What is PCNS Lymphoma?
Primary central nervous system (PCNS) lymphoma is a rare but highly aggressive cancer that develops within the central nervous system (CNS). This differs from secondary CNS lymphoma, where lymphoma starts outside the central nervous system and later spreads to the brain, spinal cord, or surrounding tissues. In addition to the brain and spinal cord, PCNS lymphoma can also involve the eyes and the cerebrospinal fluid (CSF) that surrounds the brain and spinal cord.
PCNS lymphoma is a type of non-Hodgkin lymphoma that arises from lymphocytes, usually B cells, a type of white blood cell involved in fighting infections. These cells are normally part of the body’s lymphatic and immune systems.
PCNS lymphoma most commonly affects adults over 60 years of age. People with weakened immune systems, including those with HIV infection, organ transplants, or certain inherited immune disorders also have a higher risk of developing the disease.
PCNS Lymphoma Symptoms
PCNS lymphoma can cause a wide range of symptoms depending on which part of the brain, spinal cord, or eyes is affected.
Symptoms could include:
- Headaches
- Seizures, although these are less common
- Confusion due to effects on cognitive function
- Confusion, personality changes, or problems with memory, concentration, and thinking
- Lethargy or persistent fatigue
- Hemiparesis, or weakness on one side of the body
- Back pain, weakness, numbness, or bladder and bowel problems when the spinal cord is involved
- Blurred vision or floaters when the eyes are affected
How Is PCNS Lymphoma Diagnosed?
Diagnosis of PCNS lymphoma usually begins with a contrast-enhanced MRI scan of the brain. If a patient has symptoms suggesting spinal cord involvement, doctors may also order an MRI of the spinal cord to check for tumour involvement within the CNS.
Doctors may also perform a lumbar puncture, also known as a spinal tap, to examine the cerebrospinal fluid (CSF) for lymphoma cells. This allows them to examine the CSF for lymphoma cells that may have spread through the fluid surrounding the brain and spinal cord.
Doctors may also arrange an ophthalmic examination, including a slit-lamp examination, to determine whether the lymphoma has involved the eye.
To confirm that the lymphoma is confined to the CNS, the healthcare team may request whole-body PET/CT imaging and, in selected cases, a bone marrow biopsy to look for evidence of lymphoma elsewhere in the body.
Although imaging can strongly suggest PCNS lymphoma, doctors usually confirm the diagnosis with a stereotactic biopsy. This procedure allows specialists to examine tumour tissue under the microscope and distinguish PCNS lymphoma from other conditions that can appear similar on imaging, including glioblastoma, brain metastases, inflammatory disorders, and demyelinating disease.
Living With
CNS Lymphoma
Living with PCNS lymphoma can be challenging for both patients and their families. Treatment often involves high-dose chemotherapy, sometimes combined with radiotherapy or other consolidation treatments. While these treatments can control the tumour, they may also cause significant long-term side effects, particularly neurotoxicity.
These complications can be particularly challenging in older adults, who are more vulnerable to treatment-related cognitive side effects. For this reason, doctors may avoid or delay whole brain radiotherapy (WBRT) in older patients whenever possible.
After treatment, patients may experience difficulties with attention, planning, memory, and learning. Patients may also notice problems with balance, movement, or motor coordination. These changes can affect daily activities and quality of life over time.
Regular follow-up is an important part of care after treatment. Patients usually undergo MRI scans after treatment to monitor for tumour recurrence and treatment-related effects.
After treatment, your healthcare team will create a personalised follow-up plan based on your needs. This plan may involve several specialists who can help manage long-term symptoms and support life after treatment.
CNS Lymphoma Treatment and Management Options
Treatment for PCNS lymphoma usually begins with combination chemotherapy. The most important drug used is high-dose methotrexate. Doctors give methotrexate at high doses because it does not easily cross the blood–brain barrier (BBB). Higher doses help enough of the drug reach the cerebrospinal fluid (CSF) and target tumour cells effectively.
Depending on the patient’s age, overall health, and response to treatment, chemotherapy may be followed by consolidation therapy such as reduced-dose whole-brain radiotherapy (WBRT) or autologous stem cell transplantation. Combination treatment strategies generally provide better long-term disease control than single-modality treatment alone. However, these treatments can cause significant side effects, especially neurotoxicity, which may affect brain function and cognition.
To lower the risk of treatment-related neurotoxicity, doctors may avoid or delay WBRT in older patients whenever possible. These patients may instead receive chemotherapy-based treatment strategies that minimise exposure to WBRT.
Surgery is usually not recommended for PCNS lymphoma. Removing the tumour does not improve survival compared with performing a stereotactic biopsy to confirm the diagnosis. In addition, these tumours often develop deep within the brain, where surgery carries a high risk of damaging healthy brain tissue.
If the lymphoma returns after treatment, doctors may use high-dose chemotherapy followed by autologous stem cell transplantation. Although this approach may help control the disease, it can also cause substantial side effects and toxicity.
CNS lymphoma often requires intensive treatment, including high-dose chemotherapy, which can place significant physical and emotional strain on both patients and carers.
For families, this can mean managing complex treatment schedules, hospital stays, and changes in cognitive or physical function.
Support is available to help you through this. The National Advocacy Service can help you navigate treatment pathways, access services, and advocate for appropriate care. Our Support Hub also offers practical information and resources for carers and families.
References
- Batchelor, T., & Loeffler, J. S. (2006/03/10). Primary CNS Lymphoma. Journal of Clinical Oncology, 24(8), 1281-1288. https://doi.org/10.1200/JCO.2005.04.8819
- de Koning, M. E., Hof, J. J., Jansen, C., Doorduijn, J. K., Bromberg, J. E. C., & van der Meulen, M. (2024, 2024/05/01). Primary central nervous system lymphoma. Journal of Neurology, 271(5), 2906-2913. https://doi.org/10.1007/s00415-023-12143-w
- Hoang-Xuan K, Deckert M, Ferreri AJM, Furtner J, Gallego Perez-Larraya J, Henriksson R, Hottinger AF, Kasenda B, Lefranc F, Lossos A, McBain C, Preusser M, Roth P, Rudà R, Schlegel U, Soffietti R, Soussain C, Taphoorn MJB, Touitou V, Weller M, Bromberg JEC. European Association of Neuro-Oncology (EANO) guidelines for treatment of primary central nervous system lymphoma (PCNSL). Neuro Oncol. 2023 Jan 5;25(1):37-53. doi: 10.1093/neuonc/noac196. PMID: 35953526; PMCID: PMC9825335.
- Giannini, C., Dogan, A., & Salomão, D. R. (2014). CNS Lymphoma: A Practical Diagnostic Approach. Journal of Neuropathology & Experimental Neurology, 73(6), 478-494. https://doi.org/10.1097/NEN.0000000000000076
- Pertz, M., Kowalski, T., Thoma, P., & Schlegel, U. (2021). What Is on Your Mind? Impaired Social Cognition in Primary Central Nervous System Lymphoma Patients Despite Ongoing Complete Remission. Cancers, 13(5), 943. https://www.mdpi.com/2072-6694/13/5/943