原发性中枢神经系统淋巴瘤诊断及治疗的研究进展
Research Progress in the Treatment of Primary Central Nervous System Lymphoma
DOI: 10.12677/acm.2025.15113191, PDF,   
作者: 刘敏女：西安医学院研究生工作部/研究生处，陕西 西安；胡 军*：陕西省人民医院神经内一科，陕西 西安
关键词: 中枢神经系统淋巴瘤；恶性肿瘤；Central Nervous System Lymphoma； Malignant Tumor
摘要: 原发性中枢神经系统淋巴瘤(PCNSL)是一种罕见且高度侵袭性的恶性肿瘤，主要累及大脑、脊髓或眼部。其常见症状包括头痛、癫痫、认知和运动障碍等。该病的发生与免疫系统功能异常密切相关，尤其在免疫抑制患者中更为常见，如器官移植后患者和艾滋病毒感染者。诊断通常依赖神经影像学检查和脑脊液分析，最终确诊则需通过脑组织活检。治疗方案主要包括高剂量化疗和放疗，近年来，靶向治疗和免疫疗法也取得了一定进展。然而，PCNSL的预后较差，治疗困难，复发率高，长期生存率低。因此，早期诊断和个体化治疗对改善患者预后至关重要。
Abstract: Primary central nervous system lymphoma (PCNSL) is a rare and highly aggressive malignant tumor that primarily involves the brain, spinal cord, or eyes. Common symptoms include headache, seizures, cognitive and motor impairments. The development of this disease is closely associated with immune system dysfunction, particularly among immunocompromised patients, such as those who have undergone organ transplantation or are infected with the human immunodeficiency virus (HIV). Diagnosis typically relies on neuroimaging and cerebrospinal fluid analysis, with definitive confirmation requiring a brain biopsy. Treatment regimens primarily consist of high-dose chemotherapy and radiotherapy. In recent years, targeted therapy and immunotherapy have also shown some progress. However, PCNSL carries a poor prognosis, poses significant treatment challenges, and is characterized by high recurrence rates and low long-term survival. Therefore, early diagnosis and personalized treatment are crucial for improving patient outcomes.
文章引用：刘敏女, 胡军. 原发性中枢神经系统淋巴瘤诊断及治疗的研究进展[J]. 临床医学进展, 2025, 15(11): 1055-1062. https://doi.org/10.12677/acm.2025.15113191

参考文献

[1] Hattori, K., Sakata-Yanagimoto, M., Suehara, Y., Yokoyama, Y., Kato, T., Kurita, N., et al. (2017) Clinical Significance of Disease-Specific myd88 Mutations in Circulating DNA in Primary Central Nervous System Lymphoma. Cancer Science, 109, 225-230. [Google Scholar] [CrossRef] [PubMed]
[2] Villano, J.L., Koshy, M., Shaikh, H., Dolecek, T.A. and McCarthy, B.J. (2011) Age, Gender, and Racial Differences in Incidence and Survival in Primary CNS Lymphoma. British Journal of Cancer, 105, 1414-1418. [Google Scholar] [CrossRef] [PubMed]
[3] Shiels, M.S., Pfeiffer, R.M., Besson, C., Clarke, C.A., Morton, L.M., Nogueira, L., et al. (2016) Trends in Primary Central Nervous System Lymphoma Incidence and Survival in the U.S. British Journal of Haematology, 174, 417-424. [Google Scholar] [CrossRef] [PubMed]
[4] Kang, M., Ahn, S., Ha, J., Park, S.H., Moon, J. and Chu, K. (2022) Natural Killer T-Cell Primary CNS Lymphoma Presenting as Lymphomatosis Cerebri: A Case Report and Literature Review. Journal of Neuropathology & Experimental Neurology, 82, 261-266. [Google Scholar] [CrossRef] [PubMed]
[5] Tosefsky, K., Rebchuk, A.D., Martin, K.C., Chen, D.W., Yip, S. and Makarenko, S. (2024) Preoperative Corticosteroids Reduce Diagnostic Accuracy of Stereotactic Biopsies in Primary Central Nervous System Lymphoma: A Systematic Review and Meta-Analysis. Neurosurgery, 95, 740-750. [Google Scholar] [CrossRef] [PubMed]
[6] Zhang, C., Huang, M.Z., Kehs, G.J., Braun, R.G., Cole, J.W. and Zhang, L. (2021) Intensive In-Bed Sensorimotor Rehabilitation of Early Subacute Stroke Survivors with Severe Hemiplegia Using a Wearable Robot. IEEE Transactions on Neural Systems and Rehabilitation Engineering, 29, 2252-2259. [Google Scholar] [CrossRef] [PubMed]
