Non-GCB Diffuse Large B-Cell Lymphoma With an Atypical Disease Course: A Case Report and Clinical Exome Analysis

Svetlana Tsygankova, Daria Komova, Eugenia Boulygina, Natalia Slobodova, Fedor Sharko, Sergey Rastorguev, Maria Gladysheva-Azgari, Daria Koroleva, Anna Smol’yaninova, Svetlana Tatarnikova, Tatiana Obuchova, Artem Nedoluzhko, Nelli Gabeeva, Eugene Zvonkov


Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoid tumor among other non-Hodgkin lymphomas (30-40% of all cases). This type of lymphoma is characterized by significant differences in treatment response and the heterogeneity of clinical traits. Approximately 60% of patients are cured using standard chemotherapy (CT), while in 10-15% of cases, the tumor is characterized by an extremely aggressive course and resistance to even the most high-dose programs with autologous stem cell transplantation (auto-SCT). The activated B-cell (ABC) subtype of DLBCL is characterized by poor prognosis. Here, we describe a clinical case of diffuse ABC-DLBCL with an atypical disease course. Complete remission was achieved after four courses of CT, followed by autologous hematopoietic stem cell transplantation (auto-HSCT). However, early relapse occurred 2 months after the completion of treatment. According to the results of cytogenetic studies, significant chromosome breakdowns were observed. Exome sequencing allowed for the detection of several novel mutations that affect components of the NOTCH2 and NF-kB signaling pathways, a number of epigenetic regulators (KMT2D, CREBBP, EP300, ARID1A, MEF2B), as well as members of the immunoglobulin superfamily (CD58 and CD70). Whether these mutations were the result of therapy or were originally present in the lymphoid tumor remains unclear. Nevertheless, the introduction of genomic technologies into clinical practice is important for making a diagnosis and developing a DLBCL treatment regimen with the use of targeted drugs.

World J Oncol. 2022;13(1):38-47


Lymphoma; Diffuse large B-cell lymphoma; ABC type; Exome; Sequencing; NOTCH2 pathway; NF-kB pathway; R-mNHL-BFM-90 protocol

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