Distinction between tumefactive MS and sentinel lesion of PCNSL poses a diagnostic conundrum, as exemplified in this report of a 46-year-old man who presented with partial complex seizures, prompting a right temporal resection. Multiple cerebral lesions were detected by MRI 41/2 years later, necessitating a biopsy, after which he developed a brainstem syndrome. Over the 3 years thereafter, three severe relapses occurred referable to transient lesions in the cerebrum (one lesion biopsied), brainstem, and cerebellum. Presumptive diagnosis was tumefactive MS with control by combination of immunosuppressive/modulatory therapies. Emergence of an enlarging left cerebellar mass precipitated death.

Different facets of an inflammatory demyelinative process were demonstrated in the resection specimen and biopsies. Autopsy, however, disclosed a diffuse large B-cell lymphoma in the cerebellum with widespread dissemination throughout the brain. In the background were multifocal gliotic regions of myelin/axonal loss with intermixed infiltrates of T-cells and microglia/macrophages. The biopsy sites and resection cavity showed similar findings. Overlapping features between these chronic lesions and that in the surgical specimens suggest a shared pathogenesis, supporting a concept that the sentinel lesion represents a reaction to an emerging PCNSL, either immune mediated or resorptive due to spontaneous or induced regression. Moreover, as demonstrated, PCNSL should remain a persistent consideration in the differential diagnosis, even though clinical, imaging, and pathology indices may fail in resolution between tumefactive MS, sentinel lesion, or overt PCNSL.