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伴有小管保留的睾丸弥漫性大细胞淋巴瘤——既往滤泡性淋巴瘤转化的分子遗传学证据

Testicular diffuse large cell lymphoma with tubule preservation--molecular genetic evidence of transformation from previous follicular lymphoma.

作者信息

Lasota J, Nordling S, Miettinen M

机构信息

Armed Forces Institute of Pathology, Department of Soft Tissue Pathology, Washington, DC 20306-6000, USA.

出版信息

Virchows Arch. 2000 Mar;436(3):276-83. doi: 10.1007/s004280050041.

DOI:10.1007/s004280050041
PMID:10782887
Abstract

Testicular lymphomas usually occur in older men and are mostly diffuse large B-cell lymphomas (DLBL). They may be primary manifestation of lymphoma or represent a relapse of a previous non-Hodgkin's lymphoma. This report details a testicular large cell lymphoma, which was proven to be large cell transformation of a low-grade follicular lymphoma biopsied 8 years earlier. Initially, a 38-year old man was diagnosed with cervical lymphadenopathy, and biopsy was interpreted as reactive follicular hyperplasia; no treatment was given, and the lymphadenopathy resolved spontaneously. Eight years later, the patient underwent surgery for a left testicular mass and gastroscopy for gastric symptoms. The patient died 7 months later with evidence for intra-abdominal and central nervous system lymphoma after a brief but temporary response to M-BACOD chemotherapy. Orchiectomy specimen and gastroscopic biopsy showed diffuse large B-cell lymphoma (CD20+), which infiltrated between well-preserved tubules in the testis. Histological comparison with 20 testicular lymphomas without previous lymphoma showed tubule infiltration in all cases, suggesting that the tubule-preserving infiltration pattern could be a histological marker for secondary lymphoma involvement in testis. On re-examination, the lymph node 8 years prior was verified as follicular, predominantly small, cleaved cell lymphoma with bcl2-positive follicles. The earlier follicular lymphoma and the subsequent diffuse large cell lymphoma were analyzed using polymerase chain reaction and showed identical sequences of the t(14;18) translocation and immunoglobulin heavy chain gene rearrangement. Analysis of the VH-gene sequences from the follicular lymphoma revealed sequence heterogeneity consistent with ongoing mutation. However, the transformed diffuse large cell lymphoma had no intraclonal variation, with the sequence matching with one of the subclones from the low-grade follicular lymphoma. These results confirm that the large cell transformation of follicular lymphoma occurs in a single follicular lymphoma cell. This case also indicates that the selection of the transformed clone can be part of the natural history of disease and can occur without exposure to chemotherapy.

摘要

睾丸淋巴瘤通常发生于老年男性,大多为弥漫性大B细胞淋巴瘤(DLBL)。它们可能是淋巴瘤的原发性表现,或代表先前非霍奇金淋巴瘤的复发。本报告详细描述了一例睾丸大细胞淋巴瘤,经证实是8年前活检的低级别滤泡性淋巴瘤发生的大细胞转化。最初,一名38岁男性被诊断为颈部淋巴结病,活检结果被解释为反应性滤泡增生;未给予治疗,淋巴结病自行消退。8年后,患者因左侧睾丸肿块接受手术,并因胃部症状接受胃镜检查。患者在对M-BACOD化疗有短暂但暂时的反应后7个月死亡,有腹腔和中枢神经系统淋巴瘤的证据。睾丸切除术标本和胃镜活检显示弥漫性大B细胞淋巴瘤(CD20+),其浸润于睾丸中保存完好的小管之间。与20例既往无淋巴瘤的睾丸淋巴瘤进行组织学比较,发现所有病例均有小管浸润,提示保留小管的浸润模式可能是睾丸继发性淋巴瘤累及的组织学标志物。再次检查时,8年前的淋巴结被证实为滤泡性淋巴瘤,主要为小的、有裂沟的细胞淋巴瘤,伴有bcl2阳性滤泡。使用聚合酶链反应对早期滤泡性淋巴瘤和随后的弥漫性大细胞淋巴瘤进行分析,结果显示t(14;18)易位和免疫球蛋白重链基因重排的序列相同。对滤泡性淋巴瘤的VH基因序列分析显示序列异质性,与正在进行的突变一致。然而,转化后的弥漫性大细胞淋巴瘤没有克隆内变异,其序列与低级别滤泡性淋巴瘤的一个亚克隆匹配。这些结果证实滤泡性淋巴瘤的大细胞转化发生在单个滤泡性淋巴瘤细胞中。该病例还表明,转化克隆的选择可能是疾病自然史的一部分,且可在未接触化疗的情况下发生。

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