Hyland J, Lasota J, Jasinski M, Petersen R O, Nordling S, Miettinen M
Armed Forces Institute of Pathology, Department of Soft Tissue Pathology, Washington, DC 20306-6000, USA.
Hum Pathol. 1998 Nov;29(11):1231-9. doi: 10.1016/s0046-8177(98)90250-7.
The molecular pathology of 20 lymphomas, which presented as testicular masses in patients with no evidence of previous lymphoma, was analyzed. These lymphomas occurred in men with a median age of 69 years (range, 37 to 87 years). Nine of the 14 patients with follow-up died of lymphoma (median survival, 12 months). All cases were diffuse large B-cell lymphomas that were positive for CD20 and commonly showed plasmacytoid differentiation (10 of 20 cases). Three cases were Burkitt's-like large cell lymphomas. Infiltration by lymphoma in the seminiferous tubules was seen in most cases. All lymphomas were negative for human herpesvirus 8 and Epstein-Barr virus by 35 cycles of polymerase chain reaction (PCR), suggesting that these viruses are not involved in the pathogenesis of primary testicular diffuse large B-cell lymphomas (DLBCL). PCR-based studies for t(14;18) and t(11;14) translocations, commonly seen in follicular and mantle-cell lymphomas, were negative in all cases. Nucleotide sequences of the V-D- and J segments of the immunoglobulin heavy chain gene (IgH) rearrangements obtained in 12 cases after PCR amplification were analyzed and compared with known germlines. The frequency of VH-family use in testicular DLBCL was similar to that reported for normal peripheral blood lymphocytes and follicular lymphomas. This contrasts with the previously published findings of preferential use of the VH3- or VH4-family by nodal DLBCL. Comparison with the published germlines showed a low similarity index in most of the cases, suggesting the presence of extensive somatic mutations. Ongoing mutation, as indicated by intraclonal variation in IgH sequence, was observed in all sequenced cases, suggesting direct antigen stimulation, which represents another difference between primary testicular and nodal DLBCL. Our results suggest that testicular lymphomas represent a subset of DLBCL that differs from their nodal counterparts in several respects. Their histological and molecular features show some similarities to those seen in marginal zone (MALT) lymphomas.
对20例淋巴瘤的分子病理学进行了分析,这些淋巴瘤表现为睾丸肿块,患者既往无淋巴瘤证据。这些淋巴瘤发生在男性,中位年龄为69岁(范围37至87岁)。14例接受随访的患者中有9例死于淋巴瘤(中位生存期12个月)。所有病例均为弥漫性大B细胞淋巴瘤,CD20阳性,常见浆细胞样分化(20例中的10例)。3例为伯基特样大细胞淋巴瘤。大多数病例可见淋巴瘤浸润生精小管。通过35个循环的聚合酶链反应(PCR),所有淋巴瘤的人疱疹病毒8和EB病毒均为阴性,提示这些病毒不参与原发性睾丸弥漫性大B细胞淋巴瘤(DLBCL)的发病机制。对滤泡性和套细胞淋巴瘤中常见的t(14;18)和t(11;14)易位进行的基于PCR的研究在所有病例中均为阴性。对12例PCR扩增后获得的免疫球蛋白重链基因(IgH)重排的V-D-和J片段的核苷酸序列进行分析,并与已知种系进行比较。睾丸DLBCL中VH家族的使用频率与正常外周血淋巴细胞和滤泡性淋巴瘤的报道相似。这与之前发表的关于结内DLBCL优先使用VH3或VH4家族的研究结果形成对比。与已发表的种系比较显示,大多数病例的相似性指数较低,提示存在广泛的体细胞突变。在所有测序病例中均观察到IgH序列的克隆内变异所表明的持续突变,提示直接抗原刺激,这是原发性睾丸和结内DLBCL之间的另一个差异。我们的结果表明,睾丸淋巴瘤代表了DLBCL的一个亚组,在几个方面与其结内对应物不同。它们的组织学和分子特征与边缘区(MALT)淋巴瘤有一些相似之处。