CNS Lymphoma

Primary central nervous system lymphoma (PCNSL) is a rare, aggressive (fast growing) B-cell non-Hodgkin lymphoma, that develops in the brain and or the spinal cord.

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Primary central nervous system lymphoma (PCNSL) fact sheet PDF

Overview of primary central nervous system lymphoma (PCNSL)

Primary central nervous system lymphoma (PCNSL) is a rare, aggressive (fast growing) B-cell non-Hodgkin lymphoma.  This type of lymphoma is found in the central nervous system (CNS).  CNS lymphoma mainly affects the brain.  Around 1 in 50 brain tumours are a type of CNS lymphoma.

There are 4 subtypes of CNS lymphoma

  • Primary central nervous system lymphoma
  • Secondary central nervous system
  • Intraocular lymphoma
  • Diffuse meningeal lymphoma

When lymphoma has originated in other parts of the body and at some stage has spread to the brain or spinal cord it is referred to as secondary CNS lymphoma (SCNSL)

What is the central nervous system (CNS)?

The central nervous system (CNS) is the part of the body that controls all body functions.  It includes the brain, spinal cord and eyes. 

The brain is made up of:

  • The cerebrum: this controls our speech and understanding, our sensations and voluntary movement (the movements we decide to make)
  • The cerebellum: helps with movements and controls our balance
  • The brainstem: controls essential body functions, such as our breathing, heart rate and blood pressure.

The spinal cord runs from the brain down the back within the bones of the spine.  A series of nerves join directly onto the spinal cord.  The nerves carry information about sensation from around the body and transmit messages to control the muscles of the body.

The CNS is protected from the rest of your body in several ways.

  • The meninges are protective layers of tissue that cover the brain and spinal cord – this is what becomes inflamed in ‘meningitis’.
  • A special fluid called ‘cerebrospinal fluid’ (CSF) surrounds the brain and spinal cord to cushion them.   It is found in the space between the meninges and the brain and spinal cord.
  • The blood-brain barrier surrounds the brain.  It is a barrier of cells and blood vessels that only lets certain substances reach the brain to protect it from harmful chemicals and infections.  It also prevents or interferes with many chemotherapy drugs passing from the blood to the brain.

Note: This protection is very important, but it prevents many drugs from reaching lymphoma in the CNS.

Types of central nervous system (CNS) lymphoma

Lymphoma in the central nervous system (CNS) is usually an aggressive (fast-growing) lymphoma and is most often a form of diffuse large B-cell lymphoma.  Indolent (slow growing) lymphoma can also develop in. or around the brain, but only around 1 in 20 people diagnosed with CNS lymphoma are indolent lymphoma.

There are different types of CNS lymphoma that affect different parts of the CNS and these  include:  

Primary CNS lymphoma (PCNSL)

This subtype of lymphoma is found in the central nervous system (CNS) and usually develops as one or more lumps mainly in the brain.  Around 1 in 50 brain tumours are a type of CNS lymphoma.

It is called primary central nervous system lymphoma (PCNSL) as the lymphoma cells originally form in the brain and or the spinal cord. In more than 90% of cases it is a B-cell lymphoma that may develop in the brain, spinal cord, eye or leptomeninges (the inner two membranes surrounding the brain and spinal cord).

Intraocular lymphoma

Primary CNS lymphoma can affect the eyes.  In most cases, the lymphoma is in other parts of the CNS as well as the eyes.  If lymphoma is found only in the eyes, it is called ‘primary intraocular lymphoma’.

Secondary CNS lymphoma

Secondary CNS lymphomais lymphoma that has started elsewhere but has spread to the CNS or has relapsed (come back) in the CNS.

Diffuse meningeal lymphoma

Diffuse meningeal lymphomais a lymphoma that is spread out (diffuse) only within the meninges rather than forming a lump.  It is usually a form of secondary CNS lymphoma.

There is no standard treatment for this lymphoma. Treatment is most likely to be repeated doses of high-dose methotrexate. This may be given intravenously (into the bloodstream) or intrathecally (into the cerebrospinal fluid).

Who is affected by primary central nervous system lymphoma (PCNSL)?

The cause of primary central nervous system lymphoma (PCNSL) is unknown as is the case of many lymphomas.  People are most likely to be affected between the age of 50-60 years. The average age at diagnosis is around 60 years, however it can occur at any age. 

PCNSL is slightly more common in people who have a weakened immune system, which may be caused by:

  • HIV (human immunodeficiency virus) infection: this is less common now that there are good antiviral treatments available
  • Medications that are used to suppress the immune system, such as after an organ transplant or other types of immunosuppressive treatment for autoimmune disorders, for example. rheumatological conditions.