[7] Grommes, C., Rubenstein, J.L., DeAngelis, L.M., Ferreri, A.J.M. and Batchelor, T.T. (2018) Comprehensive Approach to Diagnosis and Treatment of Newly Diagnosed Primary CNS Lymphoma. Neuro-Oncology, 21, 296-305. [Google Scholar] [CrossRef] [PubMed]
[8] Tse, E. and Kwong, Y. (2017) The Diagnosis and Management of NK/T-Cell Lymphomas. Journal of Hematology & Oncology, 10, Article No. 85. [Google Scholar] [CrossRef] [PubMed]
[9] Fukumura, K., Kawazu, M., Kojima, S., Ueno, T., Sai, E., Soda, M., et al. (2016) Genomic Characterization of Primary Central Nervous System Lymphoma. Acta Neuropathologica, 131, 865-875. [Google Scholar] [CrossRef] [PubMed]
[10] Gonzalez-Aguilar, A., Idbaih, A., Boisselier, B., Habbita, N., Rossetto, M., Laurenge, A., et al. (2012) Recurrent Mutations of myd88 and tbl1xr1 in Primary Central Nervous System Lymphomas. Clinical Cancer Research, 18, 5203-5211. [Google Scholar] [CrossRef] [PubMed]
[11] Radke, J., Ishaque, N., Koll, R., Gu, Z., Schumann, E., Sieverling, L., et al. (2022) The Genomic and Transcriptional Landscape of Primary Central Nervous System Lymphoma. Nature Communications, 13, Article No. 2558. [Google Scholar] [CrossRef] [PubMed]
[12] Nakamura, T., Tateishi, K., Niwa, T., Matsushita, Y., Tamura, K., Kinoshita, M., et al. (2015) Recurrent Mutations of cd79b and myd88 Are the Hallmark of Primary Central Nervous System Lymphomas. Neuropathology and Applied Neurobiology, 42, 279-290. [Google Scholar] [CrossRef] [PubMed]
[13] Wen, R. and Wang, D. (2022) MCD-DLBCL Arises from Germinal Center B Cells. Blood, 140, 1058-1059. [Google Scholar] [CrossRef] [PubMed]
[14] Grommes, C., Nayak, L., Tun, H.W. and Batchelor, T.T. (2018) Introduction of Novel Agents in the Treatment of Primary CNS Lymphoma. Neuro-Oncology, 21, 306-313. [Google Scholar] [CrossRef] [PubMed]
[15] Nayyar, N., White, M.D., Gill, C.M., Lastrapes, M., Bertalan, M., Kaplan, A., et al. (2019) MYD88 L265P Mutation and CDKN2A Loss Are Early Mutational Events in Primary Central Nervous System Diffuse Large B-Cell Lymphomas. Blood Advances, 3, 375-383. [Google Scholar] [CrossRef] [PubMed]
[16] Zhong, Y., Tan, G.W., Bult, J., Veltmaat, N., Plattel, W., Kluiver, J., et al. (2024) Detection of Circulating Tumor DNA in Plasma of Patients with Primary CNS Lymphoma by Digital Droplet PCR. BMC Cancer, 24, Article No. 407. [Google Scholar] [CrossRef] [PubMed]
[17] Majovsky, M., Moravec, T., Komarc, M., Soukup, J., Sedlak, V., Balasubramaniam, N., et al. (2024) Surgical Results in Patients with CNS Lymphoma. Comparison of Predictive Value of Intraoperative MRI and Intraoperative Histological Examination for Diagnostic Biopsy Yield. Brain and Spine, 4, Article ID: 103926. [Google Scholar] [CrossRef] [PubMed]
[18] Hu, L., Tang, J., Su, X., Zheng, L., Hu, C., Wu, Q., et al. (2024) The Utilization of Cytology for Intraoperative Diagnosis of Primary Central Nervous System Lymphoma. Scientific Reports, 14, Article No. 26527. [Google Scholar] [CrossRef] [PubMed]
[19] Scheichel, F., Pinggera, D., Popadic, B., Sherif, C., Marhold, F. and Freyschlag, C.F. (2022) An Update on Neurosurgical Management of Primary CNS Lymphoma in Immunocompetent Patients. Frontiers in Oncology, 12, Article ID: 884724. [Google Scholar] [CrossRef] [PubMed]
[20] Omid-Fard, N., Puac-Polanco, P., Torres, C.H., Hamilton, L. and Nguyen, T.B. (2024) Imaging Features of Immunodeficiency-Associated Primary CNS Lymphoma: A Review. Canadian Association of Radiologists Journal, 76, 113-121. [Google Scholar] [CrossRef] [PubMed]
[21] Chen, X., Huang, M., Zhang, Z., Jing, H., Zou, Y. and Bu, H. (2022) Primary Meningeal Central Nervous System Lymphoma: A Case Report and Literature Review. Medicine, 101, e32567. [Google Scholar] [CrossRef] [PubMed]
