Feng Lan, Gao Xiaohui, Jiao Zhiyun, Wang Zheng, Min Fenglin
Department of Hematology, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, Jiangsu 225009, P.R. China.
Department of Radiology, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, Jiangsu 225009, P.R. China.
Oncol Lett. 2022 Dec 15;25(2):48. doi: 10.3892/ol.2022.13634. eCollection 2023 Feb.
CD20-negative diffuse large B-cell lymphoma (DLBCL) is a rare type of lymphoproliferative disorder characterized by a high degree of aggressiveness, a tendency for extranodal invasion and chemotherapeutic resistance. CD20-negative DLBCL originating from the nervous system is rarer. In primary central nervous system lymphoma (PCNSL), >90% of cases are histologically classified as DLBCL. The present study reports the case of a 65-year-old female with CD20-negative PCNSL, whose primary clinical symptom was a persistent headache. Serum tests for human immunodeficiency virus, Epstein-Barr virus-DNA, human herpesvirus 8, hepatitis B and hepatitis C were negative. Cranial magnetic resonance imaging suggested multiple intracranial occupancies. The neoplastic cells were found to be positive for CD19, CD79α, Bcl-2 (92%) and c-Myc (50%), while showing negative results for CD20, CD138, programmed cell death protein 1 (PD-1) and programmed cell death receptor 1 ligand 1 (PD-L1). The Ki-67 proliferation index was >80%. In the tumor microenvironment, <10% of the tumor-associated macrophages expressed PD-L1. The number of PD-1-positive tumor-infiltrating lymphocytes was 30-40 cells according to high-power field microscopy. The patient's disease progressed during methotrexate-based treatment, leading to a change in the treatment regimen to the Bruton tyrosine kinase inhibitor, zanubrutinib, combined with the anti-PD-1 monoclonal antibody tislelizumab. After two courses of the combined treatment, the patient achieved complete remission (CR) and continued to receive consolidation treatment. In the 20 months of follow-up since CR was achieved, the patient's general condition was good and the disease was in continuous remission. The present case report and literature review show that a combination of drugs targeting different mechanisms may be used to treat PCNSL to prolong patient survival time. The mechanism of the enhanced efficacy of a combination of the two drugs may be related to the enhancement of antitumor T-cell immune responses and reversal of T-cell immune metabolic dysfunctions by the inhibition of glycolysis.
CD20 阴性弥漫性大 B 细胞淋巴瘤（DLBCL）是一种罕见的淋巴增殖性疾病，其特征为高度侵袭性、结外侵犯倾向和化疗耐药。起源于神经系统的 CD20 阴性 DLBCL 更为罕见。在原发性中枢神经系统淋巴瘤（PCNSL）中，超过 90%的病例在组织学上被归类为 DLBCL。本研究报告了一例 65 岁的 CD20 阴性 PCNSL 女性患者，其主要临床症状为持续性头痛。人类免疫缺陷病毒、爱泼斯坦 - 巴尔病毒 DNA、人类疱疹病毒 8、乙型肝炎和丙型肝炎的血清检测均为阴性。头颅磁共振成像提示颅内多发占位。肿瘤细胞 CD19、CD79α、Bcl - 2（约 92%）和 c - Myc（约 50%）呈阳性，而 CD20、CD138、程序性细胞死亡蛋白 1（PD - 1）和程序性细胞死亡受体 1 配体 1（PD - L1）呈阴性。Ki - 67 增殖指数>80%。在肿瘤微环境中，<10%的肿瘤相关巨噬细胞表达 PD - L1。根据高倍视野显微镜检查，PD - 1 阳性肿瘤浸润淋巴细胞数量为 30 - 40 个细胞。患者在基于甲氨蝶呤的治疗过程中病情进展，导致治疗方案改为布鲁顿酪氨酸激酶抑制剂泽布替尼联合抗 PD - 1 单克隆抗体替雷利珠单抗。经过两个疗程的联合治疗，患者达到完全缓解（CR）并继续接受巩固治疗。自达到 CR 后的 20 个月随访中，患者一般状况良好，疾病持续缓解。本病例报告及文献综述表明，针对不同机制的联合用药可用于治疗 PCNSL 以延长患者生存时间。两种药物联合增效的机制可能与增强抗肿瘤 T 细胞免疫反应以及通过抑制糖酵解逆转 T 细胞免疫代谢功能障碍有关。