Indolent lymphomas in the CNS, such as MALT lymphoma, are rare and usually occur in younger people.

People with the fastest growing types of high-grade non-Hodgkin lymphoma (NHL), for example Burkitt lymphoma, are at the highest risk of developing secondary CNS lymphoma. This occurs when lymphoma has spread from other parts of the body to the CNS.  Some people diagnosed with aggressive non-Hodgkin lymphoma are offered treatment that aims to prevent the spread of lymphoma to the CNS.  This treatment is called ‘CNS prophylaxis’.

Most people with these risk factors, however, do NOT develop PCNSL.

Symptoms of primary central nervous system lymphoma (PCNSL)

The symptoms of primary or secondary central nervous system lymphoma (PCNSL) depend on where the lymphoma is and how much lymphoma there is in the body. Lymphoma in certain parts of the brain could block the flow of CSF (cerebrospinal fluid). The build-up of CSF can cause intracranial pressure around the brain. Symptoms may include:

  • Headaches
  • Nausea and vomiting
  • A change in consciousness (becoming drowsy and unresponsive)
  • Seizures (fits)

Less obvious symptoms may include:

  • Vague confusion
  • Personality changes such as irritability
  • Expressive dysphasia which is difficulty finding the right word even though it may be something quite simple.
  • Poor attention

Other reported symptoms may include:

  • Muscle weakness in a specific limb
  • Problems with balance.

Symptoms of intraocular lymphoma

Intraocular lymphoma can affect one or both eyes in some people.  Not everyone with CNS lymphoma involving the eye notices a change in their vision but common symptoms may include:

  • Blurred vision
  • Floaters (small dots or spots that seem to float quickly across your vision).
  • Decrease or loss of vision
  • Redness or swelling of the eye
  • Increased sensitivity to light
  • Very rarely eye pain
  • May experience other central nervous system symptoms

In most patients, the lymphoma is found in the eye and in other parts of the CNS.  Patients can often have a mixture of symptoms and rarely, only the eye is affected (primary intraocular lymphoma).

Symptoms of diffuse meningeal lymphoma

Diffuse meningeal lymphoma causes similar symptoms to other CNS lymphomas.  The symptoms may be milder and less obvious than those that occur when there is a lymphoma mass (lump).  The most common are cranial nerve palsies. This occurs mainly in the facial nerve and the abducens nerve. A damaged abducens nerve can result in double vision and strabismus (eyes are not aligned).

Symptoms of spinal cord compression

It is very uncommon for CNS lymphoma to develop in the spinal cord.  However, other types of lymphoma can affect the spinal cord by pressing on it, causing spinal cord compression.  Spinal cord compression can happen with most types of lymphoma, but it is rare.

When the lymphoma compresses the spinal cord, a number of symptoms can be experienced that may include:

  • Weakness and in some cases paralysis, most often affecting the legs but sometimes also the arms and chest or abdomen (stomach)
  • Loss of sensation or a change in sensation, most often affecting the legs but sometimes also the arms, chest or abdomen
  • A change in bowel function, such as constipation or bladder function, such as not being able to pass urine.
  • A sensation around the anus (bottom)
  • Back pain

If you have symptoms of a spinal cord compression, you need to let your medical team know immediately.  It is important that it is diagnosed urgently, and immediate treatment gives you a better chance of your nerves recovering well. 

Diagnosis of primary central nervous system lymphoma (PCNSL)

biopsy is always required for diagnosis of lymphoma. A biopsy is a surgical procedure to remove part of or all of an affected lymph node or other tissue to look under the microscope by a pathologist to see what the cells look like.  The biopsy can be done under local or a general anaesthetic depending on what part of the body is being biopsied.  The type of biopsy to be done will depend on where the lymphoma is located. The biopsy could be one of the below:

  • If the lymphoma is in another part of the body as well as in the CNS, the biopsy is likely to be taken from outside the CNS.
  • If the lymphoma is only in the brain, a neurosurgeon (a specialist in diagnosing and treating problems with the CNS) takes a brain biopsy.  Lumps within the brain are biopsied using a CT scan to help guide the biopsy needle to the right area.  This is called a ‘stereotactic biopsy’.  A general anaesthetic for the biopsy will be needed as it is important not to move.
  • If the lymphoma is only in the eye, an ophthalmologist (specialist in diseases and injuries of the eye) may take a little of the vitreous (gel-like substance inside your eye) to check for lymphoma cells.
  • If there is lymphoma in the spine, a specialist radiologist may take a biopsy from the spine

Before the test, the medical team should explain the procedure and answer all questions.  

