Overview of Nodal marginal zone lymphoma (MZL)
Nodal MZL is an indolent (slow-growing) B-cell non-Hodgkin lymphoma (NHL). It is rare, accounting for around 2% of all non-Hodgkin lymphomas. Nodal MZL can be quite hard to diagnose as it can look similar to other kinds of NHLs.
Nodal MZL is a slow growing lymphoma, and in most cases, it responds well to treatment. However, this is an indolent lymphoma, and this means that it often relapses (comes back). If a relapse does happen it can usually be treated again to keep it under control.
Who is affected by nodal marginal zone lymphoma?
Nodal marginal zone lymphoma (MZL) is a rare subtype of non-Hodgkin lymphoma (NHL), accounting for less than 2% of NHL cases. It is also the least common of the MZL subtypes accounting for less than 10% of marginal zone lymphomas.
Nodal MZL is most common in people over 50 years of age. There is a rare paediatric variant of nodal MZL that affects children. This subtype typically develops in lymph nodes in the head and neck. It is usually diagnosed at an early stage and has an excellent prognosis.
It is not known what causes nodal MZL. It is not usually clear why nodal MZL develops, although it has been associated in people who have been diagnosed with the hepatitis C virus (HCV) or other autoimmune disorders. However, it is important to note that not all people diagnosed with these conditions will go on to develop nodal MZL.
Symptoms of nodal marginal zone lymphoma (MZL)
The most common symptom of nodal MZL is a painless lump that is growing often in the neck, armpit or groin that is caused by the swelling of lymph nodes due to the presence of lymphoma. There are often a number of lymph nodes affected that you may not be able to feel.
Other symptoms called B symptoms can include:
- Night sweats (drenching sleepwear or bedding)
- Persistent high fevers (especially at night >38C)
- Weight loss (unintentional)
It is important that the doctor is aware of all the symptoms as it can influence the decision around the type of treatment and when to start.
Diagnosis and staging of nodal MZL
A biopsy is always required for a diagnosis of nodal marginal zone lymphoma (nodal MZL). A biopsy is an operation to remove a lymph node or other abnormal tissue to look at it under the microscope by a pathologist to see what the cells look like. The biopsy can be done under a local or general anaesthetic depending on what part of the body is being biopsied. The biopsy can be done in one of three ways:
- Fine needle aspirate
- Core Biopsy
- Excisional node biopsy
An excisional node biopsy is the best investigative option, as it collects the most adequate amount of tissue to be able to do the necessary testing for a diagnosis.
Waiting for results can be a difficult time. It may help to talk to family, friends or a specialist nurse.
Staging of lymphoma
Once a diagnosis of nodal MZL lymphoma is made, further tests are required to see where else in the body the lymphoma has affected or is located. This is called staging. The staging of the lymphoma helps the doctor to determine the best treatment for the patient
There are four stages from stage 1 (lymphoma in one area) through to stage 4 (lymphoma that is widespread).
- Early stage means stage 1 and some stage 2 lymphoma. This can also be referred to as ‘localised’. Stage 1 or 2 means that the lymphoma is found in one area or a few areas close together.
- Advanced stage means the lymphoma is stage 3 and stage 4, and it is widespread. In most cases, the lymphoma has spread to many parts of the body that are far from each other.
Nodal MZL is often at an advanced stage at diagnosis meaning the lymphoma has affected many lymph nodes throughout the body. About 1 in 3 patients has nodal MZL present in their bone marrow. Effective treatment is available for advanced nodal MZL.
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. Nodal MZL is an indolent lymphoma. It is important to know the stage and grade of the lymphoma.
Staging scans and tests
The scans and tests needed for staging and before treatment can start may include:
- Positron emission tomography (PET) scan
- Computed tomography (CT) scan
- Bone marrow biopsy
- Lumbar puncture & magnetic resonance imaging (MRI) – If lymphoma is suspected in the brain or spinal cord
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
It may take some time for all the necessary biopsies and tests to be done (an average of 1-3 weeks), but it is important for the doctors to have a complete picture of the lymphoma and the general health of the patient in order to make the best treatment decisions
Many of the staging and organ function tests are done again after treatment to check whether the lymphoma treatment has worked and the effect this has had on the body.
It is important to note that lymphoma is what is known as a systemic cancer. It can spread throughout the lymphatic system and nearby tissue and organs. Many patients are diagnosed at an advanced stage and the lymphoma can still be successfully treated. Lymphoma is very unlike advanced stage solid tumour cancers, such as bowel or lung cancer.
