The nervous system presents unique challenges with regard to the recognition and classification of hematopoietic tumors, by virtue of combining disciplines of neuropathology and hematopathology. As the understanding of fundamental immunology has evolved, so too have a variety of lymphoma classification schemes and diagnostic modalities that variably impact patient care. The nervous system can be involved either primarily or secondarily, the latter being more common, particularly in the case of leukemias with CNS extension. Primary presentations of lymphomas and plasma cell and histiocytic proliferations raise the greatest diagnostic and pathogenetic questions. It is unclear whether these lesions arise de novo in nervous system
tissues, or metastasize from clinically occult systemic sites of malignant transformation. Furthermore, with several lymphoma classification systems promulgated over the past three decades, it may be hard to maintain fluency in appropriate hematopathologic concepts. Finally, there is no separate consideration given to CNS neoplasia in any of the lymphoma classification systems, and therefore relating histologic to prognostic variables becomes difficult if not impossible.