Gastric MALT lymphoma
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- Quentin Skinner
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1 Produced Due for revision Gastric MALT lymphoma In this article we are aiming to: explain what MALT lymphoma is and how it develops describe the symptoms you could have and the tests you will need outline how gastric MALT lymphoma is treated, how you are followed up after treatment and what the outlook is with this type of lymphoma. What is MALT lymphoma? A lymphoma is a cancer of the lymphatic system, which consists of lymph vessels and lymph glands (nodes) and other organs including the spleen. The lymphatic system is part of our immune system and one vital component of it is the lymphocyte, a special white blood cell that helps us fight off infections. When lymphocytes grow in a way that is out of control, they build up and a lymphoma develops. MALT lymphomas are one type of lymphoma. MALT lymphoma is a low-grade (indolent) type of B-cell non-hodgkin lymphoma. Unlike many other types of lymphoma it occurs at sites that are outside the spleen and lymph nodes. These are known as extra-nodal sites. It was first recognised as a specific type of lymphoma in 1983 and this was an important development because it behaves quite differently from other non-hodgkin lymphomas and is also treated differently. How did it get its name? When viewed under a microscope, the way that the lymphoma cells are organised resembles the lymphoid tissue that is normally found in the gut. This type of tissue is called mucosa-associated lymphoid tissue or MALT, where mucosa is a soft, moist, protective tissue that covers or lines many different parts of the body. MALT lymphoma only seems to arise within this special type of lymphoid tissue after it has formed as part of a reaction to an infection or to inflammation. How common is MALT lymphoma and where does it occur? Although MALT lymphoma is the third most common type of non-hodgkin lymphoma, it accounts for fewer than 1 in 10 of these tumours, so it is not a common lymphoma. Although this form of lymphoma can occur at any age, it is most common in late middle-aged and elderly people. It is roughly equally common in men and women. 1
2 MALT lymphomas have been found at almost all extra-nodal sites, including the gut, the salivary glands, the lung, the thyroid gland and around the eye. The most common site, however, is the gut. The most common site in the gut for MALT lymphoma to be found is the stomach and stomach (gastric) MALT lymphomas account for roughly a third of all MALT lymphomas. How do MALT lymphomas develop? As mentioned above, MALT lymphomas arise at sites that have acquired some MALT-type lymphoid tissue as a result of some other disorder or infection. For some MALT lymphomas this underlying condition remains a mystery. For others, more is known about the factors that might have played a part in the build-up of this kind of lymphoid tissue. For example, in the thyroid gland MALT lymphomas can develop as a result of an autoimmune inflammatory condition known as Hashimoto s thyroiditis (where autoimmune means an immune reaction against your own body tissues). Similarly, in the salivary gland MALT lymphoma can develop as a result of another autoimmune condition called Sjögren s syndrome. However, most is known about gastric MALT lymphoma, as the stomach is the commonest site for these lymphomas to develop. In the stomach, the majority of these lymphomas are associated with infection with a bacterium called Helicobacter pylori. Helicobacter infection causes inflammation of the mucosa or lining of the stomach and MALT-type lymphoid tissue develops as part of this inflammatory reaction. Once this MALT-type tissue has formed, there is continuous stimulation of the lymphocytes within it to divide and increase in number as a result of the constant presence of bacteria. This is a normal immune reaction. However, in a small number of people this constant stimulation results in a mistake occurring within the genetic material of a lymphoid cell. These faulty cells go on to multiply and they do not die off as they would normally. This eventually leads to a build-up of cells and the development of a lymphoma. What is Helicobacter pylori? Helicobacter pylori is a spiral-shaped bacterium that we know has been around for many centuries. It is unusual in that it has become adapted to survive in the acid conditions found in the stomach, conditions that would destroy most other organisms. The bacterium is thought to be passed on from person to person and close personal contact appears to make this infection spread more easily. Infection normally happens in childhood and most people will then have it for their whole life unless it is treated with special eradication therapies. 2
3 It can be quite difficult to treat this infection and eradication (complete removal) of the bacterium normally involves the use of a combination of antibiotics, together with a drug that cuts down the amount of acid that is secreted in the stomach (such as a proton-pump inhibitor or PPI). The exact combination used varies between treatment centres. In some people initial attempts to eradicate the organism can fail and different drug combinations might have to be tried before eradication is successful. How are gastric MALT lymphomas detected? Many people with a Helicobacter pylori infection have no symptoms. Some people experience the symptoms you would get with various types of gastric and duodenal disease, such as symptoms of duodenal ulcer, gastric ulcer, gastritis, gastric carcinoma (cancer of the stomach lining cells) or gastric lymphoma. In the majority of people gastric MALT lymphoma is found during tests for persistent indigestion although only a very small percentage of people with this symptom have lymphoma. The indigestion is probably more related to the presence of the Helicobacter infection than to the actual lymphoma and patients often feel better after they have had treatment to eradicate the bacterium, whether or not the lymphoma is regressing (decreasing). How is gastric MALT lymphoma diagnosed? Gastric MALT lymphoma is usually discovered unexpectedly during an endoscopy examination of the stomach (where an optical instrument is passed down through the mouth to look inside the gut). The lining of the stomach might just look generally inflamed or swollen and the diagnosis might only come to light after biopsies taken at the time are examined under the microscope. In other people, ulceration or a nodular (lumpy) mass might be seen in the stomach during endoscopy. It is very difficult, and often impossible, to tell the difference between lymphoma and carcinoma on the basis of inspection of these ulcers or nodules during the endoscopy examination. Sometimes, reaching a diagnosis can even be difficult when the samples are examined under the microscope. While trying to make a diagnosis the pathologist will assess: the size and shape of the lymphoid cells where the cells are positioned within the stomach lining how the cells interact with the other components that make up the stomach wall. 3
