What Is Malt Lymphoma?

  • Margaret Musanga MalenyaBachelor of Science - BS, Physical Therapy/Therapist, Universidad CEU San Pablo, Madrid, Spain


MALT lymphoma, or MALToma, is a type of lymphoma, a cancer of the white blood cells (lymphocytes).¹ MALT is an acronym that means “mucosa-associated lymphoid tissue.” this type of tissue is a small concentration of lymphoid cells (white blood cells) that exists in various places of the body, like the stomach, intestines, thyroid, lungs and salivary glands, whose role is to regulate immune response against diseases.¹ Most cases of MALT affect the stomach, accounting for 35% of all cases.² Gastric tumours are strongly linked to Helicobacter pylori infection, which is a bacteria known to cause gastritis and ulcers of the stomach and small intestine.³

What is a lymphoma, and types of lymphoma?

Lymphomas are a cancer that originates from white blood cells (lymphocytes).¹ They can be divided into Hodgkin lymphomas and non-Hodgkin lymphomas (NHL): the difference is seen microscopically, as the Hodgkin type has the classic Reed–Sternberg cells (that resemble an owl’s eyes), and NHL does not have it.⁶ Lymphomas, regardless of classification, are different from leukaemia: although both originate from blood cells, leukaemia originates in the bone marrow and does not result in a solid tumour, while lymphoma affects white blood cells in other parts of the body other than the bone marrow and generates a solid mass of cancerous cells (the primary tumour).⁸

MALT lymphoma is one of the many types of non-Hodgkin lymphoma (NHL), which is the most common presentation of white blood cell cancer.⁶ It has a very indolent growth, usually slow, with a good prognosis (especially if diagnosed early).² It originates from mature B-cell lymphocytes: these cells are responsible for producing antibodies against viruses, bacteria and other infectious agents in order to fight against infections.²

Causes of MALT lymphoma

Most cases of MALTomas can be associated with H. pylori infection: according to the British Medical Journal, up to 90% of cases of gastric MALT tumours are strongly associated with infection by this bacteria.⁴ When it comes to the specific carcinogenesis for gastric MALT lymphoma, Helicobacter pylori causes genetic mutation of the B-cell lymphocytes: it causes three known translocations between chromosomes 1 and 18, between chromosomes 1 and 14, and between chromosomes 14 and 18¹. These genetic mutations produce an activation of a protein called nuclear factor kappa B (NF-κB): NF-κB controls cell immunity and inflammation and also a process called apoptosis (cellular death)¹. Once mutated, the cells become malignant because they lose the ability to die, proliferating without control.

Other mutations have been associated with infection by H. pylori:

  • The bacteria stimulates the production of a ligand-protein called APRIL; this protein promotes the proliferation of B-cell lymphocytes, favouring the tumour’s growth.¹
  • H. pylori can translocate another protein known as CagA inside B-cells; CagA can inhibit apoptosis (cell’s death).¹

Besides infection by Helicobacter pylori, there are other pathogens that can cause MALT lymphoma, like hepatitis B and C virus, human immunodeficiency virus (HIV), human T-cell lymphotropic virus type 1, and Epstein-Barr virus.¹ Other bacteria like Borrelia burgdorferi have been associated with MALTomas of the skin, while Chlamydia psittaci has been linked to ocular adnexa MALToma, though none as strongly as H. pylori.¹¹ Known genetic mutations like those in the NOD2/CARD15 gene can also predispose to this type of gastric lymphoma.¹

When it comes to other sites of the disease, like the salivary glands and thyroid, chronic inflammation has been described as a potential pathway: diseases like Sjögren syndrome, Hashimoto’s thyroiditis and systemic lupus erythematosus have been linked to increased risk of MALT lymphoma.⁵ As they are inflammatory diseases, the constant stimulation of lymphoid tissue promotes the proliferation of B-cell and T-cell lymphocytes, and these cells accumulate in the tissue; as they get older and suffer mutations from environmental agents, they start proliferating without control, leading to cancer: in case of MALTomas, B-cells are the ones proliferating out of control.⁵

Risk factors

Infection by Helicobacter pylori is the number one risk factor for gastric MALT lymphoma.² Other infections by viruses like the hepatitis B virus, HIV and Epstein-Barr virus have also been noted as risk factors for MALT lymphomas.¹ In fact, non-Hodgkin lymphomas, in general, are the second most common type of cancer in HIV-positive patients.⁶

Autoimmune diseases like HIV, Sjögren syndrome, and systemic lupus erythematosus are known risk factors for MALT lymphoma due to the persistent inflammation⁵.

