Online Articles: Case ReportClonal Evolution in Primary Diffuse Large B-Cell Lymphoma of the Central Nervous SystemGarcia-Reyero, Julia MD*,†; Martinez Magunacelaya, Nerea PhD†; Gonzalez Pereña, Ainara MLT†; Marcos Gonzalez, Sara MD*; Teran-Villagra, Nuria MD, PhD*; Azueta, Ainara MD, PhD*; Batlle, Ana MD, PhD‡; Gonzalez de Villambrosia, Sonia MD‡; Revert Arce, Jose MLT§; Montes-Moreno, Santiago MD, PhD*,†,§Author Information *Pathology Department ‡Hematology Department, Cytogenetics Unit, Marques de Valdecilla University Hospital †Translational Hematopathology Lab, IDIVAL, CIBERONC §Valdecilla Tissue Bank, Santander, Spain J.G.-R. and N.M.M. contributed equally. J.G.-R., N.M.M., A.G.P., S.M.G., and J.R.A.: performed research. N.T.-V.: provided clinical data. A.A., A.B., and S.G.d.V.: provided clinical data. S.M.-M.: designed research, performed research and wrote the manuscript. Supported by grants from MINECO (PI16/1397) and IDIVAL (NEXTVAL 15/09). N.M.M. was supported by Asociación Española contra el Cancer (AECC). The study was approved by the local ethics committee (CEIC Cantabria). The authors declare no conflict of interest. Reprints: Santiago Montes-Moreno, MD, PhD, Translational Hematopathology Lab, Pathology Department, HUMV-IDIVAL, Avda. de Valdecilla s-n, Santander 39010, Spain (e-mail: firstname.lastname@example.org). Applied Immunohistochemistry & Molecular Morphology: September 2020 - Volume 28 - Issue 8 - p e68-e71 doi: 10.1097/PAI.0000000000000655 Buy SDC Metrics Abstract Primary diffuse large B-cell lymphoma (DLBCL) of the central nervous system (CNS) is an aggressive subtype of DLBCL with characteristic clinicopathologic features. Relapse outside the CNS involving extranodal locations has been found in a fraction of cases (16%). Here we describe a case of DLBCL arising in the CNS that relapsed 18 months after the initial diagnosis in the testis and bilateral adrenal glands. Both tumors showed equivalent morphology, phenotype, cytogenetic features, and clonal relationship. Somatic mutation analysis by next generation sequencing demonstrated MYD88L265P mutation in both tumors and de novo CD79B Y196S mutation exclusive to the relapse. The pattern of mutations suggest that the 2 tumors might have evolved from a common progenitor clone with MYD88L265P being the founder mutation. A meta-analysis of the literature shows a significantly high frequency of concurrent MYD88L265P and CD79B ITAM mutations in primary CNS lymphoma and testicular DLBCL, underscoring the role of B cell receptor and nuclear factor kB activation by somatic mutations in these lymphomas that colonize immune-privileged sites. In summary, here we illustrate that targeted next generation sequencing for the detection of hot spot somatic mutations in relapsed DLBCL is useful to confirm ABC phenotype and discovers relevant information that might influence therapeutic decision. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.