Department of Pathology and Laboratory Medicine, Nagoya University Hospital, Nagoya, Japan.
Department of Diagnostic Pathology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Neuropathology. 2021 Apr;41(2):99-108. doi: 10.1111/neup.12705. Epub 2020 Dec 2.
Primary diffuse large B-cell lymphoma (DLBCL) of the central nervous system (PCNS-DLBCL) is rare. Thirty-nine patients consecutively diagnosed as having PCNS-DLBCL were analyzed to highlight the prognostic value of the expression of programmed cell death ligand-1 (PD-L1) by neoplastic cells and immune cells in the microenvironment. They were positive for CD20 in all (100%), CD5 in two (5%), CD10 in nine (23%), BCL-2 in 27 (69%), BCL-6 in 34 (87%), and MUM-1 in 37 (95%). Only one case was positive for neoplastic PD-L1, with an unexpectedly long clinical course of 92 months. The remaining 38 cases were further divided into three groups based on the percentage of PD-L1 cells among microenvironmental immune cells. Cutoffs of < 5%, 5-40%, and ≥ 40% successfully stratified mean prognoses with three-year overall survival (OS) of 21%, 63%, and 100% (P = 0.009), respectively. Progression-free survival (PFS) and OS were different between the groups with and without methotrexate (MTX)-containing chemotherapy (P = 0.007 and P < 0.001, respectively). Multivariate analysis identified three independent adverse factors of OS: PD-L1 negativity (< 5%) on microenvironmental immune cells (P = 0.027), deep structure involvement (P = 0.034), and performance status (PS) 2-4 (P = 0.009). The study showed that PD-L1 expression on immune cells in the microenvironment was associated with prognosis among patients with PCNS-DLBCL.
原发性中枢神经系统弥漫性大 B 细胞淋巴瘤(PCNS-DLBCL)较为罕见。本研究分析了连续诊断为 PCNS-DLBCL 的 39 例患者,以强调肿瘤细胞和微环境中免疫细胞程序性死亡配体-1(PD-L1)的表达对预后的影响。所有患者均为 CD20 阳性(100%),CD5 阳性 2 例(5%),CD10 阳性 9 例(23%),BCL-2 阳性 27 例(69%),BCL-6 阳性 34 例(87%),MUM-1 阳性 37 例(95%)。仅 1 例肿瘤 PD-L1 阳性,临床过程出乎意料地长,达 92 个月。其余 38 例根据微环境中免疫细胞 PD-L1 细胞的百分比进一步分为三组。<5%、5-40%和≥40%的截断值成功分层,三组患者的 3 年总生存率(OS)分别为 21%、63%和 100%(P=0.009)。含甲氨蝶呤(MTX)化疗与无 MTX 化疗两组患者的无进展生存期(PFS)和 OS 不同(P=0.007 和 P<0.001)。多因素分析确定 OS 的三个独立不良因素:微环境免疫细胞中 PD-L1 阴性(<5%)(P=0.027)、深部结构受累(P=0.034)和体能状态(PS)2-4 (P=0.009)。本研究表明,PCNS-DLBCL 患者微环境中免疫细胞 PD-L1 的表达与预后相关。