Other factors that are being studied relate to obesity and metabolic syndrome, both increasing the risk of developing gastric MALT tumours.¹ Insulin resistance and hyperglycemia are also cofactors in H. pylori-induced gastric MALT lymphoma.¹ High intake of salt has also been related to an increase in expression of the CagA protein in people infected with H. pylori, worsening prognosis.¹

Signs and symptoms

Signs and symptoms vary greatly depending on the affected area. Commonly affected areas are the stomach, ocular adnexa (eye region), lung, skin and salivary glands.²

  • Stomach: nausea, vomiting, gastric pain, and GI bleeding.⁴
  • Small intestine: diarrhoea, pain, and malabsorption of nutrients.⁴
  • Salivary glands: hard mass of slow growth, either on one or both sides of the head and neck.⁴
  • Skin: can present as erythematous (red) nodules or plaques.⁶

Aside from specific signs and symptoms, systemic symptoms such as fever, fatigue, night sweats and weight loss can be present.⁶ These systemic manifestations can occur before any specific symptoms of the disease can be found.⁶


Confirmation of a diagnosis of MALT lymphoma can be made through a biopsy of the site and microscopical examination of the sample.² Differential diagnosis with other types of lymphomas like mantle-cell lymphoma, follicular lymphoma, lymphoplasmacytic lymphoma, or simply a severe H. pylori gastritis is important, so a pathologist has to look for massive proliferation of neoplastic small lymphocytes (abnormally shaped white blood cells).² There may be occasional transformation into larger cells with more prominent nuclei.² In the case of H. pylori infection within a MALToma, erosion of the stomach tissue and chronic inflammation can be found as well.²

Swelling of the lymph nodes, along with local symptoms and systemic manifestations described (fever, weight loss, fatigue, night sweat) can steer a medical professional towards a suspicion of lymphoma, and other exams can be necessary to assess the situation first, like a CT scan or a PET scan.⁶ Diagnosis can be accidental, through an X-ray of the chest for unrelated reasons that show lung tumours, or through a complete blood count (CBC) to investigate systemic symptoms.⁶

Other exams can be useful to understand the disease, like a fluorodeoxyglucose (FDG)-PET/CT scan of the chest, abdomen, and pelvis: this will locate lesions, their size, and the tumour’s metabolism.⁶ Bone marrow biopsy can be done to access cytopenia (lack of blood cells) and is recommended in non-gastric tumours.⁶ Tests for infections like HIV, hepatitis B and C are also recommended for all cases.⁷

In the case of gastric MALT tumours, an endoscopy with subsequent biopsy is recommended to test for H. pylori as well.¹

The Lugano staging system is the most widely used to classify gastric MALT lymphoma.² ⁶

Lugano stageCriteria
IEither a single primary lesion or multiple, non-contiguous lesions, confined to the GI tract
IIEither a single primary lesion or multiple, non-contiguous lesions confined to the GI tract
IIEInvasion of surrounding tissue with or without involvement of abdominal lymph nodes
IVExtranodal involvement (bone marrow, lungs, liver)

As for non-gastric MALT lymphoma, the Ann Arbor staging system is used.⁹

Ann Arbor stageCriteria
IInvolvement of a single node or group of nodes
IIInvolvement of multiple groups of nodes, but all either above or below the diaphragm
IIIInvolvement of both sides of the diaphragm
IVWidespread involvement of extralymphoid sites

The prognosis is based on different clinical and microscopical factors.²,³ A stage IIE/IV in the Lugano system or III/IV in the Ann Arbor system, resistance to H. pylori, age of 70 years or older, histological transformation of B-cells, and translocation of chromosomes 11 and 18 are factors that contribute to poor prognosis.¹,² The MALT lymphoma prognostic index (MALT-IPI) has been used to determine the prognosis as well: a combination of an Ann Arbor stage of III/IV, age above 70 years, and high levels of lactate dehydrogenase (LDH) have a poorer prognosis.¹