Waiting for test results can be a difficult time.  It may help to talk to family, friends or a specialist cancer nurse.

For more info see
Tests, Diagnosis and Staging

What is the ‘grade’ of lymphoma?

Lymphomas are also often grouped as either indolent or aggressive.  Indolent lymphomas are usually slow growing and aggressive lymphomas are fast growing.  The grade is also referred to as the clinical behaviour of the lymphoma.  PCNSL is a high-grade lymphoma.  

Staging of primary central nervous system lymphoma (PCNSL)

Once a diagnosis of PCNSL is made, there are further tests that are required to see where else in the body the lymphoma has affected or is located.  This is called staging.  It is important to know the stage and grade of the lymphoma to help the medical team determine the best treatment for the patient.  

Some of the tests needed for staging can include:

  • Magnetic resonance imaging (MRI) scans, which usually give the best images of the brain and other parts of the CNS and can also detect spinal cord compression
  • Computed tomography (CT) scan, which are usually used to detect lymphoma elsewhere in the body, but may be used to look at the bones on the spine
  • Positron emission tomography (PET)scan, which are often used in combination with a CT scan to detect active lymphoma elsewhere in the body
  • Bone Marrow Biopsy, to look for lymphoma in the bone marrow
  • Lumbar puncture, this is to take a sample of CSF to look for lymphoma cells
  • A testicular ultrasound for men, as some secondary CNS lymphomas can start in the testes

Patients may also undergo a number of baseline tests prior to any treatment commencing to check organ functions.  These are often repeated during and after the treatment has completed to assess whether the treatment has affected the functioning of organs.  Sometimes the treatment and follow-up care may need to be adjusted to help manage side effects. These may include:

  • Physical examination
  • Vital observations (blood pressure, temperature, & pulse rate)
  • Heart scan
  • Kidney scan
  • Breathing tests
  • Blood tests

Many of these staging and organ function tests are performed again after treatment to check whether the lymphoma treatment has worked and the effect this has had on your body.

For more info see
Staging Scans & Tests

Prognosis of primary CNS lymphoma

Reading into survival statistics can be confusing and difficult to understand, as it is   providing information about a group of people in the past.  They also do not consider an individual’s health   It is best to speak with the treating doctor to know the prognosis for an individual patient.

Treatment strategies for primary CNS lymphoma (PCNSL) have improved greatly over recent years. However, PCNSL can be difficult to treat and some treatments have a risk of causing long-term neurological problems (problems with the brain and eyes).  These problems become more likely with older patients when they are diagnosed with CNS lymphoma.  

The medical team will look at the general health or risk factors for the patient before deciding on the right treatment. 

Treatment of primary CNS lymphoma 

Once all the results from the biopsy and the staging scans have been completed, the doctor will review these to decide the best possible treatment for a patient.   At some cancer centres, the doctor will also meet with a team of specialists to discuss the best treatment and this is called a multidisciplinary team (MDT)meeting.  

Doctors take into consideration many factors about the lymphoma and the patient’s general health to decide when and what treatment is required.

  • The type of CNS lymphoma 
  • Where the lymphoma is growing
  • How it is affecting the patients (symptoms)
  • How urgently is treatment
  • Age, past medical history and general health
  • Personal preferences

The doctor and/or cancer nurse will explain the treatment plan and the possible side-effects. It is important you understand the treatment plan and ask questions. 

Steroid treatment

The first treatment is usually steroids to help reduce swelling in the tissues around the lymphoma. This helps to reduce some of the symptoms. Steroids are usually started after any biopsies have been taken because the lymphoma can be harder to diagnose if the steroids have already been given.  The doctor might suggest starting steroids straight away if the chances of having CNS lymphoma is high, particularly if there are symptoms, as steroids can reduce symptoms until other treatment starts.  

Steroids also help to shrink the lymphoma. Steroids are often used while a diagnosis is being confirmed. Steroids can be intravenous (through a vein) or oral (by mouth). A common steroid used is Dexamethasone.

