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Review
. 2018 Jun 21;19(8):38.
doi: 10.1007/s11864-018-0555-8.

Extranodal Diffuse Large B Cell Lymphoma: Molecular Features, Prognosis, and Risk of Central Nervous System Recurrence

Thomas A Ollila  1   2 , Adam J Olszewski  3   4
Affiliations
Review

Extranodal Diffuse Large B Cell Lymphoma: Molecular Features, Prognosis, and Risk of Central Nervous System Recurrence

Thomas A Ollila et al. Curr Treat Options Oncol. .

Abstract

Diffuse large B cell lymphoma (DLBCL) arises from extranodal organs in about 30% of cases. Its prognosis and risk of recurrence in the central nervous system (CNS) vary according to the primary site of origin. Recent studies begin to clarify these differences using molecular classification. Testicular, breast, and uterine DLBCL (as well as possibly primary cutaneous DLBCL, leg-type) share a high prevalence of the non-germinal center B cell (non-GCB) phenotype and the MYD88/CD79B-mutated (MCD) genotype. These biologic features, which resemble primary CNS lymphoma, may underlie their stage-independent propensity for CNS involvement. Management of these lymphomas should involve CNS prophylaxis, preferably using systemic high-dose methotrexate to prevent intraparenchymal recurrence. Involvement of the kidneys, adrenal glands, ovary, bone marrow, lung, or pleura usually indicates disseminated disease, conferring worse prognosis. Involvement of these sites is often associated with high CNS-International Prognostic Index (IPI), concurrent MYC and BCL2 or BCL6 rearrangements, or intravascular lymphoma-risk factors warranting CNS prophylaxis. In contrast, craniofacial, thyroid, localized bone, or gastric lymphomas have a variable prevalence of the non-GCB phenotype and lack MYD88 mutations. Their outcomes with standard immunochemotherapy are excellent, and the risk of CNS recurrence is low. We recommend individualized consideration of CNS prophylaxis based on the CNS-IPI score and anatomical proximity in cases of epidural, orbital, or skull involvement. Rituximab-containing immunochemotherapy is a standard approach for all extranodal DLBCLs. Surgery is no longer required for any primary site, but routine consolidative radiation therapy is recommended for testicular lymphoma. Radiation therapy also appears to be associated with better progression-free survival in primary bone DLBCL. Future studies should better distinguish primary from secondary sites of extranodal involvement, and investigate the association of newly identified genotypes with the risk of CNS or systemic recurrence.

Keywords: Cell of origin; Central nervous system prophylaxis; Diffuse large B cell lymphoma; Extranodal lymphoma; MYD88; Radiation therapy.

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Conflict of interest statement

Conflict of Interest

Thomas A. Ollila and Adam J. Olszewski declare they have no conflict of interest.

Figures

Figure 1.
Figure 1.
Mechanisms associated with variable prognosis and risk of CNS recurrence in extranodal DLBCL of different anatomical origin. ABC: activated B-cell subtype; CNS: central nervous system; DLBCL: diffuse large B-cell lymphoma; GCB: germinal center B-cell subtype; HGBCL: high-grade B-cell lymphoma
See this image and copyright information in PMC

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