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 extran...

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Bibliographic Details
Published in:Blood reviews 2018-05, Vol.32 (3), p.249-255
Main Authors: Twa, David D.W., Mottok, Anja, Savage, Kerry J., Steidl, Christian
Format: Article
Language:English
Subjects:
Apoptosis - genetics
Biomarkers
CD274
CIITA
Gene Expression Profiling
Humans
Immune-escape
Immunophenotyping
Lymphoma, Large B-Cell, Diffuse - diagnosis
Lymphoma, Large B-Cell, Diffuse - etiology
Lymphoma, Large B-Cell, Diffuse - metabolism
Lymphoma, Large B-Cell, Diffuse - therapy
Male
Mutation
NF-kappa B - metabolism
NF-κB
PDCD1LG2
Primary testicular diffuse large B-cell lymphoma (PT-DLBCL)
Programmed death ligands
Signal Transduction
Testicular Neoplasms - diagnosis
Testicular Neoplasms - etiology
Testicular Neoplasms - metabolism
Testicular Neoplasms - therapy
Tumor Escape - immunology
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Summary: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.
ISSN:0268-960X
1532-1681
DOI:10.1016/j.blre.2017.12.001