Primary extranodal diffuse large B-cell lymphoma: Molecular features, treatment, and prognosis

Abstract

Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin's lymphoma and represents a heterogeneous entity. One-third of DLBCL arises from extranodal organs and its prognosis often varies with regard to the sites involved. Molecular features are important to elucidate the differences in clinical features, predict the disease prognosis, and improve effective targeted therapeutic strategies. Extranodal DLBCLs originated from the breast, skin, uterus, immune-privileged sites such as the central nervous system and testes, often show a high proportion of non-germinal center B-cell-like (non-GCB) phenotypes, with a high frequency of MYD88/CD79B mutations. In contrast, extranodal DLBCLs originated from the thyroid gland and stomach show a relatively low proportion of non-GCB phenotype, with a considerably excellent prognosis. Immunochemotherapy with rituximab is the standard of care in both nodal and extranodal DLBCLs. However, approximately 40% of the patients experience treatment failure. It is critical to optimize the treatment strategy, including radiotherapy, autologous stem cell transplantation and targeted therapy according to the clinical characteristics and molecular heterogeneity. In this review, we present an overview of the key molecular pathways, prognosis assessment and innovative therapies in primary extranodal DLBCLs.