These lymphomas, termed high-grade B-cell lymphoma with MYC, BL2, and/or BL6 rearrangements or, more simply, DH/THL, are regarded as borderline DLBCL,NOS. They represent 6–14% of all DLBCL, NOS and have had long-term survival rates of only 20–25%. Another variant B-cell lymphoma that is also considered to be a borderline DLBCL, NOS is termed high-grade B-cell lymphoma, not otherwise specified (HGBCL, NOS). These two aggressive borderline B-cell lymphomas were previously grouped together as "B-cell lymphoma, unclassifiable with features intermediate between DLBCL and Burkitt lymphoma" (i.e. BCLU) but were separated into DH/THL and HGBC, NOS by the World Health Organization, 2016. The neoplastic cells in a related variant, double expresser lymphoma (i.e. DEL), express the products of MYC and BCL2 genes, i.e. c-Myc and bcl-2 proteins, respectively, but do not have translocations in either of their genes. DEL, which represents about one-third of all DLBCL, NOS cases, has a poorer prognosis than standard DLBCL, NOS but not as poor as DH/THL cases. Cases in which the neoplastic cells have alterations in the MYC gene or its expression without changes in BLC2 or BLC6 also have a poor prognosis, particularly in cases where the MYC gene translocates (i.e. rearranges) with one of the immunoglobulin gene loci. DLBCL that begin in the testicles are a variant of DLBCL, NOS that some authors suggest should be classified as a distinct DLBCL subtype. This variant, termed Primary testicular diffuse large B-cell lymphoma (PT-DLBCL), is a DLBCL, NOS that in >75% of cases involves activated B-cells, i.e. ABC.
Subtypes of diffuse large B-cell lymphoma
DLBCL subtypes have been sorted into groups based on their distinctive morphology or immunophenotype, distinctive clinical issues, and distinctive virus-driven etiology. The prognoses and treatment of these subtypes varies with their severity. Most subtypes are aggressive diseases and consequently treated in a manner similar to DLBCL,NOS. Further details on these subtypes, including their treatments, can be found in their respective main article linkages. DLBCL with a distinctive morphology or immunophenotype
T cell/histiocyte-rich large B-cell lymphoma
T-cell/histiocyte-rich large B-cell lymphoma (THRLBCL) is a DLBCL in which tumors containing small numbers of usually large neoplastic B-cells embedded in a background of reactive T-cells and histiocytes develop in the liver, spleen, bone marrow and/or, rarely other sites. Patients usually present with advanced disease; their overall 3 year survival rates in different studies range between 46% and 72%. ALK+ large B-cell lymphoma
ALK+ large B-cell lymphoma (ALK+ LBCL) is a DLBCL in which neoplastic lymphocytes that express the ALK tyrosine kinase receptor protein infiltrate lymph nodes as well as extranodal sites, e.g. the mediastinum, bones, bone marrow, nasopharynx, tongue, stomach, liver, spleen, and skin. About 60% of these individuals present with advanced disease. ALK+ LBCL has an overall 5 year survival rate of ~34%. Plasmablastic lymphoma
Plasmablastic lymphoma (PBL) is a DLBCL in which neoplastic immunoblastic or plasmablastic cells embedded in a background of other cell types infiltrate the oral/nasal cavity or much less often the gastrointestinal tract. Some 70% of individuals with PBL are infected with EBV and/or (particularly those with oral/nasal cavity disease) human immunodeficiency virus (HIV).