Rare Cases of Primary Central Nervous System Anaplastic Variant of Diffuse Large B-cell Lymphoma

Background: Primary central nervous system (CNS) diffuse large B-cell lymphoma (DLBCL) is a rare intracranial tumor, defined as DLBCL arising from the brain, spinal cord, leptomeninges and eye, with an overall annual incidence of 5 cases per million. The primary CNS anaplastic variant of DLBCL (A-DLBCL) is even less common; to our knowledge, there are only two other case reports in the literature. The aim of this report is to present rare cases of primary CNS A-DLBCL and study their clinicopathologic and genetic features.

Case Presentation: We report 3 patients, two men and one woman, aged 54, 55 and 67 years old, with primary CNS A-DLBCL. All 3 patients had a high International Extranodal Lymphoma Study Group (IELSG) score; although the patients were treated with methotrexate-based regimens and/or with radiation therapy, the overall survival was only 2, 5, and 8 months. All 3 patients presented with characteristic features of perivascular space infiltration with bizarre-shaped tumor cells, leading to the diagnosis of primary CNS A-DLBCL. Concurrent of MYC and BCL2 and/or BCL6 abnormalities and MYC/BCL2 double-expressor DLBCL occurred in all 3 patients; two patients had MYC/BCL2/BCL6 triple extra copies, and one patient had MYC extra copy and BCL6 translocation. All 3 patients displayed mutations in MYD88 L265P and nuclear positivity for RELA, RELB and/or c-Rel, indicating constitutive activation of the NF-κB pathway.

Conclusions: These cases shed light on the unique genetic alterations and biological features of primary CNS A-DLBCL. Patients with primary CNS A-DLBCL may often have a MYC/BCL2 double-expressor and concurrent MYC and BCL2 and/or BCL6 genetic abnormalities, as well as constitutive activation of the NF-κB pathway. Primary CNS A-DLBCL follows a very aggressive disease course and poor prognosis. In the future, a large number of cases should be analyzed, and the evaluation of molecular genetic characteristics could help with practical and therapeutic implications for primary CNS A-DLBCL.