the liver and bone marrow is less common than in small lymphocytic lymphoma or follicular lymphoma.2 

Histological Features

On gross examination, a biopsy of affected lymph nodes or other tissues exhibits a fleshy and soft cut surface, with effacement of the normal architecture.2 DLBCL is described as a tumor of large B cells distributed in a diffuse pattern on histological sections. The morphology of the cells and nuclei varies from case to case. Typically, the malignant lymphoid cells are large, and their nuclei are bigger than those of reactive histiocytes on microscopic examination of paraffin sections. The size of a large cell is said typically to be double that of a reactive lymphocyte.3,4 

In actuality, lymphocytes are not all the same size, and large cells are extremely pleomorphic; thus, one needs to be flexible when reporting. Neoplastic cells can occasionally also be of medium size. Single or multiple conspicuous nucleoli are noted. Bizarre-looking cells or multinucleated cell forms that resemble Reed Sternberg cells may be present.3,4 

The amount and staining characteristics of the cytoplasm differ. A diffuse infiltration of malignant lymphoid cells typically replaces the normal tissue architecture. On rare occasions, a dispersed growth pattern is observed in which the malignant cells are closely entangled with the components of normal tissue. Soft tissue outside the lymph node also frequently becomes infiltrated. Biopsy tissue frequently displays permeative growth at the margins and invasion of blood vessel walls in extranodal sites.3,4

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Histological Variants

The World Health Organization classification identifies 3 main histological variants based on morphology: centroblastic, immunoblastic, and anaplastic. In the centroblastic variant (80% of cases), there is diffuse infiltration of medium-sized to large neoplastic cells with a centroblastic appearance. Centroblasts have: round, angular, or multilobed vesicular nuclei; multiple small peripheral nucleoli; and indistinct amphophilic cytoplasm. The immunoblastic variant (8%-10% of cases) has more than 90% immunoblasts, which have round or oval vesicular nuclei, a single prominent central nucleolus, and abundant basophilic cytoplasm. In the anaplastic variant, which is rare (3% of cases), the neoplastic cells are very large with a  bizarre appearance and display marked pleomorphism.2,4,5 

In addition, numerous mitotic figures, including atypical forms, can be readily identified in biopsy sections. Areas of necrosis are also discernible. A number of additional uncommon variants have been identified, some of which have recently emerged as distinct subtypes. The enormous variations in cytological and histological features further support that DLBCL actually comprises many distinct yet partially indistinguishable entities.2,4,5 

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Immunophenotyping and Molecular Genetics

On immunophenotyping, in addition to pan B-cell markers including CD20, CD22, CD79a, and PAX-5, DLBCL expresses CD45. Surface or cytoplasmic monotypic immunoglobulin may or may not be present. CD10 (40% of patients), BCL6 (60%), BCL2 (50%), and CD5 (10%) are also present. Post-germinal center or plasma cell-associated markers such as CD38, VS38, and MUM1 are present in only a small percentage of cases. The Ki-67 labeling index is substantial. Occasionally, CD30 is expressed. Pan T-cell markers are absent.2 

Molecular genetic studies show rearrangements in immunoglobulin heavy- and light-chain genes. Hypermutation occurs in the immunoglobulin heavy-chain variable region gene. BCL6 and BCL2 gene rearrangements are observed in 30% and 20% of cases, respectively. MYC (8q24) translocation is observed in approximately 10% of cases, with fusion to a non-immunoglobulin gene, in contrast to Burkitt lymphoma.2 

The updated 2016 classification of DLBCL includes modifications for the diagnosis of this disease. It has been suggested that the classification based on cell of origin, such as germinal center B-cell (GCB) type vs activated B-cell (ABC) or non-GCB type, be included in the pathology report. Immunohistochemical expression of MYC and BCL2 has been identified as a poor prognostic indicator.3 Morphological variants of DLBCL also have specific molecular characteristics. The centroblastic variant is more frequently detected in the GCB subtype of DLBCL, whereas the immunoblastic variant is more frequently identified in the ABC subtype. Furthermore, it has been discovered that immunoblastic lymphomas usually include MYC translocations, which are associated with a poor prognosis.5 

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References

  1. Sweetenham J, Wotherspoon A, Rosenwald A, Ott G. (2007). Diffuse large B-cell lymphoma. In: Marcus R, Sweetenham J, Williams M, eds. Lymphoma: Pathology, Diagnosis and Treatment. Cambridge University Press; 2007:168-181. doi:10.1017/CBO9780511663369.013
  2. Ramnani DM. Diffuse large B-cell lymphoma. WebPathology. April 2021. Accessed August 14, 2022.
  3. Sethi A, Tandon A, Mishra H, Singh I. Diffuse large B-cell lymphoma: an immunohistochemical approach to diagnosis. J Oral Maxillofac Pathol. 2019;23(2):284-288. doi:10.4103/jomfp.JOMFP_294_18
  4. Gatter K, Pezzella F. Diffuse large B-cell lymphoma. Diagnostic Histopathology. 2010;16(2):69-81. doi:10.1016/j.mpdhp.2009.12.002 
  5. Onaindia A, Santiago-Quispe N, Iglesias-Martinez E, Romero-Abrio C. Molecular update and evolving classification of large B-cell lymphoma. Cancers (Basel). 2021;13(13):3352. doi:10.3390/cancers13133352

Reviewed by Hasan Avcu, MD, on 8/24/2022.

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