Side effects of steroids may include:

  • Difficulty sleeping (best to give steroids in the morning)
  • Increased blood sugar levels
  • Changes in mood and behaviour (this can sometimes be confused with symptoms for CNS lymphoma)

Chemotherapy 

Chemotherapy that can cross the blood-brain barrier is the main treatment for primary CNS lymphoma. Chemotherapy in combination with immunotherapy (such as rituximab) are often used.  The standard first-line treatment can include:

  • High dose methotrexate combined with or without the monoclonal antibody rituximab is given. 
  • MATRix (methotrexate, cytarabine thiotepa and Rituximab) newly diagnosed (PCNSL).
  • Methotrexate and Cytarabine– newly diagnosed (PCNSL)
  • Consolidation treatment is offered to younger patients. This is the either radiotherapy or high dose chemotherapy and stem cell transplant to decrease the risk of PCNSL ever coming back
  • Intrathecal chemotherapy is chemotherapy that is given into the spinal fluid by means of a lumbar puncture. This is done if lymphoma cells are found in spinal fluid.
  • Clinical trial participation

If the lymphoma responds to chemotherapy, the medical team may suggest whole-brain radiotherapy or an autologous stem cell transplant.  These are consolidation treatments, which means they are used to reduce the risk of relapse after successful treatment.

For more info see
Treatments

Whole-brain radiotherapy is usually used as a consolidation treatment after chemotherapy.  Until the mid-1990’s it was the main treatment for PCNSL.  It is now given in combination with chemotherapy. It is a type of external radiation therapy given to the whole brain over a period of a few weeks. Consolidation treatments aim to reduce the risk of relapse (lymphoma returning). Radiotherapy can be used on its own if the patient is unable to tolerate chemotherapy. 

Side effects of whole-brain radiotherapy include:

  • Worsening of symptoms at beginning of treatment
  • Fatigue: can take some months after treatment
  • Poor memory
  • Poor attention
  • Problems with language
  • Slowness physically and mentally (movement and speech)
  • Difficulties solving problems, planning and making decisions

These side effects might be referred to as ‘cancer related cognitive impairment’.

Indolent (slow growing) CNS lymphoma

Indolent (slow growing) CNS lymphomas are rare.  They usually respond very well to treatment, typically radiotherapy.  Sometimes surgery to remove the lump is all that is needed for low-grade CNS lymphoma

Intraocular lymphoma

Chemotherapy is given to most patients with intraocular lymphoma. Chemotherapy given is usually high-dose methotrexate. Chemotherapy may be given straight into the eye. This is called intravitreal chemotherapy. Rituximab may or may not be given

Chemotherapy is usually then followed by stem cell transplant and/or radiotherapy.

Side effects of radiotherapy may include:

  • Loss of eyelashes (temporary)
  • Dry eyes
  • Cataracts (you might need to have cataract surgery in the future)
  • Glaucoma

Treatment for secondary CNS lymphoma

Secondary CNS lymphoma might be found as lumps within the brain or occasionally in the meninges (diffuse meningeal lymphoma).  Lymphoma can relapse only in the CNS or might be found elsewhere in the body at the same time or shortly after.  Symptoms usually develop quickly.

Because secondary CNS lymphoma has spread from elsewhere in the body, treatment is usually given that can reach the CNS and the rest of the body.  If the patient is fit enough, this might be high dose chemotherapy including drugs that can reach the CNS.  This is sometimes called ‘salvage’ therapy.

Salvage chemotherapy often includes intrathecal chemotherapy, where chemotherapy is injected directly in the CNS during a lumbar puncture.  Only a limited number of drugs, including methotrexate, cytarabine and hydrocortisone (a steroid), can be safely given this way.

If the chemotherapy is given intrathecally, it may be given through an Ommaya reservoir, which is a plastic device placed under the scalp.  It avoids the need for repeated lumbar punctures.

If chemotherapy controls the lymphoma, a stem cell transplant can be given to increase the chance of remission (no evidence of lymphoma).

For patients who are not fit enough for chemotherapy or the lymphoma does not respond to treatment the doctor might suggest palliative radiotherapy to ease symptoms.

Treatment diffuse meningeal lymphoma

There is no standard treatment for this lymphoma. Treatment is most likely to be repeated doses of high-dose methotrexate. This may be given intravenously (into the bloodstream) or intrathecally (into the cerebrospinal fluid).

Treatment spinal cord compression

The first treatment is likely to be a steroid such as dexamethasone.  Steroids can help reduce swelling and ease the pressure on the nerves.  They may also shrink the lymphoma for a short time, allowing time for other treatments to be arranged.

Lymphoma within the spine is usually treated in the same way as primary CNS lymphoma in other locations, with chemotherapy regimens that include high-dose methotrexate.  Some patients also have radiotherapy to the spine.

Lymphoma that is outside the CNS but causing compression by pressing on the spine is treated with the standard chemotherapy treatment for the type of lymphoma, such as R-CHOP.  Intrathecal chemotherapy or other drugs such as high-dose methotrexate may be added.  Chemotherapy may be followed by radiotherapy to the area of spine that was affected.

