Department of Pathology and Immunology, Washington University School of Medicine, 660 S, Euclid Avenue, Box 8118, St, Louis, MO 63110, USA.
Diagn Pathol. 2013 Jun 19;8:100. doi: 10.1186/1746-1596-8-100.
We present the case of a 30 year-old man who was referred for evaluation of diffuse lymphadenopathy. Six weeks prior, he noticed darkening of his urine associated with pale stools, nausea and an eventual 30 lb weight loss within a month. The initial laboratory findings showed elevation of the liver enzymes. A CT scan showed mesenteric and periaortic lymphadenopathy with the largest lymph node measuring 2.8 cm. Other laboratory results were otherwise unremarkable (including a normal LDH) with the exception of positive serum antibodies against Epstein-Barr virus (EBV) associated antigens (IgM+ and IgG+). An excisional biopsy of 4 of the small neck lymph nodes showed a normal architecture with prominent follicles and an intact capsule. But, by immunohistochemistry two of the follicles showed aberrant coexpression of BCL-2, in addition to CD10 and BCL-6. In-situ hybridization for early Epstein-Barr virus mRNA (EBER) and immunohistochemistry for latent membrane protein-1 (LMP-1) stained both scattered positive cells, as well as BCL-2 positive B-cells. Although an original diagnosis of in-situ follicular lymphoma was favored at an outside facility, additional interphase fluorescence in situ hybridization (FISH) studies for t(14;18);(IGH-BCL2) rearrangement (performed on the BCL-2 + follicles microdissected from the tissue block; Abott probe dual colour fusion) and molecular studies (IGH gene rearrangement by PCR, also performed on the microdissected follicles) were negative. Serologic studies (positive EBV antibodies) and immunostains in conjunction with the molecular studies confirmed the reactive nature of the changes. Our case also shows direct immunopathogenic evidence of BCL-2 expression among the EBV-infected cells, which has to our knowledge not been previously documented in vivo. A diagnosis of EBV infection should, therefore, be considered when confronted with BCL-2 expression in germinal centers, particularly in younger individuals, as the diagnosis of FLIS may lead to extensive and invasive haematologic work-ups.
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我们报告了一例 30 岁男性，因弥漫性淋巴结病就诊。六周前，他注意到尿液变暗，伴有浅色粪便、恶心，最终在一个月内体重减轻了 30 磅。最初的实验室检查结果显示肝酶升高。CT 扫描显示肠系膜和主动脉旁淋巴结病，最大淋巴结直径 2.8 厘米。其他实验室结果无明显异常（包括正常的 LDH），除了针对 Epstein-Barr 病毒（EBV）相关抗原的血清抗体阳性（IgM+和 IgG+）。对 4 个颈部小淋巴结的切除活检显示正常结构，滤泡明显，包膜完整。但是，通过免疫组化，两个滤泡显示 BCL-2 的异常共表达，此外还有 CD10 和 BCL-6。针对早期 Epstein-Barr 病毒 mRNA（EBER）的原位杂交和潜伏膜蛋白-1（LMP-1）的免疫组化均显示散在的阳性细胞以及 BCL-2 阳性的 B 细胞。尽管在外部机构最初诊断为原位滤泡淋巴瘤，但对组织块中微切割的 BCL-2+滤泡进行了额外的间期荧光原位杂交（FISH）研究以检测 t（14;18）；（IGH-BCL2）重排（Abbott 探针双色融合）和分子研究（PCR 检测 IGH 基因重排，也在微切割滤泡上进行）均为阴性。血清学研究（阳性 EBV 抗体）和免疫组化与分子研究相结合，证实了这些变化的反应性质。我们的病例还显示了 EBV 感染细胞中 BCL-2 表达的直接免疫发病机制证据，据我们所知，这在体内尚未有过记录。因此，当在生发中心遇到 BCL-2 表达时，应考虑 EBV 感染的诊断，特别是在年轻人中，因为 FLIS 的诊断可能导致广泛和侵入性的血液学检查。
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