Our report identifies the first patient with a DLBCL/BL lymphoma presenting as a primary central nervous system lymphoma without any systemic involvement. The findings in our patient indicate that PCNSDLBCL/BL is characterized by an aggressive clinical course and multifocal involvement in the CNS. Pathologically, it demonstrates typical DLBCL morphology and germinal center B cell phenotype with CD10 expression and negative MUM1 expression. It expresses osteopontin strongly with nuclear and cytoplasmic staining pattern similar to other PCNSL cases [5
]. Proliferation index by Ki-67 is almost 100%. Molecularly, our case of PCNSDLBCL/BL over-expresses MYC due to t (8; 14) and BCL2 due to a gain. BCL2 overexpression was confirmed by IHC and by FISH with several probes. Lack of t(14;18) indicates that this case cannot be labeled as a double-hit lymphoma [8
]. The pathologic and genetic features clearly show that PCNSDLBCL/BL has a mixture of features of GCB-DLBCL and Burkitt lymphoma. The aggressive nature of PCNSDLBCL/ BL is likely explained by a combination of MYC overexpression driving excessive lymphoproliferation and anti-apoptotic activity of BCL2 overexpression.
PCNSDLBCL/BL appears to be a very rare variant of PCNSL. More than 95% of PCNSL cases have ABC phenotype with the remainder having GCB phenotype [2
]. Primary CNS Burkitt lymphoma is very rare. As such, the incidence of PCNSDLBCL/BL must be extremely low.
We have previously shown that osteopontin (OPN) is the most upregulated gene in PCNSL compared to non-CNS DLBCL [7
]. Our microarray findings were backed up by Rubenstein JL et al [9
]. We have shown by double immunostaining for CD20 and OPN that B lymphoma cells in PCNSL overexpressed OPN [5
]. Yuan J et al have also shown that OPN is strongly expressed by B lymphoma cells in PCNSL compared to non -CNS lymphoma [10
]. IHC in our patient confirmed that PCNSDLBCL/BL also strongly expresses OPN. Therefore, the strong expression of OPN is a unique feature of the CNS signature of PCNSL.
In conclusion, we recommend that a comprehensive FISH analysis for MYC, BCL2, and BCL6 should be performed in all PCNSL cases with aggressive clinical course, multifocal involvement of the CNS, and high proliferation index to make the correct diagnosis of PCNSDLBCL/BL. Based on our experience, patients with PCNSDLBCL/BL should be treated aggressively with a systemic therapy as early as possible. Eligible patients should be considered for high-dose chemotherapy followed by autologous stem cell transplant following intensive induction therapy consisting of high CNS penetrating agents such as high-dose Methotrexate and Ara-C combined with Rituximab. Additional research is necessary to better understand PCNSDLBCL/ BL and to determine an effective therapeutic approach.