Overview of mucosa-associated lymphoid tissue (MALT) lymphoma
Mucosa-associated lymphoid tissue (MALT) lymphoma (also known as extranodal marginal zone lymphoma), is the most common form of MZL accounting for around two thirds of all MZL cases per year and about 5% of all NHL. It occurs outside of the lymph nodes (extranodal) and can be divided into two subtypes:
- Gastric MALT lymphoma which develops in the stomach
- Non-gastric MALT lymphoma which develops outside the stomach, in places such as, small intestine, salivary gland, thyroid, structures around the eyes (ocular adnexa), breast and lungs.
‘Mucosa’ is the soft, moist, protective layer of cells that lines many parts of your body, such as your mouth, gut, airways and some internal organs. ‘Lymphoid tissue’ means a collection of lymphocytes. Mucosa-associated lymphoid tissue (MALT) refers to collections of lymphocytes in your mucosa. It includes your tonsils at the back of your throat, as well as lymphoid tissue that may be scattered around the rest of your body, such as your guts, lungs, skin, thyroid gland and salivary glands.
MALT lymphoma can form as part of your body’s normal response to inflammation. It helps protect you from infections. However, MALT lymphomas can develop if abnormal lymphocytes collect in this lymphoid tissue.
Who is affected by MALT lymphoma?
MALT lymphoma can affect people of any age, but it typically develops in people in their mid-60s. It most commonly involves the stomach, followed by ocular adnexa (eyes), lung and salivary gland. In many cases MALT lymphoma is associated with a history of chronic infection, inflammation or auto immune disorders at the affected organ.
The following table highlights infections that may cause MALT lymphoma, however it is important to remember that even though there is a link with these conditions most people with these infections or immune system disorders, will NOT go on to develop lymphoma.
|Sites of MALT lymphoma||Cause|
|Gastric MALT lymphoma||Helicobacter pylori (H. pylori), is a bacterium that is linked to stomach ulcers and is thought to cause most cases of gastric MALT lymphoma.|
|Tear ducts and tissue around the eye||Chlamydophilia psittaci (C Psittaci) is an infection linked to MALT around the tear ducts and eye tissue. This is spread by birds and can cause lung infections.|
|Skin||Borrelia burgdorferi is an infection that may be linked to MALT lymphoma of the skin. This is spread by ticks and causes LYME disease|
|Small bowel||Campylobacter jejuni is an infection that may be linked to MALT affecting the small bowel, it is a common cause of food poisoning.|
|Lungs||Achromobacter xylosoxidans is an infection that may be linked to MALT affecting the lungs. It can cause blood or lung infections mostly in people with lowered immune systems|
|Salivary glands||Sjogren’s syndrome is a disorder or the immune system which may be linked to MALT lymphoma affecting the salivary glands.|
|Thyroid gland||Hashimotos thyroiditis is a disorder of the immune system that may be linked to MALT lymphoma of the thyroid gland|
Symptoms of MALT lymphoma
The symptoms for MALT lymphoma depend on which part of your body is affected.
Gastric MALT lymphoma symptoms are related to the stomach and can include:
- Persistent indigestion (often this the only symptom)
- Stomach pain
- Nausea (feeling sick and like you are going to vomit)
- Weight loss (unintentional)
- Some people may have symptoms of anaemia (tiredness or short of breath) caused by bleeding in the stomach
Non-gastric MALT lymphoma may cause no symptoms and can often be diagnosed accidentally when the doctors are doing tests for something else. The symptoms are varied and dependant on which part of the body may be affected. Some people (around 50%) can have lymphoma in several places in the body. This can create a mixture of symptoms. It is important to tell the doctor about all symptoms as it can influence the decision around the type of treatment and when to start.
|MALT lymphoma location||Common symptoms|
|Stomach or bowel||Can make it difficult to absorb enough food Diarrhoea, bloating or stomach pain Fatigue Unintentional weight loss|
|Tear ducts or tissues around the eye||Redness of the eye Dark pink lumps inside the eyelid or the corners of the eye Double vision Droopy eyelid or a bulging eye Symptoms usually develop on one side but in around 1 in 10 cases, they can affect both eyes|
|Lungs||Often doesn’t cause any symptoms but can cause: Cough Shortness of breath Coughing up blood Chest pain|
|Salivary glands||Lump in front of ear, in mouth or jaw|
|Skin||Pink, red or purplish patches or lumps develop on the skin, most often on arms, chest or back. Can develop in one place or in several places and are very slow growing|
|Thyroid gland||Lump on the front of the neck Hoarse voice Shortness of breath Difficulty swallowing Underactive thyroid gland: feeling tired a lot, being sensitive to the cold and putting on weight|
Diagnosis of MALT lymphoma
Biopsy: a biopsy is always required for a diagnosis of MALT Lymphoma. 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 local or general anaesthetic depending on what part of the body is being biopsied. The biopsy can be done in a few different ways, depending on the suspected site of infection. There needs to be an adequate amount of tissue to be able to do the necessary testing for a diagnosis.
