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Primary lymphoid organs are pivotal in the formation, development, and maturation of lymphocytes, the white blood cells that serve as the backbone of our immune system. This crucial function underscores their fundamental role in maintaining our overall health and immunity. The two primary lymphoid organs of prime importance are the red bone marrow and the thymus.
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    Area of Science:

    • Neuro-oncology
    • Hematology
    • Immunology

    Background:

    • Primary central nervous system (CNS) lymphoma is an aggressive extranodal non-Hodgkin lymphoma.
    • It is confined to the brain, eyes, cerebrospinal fluid (CSF), or spinal cord without systemic involvement.

    Purpose of the Study:

    • Review clinical presentation, imaging, diagnosis, pathophysiology, and treatment of primary CNS lymphoma in immunocompetent patients.
    • Highlight recent advancements and novel therapeutic strategies.

    Main Methods:

    • Literature review of clinical presentation, diagnostic workup, and treatment strategies.
    • Discussion of novel pathophysiologic insights and emerging targeted therapies.

    Main Results:

    • High-dose methotrexate is the backbone of first-line chemotherapy, improving prognosis but achieving durable remission in only ~50% of patients.
    • Pathophysiologic insights reveal the importance of the B-cell receptor pathway, tumor immune microenvironment, and immune evasion.
    • Novel agents targeting these pathways, like BTK inhibitors and immunomodulatory drugs, show promise in relapsed/refractory settings.

    Conclusions:

    • Diagnosis requires high suspicion due to variable clinical signs.
    • Methotrexate-based chemotherapy is standard for induction, but optimal regimens are undefined.
    • Novel targeted agents are increasingly incorporated into the therapeutic arsenal for primary CNS lymphoma.