[22] Kim, S.Y. and Huh, H.J. (2023) Toward Standardization of Flow-Cytometric Immunophenotyping for the Diagnosis and Monitoring of Hematologic Malignancies. Annals of Laboratory Medicine, 44, 193-194. [Google Scholar] [CrossRef] [PubMed]
[23] Rimelen, V., Ahle, G., Pencreach, E., Zinniger, N., Debliquis, A., Zalmaï, L., et al. (2019) Tumor Cell-Free DNA Detection in CSF for Primary CNS Lymphoma Diagnosis. Acta Neuropathologica Communications, 7, Article No. 43. [Google Scholar] [CrossRef] [PubMed]
[24] Wang, S., Huang, K., Chou, Y., Lee, H., Wu, P., Chen, W., et al. (2023) Effect of Co-Medications and Potential Risk Factors of High-Dose Methotrexate-Mediated Acute Hepatotoxicity in Patients with Osteosarcoma. Cancer Medicine, 12, 12354-12364. [Google Scholar] [CrossRef] [PubMed]
[25] Yin, T., Liang, H., Huang, Q., Zhou, B., Tang, M., Lou, J., et al. (2023) A Survey of Therapeutic Drug Monitoring Status in China. Therapeutic Drug Monitoring, 45, 151-158. [Google Scholar] [CrossRef] [PubMed]
[26] Wang, Y.H., He, Q., Wang, F., Jiang, H., Shi, J., Ma, J., et al. (2024) Simultaneous Determination of Methotrexate Concentrations in Human Plasma and Cerebrospinal Fluid Using Two-Dimensional Liquid Chromatography: Applications in Primary Central Nervous System Lymphoma. World Journal of Oncology, 15, 825-836. [Google Scholar] [CrossRef] [PubMed]
[27] Schaff, L.R. and Grommes, C. (2022) Primary Central Nervous System Lymphoma. Blood, 140, 971-979. [Google Scholar] [CrossRef] [PubMed]
[28] Adhikari, N., Biswas, A., Gogia, A., Sahoo, R.K., Garg, A., Nehra, A., et al. (2018) A Prospective Phase II Trial of Response Adapted Whole Brain Radiotherapy after High Dose Methotrexate Based Chemotherapy in Patients with Newly Diagnosed Primary Central Nervous System Lymphoma-Analysis of Acute Toxicity Profile and Early Clinical Outcome. Journal of Neuro-Oncology, 139, 153-166. [Google Scholar] [CrossRef] [PubMed]
[29] Ferreri, A.J.M., Cwynarski, K., Pulczynski, E., Fox, C.P., Schorb, E., Celico, C., et al. (2022) Long-Term Efficacy, Safety and Neurotolerability of Matrix Regimen Followed by Autologous Transplant in Primary CNS Lymphoma: 7-Year Results of the IELSG32 Randomized Trial. Leukemia, 36, 1870-1878. [Google Scholar] [CrossRef] [PubMed]
[30] Houillier, C., Dureau, S., Taillandier, L., Houot, R., Chinot, O., Moluçon-Chabrot, C., et al. (2022) Radiotherapy or Autologous Stem-Cell Transplantation for Primary CNS Lymphoma in Patients Age 60 Years and Younger: Long-Term Results of the Randomized Phase II PRECIS Study. Journal of Clinical Oncology, 40, 3692-3698. [Google Scholar] [CrossRef] [PubMed]
[31] Grommes, C., Pastore, A., Palaskas, N., Tang, S.S., Campos, C., Schartz, D., et al. (2017) Ibrutinib Unmasks Critical Role of Bruton Tyrosine Kinase in Primary CNS Lymphoma. Cancer Discovery, 7, 1018-1029. [Google Scholar] [CrossRef] [PubMed]
[32] Grommes, C., Nandakumar, S., Schaff, L.R., Gavrilovic, I., Kaley, T.J., Nolan, C.P., et al. (2024) A Phase II Study Assessing Long-Term Response to Ibrutinib Monotherapy in Recurrent or Refractory CNS Lymphoma. Clinical Cancer Research, 30, 4005-4015. [Google Scholar] [CrossRef] [PubMed]
[33] Wang, N., Chen, F., Pan, L., Teng, Y., Wei, X., Guo, H., et al. (2023) Clinical Outcomes of Newly Diagnosed Primary Central Nervous System Lymphoma Treated with Zanubrutinib-Based Combination Therapy. World Journal of Clinical Oncology, 14, 606-619. [Google Scholar] [CrossRef] [PubMed]