4 In the past, patients often required several examinations of the stomach before a confident diagnosis of lymphoma could be made. More recently, pathologists have become better at recognising the subtle features that are characteristic of this lymphoma. However, there will still be instances when it is not possible to distinguish confidently between a lymphoma and inflammation, meaning that more than one endoscopic examination could be required. Will any other tests be needed after a MALT lymphoma is diagnosed? Once a diagnosis of MALT lymphoma has been made, you might require several further tests. Firstly, because the diagnosis is usually unsuspected, not enough samples may have been taken during the first endoscopy. If this is the case, another endoscopy might be required so that further biopsies can be taken from the area of lymphoma. It is very important that the presence of the Helicobacter organism is confirmed so that a firm diagnosis can be made. In many cases this will have been possible at the time of the initial diagnostic investigation, but sometimes there are very few organisms and they are difficult to find. If this is the case you might have a sample of blood taken to look for evidence of infection. Research has shown that the response of gastric MALT lymphoma to treatment depends very much on how deeply the tumour is situated within the stomach wall. This is best assessed by endoscopic ultrasound (EUS). In this examination a tiny ultrasound probe at the tip of the endoscope tube uses high-frequency sound waves to create images of the stomach wall. These images can be used to measure how far the lymphoma has spread through the stomach wall. Alternatively, computed tomography (CT) scanning can be used, although this is not considered to be as good as EUS for assessing the thickness of the stomach wall. As with all lymphomas, it is important to assess whether the lymphoma has spread through the body this is known as staging. You will have a full physical examination and blood tests, including a full blood count. Staging would also usually involve a CT scan to find out if any lymph nodes in the chest, abdomen or pelvis have become involved. These scans use a special kind of X-ray machine that takes pictures from different angles around your body a computer then combines these into an image of your internal organs. The bone marrow is rarely involved in MALT lymphoma (this only occurs in about 1 in 10 people with this type of lymphoma), but a bone marrow biopsy is usually performed to check for this. In this test a sample of bone marrow is removed using a special needle. 4
5 This is usually inserted through your skin, into your pelvis (hip bone) using a local anaesthetic. Unlike lymphomas that arise within the lymph node system, MALT lymphomas tend to spread to other extra-nodal sites rather than to other lymph nodes. It can spread to the thyroid gland, for example. These other extra-nodal sites would normally be studied as part of your general assessment and the staging of the lymphoma. Lastly, there are some alterations within the lymphoma cells that can have a bearing on how well the lymphoma responds to therapy. These include alterations in genes that may underlie the change from normal lymphocytes to abnormal lymphoma cells. These can normally be detected in the laboratory using the original biopsies, but the techniques are quite sophisticated and frequently take some time to complete. How is gastric MALT lymphoma treated? Until the early 1990s surgery was probably the most commonly used treatment for gastric MALT lymphoma. Since then, however, the link between gastric MALT lymphoma and Helicobacter infection has become increasingly apparent. This, together with the results of laboratory studies on cells derived from lymphomas, suggested that eradication of the Helicobacter bacterium alone might be an effective treatment for gastric MALT lymphoma. Further studies, some of which have now followed up patients for well over 10 years, have confirmed this, showing that eradication of Helicobacter infection alone can lead to regression of the tumour in 50 70% of cases. The best results with this treatment occur when the tumour has not extended very far through the gastric wall and has not spread to the lymph nodes. You would normally be prescribed an initial antibiotic-based regime for Helicobacter eradication clarithromycin and either amoxicillin or metronidazole, usually together with a PPI drug such as omeprazole. You will be followed up by repeat endoscopies and biopsies to confirm that the infection has been eradicated and to assess whether the lymphoma is regressing. The interval of time between eradication of the Helicobacter and regression of the tumour is highly variable between patients. In some people the lymphoma might be found to have regressed at the first follow-up biopsy (ie after about 4 8 weeks). In other people full regression can take a year or more. There have even been reports of patients whose lymphoma has regressed many years after Helicobacter eradication, despite their having had no other therapies. 5
