Imaging Characteristics and Clinical Management of Primary Central Nervous System Lymphoma

Understanding Primary CNS Lymphoma: A Radiological Perspective

Primary central nervous system (CNS) lymphoma is a rare but aggressive form of extranodal non-Hodgkin's lymphoma that originates within the brain, spinal cord, or leptomeninges. Unlike systemic lymphomas, this variant remains confined to the CNS without evidence of systemic involvement at diagnosis. Neuroimaging plays a pivotal role in identifying suspicious lesions, although its presentation can be highly variable and often mimics other intracranial pathologies.

Typical Imaging Features on MRI and CT Scans

On magnetic resonance imaging (MRI), CNS lymphomas most commonly appear as single or multiple hypercellular masses located near the brain's midline structures, such as the corpus callosum, periventricular regions, or basal ganglia. These lesions typically exhibit poorly defined margins and are isointense to hypointense on T1-weighted images, while appearing isointense to hyperintense on T2-weighted sequences. One distinguishing characteristic is their relatively homogeneous contrast enhancement, which may be moderate rather than intensely bright—setting them apart from more vascular tumors like glioblastoma multiforme.

Another key radiological clue is the tendency of lymphomatous lesions to surround blood vessels (perivascular distribution) and infiltrate across commissural fibers, leading to a "butterfly" pattern when crossing the corpus callosum. Additionally, due to their high cellular density, these tumors often demonstrate restricted diffusion on DWI (diffusion-weighted imaging), appearing bright on ADC maps—a feature useful in differential diagnosis.

Differentiating From Other Brain Tumors

While glioblastomas typically show irregular ring enhancement with central necrosis and significant surrounding edema, primary CNS lymphomas usually lack central necrosis and present with more uniform enhancement. This distinction, combined with clinical context—such as patient age (most cases occur in individuals over 50 or immunocompromised patients)—helps guide radiologists and neuro-oncologists toward a more accurate preoperative diagnosis.

However, imaging alone cannot confirm the diagnosis. Metastases, toxoplasmosis (especially in HIV-positive patients), and tumefactive demyelinating lesions can all mimic lymphoma radiologically. Therefore, definitive diagnosis requires histopathological evaluation.

The Critical Role of Stereotactic Biopsy

Once imaging suggests CNS lymphoma, a stereotactic biopsy is essential for tissue confirmation. This minimally invasive procedure allows precise sampling of deep-seated or multifocal lesions while minimizing surgical risk. Given that complete surgical resection is generally not curative—and may even delay appropriate treatment—biopsy remains the gold standard.

Pathology typically reveals diffuse large B-cell lymphoma (DLBCL), the most common subtype. Immunohistochemical markers such as CD20 and CD79a help confirm B-cell lineage, guiding subsequent targeted therapies.

Treatment Strategies and Prognosis

Following diagnosis, the cornerstone of management involves combined modality therapy, primarily high-dose methotrexate-based chemotherapy and radiotherapy. Recent advances have emphasized dose-adjusted regimens to reduce neurotoxicity, especially in older adults. In select cases, autologous stem cell transplantation may be considered for consolidation in younger, fit patients.

Early diagnosis significantly improves outcomes. With timely intervention, many patients achieve durable remissions and extended survival—median overall survival now ranges between 3 to 5 years, with some living much longer. Moreover, quality of life can be preserved through careful symptom management, corticosteroid use, and supportive care.

Conclusion: A Multidisciplinary Approach Is Key

Recognizing the unique imaging patterns of CNS lymphoma enables faster referrals and earlier biopsies. Collaboration among neuroradiologists, neurologists, oncologists, and neurosurgeons ensures optimal patient pathways. As research continues into novel agents like immune checkpoint inhibitors and CAR-T cell therapy, the future holds promise for even better control of this challenging disease.