The pathobiology of primary testicular diffuse large B-cell lymphoma: Implications for novel therapies

Primary testicular lymphomas (PTL) are the most prevalent type of testicular cancer arising in men over the age of 60. PTL accounts for approximately 1-2% of all non-Hodgkin lymphomas and most present with localized disease but despite this, outcome is poor. The majority of cases represent an extranodal manifestation of diffuse large B-cell lymphoma (DLBCL), known as primary testicular DLBCL (PT-DLBCL). Gene expression profiling has established that over 75% of PT-DLBCLs resemble the activated B-cell-like (ABC) or non-germinal center subtype of nodal DLBCL. In distilling the specific mutational landscape and immunophenotypic profiles, immune-escape and sustained signalling emerge as prominent features of PT-DLBCL. These include genomic alterations arising within the core components of antigen presentation (CIITA, B2M, and HLA loci) and structural rearrangements of programmed death ligands 1 (CD274) and 2 (PDCD1LG2). Enrichment for somatic mutations within NF-κB pathway genes (MYD88, CD79B, NFKBIZ, BCL10, and MALT1) also feature prominently in PT-DLBCL. Taken together, the unique molecular and clinical characteristics of PT-DLBCL have informed on aspects of the distinct disease biology of this organotypic lymphoma that may guide rational therapeutic strategies.

Blood reviews. 2017 Dec 20 [Epub ahead of print]

David D W Twa, Anja Mottok, Kerry J Savage, Christian Steidl

Department of Lymphoid Cancer Research, BC Cancer Agency, Vancouver, BC, Canada; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada., Department of Lymphoid Cancer Research, BC Cancer Agency, Vancouver, BC, Canada., Department of Lymphoid Cancer Research, BC Cancer Agency, Vancouver, BC, Canada; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada. Electronic address: .