Neurosurg Focus
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White matter diseases, including demyelinating or inflammatory disorders, may be indistinguishable clinically and radiologically from some central nervous system (CNS) tumors. In such situations, determination of the final diagnosis is difficult. An example is the differential diagnosis of non-acquired immunodeficiency syndrome-related primary central nervous system lymphoma (PCNSL) and multiple sclerosis (MS), a demyelinating disease. Unfortunately, delayed diagnosis and treatment of PCNSL can negatively affect prognosis. ⋯ In PCNSL, early definitive diagnosis and treatment are the keys to successful outcomes. Knowledge of strategies essential to early diagnosis lessens the need for brain biopsy sampling, but this procedure is still usually necessary. In such selected cases, biopsy sampling is appropriate even when pathological investigation shows MS rather than PCNSL. Complete resection is not indicated in PCNSL and can lead to additional sequelae.