Pathology Department.
Translational Hematopathology Lab, IDIVAL, CIBERONC.
Appl Immunohistochem Mol Morphol. 2020 Sep;28(8):e68-e71. doi: 10.1097/PAI.0000000000000655.
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.
原发性中枢神经系统弥漫性大 B 细胞淋巴瘤（DLBCL）是一种侵袭性的 DLBCL 亚型，具有特征性的临床病理特征。已有部分病例（16%）在外周淋巴结以外的部位（如睾丸和双侧肾上腺）出现复发。在此，我们描述了一例原发于中枢神经系统的 DLBCL 病例，在最初诊断后的 18 个月，在睾丸和双侧肾上腺复发。两个肿瘤的形态、表型、细胞遗传学特征和克隆关系均相同。下一代测序的体细胞突变分析显示，两个肿瘤均存在 MYD88L265P 突变，而仅在复发肿瘤中存在 CD79B Y196S 突变。这些突变模式提示，这两个肿瘤可能起源于一个具有 MYD88L265P 突变的共同前体细胞克隆。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弥漫性大 B 细胞淋巴瘤中同时存在 MYD88L265P 和 CD79B ITAM 突变的频率显著升高，这突显了体细胞突变在这些定殖于免疫特权部位的淋巴瘤中激活 B 细胞受体和核因子 kB 的作用。总之，我们在此说明，针对复发 DLBCL 中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。
