Rare Presentation of Double Expressor Diffuse Large B-Cell Lymphoma with Early CNS Involvement: Successful Multidisciplinary Management

Introduction/Background/Significance: Diffuse large B-cell lymphoma (DLBCL) is the most common aggressive form of non-Hodgkin lymphoma. A subset known as double-expressor lymphoma (DEL), characterized by overexpression of MYC and BCL2 proteins, carries a worse prognosis than typical DLBCL. Although central nervous system (CNS) involvement at initial diagnosis is uncommon—reported in roughly 3 to 5 percent of cases—it is associated with particularly poor outcomes and complex management challenges. There is a significant gap in evidence guiding optimal treatment for patients presenting with DEL and early CNS disease, highlighting the need for increased clinical awareness and tailored therapeutic strategies.

Materials and Methods/Case Presentation/Objective: A 62-year-old man presented with rapidly enlarging cervical lymphadenopathy, fevers, night sweats, and new neurological symptoms including headaches and unilateral weakness. Imaging studies revealed bulky lymph node masses and brain lesions suspicious for lymphoma involvement. A biopsy of a cervical lymph node confirmed diffuse large B-cell lymphoma with MYC and BCL2 overexpression, consistent with the double-expressor subtype. Cerebrospinal fluid (CSF) analysis revealed malignant lymphoma cells, confirming CNS involvement.

Given the aggressive disease presentation, a multidisciplinary team including hematologists, neuro-oncologists, pathologists, and radiologists collaborated to design an integrated treatment plan. The patient was started on a modified R-CHOP chemotherapy regimen to address systemic disease, combined with CNS-directed therapy involving high-dose methotrexate and intrathecal cytarabine. The primary objective was to achieve comprehensive disease control in both systemic and CNS compartments, while minimizing treatment-related toxicity.

Results/Description/Main Outcome Measures: The patient tolerated six cycles of combined systemic and CNS-directed chemotherapy well, with manageable side effects. Follow-up PET-CT and brain MRI demonstrated complete remission, with no residual disease detected in lymph nodes or CNS lesions. Neurological symptoms resolved fully. The patient remained in clinical and radiographic remission at twelve months following completion of therapy.

Conclusions: Early CNS involvement in double-expressor lymphoma, though rare, indicates an aggressive disease course requiring prompt recognition and specialized treatment. This case highlights the importance of integrating CNS-directed therapy with systemic chemotherapy, facilitated by a multidisciplinary approach, to achieve durable remission and neurological recovery. Clinicians managing patients with DEL should maintain a high index of suspicion for CNS disease, particularly when neurological symptoms are present, to enable early diagnosis and improve patient outcomes.