Management and treatment

Management and treatment depend on the site of the tumour. Gastric MALT tumours should be tested for H. pylori: Eradication of the bacteria is the first line of treatment when samples are positive, with a combination of a proton pump inhibitor and antibiotic for 7-14 days, independently of the stage.¹ After 3 to 6 months, a new endoscopy with biopsy should be done to access remission.¹

Surgery is no longer the first choice of treatment when it comes to gastric MALT lymphoma: it is considered when there are multiple lesions with massive infiltration of surrounding tissue, with a risk of haemorrhage and/or perforation.¹ If the eradication therapy has failed, or the patient has never been positive for H. pylori in the first place, they would benefit from either radiotherapy or chemotherapy¹. 

More indolent, slow-growing forms of MALTomas can be treated initially with watchful waiting: it means carefully observing the tumour before taking action.¹ It can be applied to tumours that are small and asymptomatic, with little to no impact on the patient’s health; instead of attacking right away with aggressive therapies that generate numerous side effects, a medical professional might suggest observing the tumour through image exams and blood work to assess its size, progression, and response to treatment.¹ This should be discussed with the patient first and foremost, and if there is growth of the tumour or new symptoms arise, other forms of treatment should be implemented.¹

Radiotherapy has been used to treat gastric MALT tumours with a negative response to eradication or with a negative test for H. pylori.¹ For non-gastric sites, radiotherapy has been used as a first-choice treatment.¹

Chemotherapy, immunotherapy and their combination (chemoimmunotherapy) have been used to treat both gastric and non-gastric MALT lymphoma when systemic treatment is necessary⁷. Failure to treat with antibiotics and radiotherapy, systemic involvement and histological transformation of the tumour are factors that favour this type of systemic approach.⁷ Cancer Research UK has listed rituximab as the most common immunotherapy agent, with combinations with chemotherapeutic agents such as bendamustine, or CVP (a combination of cyclophosphamide, vincristine, and dexamethasone), or chlorambucil.⁸

As it is a slow-growing, indolent form of cancer, the prognosis is usually good: more than 75% of cases will regress with antibiotic therapy alone, and only 23-40% of cases will present with dissemination of cancer (either to lymph nodes, bone marrow or other mucosal sites).² It responds well to immunotherapy and radiotherapy, with the surgical intervention being needed in a smaller number of cases.¹ The five-year survival rate reaches 89,8% across different ethnicities and sexes.¹¹


How can I prevent MALT lymphoma?

  • Avoid infection by Helicobacter pylori: this bacterium is transmitted through mouth-to-mouth contact (through gastric mucus or saliva) or through contact with contaminated food and/or water by faeces - this means that proper sanitary measures like washing your hands before eating, washing food properly, and having access to clean water are essential in avoiding infection.¹⁰
  • Treat infection by H. pylori: most people infected by this bacterium do not present with symptoms.¹⁰ However, once the infection has been identified, treating it early is important to avoid complications like gastritis, ulcers and MALTomas.
  • Avoid infection by HIV, hepatitis B and C, and Epstein-Barr virus: these viruses have been identified as potential pathogens in MALT lymphomas.¹ Safe sex can protect against HIV and hepatitis, among a list of many other sexually transmitted infections (STI), and there is a vaccine against hepatitis B.
  • Autoimmune diseases: though many of them cannot be prevented as they are inherited genetically, medical care can keep them under control, and a medical professional can assess the risk of developing MALT lymphoma individually and help catch any early MALTomas if necessary.
  • Healthy diet and exercise: insulin resistance, obesity, hyperglycemia, high sodium intake and metabolic syndrome are conditions that have been shown to increase the risk of gastric MALTomas¹. Maintaining a balanced diet with regular physical exercise can lower the risk of developing these conditions, among many others, besides improving quality of life.

How common is MALT lymphoma?

MALT lymphoma represents 7-8% of all B-cell non-Hodgkin lymphomas, with up to 35% of the MALT tumours being located in the stomach.² In the United Kingdom, the incidence ratio is 19.6 to every 100.000 people, and every year, more than 7000 people are diagnosed with MALT lymphoma in the UK.¹¹

Who is more at risk of developing MALT lymphoma?

