Diffuse large B‑cell lymphoma of the CNS (CNS-DLBCL) is a rare tumor that accounts for 1–3% of primary CNS tumors but is the most common tumor type encountered among primary CNS lymphomas [
17,
18]. They typically occur in the cerebral hemispheres (38%) and are less frequent in the thalamus, basal ganglia or cerebellum [
19]. For CNS-DLBCL, neither etiological nor genetic predispositions have been described [
2]. Macroscopically, CNS-DLBCLs are quite firm and granular, and often exhibit central necrosis [
2] as observed in the present case. In general, lymphomas are characterized by nutrient deprivation and hypoxia ultimately leading to tumor necrosis [
20]. Interestingly, the presence of necrosis in CT or FDG-PET can serve as a prognostic marker. Patients with tumor necrosis have a significantly worse outcome than those without tumor necrosis [
21,
22]. Histologically, tumor cells conform to mature B cells (late germinal center exit), and thus they express typical mature B cell markers such as CD20, CD19, PAX5, or CD79a. In the presented case CD10 expression of the DLBCL was negative arguing against a systemic DLBCL manifestation. CNS-DLBCLs have a significantly worse outcome than systemic DLBCL [
23]. The mechanism behind the poor prognosis of CNS-DLBCL is not fully understood. CNS-DLBCLs appear to co-express BCL2, BCL6, and/or MYC at higher frequencies than systemic DLBCL [
24]. This co-expression is an established prognostic risk factor [
25,
26] and, thus, could point towards potential mechanisms underlying the adverse prognosis of CNS-DLCBL; however, in this case we only found overexpression of BCL2 suggesting a potentially better prognosis. Important differential diagnoses of the CNS-DLBCL include other CNS lymphomas, such as immunodeficiency-associated CNS lymphomas, intravascular large B‑cell lymphoma, or T‑cell and NK/T-cell lymphomas; however, approximately 95% of all primary CNS lymphomas are DLBCL. Only 5% include the mentioned differential diagnosis, and thus, they are exceptionally rare [
27].