Rare cases of primary central nervous system anaplastic variant of diffuse large B-cell lymphoma
Rare cases of primary central nervous system anaplastic variant of diffuse large B-cell lymphoma
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原发性中枢神经系统间变性弥漫性大 B 细胞淋巴瘤的罕见病例
DOI：
10.1186/s13000-019-0826-0
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发表时间：
2019-05-20
影响因子：
2.6
通讯作者：
Wang, Zhe
中科院分区：
文献类型：
--
作者：
Xu, Tianqi;Jia, Qingge;Wang, Zhe
背景原发性中枢神经系统弥漫性大B细胞淋巴瘤(DLBCL)是一种罕见的颅内肿瘤，定义为起源于脑、脊髓、软脑膜和眼睛的DLBCL，年总发病率为5/百万。DLBCL的原发CNS间变性变异型(A-DLBCL)更不常见；据我们所知，文献中只有两例其他病例报道。本文报告3例原发性CNS A-DLBCL患者，年龄分别为54岁、55岁和67岁。3例患者均有较高的国际结外淋巴瘤研究小组(IELSG)评分；尽管这些患者接受了以甲氨蝶呤为基础的方案和/或放射治疗，但总的生存时间仅为2、5和8个月。3例患者均表现为肿瘤细胞形态奇特的血管周围间隙浸润性改变，诊断为原发性CNS A-DLBCL。3例患者同时存在MYC和BCL2和/或BCL6异常和MYC/BCL2双表达DLBCL，2例MYC/BCL2/BCL6三重拷贝，1例MYC额外拷贝和BCL6易位。3例患者均表现为MYD88 L265P突变，核阳性表达relA、RELB和/或c-Rel，提示NF-B途径被结构性激活。原发性CNS A-DLBCL患者通常存在MYC/BCL2双表达基因，并同时存在MYC和BCL2和/或BCL6基因异常，以及NF-B通路的结构性激活。原发性CNS A-DLBCL具有侵袭性强的病程，预后差。今后，需要对大量病例进行分析，分子遗传学特征的评估将有助于对原发性CNS A-DLBCL的临床应用和治疗。
BackgroundPrimary central nervous system (CNS) diffuse large B-cell lymphoma (DLBCL) is a rare intracranial tumor, defined as DLBCL arising from the brain, spinal cord, leptomeninges and eye, with an overall annual incidence of 5 cases per million. The primary CNS anaplastic variant of DLBCL (A-DLBCL) is even less common; to our knowledge, there are only two other case reports in the literature. The aim of this report is to present rare cases of primary CNS A-DLBCL and study their clinicopathologic and genetic features.Case presentationWe report 3 patients, two men and one woman, aged 54, 55 and 67years old, with primary CNS A-DLBCL. All 3 patients had a high International Extranodal Lymphoma Study Group (IELSG) score; although the patients were treated with methotrexate-based regimens and/or with radiation therapy, the overall survival was only 2, 5, and 8months. All 3 patients presented with characteristic features of perivascular space infiltration with bizarre-shaped tumor cells, leading to the diagnosis of primary CNS A-DLBCL. Concurrent of MYC and BCL2 and/or BCL6 abnormalities and MYC/BCL2 double-expressor DLBCL occurred in all 3 patients; two patients had MYC/BCL2/BCL6 triple extra copies, and one patient had MYC extra copy and BCL6 translocation. All 3 patients displayed mutations in MYD88 L265P and nuclear positivity for RELA, RELB and/or c-Rel, indicating constitutive activation of the NF-B pathway.ConclusionsThese cases shed light on the unique genetic alterations and biological features of primary CNS A-DLBCL. Patients with primary CNS A-DLBCL may often have a MYC/BCL2 double-expressor and concurrent MYC and BCL2 and/or BCL6 genetic abnormalities, as well as constitutive activation of the NF-B pathway. Primary CNS A-DLBCL follows a very aggressive disease course and poor prognosis. In the future, a large number of cases should be analyzed, and the evaluation of molecular genetic characteristics could help with practical and therapeutic implications for primary CNS A-DLBCL.