Gastroscopy: if the doctor suspects MALT lymphoma of the stomach, they may do a gastroscopy in order to take a biopsy. This involves placing a thin tube with a camera on it, through the mouth and down the digestive tract. This procedure is generally done as a day procedure.
Bronchoscopy: if the doctor suspects MALT lymphoma in the lungs a procedure called a bronchoscopy may be needed. A thin tube with a camera on the end is placed down into the lung and this allows the doctors to get a closer look at the tissue and obtain samples. In most cases, this is a same day procedure.
Breath test: this can be performed to check the H. pylori infection in the stomach by analysing and measuring the amount of certain gases that the inflammation from the bacteria releases into the system. This is called a breath test.
Faeces test: a faecal (poo) sample is sent to the laboratory to test for the H. Pylori infection.
Staging of lymphoma
Once a diagnosis of MALT 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 lymphoma helps the doctor 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.
MALT lymphomas grow slowly so most people have early stage (stage 1 or 2) lymphoma when they are diagnosed.
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. MALT Lymphoma is a low-grade 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 for MALT lymphoma
MALT lymphoma develops slowly, 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 the lymphoma does relapse it can usually be treated again to keep it under control. The doctor can give more information about a prognosis based on the grade and stage of the lymphoma.
Occasionally, MALT lymphoma can change (transform) into a faster-growing type of lymphoma. This happens in less than 1 person in every 10 people with MALT lymphoma.
If a transformed lymphoma is suspected a biopsy needs to be scheduled to check for faster-growing lymphoma cells
Transformed MALT lymphoma is treated in the same way as fast-growing (aggressive) non-Hodgkin lymphoma such as diffuse large B-cell lymphoma (DLBCL).
Treatment for MALT 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. This is based on:
- The stage of lymphoma
- Symptoms (including the size and location of the lymphoma)
- How the lymphoma is affecting the body
- Past medical history & general health
- Current physical and mental wellbeing
- Patient preferences
Before treatment is started it is important that adequate information is provided about the treatment that is planned, the possible side effects and what to expect. Education from the cancer nurses prior to receiving treatment, can be extremely helpful and should include instructions about becoming unwell or needing medical or nursing assistance.
Gastric MALT lymphoma
Standard first line treatment options for gastric MALT lymphoma is usually antibiotic treatment.
Antibiotic treatment: initial therapy is usually a combination of antibiotics which is typically given for several weeks. The antibiotics are normally given with proton pump inhibitors (PPIs), which reduce the production of stomach acid to help prevent or heal ulcers.
Approximately 70-90% of patients with evidence of Helicobacter pylori infection respond to antibiotic therapy, though it can take months (or even years) for the lymphoma to disappear. Approximately half of the patients require no further treatment.
If the lymphoma does not go away after antibiotic therapy, treatment could be with some of the following treatment options:
- Clinical trial participation
- Radiation therapy
- Rituximab (a monoclonal antibody), with or without chemotherapy
- Surgical removal
The standard first-line treatment is chemotherapy and an immunotherapy (rituximab) options for gastric MALT lymphoma and this can include:
Non-gastric MALT lymphoma
Non-gastric MALT lymphoma can affect different areas throughout the body. Therefore, treatment is usually based on the exact location and extent of spread. Treatment or management typically includes:
- Watch and wait (active monitoring) as not all MZL require immediate treatment
- Surgery for certain sites may occasionally be an option if the lymphoma is only affecting one part of the body such as the lung or breast
- Radiation therapy with or without chemotherapy
- Doxycycline: effective the area around the eye
- Immunotherapy with or without chemotherapy; for stage 3 or 4 lymphoma that may include:
- Bendamustine and rituximab
- R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone)
Common side effects of 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 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
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 MALT lymphoma
After treatment, the majority of patients can have a period of remission (no signs of lymphoma or when the lymphoma is under control) that may last for several months or years. However, MALT lymphoma usually relapses (comes back) and a different treatment is given again with the aim of achieving remission again. MALT Lymphoma often comes back in the same organ as it initially presented but it can come back in different places. Experts are discovering new and more effective treatments that are increasing the length of remissions. At that time, the choice of treatment will depend on several factors including:
- The type of treatment already received
- What is causing the MALT lymphoma, for example infection
- Time taken to relapse
- General health and age
- Stage of MALT lymphoma at relapse
- Patient’s 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 MALT lymphoma may include :
- Antibiotic treatment to treat the infection that might be linked to the lymphoma
- Watch and wait (active monitoring)
- Chemotherapy and immunotherapy
- Autologous stem cell transplant (ASCT); This treatment approach may be considered if the lymphoma has relapsed very quickly after initial treatment (may not be suitable for everyone)
- 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 MALT lymphoma 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?
Sometimes a side effect from treatment may continue or develop months or years after treatment has completed. This is called a late effect.
This can be a challenging time for many people and some of the common concerns can be related to:
- Mental wellbeing
- Emotional health
- 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.