6 Can we tell in advance whether Helicobacter eradication will be successful? It is impossible to predict with 100% accuracy whether a lymphoma will or will not respond to Helicobacter eradication therapy. Also, as we have seen, it is not possible to predict how long the lymphoma will take to decrease in size or disappear altogether if the therapy is successful. There are, however, certain features that make it less likely that the lymphoma will respond well to eradication therapy. In general, eradication therapy is usually less successful when: the Helicobacter organism cannot be identified and there is no evidence of previous infection the lymphoma has extended deeply through the stomach wall there is spread to local or distant lymph nodes. What happens if Helicobacter eradication doesn t work? Some patients therefore do not respond to Helicobacter eradication therapy alone and if this was the case you might have to have more conventional anti-lymphoma therapies such as chemotherapy or radiotherapy. Chemotherapy using only one drug (single-agent chemotherapy) is the most usual treatment. You might be prescribed an alkylating agent such as cyclophosphamide or chlorambucil, which treat cancers by damaging the cancer cell s DNA (the genetic material in the cell) and stopping these abnormal cells from multiplying. Another type of drug that your doctor might prescribe is a nucleoside analogue such as cladribine, which prevents DNA working properly so curbs the growth of lymphoma cells. These drugs appear to work equally well. Another treatment, a monoclonal antibody drug called rituximab (MabThera ) is currently being assessed in clinical trials. This works by attaching itself to the abnormal lymphoma cells (but not to normal cells) this helps the abnormal cells to die and also helps your own immune system to attack them. When rituximab is used it is usually given with other chemotherapy drugs such as chlorambucil. Less is known about how effective it is to use a combination of chemotherapy drugs for MALT lymphoma. It is generally believed, however, that multiple drugs should probably not be used in the first instance unless you have a more aggressive diffuse large B-cell type of lymphoma as well. If you are prescribed combination chemotherapy to treat gastric 6
7 lymphoma, it should be combined with a PPI drug to reduce the amount of acid secretion in the stomach. Some people who don t respond to anti-helicobacter treatment will be treated with radiotherapy and this has been found to be just as effective as chemotherapy. How are people with gastric MALT lymphoma monitored and what is the outlook? The most important investigation in the follow-up of patients with gastric MALT lymphoma is inspection of the gastric wall through an endoscope, together with close examination of any abnormal areas and of the area previously involved by lymphoma. How often these follow-up endoscopies should be done remains controversial. After confirmation of Helicobacter eradication, assessment endoscopies would normally be done every 3 4 months at first, then every 6 months and eventually once a year. The exact regime will depend on many factors, including how long it has taken for the lymphoma to regress completely in terms of both the appearance at endoscopy and the results of biopsies. In a small proportion of people who are initially treated by Helicobacter eradication, relapse is detected at follow-up endoscopies. In some patients this is associated with recurrent Helicobacter infection and this usually responds to further antibiotic-based therapy. In a few cases, relapse detected on microscopic examination of a biopsy clears spontaneously with no further treatment. In patients where there is a clear relapse of gastric MALT lymphoma, this can be treated with chemotherapy and/or radiotherapy in the same way as for those patients who do not respond to eradication therapy, with a similar success rate. Transformation of the lymphoma into a more aggressive form (a diffuse large B-cell lymphoma) occurs in fewer than 1 in 10 people with gastric MALT lymphoma and when this does happen it would normally be treated with intravenous chemotherapy using a combination of drugs, with the aim of curing this more aggressive disease. The outlook for people with gastric MALT lymphoma is usually good, with about 80% of people surviving beyond the 5-year milestone and nearly as many people (77%) being free of the disease 10 years after being diagnosed. 7
8 More information This article has been adapted from our information leaflet, Gastric MALT lymphoma. For a copy of this article or for more information about lymphoma or the treatments for lymphoma, visit our website at or telephone the Lymphoma Association s freephone helpline Talk to your key worker if you have any concerns about your health or treatment. The Lymphoma Association cannot provide information about individual diagnosis or treatment. The information provided by the Lymphoma Association is not a substitute for advice from your health professionals. About our publications: The Lymphoma Association is committed to the provision of high quality information for people with lymphoma, their families and friends. We produce our information in accordance with nationally recognised guidelines. These include the DISCERN tool for information about treatments, the NHS Toolkit for producing patient information, and the Campaign for Plain English guidelines. Our publications are written by experienced medical writers, in close collaboration with medical advisers with expertise in the appropriate field. Textbooks and professional journals are consulted to ensure that information is as up to date as possible. References are provided where they have been used. Some publications are written by professionals themselves, acting on guidance provided by the Lymphoma Association. Our publications are reviewed every two years and updated as necessary. Our publications are reviewed by a panel of volunteers with experience of lymphoma. Publications are also reviewed by members of the Lymphoma Association helpline team, who have many years collective experience of supporting those with lymphoma. In some instances, our publications are funded by educational grants from pharmaceutical companies. These sponsors do not have any involvement in the content of a publication. They are not invited to see the content and have no editorial input. Lymphoma Association Views expressed in this publication are those of the contributors. The Lymphoma Association does not necessarily agree with or endorse the comments included here. 8
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