Isolated primary CNS lymphoma: a case report and a contemporary review

Abstract

Primary central nervous system lymphoma is a rare form of extranodal non-Hodgkin lymphoma that is confined to the brain, spinal cord, leptomeninges, or eyes, representing less than one percent of all non-Hodgkin lymphomas and approximately four percent of primary brain tumors. When the disease is truly isolated to the central nervous system, with no evidence of systemic spread, it poses unique diagnostic and therapeutic challenges, particularly in immunocompetent patients. We reviewed nine recently published cases from 2021 to 2024 that described isolated primary central nervous system lymphoma without extracranial involvement. Patients ranged in age from forty-four to eighty-five years, with both immunocompetent and immunosuppressed individuals represented. Presenting symptoms include focal neurological deficits, seizures, progressive confusion, cranial neuropathies, and neurolymphomatosis. Magnetic resonance imaging findings were diverse, including intra-axial masses, leptomeningeal and cranial nerve enhancement, and mass effect. Cerebrospinal fluid analysis was variably positive for lymphoma cells. Histopathological analysis confirmed diffuse large B-cell lymphoma in all cases, although initial biopsies were sometimes inconclusive, underscoring the importance of repeat tissue sampling and expert pathology review. Treatment strategies most often included high-dose methotrexate-based chemotherapy, monoclonal antibody therapy, and radiotherapy, with some patients undergoing surgical decompression or diagnostic craniotomy. Follow-up data revealed variable survival outcomes, with a subset of patients achieving disease-free survival beyond one year. These cases highlight the wide clinical spectrum and diagnostic complexity of isolated primary central nervous system lymphoma and reinforce the need for a high index of suspicion, timely advanced imaging, multidisciplinary discussion, and appropriate tissue diagnosis to guide individualized management.

Keywords

primary central nervous system lymphoma / diffuse large B-cell lymphoma / immunocompetent / magnetic resonance imaging / brain biopsy / methotrexate-based chemotherapy / diagnostic challenges / case report

References

[1] Haldorsen IS,Espeland A,Larsson EM.Central nervous system lymphoma: characteristic findings on traditional and advanced imaging.AJNR Am J Neuroradiol.2011;32:984-92.

[2] Shah T,Venur VA.Central Nervous System Lymphoma.Semin Neurol.2023;43:825-32.

[3] Hoang-Xuan K,Deckert M,Ferreri AJM,Furtner J,Gallego Perez-Larraya J,Henriksson R,et al.European Association of Neuro-Oncology (EANO) guidelines for treatment of primary central nervous system lymphoma (PCNSL).Neuro Oncol.2023;25:37-53.

[4] Lauw MIS,Lucas CG,Ohgami RS,Wen KW.Primary Central Nervous System Lymphomas: A Diagnostic Overview of Key Histomorphologic, Immunophenotypic, and Genetic Features.Diagnostics (Basel).2020;10:1076.

[5] van der Sanden GA,Schouten LJ,van Dijck JA,van Andel JP,van der Maazen RW,Coebergh JWWorking Group of Specialists in Neuro-Oncology in the Southern and Eastern Netherlands.Primary central nervous system lymphomas: incidence and survival in the Southern and Eastern Netherlands.Cancer.2002;94:1548-56.

[6] Villano JL,Koshy M,Shaikh H,Dolecek TA,McCarthy BJ.Age, gender, and racial differences in incidence and survival in primary CNS lymphoma.Br J Cancer.2011;105:1414-8.

[7] Ferreri AJM,Calimeri T,Cwynarski K,Dietrich J,Grommes C,Hoang-Xuan K,et al.Primary central nervous system lymphoma.Nat Rev Dis Primers.2023;9:29.

[8] DeAngelis LM.Primary central nervous system lymphoma.J Neurol Neurosurg Psychiatry.1999;66:699-701.

[9] de Koning ME,Hof JJ,Jansen C,Doorduijn JK,Bromberg JEC,van der Meulen M.Primary central nervous system lymphoma.J Neurol.2024;271:2906-13.

[10] Zayed A,Abdoh Q,Sarama A,Shubietah A.Isolated primary CNS lymphoma after liver transplantation for autoimmune hepatitis: a case report.BMC Neurol.2024;24:305.

[11] Schuster Bruce A,Grammatopoulou V.Primary Skull Base Lymphoma Presenting With Ipsilateral Abducens Nerve Palsy: A Case Report.Cureus.2024;16:e73108.

[12] Kim H,Kim D,Kim S.Primary Malignant Lymphoma Presenting as an Isolated Epidural Mass.Diagnostics (Basel).2022;12:2462.

[13] Chen X,Huang M,Zhang Z,Jing H,Zou Y,Bu H.Primary meningeal central nervous system lymphoma: A case report and literature review.Medicine (Baltimore).2022;101:e32567.

[14] Lobban GB,Luke AJ,Basta P,Laziuk K,Kalra A,Kulhari A.Primary Central Nervous System Lymphoma Presenting as Isolated Multiple Cranial Neuropathies: An Extremely Rare Case.Cureus.2023;15:e41561.

[15] Khanna G,Ahlawat S,Garg N,Gupta R,Patir R.A Rare Case of Isolated Intraventricular Primary Central Nervous System Lymphoma in an 85-Year-Old Man.Asian J Neurosurg.2021;16:623-5.

[16] Sheng S,Sharma R,Samant R,Yuan J,Nalleballe K,Kapoor N.Isolated primary neurolymphomatosis with cranial multineuritis: a case presentation.Neurol Sci.2021;42:1223-6.

[17] Xue Y,Liu CC,Xiang YY,Liu XH.Primary central nervous system lymphoma initially manifesting as cerebral white matter lesions followed by isolated extracerebral relapse: a case report.Neurol Sci.2021;42:4825-8.

[18] Cheng L,Zhu H,Wang J,Wang G,Ma X,Zhao K,et al.Clinical Features, Diagnosis, and Treatment of Primary Intraventricular Lymphoma: Insights From a Monocentric Case Series.Front Neurol.2022;13:920505.