Professional Reference articles are designed for health professionals to use. They are written by UK doctors and based on research evidence, UK and European Guidelines. You may find the Stomach Cancer (Gastric Cancer) article more useful, or one of our other health articles.
Treatment of almost all medical conditions has been affected by the COVID-19 pandemic. NICE has issued rapid update guidelines in relation to many of these. This guidance is changing frequently. Please visit https://www.nice.org.uk/covid-19 to see if there is temporary guidance issued by NICE in relation to the management of this condition, which may vary from the information given below.
The body's immune system is made up of a number of masses of lymphoid tissue or organs, as well as circulating leukocytes that originate from the bone marrow. The main lymphoid organs are:
- Bone marrow, thymus, tonsils, spleen and lymph nodes.
- Mucosa-associated lymphoid tissue (MALT).
- Gut-associated lymphoid tissue (GALT).
- Bronchus-associated lymphoid tissue (BALT).
- Skin-associated lymphoid tissue (SALT).
MALT lymphoma is a subtype of non-Hodgkin's lymphoma with it's own specific pathology, histology and clinical features. It is distinct because it involves lymphoid proliferation in mucosa-associated lymphoid tissue (MALT) rather than lymph nodes.
MALT lymphomas constitute a group of low-grade extranodal B-cell neoplasms that share similar features and arise in areas of pre-existing prolonged lymphoid proliferation in mucosal sites. Many patients have a history of autoimmune disease such as Sjogren's syndrome or Hashimoto's disease or of Helicobacter pylori (H. pylori) gastritis. Marginal zone lymphomas comprise three subtypes[1, 2]:
- Nodal: involving lymph nodes.
- Extranodal (MALT type): involving GI tract, ocular adnexa, salivary gland, thyroid, lung, thymus and breast.
MALT lymphomas can be divided into:
- Gastric: the most common type and associated with H. pylori infection.
- Non-gastric: most often in the head and neck, lung and eye. Non-gastric MALT lymphomas are not associated with H. pylori infection.
- MALT can develop in nearly every organ as a result of chronic infection or an autoimmune process. If there is prolonged lymphoid proliferation, a malignant clone can emerge and a MALT lymphoma could follow.
- Gastric MALT lymphomas are strongly associated with H. pylori infection.
- Autoimmune diseases such as Hashimoto's thyroiditis and Sjögren's syndrome have also been linked to MALT lymphomas in the thyroid and salivary glands.
- There are certain karyotypic abnormalities associated with MALT lymphoma. A t(11;18)(q21;q21) translocation is a characteristic cytogenetic abnormality in patients with MALT lymphomas.
- Extranodal marginal zone lymphomas of MALT type represent about 7% of all non-Hodgkin's lymphomas in the Western world and can arise at any extranodal site.
- At least one third of them present as a primary gastric lymphoma, which in approximately two thirds of cases is associated with a chronic H. pylori infection.
- The highest incidence occurs between the age of 50 and 60 years but the incidence increases significantly in patients older than 40.
- These depend on the site involved:
- Gastric MALT lymphomas may present with dyspepsia.
- Nonspecific symptoms include fatigue, low-grade fever, nausea, constipation, weight loss and anaemia.
- Recurrent respiratory tract infections.
- Orbital MALT lymphomas may present with blurred vision and visual field defects.
- MALT lymphoma usually follows an indolent course. It can remain localised for long periods.
- Rarely, there is transformation to a more aggressive form of lymphoma.
- Relapses of MALT lymphoma may be late and lifelong observation may be required.
- General assessment: FBC, renal function tests, electrolytes, LFTs.
- Phenotyping of circulating lymphocytes, bone marrow lymphocytes or biopsy specimens.
- Imaging studies for disease staging:
- Barium contrast studies of the upper and lower gastrointestinal tract.
- CT scan and MRI scan.
- Bone marrow aspiration.
The National Institute for Health and Care Excellence (NICE) recommends:
Gastric MALT lymphoma: localised disease
- Helicobacter pylori eradication therapy, without any concurrent therapy, to people with H. pylori‑positive gastric MALT lymphoma. Also consider H. pylori eradication therapy for people with H. pylori‑negative gastric MALT lymphoma.
