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KSHV-associated and EBV-associated Germinotropic Lymphoproliferative Disorder: New Findings and Review of the Literature.

KSHV相关性和EBV相关性亲生发中心性淋巴增生性疾病:新发现及文献复习

Bhavsar T,Lee JC,Perner Y,Raffeld M,Xi L,Pittaluga S,Jaffe ES

Abstract

We report 2 cases of Kaposi sarcoma-associated herpesvirus (KSHV)-and Epstein-Barr Virus (EBV) associated germinotropic lymphoproliferative disorder. Both cases arose in patients from regions endemic for KSHV, Cape Verde, and the Democratic Republic of the Congo, presenting as localized lymphadenopathy. The affected lymph nodes showed colonization of the follicles by clusters of large atypical plasmablasts, but also showed regressive changes with vascular proliferation and interfollicular plasmacytosis, both reminiscent of human herpesvirus 8 (HHV-8) positive multicentric Castleman disease. The atypical plasmablasts showed dual positivity for HHV-8 and EBV, being positive for LANA and viral interleukin 6, as well as Epstein-Barr virus-encoded small RNA by in situ hybridization. They showed a latency I phenotype, being negative for LMP1, EBNA2, and BZLF-1. The plasmablasts were negative for immunoglobulin light chains, and in 1 case with successful DNA amplification had a polyclonal immunoglobulin rearrangement pattern. Germinotropic lymphoproliferative disorder is a rare disorder, with only 6 cases reported in the literature. We demonstrate for the first time the expression of HHV-8 viral interleukin 6 and provide evidence for latency I phenotype for EBV. In addition, 1 case progressed to an EBV-positive diffuse large B-cell lymphoma, but interestingly was negative for KSHV/HHV-8, likely indicative of tumor derived from an independent clone.

摘要

摘要:本文报道了2Kaposi肉瘤相关性疱疹病毒(KSHV)及EBV相关性亲生发中心性淋巴增生性疾病(GLD)。这两个患者发生于KSHV流行地区的佛得角和刚果民主共和国,均表现为局部淋巴结病。受累的淋巴结见大的不典型浆母细胞成簇分布于淋巴滤泡,也存在血管增生和滤泡间区浆细胞增多的退行性改变,类似HHV-8阳性的多中心性Castleman病。不典型浆母细胞显示HHV-8EBV双阳性,LANAHHV-8潜伏期相关核抗原)和病毒白介素6vIL-6)以及EBV病毒编码小RNAEBER)原位杂交均是阳性,因LMP1、EBNA2 BZLF-1均阴性,提示EBV潜伏期Ⅰ型感染。这些浆母细胞IG轻链是阴性的,其中一例DNA扩增存在多克隆IG重排模式。GLD是一种很罕见的疾病,文献复习仅仅报道了6例。本研究首次证明了HHV-8 vIL-6的表达,并提出EBV潜伏期Ⅰ型感染证据。另外,其中一个患者后来进展为EBV阳性弥漫大B细胞淋巴瘤,有意思的是KSHV/HHV-8是阴性的,可能提示该肿瘤是起源于一个独立的克隆。

 

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