Surgery may sometimes be used to remove a slowly growing lymphoma if it is compressing the spinal cord.

Common side effects from treatment

There are many different side effects of the treatment and these are dependent on the treatment that has been given.  The treating doctor and/or cancer nurse can explain the specific side effects prior to the treatment.  Some of the more common side effects of treatment may include:

  • Anaemia (low red blood cells carry oxygen around the body)
  • Thrombocytopenia (low platelets that help bleeding and clotting)
  • Neutropenia (low white blood cells help with immunity)
  • Nausea and vomiting
  • Bowel problems such as constipation or diarrhoea
  • Fatigue (tiredness or lack of energy

The medical team, doctor, cancer nurse or pharmacist, should provide information about:

  • What treatment will be given
  • What are the common and possible side effects for the treatment
  • What side effects do you need to report to the medical team
  • What are the contact numbers, and where to attend in case of emergency 7 days a week and 24 hours per day
For more info see
Side effects of treatment

What happens after treatment for PCNSL?

Sometimes, the symptoms of CNS lymphoma resolve quickly with treatment.  Initial treatment with steroids can be very effective in relieving symptoms.  However, nerve tissues grow very slowly, and it can sometimes take a long time for symptoms to improve.  Some patients see gradual improvement of their symptoms.  Some patients find their symptoms never resolve completely, especially if they were present for a long time before treatment.

Your medical team can support the recovery by referring the patient to the appropriate specialists.

Patients with muscle weakness and strength loss who do not recover quickly, should see physiotherapists and occupational therapists as they can offer help and advice to improve quality of life.  Their help might also stop symptoms from worsening or other problems developing in the longer term.

Psychologists can offer support if there are cognitive (thinking) problems, such as memory or attention problems.  Psychologists and counsellors can also support with the emotional impact of your lymphoma.

Follow-up care

Once treatment has completed, post treatment staging scans are done to review how well the treatment has worked.  The scans will show the doctor if there has been a:

  • Complete response (CR or no signs of lymphoma remain) or a
  • Partial response (PR or there is still lymphoma present, but it has reduced in size)

If all goes well regular follow-up appointments will be made for every 3-6 months to monitor the below:  

  • Review the effectiveness of the treatment
  • Monitor any ongoing side effects from the treatment
  • Monitor for any late effects from treatment over time
  • Monitor signs of the lymphoma relapsing

These appointments are also important so that the patient can raise any concerns that they may need to discuss with the medical team. A physical examination and blood tests are also standard tests for these appointments.  Apart from immediately after treatment to review how the treatment has worked, scans are not usually done unless there is a reason for them. For some patient’s appointments may become less frequent over time.

Relapsed or refractory primary CNS lymphoma (PCNSL)

Other treatments might be available if CNS lymphoma relapses or is refractory (does not respond) to treatment.  The treatment depends on how fit the patient is at the time, what treatment has already been given and how the lymphoma is affecting the patient.  The specialist can talk through the options and treatments can include:

  • More intense (stronger) chemotherapy, possibly followed by an autologous stem cell transplant (not suitable for some patients)
  • Radiotherapy (if hasn’t been given already)
  • Palliative treatments given with the aim to relieve symptoms
  • Clinical trial participation
For more info see
Relapsed and Refractory Lymphoma

Treatment under Investigation

There are many treatments that are currently being investigated in clinical trials in Australia and around the world for newly diagnosed and relapsed/refractory primary central nervous system lymphoma and can include:

  • Ibrutinib (ImbruvicaTM)
  • Lenalidomide (revlimidTM)
  • Nivolumab (OpdivoTM)
  • Obinutuzumab (GazyvaTM)
  • Pembrolizumab (KeytrudaTM)
For more info see
Understanding Clinical Trials

What happens after treatment?

Late Effects  

Sometimes a side effect from treatment may continue or develop months or years after treatment has completed.  This is called a late effect.

Finishing treatment

This can be a challenging time for many people and some of the common concerns can be related to:

  • Physical
  • Mental wellbeing
  • Emotional health
  • Relationships
  • Work, study, and social activities
For more info see
Finishing Treatment

Health and wellbeing

A healthy lifestyle, or some positive lifestyle changes after treatment can be a great help after the treatment has been finished.  Making small changes such as eating and increasing fitness can improve health and wellbeing and help the body to recover.  There are many self-care strategies that can help during the recovery phase.

For more info see
Health & Wellbeing

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