- Consider 'watch and wait' for people with gastric MALT lymphoma who respond clinically and endoscopically to H. pylori eradication therapy but who have residual disease shown by surveillance biopsies of the stomach, unless high‑risk features are present.
- For people with residual MALT lymphoma after H. pylori eradication therapy who are at high risk of progression [H. pylori‑negative at initial presentation or t(11:18) translocation], or for people with progressive gastric MALT lymphoma, consider a choice of chemotherapy (eg, chlorambucil or CVP [cyclophosphamide, vincristine and prednisolone]) in combination with rituximab, or gastric radiotherapy.
Gastric MALT lymphoma: disseminated disease
- H. pylori eradication therapy for people with disseminated H. pylori‑positive gastric MALT lymphoma.
- Chemotherapy (eg, chlorambucil or CVP) in combination with rituximab for people with disseminated gastric MALT lymphoma who need treatment - eg, people who are symptomatic or with threatened vital organ function.
- Consider 'watch and wait' in those who are asymptomatic and do not have threatened vital organ function.
Non‑gastric MALT lymphoma
- The following need to be taken into account before recommending any treatment:
- Site of involvement and potential for organ dysfunction.
- Whether it is localised or disseminated.
- Morbidity associated with any treatment proposed.
- Person's overall fitness.
- Offer chemotherapy (eg, chlorambucil or CVP) in combination with rituximab for people with non‑gastric MALT lymphoma for whom radiotherapy is not suitable or who have disseminated disease and need treatment.
- Consider radiotherapy for people with localised disease sites of non‑gastric MALT lymphoma, irrespective of stage.
- Consider 'watch and wait' (observation without therapy) for people with clinically non‑progressive localised non‑gastric MALT lymphoma that is unlikely to result in vital organ dysfunction, who are asymptomatic and for whom radiotherapy is not suitable.
Rituximab alone or in combination with chemotherapy is reported to provide high response rates and has been advocated for those with disseminated or recurrent disease.
Surgery has only a limited role in treatment. Surgery for non-gastrointestinal MALT lymphoma is usually restricted to excisional biopsies. Partial or total gastrectomy is associated with considerable morbidity and is rarely necessary.
Specific types of mucosa-associated lymphoid tissue lymphoma
Gastric MALT lymphoma
- Associated with: H. pylori infection.
- Presenting features: dyspepsia, epigastric discomfort, gastric bleeding. Systemic symptoms (night sweats, weight loss, fever, lethargy) and bone marrow involvement are less common. Most are localised to the stomach at presentation.
- Diagnosis: endoscopy and gastric biopsy. There are characteristic histological features.
- Prognosis: the overall five-year survival and disease-free survival rates are as high as 90% and 75%, respectively. 70-80% of patients reveal complete remission of MALT lymphoma following successful eradication of H. pylori.
Salivary gland MALT lymphoma
- Associated with: Sjögren's syndrome.
- Clinical features: involvement of salivary glands with MALT lymphoma is rare. May involve all salivary glands either initially or subsequently in 30% of patients.
- Prognosis: recurrences may occur in up to 35% of patients at five years but survival is not affected.
Ocular adnexa and lacrimal gland MALT lymphoma
- Clinical features: painless conjunctival injection, photophobia, orange/salmon-pink masses in the fornices. The most common manifestation site of ocular MALT lymphoma is the conjunctiva.
- Prognosis: ocular adnexal lymphoma has an overall five-year survival rate ranging between 50% and 94%, depending on the grade of histology subtype, stage at diagnosis, and age of the patient. Conjunctival lymphoma has a relatively good prognosis.
Lung MALT lymphoma
- Associated with: autoimmune diseases (Sjögren's syndrome, rheumatoid arthritis).
- Clinical features: arises from bronchus-associated lymphoid tissue (BALT). 40% are asymptomatic and present with a solitary pulmonary nodule on CXR. There may be cough, dyspnoea, haemoptysis, fever, weight loss. Can spread throughout the lung and to other MALT.
