Molecular profiling of primary central nervous system lymphomas - predictive and prognostic value?

PURPOSE OF REVIEW

Primary central nervous system lymphoma (PCNSL) is a rare but aggressive variant of non-Hodgkin lymphoma. The diagnostic gold standard remains the pathologic review of tumor tissue mainly collected though biopsies. The majority of PCNSL are diffuse large B cell lymphoma (DLBCL). Biopsies are invasive procedures, and there have been efforts to develop minimally invasive diagnostic testing using serum and cerebral spinal fluid. This article reviews multiple markers that could potentially serve as future diagnostic tools and predictors of treatment response.

RECENT FINDINGS

Many studies have attempted to classify DLBCL into different subtypes for prognostic purposes using methods such as immunohistochemistry. PCNSL often falls under the activated B-cell-like subgroup, and further genomic sequencing has identified alterations in genes within the B-cell receptor signaling axis at increased frequencies. Two such genes, MYD88 and CD79B, implicate the involvement of the NF-kB (nuclear factor kappa-light-chain enhancer of activated B cells) pathway, and targeted agents to this pathway are currently being used in the treatment of relapsed/refractory PCNSL.

SUMMARY

Although recent genomic profiling of PCNSL has increased the understanding of drivers in this disease and has also led to the introduction of targeted inhibitors, these markers have not yet been used for diagnostic and/or prognostic purposes. Further studies will need to evaluate if they hold great diagnostic potential.