The Generation of Chromosomal Alterations During Mitosis in Primary Central Nervous System Diffuse Large B-cell Lymphoma

Author(s): Ben-Zion Katz, Dan Benisty, Chen Glait-Santar, Chava Perry and Sigi Kay

A 51 year old male patient was diagnosed with primary central nervous system (CNS) non-germinal center B-cell (non-GCB) diffuse large B-cell lymphoma (DLBCL), with approximately 50% of Ki-67 positive cells. Morphological examination of the cerebrospinal fluid (CSF) at presentation revealed population of large cells, some with basophilic cytoplasm and disordered nuclear structure. 7-8% of the cells were in various stages of mitosis. Mitosis in this specimen was profoundly synchronized, with 81% of the cells in metaphase, and the rest of mitotic forms were in other stages of mitosis. As shown, individual chromosomes split from metaphase plates during metaphase, disordered metaphase plates generate aneuploidy during anaphase, and chromosomes may physically split during cytokinesis. All the alterations observed in this specimen occurred simultaneously, pointing to an extensive mechanism that drives rapid genetic diversity in this highly aggressive CNS lymphoma. The patient was treated with chemo-immunotherapy followed by autologous bone marrow transplantation, and is currently in remission.