Mucosa-associated lymphoid tissue (MALT) lymphoma

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).

Definition

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 subtypes¹²:

• Nodal: involving lymph nodes.

• Extranodal (MALT type): involving GI tract, ocular adnexa, salivary gland, thyroid, lung, thymus and breast.

• Splenic.

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.

Aetiology

• 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 infection³.

• 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 lymphomas⁴.

Epidemiology⁵

• 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 40³.

Clinical features

• 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.

Investigations

• 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.

• Endoscopy.

• Bone marrow aspiration.

Management

The National Institute for Health and Care Excellence (NICE) recommends⁶:

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 disease⁷.

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%, respectively⁸. 70-80% of patients reveal complete remission of MALT lymphoma following successful eradication of H. pylori⁹.

Salivary gland MALT lymphoma¹⁰

• 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 lymphoma¹¹

• 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 dissemination¹².

Thyroid MALT lymphoma

• Associated with: particularly associated with inflammatory conditions in the thyroid and salivary glands¹³.

• 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 clear¹⁴.

• 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 arms¹⁵.

• Prognosis: although recurrence is not uncommon, extracutaneous dissemination is very rare and prognosis is often excellent¹⁵.