- Prognosis: usually has an indolent course, remaining localised to the lung for long periods before dissemination.
Thyroid MALT lymphoma
- Associated with: particularly associated with inflammatory conditions in the thyroid and salivary glands.
- Clinical features: thyroid mass, possible obstructive symptoms.
- Diagnosis: may need open biopsy.
Skin MALT lymphoma
- Associated with: Borrelia burgdorferi infection may be associated but this is not clear.
- Clinical features: presents as a few, multiple, pink, red-to-violaceous papules, plaques, or nodules that most often involve the trunk or extremities, especially the arms.
- Prognosis: although recurrence is not uncommon, extracutaneous dissemination is very rare and prognosis is often excellent.
Further reading and references
Zinzani PL; The many faces of marginal zone lymphoma. Hematology Am Soc Hematol Educ Program. 20122012:426-32. doi: 10.1182/asheducation-2012.1.426.
Singh R, Shaik S, Negi BS, et al; Non-Hodgkin's lymphoma: A review. J Family Med Prim Care. 2020 Apr 309(4):1834-1840. doi: 10.4103/jfmpc.jfmpc_1037_19. eCollection 2020 Apr.
Violeta Filip P, Cuciureanu D, Sorina Diaconu L, et al; MALT lymphoma: epidemiology, clinical diagnosis and treatment. J Med Life. 2018 Jul-Sep11(3):187-193. doi: 10.25122/jml-2018-0035.
Mucosa-Associated Lymphoid Tissue Lymphoma Translocation Gene 1, Malt1; Online Mendelian Inheritance in Man (OMIM)
Zucca E, Copie-Bergman C, Ricardi U, et al; Gastric marginal zone lymphoma of MALT type: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2013 Oct24 Suppl 6:vi144-8. doi: 10.1093/annonc/mdt343.
Non-Hodgkin’s lymphoma: diagnosis and management; NICE Guideline (July 2016)
Olszewski AJ, Castillo JJ; Survival of patients with marginal zone lymphoma: analysis of the Surveillance, Epidemiology, and End Results database. Cancer. 2013 Feb 1119(3):629-38. doi: 10.1002/cncr.27773. Epub 2012 Aug 14.
Zullo A, Hassan C, Ridola L, et al; Gastric MALT lymphoma: old and new insights. Ann Gastroenterol. 201427(1):27-33.
Fischbach W; MALT lymphoma: forget surgery? Dig Dis. 201331(1):38-42. doi: 10.1159/000347176. Epub 2013 Jun 17.
Anacak Y, Miller RC, Constantinou N, et al; Primary mucosa-associated lymphoid tissue lymphoma of the salivary glands: a multicenter Rare Cancer Network study. Int J Radiat Oncol Biol Phys. 2012 Jan 182(1):315-20. doi: 10.1016/j.ijrobp.2010.09.046. Epub 2010 Nov 13.
Tanenbaum RE, Galor A, Dubovy SR, et al; Classification, diagnosis, and management of conjunctival lymphoma. Eye Vis (Lond). 2019 Jul 276:22. doi: 10.1186/s40662-019-0146-1. eCollection 2019.
Kocaturk CI, Seyhan EC, Gunluoglu MZ, et al; Primary pulmonary non-Hodgkin's lymphoma: ten cases with a review of the literature. Tuberk Toraks. 201260(3):246-53.
Beasley MJ; Lymphoma of the thyroid and head and neck. Clin Oncol (R Coll Radiol). 2012 Jun24(5):345-51. doi: 10.1016/j.clon.2012.02.010. Epub 2012 Apr 2.
Fernandez-Flores A; Cutaneous MALT-lymphoma: from cutaneous immunocytoma and pseudolymphoma to the current (and future) conceptions. Rom J Morphol Embryol. 201354(1):7-12.
Marmon S, Chu J, Patel R, et al; Recurrent localized primary cutaneous marginal-zone B cell lymphoma. Dermatol Online J. 2011 Oct 1517(10):27.