It affects mostly those of older age, especially 60 years old or older, with equal incidence between sexes.² However, individuals with chronic Helicobacter pylori infection, immunocompromised with HIV or other immunosuppressive disorders, or with a history of hepatitis B and C are more at risk of developing MALT lymphoma.¹ Those who suffer from chronic autoimmune diseases are also at higher risk of developing this type of cancer.⁵


MALT lymphoma is a type of non-Hodgkin lymphoma, a cancer of the white blood cells, that affects most frequently the lymphatic tissue associated with the mucosa of the stomach, followed by the ocular adnexa (eye), lung, skin and salivary glands. Causes of these types of tumour include infection by Helicobacter pylori, HIV, hepatitis B and C, Epstein-Barr virus, and autoimmune diseases like Hashimoto’s thyroiditis, Sjögren syndrome and systemic lupus erythematosus. Other risk factors include obesity, metabolic syndrome, insulin resistance and hyperglycemia. 

Common signs and symptoms are not specific to the disease, like fever, fatigue, and weight loss, but depending on the site, specific symptoms can present, such as gastric pain, nausea and GI bleeding for the stomach, swelling of the glands for salivary glands, and red nodules or plaques for the skin. Diagnosis is made through biopsy, though image exams like CT scans and PET scans can assess the dimensions of the tumour and involvement of other structures, and CBC and bone marrow biopsy can show bone marrow involvement.

Treatment consists of antibiotic eradication of H. pylori for gastric MALTomas and radiotherapy for other sites. Radiotherapy, chemotherapy, and immunotherapy are viable options for treatment-resistant tumours or when there is systemic involvement. Prognosis is usually good, with most cases of gastric MALTomas being eliminated through antibiotic therapy alone and with high rates of success in other sites with radiotherapy and immunotherapy.  


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  3. Wang F, Meng W, Wang B, Qiao L. Helicobacter pylori-induced gastric inflammation and gastric cancer. Cancer Letters. 2014 Apr;345(2):196–202.
  4. MALT lymphoma - Symptoms, diagnosis and treatment | BMJ Best Practice US [Internet]. bestpractice.bmj.com. [cited 2023 Jul 21]. Available from: https://bestpractice.bmj.com/topics/en-us/878
  5. ‌Sagaert X, De Wolf-Peeters C, Noels H, Baens M. The pathogenesis of MALT lymphomas: where do we stand? Leukaemia [Internet]. 2007 Mar 1 [cited 2023 Jul 22];21(3):389–96. Available from: https://pubmed.ncbi.nlm.nih.gov/17230229/
  6. Non-Hodgkin Lymphomas - Hematology and Oncology [Internet]. MSD Manual Professional Edition. Available from: https://www.msdmanuals.com/professional/hematology-and-oncology/lymphomas/non-hodgkin-lymphomas?query=malt%20lymphoma
  7. Zucca E, Arcaini L, Buske C, Johnson PW, Ponzoni M, Raderer M, et al. Marginal zone lymphomas: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Annals of Oncology. 2020 Jan;31(1):17–29.
  8. MALT lymphoma | non-Hodgkin lymphoma | Cancer Research UK [Internet]. www.cancerresearchuk.org. Available from: https://www.cancerresearchuk.org/about-cancer/non-hodgkin-lymphoma/types/malt
  9. Ann Arbor Staging - an overview | ScienceDirect Topics [Internet]. www.sciencedirect.com. Available from: https://www.sciencedirect.com/topics/medicine-and-dentistry/ann-arbor-staging
  10. Brown LM. Helicobacter pylori: epidemiology and routes of transmission. Epidemiologic reviews [Internet]. 2000 [cited 2019 Dec 5];22(2):283–97. Available from: https://www.ncbi.nlm.nih.gov/pubmed/11218379
  11. Cerhan JR, Habermann TM. Epidemiology of marginal zone lymphoma. Annals of Lymphoma. 2021 Mar;5:1–1.
This content is purely informational and isn’t medical guidance. It shouldn’t replace professional medical counsel. Always consult your physician regarding treatment risks and benefits. See our editorial standards for more details.

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Isabela Araújo Rosa

Doctor of Dental Surgery - DDS, Universidade Federal de Goiás, Brazil

Isabela is a board certified dentist in Brazil, with a background in Oral and Maxillofacial Pathology, Bioethics and Oral Medicine, and previous experience with medical writing and medical communication.

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