Prognosis of nodal marginal zone lymphoma (MZL)
Nodal marginal zone lymphoma (MZL) develops slowly and in most cases, it responds well to treatment. However, this is an indolent (slow growing) lymphoma and this means that it often relapses (comes back). If the lymphoma does relapse it can usually be treated again to keep it under control.
Transformed nodal MZL
Occasionally some patients with nodal MZL can change (transform) into an aggressive type of lymphoma. This happens in around 1-2 people in every 10 people with nodal MZL (very rarely).
If a transformation is suspected another biopsy is needed to check for fast-growing cells. Transformed nodal MZL is treated in the same way as fast-growing non-Hodgkin lymphoma, such as diffuse large B-cell lymphoma.
Treatment for nodal marginal zone lymphoma (MZL)
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. Before treatment starts many factors are taken into consideration:
- The stage of lymphoma
- Symptoms (including the size and location of the lymphoma)
- How the lymphoma is affecting the body
- Age
- Past medical history & general health
- Current physical and mental wellbeing
- Patient preferences
Treatment for nodal MZL varies depending on the stage and the symptoms that are present. Patients who also have the hepatitis C virus, are likely to be offered an antiviral treatment. Clearing the infection might also clear the lymphoma. If this is the case, no further treatment may be needed. Treatment options can include.
Watch and Wait
If the nodal MZL is not causing any symptoms or only minor one’s treatment may not start straight away. Instead, the doctor can suggest a watch and wait approach and the patient is monitored closely and treatment is saved until it is needed. This approach avoids the side effects of treatment for as long as possible. Delaying treatment in this way does not affect how well it works when the treatment is needed.
Early stage nodal MZL
If treatment is needed and the lymphoma is only in a few places, usually around the same area, radiotherapycould be an option. However, most patients with nodal MZL have more widespread lymphoma.
Advanced stage nodal MZL
The most likely treatment for patients with advanced stage nodal MZL is antibody therapy (such as rituximab) combined with chemotherapy. This is called chemoimmunotherapy.
Nodal MZL is rare. This makes it difficult to determine exactly which treatment gives the best outcome. The most common combinations of chemoimmunotherapy drugs used to treat nodal MZL include:
- Rituximab and chlorambucil
- Rituximab and bendamustine
- R-CVP (rituximab, cyclophosphamide, vincristine & prednisolone)
- R-CHOP chemotherapy (rituximab, cyclophosphamide, doxorubicin, vincristine & prednisolone)
- Rituximab only
- Clinical trial participation
Side effects
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 that carry oxygen around the body)
- Thrombocytopenia (low platelets that help with clotting and bleeding)
- Neutropenia (low white blood cells that help fight infection)
- Nausea and vomiting
- Fatigue (tiredness or lack of energy)
- Reduced fertility
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
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 management of nodal MZL
After treatment, the majority of patients can have a period of remission (no signs of lymphoma or the lymphoma is under control). However, nodal MZL usually relapses (comes back) and a different treatment is given with the aim of achieving a remission again. Experts are discovering new and more effective treatments that are increasing the length of remissions. If a relapse happens the choice of treatment will depend on several factors including:
- The type of treatment already received
- Time taken to relapse
- General health and age
- Stage of nodal MZL at relapse
- Patient preferences
This pattern may repeat itself over many years. Experts are discovering new and more effective treatments that are increasing the length of remissions. The treatment options for relapsed nodal MZL may include:
- Watch and wait (active monitoring)
- Radiotherapy
- Chemotherapy and rituximab (either in combination or alone)
- Autologous stem cell transplant (ASCT) – This treatment approach may be considered if the lymphoma has relapsed very quickly after initial treatment. It is not suitable for all patients
- Clinical trial participation
Treatment under investigation
There are many treatments that are currently being tested in clinical trials in Australia and around the world for patients with both newly diagnosed and relapsed lymphoma.
Some treatments that are currently under investigation to treat nodal MZL include:
- BTK inhibitors such as ibrutinib, acalabrutinib & zanubrutinib, that block signals that B-cells send to help them stay alive and divide.
- PI3K inhibitors such as idelalisib, umbralisib and copanlisib, that block a protein involved in the growth and survival of lymphoma cells
- Immunomodulators such as lenalidamide which change how your immune system works
- New antibody treatments such as obinutuzumab, which bind to proteins on the surface of lymphoma cells to help your own immune system destroy them
What happens after treatment?
Late Effects
Sometimes a side effect from treatment may continue or develop months or years after treatment has completed.
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
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.
