Booman M, Douwes J, Glas A M, de Jong D, Schuuring E, Kluin P M
Department of Pathology and Laboratory Medicine, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
J Pathol. 2006 Oct;210(2):163-71. doi: 10.1002/path.2033.
Diffuse large B-cell lymphomas (DLBCLs) constitute a heterogeneous group of lymphomas in which germinal centre B-cell-like and activated B-cell-like subtypes can be discerned based on pathology, clinical presentation, and gene expression patterns. Testicular DLBCLs form an immune-privileged site-related subgroup of DLBCLs with an unfavourable prognosis. In the present study, cDNA microarray analysis, immunohistochemistry for CD10, Bcl6 and MUM1, and somatic hypermutation analysis of the immunoglobulin heavy chain gene rearrangements were used to determine the subtype of primary testicular DLBCL. Immunohistochemistry revealed 14/22 testicular DLBCLs with an activated B-cell-like immunophenotype and 8/22 with an ambiguous immunophenotype co-expressing CD10 and high levels of MUM1. cDNA microarray analysis of these 22 and four additional cases showed a uniform activated B-cell-like gene expression pattern for both immunophenotypes. Somatic hypermutation analysis of immunoglobulin heavy chain genes showed a very high mutation load in seven cases tested, but intraclonal heterogeneity was found at low level in only one of these cases. It is concluded that primary testicular DLBCLs have uniform activated B-cell-like subtype characteristics despite a number of cases showing an ambiguous immunophenotype.
弥漫性大B细胞淋巴瘤(DLBCL)是一组异质性淋巴瘤,根据病理、临床表现和基因表达模式可区分出生发中心B细胞样和活化B细胞样亚型。睾丸DLBCL形成了DLBCL的一个与免疫豁免部位相关的亚组,预后不良。在本研究中,采用cDNA微阵列分析、CD10、Bcl6和MUM1免疫组织化学以及免疫球蛋白重链基因重排的体细胞超突变分析来确定原发性睾丸DLBCL的亚型。免疫组织化学显示,22例睾丸DLBCL中,1例具有活化B细胞样免疫表型,8/22例具有共表达CD10和高水平MUM1的模糊免疫表型。对这22例及另外4例进行的cDNA微阵列分析显示,两种免疫表型均呈现一致的活化B细胞样基因表达模式。免疫球蛋白重链基因的体细胞超突变分析显示,在检测的7例病例中突变负荷非常高,但其中只有1例发现低水平的克隆内异质性。结论是,尽管有一些病例表现出模糊的免疫表型,但原发性睾丸DLBCL具有一致的活化B细胞样亚型特征。