A new xenograft model of primary central nervous system lymphoma

Abstract

The management of primary lymphoma of the central nervous system (PCNSL) remains controversial and patients' outcome dismal. In order to investigate new selective therapeutic strategies in a controlled system, a reproducible model of PCNSL in nude rats was developed and characterized. Human B lymphoma cells (BL2) were implanted in the brain frontal area in New Zealand nude rats through a silastic device sealed to the skull. Fifteen and 30 days post-implantation, animals were sacrificed. An autopsy was performed. Representative brain sections were cut and examined for the presence of lymphoma. Immunohistochemistry was performed for proliferation (MIB1-Ki67), a B-cell marker (L26-CD20), a T-cell marker (UCHL1-CD45RO). The analysis of the brains showed tumor growth in 88% of the rats. No mortality was observed. At autopsy no extracerebral, spinal or cerebellar metastasis were found. Microscopically the brain tumors appeared non-encapsulated, highly vascularized, with a characteristic perivascular and diffuse lymphomatous spread in the parenchyma. Immunohistochemistry showed a marked positivity of the tumor cells for L26. Tumor cells were negative for UCHL1. Mean proliferation rate was 30%. The device was well tolerated and caused no local infection. Controlled studies on PCNSL in animal models are lacking. This PCNSL model in nude rats reproduces the histology and location of human CNS lymphoma. Tumor dimensions are within the resolution limits of CT and MRI and therefore suitable for stereotactic therapy. This model provides a tool to test new chemo and radiotherapeutical strategies in a controlled fashion.