Kanda M, Suzumiya J, Ohshima K, Haraoka S, Nakamura N, Abe M, Tamura K, Kikuchi M
First Department of Pathology, School of Medicine, Fukuoka University, Japan.
Virchows Arch. 2001 Oct;439(4):540-6. doi: 10.1007/s004280100398.
Intravascular large B-cell lymphoma (IVLBL) is a rare neoplasm characterized by proliferation of lymphoma cells within the blood vessels. The cell origin of IVLBL has not yet been determined. We examined cell lineage, with immunohistochemical staining and molecular analysis, using polymerase chain reaction (PCR) of the variable region of the immunoglobulin heavy chain (Ig-VH) gene. We also investigated the cell origin using direct sequence analysis of the complementary-determining region 2 (CDR2) and framework region 3 (FR3) in six cases, consisting of two male and four female patients. The sequences in five cases showed frequent mutations. The percent homology to their closest germline genes ranged from 74.7 to 91.8%. However, one case showed 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, expression of CD5 in lymphoma cells does not indicate that the origin of IVLBL is 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 presence of somatic mutation in VH genes, although some heterogeneous cases are intermingled within IVLBL.
血管内大B细胞淋巴瘤（IVLBL）是一种罕见的肿瘤，其特征为淋巴瘤细胞在血管内增殖。IVLBL的细胞起源尚未确定。我们使用免疫组化染色和分子分析，通过聚合酶链反应（PCR）检测免疫球蛋白重链（Ig-VH）基因可变区，来研究细胞谱系。我们还对6例患者（2例男性和4例女性）进行互补决定区2（CDR2）和构架区3（FR3）的直接序列分析，以研究细胞起源。5例患者的序列显示频繁突变。与最接近的种系基因的同源百分比范围为74.7%至91.8%。然而，1例患者在Ig-VH的CDR2和FR3中显示同源百分比为99.4%。所有病例均显示VH3家族基因重排。有趣的是，3例IgH基因高度突变的IVLBL病例显示CD5表达。因此，淋巴瘤细胞中CD5的表达并不表明IVLBL的起源与具有CD5表达特征的套细胞淋巴瘤相同，套细胞淋巴瘤发生于生发中心前细胞。我们的结果表明，基于VH基因中体细胞突变的存在，大多数IVLBL可能起源于生发中心后细胞，尽管IVLBL中夹杂着一些异质性病例。