[34] Grommes, C., Tang, S.S., Wolfe, J., Kaley, T.J., Daras, M., Pentsova, E.I., et al. (2019) Phase 1b Trial of an Ibrutinib-Based Combination Therapy in Recurrent/Refractory CNS Lymphoma. Blood, 133, 436-445. [Google Scholar] [CrossRef] [PubMed]
[35] Ghesquieres, H., Chevrier, M., Laadhari, M., Chinot, O., Choquet, S., Moluçon-Chabrot, C., et al. (2019) Lenalidomide in Combination with Intravenous Rituximab (REVRI) in Relapsed/Refractory Primary CNS Lymphoma or Primary Intraocular Lymphoma: A Multicenter Prospective “Proof of Concept” Phase II Study of the French Oculo-Cerebral Lymphoma (LOC) Network and the Lymphoma Study Association (LYSA). Annals of Oncology, 30, 621-628. [Google Scholar] [CrossRef] [PubMed]
[36] Tun, H.W., Johnston, P.B., DeAngelis, L.M., Atherton, P.J., Pederson, L.D., Koenig, P.A., et al. (2018) Phase 1 Study of Pomalidomide and Dexamethasone for Relapsed/refractory Primary CNS or Vitreoretinal Lymphoma. Blood, 132, 2240-2248. [Google Scholar] [CrossRef] [PubMed]
[37] Nayak, L., Iwamoto, F.M., LaCasce, A., Mukundan, S., Roemer, M.G.M., Chapuy, B., et al. (2017) PD-1 Blockade with Nivolumab in Relapsed/Refractory Primary Central Nervous System and Testicular Lymphoma. Blood, 129, 3071-3073. [Google Scholar] [CrossRef] [PubMed]
[38] Singh, A.K. and McGuirk, J.P. (2020) CAR T Cells: Continuation in a Revolution of Immunotherapy. The Lancet Oncology, 21, e168-e178. [Google Scholar] [CrossRef] [PubMed]
[39] Lacan, C., Caron, J., Tarantino, N., Fouquet, B., Cherai, M., Parizot, C., et al. (2023) CAR T-Cell Therapy for Central Nervous System Lymphomas: Blood and Cerebrospinal Fluid Biology, and Outcomes. Haematologica, 108, 3485-3490. [Google Scholar] [CrossRef] [PubMed]
[40] Ferreri, A.J.M., Cwynarski, K., Pulczynski, E., Fox, C.P., Schorb, E., La Rosée, P., et al. (2017) Whole-Brain Radiotherapy or Autologous Stem-Cell Transplantation as Consolidation Strategies after High-Dose Methotrexate-Based Chemoimmunotherapy in Patients with Primary CNS Lymphoma: Results of the Second Randomisation of the International Extranodal Lymphoma Study Group-32 Phase 2 Trial. The Lancet Haematology, 4, e510-e523. [Google Scholar] [CrossRef] [PubMed]
[41] Morales-Martinez, A., Lozano-Sanchez, F., Duran-Peña, A., Hoang-Xuan, K. and Houillier, C. (2021) Primary Central Nervous System Lymphoma in Elderly Patients: Management and Perspectives. Cancers, 13, Article No. 3479. [Google Scholar] [CrossRef] [PubMed]
[42] Rozenblum, L., Houillier, C., Soussain, C., Bertaux, M., Choquet, S., Galanaud, D., et al. (2022) Role of Positron Emission Tomography in Primary Central Nervous System Lymphoma. Cancers, 14, Article No. 4071. [Google Scholar] [CrossRef] [PubMed]
[43] Li, Y., Mo, Y., Chen, M., Zhang, W., Li, S. and Zhang, X. (2024) The Prognostic Significance of Pontine-White Matter Score in Primary Central Nervous System Lymphoma Patients. Cancers, 16, Article No. 2708. [Google Scholar] [CrossRef] [PubMed]
[44] King, R.L., Goodlad, J.R., Calaminici, M., Dotlic, S., Montes-Moreno, S., Oschlies, I., et al. (2019) Lymphomas Arising in Immune-Privileged Sites: Insights into Biology, Diagnosis, and Pathogenesis. Virchows Archiv, 476, 647-665. [Google Scholar] [CrossRef] [PubMed]
[45] Yamaguchi, J., Ohka, F., Lushun, C., Motomura, K., Aoki, K., Takeuchi, K., et al. (2022) cd79by196 Mutation Is a Potent Predictive Marker for Favorable Response to R-MPV in Primary Central Nervous System Lymphoma. Cancer Medicine, 12, 7116-7126. [Google Scholar] [CrossRef] [PubMed]

为你推荐