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Fibrin-associated EBV-positive Large B-Cell Lymphoma: An Indolent Neoplasm With Features Distinct From Diffuse Large B-Cell Lymphoma Associated With Chronic Inflammation.

纤维蛋白相关Epstein-Barr病毒(EBV)阳性大B细胞淋巴瘤:一种特征显著异于慢性炎症相关弥漫性大B细胞淋巴瘤的惰性肿瘤

Boyer DF,McKelvie PA,de Leval L,Edlefsen KL,Ko YH,Aberman ZA,Kovach AE,Masih A,Nishino HT,Weiss LM,Meeker AK,Nardi V,Palisoc M,Shao L,Pittaluga S,Ferry JA,Harris NL,Sohani AR

Abstract

Incidental cases of localized fibrin-associated Epstein-Barr virus (EBV)+ large B-cell proliferations have been described at unusual anatomic sites and have been included in the category of diffuse large B-cell lymphoma associated with chronic inflammation (DLBCL-CI) in the WHO Classification. We describe 12 cases and review the literature to define their clinicopathologic spectrum and compare features with typical cases of DLBCL-CI. Median age was 55.5 years with a M:F ratio of 3. In all 12 cases, the lymphoma was an incidental microscopic finding involving atrial myxomas (n=3), thrombi associated with endovascular grafts (n=3), chronic hematomas (n=2), and pseudocysts (n=4). All cases tested were nongerminal center B-cell origin, type III EBV latency, and were negative for MYC rearrangements and alternative lengthening of telomeres by FISH. Most showed high CD30, Ki67, and PD-L1, and low to moderate MYC and p53 expression. Among 11 patients with detailed follow-up, 6 were treated surgically, 3 with cardiac or vascular lesions had persistent/recurrent disease at intravascular sites, and 4 died of causes not directly attributable to lymphoma. Reports of previously published fibrin-associated cases showed similar features, whereas traditional DLBCL-CI cases with a mass lesion had significantly higher lymphoma-associated mortality. Fibrin-associated EBV+ large B-cell lymphoma is clinicopathologically distinct from DLBCL-CI, warranting separate classification. Most cases, particularly those associated with pseudocysts, behave indolently with the potential for cure by surgery alone and may represent a form of EBV+ lymphoproliferative disease rather than lymphoma. However, primary cardiac or vascular disease may have a higher risk of recurrence despite systemic chemotherapy.

摘要

WHO的分类中描述了发生于非寻常解剖部位的局限性纤维蛋白相关EBV阳性大B细胞增生的偶发病例,并将其归于慢性炎症相关的弥漫性大B细胞淋巴瘤中(DLBCL-CI)。我们描述了12例局限性纤维蛋白相关EBV阳性大B细胞增生的病例,通过文献复习定义其临床病理谱,并将其与典型的DLBCL-CI病例进行特征比较。此12例患者的年龄中位数为55.5岁,男女比例为3:1。所有的12例患者中,淋巴瘤是一个偶发的镜下发现,其病理改变包括心房粘液瘤(n=3),血管内移植相关的血栓(n=3),慢性血肿(n=2)和假性囊肿(n=4)。所有病例均为非生发中心B细胞起源,具有III型EBV潜伏感染,FISH发现MYC重排和端粒延长均为阴性。大多数病例呈现为CD30、Ki67和PD-L1高表达,MYC和p53呈低到中等程度表达。在具有详细随访资料的11例患者中,6例进行了手术治疗,3例心脏或血管病损在血管内持续或者反复发作,4例死亡,其死因并不直接由淋巴瘤导致。已发表的纤维蛋白相关病例表现出相似的特征,而传统的DLBCL-CI病例则呈现出肿块式病损,且淋巴瘤相关的死亡率显著升高。纤维蛋白相关的EBV阳性大B细胞淋巴瘤的临床病理与DLBCL-CI是截然不同的,需要单独地分类。绝大部分病例,特别是那些与假性囊肿相关的病例,临床呈现为惰性特征,具备单纯手术治愈的可能性,它可能代表一种EBV阳性的淋巴组织增生性疾病,而非淋巴瘤。然而,即使进行全身化疗,原发性心脏或血管疾病仍具有较高的复发风险。

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