Neural Stem Cells in Primary Central Nervous System Lymphoma

Abstract

The initial intent of this study was to examine the origins of Primary Central Nervous System Lymphoma (PCNSL), a neoplasm whose oncogenesisin immunocompetentpatients is incompletely understood. With growing information regarding the remarkable plasticity of neural stem cells, and establishment of relationships between hematopoietic and neural stem cells, we hypothesized that PCNSL arises from neural stem/progenitor cells rather than lymphocyte precursors from elsewhere in the body. Markers of neural stem cells were chosen for immunohistochemical(IHC) staining of 5 PCNSL cases and all cases contained Sox2 positive cells, whereas 8 of 9 non-CNS B cell lymphomas so stained had no positive cells. Double-staining with Sox2 and CD20, a B-cell marker, showed no co-localization of Sox2 and CD20, and no CD20-positive tumor cells had Sox2 immunopositivity. Staining of 5 metastatic carcinomas and 1 metastatic melanoma revealed a similar pattern of immunopositivityboth regarding sox2 expression and subsequent double-staining with low molecular weight cytokeratins. These findings suggest that neural stem cells are enriched in PCNSL as a reaction rather than as a source of the tumors and that sox2 expression is indicative of a neural progenitor/stem cell response to non-neural neoplasms. It follows that not all stem cell marker-positive cells in a tumor are tumor stem cells. Further understanding of the reactive response of neural stem cells is needed for understanding of neural neoplasm pathology. The presence of these findings in diverse central nervous system neoplasms and manipulation of the observation for therapeutic benefit have yet to be explored.