Analysis of the immunoglobulin heavy chain gene variable region of intravascular large B-cell lymphoma

Intravascular large B-cell lymphoma (IVLBL) is a rare neoplasm characterize d by proliferation of lymphoma cells within the blood vessels. The cell ori gin of IVLBL has not yet been determined. We examined cell lineage, with im munohistochemical staining and molecular analysis, using polymerase chain r eaction (PCR) of the variable region of the immunoglobulin heavy chain (Ig- VH) gene. We also investigated the cell origin using direct sequence analys is of the complementary-determining region 2 (CDR2) and framework region 3 (FR3) in six cases, consisting of two male and four female patients. The se quences in five cases showed frequent mutations. The percent homology to th eir closest germline genes ranged from 74.7 to 91.8%. However, one case sho wed a percent homology of 99.4% in CDR2 and FR3 of Ig-VH. All cases showed rearrangements of VH3 family genes. Interestingly, three of the IVLBL cases with hypermutated IgH genes showed the expression of CD5. Therefore, expre ssion of CD5 in lymphoma cells does not indicate that the origin of IVLBL i s the same as mantle cell lymphoma having the character of CD5 expression, which develops in pre-germinal center cells. Our results indicate that most IVLBLs may originate in the post-germinal center cells, based on the prese nce of somatic mutation in VH genes, although some heterogeneous cases are intermingled within IVLBL.