Primary diffuse large B-cell lymphoma (DLBCL) of the central nervous system (CNS) is an aggressive subtype of DLBCL with characteristic clinicopathologic features. Relapse outside the CNS involving extranodal locations has been found in a fraction of cases (16%). Here we describe a case of DLBCL arising in the CNS that relapsed 18 months after the initial diagnosis in the testis and bilateral adrenal glands. Both tumors showed equivalent morphology, phenotype, cytogenetic features, and clonal relationship. Somatic mutation analysis by next generation sequencing demonstrated MYD88L265P mutation in both tumors and de novo CD79B Y196S mutation exclusive to the relapse. The pattern of mutations suggest that the 2 tumors might have evolved from a common progenitor clone with MYD88L265P being the founder mutation. A meta-analysis of the literature shows a significantly high frequency of concurrent MYD88L265P and CD79B ITAM mutations in primary CNS lymphoma and testicular DLBCL, underscoring the role of B cell receptor and nuclear factor kB activation by somatic mutations in these lymphomas that colonize immune-privileged sites. In summary, here we illustrate that targeted next generation sequencing for the detection of hot spot somatic mutations in relapsed DLBCL is useful to confirm ABC phenotype and discovers relevant information that might influence therapeutic decision.

中文翻译：

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中枢神经系统原发性弥漫性大 B 细胞淋巴瘤的克隆进化

中枢神经系统 (CNS) 的原发性弥漫性大 B 细胞淋巴瘤 (DLBCL) 是具有特征性临床病理特征的 DLBCL 的侵袭性亚型。在一小部分病例 (16%) 中发现了涉及结外位置的 CNS 以外的复发。在这里，我们描述了一例中枢神经系统 DLBCL 病例，该病例在最初诊断睾丸和双侧肾上腺后 18 个月复发。两种肿瘤均表现出相同的形态、表型、细胞遗传学特征和克隆关系。通过下一代测序进行的体细胞突变分析表明，肿瘤中的 MYD88L265P 突变和复发独有的从头 CD79B Y196S 突变。突变模式表明这 2 个肿瘤可能是从一个共同的祖克隆进化而来的，MYD88L265P 是创始人突变。对文献的荟萃分析显示，原发性中枢神经系统淋巴瘤和睾丸 DLBCL 中并发 MYD88L265P 和 CD79B ITAM 突变的频率非常高，强调了 B 细胞受体和核因子 kB 在这些淋巴瘤中通过体细胞突变激活的作用，这些突变定植于免疫特权网站。总之，我们在此说明用于检测复发性 DLBCL 热点体细胞突变的靶向下一代测序有助于确认 ABC 表型并发现可能影响治疗决策的相关信息。