Primary CNS Lymphoma (PCNSL)
40% of all cancers spread to the brain
What is primary brain / CNS lymphoma (PCNSL)?
PCNSL is a rare form of non-Hodgkin lymphoma, which in more than 90% cases is a specific type called diffuse large B-cell lymphoma (DLBCL). Lymph cells are part of the body’s immune system and help to fight infection.
This condition is called “primary” CNS lymphoma because it starts in the lymph tissue of the brain and/or spinal cord, which together form the central nervous system (CNS). A lymphoma that starts in another part of the body but is also in the brain at diagnosis, or spreads there later, is called a secondary CNS lymphoma.
B-cells are a specialised type of lymphocyte (white blood cell). The abnormal B-cells that cause PCNSL are referred to as lymphoma cells, to indicate that they are cancerous.
Healthy lymphocytes play a crucial role in the body’s immune system and are divided into 3 types, each with a specialised role in helping our bodies to fight infections.
B-cells mature in the bone marrow of humans and have a protein on their surface known as the B-cell receptor. This protein is able to recognize and attach to specific antigens, which are markers on others cells that indicate potential threats to the human body. The B-cells attach to these antigens and then stimulate the production of antibodies that can neutralise or kill the potentially dangerous antigen and the molecule or cell to which it is attached. Memory B-cells are able to remember such antigens, enabling a faster and more effective response if the antigen is identified again in the future.
T-cells are formed in the thymus gland. T-cells divide into subsets of T-cells that have a range of functions, including stimulating the production of antibodies by B-cells.
Natural killer cells are lymphocytes that have the ability to kill other cells. They are able to recognize viruses and some types of tumour cells, and are designed to kill these cells before they cause harm.
Where does primary CNS lymphoma (PCNSL) occur?
Primary central nervous system (CNS) lymphoma can arise anywhere within the lymph tissue situated in the brain or spinal cord. It can also arise within the eye and spread into the CNS, in which case the original tumour in the eye would be classified as intra-ocular lymphoma.
Is primary CNS lymphoma (PCNSL) cancer?
Yes, unfortunately primary CNS / brain lymphoma is a form of cancer.
How common is primary CNS lymphoma (PCNSL)?
PCNSL accounts for about 2% to 5% of all primary brain tumours. It has an incidence of around 2.7 cases per million people per year.
The incidence of PCNSL rose during the 1990s due to increasing numbers of people with HIV/AIDS who also developed the condition, but with improvements in the management of HIV/AIDS these figures are now decreasing again. However, the exact figure of incidence within this patient population remains unclear.
Amongst patients with a well functioning immune system, PCNSL is usually diagnosed in people who are, on average, around 62 years old. However, this statistic does not reflect patients who are younger and have been living with a compromised immune system before developing PCNSL.
An estimated 58% of PCNSL patients are male.
Primary CNS lymphoma (PCNSL) prognosis
Unfortunately, overall survival (OS) is still poor for PCNSL and ranges between 10.9 and 61.9 months.
The prognosis is better for patients who are not living with a condition such as HIV/AIDS that results in a compromised immune system.
The prognosis is also influenced by factors such as age (younger being more favourable) and the regions of the brain that are affected by the cancer.
Treatment protocols are still developing for this disease and offer much hope for the future. For example, younger patients offered combined high‐dose chemotherapy with autologous stem cell transplantation (ASCT) followed by hyperfractionated whole
brain radiotherapy have been recorded in one study as having a five‐year overall survival (OS) rate of 87%.
Primary CNS lymphoma (PCNSL) classification
There is no standard staging system for PCNSL. Instead, scans are used to establish where the cancer has spread and whether it is contained within the CNS, so that the most effective treatment plan can be developed.
PCNSL is classed as “recurrent” if it returns after treatment.
Where are the symptoms of primary CNS lymphoma (PCNSL)?
The signs and symptoms vary between patients and depend on which parts of the central nervous system are affected, but may include:
- Nausea and vomiting
- Changes in personality or behaviour
- Double vision
- Hearing loss
- Problems with balance and/or co-ordination
- Numbness, tingling or weakness, particularly in arms and/or legs
You can read more about brain tumour symptoms here.
What causes primary CNS lymphoma (PCNSL)?
The direct cause of primary CNS lymphoma has not been clearly defined. Certain groups of people have an increased risk of developing this disease:
- People who have taken immune-suppressive drugs over a long period of time, for example to support an organ donation or control an autoimmune disease
- People with a weakened immune system, such as those diagnosed with human immunodeficiency virus (HIV) or acquired immune deficiency syndrome (AIDS)
However, most people diagnosed with PCNSL do not have other diseases related to immune system function and are referred to as “immunocompetent”, meaning that their immune system is functioning normally.
Primary CNS lymphoma (PCNSL) treatment
Initially, patients may be offered steroids to reduce swelling in the brain and hence reduce symptoms caused by PCNSL. Anti-convulsant medication would also be offered if seizures are present.
Chemotherapy, targeted therapy drugs, radiotherapy and stem cell transplants are all forms of treatment that would be considered for patients with PCNSL.
Chemotherapy and drug treatment for PCNSL
The main treatment for PCNSL is usually chemotherapy and a targeted monoclonal antibody therapy drug called rituximab. Rituximab attaches itself to a protein on the surface of lymphoma cells, making it easier for the body’s immune system to recognise and then destroy these faulty B-cells.
Chemotherapy drugs act in a more general way to target all fast-dividing cells within the body, including cancer cells. The most common chemotherapy drug for PCNS is high-dose methotrexate (HD-MTX), which would be given intravenously (in liquid form, directly into a vein), possibly alongside other chemotherapy drugs such as cytarbine or thiotepa.
Patients may also be offered temozolomide and procarbazine in tablet forms, which are used for a range of brain tumours.
Radiotherapy for PCNSL
After chemotherapy, most patients are offered radiotherapy to help kill any remaining cancer cells. This may take the form of whole brain radiotherapy (WBRT) if there are cells distributed throughout the brain, or could be targeted at a certain area such as the eye.
Autologous stem cell transplant for PCNSL
This is an intensive form of treatment that is not offered to every patient, as they need to be robust enough to be able to cope with the treatment regime and then to recover and thrive afterwards.
After initial treatment to reduce the number of PCNSL cells, some of the patient’s healthy stem cells are collected from a blood sample and stored. High dose chemotherapy is then used to destroy as much of the lymphoma as possible, before the healthy
stem cells are returned to the patient via a drip (like a blood transfusion) to help the body recover from the high dose chemotherapy.
There is more detailed information about treatments on our treatments pages.
How can we find a cure for primary CNS lymphoma (PCNSL) in the UK?
Research we are funding across all of our dedicated Research Centres will help lead towards finding a cure for a wide range of brain tumours.
Our team at the University of Plymouth Low-Grade Brain Tumour Research Centre are researching a number of molecular pathways that influence
immune system function, tumour metabolism and tumour growth in a range of low-grade brain tumours in children and adults.
The team of research and clinical experts in our Research Centre at Imperial College, London, are studying the way in which the ketogenic diet works in brain cancer, which may have the potential to influence a wide range of brain tumours.
Pioneering research at our Brain Tumour Research Centre at Queen Mary University of London is focused on using GBM stem cells to help develop unique, patient-specific treatments. Their findings are expected to translate into other types of adult and paediatric brain tumours in the future.
We also fund BRAIN UK at Southampton University, the country’s only national tissue bank registry providing crucial access to brain tumour samples for researchers from all clinical neuroscience centres in the UK, effectively covering about 90% of the UK population, and an essential component in the fight to find a cure for CNS tumours.