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.
Indolent B-cell lymphomas that are supposed to derive from the marginal zone (marginal zone lymphomas) include three specific entities: extranodal marginal zone lymphoma or mucosa-associated lymphatic tissue (MALT) lymphoma, splenic marginal zone lymphomas (SMZLs), and nodal marginal zone lymphomas (NMZLs).
MALT lymphomas follow a different course to nodal B-cell lymphomas. They tend to remain localised for longer, lack poor prognostic features and have a higher five-year survival rate. MALT lymphomas can be divided into:
- Gastric: the most common type and associated with Helicobacter 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.
- Certain infections have been associated with MALT lymphomas:
- There is H. pylori infection in 85-90% of gastric MALT lymphomas.
- Chlamydophila psittaci has been identified as a possible causative agent in ocular adnexal lymphomas.
- Borrelia burgdorferi infection has been linked to skin MALT lymphomas.
- Campylobacter jejuni has been linked to small bowel MALT lymphomas.
- There is also a possible link between hepatitis C and HIV and MALT lymphomas.
- 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.
- It is most likely to present in the sixth decade.
- Females are affected more than males.
- 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.
Management is different for gastric and non-gastric MALT lymphomas.
- Treatment with a proton pump inhibitor (PPI) and antibiotics to eradicate H. pylori is the main treatment for most gastric MALT lymphomas, which are often low-grade and remain localised for several years. Treatment with chemotherapy, surgery or radiotherapy has not been demonstrated to be superior to antibiotic treatment.
- Treatments for non-gastric MALT lymphomas include radiotherapy, chemotherapy, monoclonal antibodies and surgery.
- 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.
- Eradication of H. pylori with antibiotics and a PPI or H2-receptor antagonist can lead to a complete remission of gastric MALT lymphoma in between 65-70% of cases and is first-line treatment for early-stage disease.[1, 11]
- If H. pylori status is negative, eradication treatment may not work.
- Close follow-up using endoscopy is needed after eradication treatment to ensure a complete response.
- If there is locally-advanced or high-grade disease, chemotherapy, monoclonal antibody treatment with rituximab, or radiotherapy should be added to eradication treatment.
- Surgery is reserved for refractory disease, as gastric preservation is preferred if possible.
- Current clinical trials involving these different treatment modalities are underway.
- 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.
- Treatment: radiotherapy is the only treatment modality that improves disease-free survival.
- 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
- Associated with: C. psittaci has been associated with the pathogenesis of ocular adnexal lymphomas in some parts of the world.
- 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.
- Treatment: radiotherapy. Cataract and dry eyes are complications of this.
- Prognosis: five-year survival rate 91%.
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.
- Treatment: surgery (if localised), chemotherapy, radiotherapy.
- 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.
- Treatment: surgery ± radiation for local disease; chemotherapy added if the disease is advanced.
Skin MALT lymphoma
- Associated with: B. 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.
- Treatment: options include observation only, excision, chemotherapy, radiotherapy.
- Prognosis: although recurrence is not uncommon, extracutaneous dissemination is very rare. Prognosis is excellent with five-year survival >95%.
Further reading and references
Cohen SM, Petryk M, Varma M, et al; Non-Hodgkin's lymphoma of mucosa-associated lymphoid tissue. Oncologist. 2006 Nov-Dec11(10):1100-17.
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.
Ferreri AJ, Guidoboni M, Ponzoni M, et al; Evidence for an association between Chlamydia psittaci and ocular adnexal lymphomas. J Natl Cancer Inst. 2004 Apr 2196(8):586-94.
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.
Lecuit M, Abachin E, Martin A, et al; Immunoproliferative small intestinal disease associated with Campylobacter jejuni. N Engl J Med. 2004 Jan 15350(3):239-48.
Girard T, Luquet-Besson I, Baran-Marszak F, et al; HIV+ MALT lymphoma remission induced by highly active antiretroviral therapy alone. Eur J Haematol. 2005 Jan74(1):70-2.
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.
Raderer M, Streubel B, Woehrer S, et al; High relapse rate in patients with MALT lymphoma warrants lifelong follow-up. Clin Cancer Res. 2005 May 111(9):3349-52.
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.
Nakamura S, Matsumoto T, Suekane H, et al; Long-term clinical outcome of Helicobacter pylori eradication for gastric mucosa-associated lymphoid tissue lymphoma with a reference to second-line treatment. Cancer. 2005 Aug 1104(3):532-40.
Fischbach W, Goebeler-Kolve M, Ruskone-Fourmestraux A, et al; Most patients with minimal histological residuals of gastric MALT lymphoma after successful eradication of Helicobacter pylori can be safely managed by a watch-and-wait strategy. Experience from a large international series. Gut. 2007 Jul 16.
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.
Stefanovic A, Lossos IS; Extranodal marginal zone lymphoma of the ocular adnexa. Blood. 2009 Jul 16114(3):501-10. doi: 10.1182/blood-2008-12-195453. Epub 2009 Apr 16.
Westekemper H, Schallenberg M, Tomaszewski A, et al; [Malignant epibulbar tumours: new strategies in diagnostics and therapy]. Klin Monbl Augenheilkd. 2011 Sep228(9):780-92. doi: 10.1055/s-0029-1246068. Epub 2011 Apr 12.
Tanimoto K, Kaneko A, Suzuki S, et al; Long-term follow-up results of no initial therapy for ocular adnexal MALT lymphoma. Ann Oncol. 2006 Jan17(1):135-40. Epub 2005 Oct 19.
Uno T, Isobe K, Shikama N, et al; Radiotherapy for extranodal, marginal zone, B-cell lymphoma of mucosa-associated lymphoid tissue originating in the ocular adnexa: a multiinstitutional, retrospective review of 50 patients. Cancer. 2003 Aug 1598(4):865-71.
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.
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.
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