To present three cases of T cell lymphoma which were difficult to differentiate from inflammatory and demyelinating etiologies. 

Three patients with primary T-cell CNS lymphoma were identified within the Duke University Hospital system from March 2019 through March 2023. Their clinical information and MRI brain reports and images were personally reviewed. 

All three patients were male with median age of 38 (range 30-41). None were immunocompromised. Mortality occurred in 67% (2/3). One patient had a single supratentorial hemispheric lesion. One patient had both a supratentorial and infratentorial lesion. One patient had a right basal ganglia lesion that spread to the contralateral side. All three patients had prominent SWI changes on MRI brain, with multiple areas of microhemorrhages throughout. Contrast enhancement was heterogenous and lacked prominent restricted diffusion. All patients had worsening despite treatment including steroids, rituximab, cyclophosphamide. All three patients had two or more brain biopsies interpreted as nonspecific reactive changes with differential including lymphoma, infectious, inflammatory and demyelinating etiologies. T cell receptor gamma gene rearrangement showed positive monoclonal populations. Yet, these were interpreted as likely reactive and nonspecific. 

With these rare and difficult cases, clues to diagnosis may be found in more atypical MRI findings such as SWI changes, patterns of enhancement, and progressive nature of lesions despite immunosuppression. Additionally, if biopsy or CSF flow cytometry shows evidence of T cells, TRG should be pursued for further clues into diagnosis.