Heterogeneity among diffuse large B-cell lymphoma: new entities in WHO classification, a first step in personalized therapy

Abstract

Diffuse large B-cell lymphoma (DLBCL) is the most common type of aggressive lymphoma, being part of mature B-cell neoplasm according to the 2016 World Health Organization (WHO) Classification of lymphoid tumors. This type of non-Hodgkin's lymphoma (NHL) can develop in the lymph nodes in most cases, or in extranodal sites (the most frequent involvement being the digestive tract, but also the thyroid, central nervous system, testes, etc.). Despite being an aggressive lymphoma, DLBCL benefits of potentially curable therapy. The addition of monoclonal antibodies to standard chemotherapy in the therapeutic approach of DLBCL leads to some net superior results to those obtained by chemotherapy alone. Despite the fact that the aggressive therapy is very efficient, 10% of patients remain refractory to it, 30-40% of them after obtaining a complete response (CR) will relapse, and 90% of refractory DLBCL have poor survival rates. Based on these findings, an explanation for the differences in clinical outcome and therapy response was attempted. The important progresses made in the understanding of DLBCL heterogeneity were based on molecular biology studies and showed differences in chromosomal alterations and in signaling pathways activation. These findings have paved the way for new therapeutic targets in order to improve therapy response. The large heterogeneity of DLBCL is acknowledged by the 2016 WHO Classification of lymphoid neoplasms, with 17 DLBCL subtypes, some of them as new varieties, compared to the 2008 Classification, and others introduced as provisional entities.