SUMMARY: Lymphomas of the CNS are the second most frequent primary brain malignancy in adults after gliomas. Presurgical suspicion of lymphoma greatly impacts patient management. The radiologic features of this tumor have been widely covered in the literature for decades, but under current classifications, mainly corresponding to the most common presentations of the most frequent type: primary diffuse large B-cell lymphoma of the CNS. Nevertheless, rarer presentations of this specific lymphoma and of other World Health Organization lymphoma subtypes with different imaging features are rarely treated. Moreover, important advances in imaging techniques, changing epidemiologic factors with relevant impact on these tumors (eg, immunodeficiency/dysregulation), and recent updates of the World Health Organization Classification of CNS Tumors 2021 and Hematolymphoid Tumors 2022 may have rendered some accepted concepts outdated. In this article, the authors aim to fulfill a critical need by providing a complete update-review, emphasizing the latest clinical-radiologic features of the full spectrum of lymphomas involving the CNS.

Primary central nervous system lymphomas may present as diffuse, nonenhancing infiltrative lesions. This rare variant is termed lymphomatosis cerebri (LC). We did a systematic review and analysis of the literature, adding our own cases, to better characterize LC in order to improve early diagnosis and treatment. PubMed, ISI Web of Knowledge, and hospital databases were reviewed. Information was extracted regarding demographic, clinical, histological, cerebrospinal fluid (CSF), neuroimaging, and treatment variables. The impact of single parameters on overall survival (OS) was determined by applying univariate and multivariate analyses. Forty-two patients were included (median age: 58 y; range: 28–80 y). At consultation, 52% of patients had a poor KPS. The most common presenting symptom was cognitive decline (59.5%). Imaging studies showed supratentorial and infratentorial infiltration in 55% of patients and bilateral hemispheric involvement in 95%. CSF pleocytosis was present in 51.5% of the patients. Median time to diagnosis was 4.5 (range: 1–30) months, and the diagnosis was not established until autopsy for 33% of patients. The median OS was 2.95 (range: 0.33–56) months; however, those patients who received methotrexate had a median OS of 13.8 (range: 0.7–56) months. Analysis identified KPS ≥ 70 (HR: 0.32; 95% CI: 0.114–0.894; P = .03) and treatment with methotrexate (HR: 0.19; 95% CI: 0.041–0.886; P = .034) as independent favorable prognostic factors, whereas T-cell lymphoma was independently related with a worse outcome (HR: 6.62; 95% CI: 1.317–33.316; P = .022). LC is a misdiagnosed entity associated with considerable diagnostic delay. MRI evidence of bilateral hemispheric involvement and CSF pleocytosis should be alerts for this diagnosis. Treatment with methotrexate-based chemotherapy must be considered, especially for patients with good KPS.