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 leucocytes that originate from the bone marrow. The main lymphoid organs are:

• Bone marrow
• Thymus
• Mucosa-associated lymphoid tissue (MALT)
• Gut-associated lymphoid tissue (GALT)
• Bronchus-associated lymphoid tissue (BALT)
• Skin-associated lymphoid tissue (SALT)
• Tonsils
• Spleen
• Lymph nodes

MALT Lymphoma is a subtype of non-Hodgkin's lymphoma with it's own specific pathology, histology and clinical features.¹ It is distinct because it involves lymphoid proliferation in mucosa-associated lymphoid tissue rather than lymph nodes.

The distinction from other non-Hodgkin's lymphoma was first made by Isaacson and Wright in 1983.² It was described as a discrete form of lymphoma in 1994 in the Revised European-American Lymphoma (REAL) classification.¹ In this classification, it is classified as one of the subtypes of marginal zone B-cell lymphomas which include nodal, extranodal (MALT type) and splenic.

Extranodal, or MALT, Lymphomas follow a different course to nodal B-cell lymphomas. They tend to remain localized for longer, lack poor prognostic features and have a higher 5-year survival rate.³ They can occur in the:

• GI tract
• Orbit and conjunctiva
• Salivary glands
• Thyroid gland
• Lung
• Larynx
• Thymus
• Breast
• Skin
• Dura
• Urinary tract
• Liver
• Prostate

• 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 Helicobacter pylori infection in 85-90% of gastric MALT lymphomas.¹
  • Chlamydophila (Chlamydia) psittaci has been identified as a possible causative agent in ocular adnexal lymphomas.⁴
  • Borrelia burgdorferi infection has been linked to skin MALT lymphomas.^5,6
  • Campylobacter jejuni has been linked to small bowel MALT lymphomas.⁷
  • There is also a possible link between Hepatitis C and HIV and MALT lymphomas.^8,9,10
• 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, the most common being the translocation t(11;18)(q21;q21) found in one third of cases. Trisomy 3 and trisomy 18 are other abnormalities.^11,12,13 These abnormalities seem to drive lymphoma progression.

• MALT Lymphoma accounts for 8% of all non-Hodgkin's lymphomas.¹⁴
• It is most likely to present in the sixth decade.¹
• Females are affected more than males.¹
• Gastric MALT Lymphoma is the most common.¹⁴

• Autoimmune disease.
• H.pylori gastritis (however, most patients with this do not develop lymphoma).

These depend on the site involved. MALT Lymphoma usually follows an indolent course. It can remain localised for long periods. Disseminated disease is more likely in non-gastrointestinal MALT Lymphoma^15,16 but there is still a 5 year survival rate of 93% for this subtype.¹⁴ Rarely, there is transformation to a more aggressive form of lymphoma. Relapses of MALT Lymphoma may be late and lifelong observation may be required.¹⁷

Gastric MALT lymphoma

• Associated with: H. pylori infection.
• Presenting features: Dyspepsia, epigastric discomfort, gastric bleeding. Systemic B symptoms (nightsweats, 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.
• Treatment: Eradication of H.pylori with antibiotics and a proton pump inhibitor 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.^1,18,19 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.²⁰ 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: 5 year survival rates > 80%.²¹ Worst prognosis if there is deep infiltration of the gastric wall at presentation as spread to regional lymph nodes is more likely.²²

Salivary gland MALT lymphoma

• Associated with: Sjögren's syndrome.
• Clinical features: Parotid gland most common site. Indolent course (3-18 years progression even with no treatment).²³
• Treatment: No agreed optimum approach. Surgery, radiotherapy, chemotherapy and monoclonal antibody therapy are all used.

Ocular adnexa and lacrimal gland MALT lymphoma

• Associated with: Chlamydophila (Chlamydia) psittaci infection.
• Clinical features: Painless conjunctival injection, photophobia, orange/salmon-pink masses in the fornices.
• Treatment: Radiotherapy. Cataract and dry eyes are complications of this.²⁴
• Prognosis: 5 year survival rate 91%.²⁵

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.¹ May be cough, dyspnoea, haemoptysis, fever, weight loss. Can spread throughout the lung and to other MALT.
• Treatment: Surgery (if localised), chemotherapy, radiotherapy.

Thyroid MALT lymphoma

• Associated with: Autoimmune thyroiditis.
• Clinical features: Thyroid mass, possible obstructive symptoms.
• Diagnosis: May need open biopsy.
• Treatment: Surgery ± radiation for local disease, chemotherapy added if disease advanced.

Skin MALT lymphoma

• Associated with: Borrelia burgdorferi infection.
• Clinical features: Single or multiple brown papulonodular lesions or plaques on back or extremities.^26,27
• Treatment: Observation only, excision, radiotherapy. Possibly treatment by eradication of Borrelia burgdorferi.
• Prognosis: Indolent. 5 year survival > 95%.¹